page96-145_compressed.pdf

# Ischemic stroke: types, clinical features, and vascular territories This topic focuses on classifying ischemic strokes, detailing their clinical presentations across different cerebral vascular territories, and describing specific lacunar syndromes. ### 1.1 Ischemic stroke: types and pathogenesis Ischemic stroke is defined as focal brain ischemia leading to neuronal death due to reduced cerebral blood flow. Approximately 85% of all strokes are ischemic, making it the leading cause of neurologic disability. The core pathophysiologic concept involves reduced perfusion, creating an ischemic core and a penumbra at risk [1](#page=1) [2](#page=2) [3](#page=3). #### 1.1.1 Major categories of ischemic stroke The major categories of ischemic stroke include: * **Transient Ischemic Attack (TIA):** Characterized by a neurologic deficit that resolves within 24 hours, typically within 30 minutes, with no permanent infarction due to reperfusion. TIAs are often embolic and carry a high early risk of stroke, particularly within the first 48 hours [1](#page=1) [2](#page=2) [3](#page=3). * **Thrombotic Stroke (Large-artery disease):** This type results from atherosclerotic plaque rupture, leading to thrombosis. Onset is often stepwise, or symptoms may be present upon awakening. Common sites for thrombotic strokes include the carotid bifurcation, middle cerebral artery (MCA) branches, and the circle of Willis [1](#page=1) [2](#page=2) [3](#page=3). * **Embolic Stroke:** Embolic strokes have a sudden onset with deficits maximal at the start. Potential sources include the heart (atrial fibrillation, mural thrombus, valve disease), carotid atherosclerotic plaques, and the aorta. Paradoxical emboli can also occur through a patent foramen ovale (PFO) or atrial septal defect (ASD). The MCA is the most commonly affected artery in embolic strokes [1](#page=1) [2](#page=2) [3](#page=3). * **Lacunar Stroke (Small-vessel disease):** These strokes are caused by lipohyalinosis, often associated with chronic hypertension and diabetes mellitus. Lacunar strokes affect deep brain structures such as the internal capsule, thalamus, basal ganglia, and pons. They typically present with pure motor or sensory syndromes, without cortical signs, and healed lesions form "lacunes" or small cavities [1](#page=1) [2](#page=2) [3](#page=3). #### 1.1.2 Additional etiologic categories and key mechanisms Other etiologic categories include: * **Arteriogenic Emboli:** Originating from ulcerated plaques in neck vessels like the carotid artery [1](#page=1) [2](#page=2) [3](#page=3). * **Hypoperfusion States:** Systemic hypotension can lead to watershed infarcts [1](#page=1) [2](#page=2) [3](#page=3). * **Paradoxical Embolism:** A venous clot crosses a PFO or ASD, entering the arterial circulation and reaching the brain [1](#page=1) [2](#page=2) [3](#page=3). * **Nonvascular Global Ischemia:** This can result from low cardiac output (e.g., severe heart failure, cardiac arrest) or severe hypoxia/anoxia [1](#page=1) [2](#page=2) [3](#page=3). Key stroke mechanisms can be summarized as: embolic strokes causing sudden, abrupt deficits; thrombotic strokes with gradual or stuttering onset; lacunar strokes due to small penetrating artery occlusion with focal deficits; and hypoperfusion leading to a watershed pattern of injury [1](#page=1) [2](#page=2) [3](#page=3). ### 1.2 Clinical features and vascular territories #### 1.2.1 General clinical principles Stroke onset patterns vary: embolic strokes present suddenly with maximal deficits, thrombotic strokes can have rapid or stepwise progression, and lacunar strokes typically show gradual or small-step focal deficits. The National Institutes of Health Stroke Scale (NIHSS) is used to quantify severity and predict outcomes. Distinguishing between cortical and subcortical signs is crucial; cortical signs include aphasia, neglect, visual field defects, and gaze preference, while subcortical (lacunar) strokes present with pure motor or sensory deficits without cortical involvement [1](#page=1) [2](#page=2) [3](#page=3). #### 1.2.2 Middle cerebral artery (MCA) territory The MCA is the most commonly affected artery in ischemic strokes. Typical deficits include contralateral weakness affecting the face and arm more than the leg, and contralateral hemisensory loss with similar distribution. Hyperreflexia and Babinski signs may be present [1](#page=1) [2](#page=2) [3](#page=3). * **Dominant hemisphere (usually left) MCA infarcts:** Can cause global aphasia, Broca's aphasia (expressive), or Wernicke's aphasia (receptive). Agraphia and acalculia may also occur [2](#page=2) [3](#page=3). * **Nondominant hemisphere MCA infarcts:** May lead to hemineglect, anosognosia, and visuospatial disturbances [2](#page=2) [3](#page=3). #### 1.2.3 Anterior cerebral artery (ACA) territory ACA territory infarcts typically cause contralateral leg weakness that is more pronounced than arm weakness. Frontal lobe signs, such as abulia (lack of willpower), personality changes, and impaired judgment, can occur. Urinary incontinence may also be present due to involvement of the frontal micturition centers. These infarcts typically affect the medial frontal lobes and paracentral lobules [2](#page=2) [3](#page=3). #### 1.2.4 Posterior cerebral artery (PCA) territory PCA infarcts commonly result in contralateral homonymous hemianopia, which may spare the macula. Other potential deficits include visual agnosia and alexia without agraphia if the dominant PCA is affected. Memory impairment can occur if the medial temporal lobe or hippocampus is involved. Visual deficits are dominant in PCA infarcts due to occipital lobe involvement [2](#page=2) [3](#page=3). #### 1.2.5 Vertebrobasilar / Posterior circulation Infarcts in the vertebrobasilar system affect the brainstem and cerebellum, leading to symptoms such as dizziness, vertigo, nausea, vomiting, diplopia, dysarthria, and dysphagia. Ataxia, gait disturbances, and ipsilateral limb incoordination can also occur, alongside long-tract signs like contralateral weakness or sensory deficits. Severe cases, such as basilar artery occlusion, can result in a locked-in syndrome or coma. It is important to note that posterior circulation strokes can present with isolated cranial nerve palsies combined with long-tract signs [2](#page=2) [3](#page=3). #### 1.2.6 Lacunar syndromes Lacunar syndromes result from small-vessel disease, typically due to lipohyalinosis and arteriosclerosis of penetrating arteries, often associated with hypertension and diabetes. The classic lacunar syndromes include [2](#page=2) [3](#page=3): * **Pure motor stroke:** Affecting the internal capsule or pons, causing contralateral hemiparesis [2](#page=2) [3](#page=3). * **Pure sensory stroke:** Affecting the thalamus, causing contralateral hemisensory loss [2](#page=2) [3](#page=3). * **Ataxic hemiparesis:** Affecting the internal capsule or pons, causing weakness and incoordination [2](#page=2) [3](#page=3). * **Clumsy-hand dysarthria:** Caused by a small pontine or internal capsule lesion [2](#page=2) [3](#page=3). A key feature of lacunar strokes is the absence of cortical signs, such as aphasia or visual field cuts [2](#page=2) [3](#page=3). #### 1.2.7 Special clinical presentations * **Amaurosis fugax:** Transient monocular blindness, often described as a "curtain over the eye," usually caused by a microembolus from the carotid or ophthalmic artery [2](#page=2) [3](#page=3). * **Subclavian steal syndrome:** Occurs with proximal subclavian artery stenosis, leading to reversal of vertebral artery blood flow during arm exertion. Symptoms include vertebrobasilar ischemia (dizziness, syncope) and arm claudication. A key sign is a lower blood pressure and decreased pulse in the affected arm [2](#page=2) [3](#page=3). * **Watershed (borderzone) infarcts:** These occur in areas between major arterial territories, often during systemic hypotension or severe carotid stenosis. Symptoms can include proximal limb weakness and higher cortical dysfunction, depending on the affected watershed zone [2](#page=2) [3](#page=3). #### 1.2.8 Lateralizing signs and localizing tips Useful "exam shortcuts" for localizing the stroke based on signs include: * Face and arm > leg weakness suggests an MCA territory infarct [2](#page=2) [3](#page=3). * Leg > arm weakness suggests an ACA territory infarct [2](#page=2) [3](#page=3). * A visual field defect points to a PCA (occipital) infarct [2](#page=2) [3](#page=3). * Pure motor or sensory deficits without cortical signs strongly suggest a lacunar stroke [2](#page=2) [3](#page=3). * Vertigo combined with cranial nerve signs indicates a vertebrobasilar stroke [2](#page=2) [3](#page=3). #### 1.2.9 High-yield exam bait and ward tips * Embolic strokes are characterized by sudden, maximal deficits, prompting consideration of atrial fibrillation or mural thrombus as the source [2](#page=2) [3](#page=3). * Thrombotic strokes often present with stepwise or wake-up deficits, suggesting large-vessel atherosclerosis [2](#page=2) [3](#page=3). * Lacunar strokes are strongly associated with a history of hypertension, seen in 80-90% of cases, pointing towards small-vessel disease [2](#page=2) [3](#page=3). * Always ascertain the "time last known well" (LKW), as this is critical for decisions regarding thrombolysis with tissue plasminogen activator (tPA) [2](#page=2) [3](#page=3). * In vertebrobasilar strokes, isolated dizziness or vertigo should not be disregarded, as they can indicate a potentially life-threatening condition [2](#page=2) [3](#page=3). --- # Ischemic stroke: acute management and secondary prevention This section details the initial evaluation, diagnostic imaging, and immediate therapeutic interventions for ischemic stroke, including thrombolysis and endovascular procedures, as well as strategies for blood pressure control, complication management, and long-term secondary prevention [3](#page=3) [4](#page=4) [5](#page=5). ### 2 Initial assessment The initial assessment in the Emergency Department (ED) or on the ward is critical for timely and effective stroke management [3](#page=3) [4](#page=4) [5](#page=5). #### 3 Time metrics * **Time last known well (LKW)** is a crucial determinant for the administration of tissue plasminogen activator (tPA) and endovascular thrombectomy decisions [3](#page=3) [4](#page=4) [5](#page=5). * Distinguishing between onset and wake-up strokes is important as it impacts treatment eligibility [3](#page=3) [4](#page=4) [5](#page=5). #### 4 Immediate checks * **ABCs:** Ensure a patent airway, adequate breathing, and stable circulation [3](#page=3) [4](#page=4) [5](#page=5). * **Finger-stick glucose:** Essential to rule out hypoglycemia or hyperglycemia, which can mimic stroke symptoms [3](#page=3) [4](#page=4) [5](#page=5). * **Neurologic examination and NIHSS:** A comprehensive neurological assessment and quantification of stroke severity using the National Institutes of Health Stroke Scale (NIHSS) are vital [3](#page=3) [4](#page=4) [5](#page=5). * **IV access and labs:** Establish intravenous access and obtain blood work including a complete blood count (CBC), electrolytes, creatinine, coagulation profile, and glucose [3](#page=3) [4](#page=4) [5](#page=5). #### 5 Cardiac evaluation * **ECG:** To detect atrial fibrillation (AF) or myocardial infarction (MI) [3](#page=3) [4](#page=4) [5](#page=5). * **Cardiac monitoring/telemetry:** To identify paroxysmal AF [3](#page=3) [4](#page=4) [5](#page=5). ### 6 Imaging modalities and use Appropriate imaging is paramount for diagnosis and guiding treatment decisions [3](#page=3) [4](#page=4) [5](#page=5). #### 7 Non-contrast CT head * **First-line imaging:** Due to its speed and availability in the ED [3](#page=3) [4](#page=4) [5](#page=5). * **Primary purpose:** To exclude intracranial hemorrhage (blood appears hyperdense/white) [3](#page=3) [4](#page=4) [5](#page=5). * **Limitations:** Early ischemic changes may be subtle or absent for the first 24–48 hours [3](#page=3) [4](#page=4) [5](#page=5). * **Usefulness:** Can detect mass lesions and significant infarct effects [3](#page=3) [4](#page=4) [5](#page=5). #### 8 CT Angiography (CTA) * **Purpose:** Vascular imaging to identify large-vessel occlusions (e.g., MCA, internal carotid artery [ICA, basilar artery) [3](#page=3) [4](#page=4) [5](#page=5). * **Role:** Guides decisions regarding endovascular thrombectomy [3](#page=3) [4](#page=4) [5](#page=5). #### 9 MRI Brain (DWI) * **Sensitivity:** More sensitive than CT for detecting acute ischemia and identifying infarcts at an earlier stage [3](#page=3) [4](#page=4) [5](#page=5). * **Specific uses:** Useful for small lacunar infarcts and posterior fossa lesions [3](#page=3) [4](#page=4) [5](#page=5). #### 10 MR Angiography (MRA) / Carotid Doppler / TEE * **Purpose:** To evaluate carotid stenosis and identify cardiac sources of emboli (e.g., thrombus in the left atrial appendage [LAA via transesophageal echocardiography [TEE]) [3](#page=3) [4](#page=4) [5](#page=5). * **Application:** Used in the workup for secondary prevention [3](#page=3) [4](#page=4) [5](#page=5). ### 11 Acute treatment principles Prompt and appropriate acute treatment can significantly improve functional outcomes [3](#page=3) [4](#page=4) [5](#page=5). #### 12 General supportive care * **Airway management:** Maintain a patent airway; supplemental oxygen is indicated only if the patient is hypoxic [3](#page=3) [4](#page=4) [5](#page=5). * **Perfusion and glucose:** Maintain adequate perfusion and avoid hypotension; correct any abnormalities in blood glucose levels [3](#page=3) [4](#page=4) [5](#page=5). * **NPO status:** Patients should remain nil by mouth (NPO) until a swallow screen is performed to prevent aspiration [3](#page=3) [4](#page=4) [5](#page=5). * **DVT prophylaxis:** Initiate deep vein thrombosis (DVT) prophylaxis during hospitalization [3](#page=3) [4](#page=4) [5](#page=5). #### 13 Thrombolysis — IV alteplase (tPA) * **Indication:** Ischemic stroke with a known onset of symptoms within ≤ 4.5 hours [3](#page=3) [4](#page=4) [5](#page=5). * **Benefit:** Improves functional outcome at 3 months, with benefits being time-dependent [3](#page=3) [4](#page=4) [5](#page=5). * **Contraindications:** * Unknown or >4.5 hours since symptom onset [3](#page=3) [4](#page=4) [5](#page=5). * Active bleeding or a bleeding diathesis [3](#page=3) [4](#page=4) [5](#page=5). * Uncontrolled hypertension (systolic blood pressure >185 mm Hg or diastolic blood pressure >110 mm Hg) [3](#page=3) [4](#page=4) [5](#page=5). * Recent major surgery or trauma [3](#page=3) [4](#page=4) [5](#page=5). * History of intracranial hemorrhage [3](#page=3) [4](#page=4) [5](#page=5). * **Post-administration:** * Withhold antiplatelets and anticoagulants for 24 hours [3](#page=3) [4](#page=4) [5](#page=5). * Perform frequent neurological checks (e.g., every 15 minutes initially) [3](#page=3) [4](#page=4) [5](#page=5). * Maintain blood pressure targets <185/110 mm Hg [3](#page=3) [4](#page=4) [5](#page=5). * **Risk:** Hemorrhagic transformation, requiring close monitoring [3](#page=3) [4](#page=4) [5](#page=5). #### 14 Endovascular thrombectomy * **Indication:** Large-vessel occlusion in proximal arteries, such as the MCA, ICA, or basilar artery [3](#page=3) [4](#page=4) [5](#page=5). * **Treatment window:** Up to 6 hours from symptom onset is standard; select patients may benefit up to 16–24 hours with favorable imaging criteria [3](#page=3) [4](#page=4) [5](#page=5). * **Combination therapy:** Often administered in conjunction with IV tPA if the patient is within the tPA window and has no contraindications [3](#page=3) [4](#page=4) [5](#page=5). * **Requirements:** Requires rapid CTA/MRA and availability of a neurointervention team [3](#page=3) [4](#page=4) [5](#page=5). #### 15 Other acute measures * **Aspirin:** Administer as soon as possible if tPA is not given, ideally within 48 hours of stroke onset [3](#page=3) [4](#page=4) [5](#page=5). * **Anticoagulation:** Avoid routine anticoagulation acutely, unless there is a clear cardioembolic source; in such cases, it can be initiated later under neurovascular guidance [3](#page=3) [4](#page=4) [5](#page=5). * **Complication management:** Address potential complications such as cerebral edema (using mannitol or hyperventilation), seizures, and fever [3](#page=3) [4](#page=4) [5](#page=5). ### 16 Blood pressure management Careful blood pressure management is essential to preserve the ischemic penumbra and prevent complications [3](#page=3) [4](#page=4) [5](#page=5). #### 17 General rule Avoid aggressive blood pressure lowering in the first 24 hours after an ischemic stroke unless specific indications are present [3](#page=3) [4](#page=4) [5](#page=5). #### 18 Indications for immediate treatment * Systolic blood pressure >220 mm Hg or diastolic blood pressure >120 mm Hg [3](#page=3) [4](#page=4) [5](#page=5). * Concurrent acute myocardial infarction, aortic dissection, hypertensive encephalopathy, or severe heart failure [3](#page=3) [4](#page=4) [5](#page=5). * Patients receiving tPA must maintain blood pressure below 185/110 mm Hg before administration and below 180/105 mm Hg after [3](#page=3) [4](#page=4) [5](#page=5). #### 19 If lowering BP Lower blood pressure gradually and monitor neurological status closely to avoid compromising blood flow to the ischemic area [3](#page=3) [4](#page=4) [5](#page=5). ### 20 Complications to monitor and manage Several complications can arise following an ischemic stroke that require vigilant monitoring and prompt intervention [3](#page=3) [4](#page=4) [5](#page=5). #### 21 Cerebral edema / mass effect * **Timing:** Often occurs within 1–2 days and can persist for up to approximately 10 days [3](#page=3) [4](#page=4) [5](#page=5). * **Signs:** Decreased level of consciousness (LOC), vomiting, bradycardia, and unequal pupils [3](#page=3) [4](#page=4) [5](#page=5). * **Treatment:** Head elevation, mannitol or hyperosmolar therapy, temporary hyperventilation, and neurosurgical decompression if malignant edema develops [3](#page=3) [4](#page=4) [5](#page=5). #### 22 Hemorrhagic transformation This is a particular concern, especially after reperfusion therapies [3](#page=3) [4](#page=4) [5](#page=5). #### 23 Early seizures More common in cortical infarcts [3](#page=3) [4](#page=4) [5](#page=5). #### 24 Medical complications These include aspiration pneumonia, DVT/pulmonary embolism (PE), urinary tract infections (UTIs), and pressure sores [3](#page=3) [4](#page=4) [5](#page=5). ### 25 Secondary prevention and long-term management Long-term strategies are crucial to reduce the risk of recurrent stroke [3](#page=3) [4](#page=4) [5](#page=5). #### 26 Lifestyle and risk factor control * **Blood pressure control:** This is the single most important modifiable risk factor for stroke prevention [3](#page=3) [4](#page=4) [5](#page=5). * **Glycemic control:** Essential for patients with diabetes mellitus [3](#page=3) [4](#page=4) [5](#page=5). * **Lifestyle modifications:** Include smoking cessation, weight management, regular exercise, and a healthy diet [3](#page=3) [4](#page=4) [5](#page=5). * **Lipid management:** Treat hyperlipidemia with statin therapy [3](#page=3) [4](#page=4) [5](#page=5). #### 27 Antiplatelet therapy * **Non-cardioembolic stroke:** Aspirin, clopidogrel, or a combination of aspirin and dipyridamole [3](#page=3) [4](#page=4) [5](#page=5). * **Minor stroke/TIA:** Short-term dual antiplatelet therapy (aspirin plus clopidogrel) is recommended per guidelines [3](#page=3) [4](#page=4) [5](#page=5). * **Post-tPA:** Delay initiation of antiplatelet therapy for 24 hours after tPA administration [3](#page=3) [4](#page=4) [5](#page=5). #### 28 Anticoagulation * **Indication:** Recommended for cardioembolic strokes, such as those due to atrial fibrillation (AF). The timing of initiation should be guided by neurovascular specialists [3](#page=3) [4](#page=4) [5](#page=5). * **Acute use:** Not generally recommended for routine acute management due to the increased risk of hemorrhage [3](#page=3) [4](#page=4) [5](#page=5). #### 29 Lipid management * **High-intensity statin:** Indicated for patients with atherosclerotic stroke, irrespective of their baseline low-density lipoprotein (LDL) cholesterol levels [3](#page=3) [4](#page=4) [5](#page=5). #### 30 Carotid disease management * **Symptomatic carotid stenosis >70%:** Carotid endarterectomy (CEA) is recommended, supported by evidence from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) [3](#page=3) [4](#page=4) [5](#page=5). * **Asymptomatic carotid stenosis >60%:** Offers a small benefit; often managed medically, as per the Asymptomatic Carotid Artery Stenosis Trial (ACAS) [3](#page=3) [4](#page=4) [5](#page=5). * **Carotid stenting:** An alternative treatment option for select patients based on their anatomy and surgical risk profile [3](#page=3) [4](#page=4) [5](#page=5). ### 31 Practical ward checklist and handover points A structured approach to documentation and handover is crucial for seamless patient care [3](#page=3) [4](#page=4) [5](#page=5). * Record the time last known well (LKW) and symptom onset; document the NIHSS score [3](#page=3) [4](#page=4) [5](#page=5). * Confirm CT head has been performed and note the findings (hemorrhage or ischemia) [3](#page=3) [4](#page=4) [5](#page=5). * Document the treatment decision: if tPA was given and/or if thrombectomy was planned [3](#page=3) [4](#page=4) [5](#page=5). * Record blood pressure targets and any medications administered [3](#page=3) [4](#page=4) [5](#page=5). * Outline the plan for antiplatelet/anticoagulation therapy, including the timing of initiation [3](#page=3) [4](#page=4) [5](#page=5). * Ensure DVT prophylaxis has been started, swallow screen completed, and NPO status is maintained if indicated [3](#page=3) [4](#page=4) [5](#page=5). * Plan for swallow assessment, mobilization, chest physiotherapy, and pressure area care [3](#page=3) [4](#page=4) [5](#page=5). * Follow-up on results of carotid imaging, cardiac workup (ECG, echocardiogram, telemetry), and the ongoing secondary prevention plan [3](#page=3) [4](#page=4) [5](#page=5). --- # Hemorrhagic stroke: intracerebral hemorrhage and subarachnoid hemorrhage This section differentiates between intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), detailing their etiologies, typical locations, clinical features, diagnostic methods, complications, and acute management strategies, highlighting their significant early mortality and emergent nature [6](#page=6) [7](#page=7). ### 3.1 Overview Hemorrhagic strokes, encompassing both ICH and SAH, are characterized by bleeding within the cranial vault [6](#page=6) [7](#page=7). * **Definition:** * **ICH** involves bleeding directly into the brain parenchyma [6](#page=6) [7](#page=7). * **SAH** refers to bleeding into the subarachnoid space, which contains cerebrospinal fluid (CSF) [6](#page=6) [7](#page=7). * **Clinical significance:** * These conditions carry a high early mortality rate, with ICH mortality around 50% at 30 days and SAH mortality between 25% and 50% [6](#page=6) [7](#page=7). * Both are considered neurosurgical emergencies, emphasizing that early recognition is crucial for improving patient outcomes [6](#page=6) [7](#page=7). ### 3.2 Intracerebral hemorrhage (ICH) #### 3.2.1 Etiology / causes The primary causes of ICH include: * **Hypertension:** Responsible for 50–60% of cases, often associated with sudden blood pressure spikes and Charcot–Bouchard microaneurysms [6](#page=6) [7](#page=7). * **Amyloid angiopathy:** Commonly leads to lobar bleeds, particularly in elderly patients [6](#page=6) [7](#page=7). * **Anticoagulants / thrombolytics:** Medications that interfere with blood clotting increase the risk of hemorrhage [6](#page=6) [7](#page=7). * **Other causes:** Arteriovenous (AV) malformations, brain tumors, and illicit drug use (e.g., cocaine), which is more frequent in younger patients [6](#page=6) [7](#page=7). #### 3.2.2 Typical locations ICH commonly occurs in specific brain regions: * **Basal ganglia (putamen):** Accounts for approximately 66% of ICH cases [6](#page=6) [7](#page=7). * **Pons:** Represents about 10% of cases [6](#page=6) [7](#page=7). * **Cerebellum:** Also accounts for approximately 10% of cases [6](#page=6) [7](#page=7). * **Cortical/lobar regions:** The remaining cases are distributed in these areas [6](#page=6) [7](#page=7). #### 3.2.3 Clinical features The presentation of ICH is typically abrupt: * **Focal neurological deficit:** A sudden onset of localized neurological impairment that worsens over 30–90 minutes [6](#page=6) [7](#page=7). * **Altered consciousness:** Patients may exhibit stupor or coma [6](#page=6) [7](#page=7). * **Associated symptoms:** Headache and vomiting are common [6](#page=6) [7](#page=7). * **Signs of raised intracranial pressure (ICP) / herniation:** This can manifest as Cushing's triad (hypertension, bradycardia, and irregular respiration) [6](#page=6) [7](#page=7). #### 3.2.4 Diagnosis The diagnostic approach for ICH focuses on imaging and laboratory tests: * **Non-contrast CT head:** This is the primary imaging modality, detecting hyperdense (white) bleeds with approximately 95% sensitivity [6](#page=6) [7](#page=7). * **Laboratory tests:** Include a complete blood count (CBC), platelet count, and coagulation panel to assess for coagulopathy and plan for potential reversal strategies [6](#page=6) [7](#page=7). #### 3.2.5 Complications ICH can lead to several serious complications: * **Raised ICP and herniation:** Increased pressure within the skull can lead to brain herniation [6](#page=6) [7](#page=7). * **Seizures:** Hemorrhage can trigger epileptic activity [6](#page=6) [7](#page=7). * **Rebleeding:** The risk of the hematoma expanding [6](#page=6) [7](#page=7). * **Hydrocephalus:** Occurs if the hemorrhage extends into the ventricular system (intraventricular extension) [6](#page=6) [7](#page=7). * **SIADH / medical complications:** Syndrome of inappropriate antidiuretic hormone secretion and other general medical issues like pneumonia and deep vein thrombosis (DVT) [6](#page=6) [7](#page=7). #### 3.2.6 Acute management The acute management of ICH is multi-faceted: * **ICU admission:** Patients require close monitoring in an intensive care unit [6](#page=6) [7](#page=7). * **Airway protection:** Ensure a patent airway and consider intubation if the Glasgow Coma Scale (GCS) is low or airway is compromised [6](#page=6) [7](#page=7). * **Nil per os (NPO):** Patients should be kept NPO until a swallow screen is performed [6](#page=6) [7](#page=7). * **Blood pressure (BP) management:** Gradual reduction of systolic blood pressure (SBP) is recommended if SBP exceeds 180 mmHg or mean arterial pressure (MAP) exceeds 130 mmHg. Avoid rapid drops in BP [6](#page=6) [7](#page=7). * **Reversal of anticoagulation:** * For warfarin: Vitamin K and prothrombin complex concentrate (PCC) [6](#page=6) [7](#page=7). * For heparin: Protamine sulfate [6](#page=6) [7](#page=7). * For direct oral anticoagulants (DOACs): Specific reversal agents if available [6](#page=6) [7](#page=7). * **ICP control:** Strategies include elevating the head of the bed to 30 degrees, sedation and pain control, administration of mannitol, temporary hyperventilation, and CSF drainage via an external ventricular drain (EVD) if hydrocephalus is present [6](#page=6) [7](#page=7). * **Surgical intervention:** Urgent surgical evacuation is indicated for cerebellar hematomas. Selective surgical intervention may be considered for large superficial supratentorial bleeds or signs of herniation [6](#page=6) [7](#page=7). * **Steroids:** Steroids are **NOT** recommended for ICH management [6](#page=6) [7](#page=7). ### 3.3 Subarachnoid hemorrhage (SAH) #### 3.3.1 Etiology / causes The common causes of SAH are: * **Ruptured saccular (berry) aneurysm:** This is the most frequent cause, typically occurring at the bifurcations of the Circle of Willis [6](#page=6) [7](#page=7). * **Trauma:** Can also lead to SAH [6](#page=6) [7](#page=7). * **AV malformation:** Arteriovenous malformations are another cause [6](#page=6) [7](#page=7). * **Other causes:** Mycotic aneurysms and drug use (e.g., cocaine) [6](#page=6) [7](#page=7). #### 3.3.2 Clinical features SAH often presents with a characteristic set of symptoms: * **Sudden, severe headache:** Described as the "worst headache of my life" [6](#page=6) [7](#page=7). * **Transient loss of consciousness (LOC):** Occurs in approximately 50% of patients [6](#page=6) [7](#page=7). * **Meningeal signs:** Include neck stiffness and photophobia due to meningeal irritation [6](#page=6) [7](#page=7). * **Other symptoms:** Vomiting and potential focal neurological deficits if vasospasm or a focal bleed is present [6](#page=6) [7](#page=7). * **Retinal hemorrhages:** Can be observed in up to 30% of cases [6](#page=6) [7](#page=7). #### 3.3.3 Diagnosis Diagnosing SAH involves imaging and lumbar puncture: * **Non-contrast CT head:** Detects most SAH cases early, appearing as hyperdense blood within the cisterns and sulci [6](#page=6) [7](#page=7). * **Lumbar puncture (LP):** If the CT is negative but suspicion remains high, an LP is performed [6](#page=6) [7](#page=7). * **CSF blood:** The presence of non-traumatic blood in the CSF is diagnostic [6](#page=6) [7](#page=7). * **Xanthochromia:** This is considered the gold standard, indicating the breakdown of red blood cells and requiring some time after the bleed to appear [6](#page=6) [7](#page=7). * **Angiography:** Once SAH is confirmed, CT angiography (CTA) or digital subtraction angiography (DSA) is used to locate the source of bleeding, typically an aneurysm [6](#page=6) [7](#page=7). #### 3.3.4 Complications SAH is associated with significant complications: * **Rebleeding:** A major risk, particularly in the early period after the initial event, and a significant contributor to mortality [6](#page=6) [7](#page=7). * **Vasospasm:** Delayed cerebral ischemia can occur between days 3 and 14, peaking around day 7 [6](#page=6) [7](#page=7). * **Hydrocephalus:** Communicating hydrocephalus can develop [6](#page=6) [7](#page=7). * **Other complications:** Seizures and hyponatremia, which can be due to SIADH or cerebral salt wasting [6](#page=6) [7](#page=7). #### 3.3.5 Treatment The management of SAH aims to secure the source of bleeding and prevent complications: * **Aneurysm securement:** Urgent intervention is required, either endovascular coiling (often preferred) or surgical clipping [6](#page=6) [7](#page=7). * **Nimodipine prophylaxis:** Administered to all patients with aneurysmal SAH to reduce the risk of ischemic deficits caused by vasospasm [6](#page=6) [7](#page=7). * **Supportive care:** Includes bed rest, a dark and quiet room, stool softeners, analgesia, and maintaining euvolemia [6](#page=6) [7](#page=7). * **Hydrocephalus management:** An EVD may be necessary if hydrocephalus develops [6](#page=6) [7](#page=7). * **Vasospasm treatment:** Management involves monitoring (e.g., transcranial Doppler), hypertensive-hypervolemic therapy, and endovascular therapy for refractory cases [6](#page=6) [7](#page=7). ### 3.4 Shared practical points (ICH & SAH) Several immediate steps and considerations are common to both ICH and SAH: #### 3.4.1 Immediate steps on arrival * **Airway, Breathing, Circulation (ABCs):** Prioritize assessment and management of basic life support [6](#page=6) [7](#page=7). * **Intubation:** Consider intubation if the GCS is low or the airway is at risk [6](#page=6) [7](#page=7). * **STAT non-contrast CT head:** This is the critical first imaging study [6](#page=6) [7](#page=7). * **Labs and coagulation panel:** Essential for assessing overall health and guiding treatment [6](#page=6) [7](#page=7). * **Glucose check:** To rule out hypoglycemia or hyperglycemia as contributing factors or complications [6](#page=6) [7](#page=7). * **Neurosurgery/neurology consult:** Early consultation with specialists is vital [6](#page=6) [7](#page=7). #### 3.4.2 Imaging clues * **Hemorrhage:** Appears hyperdense (white) on CT scans [6](#page=6) [7](#page=7). * **Ischemic stroke:** Appears hypodense (dark) on CT scans [6](#page=6) [7](#page=7). * **SAH location:** Typically found in the basal cisterns and sulci [6](#page=6) [7](#page=7). * **ICH location:** Presents as an intraparenchymal collection [6](#page=6) [7](#page=7). #### 3.4.3 Prognostic flags * **Poor prognosis:** A rapid drop in GCS, a large hematoma volume, and brainstem involvement are associated with a poorer prognosis [6](#page=6) [7](#page=7). * **SAH outcome determinants:** Rebleeding and vasospasm are key factors influencing the outcome in SAH [6](#page=6) [7](#page=7). ### 3.5 Exam/OSCE high-yield mnemonics & tips * **ICH mnemonic:** "Big People Cry Often" – helps recall typical locations: **B**asal ganglia, **P**ons, **C**erebellum, **O**ther (cortical/lobar) [6](#page=6) [7](#page=7). * **SAH mnemonic:** "WORST" – aids recall of key features: **W**orst headache, **O**nset sudden, **R**ebleed risk, **S**tiff neck, **T**ell-tale CT/xanthochromia [6](#page=6) [7](#page=7). * **Practical tip:** Always ascertain the time of symptom onset. Perform a CT scan first. Reverse anticoagulants promptly. Contact neurosurgery and neurointervention services swiftly [6](#page=6) [7](#page=7). > **Tip:** Remember that pinpoint pupils can indicate a pontine lesion, poorly reactive pupils may suggest a thalamic bleed, and dilated pupils can be associated with a putaminal hemorrhage [6](#page=6). --- # Movement disorders: Parkinson disease, Huntington chorea, and tremor This section summarizes movement disorders, focusing on Parkinson disease, Huntington chorea, and various types of tremor, including their pathophysiology, clinical presentations, investigations, and management strategies. ### 4.1 Parkinson disease Parkinson disease (PD) is the most common hypokinetic movement disorder, typically presenting in individuals over 50 years of age. It is primarily a clinical diagnosis, relying on patient history and physical examination, as laboratory tests are not diagnostic. Parkinsonism refers to the syndrome, with idiopathic PD accounting for approximately 90% of cases, while about 10% are classified as Parkinson-plus syndromes [8](#page=8) [9](#page=9). #### 4.1.1 Pathophysiology The core pathophysiology of PD involves the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). This leads to a deficiency in nigrostriatal dopamine, resulting in an imbalance between the direct (GO) and indirect (STOP) basal ganglia circuits, which contributes to bradykinesia and rigidity. The histologic hallmark of PD is the presence of Lewy bodies, which are intraneuronal inclusions composed primarily of α-synuclein [8](#page=8) [9](#page=9). #### 4.1.2 Core clinical features (TRAP) The cardinal clinical features of PD are often remembered by the acronym TRAP [8](#page=8) [9](#page=9): * **Tremor:** Typically a resting tremor described as "pill-rolling," which improves with voluntary action but worsens with stress [8](#page=8) [9](#page=9). * **Rigidity:** Characterized by cogwheel rigidity (a ratchet-like resistance to passive movement) and lead-pipe stiffness [8](#page=8) [9](#page=9). * **Akinesia/Bradykinesia:** Manifests as slow movements, small steps, and freezing episodes, particularly difficulty initiating gait (first-step hesitation) [8](#page=8) [9](#page=9). * **Postural instability:** Poor postural reflexes leading to falls, often a later sign, accompanied by a stooped posture and a shuffling gait [8](#page=8) [9](#page=9). #### 4.1.3 Other features (non-motor and exam clues) Beyond the core motor symptoms, PD presents with various non-motor features and observable signs [8](#page=8) [9](#page=9): * **Facial changes:** Masked face (hypomimia) and decreased blink rate. * **Speech and swallowing:** Micrographia (small handwriting), hypophonia (soft speech), dysarthria (difficulty with articulation), and dysphagia (difficulty swallowing). * **Autonomic dysfunction:** Orthostatic hypotension, constipation, oily skin, and increased sweating. * **Neuropsychiatric symptoms:** Depression, apathy, hallucinations, and cognitive decline, which tend to appear later in the disease course. * **Progression:** Personality changes and progressive disability typically develop over 5 to 10 years [8](#page=8) [9](#page=9). #### 4.1.4 Differential diagnosis and mimics It is crucial to differentiate PD from other conditions that can mimic its symptoms [8](#page=8) [9](#page=9): * **Drug-induced parkinsonism:** Caused by medications like neuroleptics (e.g., haloperidol, chlorpromazine), metoclopramide, and reserpine. * **Vascular parkinsonism:** Resulting from multiple lacunar infarcts in the brain. * **Parkinson-plus syndromes:** A group of neurodegenerative disorders that share some features with PD but have distinct characteristics: * **Multisystem atrophy (MSA):** Characterized by early and prominent autonomic failure. * **Progressive supranuclear palsy (PSP):** Features include a vertical gaze palsy and early falls. * **Corticobasal degeneration (CBD):** Typically presents with asymmetric cortical signs. * **Young onset causes:** Wilson disease and genetic forms of parkinsonism. #### 4.1.5 Investigations While PD is primarily a clinical diagnosis, certain investigations may be employed [8](#page=8) [9](#page=9): * **Basic laboratory tests:** Thyroid function tests (TFT), vitamin B12 levels, and rapid plasma reagin (RPR) tests are used to exclude mimics. Other tests may be indicated based on clinical suspicion [8](#page=8) [9](#page=9). * **MRI brain:** Recommended if atypical features are present to rule out structural causes of parkinsonism. * **DaTscan (SPECT):** This imaging technique can help reduce diagnostic uncertainty by assessing striatal dopamine transporter levels. It shows reduced uptake in PD but normal uptake in essential tremor [8](#page=8) [9](#page=9). #### 4.1.6 Medical treatment The medical management of PD aims to alleviate symptoms and improve quality of life [8](#page=8) [9](#page=9). 1. **Levodopa + Carbidopa (Sinemet):** This is the most effective symptomatic treatment, particularly for bradykinesia and rigidity. However, long-term use (5–7 years) can lead to dyskinesias (involuntary movements) and motor fluctuations (on-off phenomena) [8](#page=8) [9](#page=9). 2. **Dopamine agonists (pramipexole, ropinirole, bromocriptine):** These are often used to delay the initiation of levodopa therapy and are beneficial in younger patients. Common side effects include impulse control disorders, somnolence, and hallucinations [8](#page=8) [9](#page=9). 3. **MAO-B inhibitors (selegiline, rasagiline):** Used as adjunct therapy or in early stages of the disease to help manage symptoms [8](#page=8) [9](#page=9). 4. **Amantadine:** Offers mild symptomatic benefit and can help manage dyskinesias in the short term [8](#page=8) [9](#page=9). 5. **Anticholinergics (trihexyphenidyl, benztropine):** Can be helpful for tremor-predominant disease in younger patients but should be avoided in the elderly or those with cognitive impairment due to potential cognitive side effects [8](#page=8) [9](#page=9). 6. **Other medications:** Amitriptyline for depression, botulinum toxin for dystonia, and treatments for orthostatic hypotension are also utilized [8](#page=8) [9](#page=9). #### 4.1.7 Surgical and advanced treatment For advanced PD with motor fluctuations and dyskinesias, more intensive treatment options are available [8](#page=8) [9](#page=9): * **Deep Brain Stimulation (DBS):** This surgical intervention is typically considered for patients with advanced PD who respond well to levodopa, generally under the age of 70 [8](#page=8) [9](#page=9). * **Continuous infusion therapies:** These include apomorphine injections and levodopa-carbidopa intestinal gel, used in selected cases to provide more consistent symptom control [8](#page=8) [9](#page=9). #### 4.1.8 Side effects and long-term issues Long-term management of PD involves addressing potential side effects and complications [8](#page=8) [9](#page=9): * **Dyskinesias:** Involuntary, choreiform movements that can occur with levodopa therapy. * **On-off motor fluctuations:** Periods of symptom improvement ("on") alternating with periods of symptom worsening ("off"). * **Psychiatric complications:** Hallucinations and impulse-control disorders. * **Medication interactions:** Worsening of symptoms with antidopaminergic drugs. #### 4.1.9 Practical ward tips and clerking Effective management of PD patients in a clinical setting requires attention to specific historical and examination findings [8](#page=8) [9](#page=9): * **History:** Focus on the asymmetry of symptoms, presence of resting tremor, response to levodopa, current medications, history of falls, and swallowing difficulties. * **Examination:** Assess for pill-rolling tremor, cogwheel rigidity, bradykinesia (using tests like finger tapping), and perform a pull test to evaluate postural instability. * **Medication review:** Crucially, check for offending drugs such as metoclopramide or antipsychotics. * **Safety:** Address fall risk, perform swallow assessments, and manage orthostatic hypotension. #### 4.1.10 High-yield mnemonics and exam bait * **TRAP:** Tremor, Rigidity, Akinesia, Postural instability [8](#page=8) [9](#page=9). * **Lewy bodies:** Histologic hallmark, composed of α-synuclein inclusions [8](#page=8) [9](#page=9). * **Levodopa:** Most effective symptomatic drug, but associated with long-term dyskinesias and on-off phenomena [8](#page=8) [9](#page=9). ### 4.2 Huntington chorea Huntington chorea (HC) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion on chromosome 4. It typically manifests between 30 and 50 years of age and follows a progressive course, usually lasting around 15 years [10](#page=10). #### 4.2.1 Pathophysiology The expanded CAG repeat leads to the production of a mutant huntingtin protein, which causes neuronal loss, particularly in the striatum (caudate nucleus). The loss of GABAergic neurons in this region contributes significantly to the characteristic choreiform movements [10](#page=10). #### 4.2.2 Clinical features The clinical presentation of HC is multifaceted [10](#page=10): * **Chorea:** Involuntary, jerky movements affecting the face, tongue, trunk, and limbs. * **Behavioral changes:** Irritability, depression, and psychosis are common. * **Cognitive decline:** Dementia is prevalent, with approximately 90% of individuals affected by age 50. * **Motor progression:** Gait becomes unsteady, eventually progressing to bradykinesia, rigidity, and incontinence. #### 4.2.3 Diagnosis Diagnosis of HC involves [10](#page=10): * **MRI:** Often reveals atrophy of the caudate heads. * **DNA testing:** Confirms the presence of a CAG repeat expansion. Genetic counseling is essential due to the autosomal dominant inheritance pattern. #### 4.2.4 Treatment Treatment for HC is primarily symptomatic [10](#page=10): * **Dopamine blockers (antipsychotics):** Used to manage chorea and psychosis. * **VMAT2 inhibitors (tetrabenazine):** Effective for chorea but require careful monitoring for depression. * **Supportive care:** Includes psychological support, speech and physical therapy, and social planning. ### 4.3 Tremor (types) Tremor is an involuntary oscillatory movement, and several types exist with distinct characteristics and causes [10](#page=10). #### 4.3.1 Physiologic tremor This is a normal phenomenon that can be amplified by factors such as anxiety, certain drugs, alcohol or drug withdrawal, and metabolic disturbances like hypoglycemia or thyroid dysfunction. Treatment involves addressing the underlying cause [10](#page=10). #### 4.3.2 Essential tremor (ET) ET is a common movement disorder, often with an autosomal dominant inheritance pattern in about one-third of cases. It is characterized by an action or postural tremor that affects the hands, head, and voice. Notably, ET often improves with alcohol consumption. Treatment options include propranolol, primidone, botulinum toxin, or deep brain stimulation for severe cases [10](#page=10). #### 4.3.3 Cerebellar (intention) tremor This tremor is typically coarse and occurs during voluntary movements, becoming more pronounced as the limb approaches its target. It is often accompanied by other cerebellar signs such as ataxia, nystagmus, and dysarthria. Causes include stroke, multiple sclerosis, tumors, and chronic alcohol abuse [10](#page=10). #### 4.3.4 Parkinsonian tremor This is the resting tremor characteristic of Parkinson disease, described as pill-rolling and improving with action. It is usually associated with bradykinesia, rigidity, and postural instability. Treatment is directed at the underlying Parkinson disease with medications like levodopa or DBS if indicated [10](#page=10). #### 4.3.5 High-yield exam points for tremor differentiation * **Huntington chorea:** Autosomal dominant inheritance, CAG repeat expansion, caudate atrophy on MRI, presenting with chorea, dementia, and psychiatric disturbances [10](#page=10). * **Essential tremor:** Improves with alcohol, managed with propranolol [10](#page=10). * **Distinguishing tremors:** * Rest tremor: Suggestive of Parkinson disease. * Intention tremor: Suggestive of cerebellar dysfunction. * Action tremor: Common in Essential Tremor. --- # Movement disorders: ataxia, restless leg syndrome, and Tourette syndrome This topic provides an overview of three distinct neurological movement disorders: ataxia, restless leg syndrome, and Tourette syndrome, covering their general characteristics, causes, clinical presentations, diagnostic investigations, and therapeutic approaches. ### 5.1 Ataxia Ataxia is characterized by gait instability, loss of balance, and impaired limb coordination [11](#page=11). #### 5.1.1 Causes Ataxia can be acquired or inherited [11](#page=11). * **Acquired causes** include alcohol abuse, vitamin deficiencies (B12, thiamine), cerebellar infarct or tumor, multiple sclerosis (MS), AIDS, and tertiary syphilis [11](#page=11). * **Inherited causes** encompass conditions like Friedreich ataxia (autosomal recessive) and Ataxia telangiectasia (autosomal recessive) [11](#page=11). #### 5.1.2 Clinical features Patients with ataxia may present with a broad-based gait, dysmetria (inability to judge distance or range of movement), dysdiadochokinesia (difficulty performing rapid alternating movements), and nystagmus (involuntary eye movements). Sensory ataxia, a subtype, is associated with a positive Romberg sign and impaired vibration and proprioception [11](#page=11). #### 5.1.3 Investigations Investigations typically include an MRI of the brain, assessment of vitamin B12 levels, thyroid function tests (TFTs), syphilis serology, and genetic testing if indicated by family history or clinical suspicion [11](#page=11). #### 5.1.4 Treatment Treatment focuses on addressing the underlying cause, such as thiamine or B12 supplementation, or cessation of alcohol intake. Neurorehabilitation and fall prevention strategies are also important components of management [11](#page=11). ### 5.2 Restless leg syndrome (RLS) Restless leg syndrome is defined by an uncomfortable urge to move the legs, particularly at rest and in the evening, which is relieved by movement [11](#page=11). #### 5.2.1 Associations RLS is often associated with iron deficiency, pregnancy, chronic kidney disease (CKD), certain medications, and neuropathy [11](#page=11). #### 5.2.2 Clinical features The hallmark clinical features are leg sensations that occur primarily in the evening or at night, leading to sleep disturbance [11](#page=11). #### 5.2.3 Investigations Investigations involve checking ferritin and iron studies, reviewing current medications, and assessing renal function [11](#page=11). #### 5.2.4 Treatment Management includes correcting iron deficiency, and if necessary, using dopamine agonists such as pramipexole or ropinirole. Gabapentin or pregabalin may also be used, alongside implementing good sleep hygiene practices [11](#page=11). ### 5.3 Tourette syndrome Tourette syndrome is characterized by multiple motor tics and at least one vocal tic, with onset typically before 21 years of age. It is frequently associated with obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) [11](#page=11). #### 5.3.1 Clinical features Motor tics can manifest as blinking, grimacing, or head jerks. Phonic tics include noises such as grunts, sniffing, or throat clearing, with coprolalia (involuntary shouting of obscenities) being a rarer presentation [11](#page=11). #### 5.3.2 Investigations The diagnosis is primarily clinical. However, if the presentation is atypical, investigations may be undertaken to rule out other conditions like seizures or tardive dyskinesia [11](#page=11). #### 5.3.3 Treatment Treatment begins with behavioral therapies, such as habit reversal training. Medications are considered if functional impairment is significant, with options including clonidine, pimozide, or haloperidol. For severe, refractory cases, deep brain stimulation (DBS) may be an option [11](#page=11). --- # Dementia: overview, differential diagnosis, and management Dementia is characterized by a progressive decline in intellect, encompassing memory, language, and executive functions, with consciousness generally preserved, and aging being the primary risk factor [12](#page=12). ### 6.1 Definition and key characteristics Dementia is defined as a progressive decline in intellect, affecting cognitive domains such as memory, language, and executive functions. A crucial characteristic is that consciousness is preserved in individuals with dementia. Age is considered the main risk factor for developing dementia [12](#page=12). ### 6.2 Differential diagnosis: reversible vs. irreversible causes The differential diagnosis of dementia involves distinguishing between potentially reversible causes and irreversible, degenerative conditions [12](#page=12). #### 6.2.1 Potentially reversible causes Several conditions can mimic dementia or contribute to cognitive impairment that may be reversible with appropriate treatment. These include [12](#page=12): * Hypothyroidism [12](#page=12). * Vitamin deficiencies, specifically vitamin B12, folate, and thiamine [12](#page=12). * Normal Pressure Hydrocephalus (NPH), which classically presents with a triad of gait disturbance, urinary incontinence, and dementia [12](#page=12). * Subdural hematoma [12](#page=12). * Depression, often referred to as pseudodementia [12](#page=12). * Medications, particularly anticholinergics, sedatives, and opiates [12](#page=12). * Infections, such as neurosyphilis, HIV, and cryptococcus [12](#page=12). > **Tip:** Always consider and investigate potentially reversible causes of cognitive decline, as their treatment can lead to significant improvement or resolution of symptoms. #### 6.2.2 Irreversible / degenerative causes The majority of dementia cases are due to irreversible, progressive neurodegenerative processes. These include [12](#page=12): * **Alzheimer disease:** This is the most common cause, accounting for approximately two-thirds of all dementia cases [12](#page=12). * **Vascular dementia:** Often resulting from multi-infarct events [12](#page=12). * **Dementia with Lewy bodies (DLB):** Characterized by visual hallucinations and parkinsonism [12](#page=12). * **Frontotemporal dementia (FTD):** Also known as Pick's disease [12](#page=12). * **Other causes:** Including Parkinson disease dementia, Huntington disease, Creutzfeldt-Jakob disease (CJD), and Progressive Multifocal Leukoencephalopathy (PML) [12](#page=12). ### 6.3 Clinical approach to diagnosis A thorough clinical approach is essential for diagnosing dementia and identifying its underlying cause [12](#page=12). #### 6.3.1 History taking A comprehensive patient history should include details about the onset and progression of symptoms, current medications, mood disturbances, and any family history of cognitive impairment [12](#page=12). #### 6.3.2 Physical and mental status examination A detailed neurological examination and a comprehensive mental status assessment, often using tools like the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA), are crucial. Gait analysis is also important, especially when considering NPH [12](#page=12). #### 6.3.3 Investigations A systematic approach to investigations helps to rule out reversible causes and identify specific degenerative patterns [12](#page=12). * **Laboratory tests:** These typically include a complete blood count (CBC), electrolytes, thyroid-stimulating hormone (TSH), vitamin B12 and folate levels, and serological tests for syphilis (RPR) and HIV, as clinically indicated [12](#page=12). * **Neuroimaging:** A CT or MRI of the brain is vital to exclude structural causes such as brain masses, subdural hematomas, or hydrocephalus [12](#page=12). * **Lumbar puncture (LP):** May be indicated for cerebrospinal fluid (CSF) analysis and biomarker assessment in specific cases [12](#page=12). ### 6.4 Management strategies Management of dementia involves addressing reversible causes, pharmacological interventions, vascular risk factor control, and comprehensive supportive care [12](#page=12). #### 6.4.1 Treatment of reversible causes The initial management step is to identify and treat any reversible causes of cognitive impairment [12](#page=12). #### 6.4.2 Medications Pharmacological treatments aim to manage symptoms and slow progression in certain types of dementia [12](#page=12). * **Cholinesterase inhibitors:** Medications such as donepezil, rivastigmine, and galantamine are commonly used for Alzheimer disease and dementia with Lewy bodies [12](#page=12). * **Memantine:** This medication is indicated for moderate to severe Alzheimer disease [12](#page=12). * **Other medications:** Antidepressants may be prescribed for co-occurring depression. Antipsychotics should be used cautiously and only if symptoms are severe, particularly in individuals with Lewy body dementia, as they can exacerbate parkinsonism and hallucinations [12](#page=12). > **Tip:** When managing depression in the elderly, Selective Serotonin Reuptake Inhibitors (SSRIs) are generally preferred over other classes of antidepressants due to a better safety profile. Avoid anticholinergic medications in elderly patients due to their potential to worsen cognitive function [12](#page=12). #### 6.4.3 Vascular risk control For patients with vascular dementia or those at risk, aggressive management of vascular risk factors is crucial. This includes controlling hypertension (HTN), diabetes mellitus (DM), and encouraging smoking cessation [12](#page=12). #### 6.4.4 Supportive care Comprehensive supportive care is a cornerstone of dementia management, focusing on improving quality of life for both the patient and their caregivers. This includes [12](#page=12): * Occupational therapy (OT) and physical therapy (PT) to maintain function [12](#page=12). * Caregiver support and education [12](#page=12). * Safety planning, including home modifications and supervision [12](#page=12). * Advanced care planning to ensure patient wishes are respected [12](#page=12). > **Tip:** Dementia management often requires a multidisciplinary approach involving neurologists, geriatricians, neuropsychologists, social workers, and therapists to address the complex needs of affected individuals and their families [12](#page=12). ### 6.5 Special syndromes and red flags Certain clinical presentations can indicate specific types of dementia or urgent conditions requiring prompt recognition [12](#page=12). * **Normal Pressure Hydrocephalus (NPH):** Characterized by the triad of gait disturbance, urinary incontinence, and dementia. Treatment may involve CSF tapping or a shunt procedure [12](#page=12). * **Lewy Body Dementia (LBD):** Key features include visual hallucinations, parkinsonism, and fluctuations in cognition. Neuroleptics (antipsychotics) should be avoided due to potential severe adverse reactions [12](#page=12). * **Rapidly progressive dementia:** A rapid onset or progression of dementia symptoms raises concern for conditions like Creutzfeldt-Jakob disease (CJD), metastatic brain disease, or autoimmune encephalitis, which require urgent investigation and management [12](#page=12). ### 6.6 High-yield exam points Key takeaways for examination purposes emphasize the most common causes, essential diagnostic steps, and crucial management principles [12](#page=12). * Alzheimer disease is the most prevalent cause of dementia, accounting for approximately 66% of cases [12](#page=12). * Always investigate reversible causes, such as vitamin deficiencies (B12) and thyroid dysfunction (TSH), as well as medication side effects [12](#page=12). * In elderly patients, avoid anticholinergic medications and opt for SSRIs for depression. Referral for multidisciplinary care is often recommended [12](#page=12). --- # Alzheimer disease: risk factors, pathophysiology, and clinical presentation Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by memory and cortical dysfunction, representing the most common cause of dementia, accounting for approximately 66% of all cases. The typical onset is after age 65, although early-onset familial forms also exist [13](#page=13). ### 7.1 Risk factors and epidemiology Several factors contribute to the risk of developing Alzheimer disease. #### 7.1.1 Age Age is considered the strongest risk factor for AD [13](#page=13). #### 7.1.2 Genetics and family history Family history and genetic predisposition play a significant role [13](#page=13). * **Early-onset familial AD** is associated with mutations in specific genes: * APP (Amyloid Precursor Protein) on chromosome 21 [13](#page=13). * PSEN1 (Presenilin 1) on chromosome 14 [13](#page=13). * PSEN2 (Presenilin 2) on chromosome 1 [13](#page=13). * **Late-onset AD** has risk alleles, such as APOE ε4, which increase the likelihood of developing the disease but are not deterministic [13](#page=13). * Individuals with **Down syndrome (trisomy 21)** have an increased risk of early-onset AD [13](#page=13). #### 7.1.3 Modifiable risk factors Modifiable risk factors that can influence AD risk include: * Vascular disease [13](#page=13). * Hypertension (HTN) [13](#page=13). * Diabetes Mellitus (DM) [13](#page=13). * Smoking [13](#page=13). * Low educational attainment [13](#page=13). * Sedentary lifestyle [13](#page=13). ### 7.2 Pathophysiology The core pathological mechanisms driving Alzheimer disease involve the accumulation of abnormal proteins and subsequent neuronal damage. #### 7.2.1 Amyloid cascade hypothesis This hypothesis posits that the abnormal cleavage of Amyloid Precursor Protein (APP) leads to the accumulation of Amyloid-β (Aβ) peptides, which aggregate into extracellular plaques. Soluble oligomers of Aβ are considered particularly toxic to synapses, leading to synaptic dysfunction [13](#page=13). #### 7.2.2 Tau pathology Tau protein is involved in stabilizing microtubules within neurons. In AD, tau becomes hyperphosphorylated, leading to the formation of neurofibrillary tangles (NFTs) inside neurons. The burden of NFTs correlates with neuronal loss and the progression of the disease [13](#page=13). #### 7.2.3 Other contributing mechanisms * **Neuroinflammation and microglial activation** are thought to contribute to disease progression [13](#page=13). * **Neurotransmitter deficits**, notably a loss of acetylcholine due to degeneration of cholinergic neurons in the nucleus basalis, significantly impair memory [13](#page=13). * **Network disconnection** resulting from hippocampal and cortical atrophy, particularly in the medial temporal lobe, is a key feature [13](#page=13). ### 7.3 Neuropathology Autopsy findings in Alzheimer disease are characterized by: * Extracellular amyloid-β plaques, which can be diffuse or neuritic [13](#page=13). * Intracellular neurofibrillary tangles composed of tau protein [13](#page=13). * Neuronal loss and gliosis, especially in the hippocampus and cortex [13](#page=13). * Macroscopically, there is cortical atrophy and enlarged ventricles (ex vacuo dilatation) [13](#page=13). ### 7.4 Clinical presentation and stages The clinical presentation of AD progresses through several stages: #### 7.4.1 Prodromal/Preclinical stage This stage may involve subjective memory complaints and mild cognitive changes, with abnormal biomarkers potentially detectable before overt symptoms appear [13](#page=13). #### 7.4.2 Early (Mild) stage * **Episodic memory impairment** is prominent, characterized by difficulties in learning new information [13](#page=13). * Patients may experience word-finding problems and subtle executive dysfunction [13](#page=13). * Personality changes and decreased concentration can also be observed [13](#page=13). #### 7.4.3 Middle (Moderate) stage * Memory deficits worsen, leading to disorientation regarding time and place [13](#page=13). * Visuospatial deficits emerge, such as getting lost [13](#page=13). * Instrumental activities of daily living (IADLs), like managing finances or medications, become impaired [13](#page=13). * Denial of the illness is common, and some individuals may experience paranoid delusions or hallucinations [13](#page=13). #### 7.4.4 Late (Severe) stage * There is a significant loss of basic activities of daily living (ADLs) [13](#page=13). * Language skills regress substantially [13](#page=13). * Incontinence becomes prevalent [13](#page=13). * Individuals are often bed-bound, exhibiting severe cognitive and motor decline [13](#page=13). #### 7.4.5 Course and prognosis The average survival after diagnosis is typically 5 to 10 years, though this is variable. Death is often a consequence of complications such as infection, aspiration, or other comorbid conditions [13](#page=13). ### 7.5 Key clinical features A checklist of key clinical features to assess in patients with suspected AD includes: * **Memory:** Primarily episodic memory impairment (difficulty with new learning) early on, with procedural memory often preserved longer [13](#page=13). * **Language:** Anomia (difficulty finding words), circumlocution (using descriptive phrases), and empty speech [13](#page=13). * **Visuospatial dysfunction:** Difficulty navigating, poor map reading, and getting lost [13](#page=13). * **Executive dysfunction:** Impairments in planning, decision-making, and multitasking [13](#page=13). * **Behavioral/psychiatric symptoms:** Apathy, depression, irritability, and psychosis (hallucinations, delusions), which tend to appear later in the disease [13](#page=13). * **Neurologic examination:** Generally, early AD does not present with focal neurological deficits; their presence may suggest alternative diagnoses [13](#page=13). > **Tip:** When evaluating a patient with suspected dementia, always consider the possibility of reversible causes before concluding an AD diagnosis. This includes checking for thyroid dysfunction, B12 deficiency, depression, normal pressure hydrocephalus (NPH), subdural hematomas, adverse medication effects (especially anticholinergics and sedatives), and infections like syphilis or HIV [13](#page=13). --- # Dementia with Lewy bodies and delirium This section provides a comprehensive overview of Dementia with Lewy Bodies (DLB), detailing its core clinical triad and management strategies, and offers an in-depth exploration of Delirium, including its definition, significant risk factors, common causes summarized by the mnemonic "MOVE STUPID," characteristic clinical features, diagnostic approaches, and treatment modalities. ### 8.1 Dementia with Lewy bodies (DLB) Dementia with Lewy Bodies (DLB) is a neurodegenerative disease characterized by the presence of Lewy bodies, which are abnormal aggregations of alpha-synuclein protein, in the cerebral cortex. It presents with a combination of cognitive and parkinsonian features and can often have a more rapid progression than other dementias, frequently presenting with early visual hallucinations [15](#page=15). #### 8.1.1 Key clinical triad of DLB The diagnosis of DLB relies on a specific clinical triad [15](#page=15): * **Fluctuating cognition or alertness:** Patients experience significant variations in their cognitive state and overall alertness [15](#page=15). * **Recurrent well-formed visual hallucinations:** These are typically vivid and detailed visual perceptions that occur repeatedly [15](#page=15). * **Spontaneous parkinsonism:** This includes the presence of parkinsonian motor symptoms such as rigidity and bradykinesia (slowness of movement) [15](#page=15). #### 8.1.2 Diagnosis and management of DLB The diagnosis of DLB is primarily clinical. A DaTscan, which is a neuroimaging technique that visualizes dopamine transporters, can be used to support the diagnosis. Cholinesterase inhibitors, such as donepezil and rivastigmine, are generally helpful in managing the cognitive symptoms of DLB [15](#page=15). > **Tip:** Patients with DLB often exhibit severe sensitivity to neuroleptic medications. It is crucial to avoid typical antipsychotics, such as haloperidol, due to the risk of serious adverse reactions. Management of parkinsonism should be cautious, and medications like selegiline may be considered [15](#page=15). ### 8.2 Delirium Delirium is an acute disturbance of cognition and attention characterized by a fluctuating level of consciousness, typically caused by an underlying medical or systemic issue, and is usually reversible [16](#page=16) [17](#page=17). #### 8.2.1 Core concepts of delirium Delirium impacts both consciousness and cognition. Consciousness is primarily regulated by the brainstem, specifically the reticular activating system, while cognition is associated with the cerebral cortex. In delirium, both of these systems are affected, leading to reduced arousal, impaired attention, and general confusion [16](#page=16) [17](#page=17). #### 8.2.2 Risk factors for delirium Several factors increase an individual's susceptibility to developing delirium [16](#page=16) [17](#page=17): * **Advanced age:** Older individuals are at higher risk [16](#page=16) [17](#page=17). * **Pre-existing cognitive impairment:** This is the strongest risk factor [16](#page=16) [17](#page=17). * **Polypharmacy:** The use of multiple medications increases risk [16](#page=16) [17](#page=17). * **Hospitalization or intensive care unit (ICU) stay, or post-operative status:** These settings can be disorienting and stressful [16](#page=16) [17](#page=17). * **Sensory impairment:** Vision or hearing loss can contribute to delirium [16](#page=16) [17](#page=17). #### 8.2.3 Causes of delirium: The "MOVE STUPID" mnemonic The mnemonic "MOVE STUPID" is a useful tool for recalling the diverse causes of delirium [16](#page=16) [17](#page=17): * **M** – Metabolic: Electrolyte imbalances, hypercalcemia [16](#page=16) [17](#page=17). * **O** – Oxygen: Hypoxia, anemia [16](#page=16) [17](#page=17). * **V** – Vascular: Myocardial infarction (MI), cerebrovascular accident (CVA) [16](#page=16) [17](#page=17). * **E** – Endocrine: Hypoglycemia, thyroid dysfunction [16](#page=16) [17](#page=17). * **S** – Seizure: Post-ictal state following a seizure [16](#page=16) [17](#page=17). * **T** – Trauma: Head injury, subdural hematoma [16](#page=16) [17](#page=17). * **U** – Uremia: Renal failure [16](#page=16) [17](#page=17). * **P** – Psychiatric: Though often a diagnosis of exclusion, severe psychiatric conditions can manifest as delirium [16](#page=16) [17](#page=17). * **I** – Infectious: Urinary tract infections (UTIs), pneumonia, sepsis [16](#page=16) [17](#page=17). * **D** – Drugs: Opiates, benzodiazepines, anticholinergics, alcohol (withdrawal or intoxication) [16](#page=16) [17](#page=17). #### 8.2.4 Clinical features of delirium Key clinical features of delirium include [16](#page=16) [17](#page=17): * **Rapid onset:** Symptoms typically develop over hours to days [16](#page=16) [17](#page=17). * **Fluctuating course:** The severity of symptoms can change significantly throughout the day [16](#page=16) [17](#page=17). * **Inattention:** Difficulty focusing or maintaining attention [16](#page=16) [17](#page=17). * **Disorientation:** Confusion regarding time, place, or person [16](#page=16) [17](#page=17). * **Altered awareness:** A reduced or altered level of consciousness [16](#page=16) [17](#page=17). * **Visual hallucinations:** Experiencing visual perceptions that are not real [16](#page=16) [17](#page=17). * **Hyperactive delirium:** Characterized by agitation and restlessness [16](#page=16) [17](#page=17). * **Hypoactive delirium:** In this form, the patient may be quiet and sleepy, which can lead to it being missed [16](#page=16) [17](#page=17). * **Sundowning:** Symptoms may worsen at night [16](#page=16) [17](#page=17). #### 8.2.5 Delirium versus dementia: Key distinctions Differentiating delirium from dementia is crucial, especially in an exam context [16](#page=16) [17](#page=17): | Feature | Delirium | Dementia | | :---------------- | :---------------------- | :------------------------- | | **Onset** | Acute (hours to days) | Insidious (months to years) | | **Course** | Fluctuating | Progressive | | **Consciousness** | Altered | Preserved (initially) | | **Hallucinations**| Common | Less common | | **Reversibility** | Often reversible | Generally irreversible | #### 8.2.6 Diagnosis of delirium The diagnosis of delirium is primarily clinical. The Confusion Assessment Method (CAM) is a validated tool that assesses for delirium based on four key features [16](#page=16) [17](#page=17): 1. Acute onset and fluctuating course. 2. Inattention. 3. Disorganized thinking OR altered level of consciousness. > **Tip:** It is paramount to always search for and identify the underlying reversible causes of delirium [16](#page=16) [17](#page=17). #### 8.2.7 Workup for delirium A thorough workup is essential to identify the underlying cause(s) of delirium [16](#page=16) [17](#page=17): * Complete Blood Count (CBC) [16](#page=16) [17](#page=17). * Electrolytes and glucose levels [16](#page=16) [17](#page=17). * Blood Urea Nitrogen (BUN) and creatinine [16](#page=16) [17](#page=17). * Urinalysis [16](#page=16) [17](#page=17). * Chest X-ray [16](#page=16) [17](#page=17). * CT scan of the brain, particularly if focal neurological signs are present or if trauma is suspected [16](#page=16) [17](#page=17). * A comprehensive medication review is critical [16](#page=16) [17](#page=17). #### 8.2.8 Treatment of delirium The management of delirium involves a multi-faceted approach [16](#page=16) [17](#page=17): 1. **Treat the underlying cause:** This is the most important step in management [16](#page=16) [17](#page=17). 2. **Non-pharmacological interventions (first-line):** * Frequent reorientation of the patient [16](#page=16) [17](#page=17). * Having family members or familiar individuals at the bedside [16](#page=16) [17](#page=17). * Normalizing the sleep-wake cycle [16](#page=16) [17](#page=17). * Ensuring adequate daylight exposure [16](#page=16) [17](#page=17). * Correcting any sensory deficits, such as vision or hearing impairments [16](#page=16) [17](#page=17). 3. **Medications (only if necessary):** * Haloperidol may be used for severe agitation [16](#page=16) [17](#page=17). * Physical restraints should be avoided if possible [16](#page=16) [17](#page=17). * Sedatives are considered a last resort due to potential for worsening confusion [16](#page=16) [17](#page=17). --- # Coma and its management Coma represents a profound state of depressed consciousness where a patient is entirely unresponsive to all stimuli, indicating a more severe impairment than delirium or stupor [18](#page=18) [19](#page=19) [20](#page=20). ### 9.1 Pathophysiology of consciousness Consciousness is a dual function composed of arousal and awareness. Arousal is primarily mediated by the brainstem, specifically the reticular activating system, while awareness is a function of the cerebral cortex. Coma ensues when both these systems are significantly impaired [18](#page=18) [19](#page=19) [20](#page=20). ### 9.2 Causes of coma The causes of coma can be broadly categorized into structural brain lesions and global brain dysfunction, with psychiatric mimics also being important to consider [18](#page=18) [19](#page=19) [20](#page=20). #### 9.2.1 Structural brain lesions These typically involve bilateral damage or unilateral lesions with significant mass effect leading to herniation. Common examples include [18](#page=18) [19](#page=19) [20](#page=20): * Intracranial hemorrhage [18](#page=18) [19](#page=19) [20](#page=20). * Large stroke [18](#page=18) [19](#page=19) [20](#page=20). * Brain tumor [18](#page=18) [19](#page=19) [20](#page=20). * Trauma [18](#page=18) [19](#page=19) [20](#page=20). A key clinical clue for structural lesions is the presence of asymmetric motor findings [18](#page=18) [19](#page=19) [20](#page=20). #### 9.2.2 Global brain dysfunction This is the more common cause of coma and arises from widespread impairment of brain function. Examples include [18](#page=18) [19](#page=19) [20](#page=20): * Metabolic disturbances such as hypoglycemia, hypercalcemia, and uremia [18](#page=18) [19](#page=19) [20](#page=20). * Hypoxia or hypercapnia [18](#page=18) [19](#page=19) [20](#page=20). * Drug intoxication, particularly opioids and sedatives [18](#page=18) [19](#page=19) [20](#page=20). * Severe infections like sepsis [18](#page=18) [19](#page=19) [20](#page=20). Symmetric motor findings are often indicative of global brain dysfunction [18](#page=18) [19](#page=19) [20](#page=20). #### 9.2.3 Psychiatric mimics While less common, conditions like conversion disorder and malingering can present with unresponsiveness that mimics coma [18](#page=18) [19](#page=19) [20](#page=20). ### 9.3 Differential diagnosis: MOVE STUPID mnemonic A useful mnemonic for remembering the broad differential diagnosis of coma is MOVE STUPID [18](#page=18) [19](#page=19) [20](#page=20): * **M** – Metabolic * **O** – Oxygen (hypoxia) * **V** – Vascular (MI, CVA) * **E** – Endocrine (hypoglycemia) * **S** – Seizure * **T** – Trauma * **U** – Uremia * **P** – Psychiatric * **I** – Infection * **D** – Drugs ### 9.4 Initial approach to the comatose patient The initial management of a comatose patient follows a systematic approach [18](#page=18) [19](#page=19) [20](#page=20): 1. **ABCs:** Ensure Airway, Breathing, and Circulation are stable. 2. **Trauma consideration:** Assume trauma in all cases and immobilize the cervical spine. 3. **Glasgow Coma Scale (GCS):** Assess and repeat the GCS serially to monitor for changes. 4. **Rapid neurologic exam:** Perform a focused neurologic examination. ### 9.5 Key neurologic clues in coma assessment Several neurologic findings can provide crucial diagnostic information [18](#page=18) [19](#page=19) [20](#page=20): #### 9.5.1 Pupils * **Pinpoint pupils:** Suggest opioid intoxication or intracranial hemorrhage [18](#page=18) [19](#page=19) [20](#page=20). * **Bilateral fixed and dilated pupils:** Indicate severe anoxia [18](#page=18) [19](#page=19) [20](#page=20). * **Unilateral dilated pupil:** Can signify compression of the oculomotor nerve (CN III), often due to herniation [18](#page=18) [19](#page=19) [20](#page=20). * **Reactive and symmetric pupils:** Suggest the brainstem is intact [18](#page=18) [19](#page=19) [20](#page=20). #### 9.5.2 Motor Exam * **Asymmetry:** Points towards a structural lesion [18](#page=18) [19](#page=19) [20](#page=20). * **Symmetric findings:** More suggestive of a metabolic or toxic cause [18](#page=18) [19](#page=19) [20](#page=20). #### 9.5.3 Brainstem reflexes Assessment of brainstem reflexes is vital: * Pupillary light reflex [18](#page=18) [19](#page=19) [20](#page=20). * Doll's eyes (oculocephalic reflex) [18](#page=18) [19](#page=19) [20](#page=20). * Corneal reflex [18](#page=18) [19](#page=19) [20](#page=20). * Gag reflex [18](#page=18) [19](#page=19) [20](#page=20). ### 9.6 Investigations A combination of laboratory tests and imaging is used to determine the cause of coma [18](#page=18) [19](#page=19) [20](#page=20): #### 9.6.1 Laboratory investigations * Complete Blood Count (CBC) [18](#page=18) [19](#page=19) [20](#page=20). * Electrolytes [18](#page=18) [19](#page=19) [20](#page=20). * Glucose [18](#page=18) [19](#page=19) [20](#page=20). * Calcium [18](#page=18) [19](#page=19) [20](#page=20). * Arterial Blood Gas (ABG) [18](#page=18) [19](#page=19) [20](#page=20). * Toxicology screen [18](#page=18) [19](#page=19) [20](#page=20). #### 9.6.2 Imaging * **CT head:** Urgent imaging is typically the first step [18](#page=18) [19](#page=19) [20](#page=20). * **MRI:** May be performed if further detail is needed [18](#page=18) [19](#page=19) [20](#page=20). #### 9.6.3 Lumbar Puncture (LP) An LP is indicated if meningitis or subarachnoid hemorrhage is suspected [18](#page=18) [19](#page=19) [20](#page=20). ### 9.7 Treatment strategies Management involves immediate interventions, correction of reversible causes, and specific management for herniation [18](#page=18) [19](#page=19) [20](#page=20). #### 9.7.1 Immediate interventions ("Do first, think later") * Administer oxygen [18](#page=18) [19](#page=19) [20](#page=20). * Establish intravenous (IV) access [18](#page=18) [19](#page=19) [20](#page=20). * Administer Naloxone for suspected opioid overdose [18](#page=18) [19](#page=19) [20](#page=20). * Administer Dextrose for hypoglycemia [18](#page=18) [19](#page=19) [20](#page=20). * Administer Thiamine BEFORE glucose in patients with a history of alcoholism to prevent Wernicke's encephalopathy [18](#page=18) [19](#page=19) [20](#page=20). #### 9.7.2 Correction of reversible causes * Normalize blood pressure [18](#page=18) [19](#page=19) [20](#page=20). * Correct electrolyte imbalances [18](#page=18) [19](#page=19) [20](#page=20). * Normalize body temperature [18](#page=18) [19](#page=19) [20](#page=20). #### 9.7.3 Herniation management Management aims to lower intracranial pressure (ICP) [18](#page=18) [19](#page=19) [20](#page=20): * Elevate the head of the bed [18](#page=18) [19](#page=19) [20](#page=20). * Consider osmotherapy (e.g., mannitol or hypertonic saline) [18](#page=18) [19](#page=19) [20](#page=20). * Intubation and mechanical ventilation may be necessary [18](#page=18) [19](#page=19) [20](#page=20). ### 9.8 Important mimics of coma #### 9.8.1 Locked-in Syndrome This is a critical condition to distinguish from true coma. Patients are fully conscious but have complete paralysis, with preserved blinking and vertical eye movements. It is typically caused by a ventral pontine infarction or hemorrhage [18](#page=18) [19](#page=19) [20](#page=20). ### 9.9 Prognostic states Following coma, certain persistent states of consciousness can emerge: #### 9.9.1 Brain Death Brain death signifies a complete and irreversible cessation of all brain and brainstem function. Key indicators include [18](#page=18) [19](#page=19) [20](#page=20): * No brain or brainstem function [18](#page=18) [19](#page=19) [20](#page=20). * No spontaneous breathing [18](#page=18) [19](#page=19) [20](#page=20). * Absence of reflexes [18](#page=18) [19](#page=19) [20](#page=20). * EEG silence [18](#page=18) [19](#page=19) [20](#page=20). * Legally considered dead [18](#page=18) [19](#page=19) [20](#page=20). #### 9.9.2 Persistent Vegetative State In a persistent vegetative state, patients may have their eyes open and exhibit random movements, but there is no awareness. The brainstem remains intact, but the cerebral cortex is not functioning with awareness. This state is distinct from brain death [18](#page=18) [19](#page=19) [20](#page=20). --- # Demyelinating diseases of the central nervous system: Multiple Sclerosis Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease affecting the central nervous system (CNS) [21](#page=21) [22](#page=22) [23](#page=23). ### 10.1 General characteristics #### 10.1.1 Definition Multiple sclerosis is defined as a chronic immune-mediated demyelinating disease of the CNS that affects both the brain and spinal cord, but not the peripheral nervous system (PNS) [21](#page=21) [22](#page=22) [23](#page=23). #### 10.1.2 Pathology The hallmark of MS pathology is the selective demyelination of CNS white matter, leading to multifocal plaques that are scattered in both time and space. Classic plaque locations include the angles of the lateral ventricles. Commonly involved tracts include the pyramidal tracts, cerebellar pathways, medial longitudinal fasciculus (MLF), optic nerve, and posterior columns [21](#page=21) [22](#page=22) [23](#page=23). #### 10.1.3 Epidemiology MS typically affects young adults, with onset usually occurring in their 20s and 30s. It is more common in women than men, with a ratio of 2 to 3 times greater incidence [21](#page=21) [22](#page=22) [23](#page=23). #### 10.1.4 Etiology The etiology of MS is unknown and is considered multifactorial, involving a combination of genetic, environmental, and immune factors [21](#page=21) [22](#page=22) [23](#page=23). ### 10.2 Clinical features #### 10.2.1 Sensory symptoms Sensory symptoms are the most common initial presentation of MS. These include paresthesias (abnormal sensations) and decreased sensation, often affecting the upper or lower limbs [21](#page=21) [22](#page=22) [23](#page=23). #### 10.2.2 Fatigue Fatigue is a very common and often disabling symptom in individuals with MS [21](#page=21) [22](#page=22) [23](#page=23). #### 10.2.3 Motor symptoms Motor symptoms are typically UMN (upper motor neuron) signs and can include weakness and spasticity, leading to progressive paresis [21](#page=21) [22](#page=22) [23](#page=23). #### 10.2.4 Visual disturbances Visual disturbances are a significant feature of MS. These can manifest as [21](#page=21) [22](#page=22) [23](#page=23): * **Optic neuritis:** Characterized by painful monocular vision loss, pain with eye movement, and a central scotoma [21](#page=21) [22](#page=22) [23](#page=23). * **Internuclear ophthalmoplegia (INO):** This occurs due to a lesion in the MLF and results in an ipsilateral adduction defect and contralateral nystagmus [21](#page=21) [22](#page=22) [23](#page=23). #### 10.2.5 Cerebellar involvement When the cerebellum is involved, symptoms can include ataxia, intention tremor, and dysarthria [21](#page=21) [22](#page=22) [23](#page=23). #### 10.2.6 Autonomic dysfunction Autonomic dysfunction in MS can present as urinary urgency or incontinence, impotence, and constipation [21](#page=21) [22](#page=22) [23](#page=23). #### 10.2.7 Cerebral involvement Cerebral involvement, often seen in later stages of the disease, can lead to memory loss, personality changes, and anxiety or depression [21](#page=21) [22](#page=22) [23](#page=23). #### 10.2.8 Neuropathic pain Neuropathic pain can occur in MS, manifesting as hyperesthesia or trigeminal neuralgia [21](#page=21) [22](#page=22) [23](#page=23). ### 10.3 Course of disease #### 10.3.1 Clinically isolated syndrome (CIS) Clinically isolated syndrome is the first neurologic episode suggestive of demyelination, which may or may not progress to MS [21](#page=21) [22](#page=22) [23](#page=23). #### 10.3.2 Relapsing-remitting MS (RRMS) Relapsing-remitting MS is the most common form of the disease. It is characterized by relapses (new or worsening neurological symptoms) followed by periods of recovery. Residual deficits from relapses can create a new baseline of disability [21](#page=21) [22](#page=22) [23](#page=23). #### 10.3.3 Secondary progressive MS (SPMS) Secondary progressive MS begins as RRMS, followed by a gradual progression of disability [21](#page=21) [22](#page=22) [23](#page=23). #### 10.3.4 Primary progressive MS (PPMS) Primary progressive MS involves a steady progression of disability from the onset of symptoms, accounting for approximately 10% of cases [21](#page=21) [22](#page=22) [23](#page=23). ### 10.4 Diagnosis #### 10.4.1 Clinical diagnosis The initial clinical diagnosis of MS is based on the occurrence of relapsing neurologic deficits in young adults [21](#page=21) [22](#page=22) [23](#page=23). #### 10.4.2 McDonald criteria . The McDonald criteria, updated in 2017, are essential for diagnosing MS. They require evidence of CNS lesions separated by both time and space [21](#page=21) [22](#page=22) [23](#page=23). #### 10.4.3 MRI Magnetic Resonance Imaging (MRI) is the most sensitive diagnostic tool for MS. Approximately 90% of individuals with MS show abnormalities on MRI. It is important to note that the number of lesions on MRI does not necessarily correlate with disease severity [21](#page=21) [22](#page=22) [23](#page=23). #### 10.4.4 CSF analysis Cerebrospinal fluid (CSF) analysis can reveal oligoclonal IgG bands in approximately 90% of MS patients [21](#page=21) [22](#page=22) [23](#page=23). #### 10.4.5 Evoked potentials Evoked potentials can show slowed nerve conduction, which is indicative of demyelination [21](#page=21) [22](#page=22) [23](#page=23). ### 10.5 Treatment #### 10.5.1 Acute relapse For acute relapses, high-dose intravenous corticosteroids are the primary treatment. Plasma exchange may be considered if the relapse is steroid-refractory [21](#page=21) [22](#page=22) [23](#page=23). #### 10.5.2 Disease-modifying therapy (DMT) Disease-modifying therapies aim to reduce the frequency and severity of relapses and slow disease progression. These include: * Interferon-β [21](#page=21) [22](#page=22) [23](#page=23). * Glatiramer acetate [21](#page=21) [22](#page=22) [23](#page=23). * Natalizumab (associated with a risk of progressive multifocal leukoencephalopathy - PML) [21](#page=21) [22](#page=22) [23](#page=23). * Oral agents such as Fingolimod, Dimethyl fumarate, and Teriflunomide [21](#page=21) [22](#page=22) [23](#page=23). #### 10.5.3 Symptomatic treatment Symptomatic treatment targets specific symptoms experienced by the patient: * **Spasticity:** Managed with medications like Baclofen or Dantrolene [21](#page=21) [22](#page=22) [23](#page=23). * **Neuropathic pain:** Treated with agents such as Gabapentin or Carbamazepine [21](#page=21) [22](#page=22) [23](#page=23). * **Depression:** Should be treated if present [21](#page=21) [22](#page=22) [23](#page=23). > **Tip:** Intravenous corticosteroids shorten the duration of relapses but do not improve the long-term outcome of MS [21](#page=21) [22](#page=22) [23](#page=23). > **Tip:** There is currently no cure for MS [21](#page=21) [22](#page=22) [23](#page=23). > **Tip:** A high suspicion for MS should be maintained in young adults presenting with relapsing neurological deficits, especially if accompanied by MRI and CSF abnormalities suggestive of demyelination. Optic neuritis and internuclear ophthalmoplegia are classic clinical clues [21](#page=21) [22](#page=22) [23](#page=23). --- # Peripheral nervous system disorders: Guillain-Barré Syndrome and Myasthenia Gravis This section outlines two distinct peripheral nervous system disorders: Guillain-Barré Syndrome (GBS), an acute inflammatory demyelinating polyneuropathy, and Myasthenia Gravis (MG), an autoimmune disorder affecting the neuromuscular junction. ### 11.1 Guillain-Barré Syndrome (GBS) #### 11.1.1 Definition and overview Guillain-Barré Syndrome (GBS) is characterized as an acute inflammatory demyelinating polyneuropathy (AIDP). It is an immune-mediated condition that targets the myelin sheath of peripheral nerves, primarily affecting motor nerves while leaving the central nervous system (CNS) uninvolved [24](#page=24) [25](#page=25). #### 11.1.2 Triggers and etiology GBS often follows an infection, typically occurring 1-3 weeks prior to symptom onset. The most common infectious trigger is *Campylobacter jejuni*, but other associated infections include Cytomegalovirus (CMV), Mycoplasma, Hepatitis, and HIV. Other less common associations include Hodgkin disease, Systemic Lupus Erythematosus (SLE), post-surgery, and HIV seroconversion. The underlying pathogenesis is believed to involve molecular mimicry, where the immune system mistakenly attacks myelin [24](#page=24) [25](#page=25). #### 11.1.3 Clinical features The hallmark of GBS is weakness, which typically has an abrupt onset and progresses as a rapidly ascending paralysis. This weakness is usually symmetric and moves from distal to proximal muscle groups. Critically, GBS can involve the facial, bulbar, and respiratory muscles, posing a significant risk of respiratory arrest [24](#page=24) [25](#page=25). While limb pain is common, true sensory loss is not typical. Importantly, mentation and sphincter control remain intact [24](#page=24) [25](#page=25). Autonomic dysfunction is a serious complication that can manifest as arrhythmias, tachycardia, postural hypotension, and blood pressure instability, which can be fatal [24](#page=24) [25](#page=25). > **Tip:** The rapidly ascending paralysis is a key clinical clue for GBS. #### 11.1.4 Diagnosis Diagnosis relies on a combination of clinical presentation, cerebrospinal fluid (CSF) analysis, and nerve conduction studies (NCS) [24](#page=24) [25](#page=25). * **CSF analysis:** A characteristic finding is an elevated protein level with a normal cell count, a phenomenon known as albuminocytologic dissociation [24](#page=24) [25](#page=25). * **Nerve conduction studies (NCS):** These studies may show a decreased motor nerve conduction velocity [24](#page=24) [25](#page=25). #### 11.1.5 Treatment Treatment focuses on supportive care and disease-modifying therapies. * **Supportive care:** This is the first priority and involves close monitoring of pulmonary function. ICU admission and mechanical ventilation may be necessary if respiratory compromise occurs [24](#page=24) [25](#page=25). * **Disease-modifying therapy:** Intravenous Immunoglobulin (IVIG) is a primary treatment, and plasmapheresis may be used for severe or progressive cases [24](#page=24) [25](#page=25). > ❌ **Crucial Exam Point:** Steroids are NOT helpful in treating GBS and represent a common exam trap [24](#page=24) [25](#page=25). #### 11.1.6 Prognosis The prognosis for GBS is generally good, with recovery typically occurring within 1-3 weeks. However, in some cases, symptoms may persist for longer than 6 weeks, indicating a chronic or relapsing course, and full recovery can take months. Approximately 5% of patients may experience mortality due to complications such as respiratory failure, arrhythmias, or pneumonia [24](#page=24) [25](#page=25). #### 11.1.7 Exam pearls * Ascending paralysis coupled with a recent infection strongly suggests GBS [24](#page=24) [25](#page=25). * Look for elevated protein with normal cells in the CSF [24](#page=24) [25](#page=25). * Consider ICU admission early for respiratory monitoring [24](#page=24) [25](#page=25). * Treatment is limited to IVIG or plasmapheresis; steroids are ineffective [24](#page=24) [25](#page=25). ### 11.2 Myasthenia Gravis (MG) #### 11.2.1 Definition Myasthenia Gravis (MG) is an autoimmune disorder affecting the neuromuscular junction (NMJ), characterized by antibodies directed against postsynaptic nicotinic acetylcholine (ACh) receptors. This leads to fatigable skeletal muscle weakness [26](#page=26) [27](#page=27). #### 11.2.2 Pathophysiology In MG, there is a reduced number of functional ACh receptors at the NMJ. While ACh is released normally from the nerve, repeated muscle use leads to a functional depletion of available ACh binding sites due to the antibody blockade. Consequently, the end-plate potential is insufficient, causing the muscle to fail to contract [26](#page=26) [27](#page=27). > **Example:** Imagine a lock (ACh receptor) with a key (ACh). In MG, antibodies act like gum in the lock, preventing the key from turning, even though the key is being produced. Repeated attempts to open the lock with gum in it will fail. #### 11.2.3 Epidemiology MG affects women more commonly in their 20s-30s and men in their 50s-70s. Overall, it is more prevalent in women [26](#page=26) [27](#page=27). #### 11.2.4 Clinical features The core feature of MG is fatigable muscle weakness that worsens with activity and improves with rest. Sensation and reflexes are preserved [26](#page=26) [27](#page=27). * **Ocular:** This is the most common initial symptom and includes ptosis (drooping eyelid), diplopia (double vision), and blurred vision [26](#page=26) [27](#page=27). * **Bulbar:** Symptoms include dysarthria (difficulty speaking), dysphagia (difficulty swallowing), and chewing fatigue [26](#page=26) [27](#page=27). * **Limb Muscles:** Weakness is typically proximal and may be asymmetric [26](#page=26) [27](#page=27). **Myasthenic Crisis:** This is a life-threatening complication characterized by severe generalized weakness, including fatigue of the diaphragm and intercostal muscles, leading to respiratory failure requiring ICU admission [26](#page=26) [27](#page=27). #### 11.2.5 Diagnosis Diagnostic tools include: * **ACh receptor antibodies:** This is the test of choice, though approximately 20% of patients may be antibody-negative [26](#page=26) [27](#page=27). * **Electromyography (EMG):** EMG may demonstrate a decremental response with repetitive nerve stimulation [26](#page=26) [27](#page=27). * **CT Chest:** This is performed to evaluate the thymus, as thymoma is found in 10-15% of patients, and thymic hyperplasia in about 75% [26](#page=26) [27](#page=27). * **Edrophonium (Tensilon) test:** This test, which shows rapid improvement in muscle strength, is rarely used due to potential false positives [26](#page=26) [27](#page=27). #### 11.2.6 Treatment Treatment strategies aim for symptomatic relief and disease control: * **First-Line (Symptomatic):** Acetylcholinesterase (AChE) inhibitors, such as Pyridostigmine, increase ACh at the synapse, providing symptomatic relief but do not alter the disease course [26](#page=26) [27](#page=27). * **Definitive / Disease Control:** * **Thymectomy:** This surgical procedure is absolute if a thymoma is present and may induce remission even in its absence [26](#page=26) [27](#page=27). * **Immunosuppressants:** Corticosteroids and agents like Azathioprine or Cyclosporine are used to suppress the autoimmune response [26](#page=26) [27](#page=27). * **Crisis Management:** In a myasthenic crisis, vital capacity (FVC) should be monitored closely; intubation is indicated if FVC is less than 15 mL/kg (approximately 1 liter). Plasmapheresis and IVIG are also used in crisis management [26](#page=26) [27](#page=27). #### 11.2.7 Drugs that worsen MG Certain medications can exacerbate MG symptoms and should be avoided. These include aminoglycosides, fluoroquinolones, beta-blockers, and antiarrhythmics like quinidine, procainamide, and lidocaine [26](#page=26) [27](#page=27). > ❌ **Exam Trap:** Be aware of drugs that can worsen MG symptoms. #### 11.2.8 Key differentiators * MG involves a postsynaptic defect at the NMJ [26](#page=26) [27](#page=27). * Sensation and reflexes are normal in MG [26](#page=26) [27](#page=27). * Muscle weakness improves with rest, which is the opposite of Lambert-Eaton syndrome [26](#page=26) [27](#page=27). --- # Neuromuscular disorders: Muscular Dystrophies This topic focuses on differentiating between Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD), exploring their genetic basis, the underlying pathophysiology related to dystrophin, and their distinct clinical presentations, diagnostic approaches, and management strategies. ### 12.1 Duchenne muscular dystrophy (DMD) #### 12.1.1 Definition Duchenne muscular dystrophy (DMD) is an X-linked recessive muscular dystrophy characterized by the **complete absence** of dystrophin, leading to severe muscle degeneration [28](#page=28). #### 12.1.2 Pathophysiology The pathophysiology of DMD stems from a mutation in the dystrophin gene. Dystrophin is a protein crucial for stabilizing the muscle cell membrane. Its absence results in muscle fiber damage, which is subsequently replaced by fat tissue. Importantly, there is **no inflammation** associated with this process [28](#page=28). #### 12.1.3 Clinical features DMD typically presents in childhood with progressive, symmetric proximal muscle weakness, initially affecting the pelvic girdle. A hallmark sign is **Gowers’ maneuver**, where individuals use their hands to push off the ground to stand up due to leg weakness. Calf enlargement, known as pseudohypertrophy, occurs as muscle tissue is replaced by fat. Involvement of respiratory muscles is common, and individuals often become wheelchair-dependent and face a reduced life expectancy, typically succumbing in the third decade of life [28](#page=28). #### 12.1.4 Diagnosis Diagnosis of DMD involves elevated levels of creatine phosphokinase (CP). The gold standard for diagnosis, however, is DNA testing [28](#page=28). #### 12.1.5 Treatment The primary pharmacological treatment for DMD is prednisone, which can improve strength and lung function. However, prednisone use carries an increased risk of scoliosis. Management also includes supportive care and may involve scoliosis surgery [28](#page=28). ### 12.2 Becker muscular dystrophy (BMD) #### 12.2.1 Definition Becker muscular dystrophy (BMD) is also an X-linked muscular dystrophy, but unlike DMD, it is characterized by **reduced, rather than absent, dystrophin** [28](#page=28). #### 12.2.2 Pathophysiology In BMD, a partial function of dystrophin is preserved, leading to a slower rate of muscle degeneration compared to DMD [28](#page=28). #### 12.2.3 Clinical features BMD typically presents later in life, during adolescence or adulthood, with milder proximal muscle weakness. The disease progression is slower, and individuals generally experience a longer life expectancy [28](#page=28). #### 12.2.4 Comparison with Duchenne BMD is considered less severe than DMD, has a longer life expectancy, and involves the presence of some dystrophin [28](#page=28). ### 12.3 Exam gold * DMD: **ABSENT** dystrophin $\rightarrow$ severe, early onset, fatal [28](#page=28). * Becker: **REDUCED** dystrophin $\rightarrow$ milder, later onset [28](#page=28). * Both conditions are X-linked and present with elevated CP levels and no inflammation [28](#page=28). * Mnemonic: “DMD Dies, Becker Breathes” [28](#page=28). --- # Neurocutaneous syndromes: Neurofibromatosis, Tuberous Sclerosis, and Sturge-Weber Syndrome This section summarizes key neurocutaneous syndromes, focusing on Neurofibromatosis types I and II, Tuberous Sclerosis, and Sturge-Weber Syndrome, detailing their genetic basis, characteristic clinical manifestations, and management strategies. ### 13.1 Neurofibromatosis Neurofibromatosis (NF) comprises a group of genetic disorders characterized by the development of tumors along nerve pathways. #### 13.1.1 Neurofibromatosis Type I (NF1) Also known as Von Recklinghausen Disease, NF1 is an autosomal dominant disorder caused by a mutation on chromosome 17, leading to the loss of the neurofibromin tumor suppressor protein [29](#page=29) [30](#page=30). ##### 13.1.1.1 Genetics of NF1 * Inheritance pattern: Autosomal Dominant [29](#page=29) [30](#page=30). * Gene location: Chromosome 17 [29](#page=29) [30](#page=30). * Pathophysiology: Loss of neurofibromin, a tumor suppressor [29](#page=29) [30](#page=30). ##### 13.1.1.2 Clinical Manifestations of NF1 **Skin Findings:** * Café-au-lait spots: Six or more are characteristic [29](#page=29) [30](#page=30). * Axillary or inguinal freckling (Crowe sign) [29](#page=29) [30](#page=30). * Cutaneous neurofibromas: Soft, disfiguring tumors [29](#page=29) [30](#page=30). **Eye Findings:** * Lisch nodules: Iris hamartomas, considered an exam gold standard for NF1 [29](#page=29) [30](#page=30). **Central Nervous System (CNS) Tumors:** * Optic nerve gliomas: Can lead to vision loss in children [29](#page=29) [30](#page=30). * Other gliomas [29](#page=29) [30](#page=30). * Meningiomas [29](#page=29) [30](#page=30). **Bone and Vascular Findings:** * Scoliosis [29](#page=29) [30](#page=30). * Congenital tibial dysplasia [29](#page=29) [30](#page=30). * Erosive bone defects [29](#page=29) [30](#page=30). * Renal artery stenosis, potentially causing hypertension [29](#page=29) [30](#page=30). * Pheochromocytoma [29](#page=29) [30](#page=30). **Neurodevelopmental Findings:** * Learning disabilities [29](#page=29) [30](#page=30). * Seizures [29](#page=29) [30](#page=30). * Macrocephaly [29](#page=29) [30](#page=30). * Short stature [29](#page=29) [30](#page=30). ##### 13.1.1.3 Management of NF1 * Surveillance: Regular monitoring for tumor development and complications [29](#page=29) [30](#page=30). * Surgical excision: Recommended if tumors become symptomatic [29](#page=29) [30](#page=30). #### 13.1.2 Neurofibromatosis Type II (NF2) NF2 is also an autosomal dominant disorder, but it primarily affects chromosome 22 [29](#page=29) [30](#page=30). ##### 13.1.2.1 Genetics of NF2 * Inheritance pattern: Autosomal Dominant [29](#page=29) [30](#page=30). * Gene location: Chromosome 22 [29](#page=29) [30](#page=30). ##### 13.1.2.2 Key Feature of NF2 The hallmark of NF2 is the development of bilateral acoustic neuromas (vestibular schwannomas), which can lead to hearing loss, tinnitus, and imbalance [29](#page=29) [30](#page=30). ##### 13.1.2.3 Clinical Manifestations of NF2 **Central Nervous System (CNS) Tumors:** * Multiple meningiomas are common [29](#page=29) [30](#page=30). **Skin:** * Café-au-lait spots may be present but are usually fewer in number than in NF1 [29](#page=29) [30](#page=30). * Neurofibromas are less common [29](#page=29) [30](#page=30). **Eyes:** * Early-onset cataracts [29](#page=29) [30](#page=30). ##### 13.1.2.4 Prognosis of NF2 The prognosis for NF2 depends on the number and location of tumors [29](#page=29) [30](#page=30). #### 13.1.3 NF1 vs. NF2 Comparison | Feature | NF1 | NF2 | | :------------------- | :---------------------------------------- | :----------------------------------------- | | **Key Locations** | Skin, Eyes, Bones, Optic gliomas | Ears, Brain (bilateral acoustic neuromas) | | **Lisch Nodules** | Present (NF1 ONLY) | Absent | | **Mnemonic** | N/A | "Two ears" (for bilateral acoustic neuromas) | | **Genetics** | Chromosome 17 | Chromosome 22 | | **Café-au-lait spots** | ≥6 | Few | | **Neurofibromas** | Common | Less common | | **Cataracts** | Rare | Early-onset cataracts | ### 13.2 Tuberous Sclerosis (TS) Tuberous Sclerosis (TS) is an autosomal dominant neurocutaneous syndrome characterized by the development of hamartomas in multiple organs [31](#page=31). #### 13.2.1 Definition and Pathophysiology of TS * Definition: Autosomal dominant neurocutaneous syndrome with hamartomas in multiple organs [31](#page=31). * Pathophysiology: Caused by mutations in the *TSC1* or *TSC2* genes, leading to uncontrolled cell growth due to loss of inhibition of the mTOR pathway [31](#page=31). #### 13.2.2 Core Clinical Triad of TS The core clinical triad, a key exam focus, includes: * Cognitive impairment or developmental delay [31](#page=31). * Epilepsy, often with early childhood onset [31](#page=31). * Skin lesions [31](#page=31): * Facial angiofibromas (also called adenoma sebaceum) [31](#page=31). * Ash-leaf hypopigmented macules [31](#page=31). * Shagreen patches (leathery skin texture) [31](#page=31). #### 13.2.3 Multisystem Involvement in TS * **Brain:** Cortical tubers leading to seizures and learning difficulties [31](#page=31). * **Heart:** Rhabdomyomas, particularly in infants [31](#page=31). * **Kidneys:** Angiomyolipomas, which can cause hematuria and present renal risks [31](#page=31). * **Eyes:** Retinal hamartomas [31](#page=31). #### 13.2.4 Diagnosis and Management of TS * **Diagnosis:** Based on clinical features supported by imaging (e.g., MRI of the brain showing cortical tubers) and genetic testing for *TSC1*/*TSC2* mutations [31](#page=31). * **Management:** There is no definitive cure. Management focuses on treating complications: * Anti-epileptic medications for seizures [31](#page=31). * Surgical intervention for obstructing tumors [31](#page=31). * mTOR inhibitors, such as everolimus, are used [31](#page=31). #### 13.2.5 High-Yield Exam Pearls for TS * Autosomal dominant inheritance. * Think TS when encountering seizures and skin lesions together. * Rhabdomyoma in a child is highly suggestive of TS. * Involvement of the mTOR pathway is a frequent exam topic. ### 13.3 Sturge-Weber Syndrome (SWS) Sturge-Weber Syndrome is a sporadic, acquired neurocutaneous syndrome characterized by capillary angiomatous malformations [32](#page=32). #### 13.3.1 Definition and Pathology of SWS * Definition: Sporadic (acquired) neurocutaneous syndrome [32](#page=32). * Pathology: Capillary angiomatous malformations, typically involving the pia mater (leptomeningeal angiomas), which can lead to chronic cortical ischemia [32](#page=32). #### 13.3.2 Key Clinical Features of SWS * Facial port-wine stain (vascular nevus): Usually distributed in the trigeminal nerve (V1) dermatome [32](#page=32). * Seizures: Very common, often presenting in early childhood [32](#page=32). * Intellectual disability or developmental delay [32](#page=32). * Hemiparesis: Resulting from cortical damage [32](#page=32). #### 13.3.3 Neurologic Consequences of SWS * Epilepsy is the primary cause of morbidity [32](#page=32). * Progressive neurologic deterioration can occur [32](#page=32). #### 13.3.4 Imaging and Genetics of SWS * **Imaging Clue:** Cortical calcifications, often described as a "tram-track" appearance on imaging [32](#page=32). * **Genetics:** SWS is *not* inherited, which is an important distinction to remember for exams [32](#page=32). #### 13.3.5 Treatment of SWS * Seizure control is the mainstay of treatment [32](#page=32). * Supportive and symptomatic management is provided [32](#page=32). --- # Spinal cord diseases: Syringomyelia and Brown-Séquard Syndrome This section summarizes two distinct spinal cord diseases: syringomyelia, characterized by central cavitation, and Brown-Séquard syndrome, resulting from a hemisection of the spinal cord, detailing their etiologies, pathophysiology, clinical presentations, and management. ### 14.1 Syringomyelia Syringomyelia is defined by the development of a central cavitation, termed a syrinx, within the spinal cord, most commonly in the cervical region [33](#page=33). #### 14.1.1 Etiology and Associations The etiology of syringomyelia is often associated with several conditions: * Arnold-Chiari malformation (Type I) is the most common association [33](#page=33). * Other causes include post-traumatic injuries, post-infectious processes, tethered cord, and intramedullary tumors [33](#page=33). #### 14.1.2 Pathophysiology The pathophysiology involves the expansion of the central canal, leading to early compression of decussating fibers. The lateral spinothalamic tract is typically affected first due to its location [33](#page=33). #### 14.1.3 Clinical Features The hallmark clinical presentation of syringomyelia is a bilateral loss of pain and temperature sensation, often described as having a "cape-like" distribution over the shoulders and arms. Early in the disease, touch and vibration senses are usually preserved. Patients may also exhibit hand muscle atrophy, indicative of lower motor neuron (LMN) signs. Thoracic scoliosis can be observed in chronic cases [33](#page=33). #### 14.1.4 Diagnosis The gold standard for diagnosing syringomyelia is an MRI of the spine [33](#page=33). #### 14.1.5 Management Management strategies for syringomyelia depend on the size of the syrinx and the presence and severity of symptoms. Neurosurgical evaluation is considered essential in all cases [33](#page=33). ### 14.2 Brown-Séquard syndrome Brown-Séquard syndrome is a neurological condition resulting from a hemisection, or damage to one half (right or left), of the spinal cord [33](#page=33). #### 14.2.1 Common Causes This syndrome can arise from various spinal cord injuries: * Trauma, particularly a stab wound, is a classic cause [33](#page=33). * Other common causes include spinal fractures, tumors, and, less frequently, abscesses [33](#page=33). #### 14.2.2 Pathophysiology The pathophysiology is directly related to the specific tracts affected by the hemisection: * The corticospinal tract, responsible for voluntary motor control, is affected ipsilaterally (on the same side as the lesion) [33](#page=33). * The dorsal columns, which carry vibration and position sense, are also affected ipsilaterally [33](#page=33). * The spinothalamic tract, responsible for pain and temperature sensation, is affected contralaterally (on the opposite side of the lesion) because its fibers cross over early after entering the spinal cord [33](#page=33). #### 14.2.3 Clinical Features The clinical presentation of Brown-Séquard syndrome is characterized by distinct ipsilateral and contralateral deficits: * **Ipsilateral to the lesion:** * Hemiparesis (weakness on one side of the body) due to UMN signs [33](#page=33). * Loss of vibration and position sense [33](#page=33). * **Contralateral to the lesion:** * Loss of pain and temperature sensation. This deficit typically begins one to two levels below the site of the spinal cord lesion [33](#page=33). > **Tip:** Remember that the key diagnostic feature of Brown-Séquard syndrome is the combination of ipsilateral motor/proprioceptive deficits with contralateral sensory (pain/temperature) deficits. #### 14.2.4 Prognosis The neurologic recovery for Brown-Séquard syndrome is generally considered very good [33](#page=33). --- # Spinal cord diseases: Transverse Myelitis Transverse myelitis is an inflammatory condition affecting the entire cross-section of the spinal cord at a single level, most commonly in the thoracic region [34](#page=34). ### 15.1 Pathophysiology The inflammation in transverse myelitis can damage various spinal cord tracts, leading to specific neurological deficits below the level of the lesion. These include [34](#page=34): * **Corticospinal tract involvement:** Results in weakness or paralysis [34](#page=34). * **Spinothalamic tract involvement:** Leads to loss of pain and temperature sensation [34](#page=34). * **Dorsal column involvement:** Causes a loss of proprioception and vibration sense [34](#page=34). * **Autonomic fiber involvement:** Contributes to bladder and bowel dysfunction [34](#page=34). ### 15.2 Clinical features Clinical manifestations of transverse myelitis are observed below the level of the spinal cord lesion. Key features include [34](#page=34): * Bilateral lower limb weakness or paralysis [34](#page=34). * A clearly defined sensory level, indicating a sharp cut-off of sensation [34](#page=34). * Back pain, particularly at the onset of the condition [34](#page=34). * Urinary retention, which is considered a highly significant symptom [34](#page=34). ### 15.3 Causes The causes of transverse myelitis are diverse and can be broadly categorized into infectious, autoimmune, and other mechanisms [34](#page=34). #### 15.3.1 Infectious causes Infectious agents that can trigger transverse myelitis include: * **Viral:** Herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), and West Nile virus [34](#page=34). * **Bacterial:** Tuberculosis (TB), Lyme disease, and *Mycoplasma* [34](#page=34). * **Parasitic:** *Toxoplasma* and *Schistosoma* [34](#page=34). * **Fungal:** *Cryptococcus* [34](#page=34). #### 15.3.2 Autoimmune causes Autoimmune conditions associated with transverse myelitis include: * Multiple sclerosis [34](#page=34). * Neuromyelitis optica spectrum disorder (NMOSD) [34](#page=34). * Systemic lupus erythematosus (SLE) [34](#page=34). * Sarcoidosis [34](#page=34). * Sjögren syndrome [34](#page=34). #### 15.3.3 Other causes Other potential etiologies include: * Post-infectious or post-vaccination reactions [34](#page=34). * Paraneoplastic syndromes, often associated with lung or breast cancer [34](#page=34). ### 15.4 Diagnosis The primary diagnostic tool for transverse myelitis is an MRI of the spine with contrast enhancement, which is considered the test of choice [34](#page=34). ### 15.5 Treatment Treatment for transverse myelitis typically involves high-dose intravenous steroids, often used in acute management. Supportive care is also a crucial component of management [34](#page=34). ### 15.6 Prognosis The prognosis for transverse myelitis is highly variable, ranging from complete recovery to death [34](#page=34). --- # Cranial nerve disorders: Horner Syndrome and Poliomyelitis This section details two distinct neurological conditions: Horner syndrome, characterized by specific ophthalmic and facial symptoms due to sympathetic pathway disruption, and poliomyelitis, a viral illness impacting the motor neurons of the spinal cord and brainstem [35](#page=35). ### 16.1 Horner syndrome Horner syndrome is defined by the interruption of the cervical sympathetic pathway to the eye [35](#page=35). #### 16.1.1 Types of Horner syndrome There are two primary types of Horner syndrome: * **Preganglionic (central):** These are considered more dangerous due to their potential underlying causes [35](#page=35). * **Postganglionic (peripheral):** [35](#page=35). #### 16.1.2 Classic triad (PAM) The classic presentation of Horner syndrome is often remembered by the acronym PAM: * **P**tosis: Mild drooping of the eyelid [35](#page=35). * **A**nhidrosis: Decreased or absent sweating on the affected side of the face [35](#page=35). * **M**iosis: Constriction of the pupil, resulting in a pinpoint pupil [35](#page=35). #### 16.1.3 Key anatomy pearl A crucial anatomical point to remember is that the levator palpebrae muscle, innervated by the oculomotor nerve (CN III), remains intact in Horner syndrome. The mild ptosis observed is due to the involvement of Müller's muscle, a smooth muscle innervated by the sympathetic nervous system [35](#page=35). #### 16.1.4 Causes of Horner syndrome Common causes of Horner syndrome include: * Idiopathic (most common) [35](#page=35). * Pancoast tumor (a tumor located in the apex of the lung) [35](#page=35). * Internal carotid artery dissection [35](#page=35). * Brainstem stroke [35](#page=35). * Cervical spine trauma [35](#page=35). #### 16.1.5 Exam clues for Horner syndrome When examining a patient, specific clues can point towards Horner syndrome: * A smoker presenting with shoulder pain and Horner syndrome should raise suspicion for a Pancoast tumor [35](#page=35). * It is essential to remember that all signs of Horner syndrome are ipsilateral to the lesion, meaning they appear on the same side of the body as the disrupted sympathetic pathway [35](#page=35). ### 16.2 Poliomyelitis Poliomyelitis, commonly known as polio, is a contagious viral disease that can cause paralysis. #### 16.2.1 Etiology of poliomyelitis Poliomyelitis is caused by infection with the poliovirus [35](#page=35). #### 16.2.2 Pathology of poliomyelitis The hallmark pathology of poliomyelitis is the destruction of anterior horn cells in the spinal cord and brainstem [35](#page=35). #### 16.2.3 Type of lesion in poliomyelitis Poliomyelitis results in a lower motor neuron (LMN) lesion [35](#page=35). #### 16.2.4 Clinical features of poliomyelitis The clinical presentation of poliomyelitis includes: * Asymmetric muscle weakness, typically affecting the legs more than the arms [35](#page=35). * Flaccid paralysis [35](#page=35). * Muscle atrophy [35](#page=35). * Absent deep tendon reflexes [35](#page=35). * Importantly, sensation remains normal [35](#page=35). #### 16.2.5 Bulbar poliomyelitis A severe form of the disease, bulbar poliomyelitis, involves the involvement of cranial nerves IX and X (glossopharyngeal and vagus nerves). This can lead to [35](#page=35): * Dysphagia (difficulty swallowing) [35](#page=35). * Respiratory and cardiovascular failure [35](#page=35). #### 16.2.6 Treatment for poliomyelitis Currently, there is no curative treatment for poliomyelitis itself [35](#page=35). #### 16.2.7 Prevention of poliomyelitis Poliomyelitis is a 100% preventable disease through vaccination [35](#page=35). --- # Vestibular disorders: Peripheral and Central Vertigo This topic differentiates between peripheral vertigo, originating in the inner ear, and central vertigo, originating in the brainstem or cerebellum, outlining their characteristic features, diagnostic clues, and common causes [36](#page=36) [37](#page=37). ### 17.1 Vertigo: Definition and initial assessment Vertigo is defined as a false sensation of spinning or movement, indicative of dysfunction within the vestibular system. The first and most crucial diagnostic step is to differentiate between peripheral and central causes of vertigo [36](#page=36) [37](#page=37). ### 17.2 Peripheral vertigo (inner ear) Peripheral vertigo arises from issues within the inner ear [36](#page=36) [37](#page=37). #### 17.2.1 General features of peripheral vertigo Key characteristics of peripheral vertigo include: * Sudden onset [36](#page=36) [37](#page=37). * Severe spinning sensation [36](#page=36) [37](#page=37). * Intense nausea and vomiting [36](#page=36) [37](#page=37). * Associated hearing loss or tinnitus [36](#page=36) [37](#page=37). * Absence of focal neurologic deficits [36](#page=36) [37](#page=37). > **Tip:** The presence of hearing loss or tinnitus is a strong indicator of peripheral vertigo [36](#page=36) [37](#page=37). #### 17.2.2 Nystagmus in peripheral vertigo Nystagmus associated with peripheral vertigo is typically unidirectional, meaning it moves in only one direction (either horizontally or torsionally) [36](#page=36) [37](#page=37). #### 17.2.3 The HINTS exam for peripheral vertigo The HINTS exam is a clinical assessment used to differentiate between peripheral and central causes of vertigo. For peripheral vertigo, the HINTS exam typically reveals: * Abnormal head impulse [36](#page=36) [37](#page=37). * Unidirectional nystagmus [36](#page=36) [37](#page=37). * No skew deviation [36](#page=36) [37](#page=37). #### 17.2.4 Causes of peripheral vertigo Common causes of peripheral vertigo include: * **Benign Paroxysmal Positional Vertigo (BPPV):** * Triggered by specific positional changes [36](#page=36) [37](#page=37). * Symptoms last for seconds to minutes [36](#page=36) [37](#page=37). * Caused by displaced otoliths (canaliths) [36](#page=36) [37](#page=37). * **Ménière Disease:** * Characterized by vertigo, tinnitus, and hearing loss (which can become permanent later) [36](#page=36) [37](#page=37). * **Acute Labyrinthitis:** Often viral in origin [36](#page=36) [37](#page=37). * **Ototoxic drugs:** Such as aminoglycosides and loop diuretics [36](#page=36) [37](#page=37). * **Acoustic neuroma (CN VIII schwannoma):** A tumor on the vestibulocochlear nerve [36](#page=36) [37](#page=37). ### 17.3 Central vertigo (brainstem / cerebellum) Central vertigo originates from issues within the brainstem or cerebellum [36](#page=36) [37](#page=37). #### 17.3.1 General features of central vertigo The general features of central vertigo are distinct from peripheral vertigo: * Gradual onset [36](#page=36) [37](#page=37). * Less intense vertigo [36](#page=36) [37](#page=37). * Mild nausea and vomiting [36](#page=36) [37](#page=37). * Presence of focal neurologic deficits [36](#page=36) [37](#page=37). > **Tip:** The presence of focal neurologic signs is a strong indicator of central vertigo [36](#page=36) [37](#page=37). #### 17.3.2 Nystagmus in central vertigo Nystagmus in central vertigo can be vertical or multidirectional [36](#page=36) [37](#page=37). > **Note:** Vertical nystagmus is considered central vertigo until proven otherwise [36](#page=36) [37](#page=37). #### 17.3.3 The HINTS exam for central vertigo The HINTS exam, when indicative of central vertigo, typically shows: * Normal head impulse [36](#page=36) [37](#page=37). * Vertical or bidirectional nystagmus [36](#page=36) [37](#page=37). * Skew deviation present [36](#page=36) [37](#page=37). #### 17.3.4 Causes of central vertigo Common causes of central vertigo include: * **Multiple Sclerosis (MS):** Due to demyelination of vestibular pathways [36](#page=36) [37](#page=37). * **Vertebrobasilar insufficiency:** Impaired blood flow to the brainstem and cerebellum [36](#page=36) [37](#page=37). * **Migraine-associated vertigo:** Vertigo that occurs in conjunction with migraines [36](#page=36) [37](#page=37). ### 17.4 Comparison of central vs. peripheral vertigo | Feature | Central Vertigo | Peripheral Vertigo | | :------------------ | :--------------------------- | :-------------------------- | | Onset | Gradual | Sudden | | Severity | Mild | Severe | | Neurologic Signs | Present | Absent | | Hearing Loss | No | Yes | | Nystagmus Direction | Vertical (or multidirectional) | Horizontal (or torsional) | ### 17.5 Exam gold pearls for vertigo assessment * Hearing loss strongly suggests peripheral vertigo [36](#page=36) [37](#page=37). * Vertical nystagmus should be considered central vertigo until proven otherwise [36](#page=36) [37](#page=37). * Focal neurologic signs are indicative of central vertigo [36](#page=36) [37](#page=37). * The HINTS exam is a more sensitive initial test than MRI for acute stroke in patients presenting with vertigo [36](#page=36) [37](#page=37). --- # Syncope: causes, diagnosis, and management Syncope is a transient loss of consciousness and postural tone due to reduced cerebral blood flow, characterized by rapid and complete recovery [38](#page=38) [39](#page=39). ### 18.1 Key principle: Cardiac vs. non-cardiac causes Differentiating between cardiac and non-cardiac causes of syncope is a key principle, as cardiac causes are associated with the worst prognosis [38](#page=38) [39](#page=39). ### 18.2 Cardiac syncope Cardiac syncope is often characterized by sudden onset, absence of a prodrome, and immediate loss of consciousness [38](#page=38) [39](#page=39). #### 18.2.1 Causes of cardiac syncope * **Arrhythmias:** This includes ventricular tachycardia (VT), supraventricular tachycardia (SVT), atrioventricular (AV) block, and sick sinus syndrome [38](#page=38) [39](#page=39). * **Obstruction to blood flow:** Conditions such as aortic stenosis, hypertrophic cardiomyopathy (HCM), pulmonary hypertension, and atrial myxoma can lead to cardiac syncope [38](#page=38) [39](#page=39). * **Pulmonary embolism:** This can also be a cause of cardiac syncope [38](#page=38) [39](#page=39). > **Exam Tip:** Syncope occurring *during* exertion should raise suspicion for hypertrophic cardiomyopathy or aortic stenosis [38](#page=38) [39](#page=39). ### 18.3 Vasovagal (reflex) syncope Vasovagal syncope is the most common cause, accounting for approximately 50% of all cases [38](#page=38) [39](#page=39). #### 18.3.1 Triggers of vasovagal syncope Common triggers include emotional stress, pain or fear, extreme fatigue, and claustrophobia [38](#page=38) [39](#page=39). #### 18.3.2 Prodrome of vasovagal syncope A significant feature is the presence of a prodrome, which typically includes pallor, diaphoresis, lightheadedness, nausea, dimming of vision, and a roaring sensation in the ears [38](#page=38) [39](#page=39). #### 18.3.3 Pathophysiology of vasovagal syncope The pathophysiology involves a decrease in sympathetic tone and an increase in vagal tone, leading to bradycardia and vasodilation. This results in reduced blood pressure and subsequent syncope [38](#page=38) [39](#page=39). #### 18.3.4 Management and prognosis of vasovagal syncope Management includes positioning the patient supine, elevating their legs, and advising them to avoid known triggers. The prognosis for vasovagal syncope is excellent [38](#page=38) [39](#page=39). ### 18.4 Orthostatic hypotension Orthostatic hypotension is characterized by a drop in blood pressure upon standing. #### 18.4.1 Causes of orthostatic hypotension Causes include volume depletion, autonomic dysfunction (e.g., Parkinson's disease, diabetes), and certain medications such as diuretics and vasodilators [38](#page=38) [39](#page=39). #### 18.4.2 Key clues for orthostatic hypotension A key clue is that the syncope occurs on standing, and is often worse with sudden or prolonged standing. It occurs only when the patient is upright [38](#page=38) [39](#page=39). #### 18.4.3 Treatment of orthostatic hypotension Treatment involves increasing fluid and salt intake, discontinuing offending drugs, and potentially prescribing fludrocortisone for recurrent episodes [38](#page=38) [39](#page=39). ### 18.5 Cerebrovascular causes of syncope Cerebrovascular causes of syncope are rare. #### 18.5.1 Examples of cerebrovascular causes This category includes vertebrobasilar transient ischemic attacks (TIAs), often referred to as "drop attacks." It is important to note that isolated syncope is almost never due to cerebrovascular causes; other neurological deficits are typically present [38](#page=38) [39](#page=39). ### 18.6 Diagnostic approach to syncope The diagnostic approach aims to rule out life-threatening causes and differentiate between cardiac and non-cardiac origins [38](#page=38) [39](#page=39). #### 18.6.1 History taking A detailed history is high-yield and should focus on the events before, during, and after the syncope episode, as well as current medications and information from witness reports [38](#page=38) [39](#page=39). #### 18.6.2 Physical examination The physical examination should include orthostatic vital signs and auscultation for cardiac murmurs suggestive of aortic stenosis or hypertrophic cardiomyopathy [38](#page=38) [39](#page=39). #### 18.6.3 Investigations * **ECG:** An electrocardiogram is recommended for all patients with syncope [38](#page=38) [39](#page=39). * **Echocardiogram:** This is indicated if structural heart disease is suspected [38](#page=38) [39](#page=39). * **Holter/event monitor:** These devices are used to detect arrhythmias [38](#page=38) [39](#page=39). ### 18.7 Prognostic keys for syncope Certain factors are associated with a poor prognosis in patients experiencing syncope: * Presence of structural heart disease [38](#page=38) [39](#page=39). * An abnormal ECG finding [38](#page=38) [39](#page=39). --- # Seizures and epilepsy: types, causes, and treatment This section outlines the definition, causes, types, diagnostic approaches, and treatment strategies for seizures and epilepsy [40](#page=40) [41](#page=41). ### 19.1 Definition of seizures and epilepsy A seizure is a sudden, abnormal electrical discharge in the brain. A single seizure event is termed a seizure. Recurrent, unprovoked seizures constitute epilepsy [40](#page=40) [41](#page=41). ### 19.2 Causes of seizures (4 M's and 4 I's) The causes of seizures can be broadly categorized into four metabolic and four insult-related factors [40](#page=40) [41](#page=41). #### 19.2.1 The 4 M's * **Metabolic:** This category includes electrolyte imbalances and organ dysfunction, such as: * Low sodium (${\downarrow}\text{Na}^+$) [40](#page=40) [41](#page=41). * Low glucose (${\downarrow}\text{Glucose}$) [40](#page=40) [41](#page=41). * Low calcium (${\downarrow}\text{Ca}^{2+}$) [40](#page=40) [41](#page=41). * Uremia [40](#page=40) [41](#page=41). * Thyroid storm [40](#page=40) [41](#page=41). * **Mass lesions:** These are structural abnormalities within the brain, including: * Tumors [40](#page=40) [41](#page=41). * Metastases [40](#page=40) [41](#page=41). * Hemorrhage [40](#page=40) [41](#page=41). * **Missing drugs:** This is a common cause, particularly in individuals with known epilepsy, due to non-adherence to medication [40](#page=40) [41](#page=41). * **Miscellaneous:** This group encompasses a variety of other conditions: * Pseudoseizures [40](#page=40) [41](#page=41). * Eclampsia [40](#page=40) [41](#page=41). * Hypertensive encephalopathy [40](#page=40) [41](#page=41). #### 19.2.2 The 4 I's * **Intoxications:** Exposure to certain substances can trigger seizures, such as: * Cocaine [40](#page=40) [41](#page=41). * Lithium [40](#page=40) [41](#page=41). * Theophylline [40](#page=40) [41](#page=41). * Carbon monoxide (CO) [40](#page=40) [41](#page=41). * **Infections:** Brain infections can lead to seizures, including: * Meningitis [40](#page=40) [41](#page=41). * Abscess [40](#page=40) [41](#page=41). * **Ischemia:** Reduced blood flow to the brain can cause seizures, particularly in older adults, such as: * Stroke [40](#page=40) [41](#page=41). * Transient ischemic attack (TIA) [40](#page=40) [41](#page=41). * **Increased intracranial pressure (${\uparrow}\text{ICP}$):** Elevated pressure within the skull can result from: * Trauma [40](#page=40) [41](#page=41). * Tumor [40](#page=40) [41](#page=41). ### 19.3 Types of seizures Seizures are broadly classified into partial (focal) and generalized types [40](#page=40) [41](#page=41). #### 19.3.1 Partial (focal) seizures Partial seizures originate in a specific area of the brain and account for approximately 70% of seizures in adults [40](#page=40) [41](#page=41). * **Simple partial seizures:** * Consciousness remains intact [40](#page=40) [41](#page=41). * Characterized by focal motor or sensory symptoms [40](#page=40) [41](#page=41). * **Complex partial seizures:** * Consciousness is impaired [40](#page=40) [41](#page=41). * Often associated with postictal confusion [40](#page=40) [41](#page=41). * May involve automatisms, such as lip smacking or chewing [40](#page=40) [41](#page=41). * Can manifest with olfactory or gustatory hallucinations [40](#page=40) [41](#page=41). * These seizures can sometimes lead to secondary generalization, where they spread to involve the entire brain [40](#page=40) [41](#page=41). #### 19.3.2 Generalized seizures Generalized seizures affect both hemispheres of the brain simultaneously [40](#page=40) [41](#page=41). * **Tonic-clonic (Grand Mal) seizures:** * Characterized by sudden loss of consciousness, often with a fall [40](#page=40) [41](#page=41). * The tonic phase involves stiffening of the body and apnea [40](#page=40) [41](#page=41). * The clonic phase consists of rhythmic jerking movements lasting at least 30 seconds [40](#page=40) [41](#page=41). * Followed by postictal confusion that can last 10 to 30 minutes or longer [40](#page=40) [41](#page=41). * **Absence (Petit Mal) seizures:** * Primarily observed in children [40](#page=40) [41](#page=41). * Manifest as a brief blank stare, lasting only a few seconds [40](#page=40) [41](#page=41). * Individuals may experience up to 100 absence seizures per day [40](#page=40) [41](#page=41). * There is no postictal confusion associated with absence seizures [40](#page=40) [41](#page=41). * May involve eye blinking or head nodding [40](#page=40) [41](#page=41). ### 19.4 Diagnostic approaches * For individuals with a known history of epilepsy, the initial diagnostic step is to check drug levels [40](#page=40) [41](#page=41). * For a first-time seizure, the diagnostic workup includes: * **Laboratory tests:** STAT analysis of sodium (${\text{Na}^+}$), calcium (${\text{Ca}^{2+}}$), and glucose levels [40](#page=40) [41](#page=41). * **Electroencephalogram (EEG):** This test is supportive of a diagnosis [40](#page=40) [41](#page=41). * **CT head:** Recommended for acute presentations [40](#page=40) [41](#page=41). * **MRI brain:** Considered the most sensitive imaging modality [40](#page=40) [41](#page=41). * A lumbar puncture (LP) is indicated if the patient presents with fever [40](#page=40) [41](#page=41). ### 19.5 Treatment #### 19.5.1 Acute seizure management For all seizure types in an acute setting: * Prioritize airway, breathing, and circulation (ABCs) [40](#page=40) [41](#page=41). * Position the patient on their side to prevent aspiration [40](#page=40) [41](#page=41). #### 19.5.2 Chronic epilepsy management Treatment for chronic epilepsy depends on the seizure type: * **Partial and tonic-clonic seizures:** * Phenytoin or Carbamazepine are commonly prescribed [40](#page=40) [41](#page=41). * **Absence seizures:** * Ethosuximide is the preferred treatment, potentially with Valproate as an adjunct [40](#page=40) [41](#page=41). * **Teratogenicity:** All anticonvulsant medications are considered teratogenic and require careful consideration in pregnant individuals [40](#page=40) [41](#page=41). #### 19.5.3 Status epilepticus Status epilepticus is defined as continuous seizure activity with unconsciousness. Management follows these steps [40](#page=40) [41](#page=41): * Secure the airway [40](#page=40) [41](#page=41). * Administer intravenous (IV) Diazepam [40](#page=40) [41](#page=41). * Follow with IV Phenytoin [40](#page=40) [41](#page=41). * For refractory cases, Phenobarbital may be used [40](#page=40) [41](#page=41). ### 19.6 Exam traps * In elderly patients presenting with their first seizure, strongly consider stroke as a potential cause [40](#page=40) [41](#page=41). * Differentiate between complex partial seizures and absence seizures, as their clinical presentations and management differ [40](#page=40) [41](#page=41). * The most frequent reason for breakthrough seizures in epileptic patients is non-compliance with their medication regimen [40](#page=40) [41](#page=41). * A normal EEG after a first seizure is associated with a lower risk of seizure recurrence [40](#page=40) [41](#page=41). --- # Motor neuron diseases: Amyotrophic Lateral Sclerosis (ALS) Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that exclusively impacts the motor system by affecting both upper and lower motor neurons [42](#page=42) [43](#page=43). ## 20. Amyotrophic lateral sclerosis (ALS) ### 20.1 Definition ALS is a progressive neurodegenerative disease that selectively affects the motor system, involving both upper motor neurons (UMNs) and lower motor neurons (LMNs). The mnemonic "ALS = Affects Lower & Superior neurons" highlights this dual involvement [42](#page=42) [43](#page=43). ### 20.2 Epidemiology The typical onset for ALS is between 50 and 70 years of age, with cases presenting before 40 years being uncommon. The majority of cases, about 90%, are sporadic, while 10% are familial. The prognosis for ALS is grim, with approximately 80% mortality within 5 years of diagnosis and nearly 100% mortality within 10 years [42](#page=42) [43](#page=43). ### 20.3 Pathophysiology The underlying pathophysiology of ALS involves the degeneration of anterior horn cells, leading to LMN signs, and the degeneration of corticospinal and corticobulbar tracts, which results in UMN signs and bulbar symptoms, respectively. The exact cause is mostly unknown, though some genetic mutations and abnormal protein accumulation are implicated [42](#page=42) [43](#page=43). ### 20.4 Clinical features The hallmark clinical features of ALS include progressive muscle weakness, which typically starts in the arms or legs and spreads in a generalized and symmetric fashion [42](#page=42) [43](#page=43). #### 20.4.1 Lower motor neuron signs LMN signs manifest as muscle atrophy, fasciculations, muscle cramps, and weakness [42](#page=42) [43](#page=43). #### 20.4.2 Upper motor neuron signs UMN signs include spasticity, hyperreflexia, and increased muscle tone [42](#page=42) [43](#page=43). #### 20.4.3 Bulbar involvement Bulbar symptoms are characterized by dysarthria (difficulty speaking), dysphagia (difficulty swallowing) which increases the risk of aspiration, and tongue wasting [42](#page=42) [43](#page=43). #### 20.4.4 Respiratory muscle weakness Weakness of the respiratory muscles leads to dyspnea on exertion and at rest, orthopnea, and sleep apnea. End-stage ALS is often characterized by respiratory failure [42](#page=42) [43](#page=43). #### 20.4.5 Intact functions Crucially for diagnosis, sensation, bowel and bladder control, cognition, extraocular muscle function, and sexual function remain normal in ALS patients [42](#page=42) [43](#page=43). > **Tip:** Remember that the preservation of sensory, cognitive, and sphincter functions is a key diagnostic feature that helps differentiate ALS from other neurological conditions. ### 20.5 Diagnosis There is no single definitive diagnostic test for ALS. Diagnosis relies on clinical findings and electrodiagnostic studies. Electromyography (EMG) and nerve conduction studies are essential to confirm LMN degeneration and to rule out neuromuscular junction disorders. Diagnostic certainty is established based on the number of regions involved: 2 regions suggest probable ALS, while 3–4 regions indicate definite ALS [42](#page=42) [43](#page=43). ### 20.6 Treatment Treatment for ALS is primarily supportive [42](#page=42) [43](#page=43). * **Riluzole:** This medication is a glutamate blocker that has been shown to extend survival by approximately 3–5 months only [42](#page=42) [43](#page=43). * **Supportive Care:** This includes respiratory support, speech and swallowing therapy, and early discussions regarding palliative care [42](#page=42) [43](#page=43). ### 20.7 Exam mnemonic A helpful mnemonic for exams is "ALS = Affects Lower & Superior neurons," emphasizing the involvement of both UMN and LMN, the motor-only deficit, and the ultimate cause of death being respiratory failure [42](#page=42) [43](#page=43). --- # Aphasia: types and localization Aphasia is a language disorder characterized by a loss or defect in speaking, fluency, reading, writing, and comprehension, typically involving the dominant hemisphere, usually the left [44](#page=44). ### 21.1 Core facts of aphasia * Aphasia is a language disorder, distinct from motor speech disorders [44](#page=44). * It affects the ability to use language, encompassing speaking, fluency, reading, writing, and comprehension [44](#page=44). * The disorder typically involves the dominant cerebral hemisphere, which is usually the left hemisphere [44](#page=44). * The most common cause of aphasia is stroke [44](#page=44). ### 21.2 Localization principle A key principle in understanding aphasia is its localization within the brain, particularly in relation to the central sulcus [44](#page=44). * **Fluent aphasia** is generally associated with lesions located **posterior** to the central sulcus [44](#page=44). * **Non-fluent aphasia** is generally associated with lesions located **anterior** to the central sulcus [44](#page=44). > **Tip:** This anterior vs. posterior localization rule is considered crucial for examinations [44](#page=44). ### 21.3 Types of aphasia There are four primary types of aphasia, each with distinct characteristics related to language production and comprehension [44](#page=44). #### 21.3.1 Wernicke aphasia * **Type:** Receptive aphasia, characterized by fluency [44](#page=44). * **Key Feature:** Impaired comprehension is the hallmark of Wernicke aphasia [44](#page=44). * **Speech Characteristics:** Speech is fluent, grammatical, but often contains nonsensical words or phrases [44](#page=44). * **Patient Awareness:** Individuals with Wernicke aphasia are typically unaware of their speech errors [44](#page=44). * **Location:** Lesions are typically found in the **posterior temporal lobe** [44](#page=44). * **Mnemonic:** "Fluent but foolish" [44](#page=44). #### 21.3.2 Broca aphasia * **Type:** Expressive aphasia, characterized by non-fluency [44](#page=44). * **Key Feature:** Comprehension is generally intact [44](#page=44). * **Speech Characteristics:** Speech is slow, effortful, and delivered in short phrases. Grammatical structure is often impaired [44](#page=44). * **Associated Symptoms:** Often accompanied by right hemiparesis [44](#page=44). * **Location:** Lesions are typically found in the **inferior frontal gyrus** [44](#page=44). * **Mnemonic:** "Broken speech, Brain intact" [44](#page=44). > **Example:** A patient with Broca aphasia might say "I... need... cup... milk" with significant pauses and effort, but would understand when asked to fetch a cup of milk [44](#page=44). #### 21.3.3 Conduction aphasia * **Core Problem:** The defining characteristic is a significant deficit in the ability to **repeat** words or phrases [44](#page=44). * **Speech Characteristics:** Speech is fluent [44](#page=44). * **Comprehension:** Comprehension is relatively intact [44](#page=44). * **Location:** Lesions are typically found in the **arcuate fasciculus**, a white matter tract connecting Wernicke's and Broca's areas [44](#page=44). * **Mnemonic:** "Connectors cut" [44](#page=44). #### 21.3.4 Global aphasia * **Characteristics:** Global aphasia represents the most severe form of aphasia, with widespread impairment across all language modalities [44](#page=44). * **Impairments:** There is severely impaired speech production (non-fluent), severely impaired comprehension, and significant deficits in reading and writing [44](#page=44). * **Associated Symptoms:** Often accompanied by right hemiparesis [44](#page=44). * **Cause:** Typically results from a large lesion affecting extensive areas of the dominant hemisphere [44](#page=44). * **Mnemonic:** "Everything gone" [44](#page=44). > **Exam Bait:** Remember to associate specific symptoms with their corresponding aphasia type. For example, fluent but nonsensical speech points to Wernicke aphasia, slow and effortful speech with good comprehension suggests Broca aphasia, difficulty repeating phrases indicates conduction aphasia, and pervasive impairment across all language functions signifies global aphasia [44](#page=44). ### 21.4 Treatment and outcome * Many individuals with aphasia show improvement within the first month following the event [44](#page=44). * Speech therapy is considered helpful, particularly in the early stages after the onset of aphasia [44](#page=44). * The benefit of speech therapy tends to be limited after a few months [44](#page=44). --- # Cranial nerve disorders: Bell Palsy and Trigeminal Neuralgia This section provides a detailed overview of two distinct cranial nerve disorders: Bell Palsy, affecting the facial nerve (CN VII), and Trigeminal Neuralgia, impacting the trigeminal nerve (CN V). ### 22.1 Bell palsy (CN VII LMN palsy) #### 22.1.1 Definition Bell palsy is an acute, unilateral lower motor neuron (LMN) facial paralysis that affects all muscles innervated by the facial nerve (CN VII). This means both the upper and lower parts of the face are involved [45](#page=45). #### 22.1.2 Pathophysiology The pathophysiology involves inflammation and edema of the facial nerve, leading to its compression within the facial canal. A viral trigger, most suspected to be herpes simplex virus type 1 (HSV-1), is often implicated [45](#page=45). #### 22.1.3 Causes While most cases are idiopathic (unknown cause), other contributing factors include viral infections (especially HSV), and immunologic factors. Bell palsy is frequently preceded by an upper respiratory tract infection (URTI) [45](#page=45). #### 22.1.4 Clinical features The hallmark symptom is acute, unilateral facial weakness that involves the forehead and mouth, a key characteristic of LMN lesions. Patients are typically unable to close their eye on the affected side. Other symptoms can include hyperacusis (due to stapedius paralysis), loss of taste on the anterior two-thirds of the tongue, and pain around the ear or jaw [45](#page=45). #### 22.1.5 Diagnosis Bell palsy is primarily a clinical diagnosis. In endemic areas, Lyme disease should be considered, and if suspected, steroids should be avoided. Electromyography (EMG) may be considered if there is no improvement after 10 days [45](#page=45). #### 22.1.6 Treatment Bell palsy is usually self-limiting. Treatment typically involves a short course of steroids, such as prednisone. Antiviral medication, like acyclovir, may be prescribed in some cases. Crucially, diligent eye care is essential, including using a night eye patch and artificial tears to prevent corneal drying [45](#page=45). > **Tip:** Eye care is critical in Bell Palsy due to the inability to fully close the eyelid, which can lead to corneal abrasions and infections. #### 22.1.7 Prognosis The prognosis for Bell palsy is generally very good, with approximately 80% of individuals recovering fully within weeks to months [45](#page=45). #### 22.1.8 Differentials Important differential diagnoses for Bell Palsy include stroke (where the forehead is typically spared due to UMN innervation), Lyme disease, acoustic neuroma, Guillain-Barré syndrome (which is usually bilateral), and herpes zoster (Ramsay Hunt syndrome) [45](#page=45). ### 22.2 Trigeminal neuralgia (tic douloureux) #### 22.2.1 Definition Trigeminal neuralgia is characterized by sudden, severe, electric shock-like facial pain that involves the trigeminal nerve (CN V) [46](#page=46). #### 22.2.2 Pathophysiology The underlying pathophysiology is believed to be compression of the trigeminal nerve, most commonly by an adjacent blood vessel. This compression can lead to demyelination and abnormal nerve firing, resulting in extreme pain [46](#page=46). #### 22.2.3 Causes While often idiopathic, trigeminal neuralgia can be caused by conditions that affect the myelin sheath, such as multiple sclerosis. Other causes include tumors or cysts, arteriovenous malformations (AVMs), and prior facial trauma or surgery [46](#page=46). #### 22.2.4 Clinical features The condition presents with brief attacks of pain, lasting from seconds to minutes, which are recurrent and severe. The pain is typically lancinating and usually unilateral. The most common divisions involved are the maxillary (V2), followed by the mandibular (V3) division, with the ophthalmic (V1) division being less commonly affected. A key feature is the presence of triggers, which can include touching the face, chewing, talking, drinking, or even wind. Importantly, there is no associated motor weakness [46](#page=46). > **Example:** A patient with trigeminal neuralgia might experience excruciating pain triggered by simply brushing their teeth or feeling a slight breeze on their face. #### 22.2.5 Diagnosis Trigeminal neuralgia is primarily a clinical diagnosis. An MRI of the brain may be performed to rule out structural causes like a posterior fossa tumor or evidence of multiple sclerosis [46](#page=46). #### 22.2.6 Treatment The drug of choice for trigeminal neuralgia is carbamazepine. Alternative medications include baclofen and phenytoin. For patients refractory to medical treatment, surgical decompression of the trigeminal nerve may be considered [46](#page=46). #### 22.2.7 Course The course of trigeminal neuralgia is typically relapsing-remitting, meaning episodes of pain may occur, subside, and then return. Over time, the pain may progressively worsen [46](#page=46). #### 22.2.8 Prognosis The prognosis varies, with approximately 85% of cases experiencing spontaneous resolution of pain. About 10% may have mild residual pain, while 5% experience persistent, severe pain [46](#page=46). --- # Principles of localizing neurologic lesions Localizing a neurologic lesion involves mapping clinical signs and symptoms to specific anatomical structures within the nervous system, progressing from the cerebral cortex down to the muscle [47](#page=47) [48](#page=48). ### 23.1 Hierarchical localization of neurologic lesions The nervous system can be systematically analyzed to pinpoint the location of a lesion. This guide outlines common clinical presentations associated with damage at various levels [47](#page=47) [48](#page=48). #### 23.1.1 Cerebral cortex Lesions in the cerebral cortex typically result in contralateral motor and sensory deficits. Deficits may disproportionately affect the face and arm compared to the leg. Specific cortical functions include aphasia (typically with left hemisphere lesions) and visuospatial neglect (typically with right hemisphere lesions) [47](#page=47) [48](#page=48). * **Mnemonic:** "Cortex = Cognition + Contralateral" [47](#page=47) [48](#page=48). #### 23.1.2 Subcortical structures (e.g., internal capsule) Damage to subcortical structures, such as the internal capsule, often leads to a complete hemiparesis affecting the face, arm, and leg. Motor and sensory deficits occur together in these regions due to the dense packing of nerve fibers [47](#page=47) [48](#page=48). * **Mnemonic:** "Packed fibers = total damage" [47](#page=47) [48](#page=48). #### 23.1.3 Cerebellum Cerebellar lesions manifest as ataxia (lack of voluntary coordination of muscle movements), intention tremor (tremor that occurs during voluntary movement), and dysmetria (inability to control the distance, power, and speed of muscular actions). Notably, there is typically no associated weakness [47](#page=47) [48](#page=48). * **Mnemonic:** "Drunk walk, strong muscles" [47](#page=47) [48](#page=48). #### 23.1.4 Brainstem Brainstem lesions present with a characteristic pattern of ipsilateral cranial nerve deficits (affecting the same side as the lesion) and contralateral body weakness or sensory loss (affecting the opposite side). This "crossroads" of neural pathways leads to these mixed ipsilateral and contralateral symptoms [47](#page=47) [48](#page=48). * **Mnemonic:** "Face same side, body opposite" [47](#page=47) [48](#page=48). #### 23.1.5 Spinal cord Spinal cord lesions are identified by upper motor neuron (UMN) signs below the level of the lesion. A pathognomonic sign is a distinct sensory level, marking the rostral extent of the damage. Bowel and bladder dysfunction is also common with spinal cord involvement [47](#page=47) [48](#page=48). * **Mnemonic:** "Level = cord" [47](#page=47) [48](#page=48). #### 23.1.6 Plexus (plexopathy) Plexopathies, affecting nerve plexuses (like the brachial or lumbosacral plexus), result in motor and sensory deficits that involve more than one nerve distribution. The distribution of symptoms is often patchy and not confined to a single nerve territory [47](#page=47) [48](#page=48). * **Mnemonic:** "Messy nerves = plexus" [47](#page=47) [48](#page=48). #### 23.1.7 Root (radiculopathy) Radiculopathy, or nerve root compression, is characterized by pain as a key feature, often described as sharp or shooting. Associated symptoms include dermatomal sensory loss (affecting skin areas supplied by a specific nerve root) and myotomal weakness (affecting muscles innervated by a specific nerve root). Reflexes related to the affected root are typically diminished or absent [47](#page=47) [48](#page=48). * **Mnemonic:** "Pain + dermatome = root" [47](#page=47) [48](#page=48). #### 23.1.8 Peripheral nerve Lesions of individual peripheral nerves typically cause distal weakness that is greater than proximal weakness. These deficits are often asymmetric. Deep tendon reflexes may be diminished or absent in the affected nerve's distribution, and sensory loss is common [47](#page=47) [48](#page=48). * **Mnemonic:** "Glove & stocking = nerve" [47](#page=47) [48](#page=48). #### 23.1.9 Neuromuscular junction Dysfunction at the neuromuscular junction is characterized by fatigability, where weakness worsens with use and improves with rest. Sensation remains normal [47](#page=47) [48](#page=48). * **Mnemonic:** "Use gets worse, rest gets better" [47](#page=47) [48](#page=48). #### 23.1.10 Muscle (myopathy) Myopathies, affecting the muscles themselves, typically present with symmetric proximal weakness, most noticeably impacting the shoulders and hips. Sensation is preserved, and fasciculations (muscle twitches) are absent [47](#page=47) [48](#page=48). * **Mnemonic:** "Can't climb stairs = muscle" [47](#page=47) [48](#page=48). --- ## Common mistakes to avoid - Review all topics thoroughly before exams - Pay attention to formulas and key definitions - Practice with examples provided in each section - Don't memorize without understanding the underlying concepts

| Term | Definition | |------|------------| | Ischemic Stroke | A condition where blood flow to a part of the brain is obstructed, leading to neuronal death. | | Transient Ischemic Attack (TIA) | A temporary episode of neurologic dysfunction caused by focal brain ischemia, with symptoms lasting less than 24 hours and no permanent infarction. | | Thrombotic Stroke | A type of ischemic stroke caused by the formation of a thrombus on an atherosclerotic plaque, often in large arteries. | | Embolic Stroke | An ischemic stroke caused by a blood clot or other debris that travels from a distant source (e.g., heart, carotid plaque) and lodges in a cerebral artery. | | Lacunar Stroke | A stroke caused by the occlusion of small penetrating arteries, typically due to lipohyalinosis secondary to hypertension and diabetes, affecting deep brain structures. | | Lipohyalinosis | A degenerative process affecting small arteries and arterioles, characterized by thickening and hyaline deposition, commonly associated with hypertension and diabetes. | | Intracerebral Hemorrhage (ICH) | Bleeding directly into the brain parenchyma. | | Subarachnoid Hemorrhage (SAH) | Bleeding into the subarachnoid space, the area between the arachnoid mater and the pia mater surrounding the brain. | | Charcot–Bouchard Microaneurysms | Small, weak outpouchings of arteries in the brain, particularly in the basal ganglia, that are prone to rupture and cause intracerebral hemorrhage, especially in hypertensive individuals. | | Vasospasm | Narrowing of cerebral arteries, often occurring after subarachnoid hemorrhage, which can lead to delayed cerebral ischemia. | | Nimodipine | A calcium channel blocker used prophylactically to reduce the risk of ischemic deficits caused by vasospasm following aneurysmal subarachnoid hemorrhage. | | Parkinson Disease | A progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms. | | TRAP | Acronym for the core clinical features of Parkinson disease: Tremor, Rigidity, Akinesia/Bradykinesia, and Postural instability. | | Rigidity | Stiffness of the limbs and trunk, often described as cogwheel or lead-pipe, a characteristic symptom of Parkinson disease. | | Bradykinesia | Slowness of movement, a hallmark symptom of Parkinson disease, affecting initiation and execution of voluntary movements. | | Postural Instability | Impairment of balance and postural reflexes, leading to falls, a later symptom of Parkinson disease. | | Lewy Bodies | Abnormal clumps of alpha-synuclein protein found in neurons, a key pathological feature of Parkinson disease and Dementia with Lewy Bodies. | | Parkinsonism | A syndrome characterized by tremor, rigidity, bradykinesia, and postural instability, which can be caused by Parkinson disease or other conditions. | | Parkinson-plus Syndromes | A group of neurodegenerative disorders that present with parkinsonian features but have distinct pathologies and clinical courses compared to idiopathic Parkinson disease. Examples include Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP). | | DaTscan (SPECT) | A type of nuclear medicine imaging test that uses a radiotracer to assess dopamine transporter levels in the brain, helpful in differentiating Parkinson disease from essential tremor. | | Huntington Chorea | An autosomal dominant neurodegenerative disorder characterized by progressive chorea (involuntary movements), behavioral changes, and cognitive decline. | | Chorea | A neurological disorder characterized by involuntary, irregular, purposeless movements of the limbs, face, and trunk. | | Essential Tremor (ET) | A common neurological disorder characterized by involuntary rhythmic shaking, typically affecting the hands and often the head and voice, which is worse with action and improved by alcohol. | | Cerebellar Tremor | A type of tremor associated with cerebellar dysfunction, characterized by coarse, involuntary movements that worsen as the limb approaches its intended target (intention tremor). | | Ataxia | A neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. | | Restless Leg Syndrome (RLS) | A neurological disorder characterized by an uncomfortable urge to move the legs, typically occurring at rest or in the evening, and relieved by movement. | | Tourette Syndrome | A neurological disorder characterized by multiple motor tics and at least one vocal tic, usually with onset before the age of 21. | | Dementia | A progressive decline in intellect, affecting memory, language, executive function, and other cognitive domains, with preserved consciousness. | | Alzheimer Disease (AD) | The most common cause of dementia, characterized by progressive neurodegeneration, memory loss, and cortical dysfunction, associated with amyloid-beta plaques and tau tangles. | | Amyloid Cascade Hypothesis | A leading hypothesis for Alzheimer disease pathogenesis, suggesting that the accumulation of amyloid-beta peptides initiates a cascade of events leading to neuronal dysfunction and death. | | Neurofibrillary Tangles | Intracellular aggregates of hyperphosphorylated tau protein, a key pathological hallmark of Alzheimer disease. | | Cholinesterase Inhibitors | A class of drugs (e.g., donepezil, rivastigmine, galantamine) used to treat Alzheimer disease by increasing acetylcholine levels in the brain, offering modest symptomatic improvement. | | Memantine | An NMDA receptor antagonist used to treat moderate to severe Alzheimer disease, which may help improve cognition and slow functional decline. | | Dementia with Lewy Bodies (DLB) | A type of dementia characterized by the presence of Lewy bodies in the brain, combining cognitive impairment with parkinsonian features and visual hallucinations. | | Delirium | An acute, fluctuating disturbance of cognition and attention, typically caused by a medical or systemic condition, which is usually reversible. | | CAM (Confusion Assessment Method) | A diagnostic tool used to assess for delirium, focusing on acute onset, fluctuating course, inattention, disorganized thinking, and altered level of consciousness. | | Coma | A profound state of unconsciousness where a person is unresponsive to all stimuli, indicating severe impairment of both arousal and awareness. | | GCS (Glasgow Coma Scale) | A neurological scale used to objectively assess the extent of a person's consciousness by measuring eye opening, verbal response, and motor response. | | Herniation | The displacement of brain tissue from one compartment to another due to increased intracranial pressure, which can lead to severe neurological deficits or death. | | Locked-In Syndrome | A condition characterized by complete paralysis of voluntary muscles except for eye movements, while consciousness and cognitive function are preserved, often due to a lesion in the ventral pons. | | Multiple Sclerosis (MS) | A chronic, immune-mediated demyelinating disease of the central nervous system, affecting the brain and spinal cord, leading to relapsing and remitting neurological deficits. | | Demyelination | The loss of the myelin sheath that surrounds nerve fibers, which impairs nerve impulse conduction. | | Plaques | Lesions in the white matter of the CNS, characteristic of multiple sclerosis, resulting from demyelination and inflammation. | | Internuclear Ophthalmoplegia (INO) | A disorder of conjugate gaze characterized by impaired adduction of one eye with nystagmus in the abducting eye, typically caused by a lesion in the medial longitudinal fasciculus (MLF). | | McDonald Criteria | Diagnostic criteria for multiple sclerosis that require evidence of lesions disseminated in time and space within the central nervous system. | | Guillain-Barré Syndrome (GBS) | An acute inflammatory demyelinating polyneuropathy of the peripheral nervous system, characterized by rapidly ascending, symmetric motor weakness, often triggered by infection. | | AIDP (Acute Inflammatory Demyelinating Polyneuropathy) | The most common form of Guillain-Barré Syndrome. | | Albuminocytologic Dissociation | A characteristic finding in the cerebrospinal fluid (CSF) of patients with Guillain-Barré Syndrome, showing elevated protein levels with a normal cell count. | | IV Immunoglobulin (IVIG) | A treatment for autoimmune and immune-mediated disorders, including Guillain-Barré Syndrome, administered intravenously. | | Plasmapheresis | A medical procedure to remove plasma from the blood and separate it from blood cells, used in conditions like Guillain-Barré Syndrome to remove harmful antibodies. | | Myasthenia Gravis (MG) | An autoimmune disorder affecting the neuromuscular junction, characterized by fatigable skeletal muscle weakness due to antibodies against postsynaptic nicotinic acetylcholine receptors. | | Neuromuscular Junction (NMJ) | The specialized synapse between a motor neuron and a muscle fiber, where neurotransmitters are released to induce muscle contraction. | | Acetylcholine Receptors (AChRs) | Receptors located on the postsynaptic membrane of muscle fibers that bind to acetylcholine, triggering muscle contraction. | | Fatigable Muscle Weakness | Weakness that worsens with repetitive use and improves with rest, a hallmark symptom of Myasthenia Gravis. | | Ptosis | Drooping of the upper eyelid. | | Diplopia | Double vision. | | Myasthenic Crisis | A severe exacerbation of Myasthenia Gravis leading to respiratory failure requiring mechanical ventilation. | | Thymoma | A tumor of the thymus gland, often associated with Myasthenia Gravis. | | Pyridostigmine | An acetylcholinesterase inhibitor used to treat Myasthenia Gravis by increasing the availability of acetylcholine at the neuromuscular junction. | | Thymectomy | Surgical removal of the thymus gland, which can induce remission in Myasthenia Gravis, especially in patients with thymoma. | | Muscular Dystrophy | A group of genetic disorders characterized by progressive muscle degeneration and weakness. | | Duchenne Muscular Dystrophy (DMD) | An X-linked recessive muscular dystrophy caused by the absence of dystrophin, leading to severe, early-onset muscle degeneration. | | Dystrophin | A protein that plays a crucial role in stabilizing the muscle cell membrane. | | Gowers’ Maneuver | A method of rising to a standing position by using the hands to support the thighs and push the body upward, often seen in children with proximal muscle weakness like Duchenne muscular dystrophy. | | Pseudohypertrophy | The apparent enlargement of a muscle that is actually due to replacement of muscle tissue with fat and connective tissue, commonly seen in the calves in Duchenne muscular dystrophy. | | Creatine Phosphokinase (CPK) | An enzyme that is released into the blood when muscle tissue is damaged. Elevated levels are indicative of muscle disorders like muscular dystrophy. | | Becker Muscular Dystrophy (BMD) | An X-linked muscular dystrophy caused by reduced but partially functional dystrophin, leading to milder symptoms and a slower disease progression than Duchenne muscular dystrophy. | | Neurocutaneous Syndromes | A group of genetic disorders characterized by abnormalities of the skin, nervous system, and sometimes other organs. | | Neurofibromatosis Type I (NF1) | An autosomal dominant disorder characterized by café-au-lait spots, Lisch nodules, neurofibromas, and increased risk of CNS tumors and bone abnormalities. | | Café-au-lait Spots | Flat, light brown birthmarks on the skin. | | Lisch Nodules | Benign, pigmented iris hamartomas characteristic of Neurofibromatosis Type I. | | Neurofibromatosis Type II (NF2) | An autosomal dominant disorder characterized by bilateral acoustic neuromas and multiple meningiomas. | | Acoustic Neuroma | A benign tumor of the Schwann cells that surround the vestibulocochlear nerve (CN VIII). | | Tuberous Sclerosis (TS) | An autosomal dominant neurocutaneous syndrome characterized by hamartomas in multiple organs, including the brain, heart, kidneys, and skin, often presenting with seizures, cognitive impairment, and skin lesions. | | Hamartoma | A benign, localized overgrowth of disorganized tissues normally found in that area. | | Angiofibromas | Small, reddish-brown benign tumors of the skin containing blood vessels and fibrous tissue. | | Ash-leaf Macules | Hypopigmented macules on the skin, characteristic of Tuberous Sclerosis. | | Shagreen Patches | Areas of leathery, raised skin, often found on the lower back or buttocks, seen in Tuberous Sclerosis. | | Rhabdomyoma | A benign tumor composed of developing muscle cells, often found in the heart of infants with Tuberous Sclerosis. | | Angiomyolipoma | A benign tumor composed of blood vessels, smooth muscle, and fat, commonly found in the kidneys of patients with Tuberous Sclerosis. | | Sturge-Weber Syndrome | A sporadic neurocutaneous syndrome characterized by a facial port-wine stain (nevus flammeus), seizures, intellectual disability, and leptomeningeal angiomas. | | Port-wine Stain | A flat, pink to deep purple birthmark caused by abnormal blood vessels. | | Leptomeningeal Angiomas | Vascular malformations involving the pia mater and arachnoid mater of the brain. | | Von Hippel-Lindau (VHL) Disease | An autosomal dominant neurocutaneous syndrome characterized by multiple hemangioblastomas in the CNS and vascular tumors/cysts in various organs, including the kidneys and adrenal glands. | | Hemangioblastoma | A benign, highly vascular tumor that typically arises in the cerebellum, brainstem, or retina. | | Renal Cell Carcinoma | A type of kidney cancer. | | Pheochromocytoma | A tumor of the adrenal medulla that produces excessive amounts of catecholamines. | | Syringomyelia | A condition characterized by the development of a fluid-filled cavity (syrinx) within the spinal cord, often causing neurological deficits. | | Syrinx | A fluid-filled cyst or cavity within the spinal cord. | | Arnold-Chiari Malformation (Type I) | A condition where the cerebellar tonsils extend below the foramen magnum, often associated with syringomyelia. | | Cape-like Distribution | A sensory deficit pattern affecting the shoulders, arms, and upper chest, characteristic of syringomyelia due to early involvement of the decussating spinothalamic fibers. | | Lower Motor Neuron (LMN) Signs | Symptoms resulting from damage to motor neurons in the spinal cord or brainstem, including weakness, muscle atrophy, fasciculations, and hyporeflexia. | | Upper Motor Neuron (UMN) Signs | Symptoms resulting from damage to motor pathways in the brain or spinal cord, including spasticity, hyperreflexia, and pathological reflexes (e.g., Babinski sign). | | Brown-Séquard Syndrome | A neurological deficit resulting from hemisection of the spinal cord, characterized by ipsilateral UMN signs and loss of vibration/proprioception, and contralateral loss of pain and temperature. | | Transverse Myelitis | An inflammatory disorder affecting the spinal cord across its entire cross-section at one level, causing bilateral weakness, sensory loss, and autonomic dysfunction below the lesion. | | Horner Syndrome | A condition characterized by a classic triad of symptoms on one side of the face due to interruption of the sympathetic nerve pathway to the eye and face: mild ptosis, anhidrosis, and miosis. | | Ptosis | Drooping of the upper eyelid. | | Anhidrosis | Reduced or absent sweating. | | Miosis | Constriction of the pupil. | | Pancoast Tumor | A type of lung cancer located in the apex of the lung, which can compress sympathetic nerves and cause Horner syndrome. | | Poliomyelitis | An infectious disease caused by the poliovirus that attacks motor neurons, leading to flaccid paralysis, muscle atrophy, and absent reflexes. | | Vertigo | A sensation of spinning or movement, either of oneself or of the surroundings, usually caused by dysfunction of the vestibular system. | | Peripheral Vertigo | Vertigo originating from the inner ear or vestibular nerve. | | Central Vertigo | Vertigo originating from the brainstem or cerebellum. | | Nystagmus | Involuntary, rhythmic movements of the eyes, which can be horizontal, vertical, or torsional, and are often indicative of vestibular or brainstem dysfunction. | | HINTS Exam | A mnemonic for a bedside examination (Head Impulse, Nystagmus, Test of Skew) used to differentiate central from peripheral causes of acute vertigo, particularly in the context of suspected stroke. | | BPPV (Benign Paroxysmal Positional Vertigo) | A common cause of peripheral vertigo characterized by brief, intense episodes of vertigo triggered by changes in head position, due to displaced otoliths in the semicircular canals. | | Ménière Disease | A disorder of the inner ear characterized by episodes of vertigo, tinnitus, hearing loss, and a sensation of fullness in the ear. | | Labyrinthitis | Inflammation of the labyrinth of the inner ear, typically caused by a viral infection, leading to vertigo, hearing loss, and tinnitus. | | Syncope | A transient loss of consciousness and posture due to a temporary reduction in cerebral blood flow, followed by rapid and complete recovery. | | Vasovagal Syncope | A common type of reflex syncope triggered by emotional stress, pain, or other stimuli, characterized by bradycardia and vasodilation leading to a drop in blood pressure. | | Orthostatic Hypotension | A significant drop in blood pressure upon standing, which can cause lightheadedness or syncope. | | Seizures | Sudden, abnormal, uncontrolled electrical discharges in the brain that can cause changes in behavior, movements, feelings, and consciousness. | | Epilepsy | A neurological disorder characterized by recurrent, unprovoked seizures. | | Status Epilepticus | A medical emergency characterized by continuous seizure activity or recurrent seizures without recovery of consciousness between them. | | Amyotrophic Lateral Sclerosis (ALS) | A progressive neurodegenerative disease that affects motor neurons in the brain and spinal cord, leading to muscle weakness, atrophy, and paralysis. | | Fasciculations | Small, involuntary muscle twitches visible under the skin, often associated with lower motor neuron disease. | | Aphasia | A language disorder resulting from damage to the language centers of the brain, affecting the ability to speak, understand, read, or write. | | Wernicke Aphasia | A fluent aphasia characterized by impaired comprehension and fluent but often nonsensical speech. | | Broca Aphasia | A non-fluent aphasia characterized by difficulty producing speech, with preserved comprehension. | | Conduction Aphasia | An aphasia characterized by difficulty repeating words or phrases, with relatively preserved fluency and comprehension. | | Global Aphasia | A severe aphasia characterized by profound impairment of all language modalities: speaking, understanding, reading, and writing. | | Bell Palsy | Acute, unilateral lower motor neuron paralysis of the facial nerve (CN VII), affecting both the upper and lower face. | | Trigeminal Neuralgia | A chronic pain condition characterized by sudden, severe, electric shock-like episodes of facial pain in the distribution of the trigeminal nerve (CN V). | | CN V (Trigeminal Nerve) | The fifth cranial nerve, responsible for sensation in the face and motor control of chewing muscles. | | CN VII (Facial Nerve) | The seventh cranial nerve, responsible for facial expression, taste sensation, and control of lacrimal and salivary glands. |