CMDT26 Ch11 Data

{"title": "Chapter 11: Neurological Disorders", "flashcards": [{"q": "What is the NIHSS and what score represents a moderate stroke?", "a": "NIH Stroke Scale (NIHSS) grades 15 neurological domains (level of consciousness, gaze, visual fields, facial palsy, limb strength, ataxia, sensory, language, dysarthria, extinction). Score 0 = no deficit; 1–4 = minor; 5–15 = moderate; 16–20 = moderate-severe; ≥21 = severe. It guides thrombolysis eligibility and predicts functional outcome."}, {"q": "Name the ILAE 2017 classification of seizure onset.", "a": "Focal onset (aware or impaired awareness → motor or non-motor features); Generalised onset (tonic-clonic, absence, myoclonic, atonic, tonic, clonic); Unknown onset (unclassified). Replaces outdated 'grand mal/petit mal/partial seizure' terminology. Onset type guides investigation and drug selection."}, {"q": "What are the CSF findings in bacterial versus viral meningitis?", "a": "Bacterial: turbid CSF; WBC >1000/µL (predominantly neutrophils); protein >1 g/L; glucose <50% plasma (usually <2.5 mmol/L); organism on Gram stain in ~60%. Viral: clear CSF; WBC 10–500/µL (predominantly lymphocytes); protein mildly raised (0.5–1 g/L); glucose normal (>50% plasma)."}, {"q": "What is the 'thunderclap headache' and what is its significance?", "a": "Thunderclap headache: sudden-onset severe headache reaching maximal intensity within 1 minute ('worst headache of life'). It is subarachnoid haemorrhage until proved otherwise. CT head (ideally ≤6h post-onset — 98% sensitive) followed by LP at ≥12 hours post-onset (for xanthochromia spectrophotometry) if CT negative. Other causes: CVT, reversible cerebral vasoconstriction syndrome (RCVS), hypertensive emergency."}, {"q": "Name four features of Parkinson's disease on clinical examination.", "a": "TRAP: Tremor (resting, 4–6 Hz, pill-rolling, suppressed by action); Rigidity (cogwheel/leadpipe); Akinesia/bradykinesia (slowness of movements, micrographia, hypomimia, reduced arm swing); Postural instability (late feature). Plus: flexed posture, festinant gait, hypophonia, sialorrhoea, seborrhoeic dermatitis. Asymmetric onset is characteristic."}, {"q": "What is the time window for IV alteplase in acute ischaemic stroke?", "a": "IV alteplase 0.9 mg/kg (max 90 mg; 10% as bolus, 90% over 60 min) is licensed within 4.5 hours of stroke onset in eligible patients. Contraindications: recent surgery, BP >185/110 (must be treated first), active bleeding, recent stroke/head injury, anticoagulant use. Tenecteplase (0.25 mg/kg single bolus) is emerging as an alternative."}, {"q": "What is the treatment for generalised convulsive status epilepticus if benzodiazepines fail?", "a": "Phase 1: IV/buccal lorazepam or diazepam (repeat once if seizure continues). Phase 2 (after 10–20 min): IV levetiracetam 60 mg/kg (preferred — ESETT trial non-inferior, safer), OR IV sodium valproate 40 mg/kg, OR IV phenytoin 20 mg/kg. Phase 3 (after 20–40 min of established SE): ICU with general anaesthesia (propofol or thiopental infusion). Identify and treat underlying cause."}, {"q": "Name three 'red flags' in headache history requiring urgent investigation.", "a": "SNOOP4: Systemic symptoms/immunocompromise (HIV, cancer); Neurological focal deficit; Onset sudden/thunderclap; Older patient (new onset >50); Postural component; Papilloedema; Progressive worsening; Precipitated by Valsalva (cough/strain). Any red flag warrants urgent CT head ± LP ± MRI brain."}, {"q": "What is the mechanism of action of levetiracetam?", "a": "Levetiracetam binds synaptic vesicle protein 2A (SV2A), a presynaptic protein involved in vesicle exocytosis. This modulates neurotransmitter release, particularly reducing rapid burst-firing of neurons during seizure activity. It has broad-spectrum efficacy across seizure types, few drug interactions (non-CYP metabolised), and can be loaded IV rapidly. Side effects: behavioural disturbance (irritability, aggression) in ~15%."}, {"q": "What is the Waterhouse-Friderichsen syndrome?", "a": "Bilateral adrenal haemorrhage from fulminant meningococcaemia, causing acute adrenal insufficiency. Characterised by: purpuric/petechial rash (non-blanching), DIC, septic shock, and bilateral adrenal haemorrhage on imaging. High-dose hydrocortisone (100 mg IV stat, then 200 mg/24h by infusion) is added to antibiotics. Mortality remains high despite treatment."}], "quiz": [{"q": "What is the most important prognostic factor for functional recovery after ischaemic stroke?", "opts": ["Patient age", "Time to reperfusion (shorter door-to-needle/door-to-groin time)", "Gender", "Prior antiplatelet use"], "ans": 1, "exp": "Time to reperfusion is the single most important determinant of outcome in large vessel occlusion ischaemic stroke. 'Time is brain' — approximately 1.9 million neurones are lost per minute during ischaemic stroke. Early thrombolysis and mechanical thrombectomy (for large vessel occlusion) maximally limit infarct core and penumbra."}, {"q": "What is the recommended antiplatelet regimen in the first 24 hours after acute minor ischaemic stroke/TIA?", "opts": ["Aspirin alone 75 mg", "Dual antiplatelet therapy: aspirin + clopidogrel for 21–30 days (POINT/CHANCE trials), then clopidogrel monotherapy", "Warfarin immediately", "Ticagrelor monotherapy"], "ans": 1, "exp": "POINT and CHANCE trials established dual antiplatelet therapy (aspirin 75 mg + clopidogrel 75 mg — or clopidogrel loading dose) for 21 days after high-risk TIA or minor stroke (ABCD2 ≥4), reducing early stroke recurrence by ~25%. THALES trial confirmed aspirin + ticagrelor also effective. Thereafter, clopidogrel monotherapy for secondary prevention."}, {"q": "A patient develops sudden unilateral limb weakness, ataxia, nystagmus, and Horner's syndrome. Which artery is occluded?", "opts": ["Middle cerebral artery", "Posterior inferior cerebellar artery (PICA) — lateral medullary syndrome (Wallenberg syndrome)", "Anterior communicating artery", "Basilar artery"], "ans": 1, "exp": "Lateral medullary (Wallenberg) syndrome results from PICA or vertebral artery occlusion. Features: ipsilateral Horner's (sympathetic tract), ipsilateral facial pain/numbness (V nucleus), ipsilateral ataxia (cerebellar connections), contralateral limb pain/temperature loss (spinothalamic tract), dysphagia/dysarthria (nucleus ambiguus), nystagmus, vertigo. Classic 'crossed sensory deficit.'"}, {"q": "What is the investigation of choice for a suspected brain tumour?", "opts": ["CT head without contrast", "MRI brain with gadolinium contrast", "PET-CT", "EEG"], "ans": 1, "exp": "MRI brain with gadolinium is the gold-standard for brain tumour characterisation — superior contrast resolution delineates tumour margins, vascularity, oedema, and mass effect. CT is used for emergency triage (detecting haemorrhage, herniation, hydrocephalus) but is insufficient for definitive tumour characterisation. MR spectroscopy and perfusion-weighted imaging provide additional information."}, {"q": "What is the mechanism of myasthenia gravis?", "opts": ["Destruction of presynaptic motor nerve terminals", "Autoimmune IgG antibodies against postsynaptic acetylcholine receptors (AChR) at the neuromuscular junction, reducing available AChRs and causing fatigable weakness", "Failure of acetylcholine synthesis", "Channelopathy affecting voltage-gated calcium channels"], "ans": 1, "exp": "Myasthenia gravis: AChR antibodies (85% of generalised MG) or MuSK antibodies block, destroy, or cross-link postsynaptic AChRs. Repetitive muscle use depletes acetylcholine at the synapse, producing characteristic fatigable weakness improving with rest. Edrophonium test (Tensilon test) or repetitive nerve stimulation supports diagnosis. Anti-AChR antibody confirms."}, {"q": "What is the most appropriate initial investigation for suspected normal pressure hydrocephalus (NPH)?", "opts": ["LP with opening pressure", "MRI brain (enlarged ventricles out of proportion to cortical atrophy, periventricular T2 signal change) followed by LP drainage (50 mL) to assess gait improvement", "EEG", "CT myelogram"], "ans": 1, "exp": "NPH presents with the classic Hakim's triad: gait dyspraxia ('magnetic gait' — shuffling, wide-based), urinary incontinence, and cognitive decline. MRI shows hydrocephalus disproportionate to atrophy with periventricular changes. LP tap test (30–50 mL CSF removal) demonstrating gait improvement predicts VP shunt response. VP shunting benefits selected patients."}, {"q": "Which drug is the treatment of choice for trigeminal neuralgia?", "opts": ["Amitriptyline", "Carbamazepine (or oxcarbazepine as better-tolerated alternative)", "Gabapentin", "Naproxen"], "ans": 1, "exp": "Carbamazepine is first-line for trigeminal neuralgia (NNT ~2), effective in 70–80% initially. Starting dose ~100 mg BD, titrating to response. Oxcarbazepine has fewer drug interactions and is better tolerated. If medical therapy fails: microvascular decompression (MVD) of the trigeminal nerve root entry zone — most durable surgical option with lowest recurrence rate."}, {"q": "A 25-year-old woman has a first unprovoked seizure. MRI and EEG are normal. What is the advice regarding driving?", "opts": ["She can drive immediately after the seizure", "She must not drive for 12 months from the seizure date (DVLA guidelines UK), notified to DVLA immediately", "She can drive after 3 months", "No driving restrictions apply for a single seizure"], "ans": 1, "exp": "DVLA (UK) regulations: after a first unprovoked seizure, ordinary driving licence (Group 1) must not be held for 12 months. The patient must inform the DVLA. Driving may resume if seizure-free for 12 months (or with satisfactory specialist assessment). Group 2 (HGV/PSV) licence requires seizure-free for 10 years off medication. Clinician has duty to advise; DVLA has duty to decide."}, {"q": "What is the first-line treatment for multiple sclerosis relapse?", "opts": ["Natalizumab", "High-dose methylprednisolone 500–1000 mg IV for 3–5 days", "Interferon beta", "Dimethyl fumarate"], "ans": 1, "exp": "Acute MS relapse causing significant functional disability is treated with high-dose methylprednisolone (500–1000 mg IV OD for 3–5 days, or equivalent oral dose). Steroids speed recovery but do not alter long-term outcome. Disease-modifying therapies (interferon, natalizumab, alemtuzumab, cladribine) prevent relapses and accumulation of disability."}, {"q": "What is Guillain-Barré syndrome (GBS) and what is its most feared complication?", "opts": ["An autoimmune demyelinating disorder of the CNS", "Acute inflammatory demyelinating polyneuropathy (AIDP) — immune attack on peripheral myelin post-infection; most feared complication is respiratory failure requiring mechanical ventilation (occurs in ~30%)", "A viral encephalitis", "A genetic motor neuron disease"], "ans": 1, "exp": "GBS is an acute immune-mediated polyradiculoneuropathy, typically triggered by Campylobacter jejuni, CMV, EBV, or influenza. Features: ascending flaccid paralysis, areflexia, albuminocytological dissociation (raised CSF protein with normal cell count). Treatment: IVIG 2 g/kg or plasma exchange. Respiratory monitoring (FVC <20 mL/kg or falling rapidly) guides ICU admission."}, {"q": "What is the difference between encephalitis and meningitis?", "opts": ["They are identical conditions", "Meningitis = inflammation of the meninges (fever, headache, neck stiffness, photophobia — sparing brain parenchyma); encephalitis = inflammation of brain parenchyma itself (altered consciousness, focal neurological signs, seizures, behavioural change) — often coexist as meningoencephalitis", "Encephalitis is only bacterial; meningitis only viral", "Meningitis causes seizures; encephalitis does not"], "ans": 1, "exp": "Encephalitis is characterised by altered brain function (encephalopathy, focal deficits, seizures, personality change) due to brain parenchymal inflammation — most commonly viral (HSV-1 most common in UK — urgent aciclovir), autoimmune (anti-NMDAR, LGI1, CASPR2), or paraneoplastic. CSF shows lymphocytic pleocytosis; MRI shows temporal lobe changes in HSE. Autoimmune encephalitis: anti-NMDAR — young women, ovarian teratoma, psychiatric features."}, {"q": "What is the mechanism of action of levodopa in Parkinson's disease?", "opts": ["Dopamine agonist", "Crosses the blood-brain barrier (dopamine cannot); converted to dopamine by DOPA decarboxylase in central dopaminergic neurones; combined with peripheral DDC inhibitor (carbidopa or benserazide) to prevent peripheral conversion and side effects (nausea, hypotension)", "Inhibits acetylcholinesterase", "Monoamine oxidase B inhibitor"], "ans": 1, "exp": "Levodopa (L-DOPA) is the most effective antiparkinsonian drug. It is a precursor to dopamine, able to cross the BBB via large neutral amino acid transporters. Co-formulated with peripheral DDC inhibitors (carbidopa in Sinemet; benserazide in Madopar) that do not cross the BBB — thus preventing peripheral dopamine formation (nausea, hypotension, cardiac arrhythmias). Long-term complications: motor fluctuations ('wearing off'), dyskinesias."}, {"q": "What is a Todd's paresis (post-ictal paralysis) and what is its significance?", "opts": ["Permanent hemiplegia after stroke", "Transient focal neurological weakness (typically hemiparesis) occurring after a focal epileptic seizure, resolving spontaneously within hours (usually <24 hours) — important because it can mimic acute stroke (TIA/CVA) and must be distinguished by history", "An epileptic aura", "A sign of increased ICP"], "ans": 1, "exp": "Todd's paresis: ipsilateral focal weakness (or other focal deficit — aphasia, visual field defect) following a motor cortex seizure due to post-ictal neuronal exhaustion. It resolves within minutes to 24 hours. It is clinically critical because it mimics acute stroke — a history of preceding seizure activity, longer onset, or EEG findings can distinguish it. Thrombolysis should not be given before stroke is confirmed if Todd's paresis is likely."}, {"q": "What are the key clinical features of motor neurone disease (MND/ALS)?", "opts": ["Upper motor neurone signs only", "Combined UMN signs (spasticity, hyperreflexia, extensor plantars) AND LMN signs (weakness, wasting, fasciculations, hyporeflexia) in bulbar and limb regions, WITHOUT sensory involvement, sphincter disturbance, or cognitive impairment (in typical ALS)", "LMN signs only", "Cerebellar signs predominate"], "ans": 1, "exp": "ALS (amyotrophic lateral sclerosis) involves both upper (corticospinal) and lower motor neurones simultaneously. Pure UMN: primary lateral sclerosis. Pure LMN: spinal muscular atrophy, Kennedy's disease. ALS typically spares sensory neurones and sphincters, distinguishing it from peripheral neuropathy. Median survival from symptom onset: 2–3 years (bulbar onset: worse; flail arm/leg: better). Riluzole (glutamate antagonist) and edaravone slow progression marginally. Respiratory support extends survival."}, {"q": "What is cerebral venous thrombosis (CVT) and which patient group is most at risk?", "opts": ["Atherosclerotic venous occlusion identical to DVT", "Thrombosis of cerebral dural venous sinuses or cortical veins causing venous infarction and haemorrhage; young women (OCP use, pregnancy, puerperium), hypercoagulable states, dehydration, head injury, infection — presents with headache, papilloedema, focal deficit, seizures", "Ischaemic stroke in elderly men only", "A benign self-limiting condition"], "ans": 1, "exp": "CVT: thrombosis of superior sagittal sinus (most common), transverse, sigmoid, or cavernous sinuses; or cortical veins. Risk factors: OCP (most common in young women), pregnancy/puerperium, thrombophilia (APS, Factor V Leiden), dehydration, malignancy, local infection (ear, sinus), head trauma. MRI brain + MR venography (T2* or SWI — 'blooming' at thrombus site) is diagnostic. Treatment: anticoagulation (LMWH then warfarin for 3–12 months) even with haemorrhagic venous infarction — reduces mortality."}, {"q": "What is the most appropriate first investigation for acute severe headache reaching maximum intensity in <1 minute?", "opts": ["MRI brain", "CT head without contrast (within 6 hours of onset — sensitivity ~98% for SAH); if CT negative, LP at ≥12 hours for xanthochromia by spectrophotometry", "ECG", "Blood cultures"], "ans": 1, "exp": "Thunderclap headache (maximal within 1 minute) = SAH until proved otherwise. CT head within 6 hours has sensitivity approaching 98% for acute SAH (sensitivity falls significantly beyond 6 hours). If CT is negative but clinical suspicion remains, LP at ≥12 hours post-headache onset for xanthochromia by spectrophotometry (bilirubin peaks at 12 hours as oxyHb degrades). CT angiography/digital subtraction angiography identifies aneurysm if confirmed."}, {"q": "What is the pathophysiology of idiopathic intracranial hypertension (IIH)?", "opts": ["Obstructive hydrocephalus from tumour", "Elevated CSF pressure (>25 cmH₂O) without identifiable structural cause; associated with obesity in young women, vitamin A toxicity, tetracyclines, steroid withdrawal; presents with headache, papilloedema, visual obscurations, pulsatile tinnitus, sixth nerve palsy; LP opening pressure diagnostic (CSF composition normal)", "Hyperosmolar CSF production", "Reduced CSF reabsorption exclusively in males"], "ans": 1, "exp": "IIH (pseudotumor cerebri): impaired CSF reabsorption at arachnoid granulations, possibly from venous hypertension or increased CSF secretion. LP shows elevated opening pressure (>25 cmH₂O in adults) with normal CSF composition. Risk of progressive visual loss from papilloedema. Management: weight loss (most effective), acetazolamide (reduces CSF production), furosemide, repeat LPs (temporary); optic nerve sheath fenestration or CSF diversion (VP shunt) for visual threat."}, {"q": "What is the most sensitive MRI sequence for detecting acute ischaemic stroke?", "opts": ["T1-weighted imaging", "Diffusion-weighted imaging (DWI) — detects restricted diffusion within minutes of ischaemia onset (cytotoxic oedema), allowing detection of infarct core long before T2/FLAIR changes appear (which take 4–6 hours)", "T2-FLAIR", "MR angiography"], "ans": 1, "exp": "DWI detects water molecule movement restricted by cytotoxic oedema in ischaemic cells within minutes. Corresponding ADC map (apparent diffusion coefficient) shows low signal in the ischaemic area ('DWI-ADC mismatch' confirms acute infarction, not T2 shine-through). DWI sensitivity for acute stroke is >95% within hours. It also detects small lacunar infarcts and posterior circulation infarcts missed by CT."}, {"q": "What is spinal muscular atrophy (SMA) type 1 and what is the mechanism of action of nusinersen?", "opts": ["An UMN disease treated with riluzole", "SMA type 1 (Werdnig-Hoffmann disease) is an autosomal recessive LMN disease from SMN1 gene deletion causing proximal muscle weakness and respiratory failure before age 2; nusinersen is an antisense oligonucleotide that modifies SMN2 pre-mRNA splicing to produce functional SMN protein — administered intrathecally", "A sporadic acquired polyneuropathy", "A mitochondrial disease"], "ans": 1, "exp": "SMA is caused by homozygous deletion/mutation of SMN1 (survival motor neuron 1) gene. SMN2 produces small amounts of functional SMN protein via exon 7 inclusion. Nusinersen (Spinraza) is an intrathecal antisense oligonucleotide that sterically blocks SMN2 exon 7 splicing silencer, increasing exon 7 inclusion and SMN protein production. Onasemnogene abeparvovec (gene therapy) and risdiplam (oral SMN2 splicing modifier) are additional approved therapies."}, {"q": "What are the clinical criteria for diagnosing multiple sclerosis?", "opts": ["Single episode of neurological symptoms alone", "McDonald 2017 criteria: dissemination in space (DIS — lesions in ≥2 of 4 typical CNS regions: periventricular, juxtacortical, infratentorial, spinal cord) AND dissemination in time (DIT — new T2/gadolinium-enhancing lesions on follow-up MRI, or simultaneous enhancing and non-enhancing lesions); OR with CSF oligoclonal bands + DIS alone", "CT showing white matter lesions", "EEG changes alone"], "ans": 1, "exp": "McDonald 2017 criteria require objective evidence of DIS and DIT by clinical examination, MRI, visual evoked potentials, or CSF findings. CSF oligoclonal bands (absent in serum — intrathecal synthesis) allow DIT to be inferred from a single MRI demonstrating DIS in clinically isolated syndrome. MRI (particularly T2/FLAIR for plaques, DWI for acute demyelination, gadolinium for active inflammation) is central to diagnosis."}]}