Neurology

Question 1

Ischaemic Stroke: Early Management

What are the general and specific initial management steps for an ischaemic stroke (requires confirmation of no haemorrhage on CT)

Answer 1

1. General
   
   1. ​Oxygen: (only if low O₂ saturations)
   2. SALT assessment: consider I.V fluid and NG tube
   3. Investigate and treat signs of fever and infection
   4. DVT prophylaxis: no LMWH initially (risk of intracranial haemorrhage > VTE), consider after 2 weeks
2. Specific:
   
   1. ​Altepase: if delivery is within 4.5h of symptom onset
   2. Aspirin: 300mg OD for 14D started 24h after thrombolysis (or ASAP if no thrombolysis)
   3. Blood Pressure: only lowered if malignant HTN, and with senior advice

Question 2

Ischaemic Stroke: Long Term Management

What is the long term medical management following TIA or completed ischaemic stroke (with or without AF)

Answer 2

1. Anti-Thrombotics:
   
   1. ​TIA: aspirin 75mg OD + dipyridamole 200mg BD
   2. Ischaemic Stroke: clopidogrel 75mg OD
   3. Associated AF: anticoagulation (warfarin or NOAC)
2. Lipid: commenced 48h after symptom onset, irrespective of serum-cholesterol concentration
3. Anti-HTN: aim for <130/80 after acute phase. Avoid β-blockers unless indicated for co-existing condition
4. Lifestyle modifications: diet, exercise, weight, smoking, alcohol intake.

Question 3

Migraine: Acute Treatment

What are the 1st and 2nd Line therapies for acute migraine? What are contraindications to their use?

Answer 3

1. Analgesics ± antiemetics (1st Line):
   
   1. Aspirin / paracetamol / NSAIDs all effective
   2. Prokinetic antiemetic (e.g. metoclopramide) reduces nausea and increases gastric emptying and absorption
2. Triptans (2nd Line):
   
   1. ​Taken during headache phase (not aura) reduce pain. 30% have recurrance within 24h - treat with another NSAID and Triptan
   2. Contraindications: CVD, cerebrovascular disease, PVD, hepatic impairment, pregnancy
   3. **Adverse effects: **flushing, tingling, tightness, weakness

Question 4

Migraine: Prophylaxis

What are general and pharmacological prophylactic options for the treatment of Migraine?

Answer 4

General measures:

1. Avoid triggers including lack of sleep, certain foods, stress and bright lights.
2. NICE 1st line:
   
   1. β-blocker (e.g. propranalol; lipid soluble - penetrates BBB)
3. NICE 2nd line:
   
   1. Anti-epileptic: topiramate. Interferes with OCP
4. Other options:
   
   1. 5-HT2 antagonists: Pizotifen (weight gain)
   2. Amitryptilline (may be more useful if features of tension type headache)

Question 5

Epilepsy: Therapeutic Options

Starting anti-epileptics is a specialist decision. However, what would be general first line for:

1. Focal seizures
2. Generalised tonic - clonic

Answer 5

1. Focal: carbamazepine or lamotrigine
2. Generalised: sodium valproate

Question 6

Anti-Epileptics: Sodium Valproate

What is the mechanism, indications, contraindications and adverse effects of Sodium Valproate

Answer 6

1. Mechanism: Na⁺ channel blocker - inhibits AP generation
2. **Indication: **primary generalised seizures
3. Contraindications: pregnancy (most teratogenic AED), acute porphyria
4. Adverse effects:
   
   1. Appetite ↑ (weight gain)
   2. Liver failure
   3. Pancreatitis
   4. Reversible hairloss
   5. Oedema
   6. Ataxia
   7. Teratogenicity, Thrombocytopenia
   8. Encephalopathy (↑ ammonia)

Question 7

Anti-Epileptics: Carbamezapine

What is the mechanism, indications, contraindications and adverse effects of carbamezapine

Answer 7

1. Mechanism: Na+ channel blocker - inhibits AP generation
2. **Indications: **first line (with lamotrigine) for focal seizures
3. **Contraindications: **unpaced AV conduction defects, BM depression, MAOi
4. Adverse effects:
   
   1. Skin reactions (e.g. SJS)
   2. Blood dyscrasias (↓WCC)
   3. ↓ Sodium (SIADH)
   4. GI Upset
   5. Interactions - many; check BNF. Importantly, reduces level of COCP. Levels increased by EtOH.

Question 8

Anti-Epileptics: Phenytoin

What is the mechanism, indications, contraindications and adverse effects of phenytoin

Answer 8

1. Mechanism: Na+ channel blocker - inhibits AP generation
2. Indications: may be used in focal, generalized and status seizures
3. Contraindications: history of cardiac dysrithmias
4. Adverse effects:
   
   1. **​Toxicitiy: **cereballar signs (DANISH), drowsiness
   2. **Chronic: **gingival hyperplasia, hirsutism and acne, ↓folate, ↓ bone density

Question 9

Status Epilepticus: Hospital Management

What is the initial management of status epilepticus in a hospitalized patient?

Answer 9

1. ABC: high flow O₂, monitor and maintain BP with fluid resuscitation if necessary
2. Bloods: glucose, blood gas, U&E, LFTs, Ca²⁺and Mg²⁺, FBC, Clotting, anti-convulsant levels
3. **D - **glucose ± thiamine if suspicion of hypoglycaemia or alcoholism
4. **Lorazepam **(4mg at 2mg / minute) urgently for seizures lasting > 5min. Repeat after 10mins if seizure recurs / fails to respond)
5. **Phenytoin: **after ~20min of seizure activity or recurrance. Contact ITU if seizures continue
6. Barbiturate: required if SE continues despite BDZ and adequate loading of phenytoin after ~45 mins. Management moved to ITU

Question 10

Acute Seizure: Community Management

What is the pharmacological management of acute seizure occurring in the community (no I.V access available)?

Answer 10

1. Diazepam (10-20mg rectal): given in either pre-monitory or established phase; prevents recurrence in 70%.
2. **Midazolam **(10mg buccal): given in premonitory phase has 75% chance of preventing recurrance. May also be given IM if IV access difficult to obtain.

Question 11

Parkinson’s Drugs: Dopamine Receptor Agonists

​What are mechanisms, examples, indications and adverse effects of dopamine receptor antagonists?

Answer 11

1. **Mechanism: **direct stimulation of dopamine receptors
2. Examples:
   
   1. Ergot derived (bromocriptine, cabergoline)
   2. Synthetic (pramipexole)
3. Indications: may be given as first line therapy for PD (synthetic > ergot - fewer S/E). Fewer motor complications than levodopa, but more neuropsychiatric problems
4. Adverse effects:
   
   1. Ergot derived:** fibrosis **(cardiac, pulmonary, retroperitoneal)
   2. Synthetic: daytime drowsiness, hypotension, impulse control disorders

Question 12

Parkinson’s Drugs: Levodopa

​What are mechanisms, indications and adverse effects of levodopa

Answer 12

1. Mechanism: amino acid precursor, increases dopamine levels in substantia nigra. Peripheral S/E reduced with addition of peripherally acting **dopadecarboxylase **→ **reduces conversion, cannot cross BBB
2. Indications: more useful in advanced disease
3. Adverse effects:
   
   1. Dyskinesia
   2. On-off phenomenon
   3. Psychological disturbance
   4. A fall in BP
   5. Mouth dryness
   6. Insomnia
   7. Nausea and vomiting (low starting dose, titrate slowly)
   8. End of dose fluctuations

Question 13

Parkinson’s Drugs: MAO-B inhibitors

​What are mechanisms, examples, indications and adverse effects of MAO-B inhibitors

Answer 13

1. Mechanism: reduce breakdown of dopamine within neurons
2. Indications: used alone, or with L-dopa for “end of dose” fluctuations. Given early, may delay need for L-dopa
3. Examples: selegiline, rasagiline.
4. Adverse effects:
   
   1. Dry mouth
   2. Dyspepsia
   3. Constipation

Question 14

Parkinson’s Drugs: Antimuscarinics

​What are mechanisms, examples, indications and adverse effects of antimuscarinics

Answer 14

Mechanism: reduce cholinergic activity in the brain; dopamine usually inhibits ACh release in the BG, hence ↓Da may ↑cholinergic activity

1. Indications: usually used for drug-induced parkinsonism → in PD dopamine agonists and L-dopa are more effective, so anti-cholinergic treatment rarely used.
2. Examples: procyclidine
3. Adverse effects: typical anticholinergic;
   
   1. Dry mouth
   2. Blurred vision
   3. Urinary retention
   4. Cognitive impairment

Question 15

Dementia: Therapeutic Options

What are the therapeutic options for Alzheimer’s type dementia, and when are they initiated and discontinued?

Answer 15

1. Acetylcholinesterase inhibitors:
   
   1. **​Examples: **donepezil, galantamine, rivastigmine
   2. **Indications: **mild / moderate dementia (MMSE > 10)
   3. Review: after 3 months; if no evidence of reduction in cognitive decline, discontinue
2. Glutamate receptor antagonists
   
   1. ​Example: memantine
   2. Indication: moderate - severe Alzheimer’s

Question 16

Hypnotics: Z Drugs and Benzodiazepines

What are the mechanisms, examples and indications for hypnotics

Answer 16

1. Mechanism: both Z-drugs and BDZ act on GABA receptors
2. Examples: (Note: no difference in efficacy, adverse effects or risk of dependency. Choice is cost based → most widely used is temazepam)
   
   1. BDZ: temazepam, loprazolam → short acting, suitable for use. Avoid long acting diazepam / nitrazepam which cause hangover effects
   2. Z-drugs: zopiclone, zolpidem
3. **Indications: **disabling symptoms, short-term use, and failure of other measures. Risk of dependency, therefore prescribe lowest dose for shortest period of time at an appropriate dose.

Question 17

Hypnotics: Temazepam

What is a suitable dose of Temazepam? What are the adverse effects, and actions in overdose?

Answer 17

1. Dose information:
   
   1. ​Half life ~8h, usually no hangover effect. It is metabolized and renally excreted, so ↓ dose required in liver / renal disease
   2. 10mg at night preferred dose; may be increased to 20mg. Lower dose in elderly or renal / liver comorbidities.
   3. Put finishing date on chart, limited supplies for outpatients
2. Adverse effects:
   
   1. ​​Drowsiness / lightheadedness next day (may affect driving)
   2. Confusion (risk of delerium, particularly in elderly)
   3. Amnesia
   4. Dependence
   5. Respiratory depression
3. **Overdose: **flumazenil **not usually used **in suspected BDZ overdose; may precipitate seizures (particularly if BDZ dependent) or if tricyclics have also been taken

Question 18

Acute Confusional State: Management

What is the management strategy for an acutely disturbed patient?

Answer 18

1. Non-pharmacological:
   
   1. Investigate and treat any obvious underlying cause
   2. Correct sensory impairment;
      
      1. Manage in well lit, uncluttered environment, large clock and calendar.
      2. Reorientate by explaining location, role etc.
      3. Correct visual / hearing impairment
      4. Promote sleep hygiene and mobilization
2. ​Pharmacological:
   
   1. **Indications: **failure of de-escalation, danger to themselves or others.
   2. **Options: **use oral not I.V therapy, and lowest available dose:
      
      1. 1st Line: **Haloperidol **0.5 - 1.5 mg TDS; review after 2h. Avoid in parkinsonism, lewy body dementia. Seizure risk
      2. 2nd Line: Olanzapine or Lorazepam. Risk of respiratory depression.