Neurology: Anatomy, Physiology and Pharmacology

🧠 Neurological anatomy, physiology and pharmacology -neurology is about where the problem is before what it is. Knowing the lobes, the cranial nerves, the blood supply, the spinal tracts, the roots and the peripheral nerves lets you localise a lesion from the history and examination. Most neurological drugs work by changing ion channels, neurotransmitters or the immune system.
Your four questions for every drug: How does it work? What is it used for? What are the important side effects and safety issues? What does it interact with, and how is it monitored?

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Neurons and Glia

• Neurons -cell body, dendrites (receive signals) and an axon (sends signals). Neurons in the brain and spinal cord can't divide and regrow poorly; peripheral nerves can regrow at about 1 mm a day if the nerve sheath is intact.
• Glial cells:
  • Astrocytes -support neurons, control the chemical environment, form part of the blood–brain barrier; scar after injury; origin of most brain tumours (astrocytoma, glioblastoma).
  • Oligodendrocytes -make myelin in the CNS (damaged in multiple sclerosis).
  • Schwann cells -make myelin in peripheral nerves (damaged in Guillain–Barré syndrome and some inherited neuropathies; origin of schwannomas such as vestibular schwannoma).
  • Microglia -the brain's immune cells.
  • Ependymal cells -line the ventricles (ependymomas).
• Myelin -speeds conduction by letting the signal jump between the nodes of Ranvier (saltatory conduction).
  • Demyelination slows or blocks conduction -on nerve conduction studies, slow velocities (demyelinating neuropathy) versus low amplitudes (axonal neuropathy).
  • Heat worsens conduction in demyelinated nerves -symptoms worse in a hot bath or with exercise in MS (Uhthoff's phenomenon).
• Blood–brain barrier -tight junctions between capillary cells:
  • Fat-soluble drugs cross easily (benzodiazepines, alcohol, anaesthetics, opioids); charged and large molecules don't.
  • Levodopa crosses (via an amino acid carrier), dopamine doesn't; carbidopa, benserazide and domperidone don't cross -so they act only outside the brain.
  • Inflamed meninges let penicillins and other antibiotics through -the reason high doses work in meningitis.
  • Some areas lack a barrier -e.g. the chemoreceptor trigger zone (area postrema), which "samples" the blood for toxins.

The Cerebral Hemispheres

Lobe	Main functions	Signs of damage
Frontal	Movement (motor cortex -precentral gyrus), planning, personality, behaviour, judgement; Broca's area (speech output, dominant side); eye movements (frontal eye fields); bladder control	Contralateral weakness; personality change, disinhibition, apathy; expressive (Broca's) dysphasia -slow, effortful speech with good understanding; primitive reflexes; urinary incontinence; eyes deviate towards the lesion (destructive) or away (seizure)
Parietal	Sensation (sensory cortex -postcentral gyrus), spatial awareness, calculation	Contralateral sensory loss (cortical -loss of two-point discrimination, astereognosis); dominant -Gerstmann's syndrome (acalculia, agraphia, finger agnosia, left–right confusion); non-dominant -neglect, dressing apraxia; contralateral inferior quadrantanopia
Temporal	Hearing, memory (hippocampus), language understanding (Wernicke's area, dominant side), emotion, smell and taste	Receptive (Wernicke's) dysphasia -fluent but meaningless speech, poor understanding; memory loss; contralateral superior quadrantanopia ("pie in the sky"); seizures with déjà vu, smell, rising stomach feeling
Occipital	Vision	Contralateral homonymous hemianopia (often with macular sparing); cortical blindness if both sides

• Each hemisphere controls the opposite side of the body -so a hemisphere lesion causes contralateral weakness and sensory loss.
• Dominant hemisphere -the left in almost all right-handed people and most left-handed people -language. The non-dominant side -spatial awareness and attention (neglect after right-sided stroke).
• Motor and sensory homunculus -the leg is on the medial surface (supplied by the anterior cerebral artery); the face and arm on the lateral surface (middle cerebral artery).
• Conduction dysphasia -damage to the connection between Broca's and Wernicke's areas (arcuate fasciculus) -fluent speech and good understanding but poor repetition.
• Limbic system (hippocampus, amygdala, cingulate gyrus) -memory and emotion; damaged in Alzheimer's (hippocampus first), herpes simplex encephalitis (temporal lobes), Wernicke–Korsakoff (mammillary bodies).

Deep Structures and Cerebellum

• Internal capsule -a narrow band of white matter carrying motor and sensory fibres; a small (lacunar) stroke here causes a pure motor stroke of face, arm and leg with no cortical signs.
• Thalamus -sensory relay station; thalamic stroke causes contralateral sensory loss and sometimes severe pain later (thalamic pain syndrome).
• Basal ganglia (caudate, putamen, globus pallidus, subthalamic nucleus, substantia nigra) -help start and smooth movement:
  • Substantia nigra loss (dopamine) -Parkinson's disease.
  • Caudate loss -Huntington's disease (chorea).
  • Subthalamic nucleus lesion -contralateral hemiballismus (violent flinging movements).
• Hypothalamus -temperature, appetite, thirst, sleep, the pituitary (see the Endocrine Anatomy, Physiology and Pharmacology chapter).
• Cerebellum -co-ordination, balance and smooth movement; each side controls the same side of the body:
  • Hemisphere lesions -ipsilateral limb ataxia: DANISH -Dysdiadochokinesia, Ataxia, Nystagmus, Intention tremor, Slurred (scanning) speech, Hypotonia and heel–shin ataxia.
  • Vermis (midline) lesions -truncal ataxia (wide-based gait, can't sit or stand unsupported) -typical of alcohol.
  • Causes -stroke, MS, alcohol, drugs (phenytoin, carbamazepine, lithium), tumours, paraneoplastic, inherited ataxias.

Brainstem and Cranial Nerves

• Brainstem -midbrain (cranial nerves III, IV), pons (V, VI, VII, VIII) and medulla (IX, X, XI, XII). It contains the long motor and sensory tracts, the breathing and cardiovascular centres, and the reticular activating system (consciousness).
• Brainstem lesions cause "crossed" signs -a cranial nerve problem on the same side with weakness or sensory loss of the body on the opposite side:
  • Lateral medullary syndrome (Wallenberg -vertebral or PICA occlusion) -ipsilateral facial numbness (pain and temperature), Horner's syndrome, ataxia, hoarseness and dysphagia; contralateral loss of pain and temperature in the body; vertigo and vomiting.
  • Weber's syndrome (midbrain) -ipsilateral third nerve palsy with contralateral hemiparesis.

Nerve	Main functions	Key clinical points
I Olfactory	Smell	Lost after head injury, with viral infections (including COVID-19), early in Parkinson's
II Optic	Vision; afferent pupil reflex	Acuity, colour, fields, fundi; relative afferent pupillary defect in optic neuritis
III Oculomotor	Most eye movements, lifts eyelid, constricts pupil	"Down and out" eye, ptosis; dilated pupil = compression (posterior communicating artery aneurysm, uncal herniation -pupil fibres run on the outside); pupil-sparing = medical (diabetes, hypertension)
IV Trochlear	Superior oblique -looks down and in	Vertical double vision, worse going downstairs; head tilted away from the affected side
V Trigeminal	Facial sensation (V1, V2, V3), chewing muscles; corneal reflex (sensory)	Trigeminal neuralgia; loss of corneal reflex is an early sign of a cerebellopontine angle tumour; shingles of V1 (Hutchinson's sign -tip of nose → eye involvement)
VI Abducens	Lateral rectus -looks out	Horizontal double vision; a "false localising sign" of raised intracranial pressure
VII Facial	Facial expression; taste (front two-thirds of tongue); tears, saliva; stapedius	Lower motor neurone (Bell's palsy) -whole face, including forehead; upper motor neurone (stroke) -forehead spared (bilateral cortical supply)
VIII Vestibulocochlear	Hearing and balance	Sensorineural deafness, vertigo; vestibular schwannoma (one-sided deafness -MRI); aminoglycoside toxicity
IX Glossopharyngeal	Taste (back third of tongue), sensation of the pharynx (gag reflex sensory), carotid sinus	Usually affected with X (bulbar palsy)
X Vagus	Palate, pharynx and larynx muscles; parasympathetic to the heart and gut	Uvula deviates away from the weak side; hoarseness (recurrent laryngeal branch)
XI Accessory	Sternocleidomastoid and trapezius	Weak shoulder shrug and head turning; injured in neck surgery
XII Hypoglossal	Tongue movement	Tongue deviates towards the weak side; wasting and fasciculations in motor neurone disease

• Bulbar palsy (lower motor neurone -IX, X, XII) -wasted, fasciculating tongue, nasal speech, absent gag (MND, Guillain–Barré, myasthenia); pseudobulbar palsy (upper motor neurone -bilateral strokes, MND, MS) -stiff, small tongue, slow "hot potato" speech, brisk jaw jerk, emotional lability.
• Cerebellopontine angle -V, VII and VIII together (vestibular schwannoma -deafness, tinnitus, reduced corneal reflex, facial weakness, ataxia).
• Cavernous sinus -III, IV, V1, V2 and VI with the internal carotid artery (cavernous sinus thrombosis, carotid–cavernous fistula, pituitary tumours).

Blood Supply of the Brain

• Anterior circulation -the internal carotid arteries → anterior and middle cerebral arteries.
• Posterior circulation -the vertebral arteries → basilar artery → brainstem, cerebellum, and the posterior cerebral arteries.
• Circle of Willis -joins the two systems (anterior and posterior communicating arteries); berry aneurysms form at junctions (most often the anterior communicating artery) → subarachnoid haemorrhage.

Artery	Supplies	Stroke signs
Anterior cerebral	Medial frontal and parietal lobes	Contralateral leg weakness more than arm; behaviour change, incontinence
Middle cerebral	Lateral hemisphere, internal capsule	Contralateral face and arm weakness more than leg, sensory loss, homonymous hemianopia; dysphasia (dominant) or neglect (non-dominant)
Posterior cerebral	Occipital lobe, thalamus	Contralateral homonymous hemianopia with macular sparing; visual agnosia
Lenticulostriate (small penetrating arteries)	Internal capsule, basal ganglia, thalamus	Lacunar syndromes -pure motor, pure sensory, ataxic hemiparesis; no cortical signs
Vertebrobasilar	Brainstem, cerebellum, occipital lobes	Vertigo, ataxia, double vision, dysarthria, crossed signs, hemianopia; basilar occlusion -coma or "locked-in" syndrome
PICA (posterior inferior cerebellar)	Lateral medulla, cerebellum	Lateral medullary syndrome

• Oxford (Bamford) classification -total anterior circulation (TACS -all three of hemiparesis, hemianopia and higher cortical dysfunction), partial (PACS -two of three), lacunar (LACS) and posterior circulation (POCS) strokes.
• Venous drainage -cortical veins → dural venous sinuses (superior sagittal, transverse, sigmoid) → internal jugular veins. Cerebral venous sinus thrombosis -headache, seizures, papilloedema, focal signs (pregnancy, the pill, dehydration, clotting disorders) -CT or MR venogram; anticoagulate.
• Bleeds by layer:
  • Extradural -middle meningeal artery (thin skull at the pterion); lucid interval then rapid decline; lens-shaped (biconvex) clot on CT.
  • Subdural -torn bridging veins; older people, alcohol, falls, anticoagulants; crescent-shaped; may be slow (chronic subdural -fluctuating confusion).
  • Subarachnoid -berry aneurysm (or trauma); thunderclap headache.
  • Intracerebral -hypertension (deep -basal ganglia, pons), amyloid angiopathy (lobar, older people), anticoagulants.
• The brain uses about 20% of the body's oxygen and has no stores -consciousness is lost within seconds of no blood flow and permanent damage begins within minutes ("time is brain").

Meninges, Ventricles and CSF

• Meninges -dura mater (tough outer layer), arachnoid mater, and pia mater (on the brain surface); CSF fills the subarachnoid space between arachnoid and pia.
• CSF -made by the choroid plexus (about 500 mL a day); total volume about 150 mL (so it's replaced about 3 times a day).
• CSF flow -lateral ventricles → foramina of Monro → third ventricle → aqueduct of Sylvius → fourth ventricle → foramina of Luschka and Magendie → subarachnoid space → absorbed into the venous sinuses by the arachnoid granulations.
• Hydrocephalus:
  • Obstructive (non-communicating) -a block in the ventricles (tumour, aqueduct stenosis, colloid cyst) -don't do a lumbar puncture (risk of herniation).
  • Communicating -poor absorption (after meningitis or subarachnoid haemorrhage).
  • Normal pressure hydrocephalus -older people: gait disturbance (magnetic gait), urinary incontinence and dementia ("wet, wobbly, wacky"); large ventricles; may improve with CSF drainage or a shunt.
• Lumbar puncture -the spinal cord ends at about L1–L2 in adults (lower in babies), so LP is done at L3–L4 or L4–L5 (a line between the iliac crests crosses about L4).
  • Layers crossed -skin, supraspinous and interspinous ligaments, ligamentum flavum (a "give"), epidural space, dura and arachnoid.
  • CT first if there is reduced consciousness, focal signs, papilloedema, new seizures, immunocompromise -but don't delay antibiotics in suspected meningitis.
  • Check clotting and platelets; hold anticoagulants as advised.
  • Post-dural puncture headache -worse sitting up, better lying down; fluids, caffeine, epidural blood patch if persistent.
• Idiopathic intracranial hypertension -usually young women with obesity; headache, papilloedema, visual loss, sixth nerve palsy; normal imaging with a high opening pressure; weight loss, acetazolamide; urgent ophthalmology if vision is threatened.

Spinal Cord and Its Tracts

Tract	Carries	Where it crosses
Corticospinal (pyramidal)	Voluntary movement	Crosses in the lower medulla (pyramidal decussation) -runs down on the same side as the muscles it controls
Dorsal columns	Vibration, joint position sense, fine touch	Runs up on the same side and crosses in the medulla
Spinothalamic	Pain and temperature (and crude touch)	Crosses within 1–2 segments of entering the cord -runs up on the opposite side
Spinocerebellar	Unconscious position sense to the cerebellum	Mostly uncrossed

• Spinal cord syndromes:
  • Complete transection -loss of all movement and sensation below the level, with a sensory level; spinal shock (flaccid) at first, then spasticity; bladder and bowel loss.
  • Brown-Séquard (cord hemisection -stab wounds, tumours, MS) -same side weakness and loss of vibration and position sense; opposite side loss of pain and temperature.
  • Anterior cord syndrome (anterior spinal artery occlusion -aortic surgery or dissection) -loss of movement, pain and temperature below the level, with vibration and position sense preserved.
  • Central cord syndrome -older people with neck hyperextension, or syringomyelia: arms worse than legs; "cape-like" loss of pain and temperature across the shoulders (crossing fibres hit first); wasting of hand muscles.
  • Dorsal column loss -B12 deficiency (subacute combined degeneration -dorsal columns plus corticospinal tracts: absent ankle jerks with upgoing plantars), nitrous oxide misuse (inactivates B12), copper deficiency, tabes dorsalis (syphilis) -positive Romberg's test, sensory ataxia.
• Cauda equina syndrome (below L1–L2 -the nerve roots, not cord) -saddle anaesthesia, urinary retention (or incontinence), bowel dysfunction, sexual dysfunction, bilateral sciatica and leg weakness with lower motor neurone signs -emergency MRI and surgery.
• Conus medullaris lesions -mixed upper and lower motor neurone signs with early bladder involvement.
• Spinal cord compression (metastatic, epidural abscess, disc, trauma) -back pain, weakness, sensory level, sphincter problems -urgent MRI of the whole spine; dexamethasone in malignant compression; radiotherapy or surgery.

Roots, Dermatomes, Myotomes and Reflexes

Root	Dermatome (sensation)	Myotome (movement)	Reflex
C5	Lateral upper arm	Shoulder abduction, elbow flexion	Biceps (C5–C6)
C6	Lateral forearm and thumb	Wrist extension, elbow flexion	Supinator (brachioradialis -C5–C6)
C7	Middle finger	Elbow, wrist and finger extension	Triceps (C7)
C8	Little finger, medial forearm	Finger flexion (grip)	Finger jerk
T1	Medial upper arm	Finger abduction (small hand muscles)	-
T4 / T10	Nipple / umbilicus	Trunk muscles	Abdominal reflexes
L1–L2	Groin, upper thigh	Hip flexion	Cremasteric (L1)
L3–L4	Front of thigh, medial knee and shin (L4)	Knee extension, ankle dorsiflexion (L4)	Knee (L3–L4)
L5	Lateral shin, top of foot and big toe	Big toe extension, ankle dorsiflexion and inversion, hip abduction	None reliable
S1	Lateral foot, sole, little toe	Plantarflexion (tiptoe), eversion	Ankle (S1–S2)
S2–S4	Perianal ("saddle") area	Bladder, bowel, anal sphincter	Anal reflex

• Reflex rhyme -"1, 2 buckle my shoe (S1–S2 ankle); 3, 4 kick the door (L3–L4 knee); 5, 6 pick up sticks (C5–C6 biceps); 7, 8 lay them straight (C7–C8 triceps)".
• Disc prolapse -a lumbar disc usually compresses the root below its level (an L4–L5 disc compresses L5; L5–S1 compresses S1). Most improve without surgery; red flags need urgent imaging.
• Cervical radiculopathy -neck and arm pain in a root distribution (C6 and C7 commonest); cervical myelopathy -cord compression: clumsy hands, gait problems, upper motor neurone signs in the legs (and often a lower motor neurone pattern at the level).
• Foot drop -root or nerve? L5 root -inversion and hip abduction are also weak (back pain, sciatica); common peroneal nerve -inversion is preserved (pressure at the fibular head).

Peripheral Nerves and Plexuses

Nerve	Common site of damage	Features
Median	Wrist (carpal tunnel)	Numbness of the thumb, index, middle and half the ring finger, worse at night; weak thumb abduction; thenar wasting. Risk factors -pregnancy, hypothyroidism, diabetes, acromegaly, RA, dialysis, obesity
Ulnar	Elbow (cubital tunnel) or wrist	Numbness of the little finger and half the ring finger; weak finger spreading; wasting of the small hand muscles (first dorsal interosseous), claw hand; Froment's sign
Radial	Spiral groove of the humerus ("Saturday night palsy"), shaft fractures	Wrist drop; numbness over the back of the thumb web space; triceps spared if the lesion is low
Axillary	Shoulder dislocation, humeral neck fracture	Weak shoulder abduction (deltoid); numbness over the "regimental badge" area
Long thoracic	Surgery (mastectomy), carrying heavy loads	Winged scapula (serratus anterior)
Common peroneal (fibular)	Fibular head -leg crossing, plaster casts, weight loss, prolonged squatting, knee surgery	Foot drop; weak eversion; inversion preserved; numbness of the top of the foot
Lateral cutaneous nerve of the thigh	Under the inguinal ligament	Meralgia paraesthetica -burning numbness of the outer thigh (obesity, tight belts, pregnancy)
Sciatic	Hip surgery, IM injections in the wrong spot, pelvic fractures	Weakness below the knee, foot drop; numbness below the knee except the medial side

• Brachial plexus (C5–T1):
  • Upper (Erb's) palsy -C5–C6 (birth injury, motorbike falls) -"waiter's tip" (arm hangs, internally rotated, wrist flexed).
  • Lower (Klumpke's) palsy -C8–T1 (arm pulled upwards, Pancoast tumour, cervical rib) -claw hand, small muscle wasting, sometimes Horner's syndrome.
• Patterns of neuropathy:
  • Mononeuropathy -one nerve (entrapment, trauma).
  • Mononeuritis multiplex -several separate nerves (vasculitis, diabetes, sarcoid, leprosy).
  • Polyneuropathy -length-dependent "glove and stocking" (diabetes, alcohol, B12 deficiency, drugs, CKD, hypothyroidism, myeloma).

Autonomic Nervous System

Feature	Sympathetic	Parasympathetic
Origin	Thoracolumbar cord (T1–L2)	Cranial nerves III, VII, IX, X and sacral S2–S4
Ganglia	Near the cord (sympathetic chain)	Near or in the target organ
Transmitter at the target	Noradrenaline (except sweat glands -acetylcholine)	Acetylcholine (muscarinic receptors)
Effects	Fast heart rate, dilated pupils, bronchodilatation, sweating, slow gut, vasoconstriction, bladder relaxation, ejaculation	Slow heart rate, small pupils, saliva and tears, gut movement, bladder emptying, erection

• Horner's syndrome -loss of sympathetic supply to the face: ptosis (mild), miosis (small pupil), anhidrosis (reduced sweating) and apparent enophthalmos. The pathway has three neurones:
  • Central (hypothalamus to T1) -brainstem stroke (lateral medullary), syringomyelia, cord lesions.
  • Preganglionic (T1 to the neck) -Pancoast tumour (lung apex), neck trauma or surgery, cervical rib.
  • Postganglionic (along the carotid) -carotid artery dissection (painful Horner's with neck pain or headache -urgent imaging), cavernous sinus, cluster headache.
• Bladder control -parasympathetic (S2–S4) contracts the detrusor; sympathetic (T10–L2) relaxes the detrusor and closes the bladder neck; the pudendal nerve (S2–S4) controls the external sphincter; the pons co-ordinates voiding.
  • Above the pons (stroke, dementia, frontal lesions) -urgency and incontinence, but complete emptying.
  • Spinal cord (MS, injury) -overactive bladder with poor co-ordination (detrusor–sphincter dyssynergia) -incomplete emptying.
  • Sacral roots or nerves (cauda equina, diabetes) -floppy bladder with retention and overflow.
• Autonomic failure -postural hypotension, gastroparesis, constipation or diarrhoea, erectile dysfunction, sweating changes, bladder problems; causes -diabetes, Parkinson's disease, multiple system atrophy, amyloid, Guillain–Barré, drugs.
• Anticholinergic drugs (blocking parasympathetic effects) -dry mouth, constipation, urinary retention, blurred vision, fast heart rate, confusion in older people ("dry as a bone, red as a beet, blind as a bat, mad as a hatter, hot as a hare").

Visual Pathway and Pupils

• Pathway -retina → optic nerve → optic chiasm (nasal fibres cross, carrying the temporal fields) → optic tract → lateral geniculate body → optic radiations (through the temporal lobe -Meyer's loop -and parietal lobe) → occipital cortex.
• Where is the lesion?
  • Optic nerve -loss of vision in one eye, poor colour vision, relative afferent pupillary defect (optic neuritis, ischaemic optic neuropathy, giant cell arteritis, compression).
  • Optic chiasm -bitemporal hemianopia (pituitary tumour, craniopharyngioma).
  • Optic tract, radiations or cortex -contralateral homonymous hemianopia (stroke, tumour).
  • Temporal lobe radiations -superior homonymous quadrantanopia; parietal -inferior quadrantanopia.
  • Occipital cortex -homonymous hemianopia with macular sparing (dual blood supply to the macular area).
• Pupillary light reflex -sensory via the optic nerve (II), motor via the oculomotor nerve (III, parasympathetic fibres from the Edinger–Westphal nucleus). Both pupils constrict when light is shone in either eye.
• Abnormal pupils:
  • Large pupil -third nerve palsy (compression), Holmes–Adie pupil (slow reaction, young women, reduced reflexes), anticholinergic drops or drugs, trauma.
  • Small pupil -Horner's syndrome, opioids, pontine haemorrhage (pinpoint pupils), organophosphates, pilocarpine drops, old age.
  • Argyll Robertson pupils -small, irregular, react to accommodation but not light (neurosyphilis, diabetes).
• Papilloedema -swollen optic discs from raised intracranial pressure (usually both eyes, vision preserved early, enlarged blind spot) -needs urgent imaging.
• Eye movements -horizontal gaze is co-ordinated by the medial longitudinal fasciculus; damage causes internuclear ophthalmoplegia (failure of the adducting eye, nystagmus of the abducting eye) -MS in young people, stroke in older people.

Action Potentials and Synapses

• Resting membrane potential -about −70 mV, kept by the sodium–potassium pump (high potassium inside, high sodium outside).
• Action potential:
  • Depolarisation -voltage-gated sodium channels open, sodium rushes in.
  • Repolarisation -sodium channels close; potassium channels open, potassium leaves.
  • Refractory period -sodium channels can't reopen immediately, so signals travel one way and can't fire too fast.
  • Drugs that block sodium channels -carbamazepine, phenytoin, lamotrigine, lacosamide (epilepsy), lidocaine and other local anaesthetics, class I antiarrhythmics, tricyclic antidepressants in overdose.
• Electrolytes and excitability:
  • Low calcium → more excitable nerves -tingling, cramps, tetany, Chvostek's and Trousseau's signs, seizures.
  • Low sodium (especially if rapid) → brain swelling → confusion, seizures, coma; correcting it too fast → osmotic demyelination (pons -quadriparesis, "locked-in").
  • Low glucose → confusion, seizures, focal signs (can mimic stroke -always check glucose).
  • Low magnesium → seizures, arrhythmias, low calcium.
• Synapse:
  • The action potential reaches the nerve ending → voltage-gated calcium channels open (target of gabapentin and pregabalin, and of antibodies in Lambert–Eaton syndrome) → calcium enters.
  • Vesicles release neurotransmitter (vesicle protein SV2A is the target of levetiracetam; botulinum toxin blocks release; tetanus toxin blocks inhibitory release in the spinal cord).
  • The transmitter binds receptors on the next cell, then is broken down or taken back up (the target of SSRIs, acetylcholinesterase inhibitors, MAO inhibitors).
• Seizures -too much synchronised excitation or too little inhibition; antiseizure drugs either reduce excitation (sodium and calcium channel blockers, glutamate blockers) or increase inhibition (GABA drugs).

Neurotransmitters

Transmitter	Role	Clinical and drug links
Glutamate	Main excitatory transmitter; learning and memory (NMDA and AMPA receptors)	Excitotoxic cell death in stroke and trauma; memantine and ketamine block NMDA; perampanel blocks AMPA; riluzole reduces release (MND)
GABA	Main inhibitory transmitter in the brain	Benzodiazepines, barbiturates, Z-drugs, propofol, alcohol enhance GABA-A; baclofen acts on GABA-B; valproate and vigabatrin raise GABA; withdrawal of these → seizures
Glycine	Inhibitory in the spinal cord and brainstem	Tetanus toxin and strychnine block it → spasms
Acetylcholine	Neuromuscular junction (nicotinic), autonomic nerves, memory and attention (brain)	Loss in Alzheimer's (donepezil); myasthenia gravis; anticholinergic drugs cause confusion
Dopamine	Four pathways: movement (nigrostriatal), reward (mesolimbic), thinking (mesocortical), prolactin control (tuberoinfundibular); also triggers nausea (CTZ)	Parkinson's (loss); antipsychotics block it (parkinsonism, raised prolactin); dopamine drugs cause nausea, hallucinations and impulse control problems
Noradrenaline	Arousal, attention, mood, pain modulation	SNRIs (duloxetine) and TCAs for neuropathic pain and depression
Serotonin (5-HT)	Mood, sleep, appetite, pain, nausea, blood vessel tone	Triptans (5-HT1B/1D agonists) in migraine; ondansetron (5-HT3); SSRIs; serotonin syndrome
Histamine	Wakefulness, vestibular signals	Sedating antihistamines (cyclizine, promethazine); pitolisant (narcolepsy)
Endorphins and enkephalins	Natural pain relief	Opioid drugs act on the same receptors
CGRP and substance P	Pain signalling and blood vessel dilatation	CGRP antibodies and gepants in migraine; capsaicin depletes substance P
Orexin (hypocretin)	Keeps us awake	Loss in narcolepsy with cataplexy

• Dopamine–acetylcholine balance in the basal ganglia -too little dopamine (Parkinson's) is partly helped by blocking acetylcholine (anticholinergics), but these cause confusion in older people.
• Serotonin syndrome -too much serotonin (SSRIs with tramadol, MAOIs, linezolid, St John's wort, MDMA): agitation, sweating, fever, tremor, clonus and brisk reflexes (legs more than arms), diarrhoea; rapid onset; stop the drugs, cooling, benzodiazepines, cyproheptadine.
• Neuroleptic malignant syndrome -dopamine blockade (antipsychotics) or sudden withdrawal of Parkinson's drugs: fever, rigidity ("lead pipe"), confusion, autonomic instability, very high CK; slower onset (days); stop the drug, cooling, fluids, ITU; dantrolene or bromocriptine in severe cases.

The Motor System

Sign	Upper motor neurone (brain, cord)	Lower motor neurone (anterior horn, root, nerve)
Tone	Increased (spastic -"clasp-knife")	Reduced (flaccid)
Weakness pattern	"Pyramidal" -arm extensors and leg flexors weakest	In the distribution of the root or nerve
Wasting	Little (disuse only)	Marked
Fasciculations	No	Yes (especially motor neurone disease)
Reflexes	Brisk, with clonus	Reduced or absent
Plantar response	Upgoing (Babinski)	Downgoing

• Motor neurone disease -a mix of upper and lower motor neurone signs, with no sensory signs and eye movements and sphincters spared.
• Acute upper motor neurone lesions (stroke, cord injury) may be flaccid with absent reflexes at first (spinal shock); spasticity appears over days to weeks.
• Basal ganglia (extrapyramidal) problems:
  • Parkinsonism -bradykinesia (slowness with decreasing size of movements -essential for the diagnosis), rigidity (lead-pipe, or cogwheel with tremor), rest tremor ("pill-rolling", often one side first), postural instability later.
  • Hyperkinetic disorders -chorea (Huntington's, levodopa dyskinesia), dystonia, tics, myoclonus, hemiballismus.
• Tremor types:
  • Rest tremor -Parkinson's.
  • Postural tremor -essential tremor (often familial, both hands, improves with alcohol), anxiety, thyrotoxicosis, drugs (salbutamol, lithium, valproate, caffeine), alcohol withdrawal.
  • Intention tremor -cerebellar disease.
• Muscle disease (myopathy) -proximal weakness (difficulty rising from a chair, combing hair), normal sensation, reflexes preserved until late; causes -statins, steroids, hypothyroidism, alcohol, inflammatory myositis (raised CK), muscular dystrophies.
• Gait patterns -spastic (stiff, scissoring), shuffling (Parkinson's -small steps, festination, freezing), ataxic (wide-based), high-stepping (foot drop or sensory loss), waddling (proximal weakness), magnetic (normal pressure hydrocephalus), antalgic (pain).

Sensation and Pain

• Two sensory systems:
  • Large fibres → dorsal columns -vibration, joint position sense, fine touch. Loss → sensory ataxia, positive Romberg's test (worse with eyes closed), reduced reflexes in neuropathy.
  • Small fibres → spinothalamic tract -pain and temperature. Loss → burning pain, numbness to pin, injuries and ulcers (diabetic foot), Charcot joints.
• Romberg's test tests proprioception -positive in sensory ataxia (dorsal column or large-fibre neuropathy); a cerebellar patient is unsteady with the eyes open and closed.
• Pain pathway:
  • Nociceptors → A-delta fibres (fast, sharp, well-localised pain) and C fibres (slow, dull, burning pain).
  • Dorsal horn of the spinal cord (glutamate, substance P) → spinothalamic tract → thalamus → cortex.
  • Gate control -touch inputs reduce pain at the dorsal horn (rubbing a knock helps; TENS).
  • Descending inhibition from the brainstem (periaqueductal grey, using endorphins, noradrenaline and serotonin) -the reason opioids, TCAs and SNRIs relieve pain.
• Types of pain:
  • Nociceptive -tissue damage (fractures, arthritis) -responds to paracetamol, NSAIDs, opioids.
  • Neuropathic -nerve damage: burning, shooting, electric shock-like, pins and needles, allodynia (pain from light touch) -responds poorly to standard painkillers; use amitriptyline, duloxetine, gabapentin or pregabalin.
  • Nociplastic (central sensitisation) -fibromyalgia, some chronic pain -exercise and psychological therapy; opioids don't help.
• Referred pain -visceral and somatic nerves share spinal segments (heart → left arm and jaw; diaphragm → shoulder tip; hip → knee).

The Neuromuscular Junction

• How it works -the nerve releases acetylcholine (calcium-dependent) → binds nicotinic receptors on muscle → muscle contracts → acetylcholine is broken down by acetylcholinesterase.
• Myasthenia gravis -antibodies against acetylcholine receptors (about 85%) or MuSK:
  • Fatigable weakness -worse with use and at the end of the day: ptosis, double vision, bulbar weakness (swallowing, speech), neck and proximal weakness; reflexes and sensation normal.
  • Linked to thymoma (CT of the chest) and other autoimmune diseases.
  • Myasthenic crisis -respiratory muscle weakness -monitor FVC (not oxygen saturations, which fall late).
• Lambert–Eaton myasthenic syndrome -antibodies against presynaptic calcium channels; proximal leg weakness that improves briefly with exercise, reduced reflexes, dry mouth and other autonomic symptoms; about half have small cell lung cancer.
• Botulism -toxin blocks acetylcholine release → descending paralysis, fixed dilated pupils, autonomic failure (wound botulism in people who inject drugs; food); antitoxin.
• Organophosphate poisoning (pesticides, nerve agents) -blocks acetylcholinesterase → too much acetylcholine: small pupils, sweating, salivation, diarrhoea, bronchorrhoea, bradycardia, then weakness and paralysis -atropine (large doses) and pralidoxime; decontaminate.
• Neuromuscular blocking drugs (anaesthesia):
  • Suxamethonium (depolarising) -fast and short; causes hyperkalaemia (avoid in burns, crush injury, neuromuscular disease), malignant hyperthermia (with volatile anaesthetics -treat with dantrolene), and prolonged paralysis with plasma cholinesterase deficiency.
  • Rocuronium, atracurium (non-depolarising) -reversed by neostigmine (with glycopyrronium) or sugammadex (rocuronium and vecuronium); people with myasthenia are very sensitive to them.

Intracranial Pressure and Cerebral Blood Flow

• Monro–Kellie doctrine -the skull is a fixed box containing brain, blood and CSF; if one increases (tumour, bleed, swelling), the others must decrease, or pressure rises steeply once compensation runs out.
• Normal ICP -about 5–15 mmHg (lying flat in adults).
• Cerebral perfusion pressure (CPP) = mean arterial pressure − ICP -aim to keep it above about 60 mmHg in brain injury (avoid low blood pressure and high ICP).
• Autoregulation -brain blood flow stays steady across a wide range of blood pressure (roughly mean arterial pressure 60–150 mmHg); lost after injury, stroke or severe hypertension -flow then depends directly on blood pressure.
• CO2 and oxygen -high CO2 dilates brain vessels (raises ICP); low CO2 constricts them (brief hyperventilation is a temporary rescue measure). Low oxygen also dilates them.
• Features of raised ICP -headache (worse lying down, on waking, coughing, straining), vomiting, papilloedema, sixth nerve palsy, reduced consciousness; Cushing's response (late, ominous) -rising blood pressure, falling heart rate, irregular breathing.
• Herniation:
  • Uncal (transtentorial) -temporal lobe pushes over the tentorium → ipsilateral dilated pupil (third nerve), then hemiparesis and coma.
  • Tonsillar (coning) -cerebellar tonsils through the foramen magnum → medulla compressed → breathing stops; risk with LP in raised posterior fossa pressure.
  • Subfalcine -under the falx; may compress the anterior cerebral artery.
• Treatment -head up 30°, avoid neck compression (ties), treat fever, seizures, hypoxia, high CO2 and low sodium; osmotherapy (mannitol or hypertonic saline); dexamethasone only for swelling around tumours or abscesses (vasogenic oedema) -not for head injury or stroke; neurosurgery (drainage, decompression).

Consciousness and Sleep

• Consciousness needs a working reticular activating system (brainstem) and the cerebral hemispheres. Coma means brainstem damage, both hemispheres affected, or a diffuse cause (metabolic, drugs, infection, seizures).
• Glasgow Coma Scale -eyes (1–4), verbal (1–5), motor (1–6); total 3–15. GCS of 8 or less -the airway is at risk (consider intubation); record each part separately (e.g. E2 V2 M5).
• Common causes of coma -drugs and alcohol, hypoglycaemia, hypoxia, sepsis, seizures (post-ictal or non-convulsive status), stroke and bleeds, head injury, metabolic (sodium, calcium, urea, ammonia, CO2), hypothermia, hypothyroidism.
• Brain death (death by neurological criteria) -irreversible loss of brainstem function after a known cause, with drugs, temperature, metabolic and endocrine causes excluded; tested by two senior doctors (absent pupil, corneal, vestibulo-ocular, gag and cough reflexes, no response to pain in cranial nerve territory, apnoea test).
• Sleep:
  • Cycles of non-REM (deep, restorative sleep -most in the first half of the night) and REM (dreaming, muscles paralysed -more in the second half).
  • REM sleep behaviour disorder -acting out dreams (paralysis fails); often an early sign of Parkinson's disease or dementia with Lewy bodies.
  • Narcolepsy -sudden sleep attacks, cataplexy (sudden muscle weakness with emotion, e.g. laughing), sleep paralysis, hallucinations at sleep onset.
• EEG -records the brain's electrical activity; helps classify epilepsy and detect non-convulsive status and encephalitis; a normal interictal EEG doesn't exclude epilepsy (see the Neurology chapters).

Normal Values and CSF Patterns

Measure	Typical adult value
CSF opening pressure	About 10–20 cmH2O (lying on the side; up to about 25 in obesity)
CSF white cells	Under 5 cells/microlitre (lymphocytes)
CSF red cells	None (a few from a traumatic tap)
CSF protein	About 0.15–0.45 g/L
CSF glucose	About 60% or more of the blood glucose (take a paired blood glucose)
CSF volume / production	About 150 mL / about 500 mL a day
Intracranial pressure	About 5–15 mmHg
Cerebral perfusion pressure	Aim above about 60 mmHg in brain injury
Phenytoin level	About 10–20 mg/L (correct for low albumin)
Carbamazepine level	About 4–12 mg/L

Condition	Cells	Protein	Glucose
Bacterial meningitis	High -neutrophils	High	Low
Viral meningitis	Raised -lymphocytes	Normal or slightly raised	Normal
TB meningitis	Raised -lymphocytes	Very high	Low
Fungal (cryptococcal)	Raised -lymphocytes	High	Low; very high opening pressure; cryptococcal antigen
Guillain–Barré	Normal	High (albuminocytological dissociation)	Normal
Multiple sclerosis	Normal or slightly raised	Normal or slightly raised	Normal; oligoclonal bands in CSF but not blood
Subarachnoid haemorrhage	Many red cells	Raised	Normal; xanthochromia (LP at least 12 hours after onset)

Antiseizure Medicines -Principles

• How they work -block sodium channels (carbamazepine, lamotrigine, phenytoin, lacosamide, oxcarbazepine), block calcium channels (ethosuximide -T-type, for absence; gabapentin, pregabalin), boost GABA (benzodiazepines, phenobarbital, valproate, vigabatrin), bind SV2A (levetiracetam, brivaracetam), or block glutamate (perampanel, topiramate). Several act in more than one way.
• Choosing a drug (NICE NG217) -by seizure type and syndrome, age, sex, pregnancy potential, other conditions and drugs:
  • Focal seizures -lamotrigine or levetiracetam first-line; carbamazepine, oxcarbazepine or zonisamide as alternatives.
  • Generalised tonic–clonic seizures -sodium valproate for males and for females unable to have children (subject to MHRA rules below); lamotrigine or levetiracetam otherwise.
  • Absence seizures -ethosuximide first-line (valproate an option).
  • Myoclonic seizures -levetiracetam or valproate.
  • Avoid carbamazepine, oxcarbazepine, phenytoin, gabapentin, pregabalin and vigabatrin in absence and myoclonic seizures -they can make them worse.
• Start one drug, increase slowly to an effective dose; about two-thirds become seizure-free on the first or second drug. Drug-resistant epilepsy (failure of two suitable drugs) -refer for specialist assessment, including surgery.
• Brand consistency (MHRA categories) -keep patients on the same manufacturer for category 1 drugs (phenytoin, carbamazepine, phenobarbital, primidone); use clinical judgement for category 2 (valproate, lamotrigine, topiramate, oxcarbazepine, clobazam, others).
• Enzyme-inducing antiseizure medicines (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate at higher doses, perampanel at higher doses):
  • Reduce the effect of the combined pill, progestogen-only pill, implant and emergency contraception -recommend a copper IUD, levonorgestrel IUS or injection; double-dose levonorgestrel or a copper IUD for emergency contraception.
  • Also reduce warfarin, DOACs (avoid), steroids, other antiseizure drugs, antiretrovirals, chemotherapy, ciclosporin, statins.
  • Long term -osteoporosis and vitamin D deficiency.
• Pregnancy:
  • Folic acid 5 mg daily before conception and in the first trimester (all women on antiseizure medicines who could become pregnant).
  • Safest options are generally lamotrigine and levetiracetam; valproate carries the highest risk; carbamazepine, phenytoin, phenobarbital and topiramate also increase birth defects.
  • Lamotrigine (and levetiracetam) levels fall in pregnancy -monitor and adjust; seizures in pregnancy are dangerous -don't stop drugs suddenly.
  • Vitamin K for babies of mothers on enzyme inducers (routine neonatal vitamin K).
• General safety -mood changes and suicidal thoughts (all antiseizure drugs -MHRA); never stop suddenly (withdrawal seizures and status); DVLA rules after a seizure; SUDEP (sudden unexpected death in epilepsy) risk falls with good control.

Antiseizure Medicines -Individual Drugs

• Sodium valproate -broad spectrum (generalised epilepsies, also bipolar disorder and migraine prevention):
  • Highly teratogenic -about 1 in 10 babies have major birth defects (neural tube defects, heart, limb) and up to 4 in 10 have developmental problems (autism, low IQ).
  • MHRA rules -must not be started in anyone under 55 (male or female) unless two specialists independently agree there is no suitable alternative; girls and women who could become pregnant must be on the Pregnancy Prevention Programme (highly effective contraception, annual risk acknowledgement form); possible small risk to children fathered by men taking valproate -counsel and advise effective contraception.
  • Side effects -weight gain, hair loss (regrows curly), tremor, nausea; hepatotoxicity (highest risk in young children on several drugs -LFTs), pancreatitis, low platelets, hyperammonaemic encephalopathy (confusion, vomiting -check ammonia), polycystic ovaries.
  • Interactions -enzyme inhibitor: doubles lamotrigine levels (rash risk -use a lower, slower lamotrigine titration); carbapenems (meropenem) cause a rapid, large fall in valproate levels (avoid -seizures).
• Lamotrigine -focal and generalised epilepsy; bipolar depression:
  • Serious rash (Stevens–Johnson syndrome, toxic epidermal necrolysis) -mostly in the first 8 weeks; risk raised by fast titration and valproate; stop at the first sign of rash and seek advice.
  • Dizziness, double vision, headache, insomnia; can worsen myoclonic seizures.
  • Oestrogen (combined pill, pregnancy) lowers lamotrigine levels -seizures; levels rise when it stops (toxicity).
  • Restarting after a gap of more than 5 half-lives needs the full slow titration again.
• Levetiracetam -focal and generalised epilepsy; IV for status:
  • Few drug interactions; excreted by the kidneys (reduce dose in CKD).
  • Mood and behaviour changes -irritability, aggression, low mood, suicidal thoughts, psychosis (ask about psychiatric history); drowsiness.
• Carbamazepine -focal epilepsy; trigeminal neuralgia (first-line); bipolar disorder:
  • Hyponatraemia (SIADH-like -especially older people and with diuretics); dizziness, double vision, ataxia; rash.
  • Serious skin reactions -test for HLA-B*1502 before starting in people of Han Chinese, Hong Kong Chinese or Thai origin (high risk of SJS); HLA-A*3101 linked in Europeans and Japanese.
  • Blood disorders (leukopenia, rarely aplastic anaemia -warn about fever, sore throat, bruising), hepatitis.
  • Strong enzyme inducer -including its own metabolism (autoinduction -levels fall over the first few weeks); many interactions (contraception, warfarin, DOACs, steroids); levels raised by clarithromycin, erythromycin, fluconazole, diltiazem, verapamil.
  • Oxcarbazepine -similar, more hyponatraemia, fewer interactions.
• Phenytoin -now mostly for status epilepticus:
  • Zero-order (saturation) kinetics at usual doses -small dose increases cause large rises in level; narrow range (about 10–20 mg/L); correct the level for low albumin.
  • Toxicity -nystagmus, ataxia, slurred speech, double vision, confusion, and paradoxically seizures.
  • Long-term effects -gum overgrowth, hirsutism, coarse facial features, acne, peripheral neuropathy, cerebellar atrophy, osteomalacia, folate deficiency (megaloblastic anaemia), lymphadenopathy.
  • IV phenytoin -hypotension, arrhythmias and heart block (give no faster than 50 mg/min with ECG and blood pressure monitoring), "purple glove" tissue damage.
  • Enzyme inducer; teratogenic (fetal hydantoin syndrome); many interactions (warfarin, valproate, fluconazole, amiodarone raise levels).
• Other antiseizure medicines (key points):
  • Topiramate -weight loss, word-finding difficulty and slowed thinking, tingling, kidney stones, acute angle-closure glaucoma, metabolic acidosis; teratogenic -MHRA Pregnancy Prevention Programme (also used for migraine).
  • Zonisamide -weight loss, kidney stones, low mood; sulfonamide (avoid in sulfa allergy).
  • Lacosamide -PR prolongation and heart block (ECG if cardiac disease); dizziness.
  • Ethosuximide -absence seizures; nausea, rarely blood disorders.
  • Clobazam and clonazepam (benzodiazepines) -add-on and short-term "cover" (e.g. around periods -catamenial epilepsy); tolerance, sedation, dependence.
  • Perampanel -aggression, hostility, mood change.
  • Phenobarbital -sedation, cognitive slowing, dependence; strong enzyme inducer; used in neonatal seizures and some status.
  • Vigabatrin -infantile spasms; permanent visual field loss (field tests).
  • Cannabidiol, stiripentol and fenfluramine (echocardiography) -specialist use in Dravet and Lennox–Gastaut syndromes.

Status Epilepticus Drugs

• Definition (practical) -a convulsive seizure lasting 5 minutes or more, or repeated seizures without recovery in between -treat urgently.
• Start -ABC, high-flow oxygen, check glucose (treat hypoglycaemia), IV access; thiamine (Pabrinex) if alcohol misuse or malnutrition is possible; think of eclampsia in pregnancy (magnesium sulfate).
• First-line -a benzodiazepine:
  • IV lorazepam 4 mg (0.1 mg/kg), repeated once after 5–10 minutes if seizures continue.
  • No IV access (or in the community) -buccal midazolam 10 mg (or rectal diazepam 10–20 mg).
  • Give no more than two doses of benzodiazepine in total (including pre-hospital doses) -risk of respiratory depression.
• Second-line (if seizures continue after benzodiazepines) -one of:
  • IV levetiracetam (about 60 mg/kg, maximum 4.5 g) over about 10 minutes.
  • IV phenytoin 20 mg/kg (no faster than 50 mg/min -ECG and blood pressure monitoring; not if the patient already takes phenytoin and levels are adequate).
  • IV sodium valproate (about 40 mg/kg) -avoid in women who could become pregnant where possible, and in liver disease.
  These have similar effectiveness (ESETT trial); follow local protocol.
• Third-line (refractory status) -about 30–45 minutes after onset: anaesthetist and ITU -rapid sequence induction with propofol, thiopental or midazolam, with EEG monitoring.
• Look for the cause -missed or stopped antiseizure drugs, alcohol or drug withdrawal, infection (meningitis, encephalitis -aciclovir), stroke or bleed, low sodium, calcium or glucose, overdose (TCAs, isoniazid -pyridoxine), non-epileptic attacks (avoid repeated benzodiazepines if suspected -get senior help).

⚠️ Safety Pearl: Count every benzodiazepine dose given before arrival (buccal midazolam by family or paramedics counts). Two doses total, then move to a second-line drug -more benzodiazepines mostly add respiratory depression.

Parkinson's Disease Drugs

• Levodopa -the most effective drug; converted to dopamine in the brain.
  • Always given with a peripheral dopa-decarboxylase inhibitor -carbidopa (co-careldopa -Sinemet) or benserazide (co-beneldopa -Madopar) -to stop conversion outside the brain (less nausea and postural hypotension; more reaches the brain).
  • Side effects -nausea, postural hypotension, sleepiness, hallucinations and confusion (especially older people), impulse control problems (less than with agonists); long term -dyskinesias (involuntary writhing at peak dose), wearing off before the next dose, sudden "on–off" switching.
  • High-protein meals reduce absorption (amino acid competition).
• Dopamine agonists -ropinirole, pramipexole, rotigotine (skin patch -useful when nil by mouth); apomorphine (injection or infusion -severe nausea, given with domperidone).
  • Impulse control disorders -gambling, hypersexuality, binge eating, compulsive shopping -warn patients and partners and ask at every review (MHRA).
  • Excessive daytime sleepiness and sudden onset of sleep -warn about driving.
  • Hallucinations, confusion, postural hypotension, ankle oedema; abrupt withdrawal causes dopamine agonist withdrawal syndrome.
  • Ergot agonists (bromocriptine, cabergoline) -fibrosis (heart valves, lungs) -rarely used now.
• MAO-B inhibitors -rasagiline, selegiline, safinamide -reduce dopamine breakdown; mild effect; caution with pethidine, tramadol, SSRIs and other serotonergic drugs (serotonin syndrome).
• COMT inhibitors -entacapone, opicapone -taken with levodopa to extend each dose (wearing off); can increase dyskinesias; entacapone turns urine orange; diarrhoea.
• Amantadine -reduces dyskinesias; hallucinations, livedo reticularis, ankle oedema; kidney excretion (dose down in CKD).
• Anticholinergics (trihexyphenidyl, procyclidine) -tremor in younger people; avoid in older people (confusion, falls, constipation, urinary retention).
• Advanced treatments -deep brain stimulation, continuous levodopa infusions (intestinal gel, or subcutaneous foslevodopa–foscarbidopa), apomorphine infusion.
• Non-motor symptoms -Parkinson's psychosis (reduce drugs in reverse order of benefit; quetiapine or clozapine -clozapine needs blood monitoring); dementia (rivastigmine); depression; constipation; postural hypotension (fludrocortisone, midodrine); drooling (glycopyrronium).
• Drugs to avoid -dopamine blockers: haloperidol, most antipsychotics, metoclopramide, prochlorperazine -they worsen Parkinson's (use domperidone for nausea, though watch QT).

⚠️ Safety Pearl: Parkinson's drugs are time-critical -give them within 30 minutes of the patient's usual time. Never stop them suddenly (rigidity, inability to swallow, aspiration and a neuroleptic malignant-like syndrome). If nil by mouth, use an NG tube or a rotigotine patch (use a dose conversion calculator and get specialist advice).

Migraine and Headache Drugs

• Acute migraine (NICE CG150):
  • Simple painkillers -aspirin 900 mg, ibuprofen or paracetamol -taken early.
  • Triptans (sumatriptan, zolmitriptan, rizatriptan, others) -5-HT1B/1D agonists -narrow cranial vessels and reduce CGRP release; often combined with an NSAID or paracetamol; take at the start of the headache (not during the aura). Side effects -tingling, tightness in the chest, throat or jaw, flushing. Avoid in ischaemic heart disease, previous stroke or TIA, peripheral vascular disease, uncontrolled hypertension. Nasal or injected forms if vomiting.
  • Antiemetics -metoclopramide or prochlorperazine (also help absorption and the headache itself).
  • Gepants (CGRP receptor blockers -rimegepant) -acute treatment when triptans fail or are contraindicated (no vasoconstriction).
  • Avoid opioids -less effective, and they cause medication overuse headache.
• Medication overuse headache -daily headache from taking triptans, opioids or combination painkillers on 10 or more days a month, or simple painkillers on 15 or more days a month; treat by stopping the overused drug (abruptly, except opioids -taper) and starting prevention.
• Migraine prevention (4 or more attacks a month, or disabling attacks):
  • Propranolol (avoid in asthma), amitriptyline (drowsiness, weight gain, anticholinergic), topiramate (teratogenic -Pregnancy Prevention Programme; reduces the combined pill's effect), candesartan (off-label).
  • CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) and atogepant or rimegepant -after 3 preventive drugs have failed (NICE TAs; specialist).
  • Botulinum toxin type A injections -chronic migraine (15 or more headache days a month).
  • Riboflavin (vitamin B2) may help some people.
• Migraine with aura and contraception -the combined pill is contraindicated (higher stroke risk) -use progestogen-only methods or an IUD.
• Cluster headache:
  • Acute -high-flow 100% oxygen (12–15 L/min via non-rebreathe mask for 15–20 minutes) and subcutaneous sumatriptan 6 mg or nasal triptan.
  • Prevention -verapamil (ECG before and during -heart block), short courses of prednisolone, occipital nerve block; lithium (specialist).
• Trigeminal neuralgia -carbamazepine first-line; refer if atypical or not responding.
• Giant cell arteritis (over 50, new headache, jaw claudication, scalp tenderness, visual symptoms) -start prednisolone immediately (40–60 mg; IV methylprednisolone if visual loss), then confirm; aspirin is not routinely needed.

Stroke Drugs

• Thrombolysis -alteplase or tenecteplase for acute ischaemic stroke within 4.5 hours of onset (or last known well) once haemorrhage is excluded on CT:
  • Main risk -brain haemorrhage (about 1 in 20); also angioedema (higher with ACE inhibitors), bleeding elsewhere.
  • Contraindications include intracranial bleeding, recent major surgery or bleeding, anticoagulation with raised INR or recent DOAC, platelets very low, uncontrolled blood pressure (lower to under 185/110 before and under 180/105 for 24 hours after), abnormal glucose (check it).
  • No antiplatelets or anticoagulants for 24 hours after thrombolysis (repeat CT first).
• Mechanical thrombectomy -for large vessel occlusion, usually up to 6 hours (and up to 24 hours in selected patients with salvageable brain on imaging), often after thrombolysis.
• Antiplatelets:
  • Acute ischaemic stroke -aspirin 300 mg daily for 2 weeks (once haemorrhage is excluded), then clopidogrel 75 mg daily long term.
  • High-risk TIA or minor stroke -aspirin plus clopidogrel for 21 days, then clopidogrel alone (follow the national guideline).
  • Add a PPI for those at high risk of GI bleeding.
• Anticoagulation for AF-related stroke -a DOAC (apixaban, edoxaban, rivaroxaban, dabigatran) rather than aspirin; timing depends on stroke size (earlier start is increasingly used; follow current guidance). Never anticoagulate until haemorrhage has been excluded.
• Statin -high-intensity atorvastatin 20–80 mg after ischaemic stroke or TIA (aim for LDL under about 1.8 mmol/L); not usually after haemorrhage unless another indication.
• Blood pressure -long-term target systolic under about 130 mmHg after stroke (if tolerated); in acute intracerebral haemorrhage, lower systolic BP to about 130–140 mmHg within 6 hours (if over 150) and reverse anticoagulation urgently -prothrombin complex concentrate plus IV vitamin K (warfarin), idarucizumab (dabigatran), andexanet alfa (factor Xa inhibitors, where available) or PCC.
• Subarachnoid haemorrhage -nimodipine 60 mg every 4 hours for 21 days (reduces delayed cerebral ischaemia; watch for hypotension); secure the aneurysm (coiling or clipping); manage hyponatraemia (often salt wasting -don't fluid restrict).
• Carotid endarterectomy -for symptomatic carotid stenosis of 50–99%, ideally within 2 weeks.

Multiple Sclerosis Drugs

• Relapses -methylprednisolone (500 mg orally daily for 5 days, or 1 g IV daily for 3–5 days) shortens relapses but doesn't change long-term disability; exclude infection (urine) first; warn about mood, sleep and glucose effects.
• Disease-modifying therapies (relapsing MS -specialist, NICE NG220 and TAs) reduce relapses and new MRI lesions:

Drug	Type	Key risks
Interferon beta, glatiramer acetate	Injectable, moderate efficacy	Flu-like symptoms, injection site reactions, low mood, LFTs (interferon); safe-ish in pregnancy planning
Dimethyl fumarate, diroximel fumarate	Oral	Flushing, GI upset, lymphopenia (rare PML) -FBC monitoring
Teriflunomide	Oral	Hair thinning, liver toxicity, teratogenic (accelerated elimination needed before pregnancy)
Fingolimod, siponimod, ozanimod, ponesimod	Oral S1P modulators	Bradycardia with the first dose (monitoring), macular oedema, shingles (check varicella immunity), skin cancer, rebound on stopping; teratogenic
Cladribine	Oral, short courses	Lymphopenia, infections (shingles), teratogenic
Ocrelizumab, ofatumumab, ublituximab	Anti-CD20 antibodies (B-cell depletion)	Infusion or injection reactions, infections, hepatitis B reactivation (screen), low immunoglobulins; ocrelizumab also for early primary progressive MS
Natalizumab	Infusion (blocks immune cells entering the brain)	PML (brain infection by JC virus) -test for JC virus antibodies and monitor with MRI
Alemtuzumab	Infusion (anti-CD52)	Secondary autoimmune disease (thyroid, ITP, kidney) -monthly blood and urine monitoring for years; stroke and infusion reactions

• Symptom treatments -spasticity (baclofen, gabapentin, tizanidine, botulinum toxin, physiotherapy); bladder (antimuscarinics or mirabegron, intermittent self-catheterisation if residual volume is high); fatigue (exercise, amantadine -NICE recommends against modafinil and others routinely); neuropathic pain; fampridine (walking speed -seizure risk; not NICE-recommended).
• Pregnancy -relapse rate falls in pregnancy and rises after delivery; plan DMT changes before conception.
• Vitamin D -check and replace deficiency.

Myasthenia and Neuromuscular Drugs

• Pyridostigmine -acetylcholinesterase inhibitor; symptom relief in myasthenia gravis.
  • Cholinergic side effects -diarrhoea, abdominal cramps, sweating, salivation, muscle twitching.
  • Too much causes cholinergic crisis (weakness that mimics a myasthenic crisis, with small pupils and secretions).
• Immunosuppression -prednisolone (start low and increase slowly in ocular or mild disease -high starting doses can cause temporary worsening), with azathioprine (check TPMT), mycophenolate or methotrexate as steroid-sparing drugs; rituximab (especially MuSK-positive).
• Newer targeted drugs (specialist) -complement inhibitors (eculizumab, ravulizumab, zilucoplan -meningococcal vaccination needed) and FcRn blockers (efgartigimod, rozanolixizumab).
• Thymectomy -for thymoma, and improves outcomes in many younger patients with AChR-antibody myasthenia.
• Myasthenic crisis -ITU, monitor FVC (consider ventilation if falling towards 15–20 mL/kg), IV immunoglobulin or plasma exchange; look for the trigger (infection, drugs, surgery, stopping treatment).
• Drugs that can worsen myasthenia -aminoglycosides (gentamicin), fluoroquinolones (ciprofloxacin), macrolides, magnesium, beta-blockers, quinine, chloroquine and hydroxychloroquine, penicillamine, lithium, phenytoin, statins (rarely), immune checkpoint inhibitors, botulinum toxin, neuromuscular blocking drugs. Check before prescribing (Myaware lists).
• Guillain–Barré syndrome -IV immunoglobulin (0.4 g/kg daily for 5 days) or plasma exchange; steroids don't help; monitor FVC, swallowing and autonomic function (arrhythmias, BP swings); VTE prophylaxis; treat neuropathic pain.
• Lambert–Eaton -treat the cancer; amifampridine (increases acetylcholine release).
• Motor neurone disease -riluzole (glutamate release blocker -modest survival benefit; check LFTs and FBC -neutropenia); NIV for breathing weakness (improves survival and quality of life); gastrostomy; specialist SOD1-targeted therapy for a small genetic subgroup.

Dementia Drugs

• Acetylcholinesterase inhibitors -donepezil, rivastigmine (tablets or patch), galantamine:
  • Uses -mild to moderate Alzheimer's disease; also dementia with Lewy bodies and Parkinson's disease dementia (NICE NG97). Not for vascular dementia alone or frontotemporal dementia.
  • Side effects -nausea, vomiting, diarrhoea, loss of appetite and weight; bradycardia, heart block and syncope (check pulse; ECG if slow or cardiac disease); vivid dreams and insomnia (donepezil -move to the morning); urinary incontinence; muscle cramps.
  • Effect is modest (stabilises symptoms for months).
• Memantine -NMDA receptor antagonist; moderate to severe Alzheimer's (alone, or added to an AChE inhibitor); dizziness, headache, constipation, drowsiness; reduce dose in CKD.
• Anti-amyloid antibodies (lecanemab, donanemab) -licensed for early Alzheimer's but not recommended by NICE for NHS use; risk of ARIA (brain swelling and microbleeds), especially in people with two APOE4 copies or on anticoagulants.
• Behavioural and psychological symptoms:
  • Look for causes first (pain, constipation, infection, retention, drugs, environment) and use non-drug approaches.
  • Antipsychotics increase the risk of stroke and death in dementia -use only for severe distress or risk, at the lowest dose, for the shortest time (e.g. risperidone, reviewed within 6 weeks).
  • In dementia with Lewy bodies and Parkinson's -severe sensitivity to antipsychotics (rigidity, falls, death) -avoid haloperidol.
• Anticholinergic burden -drugs with antimuscarinic effects (oxybutynin, TCAs, chlorphenamine, some antipsychotics) worsen confusion and are linked to dementia risk -review and deprescribe.

Neuropathic Pain Drugs

• NICE CG173 -offer one of amitriptyline, duloxetine, gabapentin or pregabalin; if it doesn't work at a tolerated dose, switch to another of the four. Carbamazepine for trigeminal neuralgia. Capsaicin cream for localised pain if oral drugs aren't wanted. Tramadol only for short-term rescue.
• Amitriptyline (and nortriptyline) -TCA; start low at night (10 mg); side effects -drowsiness, dry mouth, constipation, urinary retention, weight gain, postural hypotension, QT prolongation; dangerous in overdose (arrhythmias, seizures); caution in older people and heart disease.
• Duloxetine -SNRI; nausea (common at first), insomnia, sweating, raised blood pressure, hyponatraemia, serotonin syndrome with other serotonergic drugs; withdrawal symptoms on stopping.
• Gabapentin and pregabalin (gabapentinoids):
  • Bind the alpha-2-delta subunit of calcium channels → less transmitter release.
  • Side effects -dizziness, drowsiness, unsteadiness, weight gain, peripheral oedema, blurred vision.
  • Controlled drugs (Schedule 3) -misuse and dependence; withdraw slowly.
  • Respiratory depression, especially with opioids, in older people, COPD and kidney impairment (MHRA).
  • Excreted by the kidneys -reduce doses in CKD (toxicity -confusion, falls).
  • Pregabalin in pregnancy -possible small increase in birth defects (MHRA) -use effective contraception.
• Capsaicin -depletes substance P; burning at first; 8% patch in specialist settings.
• Lidocaine plasters -post-herpetic neuralgia (limited NHS use).
• Opioids -poor for long-term neuropathic pain; harms outweigh benefit for most chronic pain (NICE NG193).

Spasticity, Tremor and Other Neurological Drugs

• Baclofen -GABA-B agonist; spasticity (MS, stroke, spinal cord injury, cerebral palsy); drowsiness, weakness, confusion (older people, CKD -kidney excretion); never stop suddenly -withdrawal causes hallucinations, seizures, fever and rigidity (especially intrathecal pumps -an emergency).
• Tizanidine -alpha-2 agonist; drowsiness, hypotension, dry mouth, liver toxicity (LFTs); contraindicated with fluvoxamine and ciprofloxacin (CYP1A2 -large rise in levels).
• Dantrolene -acts directly on muscle (reduces calcium release); used for spasticity, and IV for malignant hyperthermia and severe NMS; liver toxicity.
• Botulinum toxin -injected into overactive muscles (focal spasticity, dystonia, blepharospasm, chronic migraine, drooling, overactive bladder); weakness can spread (swallowing and breathing problems -rare).
• Essential tremor -propranolol or primidone (sedation; enzyme inducer); topiramate or gabapentin second-line; deep brain stimulation or focused ultrasound.
• Huntington's chorea -tetrabenazine (depletes dopamine -depression and suicidal thoughts, parkinsonism), antipsychotics.
• Restless legs syndrome -check ferritin and give iron if low (ferritin under about 75 micrograms/L); gabapentinoids or dopamine agonists (low dose -augmentation: symptoms get worse and earlier over time); avoid antihistamines, antidepressants and dopamine blockers that worsen it.
• Narcolepsy -modafinil (headache, insomnia; may cause birth defects and reduce hormonal contraception -MHRA), pitolisant, sodium oxybate (cataplexy; specialist; respiratory depression).
• Vertigo:
  • BPPV -Epley manoeuvre, not drugs.
  • Vestibular neuritis -short course (up to 3 days) of a vestibular sedative (prochlorperazine, cyclizine); longer use delays recovery (compensation).
  • Ménière's disease -betahistine (prevention -evidence is weak), salt restriction; specialist referral.
• Bell's palsy -prednisolone within 72 hours (50 mg daily for 10 days, or 60 mg for 5 days then taper); eye protection (lubricants, tape at night); antivirals not routinely needed (consider in severe cases or Ramsay Hunt syndrome).
• Wernicke's encephalopathy -high-dose IV thiamine (Pabrinex).
• Viral encephalitis -IV aciclovir started immediately on suspicion (kidney toxicity -hydrate, adjust for eGFR).
• Bacterial meningitis -ceftriaxone (or cefotaxime) urgently, plus amoxicillin if Listeria is possible (over 60, immunocompromised, pregnant); dexamethasone with or just before the first antibiotic dose in adults with suspected bacterial meningitis; benzylpenicillin IM in the community for suspected meningococcal disease.

Drugs That Cause Neurological Problems

Problem	Typical drugs
Seizures (lower threshold)	Tramadol, bupropion, theophylline, ciprofloxacin and other quinolones, high-dose penicillins and carbapenems, clozapine and other antipsychotics, TCAs, lithium toxicity, isoniazid (pyridoxine), local anaesthetic toxicity, withdrawal of alcohol, benzodiazepines, baclofen or antiseizure drugs; drugs causing low sodium or glucose
Delirium and confusion	Anticholinergics, opioids, benzodiazepines, gabapentinoids, steroids, Parkinson's drugs, digoxin, lithium, antihistamines, H2 blockers, quinolones
Parkinsonism and other movement disorders	Antipsychotics, metoclopramide, prochlorperazine, valproate (tremor, parkinsonism), lithium (tremor), SSRIs; acute dystonia (metoclopramide, haloperidol); tardive dyskinesia (long-term dopamine blockers)
Serotonin syndrome	SSRIs and SNRIs with tramadol, MAOIs, linezolid, triptans (rare), St John's wort, fentanyl, MDMA
Neuroleptic malignant syndrome	Antipsychotics, metoclopramide; stopping levodopa or dopamine agonists
Peripheral neuropathy	Isoniazid, metronidazole (long courses), nitrofurantoin, vincristine, platinum drugs (cisplatin, oxaliplatin), taxanes, bortezomib, amiodarone, phenytoin, linezolid, dapsone, colchicine, some HIV drugs, nitrous oxide (B12), alcohol
Myopathy	Statins (especially with fibrates, macrolides, ciclosporin), steroids, colchicine, zidovudine, alcohol, immune checkpoint inhibitors (also myositis and myasthenia)
Raised intracranial pressure (IIH)	Tetracyclines (doxycycline, minocycline), isotretinoin and vitamin A, steroid withdrawal, lithium, growth hormone
Ototoxicity	Aminoglycosides, cisplatin, high-dose IV loop diuretics, high-dose aspirin, quinine
Cerebellar ataxia	Phenytoin, carbamazepine, lithium, alcohol, metronidazole (encephalopathy), chemotherapy (cytarabine, 5-FU)
Headache	Nitrates, calcium channel blockers, PDE5 inhibitors, medication overuse (painkillers, triptans, opioids), caffeine withdrawal
Optic nerve damage	Ethambutol, amiodarone, linezolid, PDE5 inhibitors and semaglutide (ischaemic optic neuropathy -rare)
PML (JC virus brain infection)	Natalizumab, rituximab, dimethyl fumarate, other strong immunosuppressants
Posterior reversible encephalopathy (PRES)	Ciclosporin, tacrolimus, chemotherapy, severe hypertension, eclampsia
Worsening myasthenia	Aminoglycosides, quinolones, macrolides, magnesium, beta-blockers, checkpoint inhibitors
Bleeding into the brain	Anticoagulants, antiplatelets, thrombolytics, SSRIs (small extra risk with anticoagulants)

Drug Reference Table

Drug	Key points
Sodium valproate	Broad spectrum; highly teratogenic -MHRA rules (not started under 55 without two specialists); weight gain, tremor, liver, pancreatitis, ammonia; raises lamotrigine; carbapenems lower it.
Lamotrigine	Slow titration -SJS rash (worse with valproate); oestrogen lowers levels; relatively safe in pregnancy.
Levetiracetam	Few interactions; renal dosing; mood and behaviour change; IV in status.
Carbamazepine	Trigeminal neuralgia; hyponatraemia; HLA-B*1502 testing; enzyme inducer (contraception); autoinduction.
Phenytoin	Zero-order kinetics; level 10–20 mg/L; nystagmus and ataxia in toxicity; gum overgrowth; IV max 50 mg/min with ECG.
Topiramate	Epilepsy and migraine; teratogenic (PPP); kidney stones, glaucoma, cognitive slowing.
Lorazepam / buccal midazolam	First-line in status; maximum two benzodiazepine doses.
Co-careldopa / co-beneldopa	Levodopa with decarboxylase inhibitor; time-critical; dyskinesias, wearing off, hallucinations, postural hypotension.
Ropinirole / pramipexole / rotigotine	Dopamine agonists; impulse control disorders, sudden sleep; rotigotine patch if nil by mouth.
Rasagiline / entacapone / amantadine	MAO-B inhibitor / COMT inhibitor (orange urine) / anti-dyskinesia.
Sumatriptan	5-HT1B/1D agonist; avoid in IHD, stroke, PVD; SC 6 mg for cluster headache.
CGRP antibodies / gepants	Migraine prevention after 3 failed preventives; rimegepant also acute.
Propranolol / amitriptyline	Migraine prevention; propranolol also for essential tremor.
Verapamil	Cluster headache prevention -ECG for heart block.
Alteplase / tenecteplase	Thrombolysis within 4.5 hours; haemorrhage; BP under 185/110; no antithrombotics for 24 hours.
Aspirin 300 mg then clopidogrel	Ischaemic stroke -2 weeks aspirin, then clopidogrel long term; DAPT 21 days for high-risk TIA or minor stroke.
Nimodipine	SAH -60 mg 4-hourly for 21 days; hypotension.
Methylprednisolone	MS relapse -shortens it; exclude infection.
Natalizumab / ocrelizumab / alemtuzumab	MS DMTs; PML (JC virus) / infections, hepatitis B / secondary autoimmunity.
Pyridostigmine	Myasthenia; cholinergic side effects; overdose -cholinergic crisis.
IV immunoglobulin	GBS, myasthenic crisis; monitor FVC.
Riluzole	MND; LFTs and FBC.
Donepezil / rivastigmine	Alzheimer's, Lewy body and Parkinson's dementia; bradycardia, syncope, GI effects.
Memantine	NMDA antagonist; moderate to severe Alzheimer's; renal dosing.
Gabapentin / pregabalin	Neuropathic pain; controlled drugs; respiratory depression with opioids; renal dosing.
Duloxetine	SNRI for neuropathic pain; nausea, hyponatraemia, serotonin syndrome.
Baclofen / tizanidine	Spasticity; baclofen -never stop suddenly; tizanidine -not with ciprofloxacin or fluvoxamine.
Dantrolene	Malignant hyperthermia; severe NMS.
Prednisolone (Bell's palsy, GCA)	Bell's within 72 hours; GCA -start immediately.
Aciclovir / ceftriaxone / dexamethasone	Encephalitis / meningitis (add amoxicillin for Listeria risk) / adjunct in bacterial meningitis.
Procyclidine	Acute dystonic reactions.

Spot the Answer

Clue	Answer
Fluent, meaningless speech with poor understanding	Wernicke's (receptive) dysphasia -dominant temporal lobe
Leg weakness more than arm with urinary incontinence after a stroke	Anterior cerebral artery territory
Ignores the left side of the body after a stroke	Right (non-dominant) parietal lobe -neglect
Facial weakness sparing the forehead	Upper motor neurone lesion (stroke)
Ptosis, "down and out" eye and a dilated pupil with headache	Compressive third nerve palsy -posterior communicating artery aneurysm
Ipsilateral Horner's and facial numbness with contralateral body pain loss	Lateral medullary syndrome (PICA or vertebral)
Lens-shaped bleed after a blow to the temple with a lucid interval	Extradural haematoma -middle meningeal artery
Wet, wobbly, wacky in an older man with big ventricles	Normal pressure hydrocephalus
Same-side weakness and vibration loss, opposite-side pain loss	Brown-Séquard syndrome
Absent ankle jerks with upgoing plantars after nitrous oxide use	Subacute combined degeneration (B12)
Saddle anaesthesia and urinary retention after back pain	Cauda equina syndrome -emergency MRI
Foot drop with preserved inversion after crossing legs	Common peroneal nerve palsy
Thenar wasting and night-time tingling in the thumb and fingers	Carpal tunnel syndrome (median nerve)
Painful Horner's syndrome with neck pain	Carotid artery dissection
Bitemporal hemianopia	Chiasmal compression (pituitary tumour)
CSF protein 2.1 g/L with normal cell count and ascending weakness	Guillain–Barré syndrome
Fatigable ptosis and double vision worse in the evening	Myasthenia gravis
Weakness after gentamicin in a patient with ptosis	Aminoglycoside worsening myasthenia
Rash 3 weeks after valproate was added to lamotrigine	Lamotrigine SJS risk (valproate doubles levels)
Seizures return when a patient on valproate gets meropenem	Carbapenem interaction -valproate levels crash
Nystagmus, ataxia and slurred speech after a small phenytoin dose increase	Phenytoin toxicity (zero-order kinetics)
Sodium 122 in an older woman with trigeminal neuralgia	Carbamazepine hyponatraemia
Unplanned pregnancy in a woman on carbamazepine and the combined pill	Enzyme induction -contraceptive failure
New compulsive gambling in Parkinson's	Dopamine agonist impulse control disorder
Rigid, febrile Parkinson's patient who has been nil by mouth for 2 days	Parkinsonism-hyperpyrexia (missed levodopa)
Syncope and heart rate 42 in a patient on a dementia drug	Donepezil bradycardia

Exam-style Scenarios

1. A 32-year-old man with epilepsy is fitting in A&E. He has had buccal midazolam from his partner 10 minutes ago. The seizure has now lasted 15 minutes.
Answer: Convulsive status epilepticus.

• ABC, oxygen, glucose; give one dose of IV lorazepam 4 mg (the buccal midazolam counts as the first benzodiazepine dose).
• If still fitting -IV levetiracetam, phenytoin or valproate (second-line), with ECG monitoring for phenytoin.
• Call the anaesthetist early -general anaesthesia by about 30–45 minutes if seizures continue; look for the cause (missed doses, alcohol, infection, sodium).

2. A 24-year-old woman with newly diagnosed generalised tonic–clonic seizures asks to start sodium valproate, which worked well for her father.
Answer: Valproate should not be started -offer lamotrigine or levetiracetam.

• MHRA -valproate must not be started in anyone under 55 unless two specialists agree there is no alternative; if used in women who could become pregnant, the Pregnancy Prevention Programme is required.
• Explain risks -about 1 in 10 major birth defects and up to 4 in 10 developmental problems.
• Folic acid 5 mg if she might become pregnant; discuss contraception (lamotrigine levels fall with the combined pill); DVLA advice.

3. A 78-year-old man with Parkinson's disease is nil by mouth after emergency bowel surgery. Two days later he is rigid, febrile, confused and his CK is 4,800.
Answer: Parkinsonism-hyperpyrexia syndrome from missed levodopa.

• Restart dopaminergic treatment urgently -rotigotine patch (dose conversion) or levodopa via NG tube if the gut can be used; specialist advice.
• Supportive care -fluids, cooling, monitor kidney function (rhabdomyolysis); exclude sepsis.
• Avoid haloperidol and metoclopramide; Parkinson's drugs are time-critical -flag on admission.

4. A 55-year-old woman with myasthenia gravis is given IV gentamicin for pyelonephritis. Next day she has slurred speech, difficulty swallowing and breathlessness. FVC is 1.2 L (normally 3 L).
Answer: Myasthenic crisis precipitated by an aminoglycoside (and infection).

• Stop gentamicin and choose a safer antibiotic; nil by mouth (aspiration risk).
• ITU review -monitor FVC regularly (not just saturations); prepare for ventilation.
• IV immunoglobulin or plasma exchange; continue pyridostigmine with caution (secretions); neurology input.

5. An 80-year-old woman started on carbamazepine for trigeminal neuralgia is brought in confused. Sodium 119 mmol/L. She also takes bendroflumethiazide and warfarin; her INR has fallen to 1.4.
Answer: Carbamazepine-induced hyponatraemia (worsened by the thiazide) and enzyme induction lowering warfarin effect.

• Stop the thiazide; reduce or stop carbamazepine with specialist advice; correct sodium slowly (no more than about 10 mmol/L in 24 hours).
• Recheck INR and adjust warfarin (consider a DOAC -but carbamazepine also lowers DOAC levels).
• Alternatives for trigeminal neuralgia -oxcarbazepine (also causes hyponatraemia), lamotrigine, baclofen, or referral for surgery.

Key Points

• Localise first: cortex, deep structures, brainstem, cord, root, plexus, nerve, neuromuscular junction or muscle.
• Dominant hemisphere (usually left) -language; non-dominant -neglect.
• ACA -leg; MCA -face and arm, dysphasia or neglect; PCA -hemianopia with macular sparing; lacunar -pure motor, no cortical signs.
• Brainstem lesions give crossed signs; cerebellar lesions give same-side signs (DANISH).
• UMN facial palsy spares the forehead; LMN (Bell's) doesn't.
• Compressive third nerve palsy dilates the pupil; diabetic palsy spares it.
• Extradural -middle meningeal artery, lens-shaped; subdural -bridging veins, crescent.
• Cord ends at L1–L2; LP at L3–L4 or L4–L5; CT first if signs of raised pressure.
• Dorsal columns cross in the medulla; spinothalamic tracts cross at once.
• UMN -spastic, brisk reflexes, upgoing plantars; LMN -wasting, fasciculations, absent reflexes.
• Low calcium raises nerve excitability; fast sodium correction causes osmotic demyelination.
• CPP = MAP − ICP; Cushing's response is a late sign; dexamethasone only for tumour oedema.
• CSF: bacterial -neutrophils, low glucose; viral -lymphocytes, normal glucose; GBS -high protein, normal cells.
• Focal epilepsy -lamotrigine or levetiracetam; avoid carbamazepine and phenytoin in absence and myoclonic seizures.
• Valproate -teratogenic; MHRA rules; enzyme inducers break contraception.
• Phenytoin -zero-order kinetics; IV with ECG monitoring.
• Status -two benzodiazepine doses maximum, then levetiracetam, phenytoin or valproate.
• Parkinson's drugs are time-critical; avoid haloperidol and metoclopramide; dopamine agonists cause impulse control disorders.
• Triptans -avoid in vascular disease; limit acute drugs to avoid medication overuse headache.
• Stroke -thrombolysis within 4.5 hours; aspirin 300 mg for 2 weeks then clopidogrel; nimodipine for SAH.
• Myasthenia -avoid aminoglycosides, quinolones, macrolides and magnesium; monitor FVC in crisis.
• Gabapentinoids -controlled drugs; respiratory depression with opioids; reduce doses in CKD.
• Antipsychotics in dementia raise stroke and death risk; avoid in Lewy body dementia.

Guidelines and Further Reading

• NICE NG217: Epilepsies in children, young people and adults
• MHRA Drug Safety Updates: valproate (2024 rules), topiramate, antiseizure medicine switching, lamotrigine, gabapentinoids, dopamine agonists, metoclopramide
• NICE NG71: Parkinson's disease in adults
• NICE CG150: Headaches in over 12s; NICE TAs for CGRP-targeted drugs
• National Clinical Guideline for Stroke for the UK and Ireland (Intercollegiate Stroke Working Party); NICE NG128: Stroke and TIA
• NICE NG220: Multiple sclerosis in adults
• Association of British Neurologists: Myasthenia gravis management guidelines
• NICE NG97: Dementia
• NICE CG173: Neuropathic pain -pharmacological management
• NICE NG42: Motor neurone disease
• NICE NG240: Meningitis (bacterial) and meningococcal disease
• BNF -for current doses