Key Facts

The nervous system processes sensory information, coordinates motor output, and regulates homeostasis through complex neural circuits. Understanding neurophysiology is essential for localising neurological lesions and understanding drug mechanisms.

Epidemiology

Neurological conditions account for approximately 10% of GP consultations and 20% of acute medical admissions. Stroke affects approximately 100,000 people per year in the UK. Epilepsy prevalence is approximately 0.5-1%. Multiple sclerosis affects ~130,000 people in the UK.

Aetiology

Neurological dysfunction results from:

• Structural lesions: Stroke, tumour, trauma, demyelination
• Functional disorders: Epilepsy, migraine
• Degenerative diseases: Parkinson's, motor neurone disease, dementia
• Neuromuscular: Myasthenia gravis, Guillain-Barré syndrome
• Metabolic/toxic: B12 deficiency, alcohol, drugs

Pathophysiology

Synaptic transmission:

• Action potential → Ca²⁺ entry → vesicle fusion → neurotransmitter release → receptor binding → postsynaptic potential
• Excitatory: Glutamate (NMDA, AMPA receptors) → depolarisation
• Inhibitory: GABA (GABA-A = Cl⁻ channel; GABA-B = G-protein coupled), glycine → hyperpolarisation

Motor pathways:

• Corticospinal (pyramidal) tract: Primary motor cortex → internal capsule → decussation at medullary pyramids → lateral corticospinal tract → LMN
• Extrapyramidal system: Basal ganglia, cerebellum — modulate movement (dopamine, GABA pathways)

Sensory pathways:

• Dorsal columns (DCML): Fine touch, proprioception, vibration → ipsilateral ascent → cross at medulla → thalamus → sensory cortex
• Spinothalamic: Pain, temperature, crude touch → cross at spinal level → contralateral ascent → thalamus → sensory cortex

Upper Motor Neurone Lesion

• Spastic paralysis, clasp-knife rigidity
• Hyperreflexia, clonus
• Upgoing plantar response (Babinski positive)
• No muscle wasting initially

Lower Motor Neurone Lesion

• Flaccid paralysis, hypotonia
• Hyporeflexia or areflexia
• Fasciculations, muscle wasting
• Downgoing or absent plantar response

Cerebellar Lesion

• DANISH: Dysdiadochokinesis, Ataxia, Nystagmus, Intention tremor, Slurred/scanning speech, Hypotonia

Spinal Cord Syndromes

• Brown-Séquard (hemisection): Ipsilateral UMN weakness + dorsal column loss; contralateral spinothalamic loss
• Anterior cord: Bilateral motor + spinothalamic loss; preserved dorsal columns
• Central cord: Upper limb weakness > lower limb (cape-like sensory loss)

Red Flags

• Acute onset bilateral weakness — consider cord compression (neurosurgical emergency)
• Bilateral LMN weakness ascending rapidly — Guillain-Barré syndrome (FVC monitoring)
• Thunderclap headache — subarachnoid haemorrhage until proven otherwise

Bedside

• Neurological examination: Power (MRC grading 0-5), tone, reflexes, sensation, coordination
• GCS: Level of consciousness assessment
• Fundoscopy: Papilloedema (raised ICP), optic atrophy

Bloods

• FBC, U&Es, glucose, calcium: Metabolic causes of neurological symptoms
• B12, folate, TFTs: Peripheral neuropathy workup
• CK: Raised in myopathy, NMS, rhabdomyolysis
• Autoantibodies: Anti-AChR (myasthenia), anti-ganglioside (GBS)

Imaging

• CT head: First-line in acute stroke, head injury, raised ICP
• MRI brain/spine: Demyelination, tumours, cord compression, structural lesions
• CT/MR angiography: Cerebrovascular disease assessment

Special Tests

• Nerve conduction studies (NCS): Demyelinating vs axonal neuropathy
• Electromyography (EMG): Myopathy vs neuropathy, denervation
• EEG: Epilepsy classification, encephalopathy
• Lumbar puncture: CSF analysis — infection, SAH, MS (oligoclonal bands), GBS (albumino-cytological dissociation)
• Evoked potentials: Visual (VEP), somatosensory (SSEP) — demyelination

Non-pharmacological

• Neurorehabilitation: Physiotherapy, occupational therapy, speech and language therapy
• Falls prevention strategies
• Driving advice (DVLA regulations for neurological conditions)

Pharmacological

• Stroke: Alteplase 0.9mg/kg IV (max 90mg) within 4.5 hours for ischaemic stroke; aspirin 300mg for 2 weeks then clopidogrel 75mg OD
• Epilepsy: Lamotrigine (focal/generalised), sodium valproate (generalised — avoid in women of childbearing age per MHRA), levetiracetam
• Parkinson's: Levodopa/carbidopa (co-careldopa), dopamine agonists (ropinirole, pramipexole)
• MS: Disease-modifying therapies (DMTs) — dimethyl fumarate, natalizumab, ocrelizumab
• Myasthenia gravis: Pyridostigmine 60mg QDS; immunosuppression (prednisolone, azathioprine)

Referral Criteria

• Acute focal neurology — emergency stroke pathway
• First seizure — neurology within 2 weeks
• Suspected cord compression — emergency neurosurgery
• Progressive neurological deficit — urgent neurology

• Ischaemic stroke: 30-day mortality ~10-15%; 50% have residual disability at 1 year
• GBS: 80% make full recovery; 5% mortality; 10% have significant residual disability
• MS: Median time to wheelchair use ~30 years from onset; DMTs significantly improve outcomes
• MND: Median survival 3-5 years from symptom onset; riluzole extends survival by ~3 months
• Myasthenia gravis: Good prognosis with treatment; myasthenic crisis mortality <5% with modern ICU care

Key Neurotransmitters

MRC Power Grading