Neurology: Localisation and Investigation

• Thinking like a neurologist: Where Is the Lesion, and What Is It? | Upper vs Lower Motor Neurone | Localising Weakness | Spinal Cord Syndromes | Roots, Dermatomes and Reflexes
• Head and eyes: Cranial Nerves | Visual Pathway and Field Defects | Pupils and Eye Movements
• Higher function and gait: Speech, Language and Lobe Signs | Cerebellum and Gait
• Investigations: Neuroimaging | Lumbar Puncture and CSF | EEG, Nerve Conduction and EMG | Blood Tests and Antibodies
• Revision: Localisation at a Glance | Spot the Lesion | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🧠 Neurological localisation is the foundation of neurology: a careful history and examination tell you where the problem is before any scan. This chapter covers how to localise a lesion and how to choose and interpret neurological tests. The other neurology chapters build on it.
Your four questions for every patient: Where is the lesion (brain, brainstem, cord, root, nerve, junction or muscle)? Is it one lesion or many? How fast did it come on (seconds, days, months)? Which single test is most likely to confirm it?

Where Is the Lesion, and What Is It?

Step 1 - Where? Use the examination to place the lesion:

• Brain (cortex, deep white matter, basal ganglia).
• Brainstem or cerebellum.
• Spinal cord.
• Nerve root or plexus.
• Peripheral nerve.
• Neuromuscular junction.
• Muscle.

Step 2 - What? The time course is the best clue:

• Seconds to minutes - vascular (stroke, TIA), seizure, migraine aura (spreads over minutes), syncope.
• Hours to days - inflammation (MS relapse), infection, Guillain–Barré syndrome, compression.
• Weeks to months - tumour, CIDP, subdural haematoma, B12 deficiency.
• Months to years - degeneration (Parkinson's, MND, dementia), hereditary conditions.
• Relapsing and remitting - MS, myasthenia, migraine, epilepsy, TIAs.
• Fluctuating through the day - myasthenia (worse later), Parkinson's medication timing.

Step 3 - Who? Age, risk factors, drugs, family history, travel and immune status shape the likely cause.

💡 Clinical Pearl: Try to explain everything with one lesion first. If you can't, think of multiple lesions (MS, vasculitis, metastases) or a diffuse process (neuropathy, myopathy, metabolic).

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Upper vs Lower Motor Neurone

• Acute UMN lesions (e.g. stroke, cord shock) can be flaccid with absent reflexes at first; spasticity develops over days to weeks.
• Mixed UMN and LMN signs suggest:
  • Motor neurone disease.
  • Cervical myelopathy with radiculopathy.
  • B12 deficiency (subacute combined degeneration).
  • Friedreich's ataxia; copper deficiency; HIV.
  • Absent ankle reflexes with extensor plantars is the classic pattern.

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Localising Weakness

• Cortex:
  • Weakness of the face and arm more than the leg (middle cerebral artery) or leg more than arm (anterior cerebral artery).
  • Cortical signs - aphasia, neglect, visual field loss, seizures.
• Internal capsule or pons: Pure motor weakness of the face, arm and leg equally (lacunar stroke), with no cortical signs.
• Brainstem:
  • "Crossed" signs - cranial nerve palsy on one side with weakness or sensory loss of the limbs on the other side.
  • Diplopia, vertigo, dysarthria, dysphagia, ataxia.
• Spinal cord:
  • Weakness and sensory loss below a level.
  • Bladder and bowel symptoms.
  • The face is spared.
• Nerve root (radiculopathy): Pain shooting down a limb; weakness, numbness and reflex loss in one root's territory.
• Plexus: Patchy weakness and sensory loss across several roots and nerves in one limb, often painful.
• Peripheral nerve:
  • A single nerve (mononeuropathy).
  • Several separate nerves (mononeuritis multiplex - think vasculitis, diabetes).
  • Symmetrical distal "glove and stocking" weakness and numbness (polyneuropathy).
• Neuromuscular junction:
  • Fatigable weakness that gets worse with use.
  • Ptosis and diplopia; bulbar and proximal weakness.
  • Normal sensation and reflexes.
• Muscle (myopathy):
  • Symmetrical proximal weakness (difficulty with stairs, rising from a chair, lifting arms).
  • Normal sensation; reflexes normal until late.
  • Raised CK in many.

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Spinal Cord Syndromes

• Complete cord lesion: Loss of all movement and sensation below the level; bladder and bowel loss.
• Brown-Séquard syndrome (one half of the cord - e.g. stab wound, MS):
  • Same side: Weakness (UMN) and loss of vibration and joint position (dorsal columns).
  • Opposite side: Loss of pain and temperature (spinothalamic tract, which crosses near the level it enters).
• Central cord syndrome (often a neck hyperextension injury in older people with cervical spondylosis; syringomyelia):
  • Arms weaker than legs.
  • "Cape-like" loss of pain and temperature across the shoulders (syrinx).
• Anterior cord syndrome (anterior spinal artery infarction, e.g. after aortic surgery):
  • Weakness and loss of pain and temperature below the level.
  • Vibration and joint position are preserved.
• Posterior column loss (B12 deficiency, tabes dorsalis, copper deficiency):
  • Loss of vibration and joint position.
  • Sensory ataxia - positive Romberg's test.
• Conus medullaris vs cauda equina:
  • Conus (end of the cord, about L1) - early bladder problems, saddle numbness, mixed UMN and LMN signs, less pain.
  • Cauda equina (roots below L1) - asymmetric LMN leg weakness, radicular pain, saddle anaesthesia, later bladder problems.
  • Both are emergencies - see the Neurological Emergencies chapter.

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Roots, Dermatomes and Reflexes

💡 Clinical Pearl: Foot drop is common. An L5 root lesion weakens hip abduction and foot inversion as well; a common peroneal nerve palsy (at the fibular head) spares them.

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Cranial Nerves

• I - Olfactory: Loss of smell - head injury, viral infections (including COVID-19), Parkinson's, frontal tumours (meningioma).
• II - Optic: Acuity, colour vision, fields, pupils, fundi (see below).
• III - Oculomotor: Eye "down and out", ptosis, and a dilated pupil if compressive.
• IV - Trochlear: Vertical diplopia, worse looking down (stairs, reading); head tilt away from the affected side.
• V - Trigeminal: Facial sensation (3 divisions), muscles of chewing, corneal reflex, jaw jerk (brisk in UMN lesions above the pons).
• VI - Abducens: Can't look outwards; horizontal diplopia, worse at distance. A "false localising sign" in raised intracranial pressure.
• VII - Facial:
  • LMN lesion (e.g. Bell's palsy) - the whole of one side of the face is weak, including the forehead.
  • UMN lesion (e.g. stroke) - the forehead is spared (it has supply from both sides of the brain).
• VIII - Vestibulocochlear:
  • Hearing - Rinne and Weber tests.
  • Balance.
  • Unilateral sensorineural hearing loss needs an MRI (vestibular schwannoma).
• IX and X - Glossopharyngeal and vagus: Palate and swallowing; the uvula deviates away from the weak side; hoarse voice.
• XI - Accessory: Shoulder shrug (trapezius) and head turning (sternocleidomastoid).
• XII - Hypoglossal: The tongue deviates towards the weak side; wasting and fasciculation in LMN lesions (MND).
• Bulbar vs pseudobulbar palsy:
  • Bulbar (LMN - MND, Guillain–Barré syndrome, myasthenia) - wasted, fasciculating tongue; nasal speech; absent jaw jerk.
  • Pseudobulbar (UMN - bilateral strokes, MND, MS) - stiff, small tongue; "hot potato" or spastic speech; brisk jaw jerk; emotional lability.
• Multiple cranial nerve palsies: Think of meningeal disease (cancer, TB, sarcoid), brainstem lesions, Guillain–Barré syndrome (Miller Fisher variant), cavernous sinus lesions, skull base tumours, myasthenia (mimic).

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Visual Pathway and Field Defects

• Optic nerve (in front of the chiasm):
  • Loss of vision in one eye.
  • Reduced colour vision (red desaturation).
  • Central scotoma.
  • Relative afferent pupillary defect (RAPD) - swinging torch test.
  • Causes: optic neuritis, ischaemic optic neuropathy (including GCA), compression, glaucoma.
• Optic chiasm: Bitemporal hemianopia.
  • Causes: pituitary tumour (from below - upper fields go first), craniopharyngioma (from above - lower fields first), meningioma.
• Optic tract: Homonymous hemianopia (incongruous).
• Temporal lobe (Meyer's loop): Upper homonymous quadrantanopia - "pie in the sky".
• Parietal lobe: Lower homonymous quadrantanopia - "pie on the floor".
• Occipital cortex: Congruous homonymous hemianopia, often with macular sparing (posterior cerebral artery stroke).
• Fundoscopy:
  • Papilloedema - swollen discs from raised intracranial pressure (vision is preserved early; enlarged blind spot). Causes include tumours, IIH, venous sinus thrombosis, malignant hypertension.
  • Optic atrophy - a pale disc after optic nerve damage (MS, compression, previous ischaemia, glaucoma, hereditary).
  • Retinal emboli (carotid disease) and hypertensive or diabetic changes.

⚠️ Safety Pearl: Sudden painless loss of vision in one eye in someone over 50 - check ESR and CRP and ask about headache and jaw claudication. GCA needs same-day steroids to protect the other eye.

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Pupils and Eye Movements

• Horner's syndrome - ptosis (mild), small pupil (miosis), and sometimes loss of sweating (anhidrosis) on one side. Causes by site:
  • Central (brainstem or cord) - lateral medullary stroke, syrinx, MS.
  • Preganglionic (chest and neck) - Pancoast tumour (lung apex), neck trauma or surgery, cervical rib.
  • Postganglionic - carotid artery dissection (with neck pain and headache), cavernous sinus lesions, cluster headache.
  • Painful Horner's is carotid dissection until proven otherwise - urgent CT or MR angiography.
• Third nerve palsy:
  • Pupil involved (dilated) - compression, e.g. a posterior communicating artery aneurysm (painful) or uncal herniation. This is an emergency - urgent CT angiography.
  • Pupil spared - usually microvascular (diabetes, hypertension); often recovers over 3 months.
• Internuclear ophthalmoplegia (INO):
  • Damage to the medial longitudinal fasciculus.
  • On looking to the side, the eye on the side of the lesion fails to move inwards, and the other eye shows nystagmus.
  • Young people: MS. Older people: stroke.
• Holmes–Adie pupil: A large pupil that reacts slowly to light - benign, usually in young women. With absent reflexes, it is Holmes–Adie syndrome.
• Argyll Robertson pupils: Small irregular pupils that react to accommodation but not light - neurosyphilis (or diabetes).
• Nystagmus:
  • Peripheral (vestibular) - horizontal and one-directional; suppressed by fixing the gaze.
  • Central - vertical, changes direction, or isn't suppressed by fixation (brainstem or cerebellar lesion).
  • Downbeat - craniocervical junction lesions (Chiari malformation), drugs (lithium, antiepileptics).
• Gaze palsies:
  • Eyes deviate towards a hemisphere lesion (stroke) and away from a pontine lesion.
  • Vertical gaze palsy (especially looking down) - progressive supranuclear palsy.
  • Upward gaze palsy - Parinaud's syndrome (pineal tumour).
• Fatigable ptosis and variable diplopia that don't fit a single nerve - myasthenia.

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Speech, Language and Lobe Signs

• Dysarthria - a problem with the mechanics of speech (slurred), but language is normal:
  • Cerebellar - slurred, staccato, "scanning".
  • Spastic - pseudobulbar.
  • Flaccid - bulbar, nasal.
  • Hypokinetic - quiet, monotonous (Parkinson's).
• Dysphasia (aphasia) - a language problem, usually from a left hemisphere lesion:
  • Expressive (Broca's) - frontal lobe. Halting, effortful speech; understanding is good; the patient is frustrated.
  • Receptive (Wernicke's) - temporal lobe. Fluent but meaningless speech with made-up words; poor understanding; the patient is often unaware.
  • Conduction - can't repeat phrases.
  • Global - all aspects affected (large MCA stroke).
• Dysphonia - a quiet or hoarse voice (vocal cords, recurrent laryngeal nerve, Parkinson's).
• Frontal lobe:
  • Personality change, disinhibition, apathy.
  • Poor planning.
  • Primitive reflexes (grasp).
  • Urinary incontinence.
  • Expressive dysphasia (left side).
• Temporal lobe:
  • Memory problems.
  • Receptive dysphasia (left side).
  • Upper quadrantanopia.
  • Seizures with déjà vu, smells and rising stomach sensations.
• Parietal lobe:
  • Sensory inattention.
  • Neglect of the left side (right parietal lesion).
  • Dressing and constructional apraxia.
  • Gerstmann syndrome (left side) - difficulty with writing, calculation, naming fingers, and left–right orientation.
  • Lower quadrantanopia.
• Occipital lobe: Visual field defects; visual hallucinations; cortical blindness (Anton syndrome - denies being blind).

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Cerebellum and Gait

Cerebellar signs ("DANISH"):

• Dysdiadochokinesia (clumsy rapid alternating movements).
• Ataxia (wide-based unsteady gait; truncal ataxia in midline lesions).
• Nystagmus.
• Intention tremor and past-pointing (finger–nose test).
• Slurred, staccato speech.
• Hypotonia.

Signs are on the same side as a cerebellar hemisphere lesion.

Causes of cerebellar syndrome:

• Alcohol.
• Stroke.
• MS.
• Tumours.
• Drugs (phenytoin, carbamazepine, lithium).
• Hypothyroidism.
• Paraneoplastic disease (anti-Yo - ovarian and breast cancer).
• Coeliac disease (gluten ataxia).
• B12 or vitamin E deficiency.
• Inherited ataxias (Friedreich's, spinocerebellar ataxias).
• Multiple system atrophy.

Gaits:

• Hemiplegic - stiff leg swung outwards (circumduction), arm flexed (stroke).
• Parkinsonian - small shuffling steps, stooped posture, reduced arm swing, turning "en bloc", freezing.
• Cerebellar ataxic - wide-based, staggering; worse with heel-to-toe walking.
• Sensory ataxic - stamping, watches the feet; Romberg's test positive (much worse with the eyes closed). Neuropathy, dorsal column disease.
• Waddling - proximal muscle weakness (myopathy, osteomalacia).
• High-stepping - foot drop (common peroneal palsy, L5 radiculopathy, neuropathy).
• Spastic (scissoring) - both legs stiff (cord disease, cerebral palsy).
• "Magnetic" or apraxic - feet seem stuck to the floor (normal pressure hydrocephalus, frontal and small vessel disease).
• Antalgic - painful joint.
• Functional - inconsistent, variable, often with dragging or excessive slowness; improves with distraction.

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Neuroimaging

• CT head:
  • Fast and available - first-line for acute stroke, head injury, sudden severe headache, reduced consciousness.
  • Excellent for blood and bone.
  • Poor for the posterior fossa, early infarcts, MS and small lesions.
• CT angiography / venography:
  • Large vessel occlusion (thrombectomy).
  • Aneurysms.
  • Dissection.
  • Venous sinus thrombosis.
• MRI brain:
  • The best test for most non-acute neurology - MS, tumours, posterior fossa, epilepsy, encephalitis.
  • Diffusion-weighted imaging (DWI) shows acute infarcts within minutes.
  • Gadolinium contrast shows active inflammation and tumours.
  • Specific sequences: SWI for microbleeds; FLAIR for white matter lesions.
  • Contraindications: Some pacemakers and implants (many are now MRI-conditional), metal fragments in the eye, claustrophobia.
• MRI spine: Cord compression, myelopathy, radiculopathy, MS lesions. Whole spine for suspected metastatic compression.
• Functional imaging:
  • DaTscan (dopamine transporter SPECT) - reduced in Parkinson's, PSP, MSA and dementia with Lewy bodies; normal in essential tremor, drug-induced parkinsonism and Alzheimer's disease.
  • FDG-PET - patterns in dementia (frontotemporal vs Alzheimer's); epilepsy surgery; cancer.
  • Amyloid PET - research and specialist use.
• Incidental findings (white matter spots, small aneurysms, arachnoid cysts) are common. Interpret them in context and avoid over-investigation.

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Lumbar Puncture and CSF

Before a lumbar puncture:

• CT first if there are signs of raised intracranial pressure, reduced consciousness (GCS under 13), focal signs, papilloedema, new seizures, or immunosuppression.
• Check platelets and clotting; manage anticoagulants and antiplatelets (local guidance).
• Avoid if there is skin infection at the site.
• Measure opening pressure with the patient lying on their side (normal about 10–25 cm H₂O).
• Send paired serum glucose.

Interpreting CSF:

Post-LP headache:

• Worse on sitting or standing, eased by lying down.
• Reduced by using atraumatic (pencil-point) needles.
• Treatment: simple analgesia, fluids and caffeine; an epidural blood patch if it persists.

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EEG, Nerve Conduction and EMG

• EEG (electroencephalogram):
  • Supports - but cannot exclude - epilepsy. A routine EEG is normal in about half of people with epilepsy, and minor non-specific changes are common in people without it.
  • Helps classify epilepsy (e.g. 3 Hz spike-and-wave in absence seizures; hypsarrhythmia in infantile spasms).
  • Sleep-deprived and video-EEG telemetry recordings improve diagnosis (including non-epileptic attacks).
  • Also used in non-convulsive status, encephalitis (periodic discharges in HSV), CJD (periodic sharp waves) and metabolic encephalopathy (triphasic waves).
  • Don't request an EEG to "rule out" epilepsy after a simple faint.
• Nerve conduction studies:
  • Axonal neuropathy - reduced amplitudes, near-normal speed (diabetes, alcohol, drugs, vasculitis).
  • Demyelinating neuropathy - slow conduction, conduction block, prolonged latencies (GBS, CIDP, hereditary CMT1).
  • Entrapment - focal slowing (carpal tunnel, ulnar neuropathy at the elbow).
• EMG (electromyography, a needle in the muscle):
  • Neurogenic - large long units, fibrillations, fasciculations (MND, radiculopathy).
  • Myopathic - small short units (myositis, dystrophies).
  • Myotonic discharges - "dive-bomber" sound (myotonic dystrophy).
• Neuromuscular junction tests:
  • Repetitive nerve stimulation - decrement in myasthenia; increment after exercise in Lambert–Eaton syndrome.
  • Single-fibre EMG - the most sensitive test for myasthenia ("jitter").
• Evoked potentials: Visual evoked potentials show delayed conduction after optic neuritis (MS). Somatosensory potentials are used for cord monitoring during surgery.

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Blood Tests and Antibodies

Common screening bloods:

• FBC, U&E, LFTs, glucose and HbA1c, calcium, TFTs.
• B12 and folate; ESR and CRP.
• CK (raised in myopathy, rhabdomyolysis, and after falls, seizures or exercise).
• Serum protein electrophoresis (paraproteins in neuropathy).
• HIV and syphilis serology.
• Copper, vitamin E and thiamine in selected cases.

Important antibodies:

Genetic tests: Huntington's (CAG repeat), myotonic dystrophy (DMPK), hereditary neuropathies (PMP22), SOD1 and C9orf72 (MND), spinocerebellar ataxias. Genetic counselling must come first, especially for predictive testing.

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Localisation at a Glance

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Spot the Lesion

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Exam-style Scenarios

1. A 70-year-old has progressive clumsy hands and stiff legs. There is wasting of the hand muscles, brisk leg reflexes and extensor plantars. Sensation is reduced in the hands.
Answer: Degenerative cervical myelopathy (LMN signs at the level, UMN signs below).

• Urgent MRI of the cervical spine.
• Spinal surgical referral.
• Consider MND if there are no sensory signs.

2. A 32-year-old woman has 4 days of pain on moving her right eye and blurred vision. She has reduced colour vision and a right RAPD.
Answer: Right optic neuritis.

• MRI brain and orbits (for MS lesions).
• Consider AQP4 and MOG antibodies if atypical (severe, bilateral, no pain).
• Usually recovers; steroids speed recovery but don't change the final outcome.

3. A 65-year-old has a 3-day history of left ptosis and diplopia. The pupil is normal. He has diabetes.
Answer: Pupil-sparing third nerve palsy - likely microvascular.

• Check glucose, BP and ESR (GCA).
• Many still image to exclude compression, especially if partial or with pain.
• Expect recovery within 3 months.

4. A man with severe headache and fever has GCS 15 and no focal signs. LP shows 800 white cells (90% neutrophils), protein 2.1 g/L, and CSF glucose 1.0 mmol/L (blood 6.0).
Answer: Bacterial meningitis.

• Antibiotics and dexamethasone immediately (ideally before LP if delayed).
• See the Neurological Emergencies chapter for doses.

5. A 25-year-old has 2 weeks of ascending weakness. Reflexes are absent. CSF protein is 1.5 g/L with 2 cells/mm³.
Answer: Guillain–Barré syndrome (albuminocytological dissociation).

• Nerve conduction studies (demyelinating).
• Monitor FVC; IVIg.

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Key Points

• Work out where the lesion is from the examination, and what it is from the time course.
• UMN: increased tone, brisk reflexes, extensor plantars. LMN: wasting, fasciculations, reduced reflexes.
• Mixed UMN and LMN signs: MND, cervical myelopathy, B12 deficiency.
• Crossed signs mean the brainstem; a sensory level means the cord.
• Fatigable weakness with normal sensation and reflexes means the neuromuscular junction.
• UMN facial weakness spares the forehead; LMN weakness affects the whole side.
• Bitemporal hemianopia: chiasm. Upper quadrantanopia: temporal. Lower quadrantanopia: parietal.
• A third nerve palsy with a dilated pupil is an aneurysm until proven otherwise.
• Painful Horner's syndrome - think carotid dissection.
• INO in a young adult suggests MS.
• CT first for acute problems; MRI for most others.
• CT before LP if GCS is reduced, there are focal signs, papilloedema, seizures or immunosuppression.
• CSF: low glucose with neutrophils means bacterial; lymphocytes with normal glucose means viral; high protein with no cells means GBS.
• A normal EEG doesn't exclude epilepsy.