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Neurological differential diagnosis

Unilateral UMN (pyramidal weakness)

Work down (brain to cord):

  • Intracranial – stroke, SOL → hemisensory loss
  • Brainstem – stroke, SOL → may be crossed signs
  • Spinal cord – MS, infarct/haemorrhage, SOL, disc prolapse, trauma, syringomyelia, congenital → sensory-level/segmental sensory loss

Bilateral UMN (pyramidal weakness)


  • M
  • Motor neurone disease → normal sensation
  • Myelopathy – cord compression (e.g. due to cervical myelopathy, SOL, disc prolapse, paraspinal infection), trauma, transverse myelitis,  syringomyelia, congenital → sensory-level/segmental sensory loss
  • Others – brainstem stroke, hereditary spastic paraplegia, cerebral palsy, HTLV-1, syphilis

Causes of unilateral LMN lesions – work down (nerve root to peripheral nerve)

Bilateral LMN (distal weakness)

Abnormal sensation distally (i.e. sensorimotor polyneuropathy)


  • Alcohol
  • B12/thiamine deficiency
  • Charcot-Marie-Tooth, Carcinomas (paraneoplastic)
  • Diabetes, Drugs (e.g. TB drugs, metronidazole/nitrofurantoin, vincristine/cisplatin, amiodarone)
  • Every vasculitis (e.g. SLE, RA, polyarteritis nodosa) and some infections (e.g. herpes zoster, HIV, leprosy, syphilis)

Normal sensation (i.e. distal motor neuropathy)

  • Chronic inflammatory demyelinating polyneuropathy
  • Myotonic dystrophy
  • Inclusion body myositis (proximal in legs but distal in arms)
  • Progressive muscular atrophy
  • Lead poisoning
  • Porphyria

Acute flaccid paralysis

  • Guillain-Barré syndrome
  • Some rare infections (e.g. rabies, polio, West Nile)
  • Cauda equina syndrome
  • Spinal cord shock

Proximal weakness → Normal sensation  


  • Dystrophies – Becker’s/Duchenne, limb girdle, facioscapulohumeral (shoulder, face and truncal weakness) 
  • Endocrinological – Cushing’s syndrome, hyper/hypothyroidism, diabetic amyotrophy (lower limbs)
  • Neuromuscular – myasthenia gravis (fatigable), Lambert–Eaton myasthenic syndrome
  • Inflammatory – dermato-/polymyositis, inclusion body myositis (proximal in legs but distal in arms), viral myositis
  • Metabolic/congenital/mitochondrial myopathies

Mononeuritis multiplex

  • Vasculitis – granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, polyarteritis nodosa, microscopic polyangiitis
  • Autoimmune – RA, SLE, cryoglobulinaemia, Sjögren’s syndrome, paraneoplastic
  • Infectious – Lyme disease, HIV, leprosy
  • Others – diabetes mellitus, amyloidosis, sarcoidosis


  • Motor neurone disease (no sensory deficit) 
  • Dual pathology (e.g. cervical myelopathy + polyneuropathy)
  • Myeloradiculopathy
  • Subacute combined degeneration of the cord (symmetrical UMN signs with absent reflexes, impaired posterior column function, peripheral sensory neuropathy)

NB: spinal cord lesions can cause LMN signs at the site of the lesion and UMN signs below the lesion

Cerebellar disease


  • MS
  • Alcohol
  • Vascular – thromboembolic, haemorrhagic
  • Inherited – Friedreich’s ataxia, spinocerebellar ataxia, ataxia telangiectasia           
  • SOL

Cranial nerve palsies

Optic atrophyPost-optic neuritis/MS, arteritic ischaemia (giant cell arteritis), microvascular ischaemia, compression (SOL, raised intracranial pressure), glaucoma, toxins (methanol, ethambutol), neuromyelitis optica
Third nerve palsyMedical (classically pupil-sparing), M’s: Microvascular ischaemia (diabetes), Migraine, MS/autoimmune disorders
Surgical (classically painful), C’s: posterior Communicating artery aneurysm (classic cause), Cavernous sinus lesion, Cancer (SOL)
Sixth nerve palsy Raised intracranial pressure, microvascular ischaemia, SOL, trauma
Unilateral facial nerve palsyBell’s palsy, Ramsay Hunt syndrome, SOL (e.g. acoustic neuroma, facial nerve tumour, meningioma), Lyme disease, nerve infiltration (TB, sarcoidosis, lymphoma), parotid tumour/surgery
Bilateral facial nerve palsyLyme disease, sarcoidosis, Guillain-Barré syndrome, amyloidosis
Other differentials for bilateral facial weakness: muscular dystrophies, myasthenia gravis
Bulbar palsy(LMN)Motor neurone disease, brainstem infarct/SOL, Guillain-Barré syndrome, polio, syringobulbia, neurosyphilis 
Pseudobulbar palsy(UMN)Motor neurone disease, high brainstem infarct/SOL, MS, bilateral internal capsule infarcts, traumatic brain injury, progressive supranuclear palsy

Multiple cranial nerve palsies

  • Any = mononeuritis multiplex, leptomeningeal process (e.g. tuberculosis, meningitis), SOLs, trauma, sarcoidosis, Lyme disease, neurosyphilis, vasculitis, botulism
  • CN 3-6 = cavernous sinus lesion, Miller-Fisher syndrome
  • CN 5-8 + cerebellar = cerebellopontine angle lesion
  • CN 9-10
    • + 11 = jugular foramen syndrome
    • + 12 = pseudobulbar/bulbar palsy
    • + Horner’s syndrome + cerebellar + sensory disturbance (ipsilateral face, contralateral body) = lateral medullary (Wallenberg) syndrome

Complex ophthalmoplegia

Work posteriorly (soft tissue to brainstem):

  • Soft tissue – Graves’ disease
  • Muscle – mitochondrial myopathy
  • Neuromuscular junction – myasthenia gravis (test fatigability)
  • Multiple CN’s – cavernous sinus lesion, mononeuritis multiplex, MS
  • Brainstem – stroke, SOL, trauma 


  • Unilateral
    • Third nerve palsy (pupil ‘down and out’, dilated) – complete ptosis
    • Horner’s syndrome (pupil constricted) – partial ptosis
    • Idiopathic
  • Bilateral
    • Myasthenia gravis
    • Myotonic dystrophy (frontal balding, facial muscle wasting)
    • Congenital
    • Neurosyphilis (Argyll Robertson pupils)

Horner’s syndrome

  • 1st order (central) – MS, spondylosis, SOL, syringomyelia, stroke/lateral medullary syndrome
  • 2nd order (pre-ganglionic) – Pancoast tumour, cervical rib, thyroid carcinoma/goitre
  • 3rd order (post-ganglionic) –  carotid artery dissection, radical neck dissection

Visual field defects


  • Chorea – stroke, Huntington’s disease, Sydenham’s chorea, drugs (e.g. antipsychotics, levodopa), HIV
  • Hemiballismus – subthalamic stroke (most), SOL, traumatic brain injury, HIV
  • Athetosis – asphyxia, neonatal jaundice, thalamic stroke
  • Dystonia – primary dystonia, brain trauma, drugs, Wilson’s disease, PD, Huntington’s disease, stroke, SOL, encephalitis, asphyxia  
  • Myoclonus – epilepsy, essential myoclonus, metabolic, psychological, toxins/drugs, SOL, MS, PD, Creutzfeldt-Jakob disease

NB: Wilson’s disease can cause any.


  • Parkinson’s disease
  • Vascular parkinsonism
  • Parkinson-plus syndromes: multi-system atrophy, progressive supranuclear palsy, corticobulbar degeneration, Lewy body dementia
  • Other causes: antidopaminergic drugs, Wilson’s disease, communicating hydrocephalus, supratentorial tumours

Now try some viva questions

What is pyramidal weakness? Which type of lesions causes this pattern?

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Which conditions can present with both UMN and LMN signs?

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Please can you list some causes of unilateral and bilateral facial nerve palsy?

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What are the different causes of bitemporal hemianopia?

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Now for some stations!

  1. Charcot-Marie-Tooth
  2. Motor neurone disease
  3. Bells palsy
  4. Horner’s syndrome
  5. There’s lots more!

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