Acute peripheral neuropathy

Differential of acute weakness

• Cerebral cortex – Vascular, metabolic/ischaemic encephalopathy
• Brainstem – Lower pontine haemorrhage (Locked-in)
• Spinal cord – Transverse myelitis, tumor, haemorrhage, abscess
• Peripheral nerve – Critical illness polyneuropathy, phrenic nerve injury from surgery, GBS, Arsenic, thallium, cyanide
• NMJ – Delayed reversal of NM blockade, myaesthenia gravis, Lambert-Eaton syndrome, botulism, pesticide poisoning
• Skeletal muscle – Acute necrotising myopathy, steroid myopathy, severe hypoK/hypoPO4/hypoMg, acute alcoholic myopathy, polymyositis, dermatomyositis, toxic myopathy (Colchicine, cocaine, amiodarone)

Introduction

• Peripheral nerves carry sensory, motor and autonomic signals so can have deficits in any combination of these
• Exclude central processes (e.g. stroke, spinal cord lesion) before considering an acute peripheral lesion

Central vs. peripheral lesions

• Peripheral
  • More likely to be unilateral and involve multiple sensory modalities and motor symptoms
  • Weakness with associated pain
  • Hyporeflexic, hypotonic
  • All sensory modalities involved
  • Symmetric proximal weakness
• Central
  • Hyperreflexia, hypertonia, Babinski reflexes and spasticity/clonus invariably develop in time
  • Aphasia, apraxia and vision loss are all central signs
  • Asymmetric weakness of ipsilateral upper or lower extremity suggests central cause

Localising peripheral nervous lesions

• History
  • Symmetry
  • Proximal vs. distal
  • Sensory modalities affected
  • Motor symptoms
  • Autonomic involvement
  • Recent viral illness, DM, trauma
• Examination
  • Consider deficits in terms of neuronal pathways including specific nerves and dermatomes/myotomes

Localising peripheral nervous lesions

• Investigations
  • Electromyography
    • To differentiate primary muscle or neuromuscular junction issues vs. peripheral nerve disorders
  • Nerve conduction studies
    • Differentiates axonal loss vs. demyelination
  • LP is frequently required to confirm acute or subacute inflammatory/infectious processes

Localising peripheral nervous lesions

• Treatment
  • Monitor if at risk of respiratory failure, aspiration or cardiac arrhythmias
  • Measure baseline FVC and consider ICU admission if concern exists
  • Admit if potential respiratory or autonomic compromise or with severe or rapidly progressive weakness
  • If admission not required, f/u must be organised within 7-10 days

Acute peripheral neuropathies

• GBS
• Bell’s palsy
• Ramsay Hunt syndrome
• Acute neuropathies of Lyme disease

Guillain-Barre syndrome

• Mostly AIDP (Acute inflammatory demyelinating polyneuropathy) – 85% of cases
• Acute polyneuropathy characterised by immune-mediated peripheral nerve myelin sheath OR axon destruction
• Symptoms peak at 2-4 weeks and recovery can take weeks to a year
• Clinical features
  • Classically preceding viral illness then ascending symmetric flaccid paralysis and hypo/areflexia
  • 50% experience distal paraesthesia, 25% motor weakness and 25% both
  • Autonomic dysfunction commonly seen with orthostatic or persistant hypotension, paroxysmal hypertension, bradycardia or malignant tachycardia. Paralytic ileus, sweating, urinary retention are common
  • Sensory involvement can occur and can be painful

GBS

• Variants
  • Miller-Fisher variant
    • Seen following C. jejuni infectious diarrhoea with triad of ophthalmoplagia, ataxia and decreased or absent reflexes
    • Weakness is less severe and disease course is milder
    • Strongly correlated to GQ1b antibodies
  • Acute motor axonal neuropathy (AMAN)
    • Pure motor variant also seen with C. jejuni in Japan and China
  • Acute motor and sensory axonal neuropathy (AMSAN)
    • Begins abruptly, progresses rapidly and has prolonged course and poor prognosis
    • Strong correlation to C. jejuni
  • Bickerstaff encephalitis
    • Brainstem encephalitis characterized by encephalopathy and hyperreflexia with features of Miller-Fisher
  • Pharyngeal-cervical-brachial weakness
    • Acute weakness of oropharyngeal, neck and shoulder muscles with swallowing dysfunction
    • Leg strength and reflexes usually preserved
  • Paraparetic
    • Relatively mild confined to lower limbs with upper limb reduced reflexes only
  • Acute pandysautonomia
    • May respond to IVIG very well
    • Diarrhoea, vomiting, abdominal pain, ileus, orthostatic hypotension, urinary retention, pupillary abnormalities, invariant heart rate, reduced sweating, salivation and lacrimation
    • Reflexes absent or diminished and may have sensory impairment
  • Pure sensory
    • Significant sensory ataxia with absent reflexes and minor motor involvement
  • Facial diplegia and distal limb paraethesia
    • Variant of AIDP
  • Acute bulbar palsy
    • Overlaps with Miller-Fisher and pharyngeal-cervical-brachial variants
  • Sixth nerve palsy and distal paraesthesia

GBS

• Associated viruses
  • CMV (10-22% of cases)
  • Influenza A, Para-influenza, VZV, EBV, Chickenpox, Mumps, HIV, measles, Mycoplasma
• Associated bacteria
  • Campylobacter jejuni (most common preceding infection) – 26-41% of cases
• 43% of cases following recent URTI and 21% recent GI illness

GBS

• Diagnosis
  • Mostly clinical but LP helps to confirm
  • CSF
    • Protein >45mg/dL, WCC <10cells/mm3; predominant mononuclear cells
    • If WCC >100, consider HIV, Lyme disease, syphilis, sarcoidosis, TB or bacterial meningitis, leukaemic infiltrate or CNS vasculitis
    • Nerve conduction may confirm demyelination or axonal degeneration
    • MRI shows enhancement of affected nerves
    • Level of protein does not correlate with clinical findings

GBS

• Treatment
  • Assess respiratory function
  • Avoid succinylcholine due to risk of hyperkalaemia
  • IVIG 0.4g/kg IV daily for 5 days
  • IVIG and plasmapheresis shorten time to recovery equally and no better if used together
  • IVIG carries risk of thromboembolism and aseptic meningitis
  • Plasmapheresis risks haemodynamic instability but lower rate of relapse
  • Corticosteroids are of no benefit
  • Plasma exchange most effective within 7 days of symptoms (3-5 exchanges of 1-2 plasma volumes over 1-2 weeks)
  • 10% of patients suffer relapse after treatment but most will respond to second course of treatment

GBS

• Diagnostic criteria
  • Required – Progressive weakness of more than one limb + Areflexia
  • Suggestive
    • Progressive over days to weeks
    • Recovery beginning at 2-4 weeks after cessation of progression
    • Relative symmetry
    • Mild sensory signs and symptoms
    • Cranial nerve involvement
    • Autonomic dysfunction
    • Absence of fever at onset
    • Cytoalbuminologic dissociation of CSF (high protein; low WCC)
    • Typical findings on electromyogram and nerve conduction studies

GBS

• Indications for intubation
  • Vital capacity <15mL/kg (normal 60-70mL/kg) or <30% predicted or rising PaCO2
  • Declining one breath count (1 to 25)
  • PaO2 <70mmHg on room air
  • Bulbar dysfunction (difficulty breathing, swallowing or speech)
  • Aspiration
  • Tachypnoea/dyspnoea

GBS

• Indications for ICU admission
  • 4 or more of: Inability to stand, lift head, lift elbows, insufficient cough, time from onset to hospital admission <7 days or raised LFT’s
  • Autonomic dysfunction
  • Bulbar dysfunction
  • Initial Vt <20mL/kg
  • Initial negative inspiratory pressure <-30cmH20
  • Decrease of >30% vital capacity or negative inspiratory pressure
  • Inability to ambulate
  • Treatment with plasmapheresis

GBS

• Autoantibodies
  • Anti-GM1 gangliosides common following Campylobacter
  • Anti-GD1a gangliosides (Acute motor axonal neuropathy – AMAN)
  • Anti-GD1b gangliosides (Acute motor sensory axonal neuropathy – AMSAN)

GBS

• Differential
  • Chronic inflammatory demyelinating polyradiculopathy (CIDP)
    • No preceding viral infection, more insidious onset, slowly worsening course over > 8 weeks
    • Onset over months of symmetrical sensorimotor proximal and distal motor involvement > sensory involvement
    • Non-length-dependent due to nerve root involvement
    • Cranial nerve/bulbar involvement in 10-20%
    • Also have reduced/absent reflexes
    • Sensory loss is predominantly vibrio/proprioception due to large myelinated fibre involvement and is predominantly seen in lower limbs > upper limbs
    • Painful dysaesthesias can occur as can back pain
    • Lumbar spine stenosis and cauda equina syndroe can occur in the setting of marked nerve root hypertrophy and may require surgical decompression
    • Autonomic involvement is generally mild
    • A relapsing/remitting course is seen in 1/3 of patients (usually younger)
    • Steroids and plasma exchange may be effective
  • Subacute inflammatory polyradiculopathy (SIDP)
  • Recurrent GBS

GBS

• Prognosis
  • Nadir within 2-4 weeks with gradual resolution over weeks/months
  • Of those who survive acute illness, 70% fully recovered within 1 year and 20% only minor limitations
  • Can continue to improve for up to 2 years
  • Overall mortality around 5-8%
• Poor prognostic factors
  • Age >60, rapid progression to quadriparesis within 7 days, need for mechanical ventilation (except in children), preceding diarrhoeal illness

Bell’s palsy

• Most common cause of unilateral facial paralysis
• 25/100 000 cases annually
• HSV DNA and antigens found around facial nerve in cases but antivirals are not effective
• Clinical features
  • Preceded by pain behind or around the ear
  • Acute onset facial paralysis peaking in 2-3 days
  • Facial numbness or hyperaesthesia can accompany paralysis
  • Subtle dysfunction of V, VIII, IX, and X may be seen
  • Decreased taste or hyperacusis also seen due to paralysis of stapedius
  • Forehead involvement defines lower motor neuron

Bell’s palsy

• Diagnosis
  • Need to exclude ear infection and stroke
  • Ear examination for otitis media is crucial and palpate the mastoid for tenderness
  • MCA stroke will be forehead sparing
  • Brainstem stroke CAN MIMIC Bell’s if affects area where the facial nerve wraps around the CN VI nucleus as get peripheral facial nerve palsy with forehead involvement and ipsilateral gaze palsy due to CN VI involvement
    • Therefore, test EOM in all Bell’s patients and if cannot abduct eye then = stroke
  • If high suspicion, do not need brain imaging

Bell’s palsy

• Treatment
  • Corticosteroids increases frequency of complete recovery
  • Prednisone 1mg/kg per day for 7 days
  • No benefit from antivirals
  • Greatest risk is corneal abrasions and keratitis
  • Patch or tape the affected eye at night if incomplete closure is evident and provide instructions for eye clinic follow-up to determine when patch can be removed
    • Ensure no lid movement under eye patch
  • Provide ocular lubricants with tear drops for daytime and viscous ointment for sleep
  • Most patients begin to recover within 3 weeks but 15% will have permanent paralysis
  • Ensure follow-up within 7 days with GP or ENT

Ramsay hunt syndrome

• Herpes zoster infection of geniculate ganglion
• Unilateral facial nerve palsy, severe pain and vesicular eruption in external ear canal or on face
• Indistinguishable from Bell’s if no vesicles yet
• CN VIII may also be involved with tinnitus, vertigo, nausea and hearing loss
• If active herpes zoster is suspected, treatment with steroids 1mg/kg for 7 days + acyclovir 200mg five times a day for 7 days is warranted

Focal mononeuropathies

• Usually focal nerve compression however some systemic processes can lead to mononeuropathy
• Diabetes is the common systemic cause of mononeuropathy
• DDx
  • Carpal tunnel
  • Guyon’s canal syndrome
  • Deep peroneal nerve entrapment
  • Meralgia paraesthetica

Carpal tunnel syndrome

• Most common mononeuropathy
• Compression of median nerve at carpal tunnel
• Mostly due to repetive use +- diabetes, pregnancy, amyloidosis, obesity, renal failure, RA, hypothyroidism, trauma or oedema
• Presentation
  • Pain, paraesthesia and numbness in median nerve distribution
  • Worse with extension and flexion of wrist and at night
  • May have weakness and wasting of thenar eminence
• Diagnosis
  • Tinel’s sign and Phalen’s sign
  • Electrodiagnostic testing confirms slowing of nerve conduction across carpal tunnel and can confirm diagnosis or aid decision for operative release
• Treatment
  • Wrist splint in neutral position, NSAID’s and referral to hand surgeon if refractory for steroid injection +- surgery

Deep peroneal nerve entrapment

• Can be entrapped at fibular head, anterior to ankle joint under extensor retinaculum (anterior tarsal tunnel syndrome) or distal to this point
• Develop foot drop and 1^st web space numbness
• Splint or brace ankle at 90 degrees and f/u with neurology for nerve conduction studies to rule out lumbar root or motor neuron disease

Meralgia paraesthetica

• Entrapment of lateral femoral cutaneous nerve in inguinal canal
• Causes may be pelvic (pregnancy, mass, aneurysm), extra-pelvic (trauma, tight belt, obesity) or systemic (diabetes)
• Tinel’s sign with percussion over ASIS
• Pelvic compression test
  • Turn patient on side, compress pelvis and if symptoms are relieved after 30 seconds of lateral compression confirms diagnosis
• Rx – NSAID’s, weight loss, relief from tight garments and physios
• Local injection of lignocaine + steroids provides relief
• Surgical decompression if refractory

Ulnar nerve syndrome

• Most vulnerable at cubital tunnel, then Guyon’s canal
• Guyon’s canal syndrome aka ‘handlebar palsy’ as occurs in cyclists with prolonged compression of wrist against handlebars
  • May get sensory sparing as fibres split before canal
• Presents with tingling in 5^th and lateral 4^th digit with weakness of intrinsic hand muscles
• Diagnosis
  • Tapping on cubital tunnel
  • Positive elbow flexion sign – Symptoms within 3 min of elbow held in flexion and wrist in extension
  • Froment’s sign – Inability of thumb to oppose or put pressure on index finger. If can pull paper out or thumb flexes at IP joint = positive sign
• DDx of cubital tunnel syndrome include C8 entrapment (neck pain and worsening symptoms with neck flexion) and thoracic outlet syndrome (worse with should abduction)
• Treatment
  • Eliminate habits that worsen symptoms, NSAID’s may be of benefit and refer to orthopaedist

Plexopathies

• Brachial plexopathy
• Lumbosacral plexopathy
• Cervical plexopathy
• Share common causes including trauma, surgery, neoplasm and radiation therapy

Brachial plexopathy

• C5-T1 nerve roots
• Generally manifest as weakness first followed by pain and paraesthesias
• Upper trunk is most common presenting with proximal arm and shoulder muscles
• ‘Burner’ is burning pain in one upper extremity +- numbness, paraesthesia or weakness after trauma to the neck and shoulder
  • Can be a brachial plexopathy due to traction to shoulder or injury to cervical nerve roots due to neck flexion-hyperextension
• Rx
  • Must carefully assess neck, shoulder and arm with careful neuro exam
  • C-spine imaging indicated if tender midline, limited neck ROM or bilateral symptoms (not consistent with burner)
  • May have unilateral transient weakness in C5/6 myotome
  • Tingling usually not limited to single dermatomes
  • EMG indicated if symptoms persist beyond 3 weeks

Lumbosacral plexopathy

• L1-S4 nerve roots
• Less often traumatic
• Usually radiation, diabetic amyotrophy, aortic aneurysm, retroperitoneal haemorrhage or AV malformation compression
• DDx includes cauda equina and conus medullaris syndrome
• Lumbar lesions cause weakness in hip adduction and flexion and knee extension, decreased sensation at top and inner thigh and decreased patellar reflexes
• Sacral lesions result in weak thigh abduction, hip extension and knee flexion with decreased sensation in sciatic distribution
• Ix
  • Plain X-ray of lumbosacral spine can help rule out compression fracture or neoplastic disease
  • MRI if cord injury or compression suspected
  • CT to exclude aortic aneurysm, psoas mass or retroperitoneal haemorrhage
• Rx directed at underlying cause

Cervical plexopathy

• C1-4 nerve roots
• Lease common plexopathy
• Trauma, neoplasm or post-operatively due to positioning
• Pain may be the only symptom
• CT/MRI if neoplastic process considered
• Usually managed conservatively

Neuromuscular junction disorders

• Botulism
• Tick paralysis
• Inflammatory myopathies

Botulism

• Toxin-mediated weakness leading to respiratory failure
• 76% infantile botulism (honey), 15% wound botulism and 8% food-borne
• Infantile affects 1 week to 11 month year olds
• Toxins irreversibly bind presynaptic membrane of nerves inhibiting Ach release
• Most cases are isolated events associated with improperly preserved canned foods
• Infantile botulism occurs due to ingestion of spores that germinate in higher pH of infantile GIT tract
• Wound botulism mostly in IVDU

Botulism

• Presentation
  • Onset 6-48 hours after poisoning
  • Nausea, vomiting, abdo cramps, diarrhoea/constipation similar to acute gastro
  • Descending symmetric paralysis
  • No sensory issues or pain
  • Presents with diplopia, dysarthria and dysphagia
  • Toxin-mediated reduced cholinergic output leads to anticholinergic constipation, urinary retention, dry skin, hyperthermia
  • Pupils dilated and non-reactive (important as differentiates from myaesthenia gravis in which pupils not affected)
  • Infantile botulism presents as weak cry, poor feeding, constipation and lethargy (floppy)

Botulism

• Ix
  • Confirm toxin in serum and stool
• Treatment
  • Supportive
  • Botulinum equine antitoxin reduces ventilator days
  • Human botulism immunoglobulin also reduces ventilator days, length of ICU and length of hospital stay

Tick paralysis

• Mostly in children due to tick saliva
• Presents 4-7 days after tick attachment, get non-specific flu-like stmptoms with ataxia and ascending weakness and paralysis without sensory involvement (like GBS)
• May involve bulbar nerves and diaphragm
• Diagnosis
  • Must find tick (complete body search is crucial)
  • Scalp most common
  • If no tick is found, acute ataxia and ascending weakness without sensory involvement differential include GBS, botulism (usually descending), spinal cord tumor or polio
  • Tick paralysis and GBS are indistinguishable clinically and on nerve conduction studies
• Treatment
  • Complete removal of attached tick and supportive care with recovery within hours to days if tick removed

Inflammatory myopathies

• Polymyositis or dermatomyositis present with similar symptoms to peripheral neuropathies
• Symmetric weakness progressing over weeks to months
• Presentation
  • Progressive weakness of proximal limbs, trunk and neck
  • Sensation and reflexes are normal
  • Ocular muscles usually spared
  • Can involve cardiac musculature
  • Dermatomyositis has diffuse violaceous rash over face and trunk
• Diagnosis is clinical + raised ESR, CK and leukocytosis
• Rx – Systemic corticosteroids or other immunosuppressants + supportive

Subacute and chronic peripheral neuropathies

• HIV-associated peripheral neuropathy
• Cytomegalovirus radiculopathy
• Diabetic peripheral neuropathy

HIV-associated peripheral neuropathy

• HIV neuropathy – Chronic process
• Antiretroviral-induced neuropathy – Chronic process
• High rates of mononeuritis multiplex and inflammatory myopathy resembling polymyositis
• Late-stage AIDS all have neuropathy
• Early HIV infection increases risk of GBS

CMV radiculitis

• IN later stages of AIDS, CMV can acutely infect the lumbosacral nerve roots leading to polyradiculopathy or cauda equina syndrome
• Retinitis is almost always co-existent
• Suffer acute weakness +- bladder/bowel involvement vs. more chronic HIV-associated neuropathies
• Viral DNA PCR is highly specific on CSF along with pleocytosis with PMN and increased protein
• MRI of lumbosacral spine shows swelling and clumping of cauda equina and rules out any mass lesion causing compression
• Treatment is IV ganciclovir

Diabetic peripheral neuropathy

• Most common cause of noncompressive focal neuropathy
• Most commonly distal symmetric polyneuropathy (glove and stocking)
  • Distal axonopathy with length-dependent, centripetal dying back of affected nerves
• Focal neuropathies and mononeuropathy multiplex also occur
• Hyperglycaemic neuropathy
  • Seen in newly diagnosed diabetics and improves with glycaemic control
• Insulin neuritis
  • Seen with rapid glycaemic control with reversible acute limb pain and paraesthesia
• Painful diabetic neuropathy
  • Usually intermittent and worse at night
  • If >6 months, termed chronic painful diabetic neuropathy

Diabetic peripheral neuropathy

• Treatment of painful diabetic neuropathy
  • TCA’s, anticonvulsants and topical capsaicin have all proven beneficial for symptom relief
  • Pregabalin 50mg TDS
  • Gabapentin 300mg nocte
  • Duloxetine 30mg daily (consider if concomitant depression)
  • Capsaicin
  • Oxycodone
  • Tramadol

Diabetic peripheral neuropathy

• Diabetic amyotrophy
  • Lumbosacral plexopathy with long-standing history of diabetes and presents with back pain followed by weakness
  • Acute onset of ipsilateral back pain, followed by progressive leg weakness
  • No sensory findings
  • May have reduced reflexes. Bladder and bowel function NOT affected

Foot drop

• For spinal cord pathology consider upper limb involvement, bilateral findings and bladder/bowel issues
• If lower motor neuron need to consider L5 nerve root (myotome and sensory pattern matching this) vs. sciatic (sural and peroneal nerve sensory pattern loss only) vs. common peroneal nerve (no sural nerve involvement)
• Dermatomes

• Sural nerve
  • Only sensory
  • Only posterolateral aspect of the distal third of the leg and lateral aspect of the foot, heel and ankle
• Common peroneal nerve
  • Branch off the sciatic nerve
  • Before divides it gives off sensory branches to the lateral sural cutaneous nerve supplying the skin of the upper two-thirds of the lateral leg
  • Divides into the deep peroneal nerve and the superficial peroneal nerve
  • Deep peroneal
    • Cutaneous branch only to the first web space
    • Motor branch to dorsiflexors and toe extensors
  • Superficial peroneal
    • Cutaneous innervation to dorsum of the foot (except for first web space)
    • Supplies motor supply to foot everters
    • Can still invert foot
• If both sural and common peroneal = sciatic
• If plantarflexion is weak or sensory loss on plantar aspect of foot = sciatic nerve or higher owing to tibial nerve involvement

Last Updated on March 8, 2023 by Andrew Crofton