Peripheral Neuropathies Flashcards
Describe the cellular sheath that surrounds peripheral neurons
All peripheral nerves are surrounded by Schwann cells (cellular sheath)
- only in some does the membrane of the cell ‘spiral’ around the axon, forming multilayered myelin sheath
What is saltatory conduction?
Schwann cells of myelinated nerves are separated by nodes of Ranvier - meaning at these points, the axons are not surrounded by myelin
- suring conduction, impulses jump from one node to the next
Conduction in unmyelinated nerves is slower and depends on the diameter of the axon
What are the two basic pathological processes that cause disruption in the function of peripheral nerves?
1) Wallerian degeneration
- the axon and myelin sheath degenerates distal to an axonal injury
- occurs within 7-10 days of injury
- degenerating portion of nerve is inexcitable
- regeneration can occur as the basement membrane of the Schwann cell survives and acts as a skeleton along which the axon regrows
2) Demyelination
- segmental destruction of the myelin sheath, normally with no axonal damage (secondary axonal damage can occur after a period of prolonged demyelination)
- causes marked slowing or conduction or conduction block
Definitions of neuropathies
Neuropathy
- pathological process affecting a peripheral nerve or nerves and can involve axonal degeneration or demyelination
Mononeuropathy
- when a single nerve is affected
- if multiple single nerves are affected in an asymmetrical pattern = mononeuritis multiplex
Polyneuropathy
- diffuse, symmetrical disease process that is usually distal with some proximal progression
- affected longest axons first and progressively affected shorter and shorter nerves
- can be acute, subacute or chronic
Common causes of peripheral mononeuropathies
Peripheral nerve compression and entrapment neuropathies - carpal tunnel syndrome - ulnar nerve compression - radial nerve compression - common peroneal nerve palsy - meralgia paraesthetica Mononeuritis multiplex
Common causes of peripheral polyneuropathies
Polyneuropathies associated with systemic disease - diabetes neuropathy - renal disease - paraneoplastic polyneuropathy - connective tissue diseases and vasculitides - porphyria - amyloidosis Neuropathies causes by drugs and toxins - alcoholic neuropathy - drugs - toxins Inflammatory demyelinating neuropathies - Guillian-Barre syndrome - chronic inflammatory demyelinating polyradiculoneuropathy Neuropathies caused by nutritional deficiencies - thiamine deficiency - vitamin B12 deficiency - vitamin E deficiency Hereditary neuropathies - Charoct-Marie-Tooth disease
Describe carpal tunnel nerve compression
Usually idiopathic but can be associate with
- hypothyroidism
- pregnancy
- DM
- RA
- acromeagly
Presents with tingling, pain and numbness in the hand, which often wakes the patient from sleep/or in morning
- pain can extend up arm to shoulder, and is relieved by shaking arm and hand
Weakness of thenar muscles - especially abductor pollicis brevis (may be wasting if chronic)
Sensory loss - first 3.5 fingers
Diagnosis
- clinical (tinel’s sign)
- electrophysiology confirming slow impulse across the wrist
Surgical decompression is required
Describe ulnar nerve compression
Entrapment at elbow - within olecranon groove in cubital tunnel
Can occur after trauma or prolonged/recurrent pressure at this site
Clinical features
- wasting and weakness
- numbness in ulnar 1.5 fingers = ulnar claw hand
Surgical decompression is required
Distal ulnar compressions are possible where the deep motor branch crosses the palm
- regular pressure e.g. from tools, bike handlebars or crutches
Describe radial nerve compression
Occurs when the radius nerve is compressed against the humerus
- e.g. arm draped over a chair for several hours (saturday night palsy)
Results in wrist drop and weakness of finger extension and brachioradialis
Sensation is lost in the region of the anatomical snuffbox
Recovery is spontaneous, but can take up to three months
Describe common peroneal nerve palsy
Occurs when nerve is compressed at the fibular head
Causes
- prolonged squatting or leg crossing
- wearing a plaster cast
- prolonged best rest or coma
Clinical features
- foot drop
- weakness of eversion and dorsiflexion
- sensory loss on anterolateral border of the shin and dorsum of the foot
Recovery is normal and normally takes a few months
Describe meralgia paraesthetica
Syndrome caused by entrapment of lateral cutaneous nerve of the thigh - beneath the inguinal ligament
Clinical features
- burning, tingling and numbness on the anterolateral surface of the thigh
Usually occurs in overweight patients, and resolves with weight loss
Describe mononeuritis multiplex
Certain systemic illnesses are associated with multiple mononeuropathies
Can be caused by preferential sites of entrapment, or focal pathological processes within a nerve (e.g. infarction in diabetes)
Causes
- diabetes mellitus
- connective tissue disease (polyarteritis nodosa, SLE, RA - pathology normally being small vessel vasculitis)
- sarcoidosis
- amyloidosis
- neurofibromatosis
- AIDS
- leprosy
Describe diabetic polyneuopathy
The neuropathies found in DM are related to poor glycaemic control
- exact cause of damage is unknown, but may relate to sorbitol accumulation or vascular disease in large/small vessels
Types of neuropathy that complicate diabetes
- distal, symmetrical polyneuropathy (most commonly sensory)
- proximal symmetrical motor neuropathy a.k.a diabetic amyotrophy (acutely painful, older men)
- autonomic neuropathy (gastroparesis, diarrhoea, arrhythmia and postural hypotension)
- mononeuropathies can be single or multiple (entrapment common)
- cranial nerve lesions - isolate 3rd and 6th nerve palsies are common
- mononeuritis multiplex
Describe the polyneuropathies seen in renal disease
Chronic renal failure produces a progressive sensorimotor neuropathy
Response to dialysis is variable, but neuropathy usually improves after renal transplant
Describe paraneoplastic polyneuropathy
Malignant disease (especially SCC of bronchus) produces a sensory neuropathy affecting the large fibres, leading to a sensory ataxia - associated with anti-Hu antineural antibodies Haematological malignancies (multiple myeloma and other monoclonal gammopathies) can produce peripheral neuropathies that resemble chronic, inflammatory, demyelinating polyneuropathy
Describe the polyneuropathies seen in connective tissue diseases and vasculitides
Classically produce a very painful mononeuritis multiplex
Individual diseases may produce a symmetrical, sensorimotor neuropathy (SLE), entrapment neuropathy (RA) or trigeminal neuropathy (Sjogren’s syndrome)
Describe the polyneuropathies seen in porphyria
Acute intermittent porphyria produces a motor neuropathy \+ abdominal pain \+ psychosis \+ seizures Onset is usually acute or subacute
Describe polyneuropathies seen in amyloidosis
Amyloid is deposited around vessels in the nerve, causing distortion
Neuropathy is characterised by sensory, painful, dysaesthetic features
- autonomic features are common
What drugs cause polyneuropathies, and what are the different patterns of presentation
Most produce a chronic, sensorimotor polyneuropathy and are normally reversible
- sensory axonal neuropathy (chloramphenical, isoniazid, phenytoin and Taxol)
- motor axonal neuropathy (amphotericin, dapsone and gold)
- sensorimotor axonal neuropathy (chlorambucil, cisplatin, disulfiram, nitrofuratoin and vincristine)
- sensorimotor demyelinating neuropathy (amiodarone)
What toxins can cause a peripheral polyneuropathy, and what are the patterns of presentation
Lead - motor neuropathy
Arsenic and thallium - painful peripheral sensory neuropathy
Acrylamide, trichloroethylene and fat-soluble hydrocarbons e.g. glue-sniffing
- progressive polyneuropathy
Alcoholic neuropathy - most common (30% of all cases of peripheral neuropathy)
- progresses slowly with distal sensory loss, paraesthesia and burning pains
- distal muscle weakness spreads proximally
- muscle cramps and gait disturbance
- primarily due to alcohol toxicity, and secondarily due to deficiency of vitamins (especially thiamine)
- treated with alcohol abstinence, thiamine supplementation and a balanced diet
Describe guillain-barre syndrome
Inflammatory demyelinating polyradiculoneuropathy
Often follows 1-3 weeks after URTI or diarrhoea
- can also follow vaccines or HIV seroconversion
Clinical features
- distal paraesthesia but little sensory loss
- weakness either occurs proximally, starts distally and spreads proximally or is generalised
- symptoms ascend up lower limbs and body over days/weeks
- facial weakness (50% cases)
- severe cases have respiratory and bulbar involvement meaning ventilation is required
- autonomic dysfunction i.e. arrhythmias
Diagnosis is normally clinical
- raised CSF protein and slowed conduction velocities can be seen
Treatment
- IV immunoglobulins
- recovery is gradual over many months, and is often incomplete
- some patients develop a relapsing remitting disease (5%)
Symptoms have to stop progressive after 6 weeks, or the disease becomes termed CIDP
Describe CIDP (chronic inflammatory demyelinating polyradiculoneuropathy)
A milder syndrome related to guillain-barre syndrome, but has a more protracted clinical course
Clinical, diagnostic features and pathology are similar to those of GBS
- rarely associated with preceding infection
Management
- corticosteroids
- immunosuppressive agents such as azathioprine or cyclophosphamide
- recurrent IV immunoglobulins/plasmapheresis
Describe the neuropathies caused by nutritional deficiency
Thiamine deficiency
- strongly implicated in alcohol neuropathy
- also causes Wernicke-Korsakoff syndrome
Pyridoxine deficiency
- mainly causes a sensory neuropathy
- precipitated by isoniazid therapy for TB ( why pyridoxine is given in combination)
Vitamin B12 deficiency
- causes peripheral neuropathy and subacute combined degeneration of the cord (spastic paraparesis, loss of proprioception and paraesthesia)
- also linked to optic neuropathies and dementia
- management involves intramuscular replacement injections
Describe Charcot-Marie-Tooth disease
CMT type 1 - most common form
- autosomal dominant demyelinating neuropathy with hypertrophy of nerve
- onset between ages 5 and 15
- ‘onion-bulb’ formation on electron microscopy
CMT type 2
- autosomal dominant axonal neuropathy
- onset between ages 10 and 20
CMT types 3
- autosomal dominant or recessive demyelinating neuropathy
- gross hypertrophy of peripheral nerves
- raised CSF protein due to hypertrophy of nerve roots
The main investigations of peripheral neuropathy
30% cases - no cause found
Bloods tests
- FBC, ESR, CRP, U&Es, LFTs, glucose, vitamin B12 and protein electrophoresis
Nerve conduction studies
- differentiates axonal degeneration (reduced amplitude of electrical impulse) from demyelination (reduced conduction velocity)
- characterises whether sensory or motor fibres are involved
- localises the sites of abnormalities e.g. entrapment neuropathies
CSF examination
- identifies inflammatory demyelinating neuropathies (CIDP and guillain-barre syndrome)
- protein count is raised without inflammatory cells
Extra investigations for finding the cause of peripheral neuropathy - when diagnosis isn’t certain with standard tests
Electromyography
- fine needle inserted into muscle can determine whether partial or complete denervation is present, and whether reinnervation is occuring
- helps localisation depending on the muscles affected
Nerve biopsy
- sural nerve biopsied most commonly as it is purely sensory (so resulting clinical deficit is trivial)
- light and electron microscope can gain pathological information
