Neurology - Disorders of peripheral nerves I Flashcards
3 types of connective tissue surrounding peripheral nerve
Axons present in peripheral nerves grouped into fascicles
1.) Epineurium - binds individual fascicles together; outer layer merges with the dura mater of spinal roots
- ) Perineurium - binds each fascicle with elastic fibres; acts as diffusion barrier
- ) Endoneurium - supports individual axons within each fascicle
Blood supply to peripheral nerves
Vasa nervorum - blood vessels supplying the fascicles located in the epineurium
Do all peripheral nerves have a Schwann cell?
Yes - but only in some cells (myelinated fibres) does the Scwann cell membrane spiral around the axon
What are the 3 types of fibre in peripheral nerves?
Type A (myelinated) - carries vibration and position sense; alpha motor neurones
Type B (myelinated) - autonomic preganglionic
Type C (unmyelinated) - pain and temperature afferents
3 types of pathology affecting peripheral nerves
1) Wallerian degeneration = degeneration of the axon distally following damage
- distal to the injury the axon disintegrates and the myelin breaks up into globules
- basement membrane of the Schwann cell survives and forms a skeleton along which the axon can grow
2) Segmented demyelination = scattered destruction of myelin sheath occurs without axonal damage
3) Distal axonal degeneration = damage to the cell body or the axon will cause the axon to “die back” from the periphery; myelin is lost as a secondary event
What is a mononeuropathy?
Neuropathy involving a single nerve - e.g. median nerve
If multiple single nerves are affected in an asymmetrical pattern this is called mono neuritis multiplex
Polyneuropathy
General dysfunction of peripheral nerves that is usually symmetrical
Usually starts distally with some proximal progression
Classified based on:
- ) Timing - acute or chronic (often points to the aetiology)
- ) Function - autonomic, sensory, motor or combo
- ) Pathology - axonal or demyelinating
E.g. GBS is an acute, predominantly motor, demyelinating polyneuropathy
Length dependance
Polyneuropathy affects the longest axons first and affected the worst
What are negative sensory symptoms of polyneuropathy?
Negative symptoms = loss of sensation
Large myelinated fibres - loss of touch and joint position
- Difficulty in discriminating textures
- Hands and feet feel like cotton wool
- Gait unsteady (especially in darkness where vision cannot compensate)
Small unmyelinated fibres - loss of pain and temp leading to painless trauma
- Neuropathic joints (Charcot’s joints) - painless traumatic deformity
Positive sensory symptoms of polyneuropathy
Large myelinated fibre disease can cause paraesthesia (“pins and needles”)
Small unmyelinated fibres produce painful positive phenomena:
- Analgesia
- Hyperalgesia (increased sensitivity to painful stimuli)
- Allodynia (pain provoked by non painful stimuli)
Glove and stocking distribution
= sensory loss in the feet and hands
Usually length related and therefore signs in the hand will not develop until there is sensory loss up to at least mid shin level
What are common motor symptoms in peripheral neuropathy?
Weakness is usually the main presenting feature
- distal - e.g. difficulty clearing the curb when walking
- proximal - e.g. difficulty climbing stairs or combing hair
Cramps
Fasciculations may be present (although normally associated with anterior horn cell disease)
Sensory signs in polyneuropathy
All modalities tested - large and small fibre
Identify area of total sensory loss
Sensory loss is usually symmetrical in polyneuropathy with glove and stocking distribution
Examine gait - sensory ataxia and positive Romberg’s test
Trophic changes - cold blue extremities, cutaneous hair loss
What is the “axon reflex” used for?
“Places” the lesion in a sensory pathway
Normally scratched skin leads to (1) local vasoconstriction (white reaction) then (2) local oedema (red reaction) and finally surrounding vasodilation or flare (dependent on antidromic impulses from the DRG)
Distal sensory lesion - absent flare response
Proximal root lesion (past DRG) will not impair the response
What motor signs indicate polyneuropathy?
Muscle wasting - present in axonal but absent in demyelinating neuropathies (look at 1st dorsal interosseous), fasciculations may also be present
Muscle weakness - proportional to the number of affected motor neurones
- usually starts distally and spreads proximally
- usually symmetrical
- respiratory muscle weakness can occur in severe cases
What causes loss of tendon reflexes? Are they lost in all forms of neuropathy?
Any interruption to the reflex arc leads to loss of tendon reflexes
Reflexes are lost (i) and (ii) proximally before distally
Neuropathies that affect predominantly small fibres may preserve tendon reflexes because spindle afferent fibres are large myelinated proprioceptive fibres
What polyneuropathies are acute in onset?
Acute = days up to 4 wks
A useful clue is that most have motor functional loss
1) Inflammatory (GBS) - predominantly motor + autonomic disturbance (demyelinative)
2) Diphtheria - cranial nerve onset + mixed sensory/ motor (demyelinative)
3) Porphyria - motor with minimal sensory loss + abdo pain + psychosis + seizures (may begin in arm) (axonal)
Some polyneuropathies are subacute and asymmetrical. Give some examples
Subacute = months-years
These are normally asymmetrical (cf. most are normally symmetrical) and multifocal
1) Infections:
- Leprosy - sensory neuropathy with pigmentation and thickened nerves
- HIV - range of presentations
2) Vasculitic disorders:
- PAN, Wegeners, Churg-Strauss - often painful, usually presents with mononeuritis multiplex or asymmetrical sensorimotor neuropathy (causes Wallerian degeneration + vasculitis)
There are lots of causes of subacute and chronic, symmetrical polyneuropathies. Name some metabolic or endocrine disorders
- Diabetes - distal sensorimotor most common but wide range of other forms
- Uraemia - distal sensorimotor
- Hypothyroidism - distal sensorimotor
- Acromegaly - distal sensorimotor
Most metabolic and endocrine disorders causes polyneuropathy via axonal degeneration
What nutritional deficiencies cause polyneuropathy?
1) Vit B1 (thiamine); includes alcoholic neuropathy
- Predominantly sensory with burning feet
- Weakness may develop
2) Vit B12 - predominantly sensory + SACD
What malignant diseases cause polyneuropathy?
Polyneuropathy caused by cancer = carcinomatous polyneuropathy
- Paraneoplastic - sensory or sensorimotor; may be associated with anti-Hu antibodies in serum
- Infiltrative - multifocal (often a polyradiculopthay); more common with lymphoma
What type of polyneuropathy does amyloid cause?
Amyloid causes subacute or chronic, symmetrical sensorimotor neuropathy often with autonomic involvement
Associated with thickened nerves with amyloid deposits
Inherited polyneuropathies
1) CMT
2) Refuses disease = phytanic acid storage disorder causing sensorimotor neuropathy + ichthyosis + retinitis pigments + deafness
Name some drugs and toxins that can cause polyneuropathy
Wide range of drugs induce neuropathies
- Antibiotics (isoniazid, metronidazole, dapsone)
- Chemotherapy (adriamycin, cisplatin)
- Others (amiodarone, gold, phenytoin)
Toxins
- Lead
- Arsenic
- Thallium
Key investigations in polyneuropathy
1) Bloods - FBC, U&E, LFTs, HbA1c, TFTs, Vit B12 and folate, ESR
2) Chest X ray
3) Nerve conduction studies
4) Nerve biopsy (sural nerve is usually used because it is mostly sensory)
5) CSF examination - useful in inflammatory demyelinating polyneuropathies - e.g. GBS or CIDP
How do nerve conduction studies distinguish axonal degeneration from demyelination?
Axonal degeneration - reduced amplitude of electrical impulse
Demyelination - reduced conduction velocity
Definition of GBS
Acute (i.e. symptoms reach severity in 4 wks) inflammatory demyelinating polyradiculoneuropathy
10% of cases neuropathy is axonal rather than demyelinating
Epidemiology of GBS
More common in elderly but can occur at any age
M = F
Most common cause of acute peripheral paralysis
What is the aetiology of GBS?
2/3 of patients have an infection in previous 6 wks before developing symptoms
- most often respiratory
- if GI them Campylobacter jejuni is commonest cause
Clinical presentation of GBS
Pain in lower back is often the first symptom
Pins and needles in the toes followed (within hours) by flaccid paralysis of lower limbs to involve the arms and facial muscles
Sensory symptoms are minimal or absent
Major complications of GBS
Maximal disability occurs approx 2-4 wks following onset
- Respiratory failure (weakness of respiratory muscles)
- Autonomic involvement - arrhythmia and BP
- Venous thrombosis and PE
What is Miller-Fischer variant of GBS?
Brainstem involvement
- Ataxia
- Ophthalmoplegia
- Areflexia
What other differentials are important to consider in GBS?
GBS is very acute, so differentials should consider vascular, inflammatory or toxic causes of acute weakness
E.g.
- Brainstem infarct
- Acute spinal lesion
- Infection - i.e. Lyme disease
- Inflammation
- Vasculitis
- Porphyria
Investigations in GBS
1) EMG - helps to classify subtypes based on whether axonal or demyelinating
2) LP - high CSF protein (>1g/L) with no or few white cells (NB - high WCC should prompt another diagnosis)
3) Antiganglioside antibodies - some infections share structural similarities to peripheral nerve components such as gangliosides, anti-ganglioside antibodies are found in up to 25% of patients with GBS
Are steroids useful useful for GBS?
No - steroids are useful for CIDP
RCTs show that non ambulant patients treated early (within 2 weeks of symptom onset) recover better with IVIg for 5 days or 4-6 plasma plasma exchanges
What monitoring is especially important in GBS?
Vital capacity monitoring with regular oxygen saturations (intubation and ventilation may be necessary)
Anticoagulation is also important to prevent DVTs
Prognosis of GBS
Complete recovery over several months occurs in 80-90% of individuals
Mortality in the acute phase is high (up to 10%)
Poor prognostic indicators are
- Older age
- Rapidity of onset
- Requirement of ventilation
- Evidence of axonal degeneration
- Detectable antiganglioside antibodies
What is CIDP?
CIDP = Chronic Inflammatory Demyelinating Polyneuropathy
Similar to GBS but with a progressive or fluctuating course over weeks and rarely involving cranial nerves or respiratory muscles
Mean age of onset is 35 yrs (younger = fluctuating course; older = progressive)
Pathology of CIDP
Segmental demyelination with remyelination (onion bulb formation)
How is CIDP diagnosed and what differentials are important to consider?
CIDP is diagnosed based on electrophysiology with reduced conduction velocity and conduction block
Important to distinguish from:
- Hereditary neuropathy - e.g. CMT
- Paraprotein and lymphoma associated neuropathy
- Multifocal motor neuropathy with conduction block
- HIV neuropathy
Are steroids useful in CIDP?
Yes
Steroids are started in moderate disease with plasmapheresis + IVIg + immunosuppressants added in severe disease
Why does diabetes cause polyneuropathy?
Related to poor glycemic control - neurologic complications correlate with levels of HbA1c
More common in insulin dependant diabetics
Damage is caused by either:
- metabolic disturbance with sorbitol and fructose accumulation in axons
- occlusion of nutrient vessels supplying nerves (vasa nervorum)
How many patients with diabetes develop a polyneuropathy?
30% of diabetics have polyneuropathy but only 10% are symptomatic
Distal weakness and sensory loss is usual - 2 forms of sensory neuropathy occur:
- Large fibre causing ataxia
- Small fibre causing painful anaesthesia
Diabetic autonomic neuropathy
Occurs in most patients with peripheral polyneuropathy
Occasionally the autonomic dysfunction predominates:
- Pupil abnormalities
- Loss of sweating
- Orthostatic hypotension
- Resting tachycardia
What cranial nerve palsy is common in diabetics?
CN 3 palsy - usually painless and occurs with pupillary sparing (which helps differentiate it from an aneurysmal cause where the pupil is dilated)
6th and 7th nerves may also be involved
Complete recovery is the rule
What is diabetic amyotrophy?
Much less common than polyneuropathy
Proximal muscle pain and weakness rapidly develop - anterior thigh is affected with wasting of the quadriceps, loss of knee jerk and minimal sensory loss
It is caused by anterior spinal root or plexus disease
Multifocal motor neuropathy with conduction block
Presents with asymmetric LMN weakness that is similar to MND
Neurophysiology shows “conduction block” at distal sites from possible entrapment
Antibodies to gangliosides are found in the serum
How many patients with late onset peripheral neuropathy have circulating monoclonal paraprotein in their serum? If no other cause is found what is this condition called?
10% of patients with late onset chronic peripheral neuropathy have circulating monoclonal paraprotein
If lymphoma, myeloma, amyloidosis and Woldenstrom’s macroglobinaemia are excluded the condition is called MGUS - monoclonal gammopathy of uncertain significance
IgM is reactive in 50% of cases to myelin associated glycoprotein (anti-MAG antibodies)
What is porphyria?
Acute intermittent porphyria is a rare autosomal dominant disorder with symptoms of abdo pain, psychosis, convulsions and peripheral neuropathy occur
The metabolic fault is in the liver - increased production of porphobilinogen (increased urinary concentration)
Clinical features of acute intermittent porphyria
The onset is acute and predominantly motor with upper limb and occasional cranial nerve involvement
Autonomic dysfunction is common and respiratory failure occurs in severe cases
It MUST be distinguished from GBS
Characteristic features of CMT
CMT = Hereditary motor and sensory neuropathy
Distal wasting, lower limb inverted “wine bottle” appearance
Features of CMT type I
- Age of onset
What is the pathology of CMT type I? Is this the same as type II?
Demyelination with thickened “onion bulb” areas of demyelination
Different for type II which is caused by axonal loss
What is the mode of inheritance for CMT type I?
Autosomal dominant - 70% of cases are due to duplication of PMP (peripheral myelin protein) 22
Features of CMT type II
- Age of onset > 30
- Wasting and weakness as for type I
- Foot deformities ABSENT
- Peripheral nerves not palpable
How can neurophysiology differentiate between types 1 and type II CMT?
Type I - slow conduction velocity
Type II - normal conduction velocity or slightly reduced
