Peripheral Neuropathy

Question 1

Peripheral neuropathy (polyneuropathy) can be caused by many diseases.

The 4 categories are:

Guillian-Barre syndrome

Chronic inflammatory demyelinating polyradioneuropathy

Idiopathic, sensorimotor neuropathy

Metabolic, toxic, vitamin deficiency neuropathies

Answer 1

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Question 2

What is Guillian-Barrè syndrome (GBS)?

Answer 2

Guillian-Barrè syndrome = most common acute polyneuropathy

=> inflammatory demyelinating disorder as a result of infection

=> Campylobacter jejuni and CMV infections cause severe GBS

=> Infecting organisms cause an antibody response against peripheral nerves

Question 3

What are the symptoms of Guillian-Barrè syndrome?

Answer 3

Weakness of distal limb muscles / distal numbess

Foot-drop, weak hand

Low back pain = early feature

Weakness and sensory loss progress proximally over several days to 6wks

Loss of tendon reflexes

Respiratory & facial muscle weakness (20%)

Question 4

How is Guillian-Barrè syndrome diagnosed?

What are the differential diagnosis?

Answer 4

Clinical diagnosis confirmed by nerve conduction studies

Nerve conduction studies shows:
=> slowing of conduction in common demyelinating form
=> prolonged distal motor latency
=> conduction block

CSF protein may be raised

Differential diagnosis:
=> Acute paralytic illnesses i.e. botulism, cord compression, muscle disease and myasthenia gravis

Question 5

What are the initial investigations for peripheral neuropathy?

Answer 5

Blood tests: 
=> FBC, ESR, Vit. B12
=> Renal, liver, thyroid function
=> Glucose
=> Protein electrophoresis, immunoglobulins, immunofixation
=> Anti-Nuclear antibodies (ANA)

Chest Xray

Urine: Bence Jones proteins

Question 6

How do you manage Guillian-Barrè syndrome?

Answer 6

Monitor ventilation + ventilation support if required

Low molecular weight heparin + compression stocking to reduce risk of venous thrombus

Immunoglobulin IV within first 2wks => reduces duration and severity of paralysis
=> patients should be screened for IgA deficiency (because congenital deficiency can lead to IgG led allergic reaction upon administering immunoglobulins)

Question 7

Chronic inflammatory demyelinating polyradiculoneuropathy:

=> develops over months
=> progressive or relapsing proximal and distal limb weakness with sensory loss
=> Immunosuppression with steroids to manage

Answer 7

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Question 8

Paraproteinaemic neuropathies:

=> 70% of patients with a serum paraprotein have neuropathy

=> Assoc. with monoclonal gammopathy of unknown significance (MGUS)

=> Also seen in myeloma

Answer 8

Paraproteinaemic neuropathies:

IgM paraproteins:

=> demyelinating neuropathy

=> directed against myelin assoc. glycoprotein (anti-MAG)

=> Anti-MAG phenotype = slowly progressive distal neuropathy with ataxia and prominent tremor

Question 9

Chronic sensorimotor neuropathy has no known cause.

How does it present?

What does nerve conduction studies show?

Answer 9

=> Progressive symmetrical numbness & tingling

=> In hands & feet spreading in a glove and stocking distribution

=> Distal weakness ascends

=> Tendon reflexes are lost

Nerve conduction studies show axonal degeneration

Question 10

What are the metabolic causes of peripheral neuropathy?

Answer 10

Diabetes

Uraemia

Hepatic disease

Thyroid disease

Porphyria

Amyloid disease

Malignancy

Question 11

What are the toxic causes of peripheral neuropathy?

Answer 11

Drugs i.e. phenytoin, chloramphenicol, metronidazole, isoniazid, nitrofurantoin, disulfiram, amiodarone, chloroquine, anti-retroviral drugs, vincristine

Alcohol

Industrial toxins i.e. lead

Question 12

What are the vitamin deficiency causes of peripheral neuropathy?

Answer 12

B1 (thiamine) deficiency

B6 (pyridoxine) deficiency

Nicotinic acid

B12

Question 13

What is the most common cause of peripheral neuropathy in developed countries?

Answer 13

Diabetes => 50% of patients with diabetes have neuropathy after 25 years

Question 14

What types of neuropathy occurs in diabetes?

Good glycemic control is protective against this microvascular complication

Answer 14

1. Distal symmetrical sensory neuropathy
   => glove & stocking distribution, numbness, tingling and pain e.g. worse at night
   => reduced sensation
2. Acute painful sensory neuropathy
   => reversible with improved glycemic control
3. Mononeuropathy and multiple mononeuropathy
4. Diabetic amyotrophy
   => painful wasting of quadriceps and other pelvifemoral muscles
   => reversible vasculitic plexopathy or femoral neuropathy

5. Autonomic neuropathy
=> postural BP drop
=> reduced cerebrovascular autoregulation
=> loss of respiratory sinus arrhythmia 
=> gastroparesis 
=> urine retention
=> erectile dysfunction 
=> gustatory sweating 
=> diarrhoea

Question 15

Thiamine deficiency causes beri-beri.

Beri-beri key features are:
=> polyneuropathy
=> cardiac failure

Answer 15

Thiamine deficiency also leads to Wernicke’s encephalopathy & Korsakoff psychosis

=> Alcochol is the most common cause of Wernicke-Korsakoff syndrome

Wernicke’s encephalopathy due to damage in the brainstem + its connections

Wernicke-Korsakoff syndrome signs:

1. Eye signs i.e. nystagmus, bilateral lateral rectus palsies, conjugate eye palsies
2. Ataxia i.e. broad based gait, cerebellar signs and vestibular paralysis
3. Cognitive changes i.e. stupor, coma leading to irreversible amnestic state

Question 16

Vitamin B12 deficiency causes damage to the spinal cord, peripheral nerves and brain.

It also causes subacute combined degeneration of the cord (SACD).

What is subacute degeneration of the cord (SACD)?

Answer 16

Initial stages:
=> numbness and tingling of fingers & toes
=> distal sensory loss
=> absent ankle jerks
=> with cord involvement - exaggerated knee jerks + extensor planters
=> optic atrophy & retinal haemorrhage

Later stages:
=> sphincter disturbances
=> severe generalised weakness
=> dementia

*parenteral B12 reverses nerve damage but no affect on cord and brain

Question 17

Genetic neuropathies:

What is Charcot-Marie-Tooth disease?

Answer 17

Charcot-Marie-Tooth disease is a group of heterogenous hereditary motor and sensory neuropathies.

=> Distal limb wasting and weakness esp legs
=> Progress slowly over many years
=> Variable loss of sensation and reflexes
=> Advanced disease = severe foot drop
=> Mild disease = per cavus (higher than normal arch) and toe clawing

Question 18

Other peripheral neuropathies:

=> neuropathy in cancer

=> neuropathy in systemic diseases i.e. 
SLE, 
Polyarteritis nodosa, 
Granulomatosis with eosinophilia, 
Rheumatoid disease

Answer 18

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Question 19

Autonomic neuropathy may develop in diabetes, amyloidosi, Guillian-Barrè syndrome and Parkinson’s.

What are the signs of autonomic neuropathy?

Answer 19

Postural hypertension

Urinary rentention

Erectile dysfunction

Nocturnal diarrhoea

Diminished sweating

Impaired pupillary responses

Cardiac arrhythmia