Peripheral Neuropathy

There are several patterns of peripheral nerve disease:

• Mononeuropathy
• Multiple mononeuropathy
• Symmetrical polyneuropathy
• Plexopathy
• Radiculopathy
• Polyradiculopathy

The time course may be:

• Acute - reaching its nadir in <4 weeks
  
• Subacute - reaching its nadir in 4 - 8 weeks
• Chronic - taking 8 weeks to develop.

The deficit may be:

• Motor - proximal/distal & symmetrical/asymmetrical
• Sensory - the key features to look for here is pain and ataxia
• Autonomic

The underlying pathology may be:

• Axonal
• Demyelinating
• Mixed

Pure Motor:

Differential diagnosis includes - myopathy & disease of neuromuscular junction.

• Motor Neurone Disease
• Multifocal Motor Neuropathy

Prominent Motor symptoms together with sensory symptoms include:

• AIDP/CIDP
• Acute Intermittent Porphyria
• Lead Intoxication
• Charcot's Marie Tooth Disease

Pain:

Small Nerve Fibres involvement: has normal muscle power, reflexes and vibratory/proprioceptive senses as these are carried by large fibres. There will be reduced pinprick and thermal sensation in the affected area. Vibratory sensation can be mildly reduced at the toes.

The causes are extensive

• Mostly idiopathic
  
• Impaired glucose tolerance and Diabetes Mellitus and
  
• Sjogren's syndrome
• Hypothyroidism
• HIV infection/ Hepatitis C infection
• Vitamin B12 deficiency
  
• Neurotoxic Drug Exposure

Large Nerve Fibres involvement:

Sensory Ataxia: The best recognised causes are

• A paraneoplastic syndrome associated with anti-Hu antibodies, often due to small cell lung cancer
• Sjögren’s syndrome
  
• Cisplatin toxic neuropathy
  
• Pyridoxine toxicity
• many cases remain ‘idiopathic’ despite extensive workup and careful follow-up

Autonomic Features:

• Acute: AIDP
• Chronic: Diabetes and Amyloidosis

This blog emphasied about the symmetrical generalised neuropathy.

The differential diagnosis of more or less symmetrical generalised neuropathy is much more extensive and complicated than that of mononeuropathies.

Initial Investigations for symmetrical polyneuropathy include:

• Blood Test - FBC, eLFT, Ca, TFT, ESR, HbA1c, B12/Folate, serum protein electrophoresis
• Immunology - ANA
• Radiology - CXR
• Neurophysiology - Nerve conduction study
  

Chronic Axonal neuropathy:

Causes:

• Hereditary
• Infection - leprosy and HIV
• Diabetes
• Alcohol
• Amyloidosis
• Endocrinology - myxoedema and acromegaly
• Drugs
• Toxins
• Uraemia
• Cirrhosis
• Paraneoplastic

Chronic demyelinating neuropathy

Causes:

• Chronic inflammatory demyelinating polyradiculoneuropathy
• Multifocal motor neuropathy
• Para-protein associated demyelinating neuropathy
• Charcot-Marie-Tooth disease type 1 and type X.

Chronic Inflammatory demyelinating polyradiculoneuropathy - CIDP

It is important to distinguish CIDP from chronic axonal neuropathy because it responds well to treatement with immunotherapy.

Clues are:

• A relapsing course
• Proximal as well as distal weakness
• Increased CSF protein and normal cell count ( in at least 80 % )

Management:
Corticosteroids, intravenous immunoglobulin and plasma exchange are all beneficial but prolong treatment is necessary. In pure motor CIDP, which may be worsened by corticosteroids, IV Ig should be the first choice.

Multifocal motor neuropathy:

Clinically, it may resemble amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron involvement, but muscle atrophy and more rapid progression are lacking.

Sometimes it can be confused with a pure motor form of CIDP as well.

The diagnosis depends on finding multifocal motor but not sensory conduction block at sites not subject to compression.

Management:
About 80 % of patients respond to IV Ig which has to be repeated every month.

Hereditary neuropathy:
The commonest cause is Charcot-Marie-Tooth disease. Other causes include:

• Hereditary sensory and autonomic neuropathy
• Distal hereditary motor neuropathy
• Familial amyloid polyneuropathy
• neuropathy associated with multisystem hereditary disorders such as metachromatic leukodystrophy, mitochondrial disorders and Refsum's disease.

Usually, the initial symptom of CMT is foot drop early in the course of the disease. This can also cause hammer toe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to "stork leg" or "inverted bottle" appearance. Weakness in the hands and forearms occurs in many people later in life as the disease progresses.

A definitive diagnosis for a specific type of CMT is established via genetic testing for most types.

Acute Neuropathy
Acute neuromuscular paralysis has a wide differential diagnosis but GBS is the commonest cause.

Differential diagnosis of acute neuromuscular paralysis include:
Cortical lesion- such as CVA, encephalitis
Cord lesion - compression from abscess, haematoma, tranverse myelitis
Peripheral neuropathy:

• Gullain - Barre syndrome
• Poliomyelitis
• Rabies
• Acute intermittent porphyria
• Drug induced
• Diphtheria
• Thiamine deficiency
• Critical illness neuropathy

Neuromuscular transmission:

• Tick bite paralysis
• Myasthenia gravis
• Lambert Eaton myasthenic syndrome

Disorder of muscle:

• Hypokalaemia
• Hypophosphataemia
• Inflammatory myopathy
• Periodic paralysis
• Acute rhabdomyolysis