Makindo Medical Notes

Note: In the UK and US, the most common causes of peripheral neuropathy include diabetes and alcohol abuse. Worldwide, leprosy remains a significant cause.

About

• Also refer to "Length Dependent Polyneuropathy" for more detailed information.
• Peripheral neuropathy refers to diseases of the peripheral nerves and is often secondary to primary neurological or systemic conditions.
• Clinical patterns vary widely: peripheral neuropathy can be patchy or symmetrical, distal or proximal, and may affect motor, sensory, or autonomic functions.

Aetiology

• Peripheral nerves are composed of large myelinated and small unmyelinated fibers.
  • Small fibers: Responsible for pain, temperature sensation, and autonomic functions.
  • Large fibers: Carry motor signals and sensory input for vibration and proprioception.

Different Forms of Peripheral Neuropathy

Type	Description
Wallerian Degeneration	Nerve transection leads to both axonal and myelin loss. The distal portion degenerates and regrows from proximal to distal, with varying success.
Axonal Degeneration	Commonly caused by toxins, metabolic conditions, or nutritional deficiencies. Affects the longest nerves first, resulting in a "dying back" pattern. Diabetes is the most frequent cause.
Demyelination	Loss of myelin with axonal preservation. Common causes include Schwann cell damage or immune attack on myelin (e.g., Guillain-Barré syndrome and CIDP).
Neuronal Cell Body Disease	Affects the anterior horn cell (e.g., polio, motor neuron disease, certain paraneoplastic syndromes).
Dorsal Root Ganglionopathy	Involves the dorsal root ganglia, leading to sensory loss as seen in some paraneoplastic diseases and Sjogren's syndrome.

Different Patterns of Peripheral Neuropathy

Pattern	Description
Polyneuropathy	Typically presents as a distal "glove and stocking" sensory or motor loss. Common causes include diabetes, B12/folate deficiency, alcohol abuse, and Lyme disease.
Mononeuropathy	Involves a single nerve. Examples include nerve compression or entrapment, and conditions such as diphtheria or diabetic neuropathy.
Mononeuritis Multiplex	Involves multiple nerves in a sequential or simultaneous pattern, often associated with vasculitis.
Autonomic Neuropathy	Affects autonomic nerves, with causes including diabetes, amyloidosis, porphyria, and certain medications or toxins.
Abrupt Onset Neuropathy	Often ischemic in origin, associated with PAN, RA, and certain infections like HIV/AIDS.
Cranial Nerve Involvement	May involve bilateral facial nerves (e.g., in diabetes, GBS, Lyme disease, sarcoidosis).

Common Causes of Peripheral Neuropathy

Cause	Description
Diabetes Mellitus (axonal)	Causes symmetrical distal sensory and autonomic neuropathy.
Alcohol Abuse	Leads to distal, symmetric axonal sensorimotor neuropathy, often painful.
Rheumatoid Arthritis	Causes distal motor and sensory neuropathy.
Systemic Lupus Erythematosus (SLE)	Associated with distal motor and sensory neuropathy.
Paraneoplastic Neuropathy	Includes sensory, motor, and autonomic forms, often related to malignancies like lymphoma.
B12 Deficiency (axonal)	Leads to proprioceptive loss, ataxia, and reduced reflexes.
Vasculitis	Associated with distal motor and sensory neuropathy.
Uraemia	Common in renal failure or those on dialysis.
Chemotherapy (e.g., Cisplatin)	Results in distal symmetrical neuropathy.
Guillain-Barré Syndrome (GBS)	Acute inflammatory demyelinating neuropathy with autonomic involvement, often presenting with elevated CSF protein.
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)	Chronic demyelinating neuropathy with bilateral motor and sensory deficits.
Hereditary Neuropathies	Such as CMT, which often involves distal motor and sensory loss.

Clinical Features

• Sensory Symptoms: Paraesthesia, dysesthesia, allodynia, hyperesthesia, and neuropathic pain. Loss of proprioception may cause ataxic gait.
• Motor Symptoms: Distal weakness with loss of reflexes, progressing to foot drop and high-stepping gait in advanced cases.
• Autonomic Symptoms: Can include postural hypotension, bowel and bladder dysfunction, and erectile difficulties.
• Hereditary Features: Foot deformities such as pes cavus and clawing are common in hereditary neuropathies.
• Nerve Thickening: Thickened nerves (e.g., ulnar, sural) are rare but can occur in conditions such as leprosy, CIDP, and CMT.

Rate of Onset

• Days: GBS, vasculitis
• Weeks: CIDP
• Months/Years: Diabetes, alcohol

Differentiating Clues

• Speed of onset
• History of alcohol abuse or diabetes
• Cranial nerve or autonomic involvement
• Predominantly sensory or motor symptoms
• Pattern of sensory loss: small fiber (pain/temperature) vs. large fiber (vibration/proprioception)
• Family history (e.g., CMT)

First-Line Investigations

• Blood Tests: FBC, ESR, CRP, LFTs, glucose, HBa1c, B12, folate, and TFTs to rule out metabolic causes.
• Autoimmune Panel: ANA, dsDNA, and ENA for vasculitis.
• CXR: To check for sarcoidosis, malignancy, and infections.
• EMG and Nerve Conduction Studies: Confirm neuropathy and help determine the pattern (axonal vs. demyelinating) and fiber type involvement.

Selective Tests

• CSF Analysis: For elevated protein in GBS or CIDP.
• ACE Levels: Elevated in sarcoidosis.
• ANCA: For vasculitis/Churg-Strauss syndrome.
• Hepatitis and HIV Serology: For infectious causes.
• Genetic Testing: For suspected hereditary neuropathies.
• Nerve Biopsy: Sural nerve biopsy in difficult cases.

Management

• Management depends on the underlying cause (e.g., glucose control in diabetes, cessation of alcohol, B12 replacement in deficiency).
• For neuropathic pain: consider medications such as gabapentin, pregabalin, or duloxetine.
• Physical therapy, orthotics, and lifestyle modifications are beneficial for functional improvement.