Peripheral Neuropathies Overview

Peripheral Neuropathies

• Peripheral neuropathies (PN) are a group of disorders that disrupt normal impulse conduction in peripheral nerves.

Causes of Peripheral Neuropathies

• Metabolic: Diabetes mellitus (common), renal failure, liver failure, porphyria.
• Autoimmune diseases: Guillain-Barré syndrome, systemic lupus erythematosus (SLE), rheumatoid arthritis, chronic inflammatory demyelinating neuropathy.
• Infections: Leprosy, diphtheria, varicella zoster, Epstein Barr virus (EBV), HIV.
• Toxic: Heavy metals (arsenic, lead, mercury), drugs (metronidazole, phenytoin, vincristine), organic solvents (toluene, N-hexane).
• Hereditary: Charcot-Marie-Tooth disease, Refsum's disease, Déjérine-Sottas disease, hereditary sensory neuropathy.
• Vitamin deficiencies: Vitamin B1, B3, B6, B12, E.
• Trauma to the nerve: Compression by a tumor, cutting in accidents, electric discharge.
• Others: Infiltration of the nerve by a malignant tumor, exposure to radiation, amyloid deposition in the nerve.

Clinical Features of Peripheral Neuropathies

• Combination of sensory, motor, and occasionally autonomic manifestations.

Sensory Manifestations

• Pain
• Burning
• Tingling
• Numbness

Motor Manifestations

• Muscular weakness
• Muscular twitches
• Muscular atrophy
• Paralysis
• Difficulty in breathing or swallowing

Autonomic Manifestations

• Blurred vision
• Decrease sweat
• Dizziness
• Nausea and vomiting
• Diarrhea or constipation
• Urinary incontinence

Diabetic Neuropathy

• Common complication of diabetes, causing significant morbidity and mortality worldwide.
• Significant risk for amputation.
• Four types:
  • Peripheral neuropathy: Damages peripheral nerves, affecting feet and legs, causing pain, burning, tingling, or numbness.
  • Proximal neuropathy: Affects nerves in the thighs, hips, and buttocks, causing pain and weakness in the legs.
  • Autonomic neuropathy: Affects nerves controlling bodily functions (e.g., GIT, urinary, genital, and vascular systems), causing nausea, vomiting, diarrhea, constipation, dizziness, fainting, and sexual dysfunction.
  • Focal neuropathy: Affects a specific nerve or area, causing eye pain, chest pain, Bell's palsy, etc.

Pathogenesis of Diabetic Neuropathy

• Microvascular injury: Damage to small blood vessels supplying nerves, leading to neural ischemia.
• Increased levels of glycosylated proteins in nerve tissue, reducing conduction.
• Increased levels of protein kinase C, decreasing nerve conduction.
• Increased sorbitol levels in the sorbitol/reductase pathway, leading to microangiopathy.

Guillain-Barré Syndrome (GBS)

• Definition: Acute inflammatory demyelinating disease, an immune-mediated disorder, often following a viral infection (e.g., Cytomegalovirus, Epstein-Barr virus) or Campylobacter jejuni.
• Target: Gangliosides in nerves, attacked by antibodies.
• Clinical features: A life-threatening ascending paralysis beginning in the hands and feet, progressing to proximal muscles, and often affecting respiratory muscles, causing respiratory failure.
• Symptoms: Asymmetrical weakness of lower limbs, progressing to the upper limbs and the trunk, slowed nerve conduction velocity, elevated CSF protein, and no inflammatory cells.
• Microscopic: Segmental demyelination of the nerve, chronic inflammatory cell infiltration in the nerve (microscopic details shown in images).

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

• Similar to GBS, but with a sub-acute or chronic course with relapses and remissions.
• Microscopic: Shows recurrent demyelination and remyelination - the "onion bulb" appearance.

Charcot-Marie-Tooth Disease

• Most common hereditary form of PN.
• Autosomal dominant disease.
• Defects primarily on chromosome 17 but less frequently on chromosome 1, affecting the myelin sheath.
• Occurs in young adults.
• Weakness and atrophy of calf muscles.
• Microscopic: Segmental demyelination and "onion bulb" appearance.

Refsum's Disease

• Autosomal recessive.
• Faulty accumulation of phytanic acid results in myelin sheath malformation in the nerves.
• Blood levels of phytanic acid are increased in patients (10-50 mg/dL, versus normal <0.2 mg/dL).
• Accounts for 5-30% of serum lipids in patients.
• Symptoms typically develop slowly and insidiously from childhood to adulthood and include peripheral polyneuropathy, cerebellar ataxia, and scaly skin.

Déjérine-Sottas Disease

• Autosomal dominant, mostly defects on chromosomes 17 and 1.
• Occurs in infants, often with progressive upper and lower extremity weakness, and muscle atrophy.
• Severe segmental demyelination with prominent "onion bulbs"

Neuropathies Associated with Malignancy

• Causes: Infiltration or compression by a tumor, circulation of anti-neuronal proteins (e.g., in some lung cancers), deposition of amyloid in nerves (e.g., in multiple myeloma).

Traumatic Neuropathies

• Causes: Lacerations and fractures.
• Traumatic neuromas: Painful nodules of tangled axons and connective tissue after nerve injury; examples of compression related conditions like carpal tunnel syndrome.
• Compression neuropathy: Commonly occurs in the median nerve, such as carpal tunnel syndrome.

Carpal Tunnel Syndrome

• Due to compression of the median nerve at the wrist joint.
• Most cases are idiopathic.
• Possible causes include: bone fractures, dislocation of carpal bones, hematoma, inflammatory reaction.
• Clinical manifestations: Pain, numbness, burning or tingling in the thumb, index, and middle fingers. In chronic cases, atrophy of the thenar muscles.

Explore the various causes and types of peripheral neuropathies, a group of disorders that affect nerve impulse conduction. This quiz covers metabolic, autoimmune, infectious, toxic, hereditary, vitamin deficiency causes, and more. Test your knowledge on this critical medical topic.