Diseases of peripheral nerve

• Inflammatory, traumatic, metabolic, toxic, genetic, neoplastic

Inflammatory neuropathies• Inflammatory cell infiltrates into peripheral

nerves, roots & autonomic ganglia

Immune mediated neuropathies

G. B. syndrome ( acute inflammatory demyelinating polyradiculoneuropathy )

• Most common, life threatening

• Weakness in distal limbs, rapidly advancing to proximal muscle ( asc paralysis)

• Inflammation & demyelination of peripheral nerves & spinal nerve roots

Pathogenesis • Preceded by acute infleunza like illness,

viral• Immunologically mediated disease

Morphology • Inflammation of peripheral nerve• Perivenular & endoneurial infiltration by

lymphocytes, macrophages & few plasma cells

• Segmental demyelination affecting peripheral nerve is pri.lesion

Clinical course• Dominated by asc paralysis• Deep tendon reflexes disappear early• Nerve conduction velocity slowed bcoz of

multifocal destruction of myelin segments involving axons within nerve, increase in CSF protein due to inflammation

Infectious polyneuropathies

Leprosy • Lepromatous leprosy – schwann cells

invaded by M.leprae which proliferates & infects other cells

• Evidence of segmental demyelination & remyelination & loss of both myelinated & unmyelinated axons

• Endoneurial fibrosis & multilayered thickening of perineural sheaths

• Symmetric polyneuropathy involves pain fibres, leads to loss of sensation, trophic ulcers

• Tuberculoid leprosy – active CMI with nodular granulomatous inflammation

• Inflammation injures cutaneous nerves in the vicinity, axons, schwann cells & myelin are lost

• Fibrosis of perineurium & endoneurium

Varicella zoster virus• Common viral infection • Latent infection of neuron in sensory

ganglia of spinal cord & brain stem follows chickenpox

• Painful vesicular skin eruptions in distribution of sensory dermatomes ( thoracic/trigeminal )

• Ganglia show neuronal destruction, mononuclear inflammatory infiltrate

• Regional necrosis & h’ge may be seen

Hereditary neuropathies• Grp of heterogenous, typically

progressive, often disabling syndrome

Hereditary motor & sensory neuropathies • Common• Caused by mutations in genes whose

products are involved in formation & maintainence of myelin

Type I ( HMSN I )• Childhood • Progressive muscular atrophy of calf • Duplication of large region of chromosome

17p11 – p12 -> segmental trisomy, which includes gene for peripheral myelin protein 22 (PMP22 )

Morphology • Histology shows consequences of

repetitive demyelination & remyelination with multiple onion bulbs more in distal nerves

• Schwann cell hyperplasia surrounding individual axons -> enlargement of individual p.nerves -> hypertrophic neuropathy

• AD , slowly progressive, sensorimotor deficits

Hereditary sensory & autonomic neuropathies

• Numbness, pain, orthostatic HTN

Familial amyloid polyneuropathies• Deposition of amyloid within p.nerves

Acquired metabolic & toxic neuropathies

Peripheral neuropathy in adult onset DM• Depends on duration of disease

1. Distal symmetric sensory/sensory motor neuropathy

2. Autonomic neuropathy

3. Focal/multifocal asymmetric neuropathy

Morphology • Axonal neuropathy in distal symmetric

sensorimotor neuropathy • Other types there is some segmental

demyelination• Endoneurial arterioles show thickening,

hyalinization

Clinical course• Decreased sensation in distal extremities• ulcers

Metabolic & nutritional peripheral neuropathies

• In renal failure – distal symmetric neuropathy, muscle cramps, decreased deep tendon reflexes, axonal degeneration

• Chr liver disease, chr resp insufficiency, thyroid dysfunction

• Thiamine deficiency -> axonal degeneration – Beri Beri

• Excessive consumption of alcohol -> axonal neuropathy

Neuropathies ass with malignancy• Direct infiltration/ compression of p nerves

by tumor -> mononeuropathy• Eg brachial plexopathy – lung tumor• Diffuse symmetric neuropathy in distant

CA due to paraneoplastic syndromes

• Numbness, paraesthesia

Toxic neuropathies• After exposure to industrial/environmental

chemicals, toxins, drugs – lead, arsenic

Traumatic neuropathies• Nerves injured during course of trauma• Lacerations from cutting injuries, avulsions

– tension applied to peripheral nerve

• Regeneration slow, regrowth complicated by discontinuity between proximal & distal portions of nerve sheath/ misalignment of individual fascicles

• Axons in absence of distal segment continue to grow resulting in mass of tangled axonal process -> traumatic neuroma

Compression neuropathy - occurs when p nerve is compressed

Carpal tunnel syndrome • Compression of median nerve at the level

of wrist within compartment limited by transverse carpal ligament

• Women, bilateral• Pregnancy, inflammatory arthritis,

hypothyroidism, acromegaly, DM

• Numbness, paraesthesia of tips of thumb & 1st two digits

Other• Involvement of ulnar nerve at the level of

elbow• Peroneal nerve – level of knee• Radial nerve in the underarm – sleeping

with arm improperly positioned – sat night palsy