Peripheral Neuropathy NS Lecture PDF

CNS Pathology Lecture (4) I- PERIPHERAL NEUROPATHIES Ahmed Almobarak  Peripheral Neuropathies (PN) Definition: These are group of disorders which may disrupt the normal conduction of impulses in the peripheral nerves.  Peripheral Neuropathies Causes of peripheral neurop...

CNS Pathology Lecture (4) I- PERIPHERAL NEUROPATHIES Ahmed Almobarak  Peripheral Neuropathies (PN) Definition: These are group of disorders which may disrupt the normal conduction of impulses in the peripheral nerves.  Peripheral Neuropathies Causes of peripheral neuropathies: Metabolic: – Diabetes mellitus (common). – Renal failure. – Liver failure. – Porphyria.  Peripheral Neuropathies Autoimmune diseases: – Guillain-Barré syndrome. – Systemic lupus erythematosus (SLE). – Rheumatoid arthritis. – Chronic inflammatory demyelinating neuropathy.  Peripheral Neuropathies Infections: – Leprosy. – Diphtheria. – Varicella zoster – EBV (Epstein Barr virus). – HIV (human immunodeficiency virus).  Peripheral Neuropathies Toxic: – Heavy metals: e.g. arsenic, lead, mercury. – Drugs: e.g. metronidazole, phenytoin, vincristine. – Organic solvents: e.g. toluene, N- hexane.  Peripheral Neuropathies Hereditary neuropathies: – Charcot-Marie-Tooth disease. – Refsum’s disease. – Déjérine-Sottas disease. – Hereditary sensory neuropathy.  Peripheral Neuropathies Vitamin deficiencies: – Vitamin B1 – Vitamin B3 – Vitamin B6. – Vitamin B12 – Vitamin E.  Peripheral Neuropathies 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.  Peripheral Neuropathies Clinical features of peripheral neuropathies: – Combination of sensory, motor and occasionally autonomic manifestations. Sensory manifestations: Pain. Burning. Tingling. Numbness.  Peripheral Neuropathies Motor manifestations: Muscular weakness. Muscular twitches. Muscular atrophy. Paralysis. Difficulty in breathing or swallowing.  Peripheral Neuropathies Autonomic manifestations: Blurred vision. Decrease sweat. Dizziness. Nausea and vomiting. Diarrhea or constipation. Urinary incontinence.  Peripheral Neuropathies The following topics will be discussed in details: – Diabetic neuropathy. – Guillain-Barré syndrome. – Chronic inflammatory demyelinating neuropathy. – Charcot-Marie-Tooth disease. – Refsum’s disease. – Déjérine-Sottas disease.  Peripheral Neuropathies – Neuropathies associated with malignancy. – Traumatic neuropathies.  Diabetic Neuropathy Diabetic neuropathy: – Common complication of diabetes. – Causes great morbidity and mortality world wide. – Significant risk for amputation.  Diabetic Neuropathy Four types are found: – Peripheral neuropathy: damage of the peripheral nerves, most commonly the feet and legs. It causes pain, burning, tingling, or numbness. – Proximal neuropathy: affects nerves in the thigh, hips and buttocks. It causes pain in these areas and weakness in the legs.  Diabetic Neuropathy – Autonomic neuropathy: affects the nerves that control body functions, e.g. GIT, urinary, genital, and vascular system. It causes nausea, vomiting, diarrhea or constipation, dizziness, fainting, sexual disorders, orthostatic hypotension. – Focal neuropathy: affects a specific nerve or area at any site of the body. It may cause eye pain, chest pain, Bell’s palsy, etc.  Diabetic Neuropathy Pathogenesis of diabetic neuropathy: – Micro-vascular injury: of small blood vessels that supply nerves leading to neural ischemia, usually occurs early in diabetes. – Increase level of glycosylated proteins in the nerve tissue reduces conduction. – Increase level of protein kinase C which decrease nerve conduction. – Increase level of sorbitol in sorbitol/reductase pathway, leads to microangiopathy. Pathogenesis of Diabetic PN  Guillain-Barre syndrome Guillain-Barré syndrome (GBS): Definition: Acute inflammatory demyelinating disease. Immune mediated disorder following a viral infection (Cytomegalovirus, Epstein Barr virus) or Campylobacter jejuni). The target is gangliosides, which are present in the nerves, they are attacked by antibodies.  Guillain-Barre syndrome It is a life threatening ascending paralysis, beginning in hands and feet and advancing to the proximal muscles. Affection of respiratory muscles causes respiratory failure.  Guillain-Barre syndrome Clinical features: – Symmetrical weakness of lower limbs and upper limbs, rapidly progresses to the trunk. – Nerve conduction velocity is slowed. – CSF protein is elevated, no inflammatory cells. Microscopic: – Segmental demyelination of the nerve. – Chronic inflammatory cell infiltration in the nerve. Segmental demyelination of nerves Peripheral neuritis , microscopic Nerve biopsy from a case of GBS showing infiltration of the nerve by chronic inflammatory cells. Perivascular cuffing is prominent.  Chronic Inflammatory Demyelinating Polyneuropathy Chronic inflammatory demyelinating polyneuropathy: (CIDP), chronic relapsing polyneuropathy. Similar to the GBS, but it follows sub-acute or chronic course with relapses and remissions. Microscopic: the nerves show recurrent demyelination and re-myelination and “onion bulb” appearance. Onion bulb appearance, E/M  Charcot-Marie-Tooth Disease Charcot-Marie-Tooth disease: – The most common hereditary form. – Autosomal dominant disease, the defects occur mainly on chromosome 17, but less on chromosome 1, which affect the myelin sheath. – Occurs in young adults. – There is weakness and atrophy of calf muscles. – Microscopic: there is segmental demyelination and onion bulb  Refsum’s Disease Refsum’s disease: Autosomal recessive. There is faulty accumulation of phytanic acid which lead to malformation of myelin sheath. Blood levels of phytanic acid are increased in patients with Refsum disease. These levels are 10- 50 mg/dl, whereas normal values are less than or equal to 0.2 mg/dl, and account for 5-30% of serum lipids.  Refsum’s Disease Symptoms evolve slowly and insidiously from childhood to adulthood. There is: – Peripheral polyneuropathy, – Cerebellar ataxia, and – Scaly skin (icthiosis).  PN Déjérine-Sottas disease: Occurs in infants. Autosomal dominant, the defects are on chromosomes 17 and 1. There is progressive upper and lower extremity weakness and muscle atrophy. Morphology: severe segmental demyelination with prominent onion bulbs. Neuropathies & Malignancy Neuropathies associated with malignancy Causes: – Infiltration or compression by a tumor. – Circulation of anti-neuronal protein in some malignancies as small cell lung carcinoma. – Deposition of amyloid in the nerves as in multiple myeloma. Amyloid deposition in a nerve, microscopic, congo red stain  Traumatic neuropathies Traumatic neuropathies: Causes: – Lacerations, as in cutting injuries and bone fractures. – Traumatic neuromas: painful nodules of tangled axons and connective tissue after nerve injury. – Compression neuropathy: commonly occurs in the median nerve in “carpal tunnel syndrome”.  Traumatic neuropathies Carpal tunnel syndrome: Due to compression of the median nerve at the wrest joint. Most cases are idiopathic. It may be due to: – Bone fractures, – Dislocation of carpal bones, – Hematoma inside the wrest joint. – Inflammatory reaction.  Carpal tunnel syndrome Clinical manifestations: – Pain, numbness, burning or tingling sensation in the thumb, index, and middle fingers. – In chronic cases, there may be atrophy of the thenar muscles (muscles connected to the thumb). Carpal tunnel syndrome Thank you