10.10. Nutrition Associated Neuropathies
- General features:
- Dietary nutritional deficiency in the West is most often secondary to alcoholism or specific malabsorption syndromes such as pernicious anemia, gastrectomy, sprue, intestinal surgery. Usually there are multiple vitamin deficiencies.
Alcoholic Neuropathy
- General features:
- Occurs in 9–30% of hospitalized alcoholics; seen in >80% of alcoholics with Wernicke's–Korsakoff syndrome
- Women and men equally susceptible
- Usually require 100 grams of alcohol daily for a prolonged period of time
- Pathogenesis:
- Primarily a nutritional deficiency
- Direct neurotoxic effect
- Many asymptomatic patients have both clinical and autonomic features of neuropathy
- Neuropathy may occur in a setting of severe weight loss
- Clinical Presentation:
- Subacute onset of paresthesias followed by severe burning feet (25% of patients)
- Painful calves, cramps and distal weakness
- Sensory ataxia in severe patients
- Distal areflexia that progress proximally
- Autonomic dysfunction (rare clinically)
- Associated Type II atrophy of proximal muscle
- Dying back clinical picture most common, some patients demonstrate dynamic and static mechano allodynia
- Rarely proximal lower extremity involvement
- Decreased RBC transketolase activity
- Central manifestations:
- "Martinet" anterior cerebellar gait (trunk is extensor; stiff legged)
- Central pontine myelinolysis
- Dementia, white matter primarily; partially reversible
- EMG:
- Distal denervation
- Reduced or absent SNAPs mild slowing of motor NCV
- Prolongation of distal sensory and motor latencies
- Pathology (nerve biopsy):
- Decreased are myelinated fibers of all sizes
- Axonal destruction
Thiamine B1 Deficiency
- General features:
- Occurs in the setting of starvation, alcoholism, prolonged vomiting, post gastric stapling, dialysis and a diet of carbohydrate without vitamins
- Absorbed in small intestine by passive diffusion and active transport; phosphorylated in the jejunum to thiamine pyrophosphate (TPP)
- Involved in: decarboxylation of alpha ketoacids that are transketolated to alpha ketols
- Develops with total parenteral nutrition
- Clinical presentation:
- Features of symmetric sensory motor polyneuropathy
- Evolves over weeks or months; rarely develops over several days
- Some patients develop painful small fiber neuropathy
- Distal paresthesias and weakness; ankle areflexia
- Associated Wernicke Korsakoff syndrome
- Rare involvement of vagus and recurrent laryngeal nerves; tongue and facial weakness
- Central and centrocecal scotomata; may be due to Strachan's syndrome
- EMG
- Reduced or absent SNAPs, decreased CMAP, distal denervation
- Pathology:
- Axonal degeneration
- Decreased RBC transketolase activity
B12 (Cobalamin) Deficiency
- General features:
- Most often due to autoimmune induced intrinsic factor deficiency
- Vegan diet
- Inflammatory bowel disease
- Blind loop syndrome (diphyllobothrium latum)
- Gastrectomy
- Nitrous oxide anesthesia (acute)
- In association with other autoimmune diseases
- Severe steatorrhea
- Infestation of the fish, tapeworm
- Required for methionine synthase and methylmalonic CoA reductase
- Seen with folic acid deficiency; if folate deficiency is treated without B12 replacement neurologic signs may exacerbate.
- Pathogenesis possible inhibition of the cobalamin-dependent enzyme methionine synthase
- Clinical presentation:
- Active large fiber neuropathy; paresthesias and burning in hands and feet
- Cranial nerve I and II dysfunction
- Myelopathy: spasticity; bilateral Babinski signs; posterior column dysfunction
- Reflexes intact in the face of distal atrophy
- Frontal lobe dysfunction; psychiatric manifestations
- Recovery worse for vibration sensibility; paresthesias may improve
- Cerebellar and cerebral demyelination
- Low levels of cobalamin may be associated with neurologic signs and symptoms
- Laboratory evaluation:
- Methylmalonic acid and homocysteine may be elevated
- Large hyper segmented neutrophiles; low platelets and a macrocystic anemia that may be severe <2 grams/100 ml (develops gradually)
- Intrinsic factor and parietal cell antibodies may be noted
- EMG:
- Mild slowing of motor and sensory conduction velocities
- Reduced or absent SNAPs
- Distal lower extremity denervation
- Pathology:
- Segmental peripheral neuropathy
- Posterior lateral spinal cord demyelination (vacuolar pattern)
Vitamin B6 (Pyridoxine)
- General features:
- Associated with poly nutritional deficiencies; isoniazid and hydralazine therapy
- Toxic dose greater than 200 mg/day
- Inhibits conversion of pyridoxal phosphate
- Clinical presentation:
- Distal burning paresthesias in feet and hands
- Neuropathy may improve with B6 replacement or discontinuance of INH
- Deafferentation and ataxia
- EMG:
- Decreased SNAPs
- Rarely motor axons are affected
- Slowed sensory NCVs
Pellagra (Niacin Deficiency)
- General features:
- Dermatitis; diarrhea; dementia
- Corn or sorghum occurs where the main dietary staple (Africa and Asia)
- Dermatitis: hyperkeratosis of the face, neck; dorsal limb surfaces are reddish brown
- Diarrhea usually severe with concomitant weight loss
- Clinical presentation:
- Similar to thiamine deficiency
- Axonal neuropathy; most evident when the illness is mild
Strachan's Syndrome
- General features:
- Disease of sugar cane workers' high carbohydrate diet without vitamins
- Epidemic forms
- Deficiency of thiamine, cobalamin, folate, niacin, riboflavin, sulfurated amino acids
- Clinical presentation:
- Optic neuropathy
- Painful polyneuropathy
- Urogenital dermatitis; priapus, ansa and vulva
- Corneal degeneration; stomatoglossitis
- Maculopapillary bundle visual loss (central scotoma)
- Posterior column proprioception and vibratory deficit
- Mild Corticospinal tract involvement
- Riboflavin B2 reverses dermatitis but not the optic neuropathy or myeloneuropathy
Cuban Epidemic 1992–1993 (Resembles Strachan Syndrome)
- Polyneuropathy
- VIIth nerve deficit
- Optic neuropathy
- Dorsolateral myeloneuropathy:
- Posterior column deficits
- Corticospinal dysfunction
Vitamin E Deficiency
- General features:
- Associated with chronic lipid malabsorption states (vitamin E deficiency)
- Vitamin is predominately in the alpha and gammatocopherol form; found in vegetable oils and wheat germ; absorbed in small intestines
- Incorporated into chylomicrons; component of very low density lipoproteins
- Occurs in:
- Abetalipoproteinemia lipoproteinemia (AR; Bassen Kornsweig disease)
- Cystic fibrosis
- X-linked:
- AD or AR familial syndrome
- Alpha-tocopherol transfer protein gene on chromosome 8q 13
- Cholesterotic and hepatobiliary disorders
- Short bowel syndrome
- Clinical presentations:
- May occur several years after the onset of the deficiency (5–10 years)
- Loss of vibration and position sense
- Limb ataxia
- Head titubation
- Absent ankle jerks
- Babinski signs present
- Spinocerebellar ataxia with a polyneuropathy
- Visual loss (pigmentary retinopathy)
- Ophthalmoplegia, ptosis, dysarthria
- Dystonia and bradykinesia
- Proximal weakness (myopathy)
- Rare presentation as isolated polyneuropathy
- Laboratory:
- Direct measurement of alpha-tocopherol in the serum by high performance liquid chromatography
- EMG:
- Slowed sensory NCVs
- Decreased SNAPs
- Pathology:
- Axonal spheroids in the dorsal column nuclei
- Clarke's column and dorsal and ventral spinocerebellar tracts. Loss of large diameter myelinated axons in sensory nerve
Post Gastroplasty
- General features:
- Gastric restriction procedures with prolonged vomiting
- Clinical presentation:
- Distal paresthesias
- Extremity weakness
- Wernicke–Korsakoff Syndrome
- Lumbar plexopathy
- RBC transketolase may be elevated
- Vitamin replacement early associated with recovery
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