alcoholic neuropathy

**Pathophysiology** - Primarily a length-dependent, distal axonal degeneration ("dying-back" neuropathy) affecting small and large fibers. Segmental demyelination is secondary. - Mechanisms are multifactorial: (1) direct ethanol/acetaldehyde neurotoxicity (oxidative stress, impaired axonal transport, inflammation); (2) nutritional deficiency, especially thiamine (B1), also folate, B12, pyridoxine (B6), niacin, and vitamin E; (3) impaired absorption and hepatic storage/metabolism of vitamins, which is worsened by coexisting liver disease. - Thiamine is a cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase. Deficiency causes impaired energy metabolism and neuronal injury.

**Clinical features** - Insidious onset over months. Symptoms are symmetric and begin in the feet, then progress proximally and to the hands (stocking-glove distribution). - Sensory: painful burning paresthesias, dysesthesias, allodynia, numbness, and loss of vibration, proprioception, and pinprick sensation. Small-fiber involvement causes prominent pain and autonomic symptoms. - Motor: distal weakness, foot drop, and muscle cramps, with atrophy in later disease. - Reflexes: decreased or absent ankle jerks. - Autonomic: orthostatic hypotension, erectile dysfunction, urinary dysfunction, anhidrosis or hyperhidrosis, and GI dysmotility. - Gait: sensory ataxia and a positive Romberg sign from loss of proprioception. - Often coexists with other alcohol-related disease, including Wernicke encephalopathy and Korsakoff syndrome (thiamine), cerebellar degeneration (anterior vermis, causing wide-based gait), macrocytic anemia, and cirrhosis.

**Diagnosis** - Clinical diagnosis based on a history of chronic heavy alcohol use plus exam findings. - Exclude other causes: diabetes (HbA1c), B12 deficiency (B12, MMA, homocysteine), hypothyroidism (TSH), uremia, HIV, and toxins or drugs. - Check thiamine, folate, B12, and B6 levels, and CBC (MCV is often elevated). - Nerve conduction studies/EMG show an axonal sensorimotor polyneuropathy (reduced amplitudes, relatively preserved conduction velocities).

**Management** - Alcohol abstinence is the cornerstone and halts progression. - Give thiamine (parenteral if severe or if Wernicke is suspected), along with folate, B12, and a multivitamin. In a patient at risk for Wernicke encephalopathy, give thiamine BEFORE glucose, because glucose can precipitate or worsen Wernicke encephalopathy. - Symptomatic pain control: gabapentin, pregabalin, duloxetine, or TCAs (e.g., amitriptyline). - Foot care, physical therapy, and fall prevention. - Prognosis: slow, often incomplete recovery over months to years with abstinence and nutritional repletion.

**High-yield board points** - Classic vignette: a chronic alcohol user with burning feet, stocking-glove sensory loss, and absent ankle reflexes. - Differentiate from other neuropathies. Diabetic neuropathy is also stocking-glove, but its history differs. B12 deficiency affects the dorsal columns and also causes subacute combined degeneration. Isoniazid neuropathy is prevented with B6 (pyridoxine). Dapsone causes a motor neuropathy. Vincristine causes a sensorimotor and autonomic neuropathy. - Wernicke triad: confusion, ophthalmoplegia/nystagmus, and ataxia. Korsakoff syndrome adds anterograde amnesia and confabulation, and involves the mammillary bodies and dorsomedial thalamus. - Alcohol-related neurologic conditions to remember together: peripheral neuropathy, cerebellar degeneration, Wernicke-Korsakoff, alcoholic myopathy, and Marchiafava-Bignami disease (corpus callosum demyelination).