Alcoholic Cerebellar Degeneration

Alcoholic cerebellar degeneration is a chronic, usually subacute, loss of cerebellar Purkinje cells in the anterior superior vermis and cerebellar hemispheres in people with long term heavy alcohol use. It causes a wide based gait ataxia with relative sparing of the arms and speech.

It is found in about 1 to 2% of people with chronic alcohol use disorder clinically, and in up to 25 to 40% on imaging or at autopsy. Men are affected more than women, and onset is typically after 10 or more years of heavy drinking, at 40 to 60 years.

Contributors. Thiamine deficiency, direct ethanol toxicity, malnutrition, repeated withdrawal, hepatic disease and magnesium deficiency.

Course. Gradual progression over weeks to months, then plateau. Stopping alcohol and thiamine replacement can stabilise or partly improve gait in some; continued drinking leads to progression.

Pathophysiology.

Chronic ethanol exposure and thiamine deficiency cause loss of Purkinje cells, molecular layer thinning and degeneration of the anterior vermis, which controls gait and leg coordination.

The cerebellar atrophy is often visible on MRI as widened folia in the superior vermis.

• Progressive unsteadiness of gait, with a wide based, lurching walk and difficulty with tandem walking.
• Leg ataxia (heel-to-shin) out of proportion to arm ataxia; mild dysarthria; nystagmus in some.
• Truncal instability and falls; relatively little intention tremor.
• Often coexisting alcoholic polyneuropathy, Wernicke-Korsakoff syndrome and liver disease.

Red flags.

• Acute ophthalmoplegia, confusion and ataxia (Wernicke encephalopathy).
• Sudden onset, vertigo, headache or focal signs (cerebellar stroke).
• Rapid progression with weight loss (paraneoplastic or other cause).

• Clinical diagnosis from alcohol history, gait ataxia and exclusion of other causes.
• MRI of the brain: superior vermian atrophy, sometimes with hemispheric atrophy, and exclusion of posterior fossa lesions and stroke.
• Blood tests: full blood count (macrocytosis), liver function, gamma glutamyl transferase, thiamine, B12, folate, vitamin E, magnesium, thyroid function, glucose and coeliac serology.
• Nerve conduction studies for neuropathy; paraneoplastic antibodies and genetic testing for spinocerebellar ataxias when the history is unclear.
• Assessment of alcohol use disorder severity, nutrition and mood.

Differential diagnosis. Wernicke encephalopathy, spinocerebellar ataxia, paraneoplastic cerebellar degeneration, multiple system atrophy, vitamin E deficiency, drug induced ataxia (phenytoin, lithium), hypothyroidism, coeliac disease and posterior fossa tumour.

• Alcohol abstinence is the most important treatment; offer supported withdrawal and relapse prevention.
• Thiamine for suspected or established deficiency: 200 to 500 mg intravenously every 8 hours for 3 to 5 days, then 100 mg orally three times daily. Maximum 1500 mg intravenously each day. Monitor for anaphylaxis (give with resuscitation facilities available) and for eye signs and confusion. Avoid in thiamine hypersensitivity; no renal or hepatic adjustment; acceptable in pregnancy.
• Replace folate, B12, magnesium and other vitamins; improve nutrition.
• Acamprosate to help maintain abstinence, started after withdrawal: 666 mg orally three times daily in adults over 60 kg (666 mg in the morning and 333 mg at midday and night if under 60 kg). Maximum 1998 mg daily. Continue for up to 1 year. Monitor renal function, mood and suicidal thoughts. Reduce to 333 mg three times daily when creatinine clearance is 30 to 50 mL/min; contraindicated when it is under 30 mL/min and in severe hepatic impairment; avoid in pregnancy and breastfeeding.
• Naltrexone as an alternative in patients without opioid use or severe liver disease: 25 mg orally once daily for 1 to 3 days, then 50 mg once daily. Maximum 50 mg daily. Monitor liver function every month for 3 months, then 3 monthly. Avoid with opioids, acute hepatitis and liver failure; use caution in renal impairment; avoid in pregnancy.
• Physiotherapy and balance training, gait aids, occupational therapy and falls prevention; vestibular and cerebellar rehabilitation.
• Treat neuropathy pain and mood disorder; social support and addiction services.

Monitoring. Review at 4 to 6 weeks, 3 months and 6 months; track gait scores, alcohol use, liver tests and nutrition.

Referral and escalation. Neurology, addiction services and hepatology; urgent admission for Wernicke features or severe withdrawal.

Special groups. Older adults: higher fall and fracture risk. Women: develop damage at lower intake and shorter drinking history.