|Alcoholic Cerebellar Degeneration|
Alcoholic Cerebellar Degeneration
Maria Romanova, M.D.
A 63-year-old male attorney presented with leg weakness gradually worsening for a year. Initially, he noted leg weakness and unsteadiness upon getting up from a chair and climbing the stairs. Over the next few months, his gait became increasingly clumsy, his hands and tongue started to shake and he noted it was difficult to comb his hair and to dress himself. He denied any numbness, voice changes or hearing loss.
Past medical history was significant for well-controlled hypertension and hyperlipidemia. Medications included hydrochlorothiazide, lisinopril and simvastatin, none of which had been recently started. The patient was an avid runner and tennis player. He admitted to consuming about 5 to 10 alcohol-containing beverages nightly for the past 15 to 20 years, but denied any medical or social problems related to his drinking.
Physical examination was remarkable for Dupuytren's contractures of the fourth and fifth fingers bilaterally. Neurological examination was notable for moderately decreased vibration sense over both feet, symmetrical and extending up to the ankles, decreased propriocep-tion in both greater toes, absent Achilles reflex and postural tremor. Coordination testing revealed dysme-tria on finger-to-nose and heel-knee-shin testing, mild truncal ataxia, and inability to tandem walk. The patient demonstrated marked loss of balance when he had his feet together and was asked to close his eyes. No nystagmus, oculomotor muscle or cranial nerve pathology was found, except for tongue tremulous-ness. Motor strength was tested and was normal in all major muscle groups. Plantar reflexes were down-going.
Complete blood count and electrolytes were normal. Liver function tests showed elevation of aspartate aminotransferase to 60 u/L (normal 13-35 u/L). The serum levels of thyrotropin, vitamin B12/folate, creatine kinase and rapid plasma reagin were within normal limits. Magnetic resonance imaging (MRI) of the brain demonstrated moderately severe cerebellar atrophy without significant microvascular ischemic disease or signal abnormality in the periaqueductal gray matter or thalami (see Figure 1). Nerve conduc-tion testing was consistent with peripheral neuropathy of both lower extremities. Based upon clinical history and brain imaging, a diagnosis of alcoholic cerebellar degeneration and peripheral neuropathy was made. The patient was started on thiamine supplementation and counseled on the importance of complete absti-nence from alcohol to prevent disease progression. He stopped alcohol consumption, and his weakness and ataxia remained stable, without further deterioration in the following 6 months.
Alcoholism is an extremely prevalent and well-recognized cause of morbidity and mortality nationally and worldwide. It is responsible for 100,000 deaths per year, and costs attributable to alcohol abuse approach $100 billion per year.1 Alcohol permeates every organ and tissue of the body, and causes numerous distinct disease entities.
Alcoholic cerebellar degeneration (ACD) is caused by irreversible toxic degeneration of Purkinje cells, and is clinically characterized by impaired gait, tremor and predominantly truncal ataxia. Midline cerebellar lesions with predominant involvement of the lower extremities, a chronic course and irreversibility after alcohol cessation are the hallmarks of the disease. Current literature on ACD is limited, and its exact incidence is unknown. It is thought to be caused by a combination of nutritional deficiency and alcohol neurotoxicity, likely involving glutamate.2,3 Genetics probably play a significant role in the cause of this disorder.
Alcoholic cerebellar degeneration was first described in a small series of patients in 1959, and remains largely a clinical diagnosis.4 Typically, the disease develops after more than 10 years of heavy drinking, though there is no direct relation between the "dose" of alcohol and severity of symptoms.5 Symptoms evolve in weeks or months and eventually stabilize, sometimes even with continued drinking and poor nutrition. Clinical suspicion can be confirmed by brain imaging, which can, in some cases, display distinct cerebellar shrinkage. Unlike in Wernicke's encephalopathy, cognition remains intact, and the thalami and periaqueductal gray matter look normal on MRI.
The differential diagnosis of ACD is extensive. On initial presentation, it is important to exclude endocrine and metabolic causes of cerebellar dysfunc-tion. Thyroid and parathyroid abnormalities are easily detectable through hormonal testing. Late Lyme disease (neuroborreliosis) can cause ataxia and tremor, similar to ACD. It can occur in patients with no evidence of prior Lyme disease, and who are no longer in an endemic area. As a result, travel history may be critical in considering this diagnosis.
Neurologic abnormalities, including cerebellar signs, can complicate infection by the Legionella bacterium. When Legionnaires' disease is suspected, both a urinary antigen test and Legionella culture of a respi-ratory specimen should be ordered. Similarly, in patients with mycoplasma pneumonia, ataxia heralds a complicated course and a guarded prognosis.6 Acute ataxia can be seen in many different viral infections, including varicella and infectious mononucleosis.7 It accounts for 50% of post-varicella neurolog-ical syndromes. The disorder is usually self-limited, with complete neurological recovery in 3 to 4 weeks. Paraneoplastic cerebellar degeneration can be associ-ated with ovarian, uterine, breast, lung, or bladder cancer or lymphoma. Anti-Yo (anti-parietal cell anti-bodies), anti-Tr and Nova-1 antibodies have been identified as the causative agents. The neurological symptoms can rarely precede the signs of malignancy. Therefore, careful physical examination along with proper imaging is indicated in the acute and subacute presentation of cerebellar degeneration.
Acute alcohol or sedative intoxication can be ruled out by history and toxicology analysis. Certain medications can cause neurological manifestations similar to ACD. For example, moderate lithium toxicity, seen with plasma concentration between 2.5 and 3.5 mEq/L, can cause coarse tremor, ataxia and muscle weakness.8 Ingestion or inhalation of methyl mercury results in perioral, hand and feet paresthesia, visual field constriction and ataxia, caused by neuronal destruction of cerebellar granule cells.9 In patients treated with phenytoin, lateral gaze nystagmus and ataxia may be observed if plasma concentration exceeds 30 mcg/mL.10 The group of genetic neurological conditions known as adult onset primary cerebellar degeneration also needs to be considered in the differential diagnosis.
The treatment of ACD is proper nutrition, including thiamine, and cessation of drinking. Alcohol absti-nence and adequate calorie intake, along with thiamine supplementation, may result in symptom improvement.11
Submitted on May 5, 2005