Most cerebellar ataxias cannot be cured, but cases that result from metabolic, hereditary, inflammatory, and immune-mediated etiologies can be treated with disease-modifying therapies, according to a review article published online ahead of print March 11 in Movement Disorders. Effective treatments include prescription drugs, high doses of vitamin E, and gluten-free diets.
“Clinicians must become familiar with these disorders because maximal therapeutic benefit is only possible when done early,” said Adolfo Ramirez-Zamora, MD, Philly Dake Chair in Movement Disorders at Albany Medical Center in New York. The review describes more than a dozen disorders. “These uncommon conditions represent a unique opportunity to treat incurable and progressive diseases.”
Thorough Examination Is Warranted
The initial evaluation of a patient with suspected cerebellar ataxia should include a complete assessment of his or her neurologic and non-neurologic features, said the researchers. The neurologist should determine the rate of onset or progression, family history, specific diagnostic signs, and brain MRI abnormalities. A detailed examination of potential acquired causes, which may include laboratory testing, also is recommended.
Alcohol and other commonly used drugs may cause chronic cerebellar injury, and the treatment is the removal of the drugs. Other drugs associated with ataxia are lithium, phenytoin, amiodarone, toluene, 5-fluorouracil, and cytosine arabinoside. Heavy metals, including organic-lead compounds, mercury, and thallium, may cause ataxia as well.
Treatment May Stop Progression
Ataxia with vitamin E deficiency presents as a slowly progressive spinocerebellar ataxia syndrome similar to Friedreich’s ataxia. Daily 800-mg doses of vitamin E typically stop disease progression and result in neurologic improvement, although recovery may be slow and incomplete, said the investigators. Vitamin E supplementation may be most beneficial if started in patients with less than 15 years of disease duration.
The neurologic symptoms of cerebrotendinous xanthomatosis include cerebellar ataxia, spastic paraparesis, extrapyramidal signs, sensorimotor peripheral neuropathy, seizures, and dementia. The disorder is easily treated with 250 mg of oral chenodeoxycholic acid administered three times daily. Potential side effects include diarrhea, restlessness, and irritability. “Instituting treatment as early as possible is crucial to prevent neurological deterioration,” said Dr. Ramirez-Zamora.
Patients with glucose transporter type 1 (GLUT1) deficiency syndrome may present with intellectual disability, epilepsy, motor impairment, or complex movement disorders. Data indicate that following a ketogenic diet effectively treats the manifestations of GLUT-1 deficiency and halts progression. This regimen can reduce movement disorders by 40% to 70% in most patients, regardless of the syndrome phenotype, the researchers said. Gluten ataxia often manifests as insidious-onset, progressive, pure cerebellar ataxia syndrome. Most patients with gluten ataxia have gaze-evoked nystagmus and other ocular signs of cerebellar dysfunction. Strict adherence to a gluten-free diet is the recommended treatment. In a systematic study, this diet was associated with significant improvement in performance in ataxia scores and on the subjective global clinical impression scale.
Ataxia associated with glutamic acid decarboxylase (GAD) most commonly entails gait ataxia. Limb ataxia, dysarthria, and nystagmus also may be present in patients with GAD-associated ataxia, and symptoms develop over weeks or years. “Patients with subacute presentation are more likely to respond to immunotherapy and achieve long-term response and good functional status,” said Dr. Ramirez-Zamora. The primary treatments, IV immunoglobulin and corticosteroids, have produced marked benefit.
“Recognizing potentially treatable causes of cerebellar ataxia is critical not only to implement targeted treatments, but also to institute management as early as possible to hopefully halt neurologic deterioration,” Dr. Ramirez-Zamora concluded.
—Erik Greb