Lithium Treatment for Patients With Spinocerebellar Ataxia Type I

Overview

This study will evaluate the side effects and tolerability of the drug lithium in patients with spinocerebellar ataxia type I (SCA1) an inherited disorder caused by loss of nerve cells in parts of the brain. Symptoms include ataxia (difficulty walking) and loss of muscle coordination and strength. Recent studies suggest that lithium may be helpful in treating some SCA1 symptoms. People between 18 and 65 years of age with SCA1 who have only difficulty walking or who have difficulty walking as well as tremor, hand incoordination or speech problems, may be eligible for this study. Participation requires three hospital admissions at the NIH Clinical Center and one outpatient visit. Participants undergo the following tests and procedures: Admission 1 (2-6 weeks) * Medical history, physical examination, blood and urine tests, electrocardiogram. * Evaluation of SCA1 symptoms (balance, walking, dexterity, tremor, memory, mood and concentration). * Monitoring of liquid intake and output (urine) and weight changes. * Lithium treatment Start treatment and remain in hospital until the blood level of the drug is stabilized; continue treatment at home after hospital discharge. Admission 2 (2-4 days, 4 weeks after hospital discharge). * Repeat of some or all of the procedures done at the first admission. * Continue lithium in hospital and at home after discharge, with local physician checking laboratory values as needed. Admission 3 (2-4 days, 8 weeks after Admission 2). * Repeat of some or all of the procedures done at other admissions. * Stop lithium. Outpatient Visit (4 weeks after Admission 3) * Evaluation of SCA1 symptoms. * Blood and urine tests.

Objective Evaluation of tolerability and safety of lithium in SCA1 patients. Study Population A total of 10 molecularly diagnosed SCA1 patients divided in two groups. One group would be composed of 5 patients with gait difficulty only and 5 patients with gait difficulty and tremor, hand incoordination or speech difficulties. Design Patients will be admitted to the NIH Clinical Center for initiation and titration of Lithium until high therapeutic levels currently accepted for the treatment of Bipolar affective disorder are achieved (1.0-1.2 mmol/L) or a maximum tolerated dose. During their admissions, they will have neurological evaluations, ataxia and tremor evaluations, timed-up-and-go testing, quality of life assessment, questionnaires evaluating sleep, balance confidence and depression, memory testing, alertness assessment and quantitative balance/sway evaluations. Parameters and side effect profiles will be assessed at baseline, 1 month (plus or minus 5 days) and 3 months (plus or minus 5 days) after achievement of therapeutic levels. They will also have an exit evaluation one month (plus or minus 5 days) after discontinuation of Lithium also at the NIH. For their baseline evaluation and titration, patients will be admitted to the NIH for 4 weeks plus or minus 2 weeks. Evaluation at 1 month (plus or minus 5 days) and 3 months (plus or minus 5 days) Outcome Measures Primary Outcomes 1. Incidence of side effects 2. Side effect profile Secondary Outcomes 1. Timed-up-and-go test 2. ICARS score 3. SARA score 4. Modified Falls Efficacy Scale 5. Quantitative Sway/Balance assessment 6. Tremor Rating Scale: * Part A Tremor location/severity rating * Part B Handwriting and drawings * Part C Functional disabilities resulting from tremor 7. Questionnaires related to sleep, depression (Beck Depression Inventory) (BDI), alertness (Computerized Continuous Performing Tasks) and memory (Mini Mental State Examination) 8. Dexterity evaluation At-Home Testing Program device