Transcranial Magnetic Stimulation in Spino-Cerebellar Ataxia

Spinocerebellar Ataxia (SCA) refers to a family of genetic diseases that cause progressive problems with gait and balance, as well as other debilitating symptoms. This is a randomized controlled pilot study to test a novel therapeutic intervention that uses noninvasive magnetic brain stimulation to improve functional outcomes in patients with SCA. The study will include quantitative evaluations of gait, balance, and brain physiology to examine possible objective end-points for a future, larger multi-site clinical trial. The investigators anticipate that patients receiving the real intervention will show a functional gain.

Spinocerebellar Ataxia (SCA) refers to a family of genetic diseases that cause progressive problems with gait and balance, as well as other debilitating symptoms. There is no cure for SCA and a lack of an effective symptomatic treatment.

Investigators will recruit 20 patients with genetically-confirmed SCA to use a novel approach - noninvasive transcranial magnetic stimulation (TMS) - to improve balance, gait, and posture in patients with SCA. Half will be randomly assigned to a real intervention, and half to a sham (control) intervention. The TMS intervention will consist of 20 stimulation sessions over a four week period. At baseline and follow-up, patients will undergo comprehensive assessments including several SCA rating scales, along with sophisticated tests of balance (ie. walking, standing, and muscle coordination). Patients will also complete a series of neurophysiologic tests to evaluate the function of the cerebellum and its connections before and after the intervention.

Investigators anticipate patients receiving real TMS will show better balance, fewer falls, and improved mobility, while those undergoing sham stimulation will show no benefits. If our prediction is correct, this study will provide evidence-based support for a new treatment to improve the lives of patients with SCA.

Eligibility Criteria:
Inclusion Criteria:

* Outpatients with ataxia as diagnosed by a movement disorder specialist and confirmed by clinically obtained genetic testing of the patient and/or in a first-degree relative of the patient.
* Women of child-bearing potential must use a reliable method of contraception and must provide a negative pregnancy test at entry into the study
* Stable on doses of all medications for at least 30 days prior to study entry and for the duration of the study
* The ability to ambulate
* A score of three or higher (worse) on the 'gait' subsection of the Scale of the Assessment and Rating of Ataxia (SARA) rating scale.

Exclusion Criteria:

* Any unstable illness or concomitant medical condition that, in the investigator's opinion, precludes participation in this study, including disorders that may affect gait or balance (i.e., stroke, arthritis, etc).
* The presence of clinically significant abnormalities on screening CBC, CMP or EKG.
* Pregnancy or lactation
* Concurrent participation in another clinical study
* A history of substance abuse
* The presence of psychosis, bipolar disorder, untreated depression (BDI greater than or equal to 21), or history of suicide attempt.
* Dementia or other psychiatric illness that prevents the patient from giving informed consent (Mini Mental Status Exam score less than 24).
* Legal incapacity or limited legal capacity.
* Ataxia derived from any cause other than genetically-confirmed SCA (including but not limited to alcoholism, head injury, Multiple Sclerosis, olivo-ponto-cerebellar atrophy or multiple system atrophy).
* No medication is an absolute exclusion from TMS. Medications will be reviewed by the responsible MD and a decision about inclusion will be made based on the following:

  1. The patient's past medical history, drug dose, history of recent medication changes or duration of treatment, and combination with other CNS active drugs.
  2. The published TMS guidelines review of medications to be considered with TMS.
* History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG.
* TMS and MRI-Specific exclusion criteria including:

  1. Known metal in the head (such as a surgical aneurysm clip) or a history of prior neurosurgical procedures.
  2. Ferromagnetic bioimplants activated by any electronic, mechanical or magnetic means, such as cochlear implants, pacemakers, medication pumps, vagal stimulators, deep brain stimulators, neurostimulators, biostimulators, or ventriculo-peritoneal shunts.
  3. Subjects who have or might have bullet fragments or other shrapnel (veterans or workers exposed to metal in their work environment).
  4. Subjects with metallic paint (e.g. color contact lenses, tattoos, metallic eyeliner)
  5. Subjects expressing significant claustrophobia.