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. 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.

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.