The Effects of Repetitive Paired Associative Stimulation in Dystonia

Objective:

To investigate the effects of pairing brain and peripheral nerve stimulation in organic and
psychogenic dystonia to see if this technique can differentiate them.

Study Population:

We intend to do an internal pilot study of 6 patients with organic dystonia, 6 patients with
clinically definite psychogenic dystonia and 6 age-matched healthy volunteers. We will then
perform an analysis to see how many subjects we need to prove or disprove a difference
between groups.

Design:

Subjects will have a baseline screening visit, electromyography (EMG) and nerve stimulation,
sensory threshold testing, and measurements of brain excitability using motor evoked
potentials (MEPs) from transcranial magnetic stimulation (TMS). They will then undergo rapid
TMS repetitively paired with stimulation of a nerve in the arm. Outcome variables will again
be measured immediately after (T0), 30 minutes (T30) after, and 60 minutes (T60) after the
end of brain stimulation.

Outcome Measures

Primary outcome variable: Change in MEP amplitudes at T30 from baseline

Secondary outcome variables:

- Input-output curve parameters (measured at baseline, T0, T30, and T60)

- Temporal discrimination threshold (TDT)

Exploratory Measures

- Short interval intracortical inhibition (SICI), a measure of inhibition in the motor
cortex

- Influence of Val66Met BDNF polymorphism on the output variables

Repeated measures analyses of variance (ANOVA) will be used to investigate the following
three factors on the outcome variables: time (four levels: baseline, T0, T30 and T60) and
muscle (two levels: APB and FDI) as within-subject factor and group (three levels: organic
dystonia, psychogenic dystonia, and healthy controls) as between-subjects factor. The model
of repeated measures ANOVA will include the interactions between the three factors. If the
interaction between muscle and group is significant, the interaction between time and group
will be evaluated for each muscle separately. If significance is found for time and/or group,
then the evaluation will be followed by Tukey Kramer multiple pair-wise comparisons.

- INCLUSION CRITERIA:

- For the organic dystonia group: Primary focal dystonia diagnosed or confirmed by a
movement disorders neurologist, confirmed at the initial visit by a study
investigator.

- For the psychogenic dystonia group: Clinically established psychogenic dystonia or
probable psychogenic dystonia, according to the Fahn and Williams criteria confirmed
by a movement disorders neurologist.

- For the healthy volunteers group: Age-matched healthy volunteers three will be age
matched to pyschogenic dystonia group, and three will be age matched to organic
dystonia group.

- Adult patients (at least18 years old).

- Right handed.

- Ability to provide own consent

EXCLUSION CRITERIA:

- Dystonia affecting the right APB and/or FDI, or inability of the subject to perform
full range-of-motion exercises with the right FDI and/or APB.

- Medical condition impairing the subject's ability to comply with the study protocol as
judged by study investigator, such as but not limited to seizures, brain tumor,
stroke, bipolar disorder, depression, hearing problem, uncontrolled systemic
hypertension with values above 170/100, heart disease or lung disease, active
respiratory disease needing intervention; and pain preventing lying still for up to 40
minutes.

- Current or prior use of botulinum toxin within 3 months prior to TMS intervention.

- Current or prior use of CNS drugs (including antidepressants, anxiolytics,
anticonvulsants, antipsychotics, anti-parkinsonian drugs, hypnotics, stimulants,
and/or antihistamines) within 1 week prior to TMS intervention.

- Active drug or alcohol intake more than 7 alcohol drinks/week for women and more than
14 alcoholic drinks/week for men.

- Current pregnancy and lactating women. Menopausal status will be determined by the CNS
IRB criteria. In women of childbearing potential, a pregnancy test will be performed
at least 24 hours prior to TMS procedures.

- Presence of implanted devices such as pacemakers, medication pumps or defibrillators,
metal in the cranium except mouth, history of shrapnel injury or any other
condition/device that may be contraindicated

- Inability or unwillingness of subject to provide written informed consent.