Neurophysiological Markers in Patients With Craniofacial Dystonia and Their Relatives

The objective of this study is to evaluate paired-pulse inhibition of the three responses of
the electrically elicited blink reflex (BR) and the eye blink rate (EBR)in patients with
craniofacial dystonia and their first degree relatives in order to determine whether
abnormalities of inhibition can represent a marker of genetic predisposition for the
development of dystonia. It is unclear why some relatives of patients with craniofacial
dystonia do not develop dystonic symptoms. One possible explanation is that the development
of dystonia is a two-stage process: first, loss of inhibition, which may be genetically
determined, and second, exposure to an environmental trigger such as excessive repetitive
movements. There is good evidence that focal dystonia is a genetically determined disorder,
but the responsible gene remains undetermined. Patients, their first degree relatives and
normal volunteers will undergo BR testing using validated electrophysiological tests of
recovery cycle. The main outcome measure of the study is impaired inhibition in up to 50% of
first degree relatives of patients with focal dystonia which would serve as biologic marker
for the carrier state. A second outcome measure is the EBR. In those individuals with this
genetic marker of impaired inhibition, future linkage analysis studies could be performed to
identify the causative gene.

- INCLUSION CRITERIA:

Three groups of subjects shall be studied: 1) patients with craniofacial dystonia, 2)
first degree relatives of patients with craniofacial dystonia, 3) age matched control
group. The inclusion of the group of relatives will be valuable to study, as these
individuals have shared similar environment backgrounds as patients but remain free of
symptoms. Patients and their relatives 18 years or older will be enrolled through the
Human Motor Control Clinic, NINDS, NIH under protocol 93-N-0202: "Diagnosis and Natural
History Protocol for Patients with Different Neurological Conditions". Patients with
dystonia, enrolled in Protocol 85-N-0195, "Efficacy and Pathophysiology of Botulinum Toxin
for Treatment of Involuntary Movement Disorders' will also be eligible for participation
in the study. Diagnosis of dystonia will rely on review of medical record, history, and
clinical evaluation. Age matched volunteers over 18 years-old entered into the study must
be free of neurological disease as determined by a standard physical and neurological
examination.

INCLUSION CRITERIA FOR VIDEOTAPING:

Patients with idiopathic BSP or Meige-Syndrome (=BSP plus oromandibular dystonia), their
first degree relatives and age matched volunteers

Age18 years or older

Eye blink rate at rest more than 27 per minute (patients only)

EXCLUSION CRITERIA:

Patients, their first degree relatives and normal volunteers with any significant medical
or psychiatric illness, pregnancy, history of epilepsy, concurrent use of tricyclic
antidepressants, neuroleptic agents, or any other licit or illicit drug that could affect
brainstem excitability will not be eligible for this study. Subjects who have a pacemaker,
an implanted medication pump, metal objects inside the eye or skull (for example, after
brain surgery or a shrapnel would) or any recent (less than 3 months) brain lesions will
not be included in this study. Patients who have received botulinum toxin injection less
than three months prior to the day of testing will also be excluded.

EXCLUSION CRITERIA FOR VIDEOTAPING:

Other disease with involuntary blinking (Hemifacial spasm, Tic disorder, Tardive
Dyskinesia, Blepharitis)

Taking the following medications: antidepressants, anxiolytics, anticonvulsants,
antipsychotics, antiparkinson, hypnotics, stimulants, and/or antihistamines

Subject's objection to being videotaped while performing different activities

First degree relatives and age matched volunteers who are diagnosed with a neurological or
psychiatric disease or medication that alter the blink frequency.