Neurophysiological Studies in Patients With Paroxysmal Hyperkinetic Movement Disorders

Objective: The primary objective of this study is to determine the brain regions responsible
during attacks for psychogenic paroxysmal hyperkinetic movement disorders using functional
magnetic resonance imaging (fMRI). The secondary objective is to determine the
neurophysiology during attacks for the same subjects compared to normal controls using
electroencephalography (EEG) and Startle Reflex.

Study population: Psychogenic paroxysmal hyperkinetic movement disorder patients and a
control group of healthy volunteers.

Design:

fMRI: Anatomical MRI and fMRI sequences are performed to obtain blood-oxygenation
level-dependent (BOLD) imaging of brain activation during (1) triggered or provoked
involuntary hyperkinetic movements and voluntary imitated movements in subjects with
psychogenic paroxysmal hyperkinetic movement disorders and (2) voluntary imitated movements
and rest states in healthy volunteers.

EEG: EEG will be recorded for jerk-locked back-averaging analysis.

Startle Reflex: Electromyography (EMG) will be recorded during exposure to auditory stimuli.

Outcome measures:

fMRI: BOLD will be obtained using baseline correction.

EEG

Startle Reflex: The latency, mean amplitude, and habituation of EMG amplitude will be
measured.

- INCLUSION CRITERIA:

Psychogenic paroxysmal hyperkinetic movement patients:

A. Established diagnosis of psychogenic hyperkinetic movement disorders. The diagnosis
will be established by the preliminary screening in the NINDS Movement Disorders
Outpatient Clinic, based on review of medical record, history, clinical evaluation, and
videotapes of an attack.

B. Patients with clear onset stereotyped and defined hyperkinetic attacks.

C. Patients only with paroxysmal attacks of hyperkinetic movements.

D. Age 8 or older.

E. A reproducible trigger of paroxysmal hyperkinetic attacks, such as sudden movement,
startle or prolonged exercise, which will produce attacks at least with 50% consistency.

F. Patients whose attacks can be precipitated easily.

G. Patients with typical attack involving unilateral extremities.

H. Patients taking medication that may influence the central nervous system, such as
phenytoin, phenobarbital, carbamazepine, clonazepam, and antidepressants (but not limited
to these) will be asked to hold the medication prior to the study. A sufficient drug
washout period will be established dependant upon the individual drug. Subjects may be
admitted to the NIH if necessary. They will be asked to abstain from alcohol and caffeine
24 hours prior to the study as well.

Normal Subjects:

A. Normal volunteers ranging from 8 to 65 will be included. Normal volunteers would be
recruited from people who are registered as HMCS Normal Volunteers. All subjects should
have a valid Clinical Center Medical Record Number.

B. Alcohol abstention is required for all subjects for both fMRI and EEG for 24 hours
before the study.

EXCLUSION CRITERIA:

Psychogenic paroxysmal hyperkinetic patients:

A. Age younger than 8 years old.

B. Patients with attacks that involve head and neck movements, axial movements, bilateral
limb involvement, or violent attacks that typically make patients fall to the ground. With
respect to children, violent attacks are defined as any attack that can potentially result
in injury (hitting the head, falls, violent flailing, hitting furniture or walls)

C. Previous history of or MRI findings consistent with brain tumors, strokes, trauma or
arterial venous malformations.

D. Contraindication to MRI such as having devices not compatible with MRI (pacemaker, an
implanted medical pump, brain stimulators, etc.), metallic prostheses in their body (metal
pins and rods, heart valves, cochlear implants, etc.), and history of working with metals
in the past, since such persons may potentially have small metal fragments in the eye
without being aware of it.

E. Any diagnosis of progressive neurological disorders other than psychogenic paroxysmal
hyperkinetic movement disorder.

F. Any history of significant medical disorders requiring chronic treatment with other
drugs that affects the CNS, which cannot be stopped.

G. Women who are pregnant or nursing. Female subjects of childbearing potential (including
all girls after menarche) will have specific interview and a pregnancy test prior to the
study (before each imaging procedure if required) to ensure that they are not pregnant or
nursing.

H. Any subject who is not capable of giving an informed consent. This will be determined
at the initial evaluation at NINDS clinic. Patients with Mini Mental Score less than 25 or
significant psychiatric history will be further evaluated by detailed neuropsychiatric
testing, or consultation with a psychiatrist.

Normal Volunteers:

A. Normal subjects younger than 8 years and older than 65 will be excluded.

B. Normal subjects with MRI findings consistent with organic brain lesions such as brain
tumors, stroke, trauma or AVMs will be excluded.

C. Normal subjects with a history of significant medical disorders such as cancers, or
requiring continuous treatment with drugs will be excluded.

D. Subjects with mental disorders will be excluded.

E. We will not scan pregnant women because safety of high magnetic field to fetus is not
established. Therefore, we will administer a urine pregnancy test for any female subjects
of childbearing potential 24 hours prior to functional MRI scan.