This study will examine whether the motor cortex (the part of the brain that controls
movement) works properly in patients with primary lateral sclerosis (PLS), a disorder in
which voluntary movements are very slow.
Healthy volunteers between 40 and 75 years of age and patients with ascending PLS (a subset
of PLS) may be eligible for this study. Patients with ascending PLS have a slowing of
finger-tapping movements that corresponds to a particular abnormality of certain neuronal
(nerve cell) activity.
Participants perform a finger-tapping reaction time exercise while brain wave activity
(electroencephalography, or EEG) and muscle activity (electroymogram, or EMG) are measured.
The subject is seated in front of a computer screen. A signal appears on the screen and the
subject taps a key as quickly as possible in response to the signal.
For the EEG, brain activity is recorded by placing electrodes (small metal discs) on the
scalp with an electrode cap or glue-like substance. A conductive gel is used to fill the
space between the electrodes and the scalp to make sure there is good contact between them.
The brain waves are recorded while the subject taps his or her fingers very slowly. For the
surface EMG, electrodes filled with a conductive gel are taped to the skin.
Participants also undergo magnetic resonance imaging (MRI). This test uses a strong magnetic
field and radio waves to obtain images of the brain. During the procedure, the subject lies
still on a table that can slide in and out of the scanner - a narrow metal cylinder.
Scanning time varies from 20 minutes to 3 hours, with most scans lasting between 45 and 90
minutes. Subjects can communicate with the MRI staff at all times during the scan and can
ask to be moved out of the machine at any time.
Objective: Primary Lateral Sclerosis (PLS) is a clinical syndrome of progressive
spasticity. Patients with PLS have slow voluntary movements. In PLS, degeneration of
corticospinal tracts disrupts the communication between the motor cortex and motor neurons.
Normally, voluntary movements are preceded by EEG waveform changes that begin before the
movement occurs. These waveforms are called movement related cortical potentials (MRCPs).
The first part of the MRCP represents neural activity in the motor cortex. The goal of this
study is to determine whether the motor cortex and pre-motor cortex operate normally to
generate these intrinsic signals for voluntary movement in patients with PLS.
Study population: Patients with PLS of at least 3 years duration with slow finger tapping
movements will be studied. Patients must fulfill the clinical criteria for the ascending
subtype of PLS. They must also have a loss of corticospinal excitability as measured by
transcranial magnetic stimulation. Age matched normal volunteers will be studied as a
Design: Patients and normal volunteers will undergo a session of EEG recording while making
slow finger tapping movements. They will have an MRI of the brain, for the purpose of
localizing dipole positions of the MRCP components.
Outcome parameters: The peak amplitudes of components of the MRCPs will be compared between
patients and a healthy control group as the primary outcome measure. Localization of the
dipoles of the components is a secondary outcome measure.
1. Ages 40-75
2. Fulfill the proposed diagnostic criteria for PLS of Pringle 1992.
3. Have an ascending course of symptom progression.
4. Slow hand movements, as determined by measuring finger-tapping speeds of 20-65 taps
in 15 s.
5. Absent motor evoked potentials in hand muscles with 100% output of the MagStim200
transcranial magnetic stimulator.
Healthy adult volunteers ages 40-75 who are willing to participate.
1. Neurological diseases or conditions other than PLS.
2. Implanted devices, such as pumps, pacemakers, or metal fragments in the skull or eye.
3. Pregnancy as determined by urine pregnancy test within 48 hours of MRI study in women