Evaluating the Remote Effects of Stroke With MRI and PET Scans

Objective: Following a stroke, not only is there dysfunction of the lesioned area, but there
is also remote functional depression of non-lesioned areas. This functional depression,
called diaschisis, likely contributes to the functional deficit of the patient.

The objective of this study is to obtain a better understanding of the pathophysiology of
diaschisis with the integrated methods of neuroimaging (positron emission tomography (PET)
and proton magnetic resonance spectroscopy (H-MRS)).

Study population: We will recruit patients with subcortical stroke in the subacute state and
in the chronic state, and normal controls.

Design: The stroke lesion will be the basal ganglia, internal capsule, thalamus, or
cerebellum. The frontal cortex, including the motor cortex, is chosen as a remote area.
Neurochemical changes in the diaschitic area will be investigated by measuring the glucose
metabolic rate with PET, and concentrations of neurochemically important metabolites, such
as gamma-aminobutyric acid (GABA) and glutamate, with H-MRS.

Outcome measures: Metabolic change in the diaschitic areas relative to the contra-lateral
unaffected side will be calculated as a laterality index. First, this index will be compared
among patient groups and control group. As a second analysis, the relationship of glucose
metabolism measured by PET and concentrations of the metabolites detected by H-MRS will be
evaluated.

- INCLUSION CRITERIA:

Patients will have a clinically and radiologically documented stroke in the subacute (2
weeks to 6 months to after onset) or the chronic state (more than 6 months after onset),
having a lesion in subcortical regions including the basal ganglia, thalamus, internal
capsule, or a combination of these structures, or cerebellum unilaterally. These lesions
can extend to the surrounding areas, however not including the cerebral areas where H-MRS
ROI will be located. Both ischemic infarction and hemorrhage will be included; however, in
cases of hemorrhage, we will exclude cases with deformation in the cerebral hemisphere due
to mass effect of the hemorrhage, hydrocephalus, or extension to the ventricles. Patients
will be 18 years of age or older.

Healthy controls entering the study must be free of serious somatic disease as determined
by a standard physical and neurological examination. Controls will be aged over 18 years.

Female patients and controls of child bearing potential will have a pregnancy test and
specific interview prior to the study to ensure that pregnant patients will not
participate in the study. Both patients and controls will be asked to abstain from alcohol
for one week before each of the PET and H-MRS scans.

EXCLUSION CRITERIA:

A. Patients with MRI findings consistent with brain tumors, trauma or AVMs will be
excluded.

B. Patients with multiple stroke lesions will be excluded, except for prior asymptomatic
lacunar infarctions or stroke lesions which are not known to cause diaschisis in the
frontal cortex (occipital cortex).

C. Patients with severe stenosis (greater than 70%) or occlusion in internal cervical
arteries and in the proximal portions of middle or frontal cerebral arteries detected by
angiography or MRA will be excluded. Subjects with medical disorders which can affect the
concentration of cerebral metabolites, including renal failure, hepatic failure and
untreated electrolyte abnormality will be excluded. Subjects with poorly controlled
diabetes mellitus (casual plasma glucose concentration greater than or equal to 200 mg per
dL (11.1 mmol per L) or fast plasma glucose concentration greater than or equal to 126 mg
per dL (7.0 mmol per L) will be excluded. Subjects who are taking sleeping drugs or
tranquilizers will be asked to stop taking them for two days prior to each of the PET and
H-MRS scans.

D. Subjects with a pre-stroke history of schizophrenia or bipolar disorders will be
excluded.

E. Subjects with implanted devices such as pacemakers, medication pumps or defibrillators,
metal in the cranium except mouth, intracardiac lines, history of shrapnel injury or any
other condition/device that may be contraindicated or prevent the acquisition of MRI.

F. Subjects with cancer will be excluded.

G. Patients not capable of giving an informed consent will be excluded

H. Ethnic origin and race will not be biased for inclusion.

Participation of children:

Children will be excluded from the study because we need to study a homogeneous group of
subjects by age and developmental changes in metabolites will complicate this study.
Additionally, young children will not be sufficiently cooperative for the long periods of
testing. Moreover, the radiation dose of the PET studies would subject them to relatively
greater risk than the adults.