White matter lesions and disequilibrium in older people. II. Clinicopathologic correlation.

OBJECTIVE To identify the cause of subcortical white matter lesions seen on magnetic resonance imaging in older patients with progressive deterioration of gait and balance. DESIGN Postmortem examination of three patients with objective impairment of gait and balance thought to be due to subcortical white matter lesions identified on magnetic resonance imaging. Brain sections were stained with routine methods and for glial fibrillary acid protein using an immunoperoxidase technique. PATIENTS Part of a prospective study of gait and balance problems in older people. None had a history of hypertension or discrete strokelike episodes. RESULTS Other than a few small infarcts in the basal ganglia and internal capsule in the patient with the mildest gait disorder, there were no gross or microscopic features on routine examination post mortem to explain the white matter hyperintensities on magnetic resonance imaging or the progressive gait deterioration. By contrast, immunohistochemical staining with anti-glial fibrillary acid protein showed prominent astrocytosis T2-weighted high-intensity signal areas on magnetic resonance imaging. CONCLUSIONS The astrocytes presumably swell as they take up extravasated protein at the site of a breakdown in the blood-brain barrier, and the increased water content per unit volume increases the magnetic resonance imaging proton signal. We hypothesized that the astrocytes may have been initially activated by small infarcts or subclinical ischemia, but the process then became self-perpetuating, ultimately involving most of the white matter and producing the severe gait disorder.