Sergio E. Starkstein

Paralimbic frontal lobe hypometabolism in depression associated with Huntington's disease.

We measured regional cerebral glucose metabolism using 2-[18F]-fluoro-2-deoxy-D-glucose and positron emission tomography in depressed and nondepressed patients with early Huntingtons disease (HD), compared with appropriately matched controls. Caudate, putamen, and cingulate metabolism was significantly lower in patients with HD than in control subjects, independent of mood state. Orbital frontal-inferior prefrontal cortex hypometabolism, however, differentiated depressed patients from both nondepressed patients and normal controls. These findings implicate selective dysfunction of the paralimbic regions of the frontal lobes in the mood disorder of HD. The metabolic pattern is similar to that in depression associated with Parkinsons disease, suggesting that the integrity of pathways linking paralimbic frontal cortex and the basal ganglia may be integral to the normal regulation of mood.

Mechanisms of Mania after Brain Injury: 12 Case Reports and Review of the Literature

Twelve patients who developed mania after a brain lesion are reported. Ages ranged from 20 to 83 years. Five patients had brain tumors (three frontal meningiomas, one temporal meningioma, and one temporal astrocytoma), four patients had stroke lesions (one frontal, one temporal, and two thalamocapsular), two patients had a traumatic frontal closed head injury, and one patient had a pituitary adenoma resection. Although seven patients had lesions restricted to the right hemisphere, four had bilateral or midline damage and one had a left hemisphere lesion. Damage to structures functionally connected to the obitofrontal cortex, mainly in the right hemisphere, seems to be associated with secondary mania. The possible roles of monoaminergic, genetic, and perinatal factors in the pathogenesis of secondary mania are discussed.

Neuropsychological and neuroradiological correlates in Huntington's disease.

Measurements of cortical and subcortical atrophy were made on CT scans of 34 patients with Huntingtons disease. Significant correlations were found between the bicaudate ratio (BCR) and an eye movement scale (r = 0.44, p less than 0.01), and activities of daily living scale (r = 0.57, p less than 0.001) and the Mini-Mental State Exam (r = 0.49, p less than 0.01). No correlations were found between BCR values and severity of chorea or voluntary motor impairment. A detailed neuropsychological evaluation of 18 Huntingtons disease patients showed significant correlations between the BCR and Symbol Digit Modalities test (r = 0.65, p less than 0.01), and parts A (r = 0.72, p less than 0.001) and B (r = 0.80, p less than 0.0001) of the Trail Making Test. These data support work in primates that demonstrates the role of the caudate nucleus in cognitive and oculomotor functions, but not in motor control (which is governed by putamino-subthalamic systems). The specific cognitive skills correlated with caudate atrophy in Huntingtons disease are those reported in primate work to be served by the frontal-caudate loop system: eye movements, conceptual tracking, set shifting and psychomotor speed.

Brain atrophy in Huntington's disease - A CT-scan study

SummaryCT-scan measurements of cortical and subcortical atrophy were carried out in 34 patients with Huntingtons disease (HD). While a significant correlation was observed between parameters of subcortical atrophy (bicaudate ratio, bifrontal ratio and third ventricular ratio) and duration of the disease, there was no significant correlation between these parameters and age. On the other hand, measurements of cortical atrophy (frontal fissure ratio and cortical sulci ratio) correlated significantly with age but not with duration of the disease. When a group of 24 HD patients were compared on CT-scan measurements with a group of 24 age-matched normal controls, significant differences were obtained for all the variables examined, but the bicaudate ratio showed the highest sensitivity and specificity. Even mildly affected patients, with duration of motor symptoms less than 3 years had higher bicaudate ratios than age-matched controls.

Behavioral abnormalities induced by frontal cortical and nucleus accumbens lesions

In previous studies, we have demonstrated that in male rats, unilateral right hemisphere lesions of either the frontolateral cortex or the nucleus accumbens (NAS) result in significant postoperative locomotor hyperactivity. In the present study we carried out two experiments to assess whether the production of hyperactivity in response to these two lesions is mediated through a common mechanism. In the first experiment, male Sprague-Dawley rats received either unilateral frontocortical suction and/or unilateral electrolytic lesions of the NAS. Only rats with lesions of the right hemisphere (suction and/or electrolytic) developed locomotor hyperactivity. Similar lesions in the left hemisphere did not result in behavioral changes. While both right cortical and NAS lesions alone produced hyperactivity, there was no additive effect of both lesions. In the second experiment, the effect of cortical lesions on NAS dopaminergic activity was assessed. Male Sprague-Dawley rats received either a right, left or sham frontocortical suction lesion, and were sacrificed 1, 2, and 4 weeks after surgery. Right hemisphere suction lesions produced a significant bilateral increase in NAS and caudate nucleus dopamine turnover (as measured by DOPAC/DA ratio) 4 weeks post-lesion, while similar left hemisphere lesions did not. These findings suggest that lesions in the dorsolateral frontal cortex and NAS may affect locomotor activity through a common mechanism mediated through the NAS.

Unusual Manifestations of Basilar Artery Ectasia

Three patients with unusual presentations of basilar artery ectasia are described: subarachnoid hemorrhage was manifest in one and autonomic dysfunction developed in the other two. Aneurysmal rupture was the cause in the first patient, while compression of the brainstem and/or of the baroreceptor afferences of the IXth and Xth cranial nerves is postulated to be responsible for the symptoms found in the other two. Basilar artery aneurysms should be considered in cases with subarachnoid hemorrhage or autonomic dysfunction, particularly when diagnostic procedures fail to disclose other possible etiologies.