Neill R. Graff-Radford

Nonhemorrhagic infarction of the thalamus Behavioral, anatomic, and physiologic correlates

We studied five patients with nonhemorrhagic thalamic infarction with neuropsychological tests, CT, and somatosensory evoked responses (SERs). The three patients with left thalamic lesions had abnormalities of language, memory, visuospatial processing, intellect, and personality—changes compatible with dementia. The two patients with right thalamic lesions were not aphasic and did not have verbal memory defects, but were otherwise comparable. Four lesions occurred in the tuberothalamic artery territory and one in the deep interpeduncular artery territory. SERs revealed a delay in the first negative peak after P14 in the tuberothalamic patients, and a delay in the third negative peak (N60 in all patients.

Variables predicting surgical outcome in symptomatic hydrocephalus in the elderly

We prospectively studied 30 older patients who had shunt surgery for symptomatic hydrocephalus and measured outcome using serial videotaping of gait, neuropsychological testing, and the Katz index of activities of daily living. Twenty-three patients improved and 7 did not. Using univariate analysis and the Fisher exact test, we found that the following variables were significantly related to outcome: (1) time B-waves present on 24-hour CSF pressure record; (2) anterior/posterior ratio on slice 4 of regional cerebral blood flow study; (3) duration of dementia prior to surgery; and (4) gait abnormality preceding dementia. The following variables showed a trend towards significance: (1) time CSF pressure > 15 mm Hg; and (2) scoring either pass or fail on the Multilingual Visual Naming Test. We conclude that several variables are significantly associated with surgical outcome in symptomatic hydrocephalus in the elderly and can be used in deciding whether to recommend surgery.

Elevated Gonadotropin Levels in Patients With Alzheimer Disease

OBJECTIVE To determine whether gonadotropin levels are elevated in patients with Alzheimer disease (AD). PATIENTS AND METHODS We measured luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels from stored plasma samples from 284 patients seen at a tertiary care center. We also reviewed their medical charts to record age and estrogen use in the women. The primary aim of our study was to determine whether gonadotropin levels were elevated in 134 patients with AD compared with levels from 45 patients with frontotemporal dementia (FTD) and 105 cognitively normal controls. RESULTS Although overlap between LH and FSH levels was considerable, LH (P=.046) and FSH (P=.007) were significantly elevated in estrogen-free women with AD (LH: median, 26.3 IU/L; interquartile range, 14.9-34.6 IU/ L; FSH: median, 62.0 IU/L; interquartile range, 45.9-78.5 IU/L) compared with normal controls (LH: median, 20.1 IU/L; interquartile range, 13.7-25.3 IU/L; FSH: median, 47.7 IU/L; interquartile range, 34.1-57.5 IU/L). Levels of LH were also significantly higher (P=.03) in estrogen-free women with AD compared with women with FTD (LH: median, 20.7 IU/L; interquartile range, 19.0-28.5 IU/L; FSH: median, 53.3 IU/L; interquartile range, 27.6-77.9 IU/ L). When we controlled for age, no differences in LH and FSH were observed in men with AD compared with normal controls. CONCLUSIONS Gonadotropin levels are elevated in some patients with AD, ie, women not taking estrogen. Elevated gonadotropin levels may have a role in the production of amyloid-beta protein, which is related to formation of senile plaques. Therefore, elevated gonadotropin levels may be involved in the pathogenesis of AD.

Idiopathic normal pressure hydrocephalus and systemic hypertension

Nineteen patients with idiopathic normal pressure hydrocephalus (NPH) were treated with intraventricular shunts. Ten of the 14 who improved and 14 of the total group had systemic hypertension. The prevalence of hypertension in both the improved and whole NPH groups was significantly greater than in a control group with dementia (N = 122) and the published prevalence of hypertension in the US population for this age group. Four possible mechanisms for this association are discussed.

Regional Cerebral Blood Flow in Normal Pressure Hydrocephalus

Regional cerebral blood flow (rcbf) was studied preoperatively and at 2 and 6 months postoperatively in 22 normal pressure hydrocephalus patients using xenon-133 inhalation and single photon emission computed tomography. Sixteen of the 22 patients improved (improved group) and six did not (unimproved group). The following comparisons were made: (1) preoperative rcbf in the improved group, to 14 normal elderly volunteers and to that in 59 SDAT (senile dementia of the Alzheimer type) patients; (2) preoperative rcbf in the improved and unimproved groups to determine if rcbf could predict surgical outcome; (3) pre- to postoperative rcbf in the improved group to see if increased cbf accounted for clinical improvement. The findings were: (1) preoperative rcbf in the improved group was lower than that in normal controls but was the same as that in SDAT; however, the ratios of rcbf values in anterior and posterior brain regions were significantly different between improved group and SDAT (p = 0.02); (2) an anterior/posterior ratio of 1.05 correctly classified surgical outcome in 19/22 patients; five of six in the unimproved group were above this cut off while 14/16 in the improved group were below; (3) in the improved group rcbf increased at 2 but not at 6 months after surgery without a corresponding reduction of clinical signs, supporting the notion that increase in cbf probably does not account for clinical improvement in normal pressure hydrocephalus.

The Role of Callosal Connections in Speech Prosody

A 39-year-old right-handed woman suffered an aneurysmal hemorrhage damaging the anterior four-fifths of the corpus callosum as shown on MRI. Computer-aided acoustical analyses of fundamental frequency (Fo) contours and durational patterns were performed on emotive and nonemotive utterances at 4 weeks, 4 months, and 1 year postsurgery. The patient read sentences in each of five tones (happy, sad, angry, neutral, questioning) or with emphasis on certain words. She showed little Fo distinction with intended mood at 4 weeks, but her performance improved over time. This improvement in speech production was accompanied by an improvement in perceptual judgments of her intended tone by six normal listeners. Fo patterns characteristic of emphatic stress and question forms were found at all test periods, but again improved with time. Durationally, the patient showed appropriate emotive and nonemotive distinctions on most sentences. These results provide acoustic evidence that interhemispheric connections via the corpus callosum are important to proper Fo programming, especially emotive distinctions. The results suggest that the right hemisphere contributes to Fo programming but, following callosal damage, such programming can later be performed by the left hemisphere.

Anterior choroidal artery territory infarction: a small vessel disease.

To investigate the cause(s) of infarction in the anterior choroidal artery territory, we studied 31 patients (18 men, 13 women) aged 19-82 (mean 58) years, with infarction in this territory documented by computed tomography. All patients were evaluated within 30 days after infarction and had carotid artery studies (arteriography in 17, duplex ultrasound in 14). Fifteen patients had echocardiography. Risk factors for atherosclerosis were chronic hypertension in 20 patients, smoking in 17, diabetes in 10, age greater than 69 years in eight, and elevated serum cholesterol concentration in three. The percentage of patients with extracranial carotid artery stenosis (four of 31, 13%) and the severity of stenosis (mild in two, moderate in two) were similar to that reported in neurologically asymptomatic individuals. The percentage of patients with intracranial carotid artery stenosis (one of 17, 6%) or potential cardiac sources of emboli (two of 31, 6%) was also low. Our findings suggest that infarctions in the anterior choroidal artery territory usually result from small-vessel disease. Associated carotid artery stenosis and potential sources of cardiac emboli are rare and may be coincidental.

Examining the relationship between computed tomography and neuropsychological measures in normal and demented elderly.

Correlational analysis of CT and neuropsychological measures in patients with dementia revealed more predictive relationships in degenerative and vascular subgroups that in a multi-aetiology group. Normal and dementia patients were then matched for age, sex and educational background, and analysed together. The ventricular/brain ratios of the bodies of the lateral ventricles and of the third ventricle correlated most highly with neuropsychologic performance. Canonical analysis revealed a correlation coefficient of 0.725 between the sets of CT and neuropsychological measures, which increased to 0.78 when a degenerative subgroup only was considered. Discriminant function analysis indicated that the combination of CT and neuropsychological measures was more powerful in discriminating normals from dementia patients than CT or neuropsychological measures alone.

Symptomatic congenital hydrocephalus in the elderly simulating normal pressure hydrocephalus

In a series of 30 older patients shunted for symptomatic hydrocephalus, we found 3 with a head circumference at or greater than the 98th percentile. In 2, we demonstrated deterioration over 6 and 12 months by serial videotaping of gait and neuropsychological testing. In the 3rd, serial lumbar punctures over a 6-month period gave temporary improvement. In each, CTs showed ventriculomegaly without transependymal flow. One patient had an Arnold-Chiari type I abnormality identified by MRI. All had systemic hypertension. CSF pressure monitoring showed CSF pressure > 15 mm Hg 39% of the time in 1 patient, and 100% in another. All improved with ventriculoperitoneal shunting. Patients with probable compensated congenital hydrocephalus who functioned well throughout most of their lives may become symptomatic as they age but improve with shunt surgery. The head circumference should be measured in all older hydrocephalic patients.

Unruptured fusiform aneurysms of the posterior circulation with thalamic infarction.

Three patients with unruptured fusiform aneurysms of the posterior circulation presented with nonhemorrhagic thalamic infarctions. All of the aneurysms were seen on enhanced computed tomographic (CT) scans preangiographically. Although unruptured fusiform aneurysms are probably a rare cause of nonhemorrhagic thalamic infarction, their importance lies in the therapeutic implications of this diagnosis. In patients with nonhemorrhagic thalamic infarction, we suggest careful scrutiny of the blood vessels on enhanced CT scans.