Safety of hypercapnic challenge: cardiovascular and neurologic considerations.

The hemodynamic, cerebrovascular, and neurologic effects of hypercapnia with 4% and 6% CO2 were retrospectively reviewed in 217 patients referred for regional CBF (rCBF) procedures. Inhalation of CO2 significantly increased rCBF, blood pressure, and pulse from baseline. The findings suggest a higher incidence of side effects with 6% CO2 concentration and an equivalent vasoreactivity to 4%. We recommend the use of 4% CO2 for hypercapnic stimulation, and present safety guidelines for its use.

Risk of dementia in first-degree relatives of patients with Alzheimer's disease and related disorders.

First-degree relatives of patients with Alzheimer's disease (AD) are at greater risk for dementia when compared with the relatives of their healthy peers, but not when compared with the relatives of patients with Parkinson's disease. This may indicate that the risk of dementia in these relatives is not specific to AD or that these studies are biased. We obtained a family history and vital status information on each first-degree relative of patients attending a clinic and in a group of recruited healthy elderly subjects. Patients formed two groups: probable AD and other forms of dementia or cognitive disorders without dementia. The odds of dementia in first-degree relatives did not differ between patient groups. The odds of dementia in relatives of patients with probable AD or other forms of dementia was six times that in the relatives of the healthy elderly subjects. The cumulative incidence of dementia increased with age in the first-degree relatives of all subjects. Approximately 50% of the first-degree relatives of patients with AD were demented by age 91 years, but almost the same number of the other patient group's relatives were demented as well. That figure was never reached in the healthy elderly subject's relatives. Because the risk of dementia in first-degree relatives of patients with AD was similar to that for patients with other disorders, we cannot exclude the possibility that this is the result of selection and information biases. Our investigation implies that the increased risk of dementia may not be specific to relatives of patients with AD; the risk may also be increased in first-degree relatives of patients with other neurologic disorders.

Risk factors for cerebrovascular disease as correlates of cognitive function in a stroke-free cohort.

We investigated the relationship between risk factors for cerebrovascular disease and cognitive function in 249 stroke-free community volunteers (age, 70.8 +/- 6.7 years; education, 12.3 +/- 4.6 years) who were given tests of memory, language, visuospatial, abstract reasoning, and attentional skills. Using logistic regression analyses, we examined hypertension, diabetes mellitus, myocardial infarction, angina, hypercholesterolemia, and cigarette smoking as potential correlates of performance within these cognitive domains. Controlling for demographic factors within the logistic models, diabetes mellitus was a significant independent correlate of abstract reasoning deficits (odds ratio, 10.9; 95% confidence interval, 2.2 to 54.9) and visuospatial dysfunction (odds ratio, 3.5; confidence interval, 1.2 to 10.7), while hypercholesterolemia was a significant independent correlate of memory dysfunction (odds ratio, 3.0; confidence interval, 1.4 to 6.6). Prolonged exposure to vascular risk factors such as diabetes mellitus and hypercholesterolemia may lead to atherosclerotic disease, possibly resulting in "silent" infarctions or impaired cerebral blood flow and a decline in cognitive functioning.

Diagnosis of dementia in a heterogeneous population. Development of a neuropsychological paradigm-based diagnosis of dementia and quantified correction for the effects of education.

A brief diagnostic battery of neuropsychological tests was developed for a large-scale epidemiological study of dementia. We operationally defined dementia as defective memory and defective performance in at least two other areas, including orientation, abstract reasoning, construction, and language. Criterion scores for defining defective performance on each test were developed. In a pilot study that used 51 different subjects with a working diagnosis based on physicians' assessment (ie, 32 demented and 29 nondemented subjects), the test-based diagnosis agreed with the working diagnosis in all but two cases. The test battery was then applied to 430 healthy elderly subjects. Eighteen percent of those with 8 or less years of education met criteria for dementia compared with 5% of those with more than 8 years of education. We computed education-corrected scores for each test with the use of residuals from the regression of each test score on education. Based on corrected scores, 12 subjects were reclassified as nondemented and 11 as demented. Subjects who were reclassified as demented were significantly more impaired in activities of daily living than nondemented subjects who were not reclassified. Activities of daily living in subjects who were reclassified as nondemented did not differ from those in demented subjects who were not reclassified. These findings suggest that the neuropsychological battery may have utility in the diagnosis of dementia. However, neuropsychological performance may be influenced by education, and some form of adjustment, such as correction for activities of daily living, may be required in epidemiological studies.

Diagnosis of dementia in a heterogeneous population. A comparison of paradigm-based diagnosis and physician's diagnosis.

Each of 430 subjects received a diagnosis using two independent methods: a test-based quantitative paradigm and a semistructured neurological examination by a physician. The paradigm diagnosis was based on a battery of tests that assessed short- and long-term verbal memory and short-term nonverbal memory, orientation, construction, abstract reasoning, and language. The subjects came from a community in Manhattan County, in New York City, and were characterized by diversity with respect to both ethnicity (29.1% black, 33.4% Hispanic) and educational level (23.5% with 6 or fewer years of education, 25.6% college educated). Based on the paradigm, 10.5% of subjects received diagnoses of dementia, 29.1% of cognitive impairment, and 60.5% of normal. Based on the physician's diagnosis, 9.8% were demented, 21.6% cognitively impaired, and 68.6% normal. There was agreement between the two diagnostic methods for 71.8% of subjects. Diagnostic disagreement (n = 121) was in most cases between normal and cognitively impaired (71.0%) or between cognitively impaired and demented (21.5%). There were only nine cases (7.5%) in which a subject was judged demented by one method and normal by the other. The reliability of each method with respect to the other was moderate (intraclass correlation coefficient, .62), while the reliability of a composite diagnosis based on both methods was much higher (.77). The paradigm was more likely than the physician to give the diagnosis of dementia to patients with low educational levels. The physician's diagnosis was strongly influenced by measures of functioning and by the mental status test administered in the semistructured neurological examination. Race and diagnosis were not related when the effect of education was controlled.(ABSTRACT TRUNCATED AT 250 WORDS)

Thalamic stroke. Presentation and prognosis of infarcts and hemorrhages.

Thalamic strokes in 62 patients selected from the Stroke Data Bank were studied to determine differences among 18 infarctions (INF), 23 localized hemorrhages (ICH), and 21 hematomas with ventricular extension (IVH). Stupor or coma at onset occurred more frequently in the IVH (62%) than in the INF (6%) or ICH (13%) groups and was reflected in significantly lower median Glasgow Coma Scores in the IVH group (7) than in the INF (15) and ICH (14) groups. Although ocular movements were more frequently abnormal in the IVH group compared with the ICH and INF groups, no significant differences were found in the frequency of motor or sensory deficits. Among the 62 strokes, 32 had restricted lesions of the posterolateral (n = 9), anterior (n = 3), paramedian (n = 7), and dorsal (n = 13) portions of the thalamus. Differences in consciousness and in motor, sensory, and oculomotor deficits were found among the topographic subgroups. Stroke-related deaths occurred in 52% of IVH cases, 13% of ICH cases, and no cases of INF. Median lesion volume as detected with computed tomography was greater in hemorrhages (INF, 2 cm3; ICH, 10 cm3; IVH, 16 cm3), with mortality related to increasing hematoma size. Coma, Glasgow Coma Score lower than 9, weakness score greater than 15 of a possible 30, abnormal ocular movements, and fixed pupils were also associated with stroke-related mortality. We conclude that the initial neurologic syndrome does not discriminate infarcts from intrathalamic hemorrhages. Ventricular extension, however, causes significantly more severe deficits and higher mortality.

Visual hemineglect and hemihallucinations in a patient with a subcortical infarction.

An alcoholic patient with a mainly right subcortical infarction developed contralateral left-sided neglect and then, in the context of alcohol withdrawal, unilateral hallucinations in the non-neglected right hemispace. It is hypothesized that an interruption of the striatocortical pathways could prevent the right hemisphere from representing appropriately internally produced stimuli.

Unilateral hyperhidrosis after cerebral infarction.

Unilateral hyperhidrosis occurred contralateral to acute cerebral infarctions in six patients. Two patients had localized infarctions of opercular cortex, while the other four had large strokes involving both superficial cortical and deep subcortical structures. The unilateral hyperhidrosis typically involved the face and arm and was transient, lasting 1 to 3 days. No other autonomic dysfunction occurred. One patient died, and the others had significant residual neurologic disability, thus indicating poor prognosis when this sign is present. Disruption of a pathway of cortical origin, inhibitory to contralateral sweating, is a proposed mechanism for the hyperhidrosis seen contralateral to acute cerebral infarction in these patients.

Reduced hypercapnic vasoreactivity in moyamoya disease.

We measured cerebral perfusion at rest and in response to CO2 in eight patients with moyamoya disease (MMD), using the 133xenon inhalation method to determine the effect of large-vessel occlusive disease on vasoreactivity. We studied three other groups for comparison, including four with bilateral internal carotid artery occlusions (BICAO), 11 with unilateral carotid occlusion (UICAO), and six with unilateral middle cerebral artery stem occlusion (UMCAO). Resting flows appeared to correlate with the severity of occlusive disease overall. Normocapnic perfusion was lowest in the group with BICAO and decreased in proportion to the degree of contralateral stenosis in the group with UICAO. Hypercapnic perfusion correlated with the apparent adequacy of angiographic collaterals. Reactivity was lowest in the MMD group (0.79%/mm Hg) whose collateral supply was limited to leptomeningeal anastomosis from the posterior cerebral artery, but highest in the patients with BICAO (2.72%/mm Hg), each of whom showed excellent posterior communicating artery flow. The clinical course of the MMD group was compatible with the syndrome of perfusion insufficiency with repeated ischemic attacks or a saltatory progression of an ischemic deficit; CT showed infarction in the borderzone territory. These results suggest that a severely reduced hypercapnic response may help to identify patients with ischemic syndromes due to perfusion failure in the borderzones, as in MMD.

Neurologic improvement in pure motor hemiparesis: implications for clinical trials.

Knowledge of the natural history of certain stroke subtypes is essential for the proper analysis and interpretation of clinical trials of stroke therapy. We evaluated the degree of weakness on admission and again 7 to 10 days later in 62 patients with pure motor hemiparesis (PMH) and 280 patients with motor deficits from other stroke syndromes (OSS). During the 7-to-10-day study interval, we found that the OSS group worsened slightly in motor function, whereas the PMH group improved (p = 0.01). Among those who improved in both groups, those in the PMH group improved to a greater extent than did those in the OSS group (p = 0.02). This occurred despite a greater frequency of worsening during the first 12 hours after stroke onset in the PMH group. By the fourth day following PMH onset, a majority of patients had improved, and this improvement was sustained until day 10. The two groups did not differ significantly in age, race, sex, history of cardiac disease, hematocrit, anticoagulation treatment, blood glucose, or medical complications in hospital. Lacunar infarcts occurred in 84% of PMH and 23% of OSS. Patients with PMH show significant spontaneous improvement in weakness within 7 to 10 days of admission, compared with patients with OSS. Stratification by admission stroke syndrome in clinical trials may be necessary before judging the efficacy, or lack thereof, of a therapeutic agent.

Dementia after stroke increases the risk of long-term stroke recurrence.

BACKGROUND: Although risk factors for first stroke have been identified, the predictors of long-term stroke recurrence are less well understood. We performed the present study to determine whether dementia diagnosed three months after stroke onset is an independent risk factor for long-term stroke recurrence. METHODS: We examined 242 patients (age = 72.0 +/- 8.7 years) hospitalized with acute ischemic stroke who had survived the first three months without recurrence and followed them to identify predictors of long-term stroke recurrence. We diagnosed dementia three months after stroke using modified DSM-III-R criteria based on neuropsychological and functional assessments. The effects of conventional stroke risk factors and dementia status on survival free of recurrence were estimated using Kaplan-Meier analyses, and the relative risks (RR) of recurrence were calculated using Cox proportional hazards models. RESULTS: Dementia (RR = 2.71, 95% CI = 1.36 to 5.42); cardiac disease (RR = 2.18, CI = 1.15 to 4.12); and sex, with women at higher risk (RR = 2.03, CI = 1.01 to 4.10), were significant independent predictors of recurrence, while education (RR = 1.90, CI = 0.77 to 4.68), admission systolic blood pressure >160 mm Hg (RR = 1.80, CI = 0.94 to 3.44) and alcohol intake exceeding 160 grams per week (RR = 1.86, CI = 0.79 to 4.38) were weakly related. CONCLUSIONS: Our results suggest that dementia significantly increases the risk of long-term stroke recurrence, with additional independent contributions by cardiac disease and sex. Cognitive impairment may be a surrogate marker for multiple vascular risk factors and larger infarct volume that may serve to increase the risk of recurrence. Alternatively, less aggressive medical management of stroke patients with cognitive impairment or noncompliance of such patients with medical therapy may be bases for an increased rate of stroke recurrence.

Hemodynamic role of ophthalmic artery collateral in internal carotid artery occlusion.

We performed duplex and transcranial Doppler studies in 36 patients with angiographically documented internal carotid artery occlusion (ICAO) to determine the effect of ophthalmic artery collateral (OAC) on measures of vascular resistivity both proximal and distal to the occlusion. Resistance in the common carotid artery, measured by the resistivity index, was significantly lower in the group with OAC than in those without OAC, indicating a shunt to the low resistance intracranial circuit. The pulsatility index (PI) of the Doppler signal in the ipsilateral middle cerebral artery, a measure of both inflow pressure and distal vascular resistance, did not differ between those with and without OAC. However, the presence of circle of Willis collateral pathways (anterior communicating and/or posterior communicating artery) did appear to have a significant effect on pulsatility. When both were present angiographically, PI was higher than in the group with only 1 Willisian collateral. These findings suggest that OAC has a marginal effect on vascular resistance in arterial bed distal to an ICAO, while Willisian collaterals appear to have a more important role in cerebral perfusion, as measured indirectly by Doppler methods.

Left hemiparalexia.

Three patients with left splenial lesions made paralexic errors restricted to the left end of words. Errors appeared more frequently when a correct response was highly dependent on the initial letter of the stimulus. One patient had full visual fields with hemialexia affecting the left visual field. The other two patients had complete right hemianopia. We attribute left-sided reading errors in the hemianopic patients to a retinotopically restricted disconnection pattern that selectively disrupts transfer of information originating from the peripheral left visual field. Functional resistance of the more numerous transcallosal projections representing visual field adjacent to the vertical meridian may account for such a pattern. The emergence of positional reading errors from retinotopically restricted left hemifield disconnection suggests that callosal information transfer during normal reading may primarily involve elemental sensory rather than lexical/semantic information.

The role of transcranial Doppler in confirming brain death: sensitivity, specificity, and suggestions for performance and interpretation.

We performed transcranial Doppler (TCD) examinations on 54 comatose patients over a 1-year period. Of 49 patients with technically adequate TCD examinations, 23 met criteria for determination of brain death by clinical and EEG criteria (21) or clinical criteria alone (2; EEG not performed). A TCD waveform abnormality, consisting of absent or reversed diastolic flow, or small early systolic spikes, in at least 2 intracranial arteries, occurred in 21 brain-dead patients, but in none of the other patients in coma. With appropriate guidelines for performance and interpretation, TCD could be incorporated into institutional protocols as a rapid and convenient alternative to EEG for confirmation of brain death.

Risk of dementia after stroke in a hospitalized cohort: results of a longitudinal study.

Stroke is considered the second most common cause of dementia, but the magnitude of the risk posed by stroke has not been fully clarified. The aim of this study was to determine the long-term risk of developing dementia after stroke onset in a hospitalized cohort. We prospectively examined 185 nondemented patients aged > or = 60 years hospitalized with ischemic stroke and 241 age-matched nondemented controls without stroke from the same community using neurologic, neuropsychological, and functional assessments given annually. Using criteria modified from the DSM-III-R, we diagnosed incident dementia based on the annual examination findings. We used life-table methods to estimate incidence in the two groups, Kaplan-Meier analysis to determine the proportion surviving without dementia, and Cox proportional-hazards analysis to compute the relative risk (RR) of dementia after 1 to 4 years of follow-up. The incidence of dementia was 8.4 per 100 person-years in the stroke group and 1.3 per 100 person-years in the control group. After 52 months of follow-up, the cumulative proportion (+/- SE) surviving without dementia was 66.3 +/- 5.5% for stroke and 90.3 +/- 4.3% for control subjects. The RR of dementia associated with stroke compared with controls was 5.5 (95% CI, 2.5 to 11.1) after adjusting for demographic factors. Older age at stroke onset and fewer years of education were significant covariates, but sex and race were not. A low score on the Mini-Mental State Examination at baseline was a significant predictor when added to this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Infarcts of the inferior division of the right middle cerebral artery: mirror image of Wernicke's aphasia.

We searched the Stroke Data Bank and personal files to find patients with CT-documented infarcts in the territory of the inferior division of the right middle cerebral artery. The most common findings among the 10 patients were left hemianopia, left visual neglect, and constructional apraxia (4 of 5 tested). Five patients had an agitated confusional state that was characterized by hyperactivity, restlessness, and easy distractibility. Motor and sensory abnormalities were not severe or persistent. The most common cause was cardiogenic embolism.

Confusion and memory loss from capsular genu infarction: a thalamocortical disconnection syndrome?

We examined six patients with an abrupt change in behavior after infarction involving the inferior genu of the internal capsule. The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation, suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia occurred in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients showed a focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. We infer that the capsular genu infarct interrupted the inferior and anterior thalamic peduncles, resulting in functional deactivation of the ipsilateral frontal cortex. These observations suggest that one mechanism for cognitive deterioration from a lacunar infarct is thalamocortical disconnection of white-matter tracts, in some instances leading to "strategic-infarct dementia."

Clinical discriminators of lobar and deep hemorrhages: the Stroke Data Bank.

Of the 1,805 patients with acute stroke enrolled in the Stroke Data Bank, 237 had parenchymatous hemorrhage. After excluding 34 secondary intracerebral and 31 infratentorial hemorrhage patients, a logistic regression analysis of the 172 patients with primary supratentorial intracerebral hemorrhage (ICH) elucidated clinical factors that distinguished the 65 patients with lobar hemorrhage (LH) from the 107 patients with deep hemorrhage (DH) located in the basal ganglia and thalamus. In LH, severe headache was more common than in DH, while hypertension and motor deficit were significantly less common. Patients with either LH or DH had a similar prognosis and mean Glasgow Coma Scale (GCS) scores, despite the hematoma volume measured on the initial CT being significantly greater for LH than DH. The presence of intraventricular extension (IVH) was more frequent in DH. The frequency of IVH increased with hematoma volume in LH, but remained constant for DH. Two CT variables (IVH and hematoma volume) that differed in these two hemorrhage groups were important predictors of coma (GCS less than or equal to 8) in a logistic regression model. Differences in the frequency of IVH may help explain why the degree of impairment in consciousness was similar in the two groups. Among patients with supratentorial ICH, location of the hematoma is related to both volume and IVH, which are important determinants of the level of consciousness.

Brain infarction severity differs according to cardiac or arterial embolic source.

We compared clinical and radiologic features between 246 cardiac embolism (EMB) and 66 arterial embolic (tandem arterial pathology [TAP]) patients selected from the 1,273 patients with cerebral infarction in the Stroke Data Bank. Diagnostic definitions accounted for the increased frequency of cardiac disease among patients with EMB compared with TAP (78.4% versus 29.3%), while transient ischemic attacks (32.3% versus 13.1%) and carotid artery bruit (15.1% versus 3.3%) were more prevalent in TAP than in EMB. Multiple logistic regression differentiated TAP and EMB further. The probability of a TAP diagnosis was increased by the CT finding of a superficial infarct alone (odds ratio [OR] = 4.6; 95% CI = 1.5 to 13.7) or by a higher admission hematocrit. The probability of EMB was greater in patients with an initial decreased consciousness (OR = 39.2; 95% CI = 4.0 to 381.3) or with an abnormal first CT (OR = 3.2; 95% CI = 1.2 to 8.6). These findings indicate that the two infarct subtypes differ in the location and extent of the cortical infarction, which argues for a smaller particle size, with smaller and more distal infarction in embolism from an arterial source compared with cardiogenic embolism.

Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.

Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.