Characteristics of a Diverse Cohort of Stroke Patients with SARS-CoV-2 and Outcome by Sex.

BACKGROUND AND PURPOSE: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with stroke. The role of sex on stroke outcome has not been investigated. To objective of this paper is to describe the characteristics of a diverse cohort of acute stroke patients with COVID-19 disease and determine the role of sex on outcome. METHODS: This is a retrospective study of patients with acute stroke and SARS-CoV-2 infection admitted between March 15 to May 15, 2020 to one of the six participating comprehensive stroke centers. Baseline characteristics, stroke subtype, workup, treatment and outcome are presented as total number and percentage or median and interquartile range. Outcome at discharge was determined by the modified Rankin Scale Score (mRS). Variables and outcomes were compared for males and females using univariate and multivariate analysis. RESULTS: The study included 83 patients, 47% of which were Black, 28% Hispanics/Latinos, and 16% whites. Median age was 64 years. Approximately 89% had at least one preexisting vascular risk factor (VRF). The most common complications were respiratory failure (59%) and septic shock (34%). Compared with females, a higher proportion of males experienced severe SARS-CoV-2 symptoms requiring ICU hospitalization (73% vs. 49%; p = 0.04). When divided by stroke subtype, there were 77% ischemic, 19% intracerebral hemorrhage and 3% subarachnoid hemorrhage. The most common ischemic stroke etiologies were cryptogenic (39%) and cardioembolic (27%). Compared with females, males had higher mortality (38% vs. 13%; p = 0.02) and were less likely to be discharged home (12% vs. 33%; p = 0.04). After adjustment for age, race/ethnicity, and number of VRFs, mRS was higher in males than in females (OR = 1.47, 95% CI = 1.03-2.09). CONCLUSION: In this cohort of SARS-CoV-2 stroke patients, most had clinical evidence of coronavirus infection on admission and preexisting VRFs. Severe in-hospital complications and worse outcomes after ischemic strokes were higher in males, than females.

Dipyridamole-induced headache and lower recurrence risk in secondary prevention of ischaemic stroke: a post hoc analysis.

BACKGROUND AND PURPOSE: Our objective was to investigate the association between recurrent stroke risk and headache induced by extended-release dipyridamole (ER-DP) when administered alone or with low-dose aspirin (ASA+ER-DP). METHODS: This was a post hoc analysis of prospectively collected data on recurrent stroke risk and headache as an adverse event or reason for treatment discontinuation from the PRoFESS (N = 20,332) and ESPS2 (N = 6602) trials. Hazard ratios (HRs) for recurrent stroke were calculated using the Cox model. RESULTS: In PRoFESS, the 2.5-year recurrent stroke risk in patients receiving ASA+ER-DP was 8.2% in those with headache within 7 days of starting treatment and 9.4% in those without [HR 0.85, 95% confidence interval (CI) 0.73-0.98; P = 0.03]. Recurrent stroke risk was 5.0% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.2% in those who did not (HR 0.52, 95% CI 0.35-0.77; P = 0.001). No such difference was observed in clopidogrel-treated patients. In ESPS2, risk of recurrent stroke was 6.2% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.8% in patients who did not (HR 0.62, 95% CI 0.31-1.27; P = 0.19) and 7.3% in patients who discontinued ER-DP due to headache by day 90 versus 13.2% in those who did not (HR 0.53, 95% CI 0.27-1.04; P = 0.06). CONCLUSIONS: Patients taking ASA+ER-DP in PRoFESS who developed headache had significantly reduced stroke recurrence risk versus those without headache. Similar (non-significant) findings for ASA+ER-DP and ER-DP in ESPS2 suggest that dipyridamole-induced headache may reflect better cerebrovascular function.

Baseline differences between vascular cognitive impairment no dementia reverters and non-reverters.

BACKGROUND: The underlying factors of reversion from cognitive impairment to normal cognitive functioning in stroke are not well understood. We compare demographic, cognitive and imaging factors in Vascular Cognitive Impairment, No Dementia (Vascular CIND) patients who revert to normal cognitive functioning to Vascular CIND patients who do not revert. METHODS: Thirty-one ischaemic stroke patients, who met classification criteria for Vascular CIND, were >49.5 years old, met NINDS stroke criteria, and were free from additional neurological illness, completed baseline and 1-year examinations. Forty-five per cent of the Vascular CIND participants reverted to no cognitive impairment at 1-year follow-up examination. RESULTS: There was greater cognitive impairment in non-reverters on a summary score spanning several neuropsychological domains and on psychomotor and working memory summary scores. There were no differences on demographic factors or in stroke severity between reverters and non-reverters. Structural MRI analyses revealed no baseline differences in number of strokes, stroke volume or stroke location. However, there was greater frontal white matter hyperintensity load in the non-reverter group. CONCLUSIONS: These results suggest that Vascular CIND reversion may be a function of a combination of baseline neuropsychological function and location of cerebrovascular disease.

Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novel Helicobacter species.

BACKGROUND: In the autumn of 1992, a novel form of chronic, active hepatitis of unknown etiology was discovered in mice at the National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), Frederick, Md. A high incidence of hepatocellular tumors occurred in affected animals. The disease entity was originally identified in A/JCr mice that were untreated controls in a long-term toxicologic study. PURPOSE: Our original purpose was to determine the origin and etiology of the chronic hepatitis and to quantify its association with hepatocellular tumors in mice of low liver tumor incidence strains. After a helical microorganism was discovered in hepatic parenchyma of diseased mice, we undertook characterization of the organism and investigation of its relationship to the disease process. METHODS: Hepatic histopathology of many strains of mice and rats, as well as guinea pigs and Syrian hamsters, in our research and animal production facilities was reviewed. Steiner's modification of the Warthin-Starry stain and transmission electron microscopy were used to identify bacteria in the liver. We transmitted the hepatitis with liver suspensions from affected mice and by inoculation with bacterial cultures. Bacteria were cultivated on blood agar plates maintained under anaerobic or microaerophilic conditions and characterized morphologically, biochemically, and by 16S rRNA sequence. RESULTS: We report here the isolation of a new species of Helicobacter (provisionally designated Helicobacter hepaticus sp. nov.) that selectively and persistently colonizes the hepatic bile canaliculi of mice (and possibly the intrahepatic biliary system and large bowel), causing a morphologically distinctive pattern of chronic, active hepatitis and associated with a high incidence of hepatocellular neoplasms in infected animals. CONCLUSIONS: The novel Helicobacter is a likely candidate for the etiology of hepatocellular tumors in our mice. The Helicobacter-associated chronic active hepatitis represents a new model to study mechanisms of carcinogenesis by this genus of bacteria. IMPLICATIONS: Adenocarcinoma of the stomach, the second most prevalent of all human malignancies world-wide, is associated with infection at an early age with Helicobacter pylori. Infection leads to several distinctive forms of gastritis, including chronic atrophic gastritis, which is a precursor of adenocarcinoma. H. hepaticus infection in mice constitutes the only other parallel association between a persistent bacterial infection and tumor development known to exist naturally. Study of the H. hepaticus syndrome of chronic active hepatitis and liver tumors in mice may yield insights into the role of H. pylori in human stomach cancer and gastric lymphoma.

Are there clinical differences between familial and nonfamilial Alzheimer's disease?

OBJECTIVE: The purpose of the study was to determine whether there are differences in clinical characteristics in two groups of patients with Alzheimer's disease, those reported to have a family history of dementia and those without a family history of dementia. METHOD: Using a data set from an Alzheimer's disease patient registry, funded as part of a National Institute on Aging cooperative agreement, the authors made comparisons of sociodemographic and clinical variables in a group of 462 patients with Alzheimer's disease, 172 reported to have at least one first-degree relative with dementia and 290 classified with no family history. RESULTS: Patients with a presumptive family history differed from those without a family history in two ways: the course of dementia was described as having a fast rather than a slow progression from onset of symptoms to diagnosis, and caregivers reported a higher prevalence of family history of psychiatric disorders. There were no significant differences in age at onset, duration, female gender, aphasia and apraxia, handedness, family history of Down's syndrome, or number of children, brothers, and sisters. CONCLUSIONS: The association of faster course and family history of psychiatric disorders in the patients with a family history of dementia is consistent with the hypothesis of heterogeneity, but the overall results could also be explained by a genetic-environmental model of Alzheimer's disease.

An empirical evaluation of the Global Deterioration Scale for staging Alzheimer's disease.

OBJECTIVE: Although the Global Deterioration Scale has been widely used since its publication in 1982, its stages are based on implicit assumptions about the linearity, temporality, and interdependence of cognitive, functional, and behavioral impairment in Alzheimer's disease. The authors evaluated the validity of these assumptions and tested the hypothesis that psychopathology and functional impairment would occur in earlier stages than the Global Deterioration Scale predicts. METHOD: The analyses were based on data on 324 patients with Alzheimer's disease who were selected from a registry of such patients. Data analyses included 1) descriptive statistics on the frequency of psychiatric symptoms and difficulties with activities of daily living and 2) logistic regression, with symptoms and functional impairment as independent variables, to test for significant changes in patients' status between stages of the Global Deterioration Scale. RESULTS: More than 50% of the patients at stage 2 displayed psychopathology, and 32% had two or more symptoms. The significant increase in psychiatric symptoms occurred between stages 3 and 4, not between stages 5 and 6 as predicted by the Global Deterioration Scale. Impairment in functional status was observed at all stages, and significant increases occurred between stages 3 and 4 as well as between stages 5 and 6. CONCLUSIONS: Psychiatric symptoms and functional impairment occur earlier than predicted by the Global Deterioration Scale, and the rate of change is also different from that specified in the scale. Separate scales to describe cognitive, clinical, and functional status may be the best way to describe the illness until better multidimensional instruments are developed.

Stroke prevention.

Stroke is ideally suited for prevention. It has a high prevalence, burden of illness, and economic cost, and safe and effective prevention measures. The estimated $30 billion that is being spent for stroke each year in the United States should not come as a surprise given the approximately 3 million stroke survivors and 400,000 to 500,000 new or recurrent stroke cases annually. Stroke remains the third leading cause of death among adults and has been targeted for cost containment by managed care health systems and other insurers. The US Public Health Service in conjunction with the National Health Promotion and Disease Prevention Objectives has set a goal to reduce stroke deaths to 20 per 100,000 by the year 2000. This goal could be attained as the estimate of "preventable" strokes could be as high as 80%. In this article, I will review the status of stroke risk factors, prevention approaches to reduce stroke, clinical trial data from primary and secondary stroke prevention studies, and future directions in stroke prevention.

Personality changes in Alzheimer's disease.

We profiled personality changes that were measured cross-sectionally on the Blessed Dementia Scale in 80 patients with Alzheimer's disease who were examined at a dementia clinic. The most common personality changes were diminished initiative/growing apathy (61.3%), relinquishment of hobbies (55.0%), and increased rigidity (41.3%). The least frequent personality change was sexual misdemeanor (3.8%). Discriminant function analysis showed that the Global Deterioration Scale, the Clinical Rating Scale for Symptoms of Psychosis in Alzheimer's Disease, and the duration of dementia symptoms were the best predictors to classify personality change in an overall score of personality. However, cognitive impairment, as measured by the Blessed Memory-Information-Concentration Test and Mini-Mental State Examination, was not a good predictor of overall personality change. Personality and behavioral changes are common in Alzheimer's disease and may not be attributed entirely to intellectual impairment.

Predictors of survival in clinically diagnosed Alzheimer's disease and multi-infarct dementia.

Duration of survival from time of first evaluation was studied in 61 patients with clinically diagnosed Alzheimer's disease (senile dementia of the Alzheimer type [SDAT]) and 34 patients with clinically diagnosed multi-infarct dementia (MID). Duration of survival did not differ significantly between MID and SDAT. However, since MID patients were younger at onset, MID patients had a lower life quotient than SDAT patients. Race, sex, and age at onset were not predictive of survival in SDAT. History of hypertension, elevated systolic blood pressure, lower scores on tests of Block Designs, and Logico-Grammatical Comprehension predicted shorter survival in SDAT. Age at onset and race were not predictive of survival in MID. Male sex, lower educational attainment, as well as low scores on tests of Logico-Grammatical Comprehension, Digit Span, Naming, Verbal Fluency, and receptive vocabulary, predicted shorter survival in MID.

Embolic stroke complicating systemic lupus erythematosus.

Embolic stroke complicating systemic lupus erythematosus has been infrequently reported. We examined a 25-year-old woman who suddenly became hemiplegic. Two-dimensional echocardiography identified a source of emboli. At cardiac surgery, friable thrombotic vegetations were found adhering to the mitral valve leaflets, left ventricular septal wall, and chordae tendineae. At autopsy several weeks later, careful pathologic examination of the heart failed to reveal evidence of thrombus formation or endocarditis. An embolus identical in appearance to the thrombotic vegetations described at cardiac surgery was found lodged in the left middle cerebral artery underlying the recent brain infarction. To our knowledge, this is the first report of embolic stroke in systemic lupus erythematosus caused by extensive cardiac thrombus formation in the absence of underlying endocarditis.

Lateral thalamic infarcts.

A patient with occlusion of the proximal posterior cerebral artery (PCA), a lateral thalamic infarct, and hemisensory loss later developed hemianopia and hemiparesis and had extensive PCA territory infarction in the midbrain, the lateral portion of the thalamus, and the occipital lobe noted at necropsy. Two other patients had lateral thalamic infarcts on computed tomography, normal angiographic findings, and presumed thalamogeniculate artery branch occlusion. There are three clinical syndromes associated with lateral thalamic infarction: (1) hemisensory loss, hemiataxia, and involuntary movements; (2) pure sensory stroke; and (3) sensory-motor stroke. Ataxia, adventitious movements, and sensory loss are due to infarction of the lateral, posterolateral, and posteromedial ventral nuclei caused by occlusion of the PCA proximal to the thalamogeniculate artery branches or by occlusion of large thalamogeniculate arteries. Pure sensory and sensory-motor strokes are due to smaller infarcts in the posterolateral-posteromedial ventral complex and adjacent internal capsule caused by occlusion of penetrating artery branches of the thalamogeniculate arteries.

Aphasia after left thalamic infarction.

We examined a 70-year-old woman who became aphasic after a left thalamic infarction. Computed tomographic scan showed injury that was largely limited to the ventral anterior and rostral ventral lateral thalamic nuclei. Speech was characterized by reduced voice volume, impaired auditory and reading comprehension, perseverations, intermittent use of jargon, fluctuations in the ability to perform confrontation naming, extraneous intrusions, verbal paraphasia, intact repetition skills, and fluent speech that was laconic but grammatically correct. We propose that the deficits after left thalamic injury can be grouped into the following four large clusters: extrapyramidal deficits (decreased or fading voice volume), deficits in lexical access (anomia, verbal paraphasia), deficits in vigilance (neologisms, intrusions, fluctuating performance, jargon, perseverations), and comprehension defects.

Risk factors for dementia associated with multiple cerebral infarcts. A case-control analysis in predominantly African-American hospital-based patients.

OBJECTIVE: To clarify risk factors for dementia associated with cerebral infarction. DESIGN: Case-control study. SETTING: The study was conducted in a hospital setting. PATIENTS: The subjects were consecutive patients with acute stroke with multiple cerebral infarctions who were admitted to the hospital between November 1, 1987, and December 1, 1990. They were predominantly elderly African Americans. Index cases met criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, for multi-infarct dementia, whereas control subjects were patients with multiple infarcts who did not have dementia. There were 61 multi-infarct disease index cases and 86 controls without cognitive impairment. MAIN OUTCOME MEASURES: Demographic and cardiovascular disease risk factor variables. RESULTS: Index cases were older (mean [+/- SD] age, 75.5 +/- 9.7 vs 69.6 +/- 9.1 years), were less well educated (odds ratio, 4.37; confidence interval, 2.12 to 9.04), had lower annual incomes (odds ratio, 8.82; confidence interval, 2.38 to 32.70), more frequently had a family history of dementia (odds ratio, 3.61; confidence interval, 1.09 to 11.96) and laboratory evidence of proteinuria (odds ratio, 3.66; confidence interval, 1.54 to 8.71), had lower scores on neuropsychological tests, had more neurologic signs and symptoms, and were more functionally impaired in activities of daily living. Multiple logistic regression analysis showed that advanced age, lower educational attainment, history of myocardial infarction, and recent cigarette smoking were positively associated with case status and systolic blood pressure level was negatively associated with case status. CONCLUSIONS: Cardiovascular disease risk factors may be modifiable predictors of dementia associated with cerebral infarction. Additional well-designed epidemiologic studies are needed to clarify these associations.

Caudate infarcts.

Eighteen patients had caudate nucleus infarcts (10 left-sided; 8 right-sided). Infarcts extended into the anterior limb of the internal capsule in 9 patients, and also the anterior putamen in 5 patients. Thirteen patients had motor signs, most often a slight transient hemiparesis. Dysarthria was common (11 patients). Cognitive and behavioral abnormalities were frequent, and included abulia (10 patients), agitation and hyperactivity (7 patients), contralateral neglect (3 patients, all right caudate), and language abnormalities (2 patients, both left caudate). The majority of patients had risk factors for penetrating artery disease. Branch occlusion of Heubner's artery, or perforators from the proximal anterior or middle cerebral arteries were the posited mechanism of infarction.

Calcific cerebral embolism in systemic calciphylaxis.

Calciphylaxis represents a rare complication of end-stage renal disease with hyperparathyroidism. We report the case of a 26-year-old woman with systemic calciphylaxis secondary to chronic renal failure who developed mitral annular calcification and a right middle cerebral artery stroke. The high-density lesion seen on CT scan of the brain probably represents a calcified cerebral embolus originating from the mitral valve.

Transient global amnesia and thalamic infarction.

We describe the clinical and neuroradiologic features of a patient with two episodes of transient amnesia who later developed persistent amnesia and an acute infarction in the left thalamus. The neurobehavioral manifestations were strikingly similar in all three episodes. Cranial computed tomography was normal following the first two episodes. Thalamic ischemia could explain some cases of transient global amnesia.

Symptoms of amaurosis fugax in atherosclerotic carotid artery disease.

Amaurosis fugax is a term used to describe transient monocular visual loss due to atherosclerosis of the ipsilateral internal carotid artery. It is differentiated from other causes of transient monocular blindness, especially retinal migraine. It is said that amaurosis fugax episodes are short in duration and only occasionally include "positive" visual phenomena such as scintillations. Monocular migraine is more prolonged and often accompanied by scintillations. We studied 37 patients with amaurosis fugax and angiographic evidence of carotid atherosclerosis ipsilateral to the symptomatic eye. Nearly one-third of the patients had long attacks or positive visual phenomena. In many patients, transient monocular visual loss due to carotid atherosclerosis cannot be differentiated from retinal migraine based on clinical symptoms alone.

Headache in acute cerebrovascular disease.

Headache features were compared in 51 patients with acute subarachnoid hemorrhage (SAH), 61 with intraparenchymal hemorrhage (IPH), and 160 with ischemic stroke (IS). SAH patients had more sentinel headaches, more onset headaches, and more bilateral and severe onset headaches than patients with IPH or IS. Vomiting with onset headache was more common in SAH and IPH. In stepwise logistic regression analysis, onset headache and vomiting were direct predictors of SAH, but were inversely related to IS. Sentinel headache was not a predictor of underlying stroke mechanism. The data suggest that some headache features are more frequently associated with particular stroke subtypes and that onset headache and vomiting may be important indicators of stroke mechanism.

Risk factors and their management for stroke prevention: outlook for 1999 and beyond.

Stroke is a leading cause of death and morbidity, but incidence rates vary dramatically from one population to another. The reasons for this heterogeneity are being explored in several large-scale epidemiologic studies around the world. Much of the heterogeneity in stroke can be related to the prevalence of risk factors, but some populations have a higher stroke incidence than would be predicted from risk factor levels. Hypertension, including borderline hypertension, is probably the most important stroke risk factor based on degree of risk and prevalence. However, cardiac morbidity, cigarette smoking, diabetes, physical inactivity, and high levels of alcohol consumption are also strongly related to stroke risk. High levels of blood cholesterol and homocysteine may also increase stroke risk. Mortality after stroke is highest within the first 30 days but remains elevated to a degree that depends on the presenting stroke syndrome, stroke subtype, and other co-morbidities. Lacunar strokes have the best short- and long-term prognoses. Strokes due to large-vessel atherosclerosis frequently worsen; these and cardioembolic strokes have the poorest long-term prognosis. The risk for recurrence is also highest within 30 days after a first stroke, depending on the type of infarct, history of hypertension, and blood glucose levels on admission. Predictors of late recurrence include cardiac disease, hypertension, and heavy alcohol use. Only about half of stroke survivors are independent 6 months after a stroke, and quality of life is decreased. Understanding factors that predispose to stroke and determine its outcome will help in the design of acute stroke trials and in prevention programs.

Ischemia in the territory of a hypoplastic vertebrobasilar system.

BACKGROUND: Congenital variations in the configuration and size of the cerebral vessels may predispose to ischemic stroke. OBJECTIVES/METHODS: To illustrate that a hypoplastic basilar artery may lead to posterior circulation ischemia in adults, eight cases are reported from two university medical centers. RESULTS: Five men and three women with a mean age of 49.8 years are reported. Four of the patients had other conventional stroke risk factors. Two patients had brainstem strokes, and six had TIA. All patients had hypoplastic basilar arteries. Seven patients had at least one hypoplastic vertebral artery (bilateral in five cases), and six patients had both posterior cerebral arteries originating from the internal carotid arteries. CONCLUSIONS: A hypoplastic basilar artery is frequently accompanied by vertebral artery hypoplasia, and this can predispose adults to posterior circulation ischemia. This entity can be suspected on the basis of MR angiogram, but conventional angiography will provide definitive diagnosis. Optimal medical and surgical treatment of this condition is unresolved.