Intravenous thrombolysis for large vessel or distal occlusions presenting with mild stroke severity.

BACKGROUND AND PURPOSE: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. METHODS: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. RESULTS: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 ± 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. CONCLUSIONS: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.

Sleep quality in survivors of critical illness.

PURPOSE: There is limited data regarding the sleep quality in survivors of critical illness, while the time course of the sleep abnormalities observed after ICU discharge is not known. The aim of this study was to assess sleep quality and the time course of sleep abnormalities in survivors of critical illness. METHODS: Eligible survivors of critical illness without hypercapnia and hypoxemia were evaluated within 10 days (1st evaluation, n = 36) and at 6 months after hospital discharge (2nd evaluation, n = 29). At each visit, all patients underwent an overnight full polysomnography and completed health-related quality of life questionnaires (HRQL). Lung function and electro-diagnostic tests (ED) were performed in 24 and 11 patients, respectively. RESULTS: At 1st evaluation, sleep quality and HRQL were poor. Sleep was characterised by high percentages of N1, low of N3 and REM stages, and high apnea-hypopnea index (AHI, events/h). Twenty-two out of 36 patients (61%) exhibited AHI ≥ 15 (21 obstructive, 1 central). None of the patients' characteristics, including HRQL and lung function, predicted the occurrence of AHI ≥ 15. At 6 months, although sleep quality remained poor (high percentages of N1 and low of REM), sleep architecture had improved as indicated by the significant increase in N3 [4.2% (0-12.5) vs. 9.8% (3.0-20.4)] and decrease in AHI [21.5 (6.5-29.4) vs. 12.8 (4.7-20.4)]. HRQL improved slightly but significantly at 6 months. Neither the changes in HRQL nor in lung function tests were related to these of sleep architecture. Six out of eight patients with abnormal ED at 1st evaluation continued to exhibit abnormal results at 6 months. CONCLUSIONS: Survivors of critical illness exhibited a high prevalence of obstructive sleep-disordered breathing and poor sleep architecture at hospital discharge, which slightly improved 6 months later, indicating that reversible factors are partly responsible for these abnormalities.

Burden of herpes simplex virus encephalitis in the United States.

Herpes simplex virus encephalitis (HSVE) is a disease of public health concern, but its burden on the healthcare of United States has not been adequately assessed recently. We aimed to define the incidence, complications and outcomes of HSVE in the recent decade by analyzing data from a nationally representative database. Healthcare Cost and Utilization Project databases were utilized to identify patients with primary discharge diagnosis of HSVE. Annual hospitalization rate was estimated and several preselected inpatient complications were identified. Regression analyses were used to identify mortality predictors. Key epidemiological factors were compared with those from other countries. Total 4871 patients of HSVE were included in our study. The annual hospitalization rate was 10.3 ± 2.2 cases/million in neonates, 2.4 ± 0.3 cases/million in children and 6.4 ± 0.4 cases/million in adults. Median age was 57 years and male:female incidence ratio was 1:1. Rates of some central nervous system complications were seizures (38.4%), status epilepticus (5.5%), acute respiratory failure (20.1%), ischemic stroke (5.6%) and intracranial hemorrhage (2.7%), all of which were significantly associated with mortality. In-hospital mortality in neonates, children and adults were 6.9, 1.2 and 7.7%, respectively. HSVE still remains a potentially lethal infectious disease with high morbidity and mortality. Most recent epidemiological data in this study may help understanding this public health disease, and the patient outcome data may have prognostic significance.

Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis.

Autoimmune encephalitis is a relatively new category of immune-mediated disease involving the central nervous system that demonstrates a widely variable spectrum of clinical presentations, ranging from the relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with refractory seizure. Due to its diverse clinical features, which can mimic a variety of other pathologic processes, autoimmune encephalitis presents a diagnostic challenge to clinicians. Imaging findings in patients with these disorders can also be quite variable, but recognizing characteristic findings within limbic structures suggestive of autoimmune encephalitis can be a key step in alerting clinicians to the potential diagnosis and ensuring a prompt and appropriate clinical work-up. In this article, we review antibody-mediated encephalitis and its various subtypes with a specific emphasis on the role of neuroimaging in the diagnostic work-up.

Predictors of Prolonged Hospital Stay in Status Migrainosus.

BACKGROUND: Patients with status migrainosus often need to be admitted due to the severity of their headaches. Their hospitalization is often prolonged due to poor headache control. Large sample studies looking into the factors associated with prolonged length of stay (pLOS) in status migrainosus are lacking. METHODS: We utilized the Nationwide Inpatient Sample database to identify 4325 patients with primary discharge diagnosis of status migrainosus. Length of inpatient stay (LOS) of more than 6 days (90th percentile of LOS) was defined as pLOS. Patient demographics, hospital characteristics, mood disorders, anxiety disorder, and common medical comorbidities were identified. Multivariable logistic regression was used to identify factors associated with pLOS. RESULTS: We found 402 patients with pLOS. Female gender, African American race, mood disorder, obesity, opioid abuse, congestive heart failure, and chronic renal failure were significant independent predictors of pLOS. Median inflation-adjusted cost of hospitalization was USD$3829 (interquartile range: 2419-5809). CONCLUSION: We were able to identify several factors associated with pLOS in status migrainosus. Most of the factors we found were similar to those known to increase the prevalence and severity of migraine in the general population. Knowledge of these factors may help physicians identify high-risk patients to institute early migraine abortive and prophylactic treatment in order to shorten the length of hospital stay.

Longitudinal myelitis, aseptic meningitis, and conus medullaris infarction as presenting manifestations of pediatric systemic lupus erythematosus.

A healthy boy developed subacutely progressive quadriparesis, complicated by sudden paraplegia, fever, and meningeal signs, diagnosed as longitudinal myelitis, aseptic meningitis, and conus medullaris infarction and identified as the presenting manifestations of neuropsychiatric systemic lupus erythematosus. Rapid expansion of the conus on serial neuroimaging led to emergent decompressive laminectomy and cord biopsy showing vasculitis and cord infarction. The patient had partial recovery after treatment with high-dose steroids. Increased vigilance is required when pediatric patients develop a similar subacute presentation on the ground of active systemic lupus erythematosus because it may herald the onset of a catastrophic neurological syndrome.

Predictors of recurrent stroke in African Americans.

BACKGROUND: Stroke incidence and mortality are disproportionately higher among African Americans than among whites. OBJECTIVE: To describe the recurrent stroke characteristics and determine the predictability of known vascular risk factors for stroke recurrence in African Americans. METHODS: The authors followed 1,809 African Americans in the African-American Antiplatelet Stroke Prevention Study with recent noncardioembolic ischemic stroke for recurrent stroke, recurrent stroke subtype, and disability. RESULTS: Of the subjects, 10.6% experienced a recurrent stroke during follow-up. The mean interval between eligibility and recurrent stroke was 325 days (median 287 days, SD = 224 days). Stroke recurrence resulted in an average 1.5-point increase in the National Institute of Health Stroke Scale (p < 0.001) and a 3.5-point decrease in modified Barthel Index (p < 0.001). Of previously nondisabled subjects, 48% became disabled or died after stroke recurrence (p < 0.0001). Longitudinal analysis resulted in a hazard for recurrent stroke for each 10-mm Hg increase in systolic blood pressure of 1.103 (95% CI: 1.031 to 1.179, p = 0.004), pulse pressure 1.123 (95% CI: 1.041 to 1.213, p = 0.003), and mean arterial pressure 1.123 (95% CI: 1.001 to 1.260, p = 0.048). Multivariate analysis revealed increases in the recurrent stroke hazard for increases in baseline Glasgow Outcome Score (1.449, 95% CI: 1.071 to 1.961, p = 0.016) and increases in longitudinal pulse pressure (1.009, 95% CI: 1.001 to 1.017, p = 0.029). CONCLUSION: Recurrent stroke leads to disability and disability predicts recurrent stroke. Hypertension is the most predictive modifiable stroke risk factor.

Factors determining headache at onset of acute ischemic stroke.

Headache is a frequent accompaniment of acute ischaemic stroke. The predisposing factors and underlying mechanisms are currently incompletely defined. We analysed prospectively collected data relevant to headache occurring at ischaemic stroke onset in consecutive patients included in the Henry Ford Hospital Stroke Data Bank. Patients with headache (HA+) and without headache (HA-) were compared for demographic factors, medical history, medications, examination findings, laboratory findings, and stroke localization and subtype. Group comparisons for categorical data were performed with chi(2) test, and for continuous variables with two-sample t-tests. Stepwise logistic regression analysis, including all variables with P<0.25, was used to define the independent predictors of onset headache. Three hundred and seventy-five patients had complete headache and clinical datasets and were included in the analysis (HA+, N=118; HA-, N=257). Multivariate analysis revealed that the independent predictors of HA+ were: infarct in the distribution of the posterior circulation [P=0.0076, odds ratio (OR) 2.15, 95% confidence interval (CI) 1.23, 3.77], absence of history of hypertension (P=0.0106, OR 0.48, 95% CI 0.27, 0.84), and treatment with warfarin at the time of the index stroke (P=0.0135, OR 4.89, 95% CI 1.39, 17.21). The occurrence of headache at onset of ischaemic stroke is determined by posterior circulation distribution of the ischaemic event, absence of history of hypertension and treatment with warfarin at the time of the index stroke. These results suggest that preserved elasticity and maintenance of the intracranial vasculature in a relaxed state, in combination with coagulation system derangements, and activation of dense perivascular afferent nerves, play a role in the pathogenesis of onset headache.

MRI-guided, open trial of abciximab for ischemic stroke within a 3- to 24-hour window.

The authors assessed the effect of IV abciximab on early neurologic improvement and ischemic lesion growth in 29 patients with supratentorial stroke and NIH stroke scale score (NIHSSS) > or = 4 (11.1 +/- 5.9), treated within 3 to 24 (13.6 +/- 5.5) hours of onset. The 48 to 72-hour NIHSSS improvement was 4.4 +/- 3.2 and the 24-hour lesion growth on DWI was +23% (-50%, +103%); 7/26 (27%) patients experienced lesion size decrease. Treatment of sub-24-hour stroke with abciximab improves early post-treatment neurologic status and often attenuates ischemic lesion growth.

Multiparametric MRI tissue characterization in clinical stroke with correlation to clinical outcome: part 2.

BACKGROUND AND PURPOSE: Multiparametric MRI generates different zones within the lesion that may reflect heterogeneity of tissue damage in cerebral ischemia. This study presents the application of a novel model of tissue characterization based on an angular separation between tissues obtained with the use of an objective (unsupervised) computer segmentation algorithm implementing a modified version of the Iterative Self-Organizing Data Analysis Technique (ISODATA). We test the utility of this model to identify ischemic tissue in clinical stroke. METHODS: MR parameters diffusion-, T2-, and T1-weighted imaging (DWI, T2WI, and T1WI, respectively) were obtained from 10 patients at 3 time points (30 studies) after stroke: acute (

Tissue plasminogen activator for acute ischemic stroke in patients with unruptured cerebral aneurysms.

Intracranial hemorrhage (ICH) is the most feared complication of thrombolytic therapy for acute ischemic stroke. There are limited data on the risks of thrombolysis in patients with asymptomatic intracranial aneurysm. We report 2 adults with signs of hemispheric ischemia who were successfully treated with intravenous tissue plasminogen activator (t-PA), despite the presence of asymptomatic intracranial aneurysm. The presence of an asymptomatic intracranial aneurysm may not necessarily preclude a good outcome from acute ischemic stroke treated with rt-PA. Selected patients harboring incidental, unruptured intracranial aneurysm may benefit from thrombolytics.

Agreement and variability in the interpretation of early CT changes in stroke patients qualifying for intravenous rtPA therapy.

BACKGROUND AND PURPOSE: Ischemic changes identified on CT scans performed in the first few hours after stroke onset, which are thought to possibly represent early cytotoxic edema and development of irreversible injury, may have important implications for subsequent treatment. However, insecurity and conflicting data exist over the ability of clinicians to correctly recognize and interpret these changes. We performed a detailed review of selected baseline CT scans from the NINDS rt-PA Stroke Trial to test agreement among experienced stroke specialists and other physicians on the presence of early CT ischemic changes. METHODS: Seventy baseline CT scans from the NINDS Stroke Trial were read and classified for the presence or absence of various early findings of ischemia by 16 individuals, including NINDS trial investigators, other neurologists, other emergency medicine physicians, and radiology or stroke fellows. CT scans included normal scans and scans from patients who later developed symptomatic intracranial hemorrhage, as well as scans on which the NINDS rt-PA Stroke Trial neuroradiologist identified clear-cut early CT changes. For each CT finding, kappa-statistics were used to assess the proportion of agreement beyond chance. RESULTS: kappa-Values (95% confidence interval [CI]) ranged from 0.20 (-0.20, 0.61) (fair agreement) to 0.41 (0.37, 0.45) (moderate agreement) among the 16 viewers, and the kappa-value was only 0.39 (0.29, 0.49) (fair) in answer to the question "do early CT changes involve more than one third of the MCA [middle cerebral artery] territory?" There was substantial variability within each specialty group and between groups. kappa-Values were only fair to moderate even among physicians experienced in selecting and treating acute stroke patients with rtPA. Observed agreement ranged from 68% to 85%. Physicians agreed on the finding of early CT changes involving >33% of the MCA territory 77% of the time, although the kappa-value of 0.39 suggested only moderate agreement beyond chance. CONCLUSIONS: There is considerable lack of agreement, even among experienced clinicians, in recognizing and quantifying early CT changes. Improved methods of recognizing and quantifying early ischemic brain damage are needed.

Cerebral venous thrombosis and anticardiolipin antibodies.

BACKGROUND AND PURPOSE: The association of cerebral venous thrombosis (CVT) with a variety of pathological states is well established. However, there are only rare isolated reports of CVT associated with anticardiolipin antibodies (aCL). METHODS: To clarify the clinical and neuradiological features as well as outcome of patients with CVT associated with aCL, we reviewed the records of all patients with CVT evaluated at our institution between 1989 and 1996 (retrospective and prospective) and systematically reviewed the pertinent literature. RESULTS: We identified 8 aCL+ and 7 aCL- patients with CVT. No patients with lupus anticoagulant (LA) were identified. The mean age was 23 +/- 11.01 (range, < 1 to 36) years in the aCL+ and 38 +/- 9.30 (range, 25 to 54) years in the aCL- patients (P = .016). Six of 8 aCL+ and 5 of 7 aCL- patients were women. The dural sinuses were involved in all aCL+ and in 6 of 7 aCL- patients, while deep venous system thrombosis occurred in 5 of 8 (63%) aCL+ and 1 of 7 (14%) aCL- patients. In the aCL+ patients CVT was associated with puerperium or oral contraceptive use (n = 6), and sickle cell trait (n = 1), and in the aCL- patients CVT was associated with systemic lupus erythromatosus (n = 1), myelodysplasti syndrome (n = 1), colonic cancer (n = 1), oral contraceptive use or puerperium (n = 3), and dehydration (n = 1). Seven aCL+ patients received either intrasinus urokinase or intravenous heparin sulfate, and 1 received aspirin. Four aCL+ patients developed new onset or worsening of preexisting migraine, 2 developed recurrent peripheral venous thrombosis, and 1 went on to have intracranial hypertension. Twenty additional patients with CVT associated with antiphospholipid antibodies (aPL) were found reported in the literature. The overall mean age was 36 +/- 11.6 (range, 21 to 62) years, and 14 (70%) were women. LA was present in 11 of 18 tested, aCL in 7 (35%), LA and aCL in 1, and the type of aPL was not reported in 3. The mean age for the aCL+ only group was 28 years and for the LA+ (with or without aCL+) was 34 years. Only 1 patient, whose aPL type was not specified, had thrombosis of the deep venous system in addition to involvement of the dural sinuses. CONCLUSIONS: Our series and review suggest that aCL may be an important factor contributing to development of CVT even in the presence of other potential etiologies or risk factors. Onset of aCL+ CVT occurs at a relative young age and with relatively more extensive superficial and deep cerebral venous system involvement than aCL- CVT.

A reappraisal of reliability and validity studies in stroke.

BACKGROUND: The emergence of prophylactic and therapeutic interventions in stroke has been accompanied by the widespread use of stroke classifications and scales that measure deficit (stroke scales) or resulting long-term handicap (handicap and disability scales). Although the accuracy of some scales and classifications has been studied, there is no updated systematic review appraising all of them. REVIEW: We reviewed the literature and selected 21 studies on classifications and scales. The International Classification of Diseases, 10th revision, achieved the highest interobserver agreement among seven stroke classifications. The National Institutes of Health Stroke Scale, the Canadian Neurological Scale, and the European Stroke Scale had the highest reliability across items among nine stroke scales. The Barthel Index was the most reliable disability scale. CONCLUSIONS: The identification of the most reliable stroke classifications and scales should encourage their use in selection of homogeneous populations of patients for clinical research studies and to improve communication among scientists. Further research is needed to investigate neglected aspects of the neurological examination and the validity of stroke classifications.

Cerebrovascular complications of Fabry's disease.

Fabry's disease (FD) is a rare, sex-linked disorder resulting from alpha-galactosidase deficiency. Cerebrovascular complications have been reported in the literature but have not been systematically analyzed. We report 2 patients and review 51 previously reported cases (descriptive meta-analysis) to clarify the clinical, radiologic, and pathologic features. The average age at onset of cerebrovascular symptoms was 33.8 years for hemizygous individuals (n = 43) and 40.3 years of heterozygotes (n = 10). The most frequent symptoms and signs were as follows (in descending order of frequency): hemiparesis, vertigo/dizziness, diplopia, dysarthria, nystagmus, nausea/vomiting, head pain, hemiataxia, and ataxia of gait, in the hemizygote group; and memory loss, dizziness, ataxia, hemiparesis, loss of consciousness and hemisensory symptoms, in the heterozygote group. The vertebrobasilar circulation was symptomatic in 67% of the hemizygotes and 60% of the heterozygotes. Intracerebral hemorrhage was found in 4 patients (3 hemizygotes and 1 heterozygote). Elongated, ectatic, tortuous vertebral and basilar arteries were the most common angiographic and pathologic features. For the hemizygotes, the recurrence rate for cerebrovascular disease was 76% and the death rate was 55%; 86% of the heterozygotes had recurrent cerebrovascular event(s) and 40% died. The cerebrovascular manifestations of FD, in both hemizygotes and heterozygotes, are predominantly due to dilative arteriopathy of the vertebrobasilar circulation, frequently recur, and portend a poor prognosis.