Magdy Selim

Medical complications after stroke

Patients who have had a stroke are susceptible to many complications. These individuals commonly have comorbidities such as hypertension, diabetes, heart disease, or other ailments that increase the risks of systemic medical complications during stroke recovery. However, several complications can arise as a direct consequence of the brain injury itself, from the ensuing disabilities or immobility, or from stroke-related treatments. These events have a substantial effect on the final outcome of patients with stroke and often impede neurological recovery. Cardiac complications, pneumonias, venous thromboembolism, fever, pain, dysphagia, incontinence, and depression are particularly common after a stroke and usually require specific interventions for their prevention and treatment. However, there are few data to guide the management of these complications. Systematic investigations are therefore needed to further study the effects of medical complications on stroke recovery and to improve interventions for the prevention and treatment of these events.

Clinical and Vascular Outcome in Internal Carotid Artery Versus Middle Cerebral Artery Occlusions After Intravenous Tissue Plasminogen Activator

Background and Purpose— Early reperfusion is a predictor of good outcome in acute ischemic stroke. We investigated whether middle cerebral artery (MCA) occlusions have a better clinical outcome and proportion of recanalization compared with internal carotid artery (ICA) occlusion after standard treatment with intravenous (IV) tissue plasminogen activator (tPA). Patients— In a retrospective analysis of our prospective stroke database between January 7, 1998, and January 30, 2002, we identified 36 consecutive patients who were treated with IV tPA within 3 hours after symptom onset of a stroke in the distribution of a documented ICA or MCA occlusion. The National Institutes of Health Stroke Scale (NIHSS) score was recorded before tPA, at 24 hours, 3 days, and 3 months after stroke. Three-month outcome was recorded by modified Rankin scale. Magnetic resonance angiography or computed tomographic angiography was obtained before tPA. The presence of recanalization was assessed by transcranial Doppler and/or magnetic resonance angiography within 3 days after stroke onset. Results— Nineteen patients had MCA occlusion, and 17 had ICA-plus-MCA occlusion before tPA. Although there was no difference in age and NIHSS at day 0 between the 2 groups, the MCA group had a lower day 3 NIHSS score compared with the ICA group (P =0.006) in an ANCOVA. In addition, patients who had a MCA occlusion had lower day 1 and 3 NIHSS scores compared with the ICA group (P =0.04 and P =0.03, respectively; Wilcoxon rank sum). Similarly, NIHSS was significantly lower in patients who recanalized on days 1 and 3 (P =0.004 and P =0.003 respectively, Wilcoxon rank sum). When we adjusted for NIHSS score at day 0 in an ANCOVA, the adjusted mean was lower in the group that recanalized compared with the group that did not recanalize (P <0.001). There was a significant difference between the proportion of recanalization in the MCA group (15 of 17 recanalized, 88%) at 3 days after tPA compared with that of the ICA group (5 of 16 recanalized, 31%;P =0.001, Fisher exact test). The 3-month modified Rankin scale was not different between the 2 groups. Conclusions— Despite comparable age and NIHSS scores before IV tPA, MCA occlusions have lower day 1 and 3 NIHSS scores and higher proportion of recanalization compared with ICA occlusions. A combined IV/intra-arterial or mechanical thrombolysis may be needed to achieve early recanalization in ICA occlusions.

Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis

IMPORTANCE Endovascular intervention for acute ischemic stroke improves revascularization. But trials examining endovascular therapy yielded variable functional outcomes, and the effect of endovascular intervention among subgroups needs better definition. OBJECTIVE To examine the association between endovascular mechanical thrombectomy and clinical outcomes among patients with acute ischemic stroke. DATA SOURCES We systematically searched MEDLINE, EMBASE, CINAHL, Google Scholar, and the Cochrane Library without language restriction through August 2015. STUDY SELECTION Eligible studies were randomized clinical trials of endovascular therapy with mechanical thrombectomy vs standard medical care, which includes the use of intravenous tissue plasminogen activator (tPA). DATA EXTRACTION AND SYNTHESIS Independent reviewers evaluated the quality of studies and abstracted the data. We calculated odds ratios (ORs) and 95% CIs for all outcomes using random-effects meta-analyses and performed subgroup and sensitivity analyses to examine whether certain imaging, patient, treatment, or study characteristics were associated with improved functional outcome. The strength of the evidence was examined for all outcomes using the GRADE method. MAIN OUTCOMES AND MEASURES Ordinal improvement across modified Rankin scale (mRS) scores at 90 days, functional independence (mRS score, 0-2), angiographic revascularization at 24 hours, symptomatic intracranial hemorrhage within 90 days, and all-cause mortality at 90 days. RESULTS Data were included from 8 trials involving 2423 patients (mean [SD] age, 67.4 [14.4] years; 1131 [46.7%] women), including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA. In a meta-analysis of these trials, endovascular therapy was associated with a significant proportional treatment benefit across mRS scores (OR, 1.56; 95% CI, 1.14-2.13; P = .005). Functional independence at 90 days (mRS score, 0-2) occurred among 557 of 1293 patients (44.6%; 95% CI, 36.6%-52.8%) in the endovascular therapy group vs 351 of 1094 patients (31.8%; 95% CI, 24.6%-40.0%) in the standard medical care group (risk difference, 12%; 95% CI, 3.8%-20.3%; OR, 1.71; 95% CI, 1.18-2.49; P = .005). Compared with standard medical care, endovascular thrombectomy was associated with significantly higher rates of angiographic revascularization at 24 hours (75.8% vs 34.1%; OR, 6.49; 95% CI, 4.79-8.79; P < .001) but no significant difference in rates of symptomatic intracranial hemorrhage within 90 days (70 events [5.7%] vs 53 events [5.1%]; OR, 1.12; 95% CI, 0.77-1.63; P = .56) or all-cause mortality at 90 days (218 deaths [15.8%] vs 201 deaths [17.8%]; OR, 0.87; 95% CI, 0.68-1.12; P = .27). CONCLUSIONS AND RELEVANCE Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

Predictors of Hemorrhagic Transformation After Intravenous Recombinant Tissue Plasminogen Activator Prognostic Value of the Initial Apparent Diffusion Coefficient and Diffusion-Weighted Lesion Volume

Background and Purpose— Hemorrhagic transformation (HT) is a potentially dangerous complication of thrombolytic therapy. Recent studies suggest that diffusion-weighted MRI (DWI) can help to predict the risk of intracerebral hemorrhage (ICH) after thrombolysis. We sought to examine which pretreatment DWI parameters and clinical data are predictive of ICH after intravenous thrombolysis. Methods— We retrospectively reviewed our prospective stroke database for patients with ischemic stroke treated with intravenous recombinant tissue plasminogen activator (rtPA) within 3 hours from symptom onset who had DWI before treatment and MRI with T2* sequence or CT 24 to 48 hours later to assess for ICH over the past 4 years. We measured the volumes and voxel-by-voxel apparent diffusion coefficient (ADC) values of the initial DWI lesions and retrieved demographic data, risk factors, National Institutes of Health Stroke Scale (NIHSS) scores on admission, and blood tests results. We examined several variables using univariate and multivariate regression analyses to determine predictors of ICH. Results— Twenty-nine patients fulfilled our inclusion criteria; 17 patients (58%) had ICH, and of these 4 (13%) had symptomatic ICH and fatal outcome. On univariate analysis, higher systolic blood pressure, NIHSS score, serum glucose level, volume of initial DWI lesion, and absolute number of voxels with ADC value ≤550×10−6 mm2/s were statistically associated with ICH, and all were subjected to multivariate analysis. However, only the absolute number of voxels, ie, volume of ischemic tissue on DWI, with ADC ≤550×10−6 mm2/s emerged as an independent predictor of ICH. Conclusions— Our findings suggest that volumetric ADC analysis can be used to assess ICH risk after thrombolysis. This may be particularly helpful if rtPA is to be given outside the 3-hour window.

The Stroke Patient Who Woke Up Clinical and Radiological Features, Including Diffusion and Perfusion MRI

Background and Purpose— Time of stroke onset is uncertain for patients who wake from sleep with stroke. Functional imaging techniques may allow estimation of benefit and risk of acute stroke therapy. We compared the clinical and multimodal MRI findings of patients with uncertain stroke onset with those with known onset time. Methods— Patients imaged within 24 hours of ischemic stroke onset between January 1997 and June 2000 were identified from a prospective stroke registry. Clinical and imaging data from patients with known stroke onset (group I) were compared with those who woke with stroke (group II). Results— A total of 364 patients were identified, of whom 100 (27%) woke from sleep with stroke. Group I and group II did not differ in age, gender, National Institutes of Health Stroke Scale, or TOAST (Trial of Org 10172 in Acute Stroke Treatment) diagnoses. Time from stroke onset was shorter in group I (mean 6.0 versus 13.3 hours, P <0.001); time from detection did not differ between groups (6.0 versus 5.9 hours). Within 3 hours, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) lesion volumes were similar in both groups; DWI-PWI mismatch was present in 82% of group I and 73% of group II patients. Mean apparent diffusion coefficient of water (ADC) of group I patients was negatively associated with DWI volume (&bgr;=−0.324, P =0.004) and time from stroke onset (&bgr;=−0.238, P =0.031) in multivariate analysis. The mean ADC of group II patients was lower than that of group I patients within 3 hours of stroke detection (mean 556 versus 665 &mgr;m2/s, P <0.01), but individual group II patients had ADC values as high as 742 &mgr;m2/s, in addition to a DWI-PWI mismatch pattern. Conclusions— Onset time is uncertain in over one quarter of acute ischemic stroke patients. Clinical features of these patients do not differ significantly from those with known onset time. Some patients who wake with stroke seem to have favorable imaging characteristics for acute stroke therapy. Further study is needed to determine whether criteria for therapy based on imaging parameters can safely be applied to these patients.

Atraumatic convexal subarachnoid hemorrhage Clinical presentation, imaging patterns, and etiologies

Objective: To identify patterns of clinical presentation, imaging findings, and etiologies in a cohort of hospitalized patients with localized nontraumatic convexal subarachnoid hemorrhage. Methods: Twenty-nine consecutive patients with atraumatic convexal subarachnoid hemorrhage were identified using International Classification of Diseases–9 code from 460 patients with subarachnoid hemorrhage evaluated at our institution over a course of 5 years. Retrospective review of patient medical records, neuroimaging studies, and follow-up data was performed. Results: There were 16 women and 13 men between the ages of 29 and 87 years. Two common patterns of presentations were observed. The most frequent presenting symptom in patients ≤60 years (n = 16) was a severe headache (n = 12; 75%) of abrupt onset (n = 9; 56%) with arterial narrowing on conventional angiograms in 4 patients; 10 (p = 0.003) were presumptively diagnosed with a primary vasoconstriction syndrome. Patients >60 years (n = 13) usually had temporary sensory or motor symptoms (n = 7; 54%); brain MRI scans in these patients showed evidence of leukoaraiosis and/or hemispheric microbleeds and superficial siderosis (n = 9; 69%), compatible with amyloid angiopathy (n = 10; p < 0.0001). In a small group of patients, the presentation was more varied and included lethargy, fever, and confusion. Four patients older than 60 years had recurrent intracerebral hemorrhages in the follow-up period with 2 fatalities. Conclusion: Convexal subarachnoid hemorrhage is an important subtype of nonaneurysmal subarachnoid bleeding with diverse etiologies, though a reversible vasoconstriction syndrome appears to be a common cause in patients 60 years or younger whereas amyloid angiopathy is frequent in patients over 60. These observations require confirmation in future studies.

Quantitative Analysis of the Loss of Distinction Between Gray and White Matter in Comatose Patients After Cardiac Arrest

Background and Purpose Anecdotal reports suggest that a loss of distinction between gray (GM) and white matter (WM) as adjudged by CT scan predicts poor outcome in comatose patients after cardiac arrest. To address this, we quantitatively assessed GM and WM intensities at various brain levels in comatose patients after cardiac arrest. Methods Patients for whom consultation was requested within 24 hours of a cardiac arrest were identified with the use of a computerized database that tracks neurological consultations at our institution. Twenty-five comatose patients were identified for whom complete medical records and CT scans were available for review. Twenty-five consecutive patients for whom a CT scan was interpreted as normal served as controls. Hounsfield units (HUs) were measured in small defined areas obtained from axial images at the levels of the basal ganglia, centrum semiovale, and high convexity area. Results At each level tested, lower GM intensity and higher WM intensity were noted in comatose patients compared with normal controls. The GM/WM ratio was significantly lower among comatose patients compared with controls (P <0.0001, rank sum test). There was essentially no overlap in GM/WM ratios between control and study patients. The difference was greatest at the basal ganglia level. We also observed a marginally significant difference in the GM/WM ratio at the basal ganglia level between those patients who died and those who survived cardiac arrest (P =0.035, 1-tailed t test). Using receiver operating characteristic curve analysis, we determined that a difference in GM/WM ratio of <1.18 at the basal ganglia level was 100% predictive of death. At the basal ganglia level, none of 12 patients below this threshold survived, whereas the survival rate was 46% among patients in whom the ratio was >1.18. The empirical risk of death was 21.67 for comatose patients with a value below threshold. Conclusions The ratio in HUs of GM to WM provides a reproducible measure of the distinction between gray and white matter. A lower GM/WM ratio is observed in comatose patients immediately after cardiac arrest. The basal ganglia level seems to be the most sensitive location on CT for measuring this relationship. Although a GM/WM ratio <1.18 at this level predicted death in this retrospective study, the difference in this study is not robust enough to recommend that management decisions be dictated by CT results. The results, however, do warrant consideration of a prospective study to determine the reliability of CT scanning in predicting outcome for comatose patients after cardiac arrest.

Variants at APOE influence risk of deep and lobar intracerebral hemorrhage.

Prior studies investigating the association between APOE alleles ε2/ε4 and risk of intracerebral hemorrhage (ICH) have been inconsistent and limited to small sample sizes, and did not account for confounding by population stratification or determine which genetic risk model was best applied.

The HAT Score: A simple grading scale for predicting hemorrhage after thrombolysis

Objective: To develop a grading scale to predict the risk of intracerebral hemorrhage (ICH) and prognosis after treatment with IV tissue-plasminogen activator (t-PA) in patients with ischemic stroke. Methods: We constructed a five-point scale based on NIH Stroke Scale score, extent of hypodensity on CT scan, serum glucose at baseline, and history of diabetes to predict the risk of hemorrhage after thrombolysis (HAT score). We evaluated the predictive ability of this scale, using c-statistics, in two independent cohorts: the t-PA treated group in the National Institute of Neurological Disorders and Stroke study, and consecutive patients treated with IV t-PA at our institution. Results: The percentage of patients who developed any ICH after t-PA increased with higher scores in both cohorts. Collectively, the rate of any symptomatic ICH was 2% (0 point), 5% (1 point), 10% (2 points), 15% (3 points), and 44% (>3 points). The c-statistic was 0.72 (95% CI 0.65–0.79; p < 0.001) for all hemorrhages; 0.74 (0.63–0.84; p < 0.001) for symptomatic hemorrhages; and 0.79 (0.70–0.88; p < 0.001) for hemorrhages with final fatal outcome. Similar results were obtained when each cohort was analyzed separately. The score also reasonably predicted good (mRS ≤ 2) (c-statistic 0.75; 0.69–0.80; p < 0.001) and catastrophic (mRS ≥ 5) (0.78; 0.72–0.84; p < 0.001) functional outcomes on day 90 in the National Institute of Neurological Disorders and Stroke t-PA-treated patients. Conclusions: The hemorrhage after thrombolysis (HAT) score is a practical, quick, and easy-to-perform scale that allows reasonable risk stratification of intracerebral hemorrhage after IV tissue-plasminogen activator (t-PA). However, the prognostic value of this scale and its use to predict the net benefit from t-PA needs to be refined and prospectively confirmed in a larger cohort of patients before it can be used in clinical decision-making.

Is the Association of National Institutes of Health Stroke Scale Scores and Acute Magnetic Resonance Imaging Stroke Volume Equal for Patients With Right- and Left-Hemisphere Ischemic Stroke?

Background and Purpose— The National Institutes of Health Stroke Scale (NIHSS) is an established measure of neurological impairment; however, it can award more points for tests of presumed left-hemisphere function, such as language, than for tests of right-hemisphere function, such as neglect. This difference may be important if a low NIHSS score is used to exclude patients with right-hemisphere stroke from clinical trials or established treatments. The aim of this study was to investigate whether the relationship between acute NIHSS score and acute stroke volume as determined by acute diffusion- and perfusion-weighted MRI (DWI and PWI) differs between right- and left-sided stroke. Methods— This was a retrospective study of 153 patients with acute stroke seen at Beth Israel Deaconess Medical Center between January 1995 and March 2000 who underwent an MRI examination and NIHSS within 24 hours of stroke onset. NIHSS score was recorded prospectively by the admitting stroke fellow at the time of acute presentation, immediately preceding imaging. Computerized volumetric analysis of the MRI lesions was performed by investigators blinded to clinical data. Results— There were significant correlations between the acute NIHSS scores and acute DWI lesion volumes (r =0.48 right, r =0.58 left) and between acute NIHSS scores and perfusion-weight imaging hypoperfusion volumes (r =0.62 right, r =0.60 left). For patients with NIHSS scores of 0 to 5, the DWI volume of right cerebral lesions was greater than that of left-sided lesions (mean volume, 8.8 versus 3.2 cm3;P =0.04). Among patients with DWI lesions larger than the median volume (9 cm3), 8 of 37 with right-sided stroke had an NIHSS score of 0 to 5 compared with 1 of 39 patients with left-sided stroke (P =0.01). Multiple linear regression analysis revealed a significantly lower acute NIHSS on the right compared with the left side when adjusted for stroke volume on chronic T2 imaging (P =0.03). Conclusions— Patients with right-sided stroke may have a low NIHSS score despite substantial DWI lesion volume. Acute imaging information, such as that available with multimodal MRI, may be useful to identify patients for inclusion in acute stroke protocols when there is clinical uncertainty about eligibility. Prospective evaluation of criteria incorporating acute imaging data is required.