Short-term functional outcomes of patients with acute intracerebral hemorrhage in the native and expatriate population.

Objectives: Functional outcomes in patients with intracerebral hemorrhage (ICH) have not been well characterized in the Middle East and North Africa Region. We report the 30 and 90-day clinical outcomes in the native and expatriate of Qatar with ICH. Methods: We evaluated the Glasgow Coma Scale (GCS), NIHSS, and imaging in the Qatar Stroke Registry (2013-22). The outcome measures were a modified Rankin Scale (mRS) at 90 days and mortality at 30 and 90 days. Unfavorable outcome was defined as mRS of 4-6. We performed non-parametric ROC analyses to measure the concordance index (C-index) to assess the goodness-of-fit of ICH score for predicting 30 day and 90-day mortality and functional outcome. Results: 1,660 patients (median age of 49 (41.5-58) years; male 83.1%, expatriates 77.5%) with ICH, including supratentorial deep in 65.2%, cortical in 16.2%, infratentorial 16% and primary intraventricular in 2.5% were studied. The median baseline ICH volume was 7.5 (3.2-15.8) ml. An unfavorable outcome was seen in 673 (40.5%) patients at 90 days. The unfavorable 90-day outcome (mRS 4-6) was 49.2% in the native population vs. 44.4% in Africans, 39.0% in South Asian, 35.3% in Far Eastern, and 7.7% in Caucasians, p < 0.001. Mortality at 30 days and 90 days was 10.4 and 15.1%. Increasing age [OR (95% CI), 1.02 (1.00-1.03)], lower GCS [0.77 (0.73-0.80)], prior use of antiplatelet medications [1.82 (1.19-2.08)], higher ICH volume [1.03 (1.02-1.04)], and presence of any intraventricular hemorrhage [1.57(1.19-2.08)], were associated with unfavorable outcome. Conclusion: In this relatively younger ICH cohort more than 75% were expatriates. The ICH volume, 90-day unfavorable outcome and mortality was lower in the expatriates compared to the local Arab population, likely related to the younger age and smaller size of the hemorrhages. Prognostic scoring systems may have to be modified in this population to avoid early withdrawal of care.

Appropriate use of antiplatelet medications following transient ischemic attacks and stroke: a 9-year study from the Middle East.

Background and purpose: Guidelines recommend that patients with high-risk TIAs and minor strokes presenting within 1-3 days from onset should be offered dual antiplatelet therapy (DAPT). There are little data on real-world adherence to these recommendations. We evaluated the appropriateness of DAPT use in TIA and stroke patients in a prospective database. Methods: The Qatar Stroke Database began the enrollment of patients with TIAs and acute stroke in 2014 and currently has ~16,000 patients. For this study, we evaluated the rates of guideline-adherent use of antiplatelet treatment at the time of discharge in patients with TIAs and stroke. TIAs were considered high-risk with an ABCD2 score of 4, and a minor stroke was defined as an NIHSS of 3. Patient demographics, clinical features, risk factors, previous medications, imaging and laboratory investigations, final diagnosis, discharge medications, and discharge and 90-day modified Rankin Scale (mRS) were analyzed. Results: After excluding patients with ICH, mimics, and rare secondary causes, 8,082 patients were available for final analysis (TIAs: 1,357 and stroke: 6,725). In high-risk TIAs, 282 of 666 (42.3%) patients were discharged on DAPT. In patients with minor strokes, 1,207 of 3,572 (33.8%) patients were discharged on DAPT. DAPT was inappropriately offered to 238 of 691 (34.4%) low-risk TIAs and 809 of 3,153 (25.7%) non-minor stroke patients. Conclusion: This large database of prospectively collected patients with TIAs and stroke shows that, unfortunately, despite several guidelines, a large majority of patients with TIAs and stroke are receiving inappropriate antiplatelet treatment at discharge from the hospital. This requires urgent attention and further investigation.

Diabetes: Chronic Metformin Treatment and Outcome Following Acute Stroke.

Aim: To evaluate if in patients with known diabetes, pretreatment metformin will lead to less severe stroke, better outcome, and lower mortality following acute stroke. Methods: The Qatar stroke database was interrogated for stroke severity and outcome in patients with ischemic stroke. Outcome was compared in nondiabetic vs. diabetic patients and in diabetic patients on metformin vs. other hypoglycemic agents. The National Institute of Health Stroke Scale was used to measure stroke severity and 90-day modified Rankin scale (mRS) score to determine outcome following acute stroke. Results: In total, 4,897 acute stroke patients [nondiabetic: 2,740 (56%) and diabetic: 2,157 (44%)] were evaluated. There were no significant differences in age, risk factors, stroke severity and type, or thrombolysis between the two groups. At 90 days, mRS (shift analysis) showed significantly poor outcome in diabetic patients (p < 0.001) but no differences in mortality. In the diabetic group, 1,132 patients were on metformin and 1,025 on other hypoglycemic agents. mRS shift analysis showed a significantly better outcome in metformin-treated patients (p < 0.001) and lower mortality (8.1 vs. 4.6% p < 0.001). Multivariate negative binomial analyses showed that the presence of diabetes negatively affected the outcome (90-day mRS) by factor 0.17 (incidence risk ratio, IRR, 1.17; CI [1.08-1.26]; p < 0.001) when all independent variables were held constant. In diabetic patients, pre-stroke treatment with metformin improved the outcome (90-day mRS) by factor 0.14 (IRR 0.86 [CI 0.75-0.97] p = 0.006). Conclusion: Similar to previous reports, our study shows that diabetes adversely affects stroke outcome. The use of prior metformin is associated with better outcome in patients with ischemic stroke and results in lower mortality. The positive effects of metformin require further research to better understand its mechanism.

Night-Time Non-dipping Blood Pressure and Heart Rate: An Association With the Risk of Silent Small Vessel Disease in Patients Presenting With Acute Ischemic Stroke.

Background and Purpose: Nocturnal non-dipping blood pressure and heart rate are associated with an increased risk of cardiovascular disease. The effects of such variance on cerebrovascular disease have not been well studied. Methods: The 24-h ambulatory blood pressure (ABPM) and heart rate were monitored with B-pro in patients with acute stroke within the initial week of hospital admission. The risk factor profiles, clinical presentation, imaging, and short-term prognosis were compared in nocturnal dippers and non-dippers (more than 10% nocturnal decrease) of blood pressure and heart rate. Results: We enrolled 234 patients in whom ABPM and MRI data were available. Heart rate data were available in 180 patients. Lacunar sub-cortical stroke was the most common acute lesion (58.9%), while hypertension (74%) and diabetes (41.5%) were the most common associated risk factors. ABPM revealed non-dipping in 69% of patients. On univariate analysis, Small Vessel Disease (SVD) was significantly more frequent in non-dippers vs. dippers (BP: 56.8 vs. 40.3% p = 0.02; heart rate: 57.9 vs. 40.7% p = 0.03). Silent strokes were also more frequent in non-dippers vs. dippers (BP: 40.7 vs. 26.4% p = 0.35; heart rate: 44.6 vs. 25.4% p = 0.01). Multivariate analysis revealed SVD to be significantly related to age, hypertension, blood pressure non-dipping, and severity of symptoms at index event. Conclusions: The presence of nocturnal non-dipping of blood pressure and heart rate are associated with an increased risk of silent stroke and SVD. Increased use of ABPM may allow for improved diagnosis of non-dippers.

Corneal nerve loss as a surrogate marker for poor pial collaterals in patients with acute ischemic stroke.

In patients with acute ischemic stroke, pial collaterals play a key role in limiting neurological disability by maintaining blood flow to ischemic penumbra. We hypothesized that patient with poor pial collaterals will have greater corneal nerve and endothelial cell abnormalities. In a cross-sectional study, 35 patients with acute ischemic stroke secondary to middle cerebral artery (MCA) occlusion with poor (n = 12) and moderate-good (n = 23) pial collaterals and 35 healthy controls underwent corneal confocal microscopy and quantification of corneal nerve and endothelial cell morphology. In patients with MCA stroke, corneal nerve fibre length (CNFL) (P < 0.001), corneal nerve fibre density (CNFD) (P = 0.025) and corneal nerve branch density (CNBD) (P = 0.002) were lower compared to controls. Age, BMI, cholesterol, triglycerides, HDL, LDL, systolic blood pressure, NIHSS and endothelial cell parameters did not differ but mRS was higher (p = 0.023) and CNFL (p = 0.026) and CNBD (p = 0.044) were lower in patients with poor compared to moderate-good collaterals. CNFL and CNBD distinguished subjects with poor from moderate-good pial collaterals with an AUC of 72% (95% CI 53-92%) and 71% (95% CI 53-90%), respectively. Corneal nerve loss is greater in patients with poor compared to moderate-good pial collaterals and may act as a surrogate marker for pial collateral status in patients with ischemic stroke.

Stroke Mimics: A five-year follow-up study from the Qatar Stroke Database.

BACKGROUND AND PURPOSE: Mimics comprise a third of patients presenting with an acute stroke. There is limited information on their natural history. METHODS: We evaluate long term major cardiovascular events (MACE) in stroke mimics in a prospective database from Qatar. RESULTS: Between Feb 2014 and Jan 2019, 481 patients (male: 238; female: 243) mean age 57.5 years (±18.0), with 399 (83%) medical mimics and 82 (17%) functional mimics were evaluated. Imaging revealed previous old stroke in 26.6% and small vessel disease in 5%. MACE occurred in 57 (11.9%) and there were 31 deaths (6.4%) with majority of deaths (5.6%) from cardiovascular causes. MACE was significantly higher in patients with previous stroke, p < 0.0001), coronary artery disease, p = 0.002), diabetic, p = 0.01), and hypertensive on admission, p < 0.0001. MACE were also significantly higher in patients where imaging showed a previous stroke, p = 0.006). CONCLUSION: The occurrence of MACE during follow-up suggests that patients with existing vascular disease require aggressive management of vascular risk factors.

Left Heart Factors in Embolic Stroke of Undetermined Source in a Multiethnic Asian and North African Cohort.

Background Cardiac features diverge in Asians; however, it is not known how these differences relate to embolic stroke of unknown source (ESUS) in Southeast Asian and Eastern Mediterranean regions. Methods and Results A retrospective analysis of prospectively collected acute ischemic stroke data from 2014 to 2018 was performed. Stroke subtypes were noncardioembolic stroke (large-vessel and small-vessel disease; n=1348), cardioembolic stroke (n=532), and ESUS (n=656). Subtypes were compared by demographic, clinical, and echocardiographic factors. In multivariate logistic regression, patients with ESUS in comparison with noncardioembolic stroke were twice as likely to have left ventricular diastolic dysfunction (P=0.001), 3 times the odds of global hypokinesia (P=0.001), and >7 times the odds of left ventricular wall motion abnormalities (P=0.001). In the second model comparing ESUS with cardioembolic stroke, patients with ESUS were 3 times more likely to have left ventricular wall motion abnormalities (P=0.001) and 1.5 times more likely to have left ventricular diastolic dysfunction grade I (P=0.009), and 3 times more likely to have left ventricular diastolic dysfunction grades II and III (P=0.009), whereas age (P=0.001) and left atrial volume index (P=0.004) showed an inverse relation with ESUS. ESUS in patients ≥61 years old had higher levels of traditional risk factors such as coronary artery disease, but the coronary artery disease was not significantly different in ESUS age groups (P=0.80) despite higher left ventricular wall motion abnormalities (P=0.001). Conclusions Patients with ESUS and noncardioembolic stroke were younger than patients with cardioembolic stroke. While a third of the patients with ESUS >45 years old had coronary artery disease, it was unrecognized or underreported in the older ESUS age group (≥61 years old). In patients with ESUS from Southeast Asia and Eastern Mediterranean regions, left ventricular wall motion abnormalities and left ventricular diastolic dysfunction were related to ESUS.

Sex-Specific Differences in Short-Term and Long-Term Outcomes in Acute Stroke Patients from Qatar.

BACKGROUND: Sex differences may determine presentation, utility of treatment, rehabilitation, and occurrences of major adverse cardiovascular events (MACEs) in acute stroke (AS). OBJECTIVE: The purpose of the study was to evaluate the short-term prognosis and long-term outcomes in MACEs in Qatari nationals admitted with AS. METHODS: All AS patients admitted between January 2014 and February 2019 were included. We evaluated the preadmission modified Rankin scale (mRS) score, etiology and severity of symptoms, complications, and functional recovery at discharge and 90 days. MACEs were recorded for 5 years. RESULTS: There were 891 admissions for AS (mean age 64.0 ± 14.2 years) (male, n = 519 [mean age ± SD 62.9 ± 14.1 years]; female, n = 372 [mean age ± SD 65.6 ± 14.2 years] p = 0.005). There were no differences in the preadmission mRS and severity of symptoms as measured on National Institute of Stroke Scale. At discharge, the outcome was better (mRS 0-2) in men (57.8 vs. 46.0%), p = 0.0001. This difference persisted at the 90-day follow-up (mRS 0-2, male 69.4% vs. female 53.2%, p = 0.0001). At the 90-day follow-up, more women died (total deaths 70; women 38 [10.2%] versus men 32 [6.2%], p = 0.03). MACEs occurred in 25.6% (133/519) males and 30.9% (115/372) females over the 5-year follow-up period (odds ratio 0.77, 95% confidence interval 0.57-1.0, p = 0.83). CONCLUSIONS: Female patients have a poor short-term outcome following an AS when corrected for age and comorbidities. While our study cannot explain the reasons for the discrepancies, higher poststroke depression and social isolation in women may be important contributory factors, and requires further studies are required to confirm these findings.

Corneal confocal microscopy identifies greater corneal nerve damage in patients with a recurrent compared to first ischemic stroke.

OBJECTIVES: Corneal nerve damage may be a surrogate marker for the risk of ischemic stroke. This study was undertaken to determine if there is greater corneal nerve damage in patients with recurrent ischemic stroke. METHODS: Corneal confocal microscopy (CCM) was used to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) and corneal nerve fiber tortuosity (CNFT) in 31 patients with recurrent ischemic stroke, 165 patients with a first acute ischemic stroke and 23 healthy control subjects. RESULTS: Triglycerides (P = 0.004, P = 0.017), systolic BP (P = 0.000, P = 0.000), diastolic BP (P = 0.000, P = 0.000) and HbA1c (P = 0.000, P = 0.000) were significantly higher in patients with first and recurrent stroke compared to controls. There was no difference in age, BMI, HbA1c, total cholesterol, triglycerides, LDL, HDL, systolic and diastolic BP between patients with a first and recurrent ischemic stroke. However, CNFD was significantly lower (24.98±7.31 vs 29.07±7.58 vs 37.91±7.13, P<0.05) and CNFT was significantly higher (0.085±0.042 vs 0.064±0.037 vs 0.039±0.022, P<0.05) in patients with recurrent stroke compared to first stroke and healthy controls. CNBD (42.21±24.65 vs 50.46±27.68 vs 87.24±45.85, P<0.001) and CNFL (15.66±5.70, P<0.001 vs 17.38±5.06, P = 0.003) were equally reduced in patients with first and recurrent stroke compared to controls (22.72±5.14). CONCLUSIONS: Corneal confocal microscopy identified greater corneal nerve fibre loss in patients with recurrent stroke compared to patients with first stroke, despite comparable risk factors. Longitudinal studies are required to determine the prognostic utility of corneal nerve fiber loss in identifying patients at risk of recurrent ischemic stroke.

Prevalence, Characteristics and Risk Factors for Embolic Stroke of Undetermined Source in West and South Asia and North African Population Residing in Qatar.

BACKGROUND AND PURPOSE: Embolic stroke of undetermined source (ESUS) is an important contributor to stroke worldwide. Little is known about ESUS in developing parts of the world such as South Asia, West Asia and North Africa despite the high stroke burden in these areas. The purpose of the study was to characterize the prevalence, demographic, risk factor and clinical aspects of ESUS in patients from South Asia, West Asia and North Africa residing in Qatar. METHODS: Data were retrospectively collected on 3103 stoke patients. Risk factors and clinical features of the ESUS group were compared to all other strokes using Chi-square or student's t-tests. Logistic regression was used to identify factors associated with ESUS. ESUS patients were compared based on ethnicity using Chi-square or one-way ANOVA. RESULTS: 634 patients (30·9%, 95% CI (28·9%-32·9%) met the ESUS criteria. Mean age was 56·3 years ± 13·7 and South Asian ESUS patients were younger than West Asians or North Africans (67·1 ± 13·5 versus 52·1 ± 10·8 versus 53·5 ± 14·2, P = .001). Smoking, diastolic function, prior antiplatelets and wall motion abnormalities were more common in ESUS. Logistic regression showed that South Asian ethnicity (OR 1·50, CI 1·14-1·97, P = ·003), diastolic dysfunction (OR 1·47, CI 1·23-1·75, P = ·005), global (OR 1·79, CI 1·41-2·26, P = ·001) and focal (OR 5·48, CI 3·79-7·92, P = ·001) wall motion abnormalities, predicted ESUS. CONCLUSIONS: ESUS is a major cause of stroke in patients from West Asia, South Asia and North Africa residing in Qatar. The clinical profile and risk factors for ESUS vary based on ethnicity. In South Asians, ESUS occurs at a younger age and is most likely cardiogenic in origin.

Cornea: A Window to White Matter Changes in Stroke; Corneal Confocal Microscopy a Surrogate Marker for the Presence and Severity of White Matter Hyperintensities in Ischemic Stroke.

PURPOSE: The presence of white matter hyperintensities (WMH) on MRI imaging confers an increased risk of stroke, dementia, and death. Corneal confocal microscopy (CCM) can detect nerve injury non-invasively and may be a useful surrogate marker for WMH. The objective is to determine whether corneal nerve pathology identified using CCM is associated with the presence of WMH in patients with acute ischemic stroke. METHODS: This is a cross-sectional study where 196 consecutive individuals with acute ischemic stroke were enrolled and underwent neurological examination, MRI brain imaging and CCM. Participants underwent blinded quantification of WMH and corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL). RESULTS: The prevalence of hypertension [P = .013] was significantly higher and CNFD [P = .031] was significantly lower in patients with WMH compared to those without WMH. CNFD and CNFL were significantly lower in patients with DM without WMH [P = .008, P = .019] and in patients with DM and WMH [P = .042, P = .024] compared to patients without DM or WMH, respectively. In a multivariate model, a 1-unit decrease in the CNFD increased the risk of WMH by 6%, after adjusting for age, DM, gender, dyslipidemia, metabolic syndrome, smoking, and HbA1c. DM was associated with a decrease in all CCM parameters but was not a significant independent factor associated with WMH. CONCLUSIONS: CCM demonstrates corneal nerve pathology, which is associated with the presence of WMH in participants with acute ischemic stroke. CCM may be a useful surrogate imaging marker for the presence and severity of WMHs.

Embolic Pattern of Stroke Associated with Cardiac Wall Motion Abnormalities; Narrowing the Embolic Stroke of Undetermined Source Category.

BACKGROUND: There is ambiguity regarding the role of left ventricle wall motion abnormalities (LVWMAs) as a potential cardioembolic source in patients, who satisfy embolic stroke of undetermined source (ESUS) criteria. METHODS AND RESULTS: We analyzed prospectively collected data in 345 acute stroke patients, 185 (53.6%) stroke with atrial fibrillation (SwAF), and 160 (46.4%) stroke with LVWMA. LVWMA were younger (P = .003), had significantly higher frequency of stroke risk factors and lower ejection fraction (P < .001). No significant difference was found between the stroke pattern in SwAF and LVWMA except focal cortical, cortical-subcortical lesions were more frequent in LVWMA (P = .002). Mean wall motion score index (WMSI) was 1.523 (range 1.05-2.71) without any correlation between the severity of WMSI and multiple strokes (P = .976). In subgroup analyses vertical basal WMSI (P = .030) and vertical mid cavity WMSI (P = .010) was significantly related to branch arterial stroke. LVWMA 94 (65%) patients were on antiplatelet/anticoagulation compared to 47 (52.4%) with atrial fibrillation (AF), with no significant difference in stroke recurrence during 4 years follow-up (P = .15). CONCLUSIONS: Patients with LVWMA who satisfy ESUS criteria, have stroke pattern on diffusion-weighted magnetic resonance imaging and risk of stroke recurrence similar to AF-related stroke despite being on appropriate antiplatelet medications. Further studies with anticoagulation therapy may be required in this group of patients to improve the high risk of recurrent stroke.

The Impact of Diabetes on Outcomes After Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND: Stroke in diabetics may delay recovery and increases the risk of early recurrence of stroke. We compared the outcomes of patients (with and without diabetes) admitted with an acute ischemic stroke (AIS) in the state of Qatar. PATIENTS AND METHODS: We prospectively compared the clinical presentation, complications, discharge outcome, and stroke recurrence at 90 days in patients with and without diabetes. RESULTS: Five thousand two hundred twenty-eight stroke patients were admitted between January 2014 and December 2017. Two thousand nine hundred sixty-one had confirmed AIS, 1695 (57.2%) had diabetes, 429 (14.5%) had prediabetes and 873 (29.5%) had no diabetes. Comparing diabetic patients to prediabetic and nondiabetics, they were significantly older (58.5 ± 11.9 versus 54.0 ± 12.9 versus 49.5 ± 13.8, P = .0001), had higher rates of hypertension (80.8% versus 67.4% versus 59.2%), previous stroke (18.0% versus 5.4% versus 6.2%), and coronary artery disease (12.9% versus 5.6% versus 5.0%; P = .001 for all). The percentage of patients with modified Rankin scale 3-6 at discharge (39.7% versus 32.6% versus 30.2%; P = .0001) and 90 days (26.7% versus 18.8% versus 21.4%, P = .001); 90-day mortality (6.2% versus 2.2% versus 5.2%; P = .03) and stroke recurrence (4.2% versus .7% versus 2.2%; P = .005) was significantly higher in diabetic patients. CONCLUSIONS: Patients with diabetes and AIS have more in-hospital complications, worse discharge outcomes, higher mortality and stroke recurrence at 90 days, compared to prediabetes and no diabetes.

Corneal Confocal Microscopy detects a Reduction in Corneal Endothelial Cells and Nerve Fibres in Patients with Acute Ischemic Stroke.

Endothelial dysfunction and damage underlie cerebrovascular disease and ischemic stroke. We undertook corneal confocal microscopy (CCM) to quantify corneal endothelial cell and nerve morphology in 146 patients with an acute ischemic stroke and 18 age-matched healthy control participants. Corneal endothelial cell density was lower (P < 0.001) and endothelial cell area (P < 0.001) and perimeter (P < 0.001) were higher, whilst corneal nerve fibre density (P < 0.001), corneal nerve branch density (P < 0.001) and corneal nerve fibre length (P = 0.001) were lower in patients with acute ischemic stroke compared to controls. Corneal endothelial cell density, cell area and cell perimeter correlated with corneal nerve fiber density (P = 0.033, P = 0.014, P = 0.011) and length (P = 0.017, P = 0.013, P = 0.008), respectively. Multiple linear regression analysis showed a significant independent association between corneal endothelial cell density, area and perimeter with acute ischemic stroke and triglycerides. CCM is a rapid non-invasive ophthalmic imaging technique, which could be used to identify patients at risk of acute ischemic stroke.

Peripheral neuropathy in patients with multiple sclerosis.

OBJECTIVES: To determine the prevalence and severity of neuropathic pain, sudomotor dysfunction and abnormal vibration perception in patients with MS. METHODS: 73 patients with MS and 32 age-matched healthy controls underwent assessment of expanded disability severity score (EDSS), DN4 to assess neuropathic pain, electrochemical skin conductance (ESC) to assess sudomotor function and vibration perception threshold (VPT). RESULTS: Patients with MS had a higher DN4 score (p < 0.001) with 14% fulfilling the criteria for neuropathic pain elevated VPT (p < 0.001) and lower ESC on the feet (p < 0.001) and hands (p < 0.001) compared to control participants. ESC on the feet (32% of MS patients) and hands (30% of MS patients) were lower, and DN4 (77% of MS patients) and VPT (64% of MS patients) were greater than 2SD of the healthy control values, respectively. EDSS correlated with the number of relapses (r = 0.564, p < 0.001), VPT (r = -0.457, < 0.001) and ESC on the feet (r = -0.268, p = 0.023). CONCLUSIONS: Patients with multiple sclerosis have evidence of sudomotor dysfunction and elevated vibration perception, which were associated with neurological disability from MS.