Muzaffar Siddiqui
University of Alberta
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Featured researches published by Muzaffar Siddiqui.
Stroke | 2007
Maher Saqqur; Carlos A. Molina; Abdul Salam; Muzaffar Siddiqui; Marc Ribo; Ken Uchino; Sergio Calleja; Zsolt Garami; Khaurshid Khan; Naveed Akhtar; Finton O'Rourke; Ashfaq Shuaib; Andrew M. Demchuk; Andrei V. Alexandrov
Background and Purpose— Patients may experience clinical deterioration (CD) after treatment with intravenous recombinant tissue plasminogen activator (rt-PA). We evaluated the ability of flow findings on transcranial Doppler to predict CD and outcomes on modified Rankin Scale. Methods— Patients with acute stroke received intravenous rt-PA within 3 hours of symptom onset at four academic centers. CD was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score by 4 points or more within 24 hours. Poor long-term outcome was defined by modified Rankin Scale ≥2 at 3 months. Transcranial Doppler findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion, or complete recanalization. Multiple regression analysis was used to identify transcranial Doppler flow as a predictor for CD after controlling for age, sex, baseline NIHSS, hypertension, and glucose. Results— A total of 374 patients received intravenous rt-PA at 142±60 minutes (median pretreatment NIHSS score 16 points). At the end of intravenous rt-PA infusion, transcranial Doppler showed persistent arterial occlusion in 219 patients (59%), arterial reocclusion in 54 patients (14%), and complete recanalization in 101 patients (27%). CD occurred in 44 patients: 36 had persistent arterial occlusion or reocclusion (82%), 13 symptomatic intracerebral hemorrhage (29%), and both persistent occlusion/reocclusion and symptomatic intracerebral hemorrhage in 10 patients (23%). After adjustment, patient risk for CD with persistent occlusion was OR 1.7 (95% CI: 0.7 to 4) and with arterial reocclusion 4.9 (95% CI: 1.7 to 13) (P=0.002). Patient risk for poor long-term outcomes with persistent occlusion, partial recanalization, or reocclusion was OR 5.2 (95% CI: 2.7 to 9, P=0.001). Conclusions— Inability to achieve or sustain vessel patency at the end of rt-PA infusion correlates with the likelihood of clinical deterioration and poor long-term outcome. Early arterial reocclusion on transcranial Doppler is highly predictive of CD and poor outcome.
Neurology | 2008
Maher Saqqur; Georgios Tsivgoulis; Carlos A. Molina; Andrew M. Demchuk; Muzaffar Siddiqui; José Alvarez-Sabín; Ken Uchino; Sergio Calleja; Andrei V. Alexandrov
Background: Symptomatic intracerebral hemorrhage (sICH) is the most unfavorable complication after IV thrombolytic treatment. We aimed to determine the relationship between early recanalization and the risk of sICH. Methods: Patients with acute stroke received IV tissue plasminogen activator (rt-PA) within 3 hours of symptom onset with transcranial Doppler (TCD) monitoring at four academic centers. sICH was defined as parenchymal hemorrhage on CT in relation to neurologic worsening (NIH Stroke Scale [NIHSS] ≥4) within 72 hours after treatment. Poor outcome was defined as modified Rankin Scale 3-6 at 3 months. Early recanalization was graded with Thrombolysis in Brain Ischemia (TIBI) system. Multiple logistic regression analyses were used to identify predictors of sICH. Results: A total of 349 patients received rt-PA at median 134 ± 32 minutes (mean age 69 ± 13 years, 186 men [53%]). Median pretreatment NIHSS score was 16 points (interquartile range: 12-20). Median time to TCD was 130 ± 40 minutes. At the end of rt-PA infusion, 135 patients (38%) had no recanalization, 101 (29%) partial, and 113 (32%) complete recanalization. sICH occurred in 26 patients (7.4%). Of the 135 patients without early recanalization, 18 (13%) had sICH, as compared to 4 (4%) of the 109 subjects with partial recanalization and 4 (3.5%) of 113 with complete recanalization, p = 0.005. After adjustment for age, sex, baseline NIHSS score, glucose, blood pressure, and time to treatment, patients with persistent occlusion had sixfold higher risk of sICH (OR = 6, 95% CI 1.5-21.3, p = 0.01). Conclusion: The risk of tPA-related symptomatic intracerebral hemorrhage (sICH) is low after early and complete restoration of blood flow. Arterial occlusion persistent beyond tissue plasminogen activator infusion emerges as an independent predictor of higher risk of sICH in patients treated with systemic thrombolysis.
Neuroscience Letters | 1998
Ping-An Li; Wendy Howlett; Qing Ping He; Hiro Miyashita; Muzaffar Siddiqui; Ashfaq Shuaib
The newly-developed calpain inhibitor, MDL 28170 penetrates the blood-brain barrier and inhibits brain cysteine protease activity after systemic administration. This experiment was initiated to determine if the calpain inhibitor, MDL 28170 could, by these actions, reduce neuronal damage in an animal model of global cerebral ischemia in the gerbil. The calpain inhibitor, MDL 28170 (50 mg/kg), was initiated at 0.5 and 3 h of recirculation following 5min of global ischemia. Animals subjected to ischemia but without treatment or with vehicle treatment served as controls. Evaluation by light microscopy was carried out on paraffin-embedded brain sections of gerbils which were sacrificed 7 days post-operatively. The results show that the calpain inhibitor, MDL 28170, protects against cortical neuronal damage even if the treatment is delayed until 3 h after reperfusion. However, the neuroprotective effect of this agent is less pronounced in the hippocampal CA1 sector. The results suggest that calpain-mediated proteolysis plays an important role in neuronal death due to ischemia. However, additional mechanisms by which an increased intracellular calcium concentration leads to neuronal death may exist.
Magnetic Resonance Imaging | 2008
Yusuf A. Bhagat; Muhammad S. Hussain; Robert W. Stobbe; Kenneth Butcher; Derek Emery; Ashfaq Shuaib; Muzaffar Siddiqui; Perkash Maheshwari; Fawaz Al-Hussain; Christian Beaulieu
Diffusion tensor imaging (DTI) studies of human ischemic stroke within 24 h of symptom onset have reported variable findings of changes in diffusion anisotropy. Serial DTI within 24 h may clarify these heterogeneous results. We characterized longitudinal changes of diffusion anisotropy by analyzing discrete ischemic white matter (WM) and gray matter (GM) regions during the hyperacute (2.5-7 h) and acute (21.5-29 h) scanning phases of ischemic stroke onset in 13 patients. Mean diffusivity (MD), fractional anisotropy (FA) and T2-weighted signal intensity were measured for deep and subcortical WM and deep and cortical GM areas in lesions outlined by a > or =30% decrease in MD. Average reductions of approximately 40% in relative (r) MD were observed in all four brain regions during both the hyperacute and acute phases post stroke. Overall, 9 of 13 patients within 7 h post symptom onset showed elevated FA in at least one of the four tissues, and within the same cohort, 11 of 13 patients showed reduced FA in at least one of the ischemic WM and GM regions at 21.5-29 h after stroke. The fractional anisotropy in the lesion relative to the contralateral side (rFA, mean+/-S.D.) was significantly elevated in some patients in the deep WM (1.10+/-0.11, n=4), subcortical WM (1.13+/-0.14, n=4), deep GM (1.07+/-0.06, n=1) and cortical GM (1.22+/-0.13, n=5) hyperacutely (< or =7 h); however, reductions of rFA at approximately 24 h post stroke were more consistent (rFA= 0.85+/-0.12).
Experimental Neurology | 1998
Ashfaq Shuaib; Yi Yang; Muzaffar Siddiqui; Jay Kalra
A number of models of focal ischemia have been created to mimic acute middle cerebral artery (MCA) occlusion. In the present series of experiments, we report our observations on the thrombin model of MCA occlusion and the neuroprotective effects of intraarterial thrombolysis with two doses of urokinase (2500 and 5000 units/kg). In all experiments male Wistar rats were used and the animals were allowed to recover for 48 h before assessment of neurobehavioral performance on a four-point scale. The extent of cerebral hemispheric damage was calculated as the percentage of brain infarction using TTC staining. Occlusion of the MCA was effected by the introduction of an autologous blood clot into the internal carotid artery (ICA) approximately 2 mm from the origin of the MCA. This clot was formed by the drawing of 10 microl of blood into a bovine thrombin (20 microg per animal) containing intraarterial catheter, which was inserted into the right ECA. After standing for 15 min to allow clot formation, the catheter was advanced gently through the ICA to the site of injection. MCA occlusion produced a consistent large infarction in all animals. Urokinase infusion (i.a. ) was started 2 h after arterial occlusion in the initial series. In animals treated with low dose urokinase infusion there was mild protection. Animals treated with high dose urokinase infusion showed a highly significant improvement in the motor recovery and a decrease in the extent of infarction compared to control animals. In the final group, the infusion of urokinase was delayed for 3 h. While producing protection in some animals, it also produced intracerebral hemorrhage in two of eight animals. Thus delay of infusion to 180 min increased the risk of hemorrhage. This model may in the future be used to test the protective effects of combination therapy with thrombolysis and neuroprotective medications.
Stroke | 2014
Alexander Tamm; Muzaffar Siddiqui; Ashfaq Shuaib; Kenneth Butcher; Rajive Jassal; Mikael Muratoglu; Brian Buck
Background and Purpose— Geographically distinct multidisciplinary stroke care units (SCUs) have been shown by systematic reviews to have superior patient outcomes compared with conventional care in general medical wards. However, the effectiveness of SCUs in smaller North American community hospitals is less well defined. The objective of this study was to determine the impact of establishing a specialized SCU at a community hospital on patient outcomes. Methods— This is a retrospective cohort study of 805 patients with stroke admitted to 2 community hospitals in Edmonton, Canada, from 2003 to 2009 using an administrative database. Stroke was identified by International Classification of Disease, 10th Edition, codes. One of the community hospitals established a SCU on January 1, 2007. This date was used to subdivide the patient population into 2 cohorts: phase 1 from 2003 to 2006 and phase 2 from 2007 to 2009. Outcomes measured were mortality, discharge disposition, length of stay, and complications and were adjusted for age, sex, and medical comorbidities. Results— Patient mortality decreased significantly from 17.1% to 8.3% (adjusted odds ratio [OR], 0.54; 95% confidence interval [CI], 0.31–0.95) after SCU implementation, whereas it remained ≈19% at the control hospital. SCU also increased the odds that patients would be discharged home independently (adjusted OR, 2.17; 95% CI, 1.49–3.15; P<0.001] without increasing length of stay. Conclusions— Establishing a SCU in a community hospital not only increases the survival of stroke patients, but also the proportion of patients discharged home to live independently. The benefits of SCU reported in larger tertiary centers extend to smaller community hospitals with more limited resources.
Cerebrovascular Diseases | 2010
Maher Saqqur; Vijay K. Sharma; Georgios Tsivgoulis; Thang Nguyen Huy; Ioannis Heliopoulos; Muzaffar Siddiqui; Carol Derksen; Khurshid Khan; Andrei V. Alexandrov
Background: Arterial flow velocity changes on transcranial Doppler can reflect changes in cerebral flow during position-induced ischemia if obtained during short-term monitoring of positional changes. Subjects and Methods: Our multicenter group monitored symptomatic and asymptomatic arteries in patients with recurrent neurological deficits during positional changes and documented intracranial arterial stenosis. Bilateral posterior cerebral and middle cerebral arteries were monitored dependent on clinical symptom localization. The symptomatic artery was monitored distal to the intracranial stenosis, and mean flow velocities (MFV) were recorded at different body positions. The symptomatic artery relative MFV ratio was defined as the ratio of symptomatic artery MFV in the asymptomatic position – MFV in the symptomatic position/MFV in the asymptomatic position. Results: Sixteen patients underwent transcranial Doppler monitoring: mean age 62 ± 19 years, 11 (69%) men, 6 (40%) with transient ischemic attacks. Ten patients (63%) had posterior and 6 anterior circulation symptoms. Patients developed neurological symptoms while standing up (63%) and/or sitting (44%), walking (13%) or during neck extension (6%). Symptomatic artery MFV dropped by ≧25% from the resting to the symptomatic position in all patients except for one. The mean symptomatic artery MFV relative ratio was higher compared with the mean asymptomatic artery MFV relative ratio: 0.5 ± 0.28 versus –0.02 ± 0.1 (p = 0.001, Wilcoxon test). The symptomatic artery relative ratio of >0.25 had a 94% sensitivity and 100% specificity for predicting neurological symptom development during testing (ĸ = 0.9, p < 0.001). Conclusions: A significant reduction in intracranial flow velocity distal to an intracranial stenosis can identify patients whose symptoms can worsen with positional changes. These patients may prove a target for interventional revascularization techniques.
Journal of Neuroimaging | 2013
Joseph Sebastian; Carol Derksen; Khurshid Khan; Mohammad Ibrahim; Bilal Hameed; Muzaffar Siddiqui; Michael Chow; J. Max Findlay; Ashfaq Shuaib; Maher Saqqur
Transcranial Doppler (TCD) has been subjected to criticism for detecting vasospasm (VSP). Our studys aim is to derive criteria for middle cerebral artery (MCA) vasospasm (MCA‐VSP) based on cerebral angiography (CA).
Journal of Neurosurgery | 2000
Yi Yang; Qui Li; Hero Miyashita; Wendy Howlett; Muzaffar Siddiqui; Ashfaq Shuaib
Methods | 2001
Muzaffar Siddiqui; Ashfaq Shuaib