Thrombolysis Outcomes in Patients with Diabetes and Previous Stroke: A Meta-Analysis.

BACKGROUND: Intravenous tissue-type plasminogen activator (IVtPA) is a proven treatment for acute ischemic stroke; however, diabetes mellitus (DM) and previous cerebral infarction (PCI) were considered relative contraindications for thrombolysis within the 3-4.5 h period. OBJECTIVE: The study aimed to determine the safety and efficacy of IVtPA among diabetic patients with PCI presenting with acute ischemic stroke. METHODS: Studies which evaluated the outcome of IVtPA in terms of symptomatic intracerebral hemorrhage (sICH), functional outcome in modified Rankin scale, and death among diabetic patients with PCI presenting with acute ischemic stroke within the 3-4.5 h period were systematically searched until July 2019. Screening and eligibility criteria were applied. Risk of bias was evaluated using the Newcastle-Ottawa Scale. Odds ratios (ORs) with 95% confidence interval (CI) were used to compare measures of treatment effect. Mantel-Haenszel method and random-effects model were also employed. RESULTS: Four registry-based studies with a total of 44,572 patients were included for quantitative synthesis. Giving IVtPA among DM+/PCI+ patients did not result in significantly increased rate of sICH (OR, 1.09; 95% CI, 0.88, 1.36) compared to No DM+/PCI+ patients. However, there was significantly higher mortality (OR, 1.81; 95% CI, 1.60, 2.06) in the DM+/PCI+ group. Conversely, among those who survived, the DM+/PCI+ patients were more functionally independent at 3 months (OR, 0.76; 95% CI, 0.61, 0.94). CONCLUSION: Limited evidence suggests that thrombolysis in DM+/PCI+ patients does not result in significantly higher incidence of sICH and may improve functional independence. However, the significantly higher mortality in this group warrants an assessment of the individualized risk-benefit ratio in the use of IVtPA.

Safety and Efficacy of Repeated Thrombolysis with Alteplase in Early Recurrent Ischemic Stroke: A Systematic Review.

BACKGROUND AND AIM: The current American Heart Association guidelines for the management of acute ischemic stroke advise against the use of intravenous (IV) alteplase in patients with recurrent stroke occurring within 90 days of their index event. Following these guidelines strictly, patients having early recurrent ischemic stroke would be unable to avail of this reperfusion strategy that has been proven to confer superior clinical outcomes. While some registry-based studies have demonstrated the safety of IV alteplase in this subgroup of patients, data on the repeated use of the drug are lacking. Thus, we aim to determine the safety and efficacy of repeated thrombolysis in patients with early recurrent ischemic strokes. METHODS: The following electronic databases were searched for relevant studies: the Cochrane Central Register for Controlled Trials by The Cochrane Library, MEDLINE by PubMed, Health Research and Development Information Network, Scopus, and ClinicalTrials.gov. Data on symptomatic intracranial hemorrhage, 90-day clinical outcomes, systemic hemorrhage and allergic reactionswere synthesized. RESULTS: Ten articles with 33 patients in total were included in our review. One patient developed symptomatic intracranial hemorrhage after the second reperfusion attempt and subsequently died from pneumonia. Another died from spontaneous rupture of previously unidentified infrarenal aortic aneurysm. Six of the 13 patients with available follow-up data had good clinical outcomes (Modified Rankin Score 0-2). There were no allergic reactions and other drug-related adverse events noted. CONCLUSIONS: Repeated IV alteplase can be safe and efficacious in patients who have early recurrent ischemic stroke. Larger studies, trials, or registry-based data are needed to ascertain the encouraging findings of our review.

Intravenous tenecteplase compared with alteplase for minor ischaemic stroke: a secondary analysis of the AcT randomised clinical trial.

BACKGROUND: In ischaemic stroke, minor deficits (National Institutes of Health Stroke Scale (NIHSS) ≤5) at presentation are common but often progress, leaving patients with significant disability. We compared the efficacy and safety of intravenous thrombolysis with tenecteplase versus alteplase in patients who had a minor stroke enrolled in the Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT) trial. METHODS: The AcT trial included individuals with ischaemic stroke, aged >18 years, who were eligible for standard-of-care intravenous thrombolysis. Participants were randomly assigned 1:1 to intravenous tenecteplase (0.25 mg/kg) or alteplase (0.9 mg/kg). Patients with minor deficits pre-thrombolysis were included in this post-hoc exploratory analysis. The primary efficacy outcome was the proportion of patients with a modified Rankin Score (mRS) of 0-1 at 90-120 days. Safety outcomes included mortality and symptomatic intracranial haemorrhage (sICH). RESULTS: Of the 378 patients enrolled in AcT with an NIHSS of ≤5, the median age was 71 years, 39.7% were women; 194 (51.3%) received tenecteplase and 184 (48.7%) alteplase. The primary outcome (mRS score 0-1) occurred in 100 participants (51.8%) in the tenecteplase group and 86 (47.5 %) in the alteplase group (adjusted risk ratio (RR) 1.14 (95% CI 0.92 to 1.40)). There were no significant differences in the rates of sICH (2.9% in tenecteplase vs 3.3% in alteplase group, unadjusted RR 0.79 (0.24 to 2.54)) and death within 90 days (5.5% in tenecteplase vs 11% in alteplase group, adjusted HR 0.99 (95% CI 0.96 to 1.02)). CONCLUSION: In this post-hoc analysis of patients with minor stroke enrolled in the AcT trial, safety and efficacy outcomes with tenecteplase 0.25 mg/kg were not different from alteplase 0.9 mg/kg.

Clinical uncertainty in large vessel occlusion ischemic stroke: does automated perfusion imaging make a difference? An intra-rater and inter-rater agreement study.

BACKGROUND: Limited research exists regarding the impact of neuroimaging on endovascular thrombectomy (EVT) decisions for late-window cases of large vessel occlusion (LVO) stroke. OBJECTIVE: T0 assess whether perfusion CT imaging: (1) alters the proportion of recommendations for EVT, and (2) enhances the reliability of EVT decision-making compared with non-contrast CT and CT angiography. METHODS: We conducted a survey using 30 patients drawn from an institutional database of 3144 acute stroke cases. These were presented to 29 Canadian physicians with and without perfusion imaging. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG). RESULTS: The percentage of EVT recommendations differed by 1.1% with or without perfusion imaging. Individual decisions changed in 21.4% of cases (11.3% against EVT and 10.1% in favor). Inter-rater agreement (κG) among the 29 raters was similar between non-perfusion and perfusion CT neuroimaging (κG=0.487; 95% CI 0.327 to 0.647 and κG=0.552; 95% CI 0.430 to 0.675). The 95% CIs overlapped with moderate agreement in both. Intra-rater agreement exhibited overlapping 95% CIs for all 28 raters. κG was either substantial or excellent (0.81-1) for 71.4% (20/28) of raters in both groups. CONCLUSIONS: Despite the minimal difference in overall EVT recommendations with either neuroimaging protocol one in five decisions changed with perfusion imaging. Regarding agreement we found that the use of automated CT perfusion images does not significantly impact the reliability of EVT decisions for patients with late-window LVO.

Assessment of remote ischemic conditioning delivery with optical sensor in acute ischemic stroke: Randomised clinical trial protocol.

BACKGROUND: Remote ischemic conditioning (RIC) is delivered by a blood pressure cuff over the limb, raising pressure 50 mmHg above the systolic blood pressure, to a maximum of 200 mmHg. The cuff is inflated for five minutes and then deflated for five minutes in a sequential ischemia-reperfusion cycle 4-5 times per session. Elevated pressure in the limb may be associated with discomfort and consequently reduced compliance. Continuous assessment of relative blood concentration and oxygenation with a tissue reflectance spectroscopy (a type of optical sensor device) placed over the forearm during the RIC sessions of the arm will allow us to observe the effect of inflation and deflation of the pressure cuff. We hypothesize, in patients with acute ischemic stroke (AIS) and small vessel disease, RIC delivered together with a tissue reflectance sensor will be feasible. METHODS: The study is a prospective, single-center, randomized control trial testing the feasibility of the device. Patients with AIS within 7 days from symptoms onset; who also have small vessel disease will be randomized 2:1 to intervention or sham control arms. All patients randomized to the intervention arm will receive 5 cycles of ischemia/reperfusion in the non-paralyzed upper limb with a tissue reflectance sensor and patients in the sham control arm will receive pressure by keeping the cuff pressure at 30 mmHg for 5 minutes. A total of 51 patients will be randomized, 17 in the sham control arm and 34 in the intervention arm. The primary outcome measure will be the feasibility of RIC delivered for 7 days or at the time of discharge. The secondary device-related outcome measures are fidelity of RIC delivery and the completion rate of intervention. The secondary clinical outcome includes a modified Rankin scale, recurrent stroke and cognitive assessment at 90 days. DISCUSSION: RIC delivery together with a tissue reflectance sensor will allow insight into the blood concentration and blood oxygenation changes in the skin. This will allow individualized delivery of the RIC and improve compliance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05408130, June 7, 2022.

Neuroleptic Malignant Syndrome in a Patient With Anti-N-Methyl-D-Aspartate Receptor Encephalitis: Case Report and Review of Related Literature.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe but treatable disease that presents with symptoms similar to neuroleptic malignant syndrome (NMS). CASE REPORT: We describe a 28-year old female who initially presented with headaches, behavioral changes, anxiety, lip tremors, and rigidity of extremities. She was prescribed with olanzapine and later manifested with neuroleptic malignant syndrome symptoms such as decrease in sensorium, muscle rigidity, hyperthermia and tachycardia. Further investigation showed presence of bilateral ovarian teratoma and anti-NMDAR antibodies in her serum and cerebrospinal fluid. Symptoms resolved after intravenous high-dose methylprednisolone, bilateral oophoro-cystectomy, and intravenous immunoglobulin administration. Overlapping pathological mechanisms of anti- NMDAR encephalitis and NMS were discussed. Ten patients with anti- NMDAR encephalitis and NMS were noted in a review of literature. Prognosis was favorable and intervention ranged from supportive to methylprednisolone and intravenous immunoglobulin administration, plasma exchange and teratoma resection. CONCLUSION: Anti- NMDAR encephalitis patients are at risk for NMS due to antipsychotic intolerance and other interrelated pathophysiological mechanisms. The overlap between the signs and symptoms of anti-NMDAR encephalitis and NMS poses a diagnostic dilemma and warrants a careful investigation and management.

Rocuronium as Neuromuscular Blockade in Tetanus Patients With Methamphetamine Use Disorder: A Case Report.

BACKGROUND: Spasm control is essential in the management of tetanus. Benzodiazepines are administered as initial treatment of tetanic spasms; however, sedation may be difficult to attain among patients with methamphetamine use disorder. Neuromuscular blocking agents, which act on an entire different mechanism, can be given to induce paralysis. METHODS: We describe 2 cases of patients with methamphetamine use disorder who were diagnosed with severe tetanus and our experience in the use of rocuronium to control their spasms. We performed a systematic review of the SCOPUS and PubMed databases for case reports and case series describing the use of rocuronium in tetanus patients who also have methamphetamine use disorder. We discussed the clinical features and treatment outcomes. RESULTS: A total of 4 cases of patients with substance abuse disorder who had severe tetanus were reported in the literature, including the current cases. The mean age was 28.8 years; all of them male. Trismus, generalized limb and abdominal rigidity were the most common presentation. Three patients underwent emergency tracheostomy. Rocuronium was given as 0.008mg/kg bolus in 1 patient; 2 patients received an intravenous bolus dose of 0.6mg/kg. Infusion dose ranged from 5 to 10 mcg/kg/min. Spasms were controlled within 24-48 hours after giving rocuronium in 3 out of 4 patients. One patient died from complications of dysautonomia and immobility. CONCLUSION: Rocuronium demonstrates a potential role as neuromuscular blocking agent of choice for patients with chronic methamphetamine use disorder and severe tetanus. Management challenges and complications of severe tetanus were also highlighted in this study.

Cost of hospitalization for stroke in a low-middle-income country: Findings from a public tertiary hospital in the Philippines.

BACKGROUND: Determining the cost of hospitalization for acute stroke is important in the appropriate allocation of resources for public health facilities and in the cost effectiveness analysis of interventions. Despite being the second leading cause of mortality in the Philippines, there are no published data on the cost of stroke in the country. AIM: The study aims to determine the in-hospitalization cost for stroke (IHCS) in a tertiary public hospital in the Philippines and identify the factors influencing IHCS. METHODS: The study was a retrospective review of the medical and billing records of the hospital. Adult patients admitted for acute stroke between 1 June 2017 and 31 May 2018 were included in the analysis. After the mean cost of stroke was determined, multivariate logistic regression analysis was done to determine demographic and clinical characteristics that were predictive of stroke cost. RESULTS: A total of 863 patient records were analyzed. The median in-hospitalization cost for stroke was PHP 17,141.50 or US$329.52. Independent determinants of higher cost include male sex (p = 0.021), stroke type (hemorrhagic stroke, p = 0.001; subarachnoid hemorrhage, p < 0.001), lower GCS on admission (p = 0.023), surgical intervention (p < 0.001), intravenous thrombolysis (p < 0.001), infection (p < 0.001), length of hospital stay (p < 0.001), and mechanical ventilation (p = 0.008). CONCLUSION: The study provided current data on the in-hospitalization cost of acute stroke in a public tertiary hospital in the Philippines. Male sex, stroke type, lower GCS on admission, surgical intervention, intravenous thrombolysis, infection, length of hospital stay, and mechanical ventilation were independent predictors of cost.