Rahul Rathakrishnan

Early and Continuous Neurologic Improvements after Intravenous Thrombolysis Are Strong Predictors of Favorable Long-term Outcomes in Acute Ischemic Stroke

BACKGROUND Intravenously administered tissue plasminogen activator (IV tPA) remains the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Considerable proportion of AIS patients demonstrate changes in their neurologic status within the first 24 hours of intravenous thrombolysis with IV tPA. However, there are little available data on the course of clinical recovery in subacute 2- to 24-hour window and its impact. We evaluated whether neurologic improvement at 2 and 24 hours after IV tPA bolus can predict functional outcomes in AIS patients at 3 months. METHODS Data for consecutive AIS patients treated with IV tPA within 4.5 hours of symptom onset during 2007-2011 were prospectively entered in our thrombolyzed registry. National Institutes of Health Stroke Scale (NIHSS) scores were recorded before IV tPA bolus, at 2 and 24 hours. Early neurologic improvement (ENI) at 2 hours was defined as a reduction in NIHSS score by 10 or more points from baseline or an absolute score of 4 or less points at 2 hours. Continuous neurologic improvement (CNI) was defined as a reduction of NIHSS score by 8 or more points between 2 and 24 hours or an absolute score of 4 or less points at 24 hours. Favorable functional outcomes at 3 months were determined by modified Rankin Scale (mRS) score of 0-1. RESULTS Of 2460 AIS patients admitted during the study period, 263 (10.7%) received IV tPA within the time window; median age was 64 years (range 19-92), with 63.9% being men, a median NIHSS score of 17 points (range 5-35), and a median onset-to-treatment time of 145 minutes (range 57-270). Overall, 130 (49.4%) thrombolyzed patients achieved an mRS score of 0-1 at 3 months. The female gender, age, and baseline NIHSS score were found to be significantly associated with CNI on univariate analysis. On multivariate analysis, NIHSS score at onset and female gender (odds ratio [OR]: 2.218, 95% confidence interval [CI]: 1.140-4.285; P=.024) were found to be independent predictors of CNI. Factors associated with favorable outcomes at 3 months on univariate analysis were younger age, female gender, hypertension, NIHSS score at onset, recanalization on transcranial Doppler (TCD) monitoring or repeat computed tomography (CT) angiography, ENI at 2 hours, and CNI. On multivariate analysis, NIHSS score at onset (OR per 1-point increase: .835, 95% CI: .751-.929, P<.001), 2-hour TCD recanalization (OR: 3.048, 95% CI: 1.537-6.046; P=.001), 24-hour CT angiographic recanalization (OR: 4.329, 95% CI: 2.382-9.974; P=.001), ENI at 2 hours (OR: 2.536, 95% CI: 1.321-5.102; P=.004), and CNI (OR: 7.253, 95% CI: 3.682-15.115; P<.001) were independent predictors of favorable outcomes at 3 months. CONCLUSIONS Women are twice as likely to have CNI from the 2- to 24-hour period after IV tPA. ENI and CNI within the first 24 hours are strong predictors of favorable functional outcomes in thrombolyzed AIS patients.

Response to Letter Regarding Article, “External Carotid Artery–Internal Jugular Vein Fistula: A Complication of Internal Jugular Cannulation”

We appreciate the comments and the issues raised by Thalhammer et al in their letter regarding our case report.1 Our patient presented with an episode of transient right-sided weakness. Carotid duplex was performed as part of the stroke work-up and to explore the cause of the bruit on the right side of her neck. The fistula between the external carotid …

Early electroencephalography in patients with Emergency Room diagnoses of suspected new-onset seizures: Diagnostic yield and impact on clinical decision-making

PURPOSE To assess the utility of acute electroencephalography (EEG) performed in the emergency room (ER) and its impact on subsequent management of patients with new-onset seizures. Adults who recover fully in the ER following suspected isolated new-onset seizures are usually discharged to the neurology clinic for further review. An EEG at that stage may be normal. We sought to assess the feasibility and yield of early EEG in the ER setting, its impact on management. METHODS A prospective study from January 2008 to January 2011 of patients diagnosed by ER physicians with uncomplicated suspected first episodes of unprovoked convulsive seizures. All patients underwent routine 30-min EEG in the ER prior to discharge and specialist review was arranged in the epilepsy clinic within 2 weeks of presentation. Management decisions were at the discretion of the treating neurologist. Seizure recurrence was assessed during a follow up period between 9 months and 3 years. RESULTS 136 patients were included in the study (92 males). Mean age was 32 years (range 16-73). Forty had abnormal EEGs: 16 focal epileptiform discharges, 12 focal slowing, 10 generalized spike-wave discharges and 2 generalized slowing. Using multivariate analysis, those with abnormal EEG (51% vs 11%, p = 0.003) and abnormal MRI (53% vs 28%, p < 0.001) were more likely to be commenced on anticonvulsant therapy. Abnormal MRI (p = 0.001) was independently associated with a higher risk of recurrence. CONCLUSIONS Following an ER diagnosis of new-onset uncomplicated seizure, early EEG had a high diagnostic yield. Abnormal EEG and abnormal MRI significantly contributed to decision-making regarding treatment at specialist review. Abnormal MRI was associated with significantly higher risks of subsequent seizures.

Generalised convulsive status epilepticus in Singapore: Clinical outcomes and potential prognostic markers

PURPOSE To study the characteristics, outcomes and prognostic markers of convulsive status epilepticus (SE) in Singapore. METHODS 62 adult admissions to the National University Hospital Singapore from 2002 to 2005 were studied. Ethnicity, history of epilepsy, educational subnormality, neuroimaging, seizure duration, length of stay, Modified Rankin Scale (MRS) pre and post discharge, blood glucose, creatine kinase, potassium, white cell and platelet count were recorded. An MRS> or =3 at discharge was defined as a poor outcome. ROCs of significant variables were plotted to identify the best test cut-offs. RESULTS Mean age was 59.2 years (range 20-94). 75.9% patients had epilepsy. Mean length of stay was 14 days (range 1-75). Univariate analyses revealed age (p=0.01, OR 1.075, 95% CI 1.030-1.122), length of stay in ICU (p=0.03, OR 1.299, 95% CI 1.014-1.665) and hospital (p=0.014, OR 1.203, 95% CI 1.038-1.393) and hyperglycemia (p=0.045, OR 1.327, 95% CI 1.007-1.750) associated with poor outcome. Test cut-off values for prognostic markers were established: age> or =55 years (ROC 0.790, sensitivity 72.3, specificity 85.7, PPV9 4.4%, NPV 48.8%) and serum glucose> or =7 mmol/L (ROC 0.737, sensitivity 72.3, specificity 80.0, PPV 93.5%, NPV 36.4%). A discriminant model using these variables was then constructed with probability scores for poor outcome. DISCUSSION Age, hyperglycemia and length of stay in hospital influenced outcome from convulsive SE in the local population with hyperglycemia being a novel prognostic marker. Some prognostic markers cited in the literature differed, highlighting the possibility that these indicators may vary across population groups.

The clinico-radiological spectrum of isolated cortical vein thrombosis

Isolated cortical vein thrombosis (ICVT) in the absence of sinus or great venous involvement is rare. Various MRI sequences have been proposed for diagnostic accuracy, although follow-up data are limited. The optimal management strategy remains uncertain. Patients with ICVT treated between 2006 and 2008 were retrospectively studied. Diagnostic and follow-up neuroimaging were reviewed independently, and we evaluated their treatment and outcomes. Five patients (mean age 41 years; range, 25-54 years) were included. All presented with seizures. Focal neurological deficits were noted in one patient only. T2 susceptibility-weighted MRI abnormalities were observed in all patients. T2-weighted parenchymal hyperintensities involving the cortical-subcortical regions around the ICVT had completely resolved on follow-up scans. Clinical outcomes were uniformly good, despite variable treatment strategies. We observed significant, yet reversible, parenchymal T2-weighted MRI lesions in our patients with ICVT. Follow-up clinical and radiological studies demonstrate recovery independent of treatment regimes. T2-weighted MRI was found to be a useful diagnostic tool and might improve diagnostic accuracy in carefully selected patients with new-onset seizures.

Diffuse cystic leucoencephalopathy after buprenorphine injection

Buprenorphine has been prescribed for opioid detoxification and subsequent maintenance therapy with favourable outcomes. Its high affinity for the mu receptor, higher analgesic potency than morphine, antagonistic effects at higher doses as a partial agonist, lower incidence of physical dependence, and mild withdrawal symptoms confer qualities that make it advantageous for the treatment of opioid dependence.1 Buprenorphine, marketed under the trade name Subutex, may be administered sublingually, subcutaneously, or intravenously. We describe a severe neurological effect of intravenous buprenorphine exposure that resulted in diffuse cystic leucoencephalopathy. An 18 year old man was found unconscious in his bedroom by his girlfriend. He had no past history, and no family history of neurological or metabolic diseases. He was brought to the emergency room febrile, comatose and in severe respiratory failure (pH 7.399, pO2 84 mmHg, pCO2 42 mmHg, bicarbonate 24.9 mmol/l, on 100% non-rebreathing mask). He was intubated and treated presumptively for pneumonia with intravenous imipenam and azithromycin. He did not require inotropic support. Physical examination revealed a drowsy and lethargic man, who had bilateral basal crepitations in the lungs. Apart from midrange pupils that were sluggishly reactive to light, the neurological examination was unremarkable. There was no evidence of external bruises, injuries or obvious needle track marks …

Isolated cortical vein thrombosis in a patient with arteriovenous malformation

A 46-year-old man presented with intermittent episodes of paraesthesia over 24 hours involving the left arm and face. Normal consciousness was retained with no motor symptoms. There was no headache. He had no significant medical history, did not smoke, consume alcohol or abuse recreational drugs. No clear precipitating events could be identified prior to the onset. His systemic and neurological examination was normal. Brain MRI revealed a cortical vein thrombosis (CVT) with vasogenic edema over the right post-central gyrus. A right temporal arteriovenous malformation (AVM) was also detected with no evidence of acute hemorrhage (Fig. 1). There was no anatomical relationship between the two at cerebral angiography. Routine blood

External Carotid Artery–Internal Jugular Vein Fistula A Complication of Internal Jugular Cannulation

A 75-year-old female patient was admitted to our hospital after an episode of transient right-sided weakness. Her medical history was significant for ischemic heart disease, with coronary artery bypass grafting having been performed 4 years previously. She had experienced progressive dyspnea and decreased effort tolerance in the preceding 2 years, with 2 admissions due to congestive heart failure in the past year despite medical treatment. The physical examination was remarkable for a raised jugular venous pressure on the right side, bilateral ankle edema, and basal crackles in the lungs. A right carotid bruit was heard on auscultation during systole, although no thrill was …A 75-year-old female patient was admitted to our hospital after an episode of transient right-sided weakness. Her medical history was significant for ischemic heart disease, with coronary artery bypass grafting having been performed 4 years previously. She had experienced progressive dyspnea and decreased effort tolerance in the preceding 2 years, with 2 admissions due to congestive heart failure in the past year despite medical treatment. The physical examination was remarkable for a raised jugular venous pressure on the right side, bilateral ankle edema, and basal crackles in the lungs. A right carotid bruit was heard on auscultation during systole, although no thrill was …

How temporal evolution of intracranial collaterals in acute stroke affects clinical outcomes.

Objective: We compared intracranial collaterals on pretreatment and day 2 brain CT angiograms (CTA) to assess their evolution and relationship with functional outcomes in acute ischemic stroke (AIS) patients treated with IV tissue plasminogen activator (tPA). Methods: Consecutive AIS patients who underwent pretreatment and day 2 CTA and received IV tPA during 2010–2013 were included. Collaterals were evaluated by 2 independent neuroradiologists using 3 predefined criteria: the Miteff system, the Maas system, and 20-point collateral scale by the Alberta Stroke Program Early CT Score methodology. We stratified our cohort by baseline pre-tPA state of their collaterals and by recanalization status of the primary vessel for analysis. Good outcomes at 3 months were defined by a modified Rankin Scale score of 0–1. Results: This study included 209 patients. Delayed collateral recruitment by any grading system was not associated with good outcomes. All 3 scoring systems showed that collateral recruitment on the follow-up CTA from a baseline poor collateral state was significantly associated with poor outcome and increased bleeding risk. When the primary vessel remained persistently occluded, collateral recruitment was significantly associated with worse outcomes. Interestingly, collateral recruitment was significantly associated with increased mortality in 2 of the 3 grading systems. Conclusions: Not all collateral recruitment is beneficial; delayed collateral recruitment may be different from early recruitment and can result in worse outcomes and higher mortality. Prethrombolysis collateral status and recanalization are determinants of how intracranial collateral evolution affects functional outcomes.

Complex partial status epilepticus associated with adult H1N1 infection

In the wake of the worldwide H1N1 pandemic, there has been evidence that the H1N1 influenza virus is associated with neurological complications. This is the first report describing status epilepticus in an adult patient with H1N1 virus infection, to our knowledge. This patient had no prior history of epilepsy and presented with complex partial status epilepticus. This was further illustrated on electroencephalographs and MRI brain changes that corresponded with the patients clinical state and which subsequently resolved on follow-up. Although uncommon, H1N1 infections may result in central nervous system complications in adults and it is crucial to treat such patients with urgency.