Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis.

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Ketamine to Prevent Endotracheal Intubation in Adults with Refractory Non-convulsive Status Epilepticus: A Case Series.

BACKGROUND: Non-convulsive status epilepticus (NCSE) is defined as status epilepticus (SE) with no obvious motor phenomenon and is diagnosed based on electroencephalogram (EEG). Refractory SE (RSE) is the persistence of seizures despite treatment with an adequately dosed first-line and second-line agents. Although guidelines for convulsive RSE include third-line agents such as intravenous anesthetic drugs (midazolam, propofol, or barbiturates), the therapeutic approach to NCSE is not well outlined. Treatment with traditional anesthetics invariably includes endotracheal intubation, which is associated with significant adverse events. Comparatively, ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist is not associated with significant cardiorespiratory depression and may help in avoiding intubation. OBJECTIVE: In this case series, we describe our experience with the early use of intravenous ketamine as the first anesthetic agent in patients with refractory NCSE to avoid endotracheal intubation. METHODS: We present a case series of nine patients managed in the Neurointensive Care Unit at a university-affiliated tertiary care hospital. The study was approved by the hospital and university institutional review boards and the requirement for informed consent was waived for retrospective analysis of existing data, per institutional policy. All cases of SE were identified from a prospective database, and a subsequent retrospective chart review identified all patients with a diagnosis of refractory NCSE in whom ketamine was used as the first anesthetic agent. The primary endpoint was the avoidance of endotracheal intubation while on ketamine infusion. The secondary endpoint was defined as cessation of both clinical and electrographic seizures recorded on continuous EEG within 24 h of ketamine administration. RESULTS: A total of nine patients experiencing refractory NCSE were included in this case series, with a median age of 61 (range 26-72) years and seven patients were male. The primary endpoint, avoiding intubation, was achieved in five out of nine (55%) cases. Six patients experienced resolution of refractory NCSE with ketamine administration as the sole anesthetic agent. Four patients required endotracheal intubation and three patients had a failure of seizure cessation with ketamine. Hypersalivation and pneumonia were the most common ketamine associated adverse events. In non-intubated patients, no deaths occurred. One patient was discharged home, four to subacute rehabilitation, one to a long term acute care hospital, and one patient to hospice. CONCLUSION: The use of ketamine as the primary anesthetic agent may be a reasonable option to avoid endotracheal intubation in a subset of patients with refractory NCSE. This study is limited by its small sample size, retrospective design, and reliance on information obtained from chart review.

Blood pressure variability and short-term outcomes after mechanical thrombectomy in patients with acute ischemic stroke.

OBJECTIVES: There is limited data evaluating effects of post-mechanical thrombectomy (MT) blood pressure (BP) control on short-term clinical outcomes in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). We aim to investigate the association of BP variations, after MT, with stroke early outcomes. MATERIALS AND METHODS: A retrospective study was conducted on AIS patients with LVO undergoing MT at a tertiary center over 3.5 years. Hourly BP data was recorded within the first 24- and 48-hours post-MT. BP variability was expressed as the interquartile range (IQR) of BP distribution. Short-term favorable outcome was defined as modified Rankin scale (mRS) 0-3, discharge to home or inpatient rehabilitation facility (IRF). RESULTS: Of the 95 enrolled subjects, 37(38.9%) had favorable outcomes at discharge and 8 (8.4%) died. After adjustment for confounders, an increase in IQR of systolic blood pressure (SBP) within the first 24 hours after MT revealed a significant inverse association with favorable outcomes (OR 0.43, 95% CI [0.19, 0.96], p = 0.039). Increased median MAP within the first 24 hours after MT correlated with favorable outcomes (OR 1.75, 95% CI [1.09, 2.83], p = 0.021). Subgroup analysis redemonstrated significant inverse association between increased SBP IQR and favorable outcomes (OR 0.48, 95% CI [0.21, 0.97], p = 0.042) among patients with successful revascularization. CONCLUSIONS: Post-MT high SBP variability was associated with worse short-term outcomes in AIS patients with LVO regardless of recanalization status. MAP values may be used as indicators for functional prognosis.

Descriptive analysis of Acute Ischemic stroke in COVID-19 patients through the course of the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) has been associated with Acute Ischemic Stroke (AIS). Here, we characterize our institutional experience with management of COVID-19 and AIS. Baseline demographics, clinical, imaging, and outcomes data were determined in patients with COVID-19 and AIS presenting within March 2020 to October 2020, and November 2020 to August 2021, based on institutional COVID-19 hospitalization volume. Of 2512 COVID-19 patients, 35 (1.39%, mean age 63.3 years, 54% women) had AIS. AIS recognition was frequently delayed after COVID-19 symptoms (median 19.5 days). Four patients (11%) were on therapeutic anticoagulation at AIS recognition. AIS mechanism was undetermined or due to multiple etiologies in most cases (n = 20, 57%). Three patients underwent IV TPA, and three underwent mechanical thrombectomy, of which two suffered re-occlusion. Three patients had incomplete mRNA vaccination course. Fourteen (40%) died, with 26 (74%) having poor outcomes. Critical COVID-19 severity was associated with worsened mortality (p = 0.02). More patients (12/16; 75%) had either worsened or similar 3-month functional outcomes, than those with improvement, indicating the devastating impact of co-existing AIS and COVID-19. Comparative analysis showed that patients in the later cohort had earlier AIS presentation, fewer stroke risk factors, more comprehensive workup, more defined stroke mechanisms, less instance of critical COVID-19 severity, more utilization of IV TPA, and a trend towards worse outcomes for the sub-group of mild-to-moderate COVID-19 severity. AIS incidence, NIHSS, and overall outcomes were similar. Further studies should investigate outcomes beyond 3 months and their predictive factors, impact of completed vaccination course, and access to neurologic care.

Association of External Ventricular Drain Wean Strategy with Shunt Placement and Length of Stay in Subarachnoid Hemorrhage: A Prospective Multicenter Study.

BACKGROUND: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. METHODS: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. RESULTS: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed posthospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18-1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11-0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. CONCLUSIONS: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified.

Evidence-Based Management of External Ventricular Drains.

PURPOSE OF REVIEW: The optimal management of external ventricular drains (EVD) in the setting of acute brain injury remains controversial. Therefore, we sought to determine whether there are optimal management approaches based on the current evidence. RECENT FINDINGS: We identified 2 recent retrospective studies on the management of EVDs after subarachnoid hemorrhage (SAH) which showed conflicting results. A multicenter survey revealed discordance between existing evidence from randomized trials and actual practice. A prospective study in a post-traumatic brain injury (TBI) population demonstrated the benefit of EVDs but did not determine the optimal management of the EVD itself. The recent CLEAR trials have suggested that specific positioning of the EVD in the setting of intracerebral hemorrhage with intraventricular hemorrhage may be a promising approach to improve blood clearance. Evidence on the optimal management of EVDs remains limited. Additional multicenter prospective studies are critically needed to guide approaches to the management of the EVD.

Electroencephalogram Characteristics in Critical Ill Patients Before Cardiac Arrest: A Case Series.

Background/Objectives. To illustrate characteristic electroencephalogram (EEG) features in patients prior to their first cardiac arrest. Methods. We identified 15 patients who suffered cardiac arrest during continuous EEG at our institution from June 2016 to June 2019. Eight patients were excluded due to co-administration of intravenous anesthetics (which may confound EEG) or if they had a previous prolonged cardiac arrest (>5 minutes) during the same hospitalization. We collected background information, analyzed the time span and vital signs between the initial background change and cardiac arrest. Results. The time span range (minutes) from initial background change to cardiac arrest was 4 to 483 (average 128.9), initial background change to suppression was 0 to 372 (average 75.6), suppression to cardiac arrest was 1 to 140 (average 53.3), suppression to complete suppression was 0 to 66 (average 20.4), and complete suppression to cardiac arrest was 1 to 111 (average 32.9). Three patients showed background changes more than 160 minutes before cardiac arrest. All patients showed progressive heart rate (HR) decline at or before the beginning of suppression on EEG. HR (beats/min) (mean ± SE) at background change, background suppression, complete suppression, and cardiac arrest was 86.3 ± 7.5, 63.9± 7.5, 36.0 ± 6.8, and 0, respectively. We found statistically significant HR changes (P < .05) between background change and complete suppression time points. Conclusions. Our data indicate that EEG pattern change can occur minutes to hours before the initial cardiac arrest. These patterns may be due to progressive cerebral ischemia. Further studies with broad-scale monitoring of vital signs and evoked potentials may help develop models for predicting cardiac insufficiency.

Nicardipine Associated Risk of Short-Term Mortality in Critically Ill Patients with Ischemic Stroke.

BACKGROUND: Hypertensive emergency is commonly associated with acute ischemic stroke and can be a predictor of poor outcome in these patients. Nicardipine and labetalol are commonly administered for the treatment of acute hypertension following stroke. Yet, data are lacking on the safety of these agents in this setting. OBJECTIVE: This study aimed to determine all-cause in-hospital mortality, medication-related hypotensive episodes, development of hospital acquired infections and hospital length of stay between nicardipine and labetalol use for the management of hypertension after acute ischemic stroke. METHODS: This retrospective study used a prospective database of individuals admitted to the neurointensive care unit at a university-based hospital over 39 months. Patients with confirmed ischemic strokes were included in this analysis. Data were recorded for administration of nicardipine and labetalol following acute stroke. RESULTS: A total of 244 patients with acute ischemic stroke were included in this analysis (mean age, 64.3 ± 15 years; 52.2% males). Nicardipine use after acute ischemic stroke was associated with an increased risk of 30-day mortality (odds ratio [OR]: 4.6, 95% confidence interval [CI] 1.3-15.7; P = .02). A single episode of hypotension in the first 72hours of admission was also significantly associated with mortality (OR 4.35 [95% CI 1.2-14.9]; P = .02). CONCLUSIONS: Nicardipine was associated with an increased risk of short-term mortality after acute ischemic stroke. This may have been due to hypotension, tachycardia, or pulmonary edema which were not apparent in our study. Further studies are required to elucidate the cause of this association.

Cardiac Dysfunction in Neurocritical Care: An Autonomic Perspective.

A number of neurologic disorders can cause cardiac dysfunction by involving the conductive system and contractile apparatus of the heart. This is especially prominent in the neurocritical care setting where the spectrum of cardiac dysfunction due to acute neurologic injury ranges from trivial and isolated electrocardiographic changes to malignant arrhythmias and sudden death (Table 1). The mechanism of these cardiac complications is complex and not fully understood. An understanding of the neuroanatomical structures and pathways is of immense importance to comprehend the underlying pathophysiology that culminates as cardiac damage and dysregulation. Once the process is initiated, it can complicate and adversely affect the outcome of primary neurologic conditions commonly seen in the neurocritical care setting. Not only are these cardiac disorders under-recognized, there is a paucity of data to formulate evidence-based guidelines regarding early detection, acute management, and preventive strategies. However, certain details of clinical features and their course combined with location of primary neurologic lesion on neuroimaging and data obtained from laboratory investigations can be of great value to develop a strategy to appropriately manage these patients and to prevent adverse outcome from these cardiac complications. In this review, we highlight the mechanisms of cardiac dysfunction due to catastrophic neurologic conditions or due to stress of critical illness. We also address various clinical syndromes of cardiac dysfunction that occur as a result of the neurologic illness and in turn may complicate the course of the primary neurologic condition.

Cerebral Abscess following Mechanical Thrombectomy for Ischemic Stroke: Report of a Case and Review of Literature.

Cerebral infections have been reported after endovascular interventions such as embolization and coiling. Such complications are extremely rare and only one other case has been reported in a patient who underwent an endovascular therapy for ischemic stroke. We report a 32-year-old woman, who presented to our hospital with headaches lasting four weeks after an endovascular intervention for ischemic stroke via mechanical thrombectomy. Further investigations revealed a cerebral abscess in the area of the infarct. She was effectively treated with antibiotics in combination with stereotactic drainage and was discharged after she made a good recovery. A review of literature on cerebral abscesses after minimally invasive procedures such as endovascular intervention was also done and is being presented in this paper. A cerebral abscess can occur rarely after endovascular interventions. A high degree of suspicion is important in identifying patients with an abscess and appropriate treatment can prevent significant morbidity or even death.

Inadequate benzodiazepine dosing may result in progression to refractory and non-convulsive status epilepticus.

Status epilepticus (SE) is defined as ongoing seizures lasting longer than five minutes or multiple seizures without recovery. Benzodiazepines (BZDs) are first-line agents for the management of SE. Our objective was to evaluate BZD dosing in SE patients and its effects on clinical/electrographic outcomes. A retrospective analysis was conducted from a prospective database of SE patients admitted to a university-based neurocritical care unit. The initial presentation and progression to refractory SE (RSE) and non-convulsive SE (NCSE) with coma was evaluated. Outcome measures included length of stay (LOS), rates of intubation, ventilator-dependent days, and Glasgow outcome scale (GOS). The lorazepam equivalent (LE) dosage of BZDs administered was calculated and we analysed variations in progression if 4 mg or more of LE (adequate BZDs) was administered. Among 100 patients, the median dose of LE was 3 mg (IQR: 2-5 mg). Only 31% of patients received adequate BZDs. Only 18.9% of patients with NCSE without coma received adequate BZDs (p=0.04). Among patients progressing to RSE, 75.4% had not received adequate BZDs (p=0.04) and among patients developing NCSE with coma, 80.6% did not receive adequate BZDs (p=0.07). Escalating doses of BZDs were associated with a decrease in cumulative incidences of RSE (correlation coefficient r=-0.6; p=0.04) and NCSE with coma (correlation coefficient r=-0.7; p=0.003). Outcome measures were not influenced by BZD dosing. The majority of our patients were not adequately dosed with BZDs. Inadequate BZD dosing progressed to RSE and had a tendency to lead to NCSE with coma. Our study demonstrates the need to develop a hospital-wide protocol to guide first responders in the management of SE.

Efficacy of Cilostazol in Prevention of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.

OBJECTIVES: Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce symptomatic vasospasm and improve outcome in patients with aneurysmal subarachnoid hemorrhage considering its anti-platelet and vasodilatory effects. We aimed to analyze the effects of cilostazol on symptomatic vasospasm and clinical outcome among patients with aneurysmal subarachnoid hemorrhage (aSAH). PATIENTS AND METHODS: We searched PubMed and Embase databases to identify 1) prospective randomized trials, and 2) retrospective trials, between May 2009 and May 2017, that investigated the effect of cilostazol in patients with aneurysmal aSAH. All patients were enrolled after repair of a ruptured aneurysm by clipping or endovascular coiling within 72hours of aSAH. fixed-effect models were used to pool data. We used the I2 statistic to measure heterogeneity between trials. RESULTS: Five studies were included in our meta-analysis, comprised of 543 patients with aSAH (cilostazol [n=271]; placebo [n=272], mean age, 61.5years [SD, 13.1]; women, 64.0%). Overall, cilostazol was associated with a decreased risk of symptomatic vasospasm (0.31, 95% CI 0.20 to 0.48; P<0.001), cerebral infarction (0.32, 95% CI 0.20 to 0.52; P <0.001) and poor outcome (0.40, 95% CI 0.25 to 0.62; P<0.001). We observed no evidence for publication bias. Statistical heterogeneity was not present in any analysis. CONCLUSION: Cilostazol is associated with a decreased risk of symptomatic vasospasm and may be clinically useful in the treatment of delayed cerebral vasospasm in patients with aSAH. Our results highlight the need for a large multi-center trial to confirm the observed association.

Fulminant Reversible Cerebral Vasoconstriction Syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is increasingly being recognized as a diagnosis in patients presenting with thunderclap headaches. In the vast majority of the cases, the syndrome follows a benign course and patients recover completely without any significant therapeutic intervention. In the rarest of cases, RCVS follows a monophasic course with rapid worsening, severe neurological deficits, and poor outcomes. We present the case of a 25-year-old female who presented with headaches which were worsening over 1 week. She was admitted to the hospital and rapidly worsened to develop severe neurological deficits over the next day. Initial computed tomography scan showed areas of hemorrhage and multiple ischemic strokes. Computed tomography angiogram and a conventional cerebral angiogram both revealed multifocal vasoconstriction, highly suggestive of RCVS. Despite aggressive medical and surgical management, the patient continued to worsen and eventually died. Autopsy findings did not show evidence of vasculopathy or any other underlying disorder, further supporting the diagnosis of RCVS. The RCVS is usually a benign self-remitting condition which commonly affects young females and presents with an insidious onset of headaches. Rarely, it can have a fulminant course with devastating outcomes. This case illustrates an exceptionally uncommon clinical course of RCVS and the challenges in its treatment.

Apixaban for the treatment of cerebral venous thrombosis: A case series.

BACKGROUND: Venous thrombosis affecting cerebral veins and sinuses (CVT) is an uncommon neurological condition. Traditionally patients are treated with intravenous heparin followed by an oral vitamin K antagonist like warfarin. Direct oral anticoagulants (DOACs) may offer advantages over warfarin. There is evidence to demonstrate the effectiveness of both dabigatran and rivaroxaban. No data, however, has been published describing the use of apixaban in patients with CVT. METHODS: Report of three cases of CVT and review literature on available treatment options; efficacy and safety of novel oral anticoagulants in patients with systemic thrombosis. RESULTS: All patients presented with typical features of CVT. After confirming the diagnosis, they were acutely treated with heparin and later discharged on apixaban. During follow up visits, they tolerated apixaban well and did not have any bleeding complications. Follow up scans showed resolution of the thrombus and recanalization. CONCLUSION: CVT is an uncommon neurological condition and is often complicated by associated intraparenchymal hemorrhage. Although not recommended in current guidelines, apixaban may be a safe and effective option for the treatment of CVT.

Late onset neuromyelitis optica mimicking an acute stroke in an elderly patient.

Neuromyelitis optica spectrum disorder (NMOSD) was recently proposed as a unifying term for Neuromyelitis optica (NMO) and related syndromes to incorporate patients with NMO antibody but without the full clinical spectrum. NMO is a rare, demyelinating condition which predominantly affects females with a peak incidence in the third and fourth decade of life. We report a case of NMOSD in an elderly patient with extremely late onset (>80years) of disease. The patient presented with findings of sudden onset unilateral symptoms, which is extremely unusual for NMOSD. She had frequent relapses which were treated with high dose steroids and plasmapheresis but has not had any relapse since being started on immunosuppressive therapy and continues to do well. Our case also highlights the varied clinical presentations of NMOSD and we believe that the diagnosis of NMOSD should be considered in elderly patients in the appropriate clinical setting despite the presence of unconventional symptoms.

Which Comorbidities and Complications Predict Ischemic Stroke Recovery and Length of Stay?

OBJECTIVES: Stroke is the second most common cause of death worldwide and can lead to significant disability and long-term costs. Length of stay (LOS) is the most predictive factor in determining inpatient costs. In the present study, factors that affect disability and LOS among ischemic stroke patients admitted to an urban community hospital and 2 university-based teaching hospitals were assessed. METHODS: Data for consecutive patients with acute ischemic strokes were collected, by reviewing discharge diagnosis International Classification of Diseases codes. A data mining process was used to analyze admission data. Data regarding comorbidities and complications were abstracted by mining the secondary diagnoses for their respective International Classification of Diseases-9 codes. The primary outcome was LOS, calculated from the dates of admission and dates of discharge. The second outcome of interest was disability, which was evaluated by the modified Rankin score at the time of discharge. RESULTS: LOS progressively increased with greater disability. Greater age and higher National Institute of Health Stroke Scale at admission were associated with both higher disability and longer LOS. Presence of congestive heart failure or chronic kidney disease, atrial fibrillation, other arrhythmias (preexisting or new onset), and development of acute renal failure were associated with greater LOS but not greater disability status. Patients with a previous stroke and those that developed urinary tract infection as a complication had higher disability. CONCLUSIONS: Greater age and higher National Institute of Health Stroke Scale at admission were associated with both higher disability and longer LOS. Congestive heart failure, CRF, presence of arrhythmias, and development of acute renal failure were associated with greater LOS. The development of urinary tract infection caused higher disability.

Clobazam: An effective add-on therapy in refractory status epilepticus.

Refractory status epilepticus (RSE) is a medical emergency, with significant morbidity and mortality. The use and effectiveness of clobazam, a unique 1,5-benzodiazepine, in the management of RSE has not been reported before. Over the last 24 months, we identified 17 patients with RSE who were treated with clobazam in our hospital. Eleven of the 17 patients had prior epilepsy. Fifteen patients had focal status epilepticus. Use of clobazam was prompted by a favorable pharmacokinetic profile devoid of drug interactions. Clobazam was introduced after a median duration of 4 days and after a median of three failed antiepileptic drugs. A successful response, defined as termination of RSE within 24 h of administration, without addition or modification of concurrent AED and with successful wean of anesthetic infusions, was seen in 13 patients. Indeterminate response was seen in three patients, whereas clobazam was unsuccessful in one patient. Clobazam averted the need for anesthetic infusions in five patients. Clobazam was well tolerated, and appears to be an effective and promising option as add-on therapy in RSE. Its efficacy, particularly early in the course of SE, should be further investigated in prospective, randomized trials.