Levetiracetam dosing for seizure prophylaxis in neurocritical care patients.

BACKGROUND/OBJECTIVE: Levetiracetam is used for seizure prophylaxis in patients presenting with subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). We aim to characterize the optimal levetiracetam dosage for seizure prophylaxis. METHODS: This retrospective cohort study included adult patients at an academic tertiary hospital presenting with SAH or TBI who received levetiracetam at a total daily dose (TDD) equivalent to or greater than 1000 mg. The primary outcome was combined seizure incidence, including clinical and subclinical seizures. RESULTS: We identified 139 patients (49.6% male, mean age 53 years) for inclusion. For patients receiving a 1000-mg TDD, the administration was 500 mg twice daily. For patients receiving >1000-mg TDD, 77/78 patients received 1000 mg twice daily and one patient received 750 mg twice daily. Patients receiving 1000-mg TDD had a higher seizure incidence than those receiving >1000-mg TDD (p = 0.01), despite no difference in examined confounders, including history of alcoholism (p = 0.49), benzodiazepine use (p = 0.28), or propofol use (p = 0.17). No difference in adverse effects was observed (anemia, p = 0.44; leukopenia, p = 0.60; thrombocytopenia, p = 0.86). CONCLUSIONS: Patients may experience a reduced incidence of clinical and electroencephalographic seizures with levetiracetam dosing >1000-mg TDD.

Safety and Feasibility of Phenylephrine Administration Through a Peripheral Intravenous Catheter in a Neurocritical Care Unit.

BACKGROUND/OBJECTIVE: Blood pressure optimization and maintenance of cerebral and spinal perfusion pressure are mainstays in the treatment of a neurocritically ill patient. Traditionally, central venous access has been required for vasopressor administration, with risk of inherent complications. The authors have previously reported pilot data on the safety of peripheral administration of phenylephrine in a neurocritical care unit. In this follow-up, we report the safety, feasibility, and potential efficacy of peripheral administration of low-concentration phenylephrine in a more robust cohort. METHODS: A retrospective chart review was conducted on all consecutive patients who received peripheral phenylephrine in a tertiary care hospital neurocritical care unit. RESULTS: A cohort of 125 patients were identified and included in the final analysis. The average age was 59.3 years, with an average intensive care unit (ICU) length of stay of 7.61 days. The most common indication for phenylephrine use was spinal perfusion (both with/without neurogenic shock) in 38.4% of cases, followed by postsurgical/anesthesia resuscitation in 16.8% of cases; 25.6% of patients in our cohort required escalation to central venous access (central venous catheter + peripherally inserted central catheter). A total of 2880 patient-hours were recorded with peripheral phenylephrine infusion, of which 73.9% were at goal blood pressure (either systolic or mean arterial pressure). Only one major complication of thrombophlebitis and 8 minor complications were recorded. CONCLUSIONS: Protocol-driven peripheral administration of lower concentration phenylephrine in an ICU setting is safe and feasible. This strategy is potentially effective at achieving hemodynamic targets in the majority of patients avoiding the need for central venous access.

End-of-Treatment Intracerebral and Ventricular Hemorrhage Volume Predicts Outcome: A Secondary Analysis of MISTIE III.

Background and Purpose- Trials have shown potential clinical benefit for minimally invasive clot evacuation of intracerebral hemorrhage (ICH). Prior research showing an association between ICH size and functional outcome did not fully address the spectrum of hematoma volumes seen after clot evacuation. Methods- In this secondary analysis of the MISTIE III trial (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation III), we included patients randomized to the surgical arm. The primary outcome was good outcome (modified Rankin Scale score 0-3 at 1 year from study enrollment). The primary predictors were the end-of-treatment (EoT) ICH and intraventricular hemorrhage volumes and an end-of-treatment ICH stratification scale called the EoT ICH volume score. Results- In 246 patients, the end-of-treatment computed tomography was performed an average of 5 days from onset. For patients with good versus poor outcomes, the mean end-of-treatment ICH and intraventricular hemorrhage volumes were 12.9 versus 18.0 mL (P=0.002) and 0.5 versus 2.3 mL (P<0.001), respectively. The probability of a good outcome decreased from 73% for EoT ICH volume 3 (<5 mL) to 28% for EoT ICH volume 0 (>20 mL; P=0.001). Conclusions- After surgical clot evacuation, both ICH and intraventricular hemorrhage volumes have a strong association with good neurological outcome. The EoT ICH volume score needs independent verification, but such an approach could be used for prognostication and therapeutic planning.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial.

BACKGROUND: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. METHODS: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. FINDINGS: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar. INTERPRETATION: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. FUNDING: National Institute of Neurological Disorders and Stroke.

Human Rabies - Wyoming and Utah, 2015.

In September 2015, a Wyoming woman was admitted to a local hospital with a 5-day history of progressive weakness, ataxia, dysarthria, and dysphagia. Because of respiratory failure, she was transferred to a referral hospital in Utah, where she developed progressive encephalitis. On day 8 of hospitalization, the patient's family told clinicians they recalled that, 1 month before admission, the woman had found a bat on her neck upon waking, but had not sought medical care. The patient's husband subsequently had contacted county invasive species authorities about the incident, but he was not advised to seek health care for evaluation of his wife's risk for rabies. On October 2, CDC confirmed the patient was infected with a rabies virus variant that was enzootic to the silver-haired bat (Lasionycteris noctivagans). The patient died on October 3. Public understanding of rabies risk from bat contact needs to be improved; cooperation among public health and other agencies can aid in referring persons with possible bat exposure for assessment of rabies risk.

Intravenous acetaminophen for postoperative supratentorial craniotomy pain: a prospective, randomized, double-blinded, placebo-controlled trial.

OBJECTIVE: Acute pain control after cranial surgery is challenging. Prior research has shown that patients experience inadequate pain control post-craniotomy. The use of oral medications is sometimes delayed because of postoperative nausea, and the use of narcotics can impair the evaluation of brain function and thus are used judiciously. Few nonnarcotic intravenous (IV) analgesics exist. The authors present the results of the first prospective study evaluating the use of IV acetaminophen in patients after elective craniotomy. METHODS: The authors conducted a randomized, double-blinded, placebo-controlled investigation. Adults undergoing elective, supratentorial craniotomies between September 2013 and June 2015 were randomized into two groups. The experimental group received 1000 mg/100 ml IV acetaminophen every 8 hours for 48 hours. The placebo group received 100 ml of 0.9% normal saline on the same schedule. Both groups were also treated with a standardized pain control algorithm. The study was powered to detect a 30% difference in the primary outcome measures: narcotic consumption (morphine equivalents, ME) at 24 and 48 hours after surgery. Patient-reported pain scores immediately postoperatively and 48 hours after surgery were also recorded. RESULTS: A total of 204 patients completed the trial. No significant differences were found in narcotic consumption between groups at either time point (in the treatment and placebo groups, respectively, at 24 hours: 84.3 ME [95% CI 70.2­98.4] and 85.5 ME [95% CI 73­97.9]; and at 48 hours: 123.5 ME [95% CI 102.9­144.2] and 134.2 ME [95% CI 112.1­156.3]). The difference in improvement in patient-reported pain scores between the treatment and placebo groups was significant (p < 0.001). CONCLUSIONS: Patients who received postoperative IV acetaminophen after craniotomy did not have significantly decreased narcotic consumption but did experience significantly lower pain scores after surgery. The drug was well tolerated and safe in this patient population.

Increased blood pressure variability after endovascular thrombectomy for acute stroke is associated with worse clinical outcome.

BACKGROUND AND PURPOSE: Blood pressure variability has been found to contribute to worse outcomes after intravenous tissue plasminogen activator, but the association has not been established after intra-arterial therapies. METHODS: We retrospectively reviewed patients with an ischemic stroke treated with intra-arterial therapies from 2005 to 2015. Blood pressure variability was measured as standard deviation (SD), coefficient of variation (CV), and successive variation (SV). Ordinal logistic regression models were fitted to the outcome of the modified Rankin Scale (mRS) with univariable predictors of systolic blood pressure variability. Multivariable ordinal logistic regression models were fitted to the outcome of mRS with covariates that showed independent predictive ability (P<0.1). RESULTS: There were 182 patients of mean age 63.2 years and 51.7% were female. The median admission National Institutes of Health Stroke Scalescore was 16 and 47.3% were treated with intravenous tissue plasminogen activator. In a univariable ordinal logistic regression analysis, systolic SD, CV, and SV were all significantly associated with a 1-point increase in the follow-up mRS (OR 2.30-4.38, all P<0.002). After adjusting for potential confounders, systolic SV was the best predictor of a 1-point increase in mRS at follow-up (OR 2.63-3.23, all P<0.007). CONCLUSIONS: Increased blood pressure variability as measured by the SD, CV, and SV consistently predict worse neurologic outcomes as measured by follow-up mRS in patients with ischemic stroke treated with intra-arterial therapies. The SV is the strongest and most consistent predictor of worse outcomes at all time intervals.

Safety of peripheral administration of phenylephrine in a neurologic intensive care unit: A pilot study.

Integral to the management of the neurocritically injured patient are the prevention and treatment of hypotension, maintenance of cerebral perfusion pressure, and occasionally blood pressure augmentation. When adequate volume resuscitation fails to meet perfusion needs, vasopressors are often used to restore end-organ perfusion. This has historically necessitated central venous access given well-documented incidence of extravasation injuries associated with peripheral administration of vasopressors. In this pilot study, we report our 6-month experience with peripheral administration of low-concentration phenylephrine (40 µg/mL) in our neurocritical care unit. We were able to administer peripheral phenylephrine, up to a dose of 2 µg/(kg min), for an average of 14.29hours (1-54.3) in 20 patients with only 1 possible minor complication and no major complications. This was achieved by adding additional safety measures in our computerized physician order entry system and additional nurse-driven safety protocols. Thus, with careful monitoring and safety precautions, peripheral administration of phenylephrine at an optimized concentration appears to have an acceptable safety profile for use in the neurocritical care unit up to a mean infusion time of 14hours.

Rapidly Progressive Quadriplegia and Encephalopathy.

A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

Extensive cortical diffusion restriction in a 50-year-old female with hyperammonemic encephalopathy and status epilepticus.

Comorbid hyperammonemic encephalopathy (HE) and status epilepticus (SE) leading to extensive cortical diffusion restriction (CDR) on MRI have not been previously reported. We describe a patient with HE who subsequently developed provoked SE. Sequential MRIs demonstrated a progressive CDR that involved the entire bilateral supratentorial cortex, thalami, and basal ganglia, resulting in death from cerebral edema and brain herniation. Diffuse CDR is most frequently seen after hypotension or hypoxia, which our patient did not experience. Such findings have also been described in both HE and SE (Milligan et al. (2009), Chatzikonstantinou et al. (2011), U-King-Im et al. (2011), and Bindu et al. (2009)), but not to the extent seen in our patient. Additionally, our patient had distinct radiologic features of both disease processes, suggesting a cumulative effect. The diagnosis of HE and SE in the setting of extensive CDR should not be missed and could lead to improved outcomes for two progressive, malignant, and treatable illnesses that can be easily overlooked.

Posterior reversible encephalopathy syndrome with spinal cord involvement.

OBJECTIVE: To characterize a cohort of patients with the signs and symptoms of posterior reversible encephalopathy syndrome (PRES), but with clinical and radiologic involvement of the spinal cord. METHODS: We report 2 cases of PRES with spinal cord involvement and identified an additional 6 cases in the Medline database using various search terms related to "spinal PRES," "spinal reversible posterior leukoencephalopathy syndrome," and "spinal hypertensive encephalopathy." We analyzed the clinical and imaging characteristics of the 8 cases. RESULTS: Average age was 31 years, with 5 male and 3 female patients. All patients had severe acute hypertension and a confluent, expansile central spinal cord T2 hyperintensity spanning at least 4 spinal segments, originating at the cervicomedullary junction. Of 8 patients, 7 had hypertensive retinopathy, a favorable clinical course with only antihypertensive treatment, and resolution of the spinal cord lesions on follow-up imaging. A total of 4 of 8 patients had symptoms referable to the spinal cord lesions and only 1 of 8 had a seizure. CONCLUSION: In light of the already wide definition of PRES, we propose a new syndrome named PRES with spinal cord involvement (PRES-SCI). Clinicians should suspect PRES-SCI when patients with PRES have neurologic signs referable to the spinal cord, extreme elevation in blood pressure, MRI lesions that extend to the cervicomedullary junction, or grade IV hypertensive retinopathy. These clinical scenarios should prompt a cervical spine MRI to help guide patient management decisions and prognostication. When clinicians evaluate longitudinally extensive spinal T2 hyperintensities, they should consider PRES-SCI, which, if diagnosed, would spare patients the morbidity of a standard myelitis workup and empiric treatment.

Therapeutic hypothermia for status epilepticus: A report, historical perspective, and review.

Refractory status epilepticus is a disease associated with high morbidity and mortality, which does not always respond to standard treatments, and when they fail, alternative modalities become crucial. Therapeutic hypothermia slows nerve conduction in vitro, and has been shown to abort seizures in animal models. Therapeutic hypothermia has been experimentally used in humans since 1963 for a variety of intracranial pathologies. More recently there have been multiple reports demonstrating the effectiveness of therapeutic hypothermia in treating refractory status epilepticus. We report a case of super-refractory status epilepticus successfully treated with therapeutic hypothermia, complimented by a historical and literature review of this modality. While there is limited evidence, and some risks associated with therapeutic hypothermia, it should be considered as a reasonable and potentially effective treatment option for refractory status epilepticus.

Bilateral in utero cerebellar infarction.

We report a case of complete bilateral cerebellar infarction diagnosed in utero by routine prenatal ultrasound and magnetic resonance imaging in a 26-week-old fetus. This posterior fossa ischemic stroke with secondary hemorrhage caused transient obstructive hydrocephalus and likely occurred subsequent to vertebrobasilar artery thrombosis. Such posterior fossa ischemic insults diagnosed in utero are rare with scarce clinical reports. The serial imaging characteristics, clinical, and developmental implications of this case are reviewed.