Antiseizure Prophylaxis Research Articles

A 30-year perspective of low-dose dexamethasone, a single dose of mannitol and antiseizures prophylaxis on the prognosis of pneumococcal meningitis

Objectives This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis. Methods Data have been prospectively collected for the period1977–2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5–1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin. Results In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone (p = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone (p = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone (p = 0.000). Conclusions A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients.

Primary vs. pre-emptive anti-seizure medication prophylaxis in anti-CD19 CAR T-cell therapy

IntroductionSeizures may occur in up to 30% of non-Hodgkin lymphoma patients who received anti-CD19 CAR T-cell therapy, yet the optimal anti-seizure medication (ASM) prevention strategy has not been thoroughly investigated.MethodsConsecutive patients affected by refractory non-Hodgkin lymphoma who received anti-CD19 CAR T-cells were included. Patients were selected and assessed using similar internal protocols. ASM was started either as a primary prophylaxis (PP-group) before CAR T-cells infusion or as a pre-emptive therapy (PET-group) only upon the onset of neurotoxicity development.ResultsOne hundred fifty-six patients were included (PP-group = 88, PET-group = 66). Overall, neurotoxicity and severe neurotoxicity occurred in 45 (29%) and 20 (13%) patients, respectively, equally distributed between the two groups. Five patients experienced epileptic events (PET-group = 3 [4%]; PP-group = 2 [2%]). For all the PET-group patients, seizure/status epilepticus occurred in the absence of overt CAR-T-related neurotoxicity, whereas patients in the PP-group experienced brief seizures only in the context of critical neurotoxicity with progressive severe encephalopathy. ASMs were well-tolerated by all patients, even without titration. No patients developed epilepsy or required long-term ASMs.ConclusionOur data suggest that both primary and pre-emptive anti-seizure prophylaxis are safe and effective in anti-CD19 CAR T-cell recipients. Clinical rationale suggests a possible more favourable profile of primary prophylaxis, yet no definitive conclusion of superiority between the two ASM strategies can be drawn from our study.

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

Chimeric Antigen Receptor T Cells: Toxicity and Management Considerations

Associations between Electroencephalographic Variables, Early Post-Traumatic Seizure Risk, and Outcomes following Pediatric Severe Traumatic Brain Injury

AbstractEarly post-traumatic seizures (PTS) are associated with worse outcomes in children with traumatic brain injury (TBI). Our aim was to identify the association between continuous electroencephalogram (cEEG) characteristics and early PTS risk following pediatric severe TBI. We also evaluated the relationship between cEEG background features and outcomes. A single-center retrospective cohort study was performed on children between 0 and 18 years of age admitted to the pediatric intensive care unit from 2016 to 2019 with severe TBI and cEEG monitoring within 7 days of injury. Raw cEEG tracings were reviewed by an epileptologist in accordance with American Clinical Neurophysiology Society (ACNS) Critical Care EEG terminology. Univariate comparisons were made between children with and without early PTS, as well as between those with and without varying cEEG background features. Eighteen children (31%) of the 59 included had early PTS. Interictal abnormalities, inclusive of sporadic spikes and sharp waves, rhythmic delta activity, or lateralized periodic discharges (LPDs) were more common among children with seizures (100 vs. 22%; p < 0.01). LPDs were also more common in the seizure group (44 vs. 2%; p < 0.01). Background discontinuity was associated with worse Glasgow Outcome Scale—Extended Pediatric Version (GOS-E Peds) scores at discharge and 3-, 6-, and 12-month post-discharge (p < 0.01). Lack of reactivity was also associated with worse GOS-E Peds scores at 3-, 6-, and 12-month post-discharge (p < 0.01). Interictal abnormalities and LPDs were each associated with early PTS following pediatric severe TBI. Larger studies should evaluate if high-risk patients would benefit from prolonged cEEG monitoring and/or more aggressive anti-seizure prophylaxis. Discontinuity and lack of variability were associated with worse outcomes. Future studies should attempt to clarify their role as potential early markers of prognosis.

Late-onset Seizure and Left Hemiparesis after Unusual Craniocerebral Penetrating Injury by a Rusty Sickle: A Case Report

BACKGROUND: Penetrating head injuries are a significant public health problem in worldwide, with an estimated 35.000 civilian deaths annually. Patients that survive to reach the hospital require rapid triage and imaging evaluation. This case report describes a patient with late-onset seizures and left hemiparesis after unusual craniocerebral penetrating injury by a rusty sickle. CASE PRESENTATION: A 26-year-old man reported that he had a sickle stabbed into the right-side parietal area. On admission, he had no neurological deficits. The rusty sickle was broken off just above the skull and did not protrude from the scalp. Computed tomography showed that the knife blade was in the parenchyma without underlying tract hematoma. Surgery was performed after 2 h of admission. Post-operatively, he recovered with no neurological deficit. After 16th days postoperatively, he was complaining of seizure and left hemiparesis. CT scan with contras showed edema and hypodense lesion at the right side of hemisphere. A course of intravenous phenytoin 100 mg/8 h and ceftriaxone 2 g/day was initiated. Physical therapy was done on the patient for 2 weeks. CONCLUSION: Traumatic brain injury (TBI) is the result of energy being transferred from an object to the human skull and underlying brain. Post-traumatic epilepsy is a common complication and can occur as early or late manifestations related to penetrating TBI. Prophylactic treatment of post-traumatic seizures (PTS) is currently not routinely recommended beyond 1 week following head injury (role of antiseizure prophylaxis). Phenytoin is the most rigorously tested AED for PTS.

Tisagenlecleucel Therapy Is Safe and Effective for Children with Down Syndrome with ALL in First Relapse

Introduction: Children with Down Syndrome (DS) have a 20-fold increased incidence of acute lymphoblastic leukemia (ALL) and a 70% higher risk of relapse than children with ALL and no DS. Treatment for DS children with relapsed ALL is challenging due to the high treatment-related mortality associated with both intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) as well as high rates of second relapse. Outcomes for relapsed ALL in DS are dismal, with recent studies citing an event-free survival (EFS) as low as 17%. Alternative treatment approaches are needed for this patient population. Treatment with anti-CD19 chimeric antigen receptor T-cells (CARTs) have shown high remission rates in patients with multiple relapsed/refractory ALL with an acceptable safety profile. CARTs are generally not indicated for first relapse of ALL; DS-specific indications for CARTs do not exist. In Ontario, due to the specific susceptibility of children with DS-ALL, CARTs were made available to this population upon first relapse. We describe the population-based Canadian experience using CARTs for first relapse of DS-ALL.Methods: Efficacy and safety data on all children referred for CARTs at the Hospital for Sick Children, in Toronto, Canada were retrospectively collected in a central database and validated by treating clinicians. Here we report all patients with DS suffering a first relapse of ALL at age <18 years referred for commercially available CARTs (tisagenlecleucel) between 2019 and 2021.Results: Five patients with DS received tisagenlecleucel for first relapse of ALL during the study period. Median age at original diagnosis was 6.3 years (range 3.4-11.5). Four patients presenting with National Cancer Institute (NCI) standard risk and one with NCI high-risk disease were initially treated on Children's Oncology Group based protocols. Four patients presented with relapse >36 months from diagnosis and one patient with early relapse. Mononuclear cells were successfully collected for all patients on the first attempt. Patients were bridged from collection to infusion with low intensity chemotherapy regimens. Tisagenlecleucel was successfully manufactured for all patients and infused at a median of 69 days (range 56-101) from collection of T cells. Four patients developed CRS: two patients grade 1, one patient grade 2, and one patient grade 4 requiring ICU care and treatment with tocilizumab and steroid. All patients achieved minimal residual disease (MRD) negative remission one month after infusion, with B-cell aplasia. Two patients showed early (< 6months post infusion) B-cell recovery consistent with CAR T-cell loss; both received off-label reinfusions of tisagenlecleucel and again achieved B-cell aplasia. One patient had a seizure with the first Fludarabine dose of lymphodepleting (LD) chemotherapy for re-infusion and was found to have elevated intracranial pressure. After treatment with Topiramate and anti-seizure prophylaxis the patient tolerated LD chemotherapy without further neurological events. No patient received further ALL therapy; none went on to HSCT. One patient suffered a CD19-negative relapse 7 months post infusion and was transitioned to palliative-intent treatment. Two patients developed prolonged neutropenia with one patient showing recovery (ANC>1x10E9/l) at 5 months post infusion and the patient who had relapsed disease remained neutropenic until relapse. Infectious complications in the first 6 months post infusion were rare. One patient, who was not neutropenic, required two hospital admissions for line related sepsis. With a median follow-up time of 519 days (range 197-785), the 1-year estimated EFS and overall survival were both 80% (95 th confidence interval 52-100%; Figure 1).Conclusions: Tisagenlecleucel was safe and effective in a small cohort of children with DS and first relapse of CD19+ ALL, with achievement of long-term remissions without further therapy, and an EFS superior to that seen in historical cohorts. Rate of acute complications were not increased compared with reported outcomes in patients without DS. Further evaluation of tisagenlecleucel in this setting is warranted. [Display omitted] DisclosuresKrueger: KITE/Gilead: Consultancy; Novartis: Consultancy; SOBI: Consultancy. Whitlock: Sobi Pharmaceuticals: Consultancy; Novartis: Research Funding; Amgen; Jazz Pharmaceuticals: Honoraria. Gupta: Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure:tisagenlecleucel for early B-cell recovery

Dengue fever leading to acute dengue hemorrhagic leukoencephalitis

Rationale: Dengue fever is a prevalent tropical infectious disease that has a broad panorama of presentations from mild febrile illness to life-threatening manifestations in the form of dengue hemorrhagic fever and dengue shock syndrome. Patient's concerns: A 20-year-old male presented with a 2-day history of fever, multiple episodes of vomiting, and altered sensorium. Diagnosis: Dengue fever leading to acute hemorrhagic leukoencephalitis. Interventions: Multiple transfusions of single donor platelets, intravenous methylprednisolone, intravenous immunoglobulin, anti-seizure prophylaxis, and broad-spectrum antibiotics. Outcomes: Repeat brain magnetic resonance imaging showed resolution of lesions. The patient was subsequently discharged from the hospital in a healthy state. Lessons: This report helps us to gain a better understanding of the patient's presentation, which will help to improve the timely recognition and prevention of this rare devastating presentation.

Levetiracetam for Seizure Prophylaxis in Neurocritical Care: A Systematic Review and Meta-analysis.

Levetiracetam is commonly used for seizure prophylaxis in patients with intracerebral hemorrhage (ICH), traumatic brain injury (TBI), supratentorial neurosurgery, and spontaneous subarachnoid hemorrhage (SAH). However, its efficacy, optimal dosing, and the adverse events associated with levetiracetam prophylaxis remain unclear. A systematic search of PubMed, Embase, and Cochrane central register of controlled trials (CENTRAL) database was conducted from January 1, 2000, to October 30, 2020, including articles addressing treatment with levetiracetam for seizure prophylaxis after SAH, ICH, TBI, and supratentorial neurosurgery. Non-English, pediatric (aged < 18years), preclinical, reviews, case reports, and articles that included patients with a preexisting seizure condition or epilepsy were excluded. The coprimary meta-analyses examined first seizure events in (1) levetiracetam versus no antiseizure medication and (2) levetiracetam versus other antiseizure medications in all ICH, TBI, SAH, and supratentorial neurosurgery populations. Secondary meta-analyses evaluated the same comparator groups in individual disease populations. Risk of bias in non-randomised studies - of interventions (ROBINS-I) and risk-of-bias tool for randomized trials (RoB-2) tools were used to assess risk of bias. A total of 30 studies (n = 6 randomized trials, n = 9 prospective studies, and n = 15 retrospective studies), including 7609 patients (n = 4737 with TBI, n = 701 with SAH, n = 261 with ICH, and n = 1910 with neurosurgical diseases) were included in analyses. Twenty-seven of 30 (90%) studies demonstrated moderate to severe risk of bias, and 11 of 30 (37%) studies used low-dosage levetiracetam (250-500mg twice daily). In the primary meta-analyses, there were no differences in seizure events for levetiracetam prophylaxis (n = 906) versus no antiseizure medication (n = 2728; odds ratio [OR] 0.79, 95% confidence interval [CI] 0.53-1.16, P = 0.23, fixed-effect, I2 = 26%, P = 0.23 for heterogeneity) or levetiracetam (n = 1950) versus other antiseizure prophylaxis (n = 2289; OR 0.84, 95% CI 0.55-1.28, P = 0.41, random-effects, I2 = 49%, P = 0.005 for heterogeneity). Only patients with supratentorial neurosurgical diseases benefited from levetiracetam compared with other antiseizure medications (median 0.70 seizure events per-patient-year with levetiracetam versus 2.20 seizure events per-patient-year for other antiseizure medications, OR 0.34, 95% CI 0.20-0.58, P < 0.001, fixed-effects, I2 = 39%, P = 0.13 for heterogeneity). There were no significant differences in meta-analyses of patients with ICH, SAH, or TBI. Adverse events of any severity were reported in a median of 8% of patients given levetiracetam compared with 21% of patients in comparator groups. Based on the current moderately to seriously biased heterogeneous data, which frequently used low and possibly subtherapeutic doses of levetiracetam, our meta-analyses did not demonstrate significant reductions in seizure incidence and neither supports nor refutes the use of levetiracetam prophylaxis in TBI, SAH, or ICH.Levetiracetam may be preferred post supratentorial neurosurgery.More high-quality randomized trials of prophylactic levetiracetam are warranted.

Oral levetiracetam for prevention of busulfan-induced seizures in adult hematopoietic cell transplant.

Background Antiseizure prophylaxis is recommended when high-dose of busulfan is given as part of the conditioning regimens in the allogenic hematopoietic stem cell transplant. Phenytoin has been widely used but its pharmacokinetics and pharmacodynamics profile makes its usecomplicated. Levetiracetam is a safe, effective and well tolerated antiseizure drug with good results in epileptic patients. Objective To describe our experience using oral (p.o) levetiracetam 1000mg every 12h (q12h) as an antiseizure prophylaxis, evaluating its preventive effects and adverse event rates after a high-dose of intravenous (i.v.) busulfan, as part of the conditioning regimen Methods Retrospective study of patients who underwent an allogenic hematopoietic stem cell transplantwith a conditioning regimen based on high-dose of busulfan between January and November 2017. Results The study population comprised 36 patients, of whom 18 (50%) had acute myeloid leukemia as diagnosis. No seizures occurred in any patient. Levetiracetam was well tolerated and no serious adverse events were reported. Conclusions Our results suggest that giving levetiracetam at 1000mg q12h p.o starting 12h before the administration of i.v. busulfan until 48h after the last dose, can be used as an alternative in the prevention of busulfan-induced seizures in adults.

Efficacy of antiseizure prophylaxis in chronic subdural hematoma: a cohort study on routinely collected health data.

Chronic subdural hematoma (CSDH) is a common neurosurgical condition that can result in significant morbidity. The incidence of epileptic events associated with CSDH reported in the literature varies considerably and could potentially increase morbidity and mortality rates. The effectiveness of antiepileptic prophylaxis for this indication remains unclear. The primary objective of this study was to assess the relevance of anticonvulsant prophylaxis in reducing seizure events in patients with CSDH. All consecutive cases of CSDH from January 1, 2005, to May 30, 2014, at the Hôpital de l'Enfant-Jésus in Quebec City were retrospectively reviewed. Sociodemographic data, antiepileptic prophylaxis use, incidence of ictal events, and clinical and radiological outcome data were collected. Univariate analyses were done to measure the effect of antiepileptic prophylaxis on ictal events and to identify potential confounding factors. Multivariate logistic regression was performed to evaluate factors associated with epileptic events. Antiepileptic prophylaxis was administered in 28% of the patients, and seizures occurred in 11%. Univariate analyses showed an increase in the incidence of ictal events in patients receiving prophylaxis (OR 5.92). Four factors were identified as being associated with seizures: septations inside the hematoma, membranectomy, antiepileptic prophylaxis, and a new deficit postoperatively. Antiepileptic prophylaxis was not associated with seizures in multivariate analyses. Antiepileptic prophylaxis does not seem to be effective in preventing seizures in patients with CSDH. However, due to the design of this study, it is difficult to conclude definitively about the usefulness of this prophylactic therapy that is widely prescribed for this condition.

Maternal and Perinatal Outcome in Patients with HELLP Syndrome

HELLP syndrome (haemolysis, elevated liver enzymes, and low platelets) is a component of hypertensive disorders of pregnancy which is associated with significant maternal as well as perinatal morbidity and mortality. Maternal mortality is due to consequences such as pulmonary oedema, renal failure, disseminated intravascular coagulation and subcapsular liver hematoma. Perinatal mortality appears to be primarily related to the gestational age at the time of delivery. This study evaluates the maternal and perinatal outcome in HELLP syndrome so that the management is improved resulting in reduced mortality and morbidity. Objectives: A. To study maternal outcome in patients diagnosed with HELLP syndrome. B. To study perinatal outcome in patients with HELLP syndrome. Methods: This study was conducted in department of obstetrics and gynaecology of medical college and tertiary health care centre. A consecutive series of 56 pregnant women above 24 weeks of gestational age with HELLP syndrome were admitted at a tertiary care hospital, during the period of 24 months from 30th November, 2015 to 31st October, 2017. History, clinical data, detailed laboratory investigations were studied and categorized by Mississippi classification for better analysis of complication and outcome in HELLP syndrome. Results: Total 56 cases of HELLP syndrome were studied. Majority of the patients were primigravidae belonging to lower socio-economic status, which were unbooked with no proper antenatal care. 60.71% of the patients had maternal complications. The complications were severe anemia in 21.43%, renal complication in 21.43%, DIC in 19.64%, abruption 14.29%, respiratory complication 7.15%, ascites 3.57% and septicemia in 3.57% and maternal mortality rate was 14.28%. A high incidence of perinatal morbidity and mortality (46.43%) was seen. Major contributing factors being prematurity, fetal growth restriction and birth asphyxia. Conclusion: HELLP syndrome is associated with increased maternal and perinatal morbidity and mortality. Once diagnosis is made, it warrants aggressive intervention with control of blood pressure, antiseizure prophylaxis and corticosteroid treatment and delivery. We have to increase grass root level antenatal care. Early detection and prompt management of pre-eclampsia is the most important approach to the prevention of HELLP syndrome.

Is Routine Continuous EEG for Traumatic Brain Injury Beneficial?

Severe traumatic brain injury (TBI) is associated with increased risk for early clinical and subclinical seizures. The use of continuous electroencephalography (cEEG) monitoring after TBI allows for identification and treatment of seizures that may otherwise occur undetected. Benefits of "routine" cEEG after TBI remain controversial. We examined the rate of subclinical seizures identified by cEEG in TBI patients admitted to a Level I trauma center. We analyzed a cohort of trauma patients with moderate to severe TBI (head Abbreviated Injury Score ≥3) who received cEEG within seven days of admission between October 2011 and May 2015. Demographics, clinical data, injury severity, and costs were recorded. Clinical characteristics were compared between those with and without seizures as identified by cEEG. A total of 106 TBI patients with moderate to severe TBI received a cEEG during the study period. Most were male (74%) with a mean age of 55 years. Subclinical seizures were identified by cEEG in only 3.8 per cent of patients. Ninety-three per cent were on antiseizure prophylaxis at the time of cEEG. Patients who had subclinical seizures were significantly older than their counterparts (80 vs 54 years, P = 0.03) with a higher mean head Abbreviated Injury Score (5.0 vs 4.0, P = 0.01). Mortality and intensive care unit stay were similar in both groups. Of all TBI patients who were monitored with cEEG, seizures were identified in only 3.8 per cent. Seizures were more likely to occur in older patients with severe head injury. Given the high cost of routine cEEG and the low incidence of subclinical seizures, we recommend cEEG monitoring only when clinically indicated.

Seizures and Epileptiform Discharges in Patients With Acute Subdural Hematoma.

Subdural hematomas (SDH) are associated with seizures and epileptiform discharges, but little is known about the prevalence and impact of seizures, status epilepticus (SE), and epileptiform discharges on outcomes in patients with isolated acute SDH (aSDH). Continuous EEG reports from 76 adult patients admitted to Rush University Medical Center with aSDH between January 2009 and March 2012 were reviewed. Clinical and radiographic findings, comorbidities, treatment, and outcome parameters, such as mortality, discharge destination, need for tracheostomy/percutaneous endoscopic gastrostomy placement, and length of stay (LOS), were assessed. Univariate and multivariate analyses were performed to assess the impact of clinical seizures, SE, and epileptiform EEG on outcomes. Of 76 patients with aSDH who underwent EEG monitoring, 74 (97.4%) received antiseizure prophylaxis. Thirty-two (41.1%) patients had seizures, most of which were clinical seizures. Twenty-four (32%) patients had epileptiform EEG findings. Clinical or nonconvulsive SE was diagnosed in 12 (16%) patients. Clinical seizures were not associated with outcome parameters. Epileptiform EEG findings were independently associated with longer hospital LOS (13 vs. 8 days, P = 0.04) and intensive care unit LOS (10 vs. 4 days, P = 0.002). The SE also predicted longer intensive care unit LOS (10 vs. 4 days, P = 0.002). Neither epileptiform EEG nor SE was significantly related to mortality, discharge destination, or need for tracheostomy/percutaneous endoscopic gastrostomy placement. Seizures and epileptiform EEG findings are very common in patients with aSDH despite antiseizure prophylaxis. While clinical seizures did not affect outcomes, the presence of epileptiform EEG findings and SE was independently associated with longer intensive care unit LOS and hospital LOS.

Anti-seizure prophylaxis in critically ill patients with traumatic brain injury in an intensive care unit.

The objectives of this prospective observational study were to determine the proportion of patients with traumatic brain injury who received effective anti-seizure prophylaxis. The study was conducted in a tertiary level ICU of a major trauma referral centre between February 2012 and August 2013. A total of 2361 patients were admitted to the ICU in this study period, of whom125 patients (index) with traumatic head injury were included in this study. The patients had a mean age of 45 years (SD=19), a mean score on the Glasgow Coma Scale of 9 (SD=4), a mean injury severity score of 27 (SD=13) and a mean APACHE III score of 55 (SD=27). Only 13.6 % (17 of 125) of patients were given anti-seizure prophylaxis and phenytoin levels were measured in 9.6% (12 of 125). Although all 12 patients achieved an effective concentration for phenytoin therapy (>40 µmol/l) after the loading dose, no patient had their target concentration consistently maintained in the recommended therapeutic range (40 to 80 µmol/l) throughout the seven-day monitoring period. There was wide fluctuation in phenytoin levels in the patients in this study. Twenty-two (18%) of the index patients had post-traumatic seizures, indicating a high prevalence for this study. Poor compliance with guidelines could possibly explain this phenomenon. Future studies are needed to look at the dosing and monitoring of phenytoin and/or alternative anti-seizure prophylaxis in patients with traumatic brain injury.

Blurry Vision in Patient With Watery Diarrhea: Serendipitous Diagnosis of Neurocysticercosis

Introduction: Neurocysticercosis, also known as disease of swine, is a common helminthic infection estimated to occur in 50,000 people worldwide. In 2013, 148 cases from United States were reported to the WHO. Humans become intermediate hosts of Taenia solium by ingesting its’ eggs from contaminated food specially undercooked pork. Common presentations of gastrointestinal involvement are abdominal pain, nausea, diarrhea or constipation which arise within 6-8 weeks after cyst ingestion. Neurologic symptoms including headaches and seizures may precede GI symptoms. A 26-year-old Guatamalan male without past medical history had lived in the U.S. for 13 years. He had not traveled abroad during this period. He was evaluated in the ED for a 3 day history of severe headaches, nausea, nonbloody emesis and watery diarrhea. Symptoms accompanied by blurry vision. On enquiry, he had suffered from headaches for over 2 years but these had not been associated with visual symptoms, fever, back pain, paresthesias, seizures, or a skin rash. He did not have recent exposure to sick contacts or animals. Physical examination including neurologic and fundoscopic exams were unremarkable except for mild diffuse abdominal tenderness. Laboratory data including CBC, CMP, ESR, HIV and viral hepatitis serologies, urine toxicology were all negative. Head CT scan detected low attenuation in the paramesencephalic cistern, along the basilar cisterns and extending into the left sylvian fissure reported as suspicious for gelatinous pseudocysts of cryptococcal meningitis. MRI imaging showed cerebral calcifications with multiple cystic lesions with widening of the left sylvian fissure and prominent lateral ventricle with the floor of the third ventricle depressed into the sella turcica suggesting a communicating hydrocephalus secondary to racemose neurocysticercosis. Serum ELISA for cysticercus antibody was weakly positive (>0.90). Stool tests were negative for ova and parasites. Cryptococcal antigen was negative. Dexamethasone, albendazole and antiseizure prophylaxis medications were initiated to treat neurocysticercosis. At two month follow up, patient was doing well with resolution of GI symptoms and improved vision. Taeniasis continues to be a serious public health problem especially in patients from Mexico, Guatemala and Peru. A high index of suspicion for neurocysticercosis is important in patients from these endemic areas who present with persistent GI and neurologic symptoms. In addition to praziquantel or albendazole, neurocysticercosis treatment includes supportive therapy with corticosteroids and seizure prophylaxis. Taeniasis is one of the top neglected tropical diseases of this decade whose eradication is a current challenge of the WHO.

Listeria monocytogenes meningoencephalitis in adults: analysis of factors related to unfavourable outcome.

To analyse the short-term outcome in patients with Listeria monocytogenes meningoencephalitis (LMME) to improve management and outcome. Observational study with adult patients with LMME between 1977 and 2009 at a tertiary hospital in Barcelona, Spain. Parameters that predicted outcome were assessed with univariate and logistic regression analysis. Of 59 cases of LMME, 28 occurred in the last decade. Since 1987, a new protocol has been used and 29/45 patients (64%) treated since then received adjuvant dexamethasone. In patients who received this treatment there was a trend towards fewer neurological sequelae (5 vs 33%; p = 0.052). Antiseizure prophylaxis with phenytoin was administered in 13/45 (28%) patients. Seizures occurred in 7/45 (16%) patients, all in the group who did not receive phenytoin. Hydrocephalus presented in 8/59 (14%). It was never present at admission and five patients needed neurosurgical procedures. Sequelae after 3 months were present in 8/45 (18%), mostly cranial nerve palsy. Rhombencephalitis (RE) was related to the presence of neurologic sequelae (OR: 20.4, 95% CI: 1.76-236). Overall mortality was 14/59 (24%), 9/59 (15%) due to neurological causes related to hydrocephalus or seizures. Mortality was defined as early in 36% and late in 64%. In the multivariate analysis, independent risk factors for mortality were presence of hydrocephalus (OR: 17.8, 95% CI: 2.753-114) and inappropriate empirical antibiotic therapy (OR: 6.5, 95% CI: 1.201-35). Outcome of LMME may be improved by appropriate empirical antibiotic therapy, suspicion and careful management of hydrocephalus. Use of adjuvant dexamethasone or phenytoin in a subgroup of these patients might have a benefit.

Energy Expenditure in Children After Severe Traumatic Brain Injury

To evaluate energy expenditure in a cohort of children with severe traumatic brain injury. A prospective observational study. A pediatric neurotrauma center within a tertiary care institution. Mechanically ventilated children admitted with severe traumatic brain injury (Glasgow Coma Scale < 9) with a weight more than 10 kg were eligible for study. A subset of children was co-enrolled in a phase 3 study of early therapeutic hypothermia. All children were treated with a comprehensive neurotrauma protocol that included sedation, neuromuscular blockade, temperature control, antiseizure prophylaxis, and a tiered-based system for treating intracranial hypertension. Within the first week after injury, indirect calorimetry measurements were performed daily when the patient's condition permitted. Data from 13 children were analyzed (with a total of 32 assessments). Measured energy expenditure obtained from indirect calorimetry was compared with predicted resting energy expenditure calculated from Harris-Benedict equation. Overall, measured energy expenditure/predicted resting energy expenditure averaged 70.2% ± 3.8%. Seven measurements obtained while children were hypothermic did not differ from normothermic values (75% ± 4.5% vs 68.9% ± 4.7%, respectively, p = 0.273). Furthermore, children with favorable neurologic outcome at 6 months did not differ from children with unfavorable outcome (76.4% ± 6% vs 64.7% ± 4.7% for the unfavorable outcome, p = 0.13). Contrary to previous work from several decades ago that suggested severe pediatric traumatic brain injury is associated with a hypermetabolic response (measured energy expenditure/predicted resting energy expenditure > 110%), our data suggest that contemporary neurocritical care practices may blunt such a response. Understanding the metabolic requirements of children with severe traumatic brain injury is the first step in development of rational nutritional support goals that might lead to improvements in outcome.

More harm than good

The purposes of this study were to examine the current Brain Trauma Foundation recommendation for antiseizure prophylaxis with phenytoin during the first 7 days after traumatic brain injury (TBI) in preventing seizures and to determine if this medication affects functional recovery at discharge. The records of adult (age ≥ 18 years) patients with blunt severe TBI who remained in the hospital at least 7 days after injury were retrospectively reviewed from January 2008 to January 2010. Clinical seizure rates during the first 7 days after injury and functional outcome at discharge were compared for the two groups based on antiseizure prophylaxis, no prophylaxis (NP) versus phenytoin prophylaxis (PP). Statistical analysis was performed using χ2. A total of 93 adult patients who met the previously mentioned criteria were identified (43 [46%] NP group vs. 50 [54%] PP group). The two groups were well matched. Contrary to expectation, more seizures occurred in the PP group as compared with the NP group; however, this did not reach significance (PP vs. NP, 2 [4%] vs. 1 [2.3%], p = 1). There was no significant difference in the two groups (PP vs. NP) as far as disposition are concerned, mortality caused by head injury (4 [8%] vs. 3 [7%], p = 1), discharge home (16 [32%] vs. 17 [40%], p = 0.7), and discharge to rehabilitation (30 [60%] vs. 23 [53%], p = 0.9). However, with PP, there was a significantly longer hospital stay (PP vs. NP, 36 vs. 25 days, p = 0.04) and significantly worse functional outcome at discharge based on Glasgow Outcome Scale (GOS) score (PP vs. NP, 2.9 vs. 3.4, p < 0.01) and modified Rankin Scale score (2.3 ± 1.7 vs. 3.1 ± 1.5, p = 0.02). PP may not decrease early posttraumatic seizure and may suppress functional outcome after blunt TBI. These results need to be verified with randomized studies before recommending changes in clinical practice and do not apply to penetrating trauma. Therapeutic study, level IV; epidemiologic study, level III.

Enteral administration of antiepileptic agents could have efficacy for prevention of post-traumatic seizures in severe traumatic brain injury

Antiseizure prophylaxis is recommended for preventing only early post-traumatic seizures (PTS) in the guidelines for the management of severe traumatic brain injury (TBI) by the Brain Trauma Foundation. Phenytoin is recommended to reduce the incidence of early PTS prophylaxis. Early enteral nutrition has recently shown theoretical advantages for prevention of bacterial translocation to maintain normal turnover of gut mucosa and is commonly used for TBI patients. Our hypothesis is that the enteral administration of antiepileptic agents is also useful for early PTS.

Levetiracetam for busulfan‐induced seizure prophylaxis in children undergoing hematopoietic stem cell transplantation

Anti-seizure prophylaxis is routinely utilized during busulfan administration for HSCT. We evaluated the feasibility and efficacy of levetiracetam in children undergoing HSCT. A total of 28 children and young adults received levetiracetam during HSCT and the outcomes and costs were compared to a historical, but similar cohort of 25 patients who had received fosphenytoin. Levetiracetam was well tolerated and was efficacious in preventing seizures. Cost of drug, administration, and monitoring were also similar among the two groups. Due to non-induction of the hepatic cytochrome P450 enzymes, levetiracetam may lead to better dose assurance of busulfan in targeted dose regimens for HSCT.