Cecil D. Hahn

Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder defined clinically by severe gastrointestinal dysmotility; cachexia; ptosis, ophthalmoparesis, or both; peripheral neuropathy; leukoencephalopathy; and mitochondrial abnormalities. The disease is caused by mutations in the thymidine phosphorylase (TP) gene. TP protein catalyzes phosphorolysis of thymidine to thymine and deoxyribose 1‐phosphate. We identified 21 probands (35 patients) who fulfilled our clinical criteria for MNGIE. MNGIE has clinically homogeneous features but varies in age at onset and rate of progression. Gastrointestinal dysmotility is the most prominent manifestation, with recurrent diarrhea, borborygmi, and intestinal pseudo‐obstruction. Patients usually die in early adulthood (mean, 37.6 years; range, 26–58 years). Cerebral leukodystrophy is characteristic. Mitochondrial DNA (mtDNA) has depletion, multiple deletions, or both. We have identified 16 TP mutations. Homozygous or compound heterozygous mutations were present in all patients tested. Leukocyte TP activity was reduced drastically in all patients tested, 0.009 ± 0.021 μmol/hr/mg (mean ± SD; n = 16), compared with controls, 0.67 ± 0.21 μmol/hr/mg (n = 19). MNGIE is a recognizable clinical syndrome caused by mutations in thymidine phosphorylase. Severe reduction of TP activity in leukocytes is diagnostic. Altered mitochondrial nucleoside and nucleotide pools may impair mtDNA replication, repair, or both. Ann Neurol 2000;47:792–800

Human parechovirus causes encephalitis with white matter injury in Neonates

To assess the role of human parechoviruses (HPeVs) as a cause of neonatal cerebral infection and to report neuroimaging findings of newborn infants with encephalitis caused by HPeVs.

Intravenous ketamine for the treatment of refractory status epilepticus: A retrospective multicenter study

To examine patterns of use, efficacy, and safety of intravenous ketamine for the treatment of refractory status epilepticus (RSE).

Seizure burden is independently associated with short term outcome in critically ill children

Seizures are common among critically ill children, but their relationship to outcome remains unclear. We sought to quantify the relationship between electrographic seizure burden and short-term neurological outcome, while controlling for diagnosis and illness severity. Furthermore, we sought to determine whether there is a seizure burden threshold above which there is an increased probability of neurological decline. We prospectively evaluated all infants and children admitted to our paediatric and cardiac intensive care units who underwent clinically ordered continuous video-electroencephalography monitoring over a 3-year period. Seizure burden was quantified by calculating the maximum percentage of any hour that was occupied by electrographic seizures. Outcome measures included neurological decline, defined as a worsening Paediatric Cerebral Performance Category score between hospital admission and discharge, and in-hospital mortality. Two hundred and fifty-nine subjects were evaluated (51% male) with a median age of 2.2 years (interquartile range: 0.3 days-9.7 years). The median duration of continuous video-electroencephalography monitoring was 37 h (interquartile range: 21-56 h). Seizures occurred in 93 subjects (36%, 95% confidence interval = 30-42%), with 23 (9%, 95% confidence interval = 5-12%) experiencing status epilepticus. Neurological decline was observed in 174 subjects (67%), who had a mean maximum seizure burden of 15.7% per hour, compared to 1.8% per hour for those without neurological decline (P < 0.0001). Above a maximum seizure burden threshold of 20% per hour (12 min), both the probability and magnitude of neurological decline rose sharply (P < 0.0001) across all diagnostic categories. On multivariable analysis adjusting for diagnosis and illness severity, the odds of neurological decline increased by 1.13 (95% confidence interval = 1.05-1.21, P = 0.0016) for every 1% increase in maximum hourly seizure burden. Seizure burden was not associated with mortality (odds ratio: 1.003, 95% confidence interval: 0.99-1.02, P = 0.613). We conclude that in this cohort of critically ill children, increasing seizure burden was independently associated with a greater probability and magnitude of neurological decline. Our observation that a seizure burden of more than 12 min in a given hour was strongly associated with neurological decline suggests that early antiepileptic drug management is warranted in this population, and identifies this seizure burden threshold as a potential therapeutic target. These findings support the hypothesis that electrographic seizures independently contribute to brain injury and worsen outcome. Our results motivate and inform the design of future studies to determine whether more aggressive seizure treatment can improve outcome.

MRI criteria for multiple sclerosis Evaluation in a pediatric cohort

This study assessed the validity of established MRI criteria for multiple sclerosis (MS) in a cohort of 20 children with clinically definite MS. The authors found that many pediatric MS patients did not meet the MRI criteria established for adult-onset MS, particularly the McDonald MRI criteria for dissemination in space. The authors thus suggest that MRI criteria for adult MS be applied cautiously to pediatric MS patients.

Consensus Statement on Continuous EEG in Critically Ill Adults and Children, Part I: Indications

Introduction: Critical Care Continuous EEG (CCEEG) is a common procedure to monitor brain function in patients with altered mental status in intensive care units. There is significant variability in patient populations undergoing CCEEG and in technical specifications for CCEEG performance. Methods: The Critical Care Continuous EEG Task Force of the American Clinical Neurophysiology Society developed expert consensus recommendations on the use of CCEEG in critically ill adults and children. Recommendations: The consensus panel recommends CCEEG for diagnosis of nonconvulsive seizures, nonconvulsive status epilepticus, and other paroxysmal events, and for assessment of the efficacy of therapy for seizures and status epilepticus. The consensus panel suggests CCEEG for identification of ischemia in patients at high risk for cerebral ischemia; for assessment of level of consciousness in patients receiving intravenous sedation or pharmacologically induced coma; and for prognostication in patients after cardiac arrest. For each indication, the consensus panel describes the patient populations for which CCEEG is indicated, evidence supporting use of CCEEG, utility of video and quantitative EEG trends, suggested timing and duration of CCEEG, and suggested frequency of review and interpretation. Conclusion: CCEEG has an important role in detection of secondary injuries such as seizures and ischemia in critically ill adults and children with altered mental status.

American clinical neurophysiology society standardized EEG terminology and categorization for the description of continuous EEG monitoring in neonates: report of the American Clinical Neurophysiology Society critical care monitoring committee.

BACKGROUNDCritically ill neonates are at high risk for adverse neurologic sequelae, but the bedside evaluation of a neonates neurologic status, especially cortical functioning, is extremely limited. In such circumstances, continuous video EEG provides particularly useful information about brain

Diagnostic yield of genetic testing in epileptic encephalopathy in childhood

Epilepsy is a common neurologic disorder of childhood. To determine the genetic diagnostic yield in epileptic encephalopathy, we performed a retrospective cohort study in a single epilepsy genetics clinic.

Seizure identification in the ICU using quantitative EEG displays

Objective: To evaluate the diagnostic accuracy of 2 quantitative EEG display tools, color density spectral array (CDSA) and amplitude-integrated EEG (aEEG), for seizure identification in the intensive care unit (ICU). Methods: A set of 27 continuous EEG recordings performed in pediatric ICU patients was transformed into 8-channel CDSA and aEEG displays. Three neurophysiologists underwent 2 hours of training to identify seizures using these techniques. They were then individually presented with a series of CDSA and aEEG displays, blinded to the raw EEG, and asked to mark any events suspected to be seizures. Their performance was compared to seizures identified on the underlying conventional EEG. Results: The 27 EEG recordings contained 553 discrete seizures over 487 hours. The median sensitivity for seizure identification across all recordings was 83.3% using CDSA and 81.5% using aEEG. However, among individual recordings, the sensitivity ranged from 0% to 100%. Factors reducing the sensitivity included low-amplitude, short, and focal seizures. False-positive rates were generally very low, with misidentified seizures occurring once every 17–20 hours. Conclusions: Both CDSA and aEEG demonstrate acceptable sensitivity and false-positive rates for seizure identification among critically ill children. Accuracy of these tools would likely improve during clinical use, when findings can be correlated in real-time with the underlying raw EEG. In the hands of neurophysiologists, CDSA and aEEG displays represent useful screening tools for seizures during continuous EEG monitoring in the ICU. The suitability of these tools for bedside use by ICU nurses and physicians requires further study.

Electrographic seizures in pediatric ICU patients Cohort study of risk factors and mortality

Objectives: We aimed to determine the incidence of electrographic seizures in children in the pediatric intensive care unit who underwent EEG monitoring, risk factors for electrographic seizures, and whether electrographic seizures were associated with increased odds of mortality. Methods: Eleven sites in North America retrospectively reviewed a total of 550 consecutive children in pediatric intensive care units who underwent EEG monitoring. We collected data on demographics, diagnoses, clinical seizures, mental status at EEG onset, EEG background, interictal epileptiform discharges, electrographic seizures, intensive care unit length of stay, and in-hospital mortality. Results: Electrographic seizures occurred in 162 of 550 subjects (30%), of which 61 subjects (38%) had electrographic status epilepticus. Electrographic seizures were exclusively subclinical in 59 of 162 subjects (36%). A multivariable logistic regression model showed that independent risk factors for electrographic seizures included younger age, clinical seizures prior to EEG monitoring, an abnormal initial EEG background, interictal epileptiform discharges, and a diagnosis of epilepsy. Subjects with electrographic status epilepticus had greater odds of in-hospital death, even after adjusting for EEG background and neurologic diagnosis category. Conclusions: Electrographic seizures are common among children in the pediatric intensive care unit, particularly those with specific risk factors. Electrographic status epilepticus occurs in more than one-third of children with electrographic seizures and is associated with higher in-hospital mortality.