Faculty Bibliography

We describe the short-term effects of high-dose oral diazepam on sleep-potentiated epileptiform activity in patients with electric status epilepticus during sleep. We enrolled patients treated with high-dose oral bedtime diazepam from 2001-2009. We defined spike percentage as the percentage of 1-second bins containing at least one spike, and calculated it during three randomly selected 5-minute samples of wakefulness throughout the day and during the first 5 minutes of every hour of non-rapid eye movement sleep at night. In this study, patients were considered to demonstrate sleep-potentiated epileptiform activity when their spike percentage during sleep was increased by >/=50% compared with wakefulness. Twenty-nine children (18 boys) were included (median age, 7.4 years). Twenty-four hours after receiving high-dose diazepam, epileptiform activity was significantly reduced (76.7% at baseline vs 40.8% 24 hours after high-dose diazepam; Wilcoxon signed ranks test, Z = -4.287, P < 0.0001). Seven patients (24.1%) manifested mild, reversible side effects during the first 48 hours after diazepam administration. High-dose oral diazepam effectively and safely reduced epileptiform activity in patients with electric status epilepticus during sleep.

Hemimegalencephaly (HMG) is a developmental brain disorder characterized by an enlarged, malformed cerebral hemisphere, typically causing epilepsy that requires surgical resection. We studied resected HMG tissue to test whether the condition might reflect somatic mutations affecting genes critical to brain development. We found that two out of eight HMG samples showed trisomy of chromosome 1q, which encompasses many genes, including AKT3, a gene known to regulate brain size. A third case showed a known activating mutation in AKT3 (c.49G-->A, creating p.E17K) that was not present in the patient's blood cells. Remarkably, the E17K mutation in AKT3 is exactly paralogous to E17K mutations in AKT1 and AKT2 recently discovered in somatic overgrowth syndromes. We show that AKT3 is the most abundant AKT paralog in the brain during neurogenesis and that phosphorylated AKT is abundant in cortical progenitor cells. Our data suggest that somatic mutations limited to the brain could represent an important cause of complex neurogenetic disease.

Untreated maple syrup urine disease (MSUD) leads to encephalopathy in neonates and causes abnormalities on the electroencephalogram (EEG). A case is presented of MSUD with unique features consisting of a comb-like rhythm before the therapy and its disappearance with therapy is presented. This case illustrates the potential use of the EEG in the identification of this specific cause of a neonatal encephalopathy.

Hypothalamic hamartomas present with isolated fits of ictal laughter (gelastic epilepsy) or a combination of gelastic and other types of seizures. Many of these patients also suffer from cognitive decline, neuropsychiatric comorbidities and precocious puberty. Although there is a large body of anecdotal evidence about hypothalamic hamartomas and gelastic seizures, many questions still remain to be answered. For instance, which specific hypothalamic regions are most affected by the location of hamartomas causing laughing versus other types of seizures? Does the neuroanatomical localization of the lesions differ in cases with only gelastic seizures or a combination of gelastic and other types of seizures? Does the location of the lesions correlate with the presence of precocious puberty, and does the type of lesion influence the severity or the type of seizures? In a retrospective review of clinical and structural neuroimaging data from 100 cases of gelastic epilepsy and hypothalamic hamartoma, we aimed to address these questions by analysing the clinical presentation and the neuroanatomical features of the hypothalamic lesions in these patients. Our findings suggest that in all 100 cases, lesions were centred at the level of the mammillary bodies in the posterior hypothalamus. Compared with the patients with pure gelastic seizures (n = 32), those with gelastic and other types of seizures (n = 68) had significantly longer duration of epilepsy (P < 0.001), whereas age of seizure onset, the volume of lesions and the proximity to the mammillary bodies were not different between the two groups. In contrast, patients with cognitive or developmental impairment and those with precocious puberty had significantly larger lesions involving the anterior and posterior hypothalamus

PURPOSE: Generalized periodic epileptiform discharges (GPEDs) are a specific periodic EEG pattern, reported with status epilepticus (SE) or a metabolic or an anoxic encephalopathy in critically ill patients. In this study, we examined the clinical course and evolution of EEG findings associated with GPEDs in children with refractory convulsive SE. METHODS: The EEG reports of 279 children with SE diagnosed between 2002 and 2010 were reviewed to detect GPEDs. Ten children were identified with GPEDs on continuous EEG recording. The entire EEG recording was available for review in only six children. In the clinical course, seizure characteristics and evolution of EEG findings were analyzed. RESULTS: Six children (age, 5 to 17 years) were admitted to the intensive care unit with refractory convulsive SE. All had acute symptomatic SE except for one child with a history of epilepsy and developmental delay. Intravenous anesthetic agents were used to treat convulsive SE in five children. After tapering the intravenous anesthetic agents, GPEDs were seen on the continuous EEG recording, nonconvulsive seizures occurred in five, and nonconvulsive SE in four children. None of the children returned to baseline, and three children died. CONCLUSIONS: Generalized periodic epileptiform discharges are seen during the treatment course of convulsive SE in children and heralded seizure recurrence. We found a sequential evolution of the EEG patterns after the control of convulsive SE, with GPEDs occurring in a dynamic fashion in a continuum along with burst suppression and electrographic seizures. Recognizing that GPEDs represent a still active epileptic state after the control of convulsive SE with intravenous anesthetic agents and modifying the treatment regimen to control GPEDs may prevent immediate seizure recurrence.

Neurocritical care (NCC) is now an essential field in child neurology that requires dedicated training. NCC applies the basic principles of neuroresuscitation to all situations, integrates this with modern technology. and emphasizes that brain protection is not limited to the intensive care unit. We outline the essential competencies needed and how to obtain these

OBJECT: Neurophysiological monitoring of motor evoked potentials (MEPs) during complex spine procedures may reduce the risk of injury by providing feedback to the operating surgeon. While this tool is a well-established surgical adjunct in adults, clinical data in children are sparse. The purpose of this study was to determine the reliability and safety of MEP monitoring in a group of children younger than 3 years of age undergoing neurosurgical spine procedures. METHODS: A total of 10 consecutive spinal procedures in 10 children younger than 3 years of age (range 5-31 months, mean 16.8 months) were analyzed between January 1, 2008, and May 1, 2010. Motor evoked potentials were elicited by transcranial electric stimulation. A standardized anesthesia protocol for monitoring consisted of a titrated propofol drip combined with bolus dosing of fentanyl or sufentanil. RESULTS: Motor evoked potentials were documented at the beginning and end of the procedure in all 10 patients. A mean baseline stimulation threshold of 533 +/- 124 V (range 321-746 V) was used. Six patients maintained MEP signals >/= 50% of baseline amplitude throughout the surgery. There was a greater than 50% decrease in intraoperative MEP amplitude in at least 1 extremity in 4 patients. Two of these patients returned to baseline status by the end of the case. Two patients had a persistent decrement or variability in MEP signals at the end of the procedure; this correlated with postoperative weakness. There were no complications related to the technique of monitoring MEPs. CONCLUSIONS: A transcranial electric stimulation protocol monitoring corticospinal motor pathways during neurosurgical procedures in children younger than 3 years of age was reliably and safely implemented. A persistent intraoperative decrease of greater than 50% in this small series of 10 pediatric patients younger than 3 years of age predicted a postoperative neurological deficit. The authors advocate routine monitoring of MEPs in this pediatric age group undergoing neurosurgical spine procedures

Generalized convulsive status epilepticus (GCSE) has a high morbidity and mortality, such that the rapid delivery of anticonvulsant therapy should be initiated within minutes of seizure onset to prevent permanent neuronal damage. GCSE is not a specific disease but is a manifestation of either a primary central nervous system (CNS) insult or a systemic disorder with secondary CNS effects. It is mandatory to look for an underlying cause. First-line therapies for seizures and status epilepticus include the use of a benzodiazepine, followed by an infusion of a phenytoin with a possible role for intravenous valproate or phenobarbital. If these first-line medications fail to terminate the GCSE, treatment includes the continuous infusion of midazolam, pentobarbital, or propofol