The impact of hypsarrhythmia on infantile spasms treatment response: Observational cohort study from the National Infantile Spasms Consortium.

OBJECTIVE: The multicenter National Infantile Spasms Consortium prospective cohort was used to compare outcomes and phenotypic features of patients with infantile spasms with and without hypsarrhythmia. METHODS: Patients aged 2 months to 2 years were enrolled prospectively with new-onset infantile spasms. Treatment choice and categorization of hypsarrhythmia were determined clinically at each site. Response to therapy was defined as resolution of clinical spasms (and hypsarrhythmia if present) without relapse 3 months after initiation. RESULTS: Eighty-two percent of patients had hypsarrhythmia, but this was not associated with gender, mean age, preexisting developmental delay or epilepsy, etiology, or response to first-line therapy. Infants with hypsarrhythmia were more likely to receive standard treatment (adrenocorticotropic hormone, prednisolone, or vigabatrin [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4-4.7] and preexisting epilepsy reduced the likelihood of standard treatment (OR 3.2, 95% CI 1.9-5.4). Hypsarrhythmia was not a determinant of response to treatment. A logistic regression model demonstrated that later age of onset (OR 1.09 per month, 95% CI 1.03-1.15) and absence of preexisting epilepsy (OR 1.7, 95% CI 1.06-2.81) had a small impact on the likelihood of responding to the first-line treatment. However, receiving standard first-line treatment increased the likelihood of responding dramatically: vigabatrin (OR 5.2 ,95% CI 2-13.7), prednisolone (OR 8, 95% CI 3.1-20.6), and adrenocorticotropic hormone (ACTH; OR 10.2, 95% CI 4.1-25.8) . SIGNIFICANCE: First-line treatment with standard therapy was by far the most important variable in determining likelihood of response to treatment of infantile spasms with or without hypsarrhythmia.

Spectral Electroencephalogram Analysis for the Evaluation of Encephalopathy Grade in Children With Acute Liver Failure.

OBJECTIVE: Spectral electroencephalogram analysis is a method for automated analysis of electroencephalogram patterns, which can be performed at the bedside. We sought to determine the utility of spectral electroencephalogram for grading hepatic encephalopathy in children with acute liver failure. DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric hospital. PATIENTS: Patients between 0 and 18 years old who presented with acute liver failure and were admitted to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electroencephalograms were analyzed by spectral analysis including total power, relative δ, relative θ, relative α, relative ß, θ-to-Δ ratio, and α-to-Δ ratio. Normal values and ranges were first derived using normal electroencephalograms from 70 children of 0-18 years old. Age had a significant effect on each variable measured (p < 0.03). Electroencephalograms from 33 patients with acute liver failure were available for spectral analysis. The median age was 4.3 years, 14 of 33 were male, and the majority had an indeterminate etiology of acute liver failure. Neuroimaging was performed in 26 cases and was normal in 20 cases (77%). The majority (64%) survived, and 82% had a good outcome with a score of 1-3 on the Pediatric Glasgow Outcome Scale-Extended at the time of discharge. Hepatic encephalopathy grade correlated with the qualitative visual electroencephalogram scores assigned by blinded neurophysiologists (rs = 0.493; p < 0.006). Spectral electroencephalogram characteristics varied significantly with the qualitative electroencephalogram classification (p < 0.05). Spectral electroencephalogram variables including relative Δ, relative θ, relative α, θ-to-Δ ratio, and α-to-Δ ratio all significantly varied with the qualitative electroencephalogram (p < 0.025). Moderate to severe hepatic encephalopathy was correlated with a total power of less than or equal to 50% of normal for children 0-3 years old, and with a relative θ of less than or equal to 50% normal for children more than 3 years old (p > 0.05). Spectral electroencephalogram classification correlated with outcome (p < 0.05). CONCLUSIONS: Spectral electroencephalogram analysis can be used to evaluate even young patients for hepatic encephalopathy and correlates with outcome. Spectral electroencephalogram may allow improved quantitative and reproducible assessment of hepatic encephalopathy grade in children with acute liver failure.

Imaging of Glutamate Concentration in Sturge-Weber Syndrome.

Investigators from Wayne State University studied a cohort of children with Sturge-Weber syndrome (SWS) and epilepsy using both glucose-based positron emission tomography (FDG-PET) to evaluate metabolic activity and proton magnetic resonance spectroscopic imaging (MRSI) to evaluate glutamate turnover.

Prognosis with Incidental Rolandic Spikes.

Investigators from Johns Hopkins University reported a cohort of 27 patients with incidentally-noted rolandic spikes (RS) on EEG.

Case Report: Intravenous and Oral Pyridoxine Trial for Diagnosis of Pyridoxine-Dependent Epilepsy.

Pyridoxine-dependent epilepsy is a rare, autosomal recessive, treatable cause of neonatal seizures. Genetic testing can confirm mutations in the ALDH7A1 gene, which encodes antiquitin. To avoid delays in initiating treatment while awaiting confirmatory genetic testing, it is recommended that all neonates with unexplained seizures should receive trial of intravenous (IV) pyridoxine to assess for responsiveness. However, oral pyridoxine is not commonly continued in the absence of the typical EEG changes. Two cases are presented that highlight the potential inadequacy of this single-step approach. One neonate ultimately diagnosed with pyridoxine-dependent seizures had no EEG changes after administration of IV pyridoxine. In contrast, another neonate who did not have this diagnosis had profound EEG changes after pyridoxine administration. We present 2 cases that highlight the difficulties in using initial EEG response to IV pyridoxine in establishing a diagnosis of pyridoxine-dependent seizures in the neonate. Given the availability of biochemical markers and gene testing, we suggest that oral pyridoxine treatment should be continued until biochemical and/or genetic testing has confirmed the presence or absence of pyridoxine-dependent epilepsy.

Frequency of epileptiform discharges in the sleep-deprived electroencephalogram in children evaluated for attention-deficit disorders.

The authors determined the frequency of epileptiform discharges in the electroencephalogram (EEG) of a cohort of children and adolescents referred to a neurology specialty clinic for evaluation of attention-deficit disorders. Of 624 records, 461 (73.9%) were normal and 163 (26.1%) abnormal. Of abnormal EEGs, 70 (42.9%) had focal epileptiform discharges only, 68 (41.7%) had generalized epileptiform discharges only, and 19 (11.6%) had both independent focal and generalized spikes. Focal spikes were localized chiefly in central, frontal, and temporal regions. Of 163 records with abnormalities, 154 (94.5%) were sleep deprived and 159 (97.5%) were sleep records. One-quarter of the nonepileptic children evaluated for attention-deficit disorder have epileptiform discharges in the EEG, and just more than half are focal. Sleep-deprived sleep is essential to exclude epileptiform abnormalities. The utility of the EEG in the management of attention-deficit disorders and selection of stimulant or nonstimulant medication deserves further study.

Utility of the electroencephalogram in attention deficit hyperactivity disorder.

An electroencephalogram (EEG) has not been routinely utilized in the evaluation of children with attention deficit hyperactivity disorder (ADHD). The utility of the EEG in ADHD is unclear. A recent study in our laboratory using sleep and sleep deprivation routinely found one in four non-epileptic children evaluated for attention deficit disorder has epileptiform discharges in the EEG, more than half focal. The majority of abnormalities (97.5%) occur in sleep and sleep-deprived records compared to 7% in prior wake only records. A review of eight publications showed that laboratories using awake only as routine EEG recordings report a relatively low prevalence of epileptiform discharges, whereas the higher prevalence of epileptiform discharges is seen in those with more prolonged sleep recordings. We have determined that sleep deprivation and sleep are essential to rule out an abnormal EEG in attention deficit disorder. In patients with attention deficit disorder complicated by epilepsy, stimulant therapy is generally safe, provided seizures are controlled by antiepileptic medication. Patients with epilepsy or subclinical electrographic abnormalities not treated with anticonvulsants are at increased risk of seizures when stimulant therapy is introduced, especially extended-release methylphenidate. Apart from an increase in risk of seizures and need for caution in use of stimulants, studies show that epileptiform discharges in the electroencephalogram are linked to a better response of attention deficit to methylphenidate and a higher cognitive performance. Transient cognitive impairment related to subclinical electrographic abnormalities responds to antiepileptic medication. An EEG is important in selected cases of attention deficit disorder and is useful in choice of medication, especially in children with lack of awareness and transient cognitive impairment.

Ictal asystole and anti-N-methyl-D-aspartate receptor antibody encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) antibody encephalitis is a recently identified autoimmune disorder that is increasingly recognized in children. Most cases occur in girls and women and may be paraneoplastic with an associated ovarian teratoma. Characteristic clinical features include neuropsychiatric symptoms, dyskinesias, decreased consciousness, and autonomic instability. We report the first case of asystole associated with temporal lobe seizures in this disorder and highlight the need for careful monitoring for this potentially fatal complication. A 15-year-old previously healthy girl presented with focal seizures and personality changes that progressed to periods of agitation and confusion alternating with catatonia. Anti-NMDAR antibodies were detected in the cerebrospinal fluid and serum. Twenty-six days after initial presentation, new seizures developed characterized by bradycardia and oxygen desaturation. Continuous video-electroencephalogram monitoring captured 3 seizures with left-temporal onset and associated asystole. An ovarian teratoma was diagnosed by pelvic ultrasound and computed tomography, and surgical resection was followed by gradual improvement in her neuropsychiatric symptoms. Treatment with phenobarbital beginning on day 26 lead to the cessation of seizures. However, asymptomatic bradycardia and pauses of 3 seconds continued. After insertion of a demand pacemaker on day 46, there were no further cardiac events. The patient was also treated with 2 courses of intravenous immunoglobulin. Outpatient follow-up at 4 months revealed near-complete neurologic recovery and no cardiac events. To our knowledge, ictal asystole has not previously been described as a complication of anti-NMDAR encephalitis; it is a preventable cause of death in this emerging pediatric disorder, which presents with protean symptoms and is easily misdiagnosed.