Ala Birca

Rapamycin as an alternative to surgical treatment of subependymal giant cell astrocytomas in a patient with tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is associated with the potential development of benign hamartomas, including subependymal giant cell astrocytomas (SEGAs). Intracranial hypertension can be caused by SEGAs due to their propensity to block the foramen of Monro. The traditional management approach is to monitor SEGAs with periodic neuroimaging and to resect those that exhibit serial growth and/or cause clinical signs of intracranial hypertension. Recent observations suggest that rapamycin therapy may induce partial regression of SEGAs, therefore providing a potential alternative to resection. The authors present the case of an 8-year-old girl with bilateral SEGAs that led to progressive hydrocephaly and incipient signs of papilledema. Three months after initiating rapamycin therapy, the SEGAs exhibited significant reduction in size (82.6% on the left and 46.7% on the right), and the lesions remained stable 5 months later. Compared with previous case reports, similar or even greater antitumor efficacy was achieved with much lower trough levels of rapamycin (10–15 compared with 3.3–4.5 ng/ml, respectively). The authors discuss various aspects of rapamycin therapy and address unresolved issues that highlight the need for further prospective clinical trials.

Interaction between the flash evoked SSVEPs and the spontaneous EEG activity in children and adults.

OBJECTIVE To evaluate the interaction between the steady-state visual evoked potentials (SSVEPs) recorded during the intermittent photic stimulation (IPS) and the spontaneous EEG activities both in children and adults. METHODS EEG was recorded during the rest and under 5, 7.5, 10 and 12.5 Hz IPS in 41 children between 3 and 16 years and 10 adults. We distinguished between the spontaneous resting EEG spectra, SSVEPs (1st harmonic) and undriven (ongoing) EEG spectra recorded during the IPS. RESULTS We show that IPS influences spontaneous EEG activity by specifically suppressing or desynchronizing individual posterior dominant resting EEG frequencies (DF) in both children and adults. Further, this highly significant and consistent suppressing effect positively correlates with the SSVEPs amplitude. CONCLUSIONS Our data suggest that the desynchronization of the spontaneous EEG activity under IPS and the SSVEPs are related to each other. SIGNIFICANCE These relationships could be interesting to study in pathological conditions where the neural synchronization and the responses to IPS have been shown to be affected, such as epilepsy and schizophrenia.

Transient Creatine Phosphokinase Elevations in Children: A Single-Center Experience

OBJECTIVES To determine the etiologies and evolution of rhabdomyolysis in children. STUDY DESIGN We performed a retrospective study of patients with rhabdomyolysis who were seen in our tertiary care university-affiliated pediatric hospital. Patients in outpatient clinics, seen in the emergency department, or admitted from 2001 to 2002 were selected. With a standardized case report form, we collected predetermined data from each patients chart. RESULTS A total of 130 patients with rhabdomyolysis were included in the study (male, 56%; mean age, 7.5 ± 5.9 years). The median elevation of creatine phosphokinase was 2207 IU/L (range, 1003 to 811 428 IU/L). The most frequent diagnoses were viral myositis (29, 22.3%), trauma (24, 18.4%), surgery (24, 18.4%), hypoxia (12 , 9.2%), and drug reaction (8, 6.2%). Metabolic myopathy was found only in one patient (0.8%). In 17 patients (13.1%), no definite diagnosis could be made. CONCLUSIONS Etiologies of rhabdomyolysis in children are varied and differ from those reported in adults. In most patients, rhabdomyolysis is benign and without recurrence. In our series, rhabdomyolysis was the initial symptom of a metabolic myopathy in only one patient.

Gamma frequency SSVEP components differentiate children with febrile seizures from normal controls

Gamma band electroencephalography (EEG) abnormalities have been reported in patients with epilepsy. We aimed to investigate whether patients with febrile seizures (FS) show abnormalities of the gamma frequency steady‐state visual evoked potential (SSVEP) components evoked by intermittent photic stimulation (IPS). We analyzed the magnitude and phase alignment of the 50–100 Hz SSVEP components elicited by IPS from 12 FS patients, 5 siblings of FS patients, and 15 control children between 6 and 36 months of age. Patients with FS showed significantly higher SSVEP magnitude and phase alignment values when compared to both the siblings and control groups. Detected abnormalities could either represent the direct consequence of seizures or indicate a preexisting tendency to hypersynchrony in FS patients. Future prospective studies could assess whether SSVEP abnormalities are associated with complex rather than simple FS, or have a prognostic value for the development of epilepsy following FS.

Efficacy and safety of lacosamide as an adjunctive therapy for refractory focal epilepsy in paediatric patients: a retrospective single-centre study.

AIM Lacosamide is an antiepileptic drug approved for the treatment of focal epilepsy in adult patients. The aim of this observational study was to review our centres experience with lacosamide and to characterize its effectiveness and tolerability as an adjunctive antiepileptic drug in a retrospective cohort of children with refractory focal epilepsy. METHODS We retrospectively reviewed the medical records of 22 patients who received lacosamide from November 2009 to April 2014 at the CHU Ste-Justine, University of Montreal. Treatment responders were defined as children with a ≥50% reduction in seizure frequency compared to baseline, and this was determined three months after the initiation of treatment and at the last follow-up visit. RESULTS We included 14 boys and eight girls with a mean age of 12.9 years (SD: 5.2; range: 5.2-20.7 years) at the initiation of treatment. The average length of follow-up was 11.9 months. Patients had previously received an average of 7.5 antiepileptic drugs. The mean number of concomitant antiepileptic drugs was 2.3. The mean initial and maintenance doses were 2.9 and 8.4 mg/kg/d, respectively. Thirteen (59%) and ten (45%) patients were responders after three months of treatment and at the last follow-up visit, respectively. One became seizure-free. Adverse effects were reported in 11 patients and none were severe. Responders and non-responders were identical with respect to all studied parameters except gender, with the proportion of responders being greater in girls than in boys (75% vs 29%; p=0.035). CONCLUSION Our study adds evidence that lacosamide appears to be a safe and effective adjunctive therapy for children with refractory focal epilepsy.

Interplay of brain structure and function in neonatal congenital heart disease.

To evaluate whether structural and microstructural brain abnormalities in neonates with congenital heart disease (CHD) correlate with neuronal network dysfunction measured by analysis of EEG connectivity.

Rewarming affects EEG background in term newborns with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.

OBJECTIVE To investigate how rewarming impacts the evolution of EEG background in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). METHODS We recruited a retrospective cohort of 15 consecutive newborns with moderate (9) and severe (6) HIE monitored with a continuous EEG during TH and at least 12h after its end. EEG background was analyzed using conventional visual and quantitative EEG analysis methods including EEG discontinuity, absolute and relative spectral magnitudes. One patient with seizures on rewarming was excluded from analyses. RESULTS Visual and quantitative analyses demonstrated significant changes in EEG background from pre- to post-rewarming, characterized by an increased EEG discontinuity, more pronounced in newborns with severe compared to moderate HIE. Neonates with moderate HIE also had an increase in the relative magnitude of slower delta and a decrease in higher frequency theta and alpha waves with rewarming. CONCLUSIONS Rewarming affects EEG background in HIE newborns undergoing TH, which may represent a transient adaptive response or reflect an evolving brain injury. SIGNIFICANCE EEG background impairment induced by rewarming may represent a biomarker of evolving encephalopathy in HIE newborns undergoing TH and underscores the importance of continuously monitoring the brain health in critically ill neonates.

Children with a history of atypical febrile seizures show abnormal steady state visual evoked potential brain responses

Atypical febrile seizures (FSs) are considered a risk factor for the onset of epilepsy in later life as well as for potential cognitive impairment. However, distinctive characteristics defining the group of children at risk for negative outcomes are not well established. In the following study, children from 6 to 59 months with a history of atypical FSs were investigated using steady state visual evoked potentials (ssVEP), a brain response known to increase with age. Abnormally, low theta and alpha ssVEP brain responses were found in children with a history of atypical FSs.

Maturational changes of 5 Hz SSVEPs elicited by intermittent photic stimulation

We investigated the development of the magnitude and phase alignment of steady-state visual evoked potentials induced by 5 Hz intermittent photic stimulation in 46 children (3 to 16 years) and 8 adults, as a function of age. We found that, over the occipital region, magnitude values were the highest in 8-11-year old children, but decreased with age over all other cerebral regions. Phase alignment values increased with age over the occipital, parietal and frontal cerebral regions. We interpret these findings in terms of the development of functional interactions between different cortical areas involved in the processing of visual stimuli.

Periictal activity in cooled asphyxiated neonates with seizures

PURPOSE Seizures are common in critically ill neonates. Both seizures and antiepileptic treatments may lead to short term complications and worsen the outcomes. Predicting the risks of seizure reoccurrence could enable individual treatment regimens and better outcomes. We aimed to identify EEG signatures of seizure reoccurrence by investigating periictal electrographic features and spectral power characteristics in hypothermic neonates with hypoxic-ischemic encephalopathy (HIE) with or without reoccurrence of seizures on rewarming. METHODS We recruited five consecutive HIE neonates, submitted to continuous EEG monitoring, with high seizure burden (>20% per hour) while undergoing therapeutic hypothermia. Two of them had reoccurrence of seizures on rewarming. We performed quantitative analysis of fifteen artifact-free consecutive seizures to appreciate spectral power changes between the interictal, preictal and ictal periods, separately for each patient. Visual analysis allowed description of electrographic features associated with ictal events. RESULTS Every patient demonstrated a significant increase in overall spectral power from the interictal to preictal and ictal periods (p<0.01). Alpha power increase was more pronounced in the two patients with reoccurrence of seizures on rewarming and significant when comparing both interictal-to-preictal and interictal-to-ictal periods. This alpha activity increase could be also appreciated using visual analysis and distinguished neonates with and without seizure reoccurrence. CONCLUSION This distinct alpha activity preceding ictal onset could represent a biomarker of propensity for seizure reoccurrence in neonates. Future studies should be performed to confirm whether quantitative periictal characteristics and electrographic features allow predicting the risks of seizure reoccurrence in HIE neonates and other critically ill patients.