Shelly K. Weiss

Practice Parameter: Medical Treatment of Infantile Spasms Report of the American Academy of Neurology and the Child Neurology Society

Objective: To determine the current best practice for treatment of infantile spasms in children. Methods: Database searches of MEDLINE from 1966 and EMBASE from 1980 and searches of reference lists of retrieved articles were performed. Inclusion criteria were the documented presence of infantile spasms and hypsarrhythmia. Outcome measures included complete cessation of spasms, resolution of hypsarrhythmia, relapse rate, developmental outcome, and presence or absence of epilepsy or an epileptiform EEG. One hundred fifty-nine articles were selected for detailed review. Recommendations were based on a four-tiered classification scheme. Results: Adrenocorticotropic hormone (ACTH) is probably effective for the short-term treatment of infantile spasms, but there is insufficient evidence to recommend the optimum dosage and duration of treatment. There is insufficient evidence to determine whether oral corticosteroids are effective. Vigabatrin is possibly effective for the short-term treatment of infantile spasm and is possibly also effective for children with tuberous sclerosis. Concerns about retinal toxicity suggest that serial ophthalmologic screening is required in patients on vigabatrin; however, the data are insufficient to make recommendations regarding the frequency or type of screening. There is insufficient evidence to recommend any other treatment of infantile spasms. There is insufficient evidence to conclude that successful treatment of infantile spasms improves the long-term prognosis. Conclusions: ACTH is probably an effective agent in the short-term treatment of infantile spasms. Vigabatrin is possibly effective.

Magnetoencephalographic localization in pediatric epilepsy surgery: Comparison with invasive intracranial electroencephalography

The object of this study was to determine the concordance of the anatomical location of interictal magnetoencephalographic (MEG) spike foci with the location of ictal onset zones identified by invasive ictal intracranial electroencephalographic recordings in children undergoing evaluation for epilepsy surgery. MEG was performed in 11 children with intractable, nonlesional, extratemporal, localization‐related epilepsy. Subsequently, chronic invasive intracranial electroencephalographic monitoring was performed by using subdural electrodes to localize the ictal onset zone and eloquent cortex. Based on the invasive monitoring data, all children had excision of, or multiple subpial transections through, ictal onset cortex and surrounding irritative zones. In 10 of 11 patients, the anatomical location of the epileptiform discharges as determined by MEG corresponded to the ictal onset zone established by ictal intracranial recordings. In all children, the anatomical location of the somatosensory hand area, determined by functional mapping through the subdural electrode array, was the same as that delineated by MEG. Nine of 11 patients became either seizure‐free or had a greater than 90% reduction in seizures after surgery, with a mean follow‐up of 24 months. MEG is a powerful and accurate tool in the presurgical evaluation of children with refractory nonlesional extratemporal epilepsy.

Evidence-based guideline update: Medical treatment of infantile spasms Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society

Objective: To update the 2004 American Academy of Neurology/Child Neurology Society practice parameter on treatment of infantile spasms in children. Methods: MEDLINE and EMBASE were searched from 2002 to 2011 and searches of reference lists of retrieved articles were performed. Sixty-eight articles were selected for detailed review; 26 were included in the analysis. Recommendations were based on a 4-tiered classification scheme combining pre-2002 evidence and more recent evidence. Results: There is insufficient evidence to determine whether other forms of corticosteroids are as effective as adrenocorticotropic hormone (ACTH) for short-term treatment of infantile spasms. However, low-dose ACTH is probably as effective as high-dose ACTH. ACTH is more effective than vigabatrin (VGB) for short-term treatment of children with infantile spasms (excluding those with tuberous sclerosis complex). There is insufficient evidence to show that other agents and combination therapy are effective for short-term treatment of infantile spasms. Short lag time to treatment leads to better long-term developmental outcome. Successful short-term treatment of cryptogenic infantile spasms with ACTH or prednisolone leads to better long-term developmental outcome than treatment with VGB. Recommendations: Low-dose ACTH should be considered for treatment of infantile spasms. ACTH or VGB may be useful for short-term treatment of infantile spasms, with ACTH considered preferentially over VGB. Hormonal therapy (ACTH or prednisolone) may be considered for use in preference to VGB in infants with cryptogenic infantile spasms, to possibly improve developmental outcome. A shorter lag time to treatment of infantile spasms with either hormonal therapy or VGB possibly improves long-term developmental outcomes.

Focal resection of fast ripples on extraoperative intracranial EEG improves seizure outcome in pediatric epilepsy

Purpose:  High‐frequency oscillations (HFOs), termed ripples at 80–200 Hz and fast ripples (FRs) at >200/250 Hz, recorded by intracranial electroencephalography (EEG), may be a valuable surrogate marker for the localization of the epileptogenic zone. We evaluated the relationship of the resection of focal brain regions containing high‐rate interictal HFOs and the seizure‐onset zone (SOZ) determined by visual EEG analysis with the postsurgical seizure outcome, using extraoperative intracranial EEG monitoring in pediatric patients and automated HFO detection.

MEG Predicts Outcome Following Surgery for Intractable Epilepsy in Children with Normal or Nonfocal MRI Findings

Summary:  Purpose: To identify the predictors of postsurgical seizure freedom in children with refractory epilepsy and normal or nonfocal MRI findings.

Dysembryoplastic neuroepithelial tumors in childhood Long-term outcome and prognostic features

Background: Dysembryoplastic neuroepithelial tumors (DNTs) are associated with medically intractable epilepsy and a favorable prognosis after surgical resection. The authors describe the clinical, radiologic, and pathologic characteristics and outcomes in children after surgical resection of pathologically confirmed DNT to ascertain prognostic features for seizure recurrence following surgery. Methods: Neurology, neurosurgery, and pathology databases from 1993 to 2002 at the Hospital for Sick Children were searched to retrospectively identify children with confirmed DNT and presentation with seizures. Risk factors for postoperative seizure recurrence were examined with respect to seizure outcome at 12 months and long-term follow-up. Results: Of the 26 children identified (mean age at surgery 10.0 years) seizure outcome was good in 22 children (85%) at 12 months (Class 1). At longer follow-up (mean 4.3, range 1.0 to 11.0 years) only 16 (62%) remained seizure-free. Residual DNT was evident in 15 of the 24 children with available postoperative MRI. Three children demonstrated recurrence of tumor. At 12 months follow-up, older age (>10 years) and longer duration of epilepsy (>2 years) were associated with seizure recurrence. The presence of residual tumor was a risk factor for seizure recurrence at long-term follow-up (p = 0.02). Conclusions: Children with DNT and epilepsy may benefit from surgical management; however, seizure outcome is not always favorable. Although the majority of children remain seizure free after surgical excision of DNT, a considerable number have recurrent seizures. Short-term outcome is influenced by older age at surgery and longer duration of epilepsy. Residual tumor is a significant risk factor for poor seizure outcome. Recurrent tumor can occur.

The Prevalence of Autistic Spectrum Disorder in Children Surveyed in a Tertiary Care Epilepsy Clinic

Summary:  It is well documented that children with autistic spectrum disorder (ASD) have an increased prevalence of seizures; however, studies have not been done to evaluate the prevalence of ASD in children with epilepsy. This comorbidity is important to define as early diagnosis and intervention in some children with ASD has been shown to improve outcome.

Canadian 24-Hour Movement Guidelines for Children and Youth: An Integration of Physical Activity, Sedentary Behaviour, and Sleep1

Leaders from the Canadian Society for Exercise Physiology convened representatives of national organizations, content experts, methodologists, stakeholders, and end-users who followed rigorous and transparent guideline development procedures to create the Canadian 24-Hour Movement Guidelines for Children and Youth: An Integration of Physical Activity, Sedentary Behaviour, and Sleep. These novel guidelines for children and youth aged 5-17 years respect the natural and intuitive integration of movement behaviours across the whole day (24-h period). The development process was guided by the Appraisal of Guidelines for Research Evaluation (AGREE) II instrument and systematic reviews of evidence informing the guidelines were assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Four systematic reviews (physical activity, sedentary behaviour, sleep, integrated behaviours) examining the relationships between and among movement behaviours and several health indicators were completed and interpreted by expert consensus. Complementary compositional analyses were performed using Canadian Health Measures Survey data to examine the relationships between movement behaviours and health indicators. A stakeholder survey was employed (n = 590) and 28 focus groups/stakeholder interviews (n = 104) were completed to gather feedback on draft guidelines. Following an introductory preamble, the guidelines provide evidence-informed recommendations for a healthy day (24 h), comprising a combination of sleep, sedentary behaviours, light-, moderate-, and vigorous-intensity physical activity. Proactive dissemination, promotion, implementation, and evaluation plans have been prepared in an effort to optimize uptake and activation of the new guidelines. Future research should consider the integrated relationships among movement behaviours, and similar integrated guidelines for other age groups should be developed.

Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation.

KCNQ2 mutations have been found in patients with benign familial neonatal seizures, myokymia, or early onset epileptic encephalopathy (EOEE). In this study, we aimed to delineate the clinical spectrum of EOEE associated with KCNQ2 mutation.

Temporal lobe surgery for intractable epilepsy in children: an analysis of outcomes in 126 children.

OBJECTIVETemporal lobectomy is a well-established neurosurgical procedure for temporal lobe epilepsy. In this study, we conducted a retrospective review of children with drug-resistant temporal lobe epilepsy to evaluate seizure outcome after temporal lobe surgery. METHODSWe reviewed the medical records of 126 children who had surgery for temporal lobe epilepsy at The Hospital for Sick Children between 1983 and 2003. The records were examined for preoperative and intraoperative factors that could predict patient outcome after surgery. RESULTSThe mean age at seizure onset was 5.9 years. The mean seizure duration before surgery was 5.6 years. All patients had preoperative computed tomographic scans, magnetic resonance imaging scans, or both. The mean age at the time of surgery was 13.5 years. Sixty-two patients underwent left temporal resections and 64 patients underwent right temporal resections. The histopathology of the temporal resections revealed low-grade brain tumors in 65 children (52%) and cavernous malformations in four children. Ganglioglioma and astrocytoma were the most common tumors encountered. Mesial temporal sclerosis was found in 16 patients (13%), astrogliosis in 15 patients (12%), and cortical dysplasia in eight patients (7%). Postoperative follow-up of at least 2 years was available for 106 patients and ranged up to 13.0 years. Seventy-four percent of patients had an Engel Class I or II outcome. Patients with temporal lobe lesions had better outcomes compared with those without lesions (P < 0.05). Patients without a history of secondary generalization of seizures also had a better outcome when compared with those with secondary generalization. Complications in the form of contralateral homonymous hemianopsia, dysphasia, and infection were found in 5% of patients. Twelve patients had a second temporal lobe procedure for intractable recurrent seizures. After a second procedure, seven patients returned to a seizure-free state. CONCLUSIONTemporal lobe resections for epilepsy in children are effective and safe procedures, with a favorable impact on seizure control. Repeat temporal resections for recurrent seizures may also be effective in restoring a seizure-free outcome to children.