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.

Magnetoencephalographic spike sources associated with auditory auras in paediatric localisation-related epilepsy.

OBJECTIVE: To characterise magnetoencephalographic spike sources in paediatric patients with auditory auras and recurrent localisation-related epilepsy. METHODS: Six patients (four boys and two girls (ages 7-14 years) were retrospectively studied. All patients had auditory auras as part of their initial seizure manifestation, including four patients who underwent previous brain surgery. Scalp video electroencephalography and magnetoencephalography (MEG) were carried out in six patients, intraoperative electrocorticography in three patients and extraoperative intracranial video electroencephalography in one patient. MEG auditory-evoked fields (AEFs) were studied in four patients. RESULTS: Three patients had elementary auditory auras, one had complex auditory aura and two had both complex and elementary auras. All six patients had clustered MEG spike sources with coexisting scattered spike sources. MEG clusters were localised in the superior temporal gyrus with surrounding scatters in four patients (two left and two right); two patients had scattered spikes in the superior temporal gyrus in addition to clustered MEG spike sources in the left inferior and middle frontal gyri or parieto-occipital region. AEFs were located within an MEG cluster in one patient and within 3 cm of a cluster in two patients. Surgical resection, including the regions of MEG clusters, was carried out in four patients. Three of four patients who had previous surgeries were seizure free at 2 years after excision of the MEG cluster region. CONCLUSIONS: MEG spike sources clustered in the superior temporal gyrus in six patients with auditory auras. These spike sources were in close proximity or seemed to engulf the magnetic AEF. Areas with MEG spike sources contained the residual or recurrent epileptogenic zone after incomplete cortical excision for lesional epilepsy.

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.

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.

Malformations of cortical development with balloon cells: clinical and radiologic correlates.

BACKGROUND: Balloon cells are a key feature of tuberous sclerosis (TS) but are also seen in focal cortical dysplasia (FCD). The authors compare the clinical and MRI characteristics in children with medically refractory localization-related epilepsy who were found to have balloon cells on histology after cortical resections. METHODS: A retrospective review of clinical and MRI data in cases ascertained from a search of pathology records from 1990 until 2000 for those with a diagnosis of FCD or TS. Seventeen patients were identified with malformations of cortical development with balloon cells on histology. Seven had clinical diagnosis of TS and the remaining 10, FCD with balloon cells (FCDBC). RESULTS: Seventy percent of patients with FCDBC (mean follow-up 3.3 years) and 33% of patients with TS (mean follow-up 5.1 years) are seizure free after surgery. There was agreement between the diagnosis based on preoperative MR imaging and on histology in 60% of patients with FCDBC and 71% of patients with TS. Myelin depletion and calcification were noted more frequently in patients with TS. CONCLUSIONS: No significant differences were noted between patients with refractory epilepsy caused by TS or FCDBC. There was a trend toward better postoperative seizure control in the FCDBC group. These two conditions are difficult to distinguish on the basis of MR and histologic appearances. The authors conclude that FCDBC likely represents a phenotypic variation of TS, and as such, all patients with balloon cell dysplasias should be carefully screened for other features of TS to enable appropriate genetic counseling.

Extraoperative cortical stimulation of motor function in children.

The purpose of the study was to investigate factors altering the amperage threshold needed to provoke functional responses in children with epilepsy. Twenty patients (4-18 years of age) who underwent epilepsy surgery at our institution from 1996-2000 after insertion of subdural grid electrodes were reviewed retrospectively. Extraoperative electrical cortical stimulation was performed with 50-Hz biphasic pulses of 0.2 ms in duration using a "distance reference" technique. Amperage thresholds of primary motor responses and afterdischarges were evaluated. The patients were grouped according to underlying pathology: eight with neuronal migration disorders (group A) and 12 with other disorders (group B). The motor cortex was defined successfully in all children because the afterdischarges threshold was higher than the motor cortical threshold. Amperage thresholds ranged from 2-20 mA (mean = 7.7) for primary motor function. An inverse relationship was found between amperage threshold and age: the younger the patient, the higher the threshold (P = 0.0005). Patients in group A required a higher amperage (2-20 mA, mean = 8.6) for motor cortical mapping than those in group B (2-14 mA, mean = 6.4). Younger children with neuronal migration disorders require a higher amperage threshold to achieve adequate motor functional mapping with careful observation of afterdischarges.

Cyclosporine A neurotoxicity in a patient with idiopathic renal magnesium wasting.

We report a female child who had idiopathic renal magnesium wasting secondary to suspected Gitleman syndrome and cyclosporine A neurotoxicity after a heart transplant. The child had acute, progressive encephalopathy, intractable seizures, quadriparesis, and extensive, bilateral cortical involvement on neuroimaging. Two days after discontinuation of the cyclosporine, the child's condition improved dramatically, including an improved level of consciousness, and she became seizure free. By 6 weeks, she was fully ambulatory. Follow-up magnetic resonance imaging and electroencephalograms demonstrated significant improvement. This patient had drug-induced neurotoxicity, exacerbated by hypomagnesemia. Cyclosporine should be used cautiously in transplant patients with Gitelman syndrome or other acquired magnesium homeostasis disorders because of the possible increased risk of neurotoxicity. This report is the first case of a patient with both cyclosporine neurotoxicity and magnesium-wasting nephropathy.

Ethyl chloride: 11-day continuous exposure inhalation toxicity study in B6C3F1 mice.

Groups of seven B6C3F1 mice per sex were exposed for 23 hr/day to 0, 250, 1250, or 5000 ppm ethyl chloride (EtCl) for 11 consecutive days to evaluate the potential toxicity of EtCl under near-continuous exposure conditions. On the day following the last exposure, a neurobehavioral observation battery was performed, samples were obtained for clinical chemistry and hematology, and necropsies were conducted. Histopathologic examination was subsequently performed. The only observed effects were increased relative liver weights and a slight increase in hepatocellular vacuolation (glycogen or fat) in 5000 ppm-exposed mice. Exposures to EtCl were well tolerated despite the unusually long exposure periods.

Diethylene glycol monomethyl ether 13-week vapor inhalation toxicity study in rats.

Male and female Fischer 344 rats were exposed to 0, 30, 100, or 216 ppm diethylene glycol monomethyl ether (DEGME) vapors (0, 0.15, 0.49, or 1.06 mg/liter) 6 hr/day, 5 days/week, for 13 weeks. The 216-ppm exposure level was the maximum practically attainable concentration, and it was more than 60% of the theoretical maximum vapor concentration for DEGME at 25 degrees C and 1 atm pressure. Body weights, organ weights, hematological analyses, clinical chemistry analyses, urinalyses, and gross and histopathological examinations revealed no indication of a treatment effect in either male or female rats. Based on the absence of treatment-related effects in this study and the low vapor pressure of the material, DEGME should not present the same degree of inhalation hazard as its structural homolog, ethylene glycol monomethyl ether.