Multicenter Research Data of Epilepsy Management in Patients With Sturge-Weber Syndrome.

BACKGROUND: Epilepsy in typical Sturge-Weber syndrome (SWS) is common, and many questions remain regarding the treatment outcomes. We analyzed a large multicenter database with focus on neurological drug treatment in different demographic and SWS characteristic groups. METHODS: A total of 268 patients with brain involvement and a history of seizures were selected from a research data registry generated from a multicenter cross-sectional questionnaire. We examined associations between medication use and binary variables such as sex, ethnicity, and brain, skin, and eye involvement laterality. We analyzed group differences in mean number of antiseizure medications and age at diagnosis, enrollment, and seizure onset and examined differences in median SWS neurological scores in groups of interest. RESULTS: The most frequently used medications were levetiracetam (48.1%), low-dose aspirin (44.8%), oxcarbazepine (39.9%), and phenobarbital (14.9%). Lamotrigine was more frequently used in adults than in children (P = 0.001). History of neurosurgery was associated with no current antiseizure medication use (P = 0.001), whereas bilateral brain involvement and family history of seizures were associated with using a higher number of antiseizure medications (P = 0.002, P = 0.027, respectively). Subjects with bilateral brain involvement and early seizure onset were associated with using a higher number of antiseizure medications (P = 0.002) and phenobarbital use (0.003). CONCLUSIONS: Levetiracetam, low-dose aspirin, and oxcarbazepine were the most frequently used medications. More severely affected patients were frequently on a greater number of antiseizure medications. Surgery for epilepsy was associated with the ability to discontinue antiseizure medication. Longitudinal studies are needed to further investigate medication use in patients with SWS.

Physical and Family History Variables Associated With Neurological and Cognitive Development in Sturge-Weber Syndrome.

BACKGROUND: Sturge-Weber syndrome (SWS) is caused by a somatic mutation in GNAQ leading to capillary venous malformations in the brain presenting with various neurological, ophthalmic, and cognitive symptoms of variable severity. This clinical variability makes accurate prognosis difficult. We hypothesized that the greater extent of physical factors (extent of skin, eye, and brain involvement), presence of possible genetic factors (gender and family history), and age of seizure onset may be associated with greater symptom severity and need for surgery in patients with SWS. METHODS: The questionnaire was collected from 277 participants (age: two months to 66 years) with SWS brain involvement at seven US sites. RESULTS: Bilateral brain involvement was associated with both learning disorder and intellectual disability, whereas port-wine birthmark extent was associated with epilepsy and an increased likelihood of glaucoma surgery. Subjects with family history of vascular birthmarks were also more likely to report symptomatic strokes, and family history of seizures was associated with earlier seizure onset. Learning disorder, intellectual disability, strokelike episodes, symptomatic stroke, hemiparesis, visual field deficit, and brain surgery were all significantly associated with earlier onset of seizures. CONCLUSION: The extent of brain and skin involvement in SWS, as well as the age of seizure onset, affect prognosis. Other genetic factors, particularly variants involved in vascular development and epilepsy, may also contribute to neurological prognosis, and further study is needed.

Active comparator-controlled, rater-blinded study of corticotropin-based immunotherapies for opsoclonus-myoclonus syndrome.

To test the efficacy and safety of corticotropin-based immunotherapies in pediatric opsoclonus-myoclonus syndrome, 74 children received corticotropin alone or with intravenous immunoglobulin (groups 1 and 2, active controls); or both with rituximab (group 3) or cyclophosphamide (group 4); or with rituximab plus chemotherapy (group 5) or steroid sparers (group 6). There was 65% improvement in motor severity score across groups (P < .0001), but treatment combinations were more effective than corticotropin alone (P = .0009). Groups 3, 4, and 5 responded better than group 1; groups 3 and 5 responded better than group 2. The response frequency to corticotropin was higher than to prior corticosteroids (P < .0001). Fifty-five percent had adverse events (corticosteroid excess), more so with multiagents (P = .03); and 10% had serious adverse events. This study demonstrates greater efficacy of corticotropin-based multimodal therapy compared with conventional therapy, greater response to corticotropin than corticosteroid-based therapy, and overall tolerability.

Intracranial hemorrhage in children: an evolving spectrum.

BACKGROUND: Nontraumatic intracranial hemorrhages (ICHs) are uncommon in children, but are important causes of death and injury. OBJECTIVES: To determine whether the risk factors for ICH have changed compared with those in earlier published series and to estimate the residual deficits in the survivors. DESIGN, SETTING, AND PATIENTS: We performed a retrospective review of patients admitted to a single tertiary care, academic pediatric hospital from January 1, 2000, through May 31, 2007. Records were retrieved if the diagnostic codes from the International Classification of Diseases, Ninth Revision, were pertinent to ICHs. We searched reports from computed tomograms and magnetic resonance images of the brain for terms pertaining to ICH. MAIN OUTCOME MEASURES: Risk factors and functional outcome. Secondary measures were hemorrhage type and clinical presentation. RESULTS: We identified 85 children who had nontraumatic ICH. There were 10 subarachnoid, 61 intracerebral, and 14 subdural hemorrhages. Intracranial vascular anomalies were the most frequent risk factor, followed by congenital heart disease and brain tumors. Arteriovenous malformations did not account for as large a percentage as in previous studies. Twenty-nine children died. Of the 48 survivors for whom follow-up information was available, 26 had no reported deficits and 22 had deficits ranging from mild to severe. CONCLUSIONS: In this series, brain tumors and congenital heart disease accounted for a greater proportion of ICHs than in previous studies. The mortality due to ICH remains high but may be related as much to the severity of the underlying illnesses as to the hemorrhage itself. We found significant long-term morbidity, but more than half of the survivors for whom follow-up data were available had no detectable deficits. A long-term outcome study of pediatric ICH is needed.

Isolated neurosarcoidosis presenting as headache and multiple brain and spinal cord lesions mimicking central nervous system metastases.

Sarcoidosis is uncommon in children. Although isolated neurosarcoidosis has been seen in 15% adults with sarcoidosis, pediatric neurosarcoidosis is rarely reported. Neurosarcoidosis may present with cranial neuropathy, including facial palsy, optic nerve or other cranial nerve involvement, peripheral neuropathy, or manifestations of the central nervous system affecting the hypothalamus, pituitary gland, cerebral cortex, cerebellum, meninges, and spinal cord. The useful diagnostic investigations include magnetic resonance imaging of the brain and spinal cord, cerebrospinal fluid studies, brain and meningeal biopsy if feasible, chest radiography to reveal sarcoidosis, angiotensin-converting enzyme level in the serum or cerebrospinal fluid, and Kveim test when available. We herein report a case of isolated brain biopsy-confirmed neurosarcoidosis in a 17-year-old boy presenting with severe unilateral headache and multiple brain and spinal cord MRI lesions mimicking central nervous system metastases.

Induction of apoptosis by the p53-related p73 and partial inhibition by the baculovirus-encoded p35 in neuronal cells.

To better understand whether the p53-related p73 gene could induce neuronal apoptosis, we tested whether p73 induced cell killing in three neuronal cell lines and whether apoptosis could be inhibited by p35, a baculovirus-encoded protein that blocks caspase 3. Recombinant adenoviruses carrying the hemagglutinin (HA)-tagged p73beta or p35, or the green fluorescent protein gene driven by the cytomegalovirus immediate-early promoter were constructed, and used to infect human SK-N-AS and SK-N-SH neuroblastoma, and rat PC12 pheochromocytoma cells. Infection with Adp73beta virus resulted in p73beta over-expression and substantial reduction of cell viability due to apoptosis in all three neuronal cell lines as compared with the control AdGFP virus. These results indicate that p73beta over-expression in neuronal cells could induce apoptotic cell death regardless of the endogenous expression of p73. The p73 effect was partially blocked by co-expression of the wild-type p35, suggesting caspase-mediated cell killing. Insertion of a hemagglutinin (HA) tag at the N-terminus of p35 markedly reduced its ability to inhibit the p73 effect compared with the wild-type p35, while insertion of an HA tag to the C-terminus of p35 had no appreciable effect. Taken together, our results suggest that the N-terminal structure of p35 is critical for its anti-apoptotic activity on p73-induced apoptosis in neuronal cells.