Cerebral venous sinus thrombosis in children: a multicenter cohort from the United States.

This study presents a large multicenter cohort of children with cerebral venous thrombosis from 5 centers in the United States and analyzes their clinical findings and risk factors. Seventy patients were included in the study (25 neonates, 35%). The age ranged from 6 days to 12 years. Thirty-eight (55%) were younger than 6 months of age, and 28 (40%) were male. Presenting features included seizures (59%), coma (30%), headache (18%), and motor weakness (21%). Common neurological findings included decreased level of consciousness (50%), papilledema (18%), cranial nerve palsy (33%), hemiparesis (29%), and hypotonia (22%). Predisposing factors were identified in 63 (90%) patients. These included infection (40%), perinatal complications (25%), hypercoagulable/hematological diseases (13%), and various other conditions (10%). Hemorrhagic infarcts occurred in 40% of the patients and hydrocephalus in 10%. Transverse sinus thrombosis was more common (73%) than sagittal sinus thrombosis (35%). Three children underwent thrombolysis, 15 patients received anticoagulation, and 49 (70%) were treated with antibiotics and hydration. Nine (13%) patients (6 of them neonates) died. Twenty-nine patients (41%) were normal, whereas 32 patients (46%) had a neurological deficit at discharge. Seizures and coma at presentation were poor prognostic indicators. In conclusion, cerebral venous thrombosis predominantly affects children younger than age 6 months. Mortality is high (25%) in neonatal cerebral venous thrombosis. Only 18 (25%) patients were treated with anticoagulation or thrombolysis.

Prolonged hemiplegic episodes in children due to mutations in ATP1A2.

BACKGROUND: Familial hemiplegic migraine (FHM) is an unusual migraine syndrome characterised by recurrent transient attacks of unilateral weakness or paralysis as part of the migraine aura. Genetically and clinically heterogeneous, FHM1 is caused by mutations in CACNA1A and FHM2 by mutations in ATP1A2. AIM: Three children with prolonged hemiplegia were tested for mutations in CACNA1A or ATP1A2. METHODS: Mutations in CACNA1A and ATP1A2 were screened for by denaturing high performance liquid chromatography and confirmed by sequencing. Expression studies were performed to characterise the functional consequences of these mutations. RESULTS: No mutation was found in the FHM1 gene while three mutations were identified in the FHM2 gene. All three mutations were missense: two were novel and one was de novo; none was found in controls. Functional studies in HeLa cells showed complete loss of mutant pump function without interfering with the wild-type pump, consistent with haploinsufficiency. CONCLUSION: We identified novel disease causing mutations in the FHM2 gene. Genetic screening for FHM should be considered in a child with prolonged hemiplegia even if there is no prior history or family history of migraine or hemiplegic episodes.

Diagnostic criteria for schwannomatosis.

The neurofibromatoses are a diverse group of genetic conditions that share a predisposition to the development of tumors of the nerve sheath. Schwannomatosis is a recently recognized third major form of neurofibromatosis (NF) that causes multiple schwannomas without vestibular tumors diagnostic of NF2. Patients with schwannomatosis represent 2.4 to 5% of all patients requiring schwannoma resection and approximately one third of patients with schwannomatosis have anatomically localized disease with tumors limited to a single limb or segment of spine. Epidemiologic studies suggest that schwannomatosis is as common as NF2, but that familial occurrence is inexplicably rare. Patients with schwannomatosis overwhelmingly present with pain, and pain remains the primary clinical problem and indication for surgery. Diagnostic criteria for schwannomatosis are needed for both clinicians and researchers, but final diagnostic certainly will await the identification of the schwannomatosis locus itself.