Ayuko Igarashi

Efficacy and safety of fosphenytoin for benign convulsions with mild gastroenteritis

OBJECTIVE To clarify the efficacy and safety of fosphenytoin for seizures in children with benign convulsions and mild gastroenteritis. METHODS Using the mailing list of the Annual Zao Conference on Pediatric Neurology, we recruited patients who met the following criteria: (1) clinical diagnosis of benign convulsions with mild gastroenteritis and (2) treatment with intravenous fosphenytoin. Benign convulsions with mild gastroenteritis were defined as a condition of (a) seizures associated with gastroenteritis without electrolyte imbalance, hypoglycemia, or dehydration in patients (b) between 6 months and 3 years of age with (c) no preexisting neurological disorders, (d) no impaired consciousness, and (e) a body temperature less than 38.0 °C before and after the seizures. The efficacy of fosphenytoin was categorized as effective when cessation of seizures was achieved. RESULTS Data from 16 child patients were obtained (median age, 20 months). Seizures were completely controlled after the initial dose of fosphenytoin in 14 of 16 patients. The median loading dose of fosphenytoin was 22.5 mg/kg. In 10 patients, fosphenytoin was administered after other antiepileptic drugs such as diazepam and midazolam were used. Adverse effects of fosphenytoin, excessive sedation, or intravenous fluid incompatibility were not observed in any patients. CONCLUSION Fosphenytoin is effective and well tolerated among children with benign convulsions with mild gastroenteritis.

Anti-aquaporin 4 antibody-positive acute disseminated encephalomyelitis

OBJECTIVE To describe the clinical and neuroimaging features of a young female patient with acute disseminated encephalomyelitis associated with anti-aquaporin-4 antibodies. METHODS The patient had mild encephalopathy 14 days after influenza vaccination. Cerebrospinal fluid analysis revealed an increased cell count and a marked increase in myelin basic protein. Magnetic resonance imaging (MRI) demonstrated multiple lesions in the juxtacortical white matter. The patient was diagnosed with acute disseminated encephalomyelitis and treated with methylprednisolone pulse therapy. She recovered in 1 month. However, right retrobulbar optic neuritis appeared 2 months after discharge, and serum anti-aquaporin 4 antibodies were measured with a cell-based assay. RESULTS Anti-aquaporin 4 antibodies were present in the patients serum. She was treated with a prolonged course of oral prednisolone. The patient was negative for serum anti-aquaporin 4 antibodies 8 months after the second clinical event, and prednisolone was discontinued 13 months after the second clinical event. Serum anti-aquaporin 4 antibodies remained negative 4 months after the discontinuation of prednisolone. There was no evidence of relapse at 9 months after discontinuation of steroids. CONCLUSIONS This case will expand the spectrum of anti-aquaporin-4 antibody-related central nervous system disorders. The measurement of anti-aquaporin 4 antibody may be considered in patients with a clinical diagnosis of acute disseminated encephalomyelitis and a second clinical event within a short interval.

Focal seizures and epileptic spasms in a child with Down syndrome from a family with a PRRT2 mutation.

We describe a girl with Down syndrome who experienced focal seizures and epileptic spasms during infancy. The patient was diagnosed as having trisomy 21 during the neonatal period. She had focal seizures at five months of age, which were controlled with phenobarbital. However, epileptic spasms appeared at seven months of age in association with hypsarrhythmia. Upon treatment with adrenocorticotropic hormone, her epileptic spasms disappeared. Her younger brother also had focal seizures at five months of age. His development and interictal electroencephalogram were normal. The patients father had had infantile epilepsy and paroxysmal kinesigenic dyskinesia. We performed a mutation analysis of the PRRT2 gene and found a c.841T>C mutation in the present patient, her father, and in her younger brother. We hypothesized that the focal seizures in our patient were caused by the PRRT2 mutation, whereas the epileptic spasms were attributable to trisomy 21.

Sustained improvement of attitudes about epilepsy following a reduction in media coverage of car accidents involving persons with epilepsy

To evaluate changes in the attitudes of nonmedical students about epilepsy, the present study compared the results of a questionnaire that was completed in three different time periods: before media coverage of car accidents associated with epilepsy, during a period of abundant media coverage about epilepsy-related accidents, and after media coverage of epilepsy-related accidents. The nonmedical students who completed the questionnaire were divided into three groups: Years 08-10 (preaccident era), Years 11-12 (media coverage era), and Years 13-14 (postmedia coverage era). The rates of students who had read or heard about epilepsy and of students who did not think that epilepsy was a mental disorder increased annually throughout the study period. There was an improvement in attitudes about epilepsy after the media coverage era, and this change was not altered even after a decrease in the media coverage of epilepsy-related car accidents. Additionally, the rate of positive answers did not differ between Years 11-12 and Years 13-14. These findings demonstrate that the familiarity with and improved attitudes about epilepsy were sustained even after the media coverage of car accidents involving persons with epilepsy had decreased.

Attitudes toward driver's licenses for people with epilepsy: 2012 versus 2014.

We compared knowledge about and attitudes toward epilepsy and the issuing of drivers licenses to people with epilepsy among non‐medical students before and after media controversies.

Clinically silent seizures in a neonate with tuberous sclerosis

Although seizures during infancy in patients with tuberous sclerosis complex are common, seizures in neonates are infrequent. Here, we report the clinical course and electroencephalography (EEG) findings of a neonate with tuberous sclerosis complex associated with clinically silent seizures. The patient was a girl in whom cardiac tumors were detected on fetal ultrasonography. Brain magnetic resonance imaging during the neonatal period showed subependymal and cortical tubers. Routine EEG indicated unexpected ictal changes with no noticeable clinical symptoms. Ictal EEG was associated with a subtle increase in heart rate and a brief increase in chin electromyogram. These changes were difficult to identify clinically. The patient later developed focal seizures and epileptic spasms and had severe psychomotor delay. The present case suggests the occurrence of clinically silent seizures before the appearance of epileptic spasms in infants with tuberous sclerosis, and that EEG is an option for neonates with a prenatal diagnosis.

Fulminant encephalopathy with marked brain edema and bilateral thalamic lesions.

We encountered two children with acute encephalopathy associated with unique clinical manifestations. Both the patients had status epilepticus at onset and neuroimaging studies revealed marked brain edema and bilateral thalamic lesions. Although they were treated with steroids and immunoglobulin, their outcomes were very poor. A thermolabile variant of carnitine palmitoyltransferase II and an elevated interleukin-6 level in cerebrospinal fluid were observed in one patient each. The constellation of clinical and neuroimaging findings in our patients is apparently not consistent with any established subtype of acute encephalopathy/encephalitis.

Efficacy and tolerability of high-dose phenobarbital in children with focal seizures

OBJECTIVE We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. METHODS We reviewed data on children (aged<15 years) with focal seizures treated with high-dose phenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. RESULTS Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. CONCLUSION Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult.

Amplitude-integrated EEG revealed nonconvulsive status epilepticus in children with non-accidental head injury

OBJECTIVE We describe the clinical course and amplitude-integrated EEG findings in three children with non-accidental head injury and discuss on the importance of continuous aEEG monitoring in infants. METHODS NCSE was defined as a continuous 30-min seizure or briefer seizures occurring consecutively comprising at least 30 min of any 1-h period. Non-accidental head injury was diagnosed on the basis of neuroimaging findings such as subdural hemorrhage. Antiepileptic treatment was performed with continuous amplitude-integrated EEG monitoring. RESULTS The age of the patients ranged from 48 days to nine months. All of them had loss of consciousness and seizures on presentation. Nonconvulsive status epilepticus without clinical symptoms were recognized in all patients. Vigorous antiepileptic treatment against nonconvulsive status epilepticus was made in two patients, whereas nonconvulsive status epilepticus disappeared within one hour without additional treatment in one. CONCLUSIONS Our experience indicates that nonconvulsive status epilepticus were not uncommon in children with non-accidental head injury. Continuous amplitude-integrated EEG monitoring will be one of the useful methods in encephalopathic children in order to estimate seizure burden objectively and to treat seizures appropriately.

Acute limbic encephalitis with focal hyperperfusion on single photon emission computed tomography.

Here we report an 11-year-old boy with acute encephalopathy with neuropsychiatric symptoms. The patient had mildly decreased consciousness, delirious behavior, and affective changes next day of fever onset. Hematologic, biochemical, and metabolic examinations were unremarkable. CSF analysis revealed cell counts of 278 cells/mm(3) and a protein level of 87 mg/dL. Although MRI revealed no abnormal findings, an increase in regional cerebral blood flow was present in the bilateral frontal lobes, mesial temporal lobes, and basal ganglia on single photon emission computed tomography. The measurement of the concentrations of biomarkers such as cytokines in the patients serum and cerebrospinal fluid revealed elevated levels of IL-4 and TNF-α in the cerebrospinal fluid. Immunohistochemical studies applying control human brain sections did not demonstrate the presence of autoantibodies. We considered that innate immunity rather than autoantibody response may have contributed to the neuropsychiatric symptoms of our patient. These results suggest heterogeneity of patients with acute encephalopathy with neuropsychiatric symptoms.