Objective: We studied the effects and tolerability of lamotrigine (LTG) on refractory epilepsies in persons with severe motor and intellectual disabilities (SMID).
  Methods: We introduced LTG to 40 subjects all who were severely retarded and suffered from symptomatic epilepsies consisting of six cases of generalized epilepsy (GE), 33 of partial epilepsy (PE), and one of unclassified epilepsy (according to the 1989 ILAE classification standards). We evaluated the efficacy of LTG in seizure reduction and its tolerability for persons with SMID.
  Results: Following treatment, 83% of GE and 42% of PE cases showed a 50% reduction in seizure frequency. From the seizures observed in our study cohort, a response rate (RR) with an over 50% reduction was found in 54% of secondarily generalized tonic-clonic (n=24), 30% of complex partial (n=18), and 25% of myoclonic seizures (n=16). As for adverse effects, nine subjects (22.5%) experienced sleep problems, six subjects (15%) experienced excitement mainly during night-time, and four cases each (10%) experienced involuntary movements and sleepiness. As for additional effects on patients' quality of life (QOL), even in poor responder (<50%RR) patients, LTG improved “alertness” in six cases, improved “activity of daily life” in four cases, and helped to diminish “appetite loss” in three cases.
  Conclusions: LTG therapy for epileptic conditions in persons with SMID has potential for not only reducing seizure frequency, but also for improving QOL.

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  Objective: We examined the clinical and neurophysiological features of Japanese patients with congenital myasthenic syndrome (CMS).
  Method: Subjects were five patients who were diagnosed with CMS on the basis of clinical course, repetitive nerve stimulation (RNS), and genetic analysis.
  Results: Four patients manifested motor retardation within one year of birth, while one manifested motor intolerance at three years of age. The most characteristic symptom observed in all the patients was fluctuating muscle weakness, which varied on a daily basis or continued for several days after the late infancy period. Only one patient manifested daily fluctuation of muscle weakness. RNS of the accessory nerve evoked a decrementing response in three patients who were examined; however, RNS of the median, ulnar, and tibial nerves (one patient each) did not evoke such responses. After the edrophonium chloride test, no improvement was seen even if the patients manifested ptosis. For judgment of this test, improvement in decrementing rate observed while performing RNS was useful. All five patients who were administered medication based on the results of genetic analysis demonstrated an improvement in their symptoms.
  Conclusion: We suggest that CMS can be diagnosed based on careful examination and electrophysiological results. CMS is a treatable disorder, and therefore, correct diagnosis is important.

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  Objective: We investigated the efficacy, safety, and tolerability of high-dose topiramate with rapid dose titration in 12 children with symptomatic West syndrome who suffered from severe motor and intellectual disabilities.
  Methods: Topiramate was introduced as add-on therapy at the daily dose of 1 mg/kg/day, followed by increments of 2 mg/kg at 3-or 4-day intervals, up to a maximum of 19 or 20 mg/kg/day. The ages at the start of topiramate therapy ranged from 5 to 22 months. Prior to the topiramate therapy, the patients had received 2 to 6 antiepileptic agents with (8 patients) or without ACTH (4 patients).
  Results: Topiramate appeared to be effective in 8 of the 12 patients (67%) ; four became seizure-free; three showed greater than 90% seizure reduction; one showed greater than 50% seizure reduction. The maintenance dose was 7 to 20 mg/kg/day (mean: 17.9±3.9 mg/kg/day). In 4 of these 8 patients (50%), the spasms relapsed several months after complete cessation or diminution in the frequency of the spasms following treatment with topiramate. All of the 8 topiramate-responsive patients could continue the topiramate therapy throughout this study. The duration of topiramate therapy was 7 to 42 months (median: 12.5 months). There were no severe side effects that necessitated discontinuation of topiramate, including kidney stones.
  Conclusions: High-dose topiramate with rapid dose titration was revealed to be effective, safe, and well-tolerated in children with symptomatic West syndrome.

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  Objective: We investigated the effectiveness of intravenous injection of phenobarbital (PB) in patients referred to Himeji Red Cross Hospital, Hyogo, Japan, with benign convulsions with mild gastroenteritis (CwG) between November 2009 and June 2011.
  Methods: The patients who had a single seizure at the time of consultation were, in principle, followed without any treatment, and those with repeated seizures were treated with intravenous injection of 10 mg/kg PB.
  Results: During the study, 24 of 33 patients with CwG were administered PB intravenously. PB was administered after a single seizure in one patient, and the remainder were treated after 2-7 seizures, no patient had repeated seizures. The side effects were temporary and mild, although somnolence was seen in five patients, and two also showed staggering.
  Conclusions: It was considered that intravenous injection of PB was effective for CwG. Intravenous injection of PB should be given to patients with CwG, regardless of whether they have vomiting and diarrhea.

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  Objective: As information required to rehabilitate, we aimed to clarify the use of switch devices, language development, upper extremity function, and quality of life (QOL) in patients with spinal muscular atrophy (SMA) type 1 in Japan.
  Methods: A questionnaire survey was conducted on the parents of these patients.
  Results: A total of 48 completed questionnaires were collected. The median age of patients with SMA type 1 was 8 years (range, 13 months to 27 years). The patients used a switch device were 46.5%. Their language development was delayed, and their voluntary movement in the distal upper extremities was relatively retained. In QOL, parents' labor and burden for the care of patients were high.
  Conclusions: It is necessary to provide specialist support that contributes to the spread of communication devices, which improve their motor function, language development and overall QOL.

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  Objective: Patients with epilepsy after encephalitis/encephalopathy (EAE) are often on polytherapy with anti-epileptic drugs (AEDs), and are at risk of adverse reactions. We examined the adverse effects of AEDs, especially sleepiness, in these patients.
  Methods: In this retrospective study, the medical records of 66 patients who were diagnosed with EAE in our hospital were reviewed and the clinical characteristics were analyzed. Immunological biomarkers including cytokines, chemokines, granzyme B, soluble tumor necrosis factor receptor 1, matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were also investigated.
  Result: The mean onset age of acute encephalitis was 9 years and 1 month and the mean interval from onset of acute encephalitis to onset of epilepsy was 6.4 months. Sleepiness induced by AEDs was observed in 26 of 66 patients (39.3%). The incidence of sleepiness was high in patients treated with clorazepate (75%), lamotrigine (66.7%), and ethosuximide (40%). Comparing the AEDs used by more than 20 patients, the incidence of sleepiness was high for clonazepam (30.4%) and phenytoin (25.8%). IgG, protein, and albumin levels in cerebrospinal fluid were significantly higher in patients affected by sleepiness than in those not affected. IL-8 in cerebrospinal fluid was significantly higher in the group with sleepiness compared to that without. Serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels were not different between the two groups.
  Conclusion: Long-lasting blood-brain barrier dysfunction and proliferation of immature vessels induced by IL-8 may contribute to the occurrence of sleepiness as an adverse effect of AEDs in patients with EAE. We recommend to assess for blood-brain barrier dysfunction when choosing AEDs for treating patients with intractable EAE.

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  We report the cases of 2 girls, aged 13 and 15 years, who experienced exacerbation of migraine at 2-3 years after its onset. The chronic headaches were refractory to various anti-migraine and analgesic agents, persisted for 3-6 months in each patient, and rendered them unable to attend school. These headaches commonly manifested with symptoms of orthostatic dysregulation and paroxysmal back/limb pain. In addition, T2-weighted magnetic resonance images showed dots of highly intense signals in the bilateral cerebral white matter. Neurotropin, a non-protein extract isolated from the dermis of rabbits and inoculated with the vaccinia virus, induced prompt significant effects on the headache and back/limbs pain in both the girls. The symptom of orthostatic dysregulation was also gradually ameliorated after the resolution of the headache. Neurotropin has an analgesic action that is not common to other drugs since it enhances the descending pain inhibitory systems, and its effect has been reported in cases of post-herpetic and other neuralgia as well as in cases of primary headaches in adulthood. This agent may also be promising for the treatment of intractable primary headaches during childhood.

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  We assessed a 6-year-old girl who developed status epilepticus and exhibited transient aphasia during the course of acute encephalopathy with late reduced diffusion, and who had a residual reading disorder in the recovery period. The aphasia appeared to be fluent aphasia and anomia, suggesting that the reading disorder during the recovery process was due to impairment of the phonological process. There were no biphasic seizures during the course of the patient's illness, but this case was acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) from the standpoint of the characteristic imaging findings. Lesions in the left parietal and temporal lobes were detected on MRI diffusion-weighted images and by SPECT and MRS, and they appeared to be the lesions responsible for the aphasia and residual reading disorder. This case appears to be important from the standpoint of assessing the pathophysiology and the treatment of coexisting illness observed in acute encephalopathy.

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  Acute necrotizing encephalopathy (ANE) has a characteristic imagimg finding of bilateral symmetrical thalamic lesions. Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is characterized by biphasic clinical course and high intensity of subcortical white matter in MRI diffusion images appearing around the late seizure. We herein report a case of an 8-month-old girl who presented with fever and status epilepticus associated with human herpes 6 infection.
  Although MRI first demonstrated images of ANE, typical AESD images were observed several days after the onset. We therefore concluded that this case had a combination of ANE and AESD. A proper therapeutic strategy should be established, and acute encephalopathy needs to be better clarified by identifying diagnostic markers and improving the genetical analysis.

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  A girl with Rett syndrome was suffered from severe apneusis attacks, resulting in cardiopulmonary arrest, which required resuscitation. Her apneusis attacks did not respond at all to diazepam, magnesium citrare or tricyclic antidepressants but ceased by tracheostomy with oral imipramine. The breathing abnormality appeared to involve difficulty in terminating inspiration. This supports the idea that a lack of serotonin may cause her apneusis attacks.

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[in Japanese]

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