No To Hattatsu最新文献

Objective: To elucidate the pathophysiology of West syndrome and mechanism of immunoglobulin therapy for this syndrome, we investigated serum and cerebrospinal fluid (CSF) cytokine levels before and after high-dose intravenous immunoglobulin (IVIG) therapy in patients with West syndrome. Methods: We measured serum and CSF cytokine levels of 11 patients with West syndrome who was referred to Saitama Children’s Medical Center from April 2010 to May 2014. All patients received IVIG, ranging from 200 to 500 mg/kg/day for 3 consecutive days (initial IVIG treatment), before adrenocorticotrophic hormone therapy. When spasms disappeared within 2 weeks after initial IVIG treatment, maintenance IVIG treatment was commenced. We measured cytokines level in patients before and after initial IVIG treatment. We compared the levels of cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-17, Interferon γ, Granulocyte macrophage colony stimulating factor, IL-18, Tumor necrosis factor-α〔TNF-α〕) in serum and CSF, and between the seizure-free group and seizure-persisting group. Seizure free was defined as remission of spasms within 2 weeks after initial IVIG treatment and no relapse for at least 1 week after remission. Results: After IVIG therapy, 5 of 11 patients were in the seizure-free group (4 males, 1 cryptogenic) while 6 were in the seizure-persisting group (2 males, 1 cryptogenic). Levels of IL-1β, IL-10, IL-18, and TNF-α in serum were significantly higher than those in CSF before initiation of IVIG. Before IVIG treatment, the level of IL-8 in CSF was significantly higher than that in serum, while the serum IL-18 level in the seizure-free group was significantly lower than that in the seizure-persisting group. Alterations of serum IL-18 level and CSF IL-8 level were different between the seizure-free and seizure-persisting groups. Conclusions: Serum IL-18 and CSF IL-8 may be important factors for elucidating the pathophysiology of West syndrome and mechanism of IVIG therapy.

Objective: This study investigated the factors associated with antisocial behavior (AB) in children with developmental disorder and effective treatments. Methods: Participants were 110 schoolchildren with developmental disorder and with or without accompanying AB who visited our hospital between October 2009 and October 2012. Among the children with AB, those who exhibited one or more symptoms of conduct disorder (CD) were assigned to the CD subgroup. We examined the background characteristics, past history, type of antisocial behavior, and symptom improvement after treatment in the children with AB and compared the relevant factors with children with developmental disorder without AB. Results: Of the 110 participants, 72 (65.5%) did not exhibit AB and 38 (34.5%) did, 7 (5.5%) of whom fulfilled the criteria for CD. Compared to the children without AB, the children with AB showed a significantly higher occurrence of attention deficit/hyperactivity disorder (AD/HD), maltreatment, institutionalization due to maltreatment, parental mental/psychological problems, and family instability. After medical treatment combined with social-skills training and parental education, 22 of the 38 children with AB showed improved behavior. In the CD subgroup, 4 children were diagnosed with AD/HD and 3 with pervasive developmental disorder, and none of the 7 improved with treatment. Conclusion: AB was associated with AD/HD, maltreatment, institutionalization, parental mental/psychological problems, and family instability. The most effective therapy was parental education. Children with AB need early intervention given that those who already exhibited symptoms of CD showed little improvement with treatment.

Objective: This study aimed to investigate the effectiveness of vigabatrin (VGB) for intractable generalized epilepsy in infants and young children. Methods: We retrospectively examined the data of 12 patients who received VGB at our department. There were eight patients with West syndrome, two with early-infantile epileptic encephalopathy, one with symptomatic generalized epilepsy, and one with early myoclonic encephalopathy. Results: All patients had drug-resistant epilepsy and received at least three antiepileptic drugs (range, 3-10 ; median, 5) before receiving VGB. These drugs included valproate (11 patients), nitrazepam (six patients), adrenocorticotropic hormone (ACTH ; five patients), clonazepam (four patients), and zonisamide (four patients). VGB was effective in only one case of symptomatic West syndrome associated with tuberous sclerosis. In two cases of cryptogenic West syndrome, VGB showed transient effects. Conclusions: VGB showed poor effectiveness for intractable generalized epilepsy in infancy and early childhood, except for West syndrome associated with tuberous sclerosis. Therefore, it is important to carefully select the cases for VGB administration.

Objective: Patients with childhood-onset epilepsy often need continued epilepsy treatment into adulthood. We investigated parents’ opinions of the changes in their children’s epilepsy treatment during the transition from childhood to adulthood using questionnaires and formulated agendas to build the appropriate medical treatment system for epilepsy. Methods: We distributed questionnaires to parents of patients with epilepsy who were 12 to 18 years old. Results: We distributed 176 questionnaires, and analyzed 79 (45%) questionnaires. Most parents (59%) wanted their child to continue treatment for epilepsy in the pediatrics department because of confidence in the current treatment environment. Most parents (73%) were anxious about their child not being treated in the pediatrics department during future epilepsy medical treatments because of concerns about whether a proper handover from the pediatrics department to other departments is possible. No parent was recommended the departmental transition by the primary pediatrician to other courses for future epilepsy treatment, while 19% of par-ents had a sense of incongruity regarding epilepsy treatment at the current pediatrics department. Parents who were anxious about future epilepsy treatments had significantly fewer general-school students than parents without anxiety. In addition, their children had more seizures than children of parents who were not anxious. Furthermore, they wanted their child to continue treatment for epilepsy in the pediatrics department more than the parents without anxiety. Conclusions: Approximately 70% of the parents were anxious about obtaining future epilepsy treatment in clinical departments other than the pediatrics department. To build a satisfactory medical treatment system for patients with epilepsy having different backgrounds and requiring continued treatment in adulthood, it is important to create a cooperating network consisting of pediatricians, neurologists, neurosurgeons, psychiatrists, and epileptologists.

We report the case of a 5-year-old boy with acute encephalopathy presenting with transient executive dysfunction such as functional disability in various new tasks and hypoperfusion of the right frontal and temporal lobes on single photon emission tomography (SPECT). He presented with a 2-day history of disturbed consciousness, and electroencephalography in an awaked state showed diffuse high-voltage slow waves. Although MRI did not show any abnormality 3 days after initial onset of illness, SPECT showed hypoperfusion of the right frontal and temporal lobes at the same time. At 20 days after onset, the Kaufman assessment battery for children (K-ABC) test showed that sequential processing scale scores were significantly lower than simultaneous processing scale and achievement scale scores. He showed transient executive dysfunction such as functional disability in various new tasks at the same time. Abnormal brain perfusion on SPECT was improved at 8 months after onset and the sequential processing scale of K-ABC was likewise improved at 12 months after onset. These findings suggest that SPECT is helpful for diagnosing pathophysiological mechanisms with acute encephalopathy, and the combination of neuropsychological examination and SPECT study is useful for evaluating higher brain dysfunctions such as executive dysfunction.

Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder, which is characterized by progressive muscle wasting, ultimately resulting in the death of patients in their twenties or thirties. In DMD the dystrophin gene is mutated, which results in a deficiency of the muscle dystrophin. Although expression of dystrophin is a fundamental treatment for DMD, no effective treatment for DMD is available until now. Promising molecular therapies which are mutation-specific have been developed. Antisense oligonucleotide-mediated exon skipping that convert out-of-frame mRNA into in-frame mRNA, thereby enabling semifunctional dystrophin production, is recognized as the most promising treatment for DMD. We demonstrated that the intravenous administration of the antisense oligonucleotide against the splicing enhancer sequence induced exon skipping and produced the dystrophin protein in DMD case for the first time. After extensive studies, antisense oligonucleotides comprising different monomers have undergone clinical trials and provided favorable results, enabling improvements in ambulation of DMD patients Induction of the read-through of nonsense mutations is expected to produce dystrophin in DMD patients with nonsense mutations. The clinical effectiveness of gentamicxin and PTC124 has been reported. We have demonstrated the effectiveness of arbekacin-mediated read-through in vitro. We have already begun an investigator initiated clinical trial of nonsense mutation read-through therapy using arbekacin. Some of these drug candidates are planned to undergo submission for approval to regulatory agencies in the US and EU. We hope that these molecular therapies will contribute towards DMD treatment.

Objective: As a treatment for cases of developmental disorder accompanied with epilepsy, the author examined the efficacy and tolerability of combined administration of levetiracetam (LEV) on the cases. Methods: There were 21 participants (male-to-female-ratio was 16 to 5, 6 in their 10s, 7 in their 20s, 7 in their 30s and 1 in their 40s) to whom LEV was prescribed from October 2011 to December 2014. The effect was classified as loss of seizure, effective (more than 75% reduction in the number of seizures, more than 50% reduction in the number of seizures), unchanged (no change), and aggravation (increase in the number of seizures). Results: The study included 19 autistic spectrum disorder (ASD) cases (13 with profound intellectual disability, 5 with severe intellectual disability, and 1 with high functioning autism), 1 borderline intelligence case, and 1 attention deficit/hyper activity disorder (AD/HD) case. By classification of epilepsy seizure, there were 15 symptomatic localization-related epilepsy cases and 6 generalized epilepsy cases. The initial dose of LEV was an average of 488.1 mg/day, and the maintenance dose was an average of 1,714.2 mg/day. The average duration of administration was 2 years and 3 months. In terms of the response rate, there were 11 cases of loss of seizure (52.4%), 4 cases of more than 75% reduction in the number of seizures, (19.0%), and 3 cases of more than 50% reduction in the number of seizures (14.3%). The overall response rate was 85.7% (18 cases). 14.3% was unchanged (3 cases). No aggravation case was observed. There was only one case of dizziness in the initial period, but all cases continued taking LEV. The kinds of anticonvulsant agent could be adjusted from 2.5 at the beginning of LEV administration to 1.5. Emotional stability was also observed. Some cases could stop taking tranquilizers. Conclusions: LEV showed high response rate and tolerability on the cases of ASD and other developmental disorder accompanied with epilepsy. Administration of this drug led to reduction in the number of concomitant medications, which indicates the possibility that LEV may contribute to enhancing compliance.

A 6-year-old boy with normal development experienced tonic-clonic seizures and myoclonus. His electroencephalogram showed epileptic discharge and he was administered antiepileptic drugs ; however, they were ineffective. Antiepileptic drugs were discontinued temporarily because of no ictal recordings. He could not walk unaided and his speech reduced gradually. He was admitted to our hospital at the age of seven years and eight months. He experienced daily tonic-clonic seizures and myoclonus. Epileptic encephalopathy related to autoimmunity was suspected as he had psychomotor regression and his cerebrospinal and serum anti-glutamate receptor antibody (anti-GluR) levels were elevated. After being administered immunoglobulins, his motor and cognitive functions improved and his seizures almost stopped. After one year, he could walk unaided and speak fluently. We strongly suspect an autoimmune reaction to be the pathological cause because of the effectiveness of immunoglobulin treatment. Immunoglobulin interventions should be considered in patients with unknown-cause, sub-acute onset, and destructively progressive epileptic encephalopathy.