Survey of Japanese pediatricians on vaccination of children with neurological disorders.

BACKGROUND: Primary care physicians in Japan are often unwilling to vaccinate children with neurological disorders. The aim of the present study was to determine the state of vaccination in children who are severely handicapped and/or have convulsive disorders, in order to increase the vaccination rate in this patient population. METHODS: Six hundred and eighty pediatricians belonging to Osaka Shonika Ikai were asked to answer a questionnaire, and 359 doctors responded. RESULTS: Two hundred and thirty-four doctors consulted for febrile seizures (Fs), 190 for epilepsy and 145 for conditions affecting severely handicapped children, responded that they refused to vaccinate. The reasons for reluctance to vaccinate these children were short interval since the last seizure, including febrile (226 doctors) and epileptic (121 doctors) seizures. It was especially likely that a child with a past history of status epilepticus would be refused vaccination. Primary care doctors are very cautious about the indications for vaccination, especially the inoculation of live vaccines, because they often induce post-vaccination fever-associated convulsions. Intractable daily epileptic seizures was the most common reason for refusal to vaccinate severely handicapped children. Examples of inadequate decision-making as regards the indications for vaccination were: "need more than 6 months observation since last seizure whether Fs or epileptic", "need EEG examination for Fs", "contraindication because of low bodyweight and/or chronic wheezing in severely handicapped children". CONCLUSIONS: There is a need to provide correct information about the adverse effects of vaccination and for greater cooperation between primary care doctors and pediatric neurologists.

A pilot study on the changes in immunity after ACTH therapy in patients with West syndrome.

Adrenocorticotropic hormone (ACTH) has been the first-line drug for the treatment of West syndrome, although the therapy has various adverse effects. ACTH depresses resistance to a variety of bacterial, viral, protozoal, and fungal agents. The timing of the various vaccinations is delayed after ACTH therapy in Japan, because the immune system is believed to be affected for approximately 6 months. However, the duration of the effect of ACTH on the immune system is not known. Therefore, we examined changes in the immunity levels before and after ACTH therapy. We measured white blood cell counts, lymphocyte counts, T/B cell counts, CD4(+) and CD8(+) T cell counts, CD 4/8 ratio, lymphocyte blastoid transformation by PHA or Con-A, and the levels of IgA, IgM, and IgG before, immediately after, and 1, 3, 6, and 12 months after ACTH therapy. The lymphocyte counts and CD4(+) T cell counts were significantly decreased immediately after and at 1 and 3 months after the therapy, and did not return to the previous levels even at 6 months and 12 months after ACTH treatment; however, these levels returned to within normal limits (within the 95% confidence interval). Immunoglobulin levels did not change after the ACTH therapy. Helper T cells were more depressed than cytotoxic T cells after ACTH therapy.

Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome)--a nationwide questionnaire survey in Japan.

UNLABELLED: The aim of this study was to establish strategies for prophylaxis against status epilepticus (SE) associated with high fever and for management of ongoing SE in children with severe myoclonic epilepsy in infancy (SMEI). METHODS: The investigation was performed retrospectively using a questionnaire, asking about medications, which was distributed to epilepsy specialists throughout Japan. All respondents were members of the Japan Epilepsy Society (JES) and/or the Japanese Society of Child Neurology (JSCN). Data from 109 SMEI patients (51 males and 58 females), 1-37 (M+/-SD, 10.7+/-6.53) years old, were used for this study. Of these 109 patients, 10 were excluded because they had not experienced SE, such that data from 99 patients were analyzed. RESULTS: Among the anti-epileptic drugs (AEDs) used daily, excellent efficacy against SE evolution was obtained with the following: potassium bromide (KBr) (41.7%), zonisamide (ZNS) (13.5%), clobazam (CLB) (10.0%), valproate (VPA) (8.0%), phenobarbital (PB) (6.7%), and phenytoin (PHT) (2.6%). Excellent efficacy was not obtained with either clonazepam (CZP) or carbamazepine (CBZ). The diazepam (DZP) suppository was the most frequently given drug for prophylaxis against SE triggered by fever, but only 2 (2.4%) cases showed excellent results. Excellent efficacy in terminating ongoing SE was obtained with the following medications; intravenous barbiturates (75-100%), intravenous midazolam (MDZ) (68.8%), intravenous DZP (54.3%), intravenous lidocaine (Lid) (21.4%), and intravenous PHT (15.4%). CONCLUSIONS: Daily KBr was most efficacious for controlling seizures in SMEI patients. Early use of intravenous barbiturates is the most effective strategy in stopping SE in a subset of patients. Reliable efficacy in SE was not obtained with prophylactic DZP, intravenous benzodiazepines (BZPs), PHT and Lid.

Dermal testing of vaccines for children at high risk of allergies.

Vaccinations for children with allergic diseases often need to be postponed or terminated because of the presumed risk of an immediate-type allergic reaction such as anaphylaxis. A new skin test protocol for predicting allergic reactions using the vaccine itself and the following stepwise vaccination method were developed and tested. Intradermal tests using 1:10 and 1:100 diluted measles vaccine indicated that the former was superior to the latter because a positive reaction against 1:10 diluted vaccine was found in 28.6% of 49 patients with severe allergic diseases including bronchial asthma, atopic dermatitis, food allergies and allergies to two or more allergens with high levels of IgE, as compared with the reaction against 1:100 diluted vaccine in 10.2% of the patients. Patients negative for 1:10 skin tests were safe from the following full-dose vaccine shots. Three patients showed very strong local reactions against measles vaccine, and avoided receiving the following full-dose shot. Positive reactions to skin tests of 1:10 diluted vaccine were found in 11 patients, who were given stepwise vaccinations. Three patients had adverse reactions, and two of them had been negative for 1:100 skin tests. In the case of influenza vaccine, skin tests were again more sensitive to 1:10 than to 1:100 diluted vaccine, because 3 out of 14 patients with positive reactions showed immediate-type adverse reactions against the following stepwise vaccinations, and 1 of them was negative for the 1:100 skin test. Moreover, the results of the skin prick test (undiluted vaccine) and the intradermal skin test (1:10 diluted vaccine) indicated that the latter was more useful in both cases of measles (54 patients) and influenza vaccine (69 patients). Overall, the skin test using 1:10 diluted vaccine was the more suitable for predicting an immediate-type reaction to measles and influenza vaccinations. Patients having negative 1:10 skin tests can be expected to show no adverse reactions to the remaining injections and even the positive subjects will complete the course of vaccine doses by the stepwise method.

[Survey of vaccination and viral infections for children with severe myoclonic epilepsy in infancy].

A study group for establishment of a proposed immunization program for neurologically high risk children (Chief, Kihei Maekawa) sponsored by the Ministry of Health, Labour and Welfare of Japan is preparing a proposal for patients with epilepsy. Severe myoclonic eplepsy in infancy (SMEI) is an intractable epilepsy which often presents with status epilepticus and triggered by hyperthermia and viral infections. In this study we investigated the history of vaccination in children with SMEI to compare the risk of vaccination with that of natural contraction of infection. Fifty-eight patients with SMEI, aged from 2 to 25 years, were enrolled in this study. A total of 359 vaccines were given to these subjects. The vaccination rates were high for BCG (71%) and polio (1st; 71%, 2nd; 53%), and then fell gradually after the onset of SMEI (DPT-1st; 48%. DPT-2nd; 45%, DPT-3rd; 38%, DPT-4th; 24%, mumps; 21%, varicella; 19%, rubella 31%). However, the measles vaccine was given at a relatively high rate (55%) before the age of three. When patients suffered from measles, rubella, mumps or influenza, they had a high risk of severe neurological complications, such as convulsive status, disturbance of consciousness and encephalopathy. These complications were documented in 63% of all episodes of naturally contracted infections. This rate was significantly higher (p < 0.0001) than that associated with vaccination (7.2%). However, hyperthermia and convulsion developed more frequently (p = 0.012) after measles vaccine was given, as compared to other vaccines. Thus, administration of these vaccines to patients with SMEI in conjunction with other preventive measures against seizure induced by hyperthermia, may meet the needs of their parents.

High-dose immunoglobulin therapy for Guillain-Barré syndrome in Japanese children.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute acquired demyelinating polyneuropathy, presumed to be immune-mediated. Intravenous immunoglobulin (IVIg) has been used to treat GBS and was found to be effective. However, a well-controlled study of pediatric GBS has not been conducted in Japan. Therefore, to evaluate the efficacy of IVIg in the treatment of GBS, an open-labeled study was performed in pediatric patients. METHODS: Participants in the study were required to be younger than 15 years old, and diagnosed as having moderate or severe GBS. IVIg (400 mg/kg per day) was administered to patients for five consecutive days. Predefined outcome measures were defined on a seven-point scale of motor function (Hughes' functional grade [FG]). RESULTS: Eleven patients were treated with IVIg. The median time taken to improve by one grade on the FG scale was 10.0 days after initial treatment. Two weeks after initial treatment, 72.7% of patients treated with IVIg improved by one or more grades, and 36.4% improved by two or more grades, measured on the FG scale. After 4 weeks an improvement by one or more grades was observed in 81.8% of patients, and two or more grades in 63.6% of patients. These improvement rates were markedly greater than would occur with the natural course of GBS1. Adverse events (subjective symptoms or abnormal laboratory findings) were observed in four patients, although all were temporary and mild. CONCLUSIONS: The authors conclude that IVIg is a safe and effective treatment for childhood GBS, which shortens the time to recovery.