[The study of the recognition gap on the quality of life in people with epilepsy between the affected pediatric and adolescent patient's families and the attending physicians].

The aims of this study were to investigate the recognition gap on the quality of life (QOL) in people with epilepsy (PWE) between the affected pediatric and adolescent patient's families and the attending physicians, and to devise future management strategies for epilepsy based on the results. We conducted a large-scale questionnaire survey on the QOL in 5,122 PWE/their families who were members of the Japanese Epilepsy Association in 2006 and 1,701 PWE/their families and 502 attending physicians responded. Out of the responders, 107 matched pairs of PWE aged under 16 years (with an adult family member actually responding by proxy) and their physicians responding to the questionnaire were examined. The results demonstrated that the physicians were not sufficiently aware of 1) concern about drug therapy for epilepsy from the perspective of their patients/families, 2) ictal and post-ictal symptoms recognized by the patients/their families, and 3) the worry about the disease of the patients/their families. Thus, efforts are needed to minimize the recognition gap within the limited consultation hour in routine clinical practice between children and adolescents having epilepsy/their families and physicians : physicians should efficiently acquire necessary information from PWE/their families, and should negotiate with PWE/their families about the goal of therapy and future management strategies for epilepsy.

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.

Assessment of health-related quality of life and influencing factors using QOLIE-31 in Japanese patients with epilepsy.

The aim of epilepsy treatment is not only to eliminate seizures, but also to improve health-related quality of life (HRQOL). We conducted a postal self-administered survey of HRQOL for Japanese patients using the Quality of Life in Epilepsy inventory (QOLIE-31), Version 1.0, and analyzed factors influencing their quality of life (QOL). Data from 599 analyzable patients were evaluated and a number of factors influencing QOL were identified, including severity and frequency of seizures, seizure control, type of epilepsy, contributing events such as injuries and falls during seizures, number of antiepileptic drugs, employment status, and surgical outcome. These findings suggest that comprehensive management of the patient should be emphasized. Consideration of all the results led to classification of these factors as one of two types: "all or nothing" and "linear." With respect to "all or nothing" factors (e.g. "daytime remarkable seizures"), patients may not be able to improve their QOL unless these factors can be completely controlled. Comparison of each score on the QOLIE-31 subscales with published data revealed that the scores for the subscale Medication Effects were markedly low.

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.

In vivo confocal microscopy of hereditary sensory and autonomic neuropathy.

PURPOSE: To observe the morphology of the corneal cells and corneal nerve fibers in patients with type IV or V hereditary sensory and autonomic neuropathy (HSAN) by in vivo confocal microscopy and elucidate the mechanism leading to the loss of corneal sensation in this disease. METHODS: In vivo confocal microscopy was performed on the central cornea of the right eye in 3 patients with HSAN (ages 17, 20, and 32 years), and their corneal morphology was compared with that of 3 healthy subjects (ages 28, 30, and 36 years). Corneal sensation was tested with a Cochet-Bonnet esthesiometer. RESULTS: The superficial epithelial cell density was lower in the HSAN patients compared with the healthy subjects (1525, 1225, and 1250/mm(2) vs. 2225, 1750, and 2500/mm(2)), but the basal epithelial cell density of the patients was similar to that of the healthy subjects. Nerve bundles were clearly observed in the sub-basal nerve plexus layer of the cornea in the healthy subjects, but were undetectable at the central cornea in the patients with HSAN. The corneal sensation of the patients with HSAN was much weaker than that of the healthy subjects (2.79, 40.30, and 132.50 g/mm(2) vs. 1.47, 1.47, and 1.47 g/mm(2)). CONCLUSIONS: Superficial keratopathy accompanied with neurotrophic keratopathy and tear film instability observed clinically agrees with the large keratinized cells in the superficial corneal epithelium by in vivo confocal microscopy in these patients. Our findings suggest that the loss of corneal nerves contributes to impairment of corneal sensation in patients with type IV or V HSAN.

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.

[Acute non-herpetic encephalitis with severe refractory status epilepticus --its overwhelming ictogenicity, epileptogenicity, long-term prognosis and review of the literature].

In 1980s, the authors experienced 5 patients with "a peculiar form of acute encephalitis/encephalopathy "which is characterized by three features: 1. Complex partial seizures with secondary generalization recur incessantly or continue persistently without regaining consciousness for many days in spite of intensive diazepam (DZP) therapy; usually general anesthesia at ICU setting for 2-3 weeks becomes mandatory. 2. After weaning from long-run anesthesia, seizures of the same type still persist, though much less frequent, during the convalescent and chronic phases of the disease throughout. There is no seizure-free interval between the acute and chronic stages. 3. Etiology is totally unknown;extensive laboratory examinations mostly remain within normal ranges, though clinical features such as acute onset, frequent accompaniment of fever, etc., mimic those of acute encephalitis/encephalopathy. The synopsis of our 5 patients were; age ranged from 2 to 5 years old, no antecedent history of seizures, fever of moderate degree preceded seizures a few days and persisted in the acute stage; complex partial seizures with secondary generalization recurred several times every hour. Circulatory/respiratory compromise necessitated a drastic intervention with barbiturate coma at ICU. Etiology was unknown. Follow-up for 19 years in average revealed mental retardation and chronic epilepsies in all patients. Since our first report in 1987, 49 similar cases with ours have been sporadically reported. The majority of the reported cases had been submitted to longstanding general anesthesia and placed in barbiturate coma for weeks to 2 months. The death occurred in 7 patients. In all reported cases, the first line drugs such as DZP iv, phenytoin iv, etc did not work, and it was highly recommended to place the patient under barbiturate coma as early as possible.

Ocular manifestations of congenital insensitivity to pain with anhidrosis.

PURPOSE: To describe ocular manifestations in Japanese patients with congenital insensitivity to pain with anhidrosis (CIPA), focusing particularly on the status of the ocular surface. DESIGN: Observational case series. METHODS: Eighteen patients with CIPA underwent applicable ophthalmologic examinations, including visual acuity, refraction, slit-lamp examination, fundus examination, tear breakup time, Schirmer 1 test, corneal sensitivity, and corneal topography. RESULTS: Superficial punctate keratopathy (SPK) was observed at the interpalpebral area in 23 (64%) of 36 eyes. Corneal opacity was observed in three eyes (8.3%). Tear breakup time was below the lower limit of the normal range in all examined eyes, and the value of Schirmer 1 test was above the lower limit of the normal range in most of the examined eyes. CONCLUSIONS: Superficial punctate keratopathy is observed in most cases of CIPA, which might predispose patients to corneal infection. Investigation of dry eye in patients with CIPA will provide unique opportunities to explore the critical roles of the autonomic sympathetic nervous system as well as the sensory nervous system in the physiology of tear production.

[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.

Clinical and EEG analysis of initial status epilepticus during infancy in patients with mesial temporal lobe epilepsy.

This study investigated the clinical and EEG characteristics of initial status epilepticus (SE) during infancy in patients with mesial temporal lobe epilepsy (MTLE). The subjects were six patients who had been brought to our emergency clinic and treated for their initial SE between 1977 and 1988, and later developed MTLE. We reviewed the medical records and laboratory findings at the time of the initial SE, and the clinical evolution up to the development of MTLE. The six patients included four females and two males. The initial SE developed at ages ranging from 7 months to 2 years and 9 months with a mean of 1 year and 2 months. These episodes were characterized by an elevated temperature of more than 38 degrees C (4/6 cases), clusters of prolonged seizures during one episode of SE (4/6 cases), long-lasting SE (120-380 min, mean 227 min, 6/6 cases), postictal prolonged loss of consciousness (median 5 h, 6/6 cases), and the presence of Todd's paralysis (3/6 cases). The lateralization of the ictal or postictal EEGs of the SE in five of the six cases was identical to that of the hippocampal atrophy later confirmed by MRI. Follow-up EEG examinations at a 6 month interval demonstrated temporal spike discharges appearing only after the onset of complex partial seizures. Two patients, who had no fever at the initial SE, were characterized by a very early appearance of epileptic EEG abnormality and a short interval between the initial SE and the development of complex partial seizures, suggesting that the SE was the first epileptic manifestation. The result of this study showed that SE progressing to MTLE tends to have complicated clinical manifestations characterized by clusters of unilateral or generalized SE followed by prolonged postictal unconsciousness, generalized clinical manifestations despite lateralized ictal EEG discharges, and the Todd's paresis in addition to the prolonged seizure duration.

Wisconsin card sorting test in children with temporal lobe epilepsy.

To search for the origin of frontal lobe dysfunction identified by the Wisconsin card sorting test (WCST) in temporal lobe epilepsy (TLE) patients, we investigated the WCST performance among 19 children with TLE (with hippocampal atrophy (HA group N=12), without structural lesions (NSL group N=7)), 15 patients with frontal lobe epilepsy (FLE group), and age-matched normal controls (N group). The paired verbal association learning test (PVALT) and Benton visual retention test (BVRT) were also performed. HA group and FLE groups achieved significantly fewer categories and demonstrated more perseverative errors on the WCST than NSL and N groups. In addition, category achievement in WCST showed significant inverse correlation to age at the initial status convulsivus in the HA group (P<0.05). The achievement on PVALT and BVRT did not show any significant differences between HA and FLE groups (P>0.05). Thus, the frontal lobe dysfunction in the HA group is found to exist as early as 7 years old, when they seem to have only a short seizure history or to receive a little electrical interference from the temporal lobe focus to the frontal region. These facts would underscore the importance of prefrontal dysfunction persisting from the early insults and only becoming apparent after maturation of the prefrontal region in patients with mesial TLE.

Anesthesia for patients with congenital insensitivity to pain and anhidrosis: a questionnaire study in Japan.

UNLABELLED: We investigated the anesthetic management of patients with congenital insensitivity to pain and anhidrosis (CIPA) in Japan. CIPA is a rare inherited disease characterized by a lack of pain sensation and thermoregulation. Although lacking pain sensation, some patients do have tactile hyperesthesia. Thus, anesthetics are a necessity during operations. We also determined that because patients with CIPA have problems with thermoregulation, temperature management is a concern during the perioperative period and sufficient sedation is necessary to avoid accidental fractures. Additionally, it was found that the use of muscle relaxants does not present a problem, malignant hyperthermia is not associated with CIPA, and that the possibility of abnormalities in the autonomic nervous system must be taken into consideration. Therefore, patients with CIPA can be safely managed with anesthesia. IMPLICATIONS: We investigated the anesthetic management of patients with congenital insensitivity to pain and anhidrosis. We clarified the following three important points: anesthesia is necessary, temperature management must be maintained, and there must be sufficient perioperative sedation in the anesthetic management of patients with congenital insensitivity to pain and anhidrosis.