Prognostic factors in the early phase of acute encephalopathy.

BACKGROUND: Neurological sequelae occur in 40% of patients with acute encephalopathy (AE). The early prediction of poor outcomes is critical to the initiation of appropriate treatment. The aim of the present study was therefore to elucidate prognostic factors that can be quickly and feasibly evaluated on hospital admission in patients with AE. METHODS: We analyzed data from 51 AE patients admitted to Hirakata City Hospital between January 2005 and December 2014. Age at onset, sex, underlying disease, status epilepticus (SE), presence of benzodiazepine-resistant SE (BZD-resistant SE), and basic blood serum parameters on admission were evaluated in relation to each patient's outcome. RESULTS: On univariate analysis age at onset, BZD-resistant SE, and serum aspartate aminotransferase (AST), alanine aminotransferase, lactate dehydrogenase, and platelet count varied significantly according to outcome. On multivariate analysis age at onset (≤21 months), presence of BZD-resistant SE, and AST (≥46 IU/L) were identified as independent variables associated with poor outcome. CONCLUSION: Age at onset, presence of BZD-resistant SE, and AST are associated with a poor prognosis in AE.

Clinical features of long-term low-dose levetiracetam treatment for epilepsy.

BACKGROUND: The aim of this study was to assess the rate of response to long-term low-dose levetiracetam (LEV) treatment and the clinical factors associated with response. METHODS: The response to low-dose LEV of 43 patients with epilepsy (22 male, 21 female; age range, 5-39 years; median age, 13 years) was retrospectively assessed. Patients aged <15 years received <20 mg/kg/day LEV, whereas those aged ≥15 years received <1000 mg/day LEV. Clinical features were compared between responders to low-dose LEV, responders to the recommended dose, and non-responders. RESULTS: Of the 43 patients who received low-dose LEV, 13 (30%) showed improvement, defined as seizure cessation or >75% seizure reduction over 6 months for patients with monthly, weekly, and daily seizures; and over 1 year for patients with yearly seizures. Efficacy was maintained for >1 year in 10 (77%) of the 13 patients. Long-term response to low-dose LEV was significantly associated with older age at onset and fewer previous treatments with ineffective anti-epileptic drugs. All patients showing long-term response to low-dose LEV developed only focal seizures. CONCLUSIONS: Titration of LEV starting from a low dose may be effective in selected patients. Once patients respond to low-dose treatment, maintenance of the effective dosage may prolong response.

Parents'opinions of the changes in their children's epilepsy treatment during the transition from childhood to adulthood.

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.

Incidence of febrile seizure in patients with Down syndrome.

BACKGROUND: It is unclear whether the incidence of febrile seizure (FS) in children with Down syndrome (DS) is higher or lower than in the general population. In this study, we investigated the incidence of FS in DS patients using mailed questionnaires. METHODS: The questionnaires were distributed to parents or caregivers of DS patients attending Osaka Medical College Hospital and six other facilities. The questionnaires were returned by mail from February 2012 to September 2013 from 323 families of DS patients (176 male, 147 female; age range, 3 months-47 years; median age, 5.0 years). To assess the incidence of FS in DS, we performed the following two analyses: (i) we calculated the incidence of FS among DS patients between the ages of 4 and 20 years (n = 199; 113 male, 86 female), and (ii) we extracted families with both DS and healthy siblings between the ages of 4 and 20 years (n = 150; 77 male, 73 female) and compared the incidence of FS in these sibling groups. RESULTS: Five DS patients had a past history of FS. The incidence of FS in DS was 2.5%. The incidence of FS was significantly lower in DS patients compared with healthy siblings (P < 0.003; OR, 0.14). CONCLUSION: The incidence of FS is lower in DS patients than in the general population.

Delirious behavior or mild reduction of consciousness mimicking influenza-associated encephalopathy.

BACKGROUND: During the A/H1N1 pandemic, patients suffered from impaired consciousness. They were suspected of or diagnosed as having influenza-associated encephalopathy (IAE) in an emergency situation. Their symptoms resembled those of a recently described 'unique clinical group', which were reported to have a favorable prognosis. METHODS: We retrospectively examined 46 patients and divided them into two groups. Group IC contained the 26 patients with persisting impaired consciousness. The remainder of the patients were categorized into group R, consisting of patients with only neurological symptoms without impaired consciousness. RESULTS: Male predominance (22 male/four female) was noted in group IC. Patient age ranged from 5 to 12 years old (mean ± SD, 7.7 ± 2.3 years). Impaired consciousness such as delirious behavior or mild reduction of consciousness lasted continuously or intermittently from 5 min to 2.5 days. On electroencephalogram, semi-rhythmic high-voltage slow waves in the parieto-occipital regions and diffuse high-voltage slow waves were observed in eight and in two patients, respectively. In group R, there was no gender predominance. Patient age ranged from 1 to 9 years old (mean ± SD, 4.1 ± 2.5 years). All group R patients were clinically diagnosed with febrile seizure. CONCLUSIONS: Some of the characteristics in group IC resembled those of the unique clinical group, and are part of a continuous clinical spectrum. Some patients may have favorable outcome without specific treatment.

Factors related to patterns of body mass index in early infancy: 18 month longitudinal study.

BACKGROUND: Children with early adiposity rebound (AR), measured using individual body mass index (BMI) growth curves, have an increased risk of metabolic disease as adults. The children with early AR, however, are not fully characterized. The aim of this study was to investigate the prevalence and characteristics of the infants who develop early AR. METHODS: A total of 1248 full-term children and their mothers participated in the present study. Pre-pregnancy, prenatal, birth, 4 month and 18 month records were collected. Children were classified into two groups: a decrease (D) group, in which the 18 month BMI was lower than the 4 month BMI (n = 1097), in keeping with the standard BMI percentile curve, and an increase (I) group, in which the 18 month BMI was higher than the 4 month BMI (n = 151). RESULTS: Although children in both groups had similar body size at birth, those in the I group had a lower weight at 4 months and higher weight at 18 months than those in the D group (P < 0.001). Fewer mothers in the I group exclusively breast-fed their infants (P = 0.012). These characteristics of infants in the I group suggested a pattern of low fatness level followed by rapid increased fat gain. CONCLUSIONS: Approximately 10% (151/1248) of infants did not follow the standard BMI percentile curves between 4 months and 18 months of age. They were more likely not to be exclusively breast-fed. This finding further stresses the importance of breast-feeding in early infancy.

Safety evaluation of laninamivir octanoate hydrate through analysis of adverse events reported during early post-marketing phase vigilance.

BACKGROUND: Abnormal behavior and delirium are common in children with influenza. While abnormal behavior and delirium are considered to be associated with influenza encephalopathy, an increased risk of such neuropsychiatric symptoms in patients receiving neuraminidase inhibitor treatment is suspected. Laninamivir octanoate hydrate, recently approved in Japan, is a long-acting neuraminidase inhibitor. It is important to establish a safety profile for laninamivir early, based on post-marketing experiences. METHODS: Spontaneous safety reports collected in the early post-marketing phase vigilance were analyzed. Adverse events of interest such as abnormal behavior/delirium, dizziness/vertigo, respiratory disorders, shock/syncope, and any other serious events were intensively reviewed by the Safety Evaluation Committee. RESULTS: Abnormal behavior/delirium was a frequently reported event. Almost all the reported cases were considered to be due to influenza and not laninamivir. There were 32 cases of abnormal behavior/delirium that could lead to dangerous accidents, and these were observed more frequently in males and teenagers. Syncope probably related to the act of inhalation per se of laninamivir was reported during this survey. CONCLUSIONS: This safety review revealed that the safety profile of laninamivir for abnormal behavior/delirium and syncope was similar to that of other neuraminidase inhibitors. As stated in the labeling, teenage patients inhaling laninamivir should remain under constant parental supervision for at least 2 days and should be closely monitored for behavioral changes to prevent serious accidents associated with abnormal behavior/delirium. Furthermore, to avoid syncope because of inhalation, patients should be instructed to inhale in a relaxed sitting position.

Hippocampal damage after prolonged febrile seizure: one case in a consecutive prospective series.

The factors that contribute to hippocampal damage as a sequela, and its frequency, in patients experiencing febrile status epilepticus, remain unknown. Of the 472 patients with febrile seizures admitted to our hospital between February 2004 and August 2008, 77 had prolonged seizures. Among them, 59 underwent magnetic resonance imaging (MRI). A 21-month-old girl showed hippocampal changes after her first episode of febrile status epilepticus. The seizure lasted about 35 min, with eye deviation to the right and ictal rhythmic discharges in the left hemisphere. MRI at 72 h after the seizure revealed high-signal intensities in T(2) and fluid-attenuated inversion recovery (FLAIR) images of the left hippocampus. Left hippocampal volume diminished over the next several months suggesting the occurrence of neuronal cell death. In no other cases, not even those with longer seizure durations, did significant hippocampal changes develop. The frequency of hippocampal damage was 1.7% in this case series. The involvement of factors other than seizure duration merits further study.

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.

[Neuropsychological profile of children with cryptogenic localization-related epilepsy and its association with age at onset].

The aim of this study was to investigate the neuropsychological profile of children with cryptogenic localization-related epilepsy (CLRE). Neuropsychological evaluations were performed in 16 CLRE children and 14 children with idiopathic localization-related epilepsy (ILRE) for control within 8 months (average 2.1 months) of initial seizure. The neuropsychological tests used in this study are as follows: the Wechsler Intelligence Scale for Children-Third Edition, Wechsler Intelligence Scale for Children-Revised, and Wechsler Preschool and Primary Scale of Intelligence. Age at onset and test differed significantly between CLRE and ILRE, while the duration between onset and test and the number of seizures before test did not. No marked difference was observed in the neuropsychological profile between 2 groups; however, the discrepancy between VIQ and PIQ was significantly larger in CLRE than in ILRE. This discrepancy was negatively correlated with age at the time of seizure onset (r = -0.615, and p = 0.011). The laterality in discrepancy between VIQ and PIQ was associated with the dominance of interictal discharge. In conclusion, children with lower age at the time of seizure onset were likely to have had a larger discrepancy between VIQ and PIQ.

[Efficacy of topiramate for relapsed epileptic spasms with tuberous sclerosis: report of three cases].

Topiramate (TPM) has been shown to be effective for epileptic spasms (ES) in children, but there is little clinical experience with TPM use in Japan. We report three tuberous sclerosis (TS) patients with relapsed ES, who became spasm-free while receiving TPM treatment. All three patients were treated with a starting dose of 0.5 mg/kg/day. The dosage was increased by 0.5 mg/kg/day every 2 weeks. Although the dose of TPM and the period until the relapsed ES subsided differed among these patients, spasm frequency was clearly reduced by a 1 mg/kg/day dose of TPM. Therefore, efficacy against relapsed ES appeared within one month in all three patients. All three became spasm-free, and there have been no ES relapses for more than 5 months to date. In case 2, seizures were well controlled by TPM alone. Cases 2 and 3 were able to discontinue zonisamide treatment. No adverse effects occurred in any of these patients.

Reversible splenial lesions during febrile illness with or without white matter lesions.

OBJECTIVE: Reversible splenium lesions during febrile illness (RESLEF) are found in a spectrum. There are two types of corpus callosum (CC) lesions: CC-only type, with limited lesions and the CC (+) type, with extensive white-matter lesions. This retrospective study aimed to describe the differences in clinical findings between CC-only and CC (+) lesions and the association between onset age and clinico-radiological features in RESLEF. METHODS: Fifty-two episodes of CC-only or CC (+) lesions accompanied by neurological symptoms, e.g., seizures, delirious behavior (DB), and disturbance of consciousness (DC), from January 2008 to October 2019 were included. We analyzed the etiology (pathogen), clinical course, laboratory data, magnetic resonance imaging and electroencephalography findings, therapy, and prognosis. RESULTS: The rate of DC in the CC (+) was significantly higher than that in the CC-only group (5/6 [83%] vs 7/46 [15%]; p = 0.0016). The median number of seizures in the CC (+) was also significantly higher than that in the CC-only group (4 [0-7] vs 0 [0-7]; p = 0.034). Further, in RESLEF, the median onset age (months) in the seizure was significantly lower than that in the no-seizure group (39 [12-74] vs 83 [28-174]; p = 0.0007). The median onset age (months) in the DB was significantly higher than that in the no-DB group (74.5 [26-174] vs 28 [12-139]; p = 0.003). CONCLUSIONS: In RESLEF, CC (+) is a more severe neurological symptom than CC-only. Furthermore, the onset age is related to the type of neurological symptoms that appear.

Rapid-onset dystonia-parkinsonism with ATP1A3 mutation and left lower limb paroxysmal dystonia.

BACKGROUND: Rapid-onset dystonia-parkinsonism (RDP) is a disease characterized by an abrupt onset of dystonia accompanied by signs of parkinsonism and prominent bulbar symptoms. CASE REPORT: We describe a case of a female patient, born after normal delivery, but diagnosed with mild intellectual disability at age 7. She presented with an abrupt onset of upper limb dystonia and bradykinesia without tremor in parkinsonism, as well as dysarthria and dysphagia caused by prominent bulbar symptoms, at age 9. She had normal findings on brain magnetic resonance imaging, electroencephalography, and blood examination but was diagnosed with a psychogenic disorder. At age 10, she developed left lower limb paroxysmal stiffness with pain, and at 14, she was hospitalized due to lasting paroxysmal symptoms. Whole-exome sequencing was performed for this index case and her parents, and a de novo missense variant c.829G > A, p.Glu277Lys in ATP1A3 was identified. DISCUSSION: This RDP case highlights a rare clinical feature of paroxysmal dystonia that affects the lower left limb and develops after the abrupt onset of permanent dystonia. Currently, there are only three reported RDP cases associated with the same missense mutation, and we summarized the clinical features of all cases including ours, such as onset of age, time for stable, RDP score, relapse and exacerbation. Various symptoms owing to ATP1A3 mutation could develop as ATP1A3-related neurological disorders beyond classical phenotypes such as alternating hemiplegia of childhood (AHC) or RDP. Although RDP is extremely rare during childhood, it is important to understand its clinical characteristics in children.

Clinical findings in patients with febrile seizure after 5 years of age: A retrospective study.

OBJECTIVE: Febrile seizures (FSs) typically occur in infants and children between 6 and 60 months of age. Rarely, FS can occur in late childhood (late FS [LFS]; >5 years of age); however, the clinical features of LFS remain unclear. We aimed to clarify the clinical features of LFS. METHODS: We retrospectively analyzed data from patients with LFS who visited Hirakata City Hospital between January 2004 and December 2014. We defined LFS as a seizure accompanied by fever (temperature ≥38 °C) occurring after 5 years of age, without a central nervous system infection. RESULTS: A total of 505 patients (349 boys, 156 girls: 5-14 years old) were included. A history of FS before 60 months of age was observed in 319 of 460 patients (69.3%) with sufficient information about previous FS history among the 505 patients enrolled. LFS was more likely to occur in males (69.1%). Seizure duration was ≤15 min in 87.4% of cases. A family history of FS in first-degree relatives was observed in 103/327 cases (31.5%). Among LFS cases, 45% occurred at 5 years of age, and 92.1% experienced only one seizure after 5 years of age. The number of seizure episodes gradually lessened with age, decreasing drastically to 5.6% of cases older than 9 years. CONCLUSIONS: Our findings suggest that sex differences, seizure duration, and family history were similar for LFS and FS. Over 90% patients with LFS experienced no recurrence after 5 years of age. Further study is needed to verify the recurrence rate of LFS.

The effect of the guidelines for management of febrile seizures 2015 on clinical practices: Nationwide survey in Japan.

OBJECTIVE: To investigate the effect of guidelines for management of febrile seizures on the clinical practice, we conducted a nationwide survey in Japan. METHODS: The Japanese guidelines for management of febrile seizures 2015 (GL2015) was released in 2015. In 2016, a questionnaire was sent to all 512 certified hospitals (3 pediatricians each) of the Japan Pediatric Society and all 47 prefecture Pediatric Associations (10 private pediatricians each) in Japan asking about management policies for febrile seizures (FSs) during 2013-2014 and 2016. The questionnaires were about the following procedures: (1) lumbar punctures, blood examinations, and diazepam suppositories for children after a first simple FS at emergency departments; and (2) prophylactic diazepam during febrile illnesses in children with two or three past simple FSs, with no known predictors of recurrence. RESULTS: A total of 1327 pediatricians (66.2%) answered the questionnaire. Numbers of pediatricians performing lumbar punctures and blood examinations, and giving diazepam suppositories after a first simple FS were less in 2016 than in 2013-2014 (1.2% and 2.0%, 53.1% and 61.3%, and 36.7% and 51.9%, respectively). Pediatricians recommending prophylactic diazepam for children with two and three FSs decreased from 45.7% and 82.4% in 2013-2014 to 31.0% and 65.0% in 2016, respectively. CONCLUSION: GL2015 had an effect on the clinical practices of pediatricians. On the other hand, 65% recommended prophylactic diazepam to children with three simple FSs even though GL2015 did not recommend use of diazepam based on number of previous FS. Anxiety about frequent seizures may affect pediatricians' clinical practice.

[Seizure characteristics in Kawasaki disease].

It is well known that convulsions may occur in clinical course of Kawasaki disease. However, the features of such seizures remain unclear. Recent reports have hypothesized that proinflammatory cytokines may contribute to the genesis of febrile convulsions (FC). In the acute phase of Kawasaki disease, proinflammatory cytokines are elevated in serum and CSF. If cytokines play a role in seizure phenomena in patients with Kawasaki disease, FC and seizures in Kawasaki disease might share some clinical features. To clarify the clinical features of convulsion in Kawasaki disease, we investigated 7 patients with Kawasaki disease with convulsions who were diagnosed and treated from November 2003 to November 2005. We found several features of the seizures, as well as the onset age, were diffrent among these clinical entities. The onset of Kawasaki disease was characteristically before six months of age in all patients. Seizure clustering was seen in 5 patients and partial seizures in 4. Prolonged unconsciousness after seizures was seen in one patient, syndrome of inappropriate secretion of ADH (SIADH) in one other. One patient had markedly elevated IL-6 in CSF. These observations led us to speculate that the convulsion of Kawasaki disease may be attributable to an encephalitis. The results of this study suggest that seizure pathophysiology differs between FC and Kawasaki disease.

Acetaminophen and Febrile Seizure Recurrences During the Same Fever Episode.

OBJECTIVES: To confirm the safety of using acetaminophen for febrile seizures (FSs) and to assess its efficacy in preventing FS recurrence during the same fever episode. METHODS: In this single-center, prospective, open, randomized controlled study, we included children and infants (age range: 6-60 months) with FSs who visited our hospital between May 1, 2015, and April 30, 2017. The effectiveness of acetaminophen was examined by comparing the recurrence rates of patients in whom rectal acetaminophen (10 mg/kg) was administered every 6 hours until 24 hours after the first convulsion (if the fever remained >38.0°C) to the rates of patients in whom no antipyretics were administered. No placebo was administered to controls. The primary outcome measure was FS recurrence during the same fever episode. RESULTS: We evaluated 423 patients; of these, 219 were in the rectal acetaminophen group, and 204 were in the no antipyretics group. In the univariate analysis, the FS recurrence rate was significantly lower in the rectal acetaminophen group (9.1%) than in the no antipyretics group (23.5%; P < .001). Among the variables in the final multiple logistic regression analysis, rectal acetaminophen use was the largest contributor to the prevention of FS recurrence during the same fever episode (odds ratio: 5.6; 95% confidence interval: 2.3-13.3). CONCLUSIONS: Acetaminophen is a safe antipyretic against FSs and has the potential to prevent FS recurrence during the same fever episode.

Febrile seizures associated with influenza A.

To clarify the clinical impact of influenza A on the development of febrile seizures (FS), consecutive FS patients brought to our hospital between October 2003 and September 2004 were prospectively surveyed. Patients infected with influenza A (influenza A patients) and those uninfected with influenza (non-influenza patients) were compared with regard to clinical characteristics of FS. Influenza infection was determined by rapid antigen test and/or serologically. Associations of influenza A with atypical findings of FS, including partial seizures, prolonged seizures, multiple seizures during the same illness, and 30-min or longer prolonged postictal impairment of consciousness (PPIC), were analyzed by multiple logistic regression. A total of 215 patients (47 influenza A and 168 non-influenza patients) were enrolled in the study. Age was significantly higher in the influenza A group (39.85+/-22.16 months vs. 27.51+/-17.14 months, P<0.001). Of 42 patients aged 48 months or older, which corresponded to the 80th percentile for age, 15 (35.7%) were influenza A patients, with a significantly higher incidence of such patients than in the subgroup of patients aged 47 months or younger (32/173, 18.5%) (P=0.015). On multiple logistic regression analysis, influenza A was independently associated with PPIC (odds ratio: 4.44, 95% confidence interval: 1.52-12.95, P=0.006), but not with other atypical findings. The positive association of influenza A with PPIC suggests that influenza may affect state of consciousness at the same time that it induces seizures with fever.

Oseltamivir use and severe abnormal behavior in Japanese children and adolescents with influenza: Is a self-controlled case series study applicable?

OBJECTIVE: Since the 1990s, self-controlled designs including self-controlled case series (SCCS) studies have been occasionally used in post-marketing evaluation of drug or vaccine safety. An SCCS study was tentatively applied to evaluate the relationship between oseltamivir use and abnormal behavior Type A (serious abnormal behavior potentially leading to an accident or harm to another person) in influenza patients. METHODS: From the original prospective cohort study with approximately 10,000 Japanese children and adolescents with influenza (aged <18years), 28 subjects (mean age: 7.3years) who developed abnormal behavior Type A after the first visit to the collaborating hospitals/clinics were analyzed. We hypothesized four combination patterns of the effect period (i.e., the period that effect of oseltamivir on occurrence of abnormal behavior Type A is likely) and the control period. Mantel-Haenszel rate ratio (M-H RR) and its 95% confidence interval (CI) were calculated as the relative risk estimate. RESULTS: Among 28 subjects in the SCCS study, 24 subjects (86%) were administered oseltamivir and 4 subjects (14%) were not. Abnormal behavior Type A was more likely to occur in the effect period than the control period in every pattern (M-H RR: 1.90-29.1). We observed the highest estimate when the effect period was set between the initial intake of oseltamivir and Tmax (M-H RR: 29.1, 95% CI: 4.21-201). CONCLUSION: Abnormal behavior Type A was more likely to develop up to approximately 30 times during the period between the initial intake of oseltamivir and Tmax. However, this period overlapped with the early period of influenza where high fever was observed. Since useful approaches to control the influence of the natural disease course of influenza were not available in this study, we could not deny the possibility that abnormal behavior was induced by influenza itself. The SCCS study was not an optimal method to evaluate the relationship between oseltamivir use and abnormal behavior.