Adrenocortical Function Recovery from Secondary Adrenal Insufficiency After ACTH Therapy in a Patient with West Syndrome: A Case Report and Literature Review.

We report a 1-year-7-month-old boy with West syndrome who had associated secondary adrenal insufficiency as a side effect of synthetic ACTH therapy. Serial investigation using corticotropin-releasing hormone (CRH) stimulation tests revealed the time course of his hypothalamic-pituitary-adrenal (HPA) axis recovery after the secondary adrenal insufficiency. Three days after completion of the ACTH therapy, the basal cortisol, peak cortisol, and peak ACTH levels were all low. One month after ACTH therapy, the basal cortisol level exceeded the cutoff level for intact adrenocortical function, and the peak ACTH level had improved. Five months after ACTH therapy, the peak cortisol level exceeded the cutoff level for intact adrenocortical function. The secondary adrenal insufficiency after ACTH therapy and the four months' time lag between the recovery timing of the basal and peak cortisol levels on CRH stimulation tests were notable findings. This follow-up data is valuable information for understanding the timeline for the process of recovery of the HPA axis from secondary adrenal insufficiency, that should lead to appropriate protocols for adrenal testing and adrenocorticosteroid replacement for patients who have undergone ACTH therapy. We also reviewed previous studies on secondary adrenal insufficiency after ACTH therapy in terms of incidence rate, onset risk factors, and recovery from it. Based on our own experience and previous reports, we suggest secondary adrenal insufficiency after ACTH therapy as follows: regarding the total synthetic ACTH dose administered, approximately 0.2 mg/kg of ACTH could cause secondary adrenal insufficiency. As for the required period for convalescence from secondary adrenal insufficiency, it would take from two to five months.

Efficacy of long-term adrenocorticotropic hormone therapy for West syndrome: A retrospective multicenter case series.

OBJECTIVES: Long-term adrenocorticotropic therapy (LT-ACTH), which consisted of 2-4 weeks of daily injections of adrenocorticotropic hormone (ACTH) and subsequent months of weekly injections, was tried for relapsed West syndrome (WS) or other intractable epilepsies in small case reports. Our aim was to explore the efficacy of LT-ACTH for preventing WS relapse, as well as the prevalence of its adverse events. METHODS: This is a retrospective, nationwide, multicenter case series of patients with WS who underwent LT-ACTH. Clinical information of the patients and protocol of LT-ACTH were collected from participating institutes in this study. We defined clinical response to ACTH as achievement of hypsarrhythmia and epileptic spasms resolution. Patients who responded to daily ACTH injections were identified and assessed whether they experienced WS relapse during/after the weekly ACTH injection period. The outcome was measured by the nonrelapse rate at 24 months after daily ACTH injections using the Kaplan-Meier method. RESULTS: Clinical information of 16 children with WS was analyzed. The median age at LT-ACTH initiation was 14.5 months (range: 7-68 months). Thirteen (81%) patients had previously undergone conventional ACTH treatment. The LT-ACTH regimens comprised a median of 16 days of daily injections (range: 11-28 days) and 10 months of weekly injections (range: 3-22 months). Seven patients experienced WS relapse during/after subsequent weekly ACTH period, and the nonrelapse rate at 24 months after daily injections was estimated at 60.6% (95% confidence interval: 32.3%-80.0%). Height stagnation, hypertension, and irritability were observed; lethal adverse events were not reported. SIGNIFICANCE: Our study firstly explored the efficacy of LT-ACTH for preventing WS relapse. LT-ACTH might be a treatment option for patients with relapsed or intractable WS; however, we note that our study is limited by its small sample size and the lack of an appropriate control group.

Distinguishing Acute Encephalopathy with Biphasic Seizures and Late Reduced Diffusion from Prolonged Febrile Seizures by Acute Phase EEG Spectrum Analysis.

BACKGROUND: To differentiate the features of electroencephalography (EEG) after status epileptics in febrile children with final diagnosis of either febrile seizure (FS) or acute encephalopathy for an early diagnosis. METHODS: We retrospectively collected data from 68 children who had status epilepticus and for whom EEGs were recorded within 120 h. These included subjects with a final diagnosis of FS (n = 20), epileptic status (ES; n = 11), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 18), mild encephalopathy with a reversible splenial lesion (MERS; n = 7), other febrile encephalopathies (n = 10), hypoxic-ischemic encephalopathy (n = 1), and intracranial bleeding (n = 1). Initially, all EEGs were visually assessed and graded, and correlation with outcome was explored. Representative EEG epochs were then selected for quantitative analyses. Furthermore, data from AESD (n = 7) and FS (n = 16) patients for whom EEG was recorded within 24 h were also compared. RESULTS: Although milder and most severe grades of EEG correlated with neurological outcome, the outcome of moderate EEG severity group was variable and was not predictable from usual inspection. Frequency band analysis revealed that solid delta power was not significantly different among the five groups (AESD, MERS, FS, ES and control), and that MERS group showed the highest theta band power. The ratios of delta/alpha and (delta + theta)/(alpha + beta) band powers were significantly higher in the AESD group than in other groups. The alpha and beta band powers in EEGs within 24 h from onset were significantly lower in the AESD group. The band powers and their ratios showed earlier improvement towards 24 h in FS than in AESD. CONCLUSION: Sequential EEG recording up to 24 h from onset appeared to be helpful for distinction of AESD from FS before emergence of the second phase of AESD.

Successful treatment of migrating partial seizures in Wolf-Hirschhorn syndrome with bromide.

A girl with mild psychomotor developmental delay developed right or left hemiclonic convulsion at 10months of age. One month later, clusters of hemiclonic or bilateral tonic seizures with eyelid twitching emerged, resulting in status epilepticus. Treatment with phenobarbital and potassium bromide completely terminated the seizures within 10days. Ictal electroencephalography revealed a migrating focus of rhythmic 3-4Hz waves from the right temporal to right frontal regions and then to the left frontal regions. Genetic analysis was conducted based on the characteristic facial appearance of the patient, which identified a 2.1-Mb terminal deletion on chromosome 4p. This is the first case of Wolf-Hirschhorn syndrome complicated by epilepsy with migrating partial seizures.

Early predictors of status epilepticus-associated mortality and morbidity in children.

BACKGROUND: Early predictors of status epilepticus (SE)-associated mortality and morbidity have not been systematically studied in children, considerably impeding the identification of patients at risk. OBJECTIVES: To determine reliable early predictors of SE-associated mortality and morbidity and identify the etiology of SE-associated sequelae in Japanese children. METHODS: We conducted a prospective multicenter study of clinical findings and initial laboratory data acquired at SE onset, and assessed outcomes at the last follow-up examination. In-hospital death during the acute period and neurological sequelae were classified as poor outcomes. RESULTS: Of the 201 children who experienced their first SE episode, 16 exhibited poor outcome that was most commonly associated with acute encephalopathy. Univariate analysis revealed that the following were associated with poor outcomes: young age (⩽24 months); seizure duration >90 min; seizure intractability (failure of the second anticonvulsive drug); biphasic seizures; abnormal blood glucose levels (<61 or >250 mg/dL); serum aspartate aminotransferase (AST) ⩾56 U/L; and C-reactive protein (CRP) levels >2.00 mg/dL. Multivariate analysis revealed that young age, seizure intractability, abnormal blood glucose levels, and elevated AST and CRP levels were statistically significant. CONCLUSIONS: Young age and seizure intractability were highly predictive of poor outcomes in pediatric SE. Moreover, abnormal blood glucose levels and elevated AST and CRP levels were predictors that might be closely associated with the etiology, especially acute encephalopathy and severe bacterial infection (sepsis and meningitis) in Japanese children.

Cough and asthma diagnosis: physicians' diagnosis and treatment of patients complaining of acute, subacute and chronic cough in rural areas of Japan.

BACKGROUND: Cough is one of the most common reasons for visiting a clinic. The causes of cough differ according to the duration of cough. Infectious disease is commonly observed in acute cough while noninfectious disease is commonly observed in chronic cough. On the other hand, cough is frequently observed in patients with asthma/cough variant asthma (CVA). OBJECTIVE: In this study, we investigated the causes of cough in a rural region in Japan and the clinical examination and treatment for the patients diagnosed as asthma/CVA. METHODS: We analyzed 124 patients who complained of cough. RESULTS: The most common reason for acute cough was respiratory tract infection while asthma/CVA is the most common reason for subacute and chronic cough. The diagnostic procedure for asthma/CVA depends on clinical symptoms in asthmatic patients with acute cough. While in asthmatic patients with subacute and chronic cough, diagnosis of asthma depends on clinical examinations including chest radiogram, immunoglobulin E, white blood cells counts, sputum examination or spirometry as well as symptoms. For the treatment of asthma, the use of long-acting beta(2)-stimulant was dominant in asthmatic patients with acute cough while the use of leukotriene receptor and inhaled corticosteroid were dominant in asthmatic patients with subacute or chronic cough. CONCLUSIONS: Diagnosis and treatment for asthma differs according to the duration of cough. Simple guidelines for asthma/CVA according to the duration of cough might be necessary for diagnosis and treatment of asthma/CVA for general physicians especially in rural areas.

Environmental tobacco smoke and its effect on the symptoms and medication in children with asthma.

Environmental tobacco smoke (ETS) worsens asthmatic symptoms. We analyzed the relationship between levels of ETS and asthmatic symptoms and medication. We asked parents of 282 asthmatic children about the general condition, smoke exposure and medication. Patients were classified into three groups: no-ETS (no smoking), mild-ETS (smoking in the house but not in the same room as patient), and heavy-ETS (smoking in the same room as patient). We classified 116 children in no-ETS group, 124 children in mild-ETS group and 42 children in heavy-ETS group. The symptoms were worst and prevalence of leukotriene receptor antagonist and long-acting beta(2)-agonist use were highest in heavy-ETS group. However, there was no statistical difference between no-ETS and mild-ETS groups in prevalence of anti-asthmatic drug use and symptoms. We conclude that a smoking ban in rooms used by asthmatic children is an easy way to reduce ETS, asthmatic symptoms and the use of anti-asthmatic drugs.

Rotavirus-associated encephalopathy with a reversible splenial lesion.

The case is reported of a 2-year-old boy with a rotavirus-induced mild encephalopathy that presented as transient intensified signal on the splenium of the corpus callosum. The boy also experienced persistent diarrhea, vomiting, fever, and sudden disturbance of consciousness. Although cerebrospinal fluid analysis did not manifest pleocytosis, electroencephalography demonstrated global diffuse slow waves and cranial magnetic resonance imaging demonstrated intensified signal on the splenium of the corpus callosum. Methylprednisolone was infused for 3 days. The disturbance of consciousness disappeared within 24 hours without any other complications, and the splenial signal and electroencephalogram returned to normal within 6 days.

[A case of myoclonic astatic epilepsy with autoantibody for glutamate receptor epsilon 2].

A 3-year-old boy was admitted to our hospital with repetitive drop attacks and generalized tonic-clonic seizures. Brain MRI, SPECT and blood laboratory tests did not show any abnormalities, while antibody to glutamate receptor epsilon 2 (GluR epsilon 2) in spinal fluid was positive. Interictal EEG showed generalized 6 to approximately 7 Hz slow, wave and ictal EEG showed 1 to approximately 2 Hz high amplitude generalized spike and slow wave burst. We made a diagnosis as myoclonic astatic epilepsy (MAE). However, his seizures were refractory to almost all antiepileptic drugs, steroid pulse therapy and gamma-globulin therapy. Eight months after the first attack, administration of ACTH therapy was effective. Seizures disappeared and EEG findings improved. To our knowledge, there have been no previous reports of MAE in which autoantibody to GluR epsilon 2 was positive. It is suggested that autoimmunity in this case was associated with the pathogenesis of MAE.

Distal myopathy with rimmed vacuoles in a case of opercular syndrome.

We report the case of a 30-year-old man with opercular syndrome who developed distal myopathy with rimmed vacuoles (DMRV). Muscle biopsy showed variation in fiber size and scattered fibers with rimmed vacuoles. The identification of a homozygous c. 1714G>C (p. V572L) mutation in the GNE gene genetically confirmed the diagnosis of DMRV, which is thought to be identical to hereditary inclusion body myopathy (HIBM). Our results indicate the possibility that other organs such as the central nervous system could be affected in DMRV/HIBM, although bilateral opercular lesions might have been caused by destructive events either in utero or in the perinatal period.

Two Japanese families with hyperekplexia who have a Arg271Gln mutation in the glycine receptor alpha 1 subunit gene.

We report two Japanese patients from two families with hyperekplexia who have a Arg271Gln mutation in the glycine receptor alpha 1 subunit gene. The clinical course of both patients was typical for hyperekplexia, characterized by neonatal hypertonia and exaggerated startle response, and which improved gradually with age. One was associated with umbilical hernia and hip dislocation, diagnosed at 11 months, while the other was diagnosed at 1 month. Both showed positive head retraction reflex. Four Japanese families have been reported as having hyperekplexia including our cases, of which three have shown the same missense Arg271Gln mutation, most frequently found in patients from Northern Europe and the United States.

Underrecognition of the severity of asthma and undertreatment of asthma in a rural area of Japan.

BACKGROUND AND AIM: Revised guidelines were released in Japan in 2003 for the assessment, treatment, and management of adult asthmatics, and similar guidelines for child asthmatics were released in 2002. We reassessed the severity and possible undertreatment of asthma according to these guidelines in stable asthmatics. METHODS: We reviewed medical records of 861 well-controlled asthmatic patients who, in April through June 2004 were cared for by 47 pulmonologists at 29 medical centers and 13 asthma clinics in a rural community in the San-in area of Japan. The physician obtained completed medical records about their symptoms and current treatment of the subjects, 726 adult and 135 children (aged 6 years or older) who were in stable condition and had had no exacerbations in the previous 3 months. The severity of asthma and current treatment for each patient were assessed according to the newly revised Japanese guidelines for the assessment, treatment, and management of adult and child asthmatics. RESULTS: In adult and child asthmatics, the percentage of predicted forced expiratory volume at 1 second (FEV1.0) was smaller and has a narrower distribution range than the percentage of predicted peak expiratory flow (PEF). When the severity of asthma was classified according to symptoms alone, 50% and 35% of those classified as mildly asthmatics patients with adults and children, respectively, had moderate to severe airflow limitation. Inhaled corticosteroids were prescribed to 90.6% of adult and 14.9% of child patients. When we compared the treatments that patients were actually receiving against the optimal treatments indexed according to a combined symptoms-FEV1.0 classification, we found that 49% of adult asthmatics were overtreated, 21% were properly treated, and 30% were undertreated. Among children, the respective percentages were 35%, 25%, and 40%. CONCLUSION: In well-controlled adult and child asthmatics, the severity of asthma is poorly judged when symptoms alone are considered. We suggest that the severity of asthma should be assessed through a combination of symptoms and the measurement of FEV1.0 during office visits. We also suggest that the proper dose of inhaled steroid needed to maintain stable conditions should be judged according to this combined symptoms-FEV1.0 classification.

Brain stem glioblastoma with multiple large cyst formation and leptomeningeal dissemination in a 4-year-old girl.

The authors report a 4-year-old girl who developed brain stem glioblastoma. Meningeal irritation was present at onset. Magnetic resonance imaging revealed intracranial and intraspinal leptomeningeal dissemination, which progressed faster than the original tumor. Multiple large cysts developed at the interhemispheric and prepontine cisterns, resulting in progressive obstructive hydrocephalus. The patient survived only 5 months after presentation. Histology was verified by autopsy.

[Juvenile myoclonic epilepsy misdiagnosed as focal epilepsy: variability of myoclonic seizures].

We report two male patients with juvenile myoclonic epilepsy. They had been diagnosed as having partial epilepsy for three years. They had various myoclonic seizures characterized by truncal and head torsion, stepping backward, and inability to reach objects, as well as asymmetric myoclonic jerks of the upper extremities. For early diagnosis of juvenile myoclonic epilepsy, it is important to take account of the variability of myoclonic seizures.

Hemiconvulsion-hemiplegia syndrome and elevated interleukin-6: case report.

We report a 2-year-old boy who developed hemiconvulsion-hemiplegia syndrome with left-sided hemiplegia after a seizure lasting 35 minutes. The interleukin-6 level in the cerebrospinal fluid 2 hours after seizure onset was elevated to levels seen in patients with encephalitis. At 1 year after onset of the seizure, the patient remained hemiplegic on the left side, and magnetic resonance imaging showed severe right hemispheric atrophy. Acute changes seen on imaging studies and electroencephalograms in this patient were consistent with seizure-induced brain damage. Elevation of cerebrospinal fluid interleukin-6 may be related to the severe neurologic sequelae of our patient despite the relatively short seizure duration.

Serial magnetic resonance angiography in cerebral infarction after varicella infection.

The case of a 1-year-8-month-old-boy with cerebral infarction after varicella infection is reported here. Brain magnetic resonance (MR) angiography revealed segmental narrowing of the left middle cerebral artery which became normal 8 months later. The MR angiography well demonstrated the time course of the vascular involvement in the present patient. In cerebral infarction after varicella infection, the proximal portion of the main cerebral arteries were frequently damaged therefore MR angiography is useful for diagnosis and therapeutic decision-making. Moreover, serial MR angiographic studies can clarify the natural course of vascular changes in varicella virus-related cerebral infarction.

A girl with partial trisomy 5q35-->qter and partial trisomy 13pter-->q31 derived via a maternal balanced translocation.

A girl with partial trisomy 5q35qter and partial trisomy 13pterq31 shows a less severe clinical course.