Kazuyoshi Watanabe

Serum levels of cytokines and EEG findings in children with influenza associated with mild neurological complications

We studied the relation among serum cytokine levels, EEG changes, and mild neurological complications (delirium and febrile seizure) in children with influenza. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and soluble tumor necrosis factor receptor-1 (sTNFR-1) were measured in 27 children with proven influenza infection with mild neurological complications (10 patients with delirium and 17 with febrile seizures) and seven control children. EEG was recorded in 14 children with neurological complications. EEG showed focal slowing in four of nine patients with delirium and in four of five with febrile seizures. Generalized slowing was observed in one patient with delirium. The median serum IL-6 level was 31.2+/-15.1 pg/ml (range, 7.5-64.5 pg/ml) in the delirium group, 42.3+/-44.0 pg/ml (range, 8.0-196.0 pg/ml) in the febrile seizure group, and 15.4+/-7.0 pg/ml (range, 7.2-28.0 pg/ml) in the control group. Serum TNF-alpha and sTNFR-1 levels were not different among three groups. Mild neurological complications associated with influenza were related to the mildly abnormal serum IL-6 levels and EEG findings. The combination of these parameters will be useful for early diagnosis and differentiation of neurological complications in children with influenza. Further studies will be necessary for investigating that IL-6 has the diagnostic value for differentiation between severe encephalopathy and mild neurological complications in children with influenza.

Current treatment of west syndrome in Japan

About 10 years have passed since a previous survey on the treatment of West syndrome in Japan. To elucidate current practice, a questionnaire was sent to 113 institutes. It included (1) the drugs used for the treatment, (2) their dosage, and (3) the dosage and the schedule of adrenocorticotropic hormone therapy. Response rate was 51.3%. Adrenocorticotropic hormone, valproic acid, vitamin B6, and zonisamide were frequently used. Vitamin B6 was used most frequently as the first-choice drug followed by valproic acid, zonisamide, and adrenocorticotropic hormone. The most frequently used dose of synthetic adrenocorticotropic hormone-Z was 0.0125 mg/kg/d. Adrenocorticotropic hormone was administered every day for 2 weeks and then tapered off in more than 80% of the institutes. Although therapeutic strategy and drug usage have not changed largely during these 10 years, 2 alterations were observed: an increased use of zonisamide and a shortened duration of adrenocorticotropic hormone therapy.

Benign partial epilepsy in infancy.

The aim was to examine the occurrence of benign partial epilepsy in infancy (BPEI). BPEI was defined as epilepsies with complex partial seizures (CPS) or secondary generalised seizures (SGS), or both, compatible with the following characteristics: normal development before and after onset, no underlying disorders, normal interictal electroencephalograms (EEGs), and good response to treatment. All 75 patients who developed epilepsy within the first 2 years of age between 1987 and 1993 were evaluated: 22 patients fulfilled the definition completely; eight had CPS only, four SGS only, and 10 had both CPS and SGS; 17 had clusters of seizures. Eight patients had a positive family history. The average age of onset of seizures was 5.9 months. Interictal EEGs were all normal. Response to treatment was excellent and the average period of seizure persistence was 3.0 months. All had normal psychomotor development. Patients with BPEI were more common in this study than previously reported.

Ictal EEG in patients with convulsions with mild gastroenteritis.

The aim of this study is to reveal detailed clinical manifestations and an evolution of ictal EEG discharges of convulsions with mild gastroenteritis (CwG). We recorded ictal EEGs of six patients with CwG. Clinical manifestations included loss of responsiveness, motion arrest, cyanosis, lateral eye deviation, and hemifacial convulsion. Automatism was not observed in any patients. A generalized tonic-clonic convulsion was observed in five of six patients. Ictal EEGs demonstrated that all seizures were of focal onset that evolved into a secondarily generalized seizure. The region of the onset of ictal discharge was the occipital area in three patients, parietal in one, central in one, and frontal in one, respectively. The seizure of patients with CwG is likely to be a partial seizure with secondary generalization.

Long-term Follow-up of Patients with Benign Partial Epilepsy in Infancy

Summary:  Purpose: The aim of this study was to investigate the long‐term outcome of children with benign partial epilepsy in infancy (BPEI).

Association of nonsense mutation in GABRG2 with abnormal trafficking of GABAA receptors in severe epilepsy

Mutations in GABRG2, which encodes the γ2 subunit of GABAA receptors, can cause both genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome. Most GABRG2 truncating mutations associated with Dravet syndrome result in premature termination codons (PTCs) and are stably translated into mutant proteins with potential dominant-negative effects. This study involved search for mutations in candidate genes for Dravet syndrome, namely SCN1A, 2A, 1B, 2B, GABRA1, B2, and G2. A heterozygous nonsense mutation (c.118C>T, p.Q40X) in GABRG2 was identified in dizygotic twin girls with Dravet syndrome and their apparently healthy father. Electrophysiological studies with the reconstituted GABAA receptors in HEK cells showed reduced GABA-induced currents when mutated γ2 DNA was cotransfected with wild-type α1 and β2 subunits. In this case, immunohistochemistry using antibodies to the α1 and γ2 subunits of GABAA receptor showed granular staining in the soma. In addition, microinjection of mutated γ2 subunit cDNA into HEK cells severely inhibited intracellular trafficking of GABAA receptor subunits α1 and β2, and retention of these proteins in the endoplasmic reticulum. The mutated γ2 subunit-expressing neurons also showed impaired axonal transport of the α1 and β2 subunits. Our findings suggested that different phenotypes of epilepsy, e.g., GEFS+ and Dravet syndrome (which share similar abnormalities in causative genes) are likely due to impaired axonal transport associated with the dominant-negative effects of GABRG2.

Guillain-Barré syndrome associated with central nervous system lesions

We report the clinical course, and neurophysiological and neuroimaging findings of a patient with Guillain-Barré syndrome associated with central nervous system lesions. During a course of intravenous immunoglobulin therapy, she had headache with meningism. Cerebral magnetic resonance imaging showed lesions in both frontal and right occipital lobes. Cerebrospinal fluid showed a raised protein concentration accompanied by mild pleocytosis. Her symptoms resolved within two months. Subsequent magnetic resonance imaging revealed cavity formation in the deep white matter and atrophic changes in the right occipital lobes.

Comparison of two low dose ACTH therapies for West syndrome : their efficacy and side effect

In order to clarify the appropriate usage of adrenocorticotropic hormone (ACTH), the efficacy and side effects of two different regimens of low dose ACTH therapy were compared. Thirty-four patients with West syndrome (WS) were treated with ACTH. The dose of synthetic ACTH-Z was 0.015 mg/kg/dose in 18 patients who were treated between 1996 and 1998 (regimen A), and 0.010 mg/kg/dose in 16 patients who were treated between 1999 and 2001 (regimen B). Patients were classified into cryptogenic and symptomatic groups. Efficacy and adverse effects of ACTH were compared between regimens A and B. Similar analyses were performed after stratification into cryptogenic and symptomatic groups. The efficacy of ACTH was not different between regimens A and B. However, among patients with symptomatic WS, the number of ACTH injections and the dose of ACTH until cessation of spasms were significantly smaller in regimen A than in regimen B. There was no significant difference in these variables between the regimens among those with cryptogenic WS. Adverse effects were not different between regimens A and B. 0.010 mg/kg per day of ACTH will be adequate for cryptogenic WS, but 0.015 mg/kg per day of ACTH is recommended for symptomatic WS.

Serial diffusion-weighted imaging of neonatal herpes encephalitis: A case report

We reported a patient with neonatal herpes simplex encephalitis in whom diffusion-weighted imaging was performed repeatedly. Diffusion-weighted imaging at 20h after the onset of seizures revealed scattered small spotty high intensity lesions in both hemispheres and a high intensity area in the left fronto-temporal lobe. There was no abnormal finding on conventional magnetic resonance imaging. Second diffusion-weighted imaging 72h after the onset revealed expanded scattered high intensity lesions in the bilateral hemisphere, a high intensity area in the left fronto-temporal lobe, and a new high intensity area in the right temporal lobe. There was no report on neonatal herpes simplex encephalitis that showed scattered high intensities in diffusion-weighted imaging. Scattered small high intensities on diffusion-weighted imaging may suggest endothelial cell infection with swelling and small vessel necrosis. Early diffusion-weighted imaging will be valuable for early detection and diagnosis of neonatal herpes simplex encephalitis.

Clustered subclinical seizures in a patient with acute encephalopathy with biphasic seizures and late reduced diffusion

Using single-channel amplitude-integrated electroencephalography (aEEG), we monitored clustered seizures in a 12-month-old boy suffering from acute encephalopathy with biphasic seizures and late reduced diffusion (AESD). He was admitted to our hospital after losing consciousness and experiencing repeated seizures in association with fever. Although the patients state of consciousness improved the next day, it declined on the fifth day of illness, and clinical seizures were observed. Diffusion-weighted images revealed abnormal high intensities in the frontal area bilaterally. On the same day, aEEG monitoring revealed an unexpected cluster of subclinical seizures. Attending pediatricians, nurses, and other caregivers did not recognize the presence of these frequent subclinical seizures. The efficacy of antiepileptic drugs could also be objectively assessed from aEEG findings. aEEG is useful for continuous monitoring in children with acute encephalopathy, may disclose subclinical seizures, and can contribute to an objective evaluation of the efficacy of antiepileptic drugs.