Noriko Kamiyama

The evaluation of oxidative DNA damage in children with brain damage using 8-hydroxydeoxyguanosine levels

Urinary and cerebrospinal fluid (CSF) levels of 8-hydroxydeoxyguanosine (8-OHdG) were examined to estimate the relevance of oxidative stress in children with brain damage. Urinary 8-OHdG levels were measured in 51 children with various forms of central nervous system (CNS) disorders (status epilepticus [SE], hypoxic-ischemic encephalopathy [HIE], CNS infections and chronic epilepsy) and these levels were compared with those in 51 healthy children. CSF 8-OHdG levels were measured in 25 children with brain damage and in 19 control subjects. In addition, urinary and CSF levels of 8-OHdG were compared between the children with brain damage and healthy children. Finally, the relationship between urinary and CSF levels of 8-OHdG was determined in 12 children that provided both urinary and CSF samples. Our results showed that urinary 8-OHdG levels in children with HIE and CNS infections were higher than those of controls (Steel test; p < 0.05 and p < 0.05, respectively) and that CSF 8-OHdG levels were higher in children with SE, HIE, and CNS infections than in control subjects (Steel test; p < 0.01, 0.05 and 0.05, respectively). In addition, a positive correlation between the levels of urinary and CSF 8-OHdG was noted in the 12 children that provided both CSF and urinary samples (Spearmans rank correlation; rho = 0.82, p < 0.01). Further, we observed changes in the urinary 8-OHdG in a patient with HHV-6 encephalopathy, and found that the changes correlated well with the patients clinical condition. These results suggest that oxidative stress is strongly related to acute brain damage in children, and that 8-OHdG is a useful marker of brain damage. Therefore, repeated measurements of urinary 8-OHdG may be helpful in estimating the extent of brain damage.

Liposteroid (dexamethasone palmitate) therapy for West syndrome: a comparative study with ACTH therapy.

Dexamethasone palmitate (liposteroid) was used for the treatment of West syndrome and compared with adrenocorticotropic hormone (ACTH) therapy. A single intravenous injection of liposteroid (0.25 mg/kg) was administered seven times in 3 months (total dosage = 1.75 mg/kg) to five symptomatic patients with West syndrome, aged 4-11 months. ACTH (0.025 mg/kg/day) was administered intramuscularly for 6 weeks according to the conventional therapy in Japan (total dosage = 0.625 mg/kg) to five symptomatic patients with West syndrome, aged 6-10 months. Nodding spasm and hypsarrhythmia on EEG disappeared in all patients in the liposteroid therapy group within four doses; however, partial seizures and focal spikes on EEG reappeared in three patients 2 months after the end of liposteroid therapy. In the ACTH therapy group, nodding spasm and hypsarrhythmia on EEG similarly disappeared during treatment in all patients, but nodding spasm reappeared 2 months after therapy in two patients and partial seizures reappeared in one patient 3 months after therapy. No notable adverse reactions occurred in the liposteroid group, but transient dysfunction of the thyroid and anterior pituitary gland and increased levels of serum cortisol were experienced in the ACTH group. These results suggest that glucocorticoid incorporated in a lipid emulsion is useful for the treatment of West syndrome.

Studies on cerebrospinal fluid ionized calcium and magnesium concentrations in convulsive children

Abstract Background : The concentrations of ionized calcium (iCa) and ionized magnesium (iMg) were measured in the cerebrospinal fluid (CSF) of convulsive and non‐convulsive children, to investigate the relationship between seizure manifestation and CSF iCa and iMg concentrations. Standard concentrations of CSF iCa and iMg were also established.

A new trial liposteroid (dexamethasone palmitate) therapy for intractable epileptic seizures in infancy

West syndrome (WS) is a severe age-dependent intractable epilepsy in infants that frequently results in mental retardation. ACTH or glucocorticoids are among several effective treatments in WS, but the relative advantages and disadvantages of these two therapies are still unknown. In a previous study, liposteroid (LS; dexamethasone palmitate) was used for the treatment of WS and compared with ACTH therapy in relation to therapeutic effect and adverse reactions. In this study, a new regimen of LS therapy was tried for WS and its related syndrome in an attempt to hasten the onset of the therapeutic effect and reduce the relapse rate. A single intravenous injection of LS (0.25mg/kg) was administered 12 times in 1 month (total dosage 3.0mg/kg) to four patients with WS and with post-WS aged 5-25 months, and one patient with Lennox-Gastaut syndrome (post-WS) aged 84 months. All five patients had daily seizures uncontrolled by conventional antiepileptic drugs, such as VPA, CZP or ZNS. Nodding spasm and hypsarrhythmia on EEG disappeared in one patient with WS within four doses. More than 50% decrease in seizures, and EEG improvement, were found in other two patients. No notable effects were seen in the other two patients. There were no clinically significant adverse reactions throughout the therapy. Efficacy can be determined in this new experimental LS therapy earlier than with conventional LS therapy. In this small study, a new protocol for LS therapy could be completed safely. This regimen may be useful for those susceptible to adverse reactions from conventional treatment or those unresponsive to other treatments.

Spontaneous resolution of intractable epileptic seizures following HHV-7 infection

PURPOSE We report a three-year-old female with intractable epilepsy post West syndrome whose seizures disappeared following an acute viral infection, without changes in anti-epileptic therapy. METHODS The female infant was born at term to a healthy mother after an uneventful pregnancy and delivery. At the age of five months, she developed intractable brief tonic spasms which had a series of infantile spasms, and an electroencephalogram indicated hypsarrhythmia. She was diagnosed with West syndrome. The seizures were uncontrollable with conventional therapy, including ACTH, vigabatrin, sodium valproate, clonazepam, zonisamide, and ketogenic diet. Daily multiple generalized tonic seizures and brief tonic spasms were observed before an episode of viral infection. RESULTS At the age of three years, the intractable seizures disappeared after a febrile rash illness due to human herpesvirus 7 (HHV-7) infection, without changes in anti-epileptic drugs. CONCLUSIONS The disappearance of intractable epileptic seizures following acute viral infections might be related to the inflammatory or immunologic processes associated with viral infections. This is the first documented case of spontaneous remission of intractable epileptic seizures following HHV-7 infection.

A Case of Congenital Left Internal Carotid Artery Defect Associated with Partial Epilepsy.

てんかん発作の出現を契機に発見された左内頸動脈欠損症の12歳男児例を報告した。生来健康であったが、6カ月の間にテレビ視聴中のけいれん発作を2回繰り返し来院した。精査目的で施行した頭部MRIにおいて左内頸動脈のflow voidが描出されず、MRA及び骨条件の頭部CTより左内頸動脈欠損症と診断した。脳波上右中側頭及び後頭に鋭波を認めたため、けいれんはてんかんによるものと考えられた。しかし欠損側と脳波上の発作波出現部位は対側であり、明らかな症候性てんかんとは断定できなかった。カルバマゼピンの内服開始後、発作はコントロールされている。