Purpose: Proper judgement of the aptitude of people with epilepsy (PWE) for driving is a critical issue, both medically and socially. One thus far reported approach is a quantitative comparison of the risk of fatal traffic accidents caused by PWE drivers and that by subgroups of drivers in the general population. We propose a new approach that compares the risk posed by PWE drivers and that by sudden death of occupational drivers, and the maximum driving time for PWE based on that comparison.
Method: The risk of fatal traffic accidents was estimated using four variables. The value assigned to each variable was determined using reports and statistics.
Results: The risk of fatal traffic accidents caused by sudden death of occupational drivers was estimated to be 7.6×10-5/year, 4.9×10-5/year, and 1.7×10-5/year for large-sized, mid-sized and normal-sized vehicles. The risk of fatal traffic accidents caused by PWE drivers was estimated to be 5.3×10-5/year and 3.2×10-5/year for PWE with seizure-free periods of 1 year and 2 years, respectively. The maximum acceptable driving time for PWE having a 2-year seizure-free period at the equivalent risk caused by sudden death of occupational drivers of mid-sized vehicles was estimated to be 304 min/week.
Conclusion: The risk of fatal traffic accidents caused by PWE drivers can be evaluated by comparing to that caused by sudden death of occupational drivers. Such risk posed by PWE drivers having a 2-year seizure-free period was less than that caused by sudden death of occupational drivers of mid-sized vehicles. Assuming that the society accepts the latter risk, PWE may be permitted to drive for an estimated maximum time at the equivalent risk of causing a fatal accident.
Purpose: To investigate the adverse effects of adrenocorticotropic hormone (ACTH) therapy on function of the hypothalamic-pituitary-adrenal (HPA) axis and the necessity of subsequent adrenocortical hormone replacement therapy (HRT).
Methods: We conducted a retrospective review of patients with epilepsy who received ACTH therapy and underwent assessment of HPA axis function.
Results: Six cases analyzed for hormones, including a symptomatic patient with HPA axis insufficiency (HPAI), were studied. Serum cortisol concentrations in the morning were at HPAI levels (<5.0 µg/dL) in three cases, at suspected HPAI levels (>5.0 and <13 µg/dL) in two cases, and normal in one case. However, in the corticotrophin-releasing hormone (CRH) test, while both serum cortisol and plasma ACTH levels were reactive in five cases, only one case exhibited lazy patterns in the time courses of serum cortisol and plasma ACTH levels. Consequently, all six patients who received ACTH therapy had some degree of HPA axis hypofunction for approximately 2-3 months after ACTH therapy and were treated with HRT.
Conclusion: Patients who receive ACTH therapy may be at r isk of HPA axis hypofunction for a certain period and HRT may be recommended until their serum cortisol levels return to basal levels.
Purpose: To elucidate the effects of antiepileptic drugs (AEDs) on microglial cytokine production, polarization, and morphology.
Methods: MG6, an immortalized mouse microglial cell line, was stimulated with lipopolysaccharides (LPS) and the levels of pro-inflammatory cytokines were measured by enzyme linked immunosorbent assay, quantitative polymerase chain reaction (q-PCR), and intracellular staining using flow cytometry. M1 and M2 signatures of microglia after polarization were assessed using quantitative PCR and flow cytometry. Primary microglia prepared from CX3CR1-GFP mice were used to study the effects of AEDs on microglial morphology.
Results: Valproic acid (VPA) or gabapentin (GBP) augmented LPS-induced interleukin-6 (IL-6) production, while phenobarbital (PB) suppressed it. Tumor necrosis factor α (TNFα) production was enhanced by VPA, but was suppressed by PB and GBP. Levetiracetam did not alter cytokine production. It was difficult to assess the effects of water-insoluble AEDs because dimethyl sulfoxide solvent markedly suppressed IL-6 production. The mechanism of altered IL-6 production by AEDs was independent of their transcription or extracellular release. VPA augmented microglial M1 polarization. AEDs did not substantially affect the expression of microglial surface markers and had limited effect on the morphology of primary microglia.
Discussion: Although VPA increased microglial production of pro-inflammatory cytokines, partly due to augmented M1 polarization, most of the AEDs tested in the present study had neither beneficial nor adverse effects on inflammation in clinical practice.
Purpose: Recent developments in advanced diffusion imaging techniques are expected to improve our knowledge regarding epilepsy. Here we investigated neurite density and dispersion in idiopathic generalized epilepsy (IGE) using neurite orientation dispersion and density imaging (NODDI).
Methods: We recruited 14 patients with IGE and 16 age- and gender-matched healthy controls. With diffusion images at two b-values (1000 and 2000 s/mm2), NODDI calculated the intracellular volume fraction (ICVF) and orientation dispersion index (ODI) in each subject. These images were spatially normalized with each subject's T1-weighted image and subjected to a whole-brain group comparison. Statistical Parametric Mapping 12 software (SPM12) was used for the normalization and statistical analysis. We also examined fractional anisotropy (FA) and mean diffusivity (MD) by performing a tract-based spatial statistics (TBSS) analysis.
Results: Although there wer e no significant between-group differences in ICVF, gray matter volumes, and FA/MD, we found a weak significance of reduced ODI in the mediobasal frontal areas of the IGE group.
Discussion: We speculate that our exploratory application of NODDI may provide initial insights about neurites abnormality in IGE. The slightly deceased regional ODI appears to be consistent with thalamo-frontal dysfunction in IGE. Otherwise, there might be no abnormality in the neurites of individuals with IGE, but further investigation with more samples and/or cognitive assessment is needed.
Recently, attention has been focused on the anticancer properties of an aromatic component; 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), in a typical Japanese spice, wasabi. 6-MITC shows selective sensitivity to human breast cancer and melanoma cell lines in 39 human cancer cell lines. Furthermore, 6-MITC is active against pulmonary metastasis of B16-BL6 mouse melanoma cells. In the present study, we investigated the antiepileptic effects of 6-MITC using epileptic mutant EL mice. To explore the mechanisms of antiepileptic effects of 6-MITC, we analyzed the changes in cell cycle reentry (CCR), cytokine systems, and GABAA receptor subunits during epileptogenesis in EL mice, using semi-quantitative Western blotting techniques. Our results suggest that the antiepi-leptic mechanisms of 6-MITC is related to repair of abnormal plasticity, which is supported by CCR inactivation, together with activation of endogenous cytokines as well as induction of extra-synaptic GABAA receptor subunits, both of which play antiepileptic roles.
Purpose: This study aimed to identify impor tant factor s to achieve successful nur sing car e for patients with epilepsy, from the experiences of women with epilepsy who were told of the disease in childhood and subsequently acquired a positive attitude toward the disease.
Methods: A semi-structured interview was conducted in 7 young women with childhood-onset epilepsy treated at specialized epilepsy outpatient clinics. Then a transcript was prepared from the interview data and analyzed qualitatively according to Burnard's method.
Results: One patients had gener alized seizur e and 6 patients had par tial epilepsy (fr ontal lobe epilepsy in 2 and temporal lobe epilepsy in 4). The childhood experiences of the women with epilepsy were classified into six categories; (1) stage when disease was not clearly understood, (2) stage when being told of the diagnosis, (3) stage of self-isolation for having epilepsy, (4) stage of attempt to adjust to disease, (5) stage of rehabilitation of the mind, and (6) stage of appreciation to people and anticipation of the future. In the interview contents, “mother” was the most mentioned family member.
Discussion: For young women with childhood-onset epilepsy and their families, maintaining good medication compliance was an important personal experience for the child and their parents. Acceptance of independent spirit and behavior may foster a positive attitude and rehabilitation of the mind. Even patients with high seizure frequencies at onset and complicated by anxiety and depression talked passionately during the interviews about the process of acquiring a forward looking psychological state as their seizures became controlled.
Conclusion: The effects of epilepsy sever ity and seizur e type on psychological outcome r emain unknown. In providing nursing care for women with epilepsy and their families, it is necessary to understand the psychological state of the patients, provide specialist information oriented toward their future life stage, and coordinate with other health personnel to facilitate their AED treatment.
We examined the effects of switching from carbamazepine to lacosamide on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone in two patients with partial epilepsy manifesting epileptic psychosis. Within 1 week of switch, increases of 52.5-347% in plasma levels of risperidone and 9-hydroxyrisperidone were observed, along with improvements in psychiatric symptoms as shown by Positive and Negative Syndrome Scale scores (PANSS). Neither of the patients showed extrapyramidal symptoms or seizures during 3 months after switching. The present results support the notion that carbamazepine (CBZ) administration induces hepatic microsomal enzyme systems that regulate inactivation of antipsychotic drugs. When CBZ and psychotropic agents are used in combination, a switch from CBZ to lacosamide may be effective in patients with treatment-resistance epileptic psychosis.
Purpose: Psychogenic non-epileptic seizures (PNES) are psychogenic disorders that often resemble epileptic seizures. Herein, we describe the recent clinical trends of PNES by using the data from a large, claims-based Japanese database obtained from the Japan Medical Data Center.
Methods: A 10-year epidemiological study of patients of all ages with newly diagnosed PNES was conducted. Data were extracted using the International Classification of Diseases 10th Revision (ICD-10) diagnostic codes. Prevalence in new epilepsy patients and period of the diagnostic delay of PNES after epilepsy diagnosis were retrieved from the data. The study endpoint was change in frequency of hospital visits. Data of 413 patients with PNES were retrieved using the criterion of “PNES diagnosis after epilepsy diagnosis.”
Results: The highest PNES prevalence in new epilepsy patients was observed in the 40-49 year age group (4.3%) for males, and in the 30-39 age group (4.9%) for females. The ratio of the prevalence in males to that in females was 1:2 for 0-9, 10-19, and >60 age groups, and 1:1 for the other age groups. A significant and positive correlation was found between the frequency of hospital visits and duration of the diagnostic delay of PNES. After PNES diagnosis, the average number of monthly hospital visits decreased over time.
Discussion: The differences in the duration of diagnostic delay of PNES among cases and also a decrease in the frequency of hospital visits after PNES diagnosis highlight the importance of early differentiation between epilepsy and PNES.
Dysembryoplastic neuroepithelial tumor (DNET) is a benign tumor that causes intractable epilepsy at young ages. In this report, we present a rare case of a 28-year-old female with a DNET in the temporal lobe showing extracortical extension to the basal cistern. Enlarging contrast enhancement on MRI, a trait unusual for a benign tumor, suggested the possibility of a malignant glioma. An intraoperative rapid pathological diagnosis of a low-grade glioma in conjunction with electrocorticographic findings supported a surgical strategy of tumor resection alone with preservation of the hippocampus. For this type of DNET with uncommon extension and MRI features, a combination of electro-physiological and morphological analyses based on preoperative studies for epileptogenic focus detection is key to achieving good seizure control and tumor removal with preservation of the patient's memory function.
Purpose: Epilepsy is a common neurological disease that places severe burdens on patients over a very long period. Current treatments mainly involve antiepileptic drugs, but these do not cure epilepsy. Improvements in treatment methods and targets have thus been awaited. Antiepileptic drugs given before the onset of epilepsy have been shown to exert beneficial effects on epilepsy prognosis in rodent and human studies. To establish preventive approaches to epilepsy, we organized a study team to clarify the mean age at onset of each epilepsy phenotype classified into genetic generalized epilepsy.
Methods: Patients with genetic generalized epilepsy including epilepsy with generalized tonic-clinic seizures on awakening, juvenile myoclonic epilepsy, juvenile absence epilepsy and childhood absence epilepsy, who visited our institutes between 2014 to 2016 were studied. Demographic data from these patients and their offspring were analyzed. Offspring were regarded as a high-risk group because of high hereditability of epilepsy.
Results: The study population comprised 154 patients (generalized tonic-clonic seizures on awakening, n=76; juvenile myoclonic epilepsy, n=52; juvenile absence epilepsy, n=17; childhood absence epilepsy, n=9) and 30 offspring. Mean (±standard deviation) age of patients was 27.78±9.69 years. Mean age at onset was 16.05±6.44 years, and mean duration of disease was 11.36±9.84 years. A high rate of multiple antiepileptic drug use and long duration of disease were found in all types of epilepsy studied.
Conclusion: This preliminary study highlights the necessity for identification of offspring warranting early treatment together with optimal timing of such treatment.
Resective surgery is considered if the lesion location is concordant with the epileptogenic zone evaluated by electrophysiological assessment. Diffuse epileptic abnormalities may lead to extended resection or preclude an indication for surgical treatment. We report a 17-year-old boy with a small cavernous malformation presenting drug-resistant epilepsy. Although pre-surgical evaluations revealed epileptic abnormalities widely around the lesion, and invasive evaluation with implanted subdural electrodes failed to localize seizure onset to the lesion, his seizures were significantly improved after simple lesionectomy. A small cavernous malformation could cause apparently diffuse functional abnormalities, and simple lesionectomy may be a reasonable option for drug-resistant epilepsy associated with a cavernous malformation.
High-dose vitamin B6 (VB6) treatment is one of the therapeutic options for West syndrome (WS), particularly for cases without cerebral lesions. The effects of VB6 in patients with brain pathologies, however, may shed light on its presently unknown mechanisms of action for WS. We herein report an infant with WS caused by a very severe brain injury mainly involving the left temporal lobe, who responded dramatically to pyridoxal-5′-phosphate (PLP), the active form of VB6. The patient achieved long-term freedom from seizure with marked EEG improvement. His successful treatment indicated that VB6 should not be precluded from the therapeutic options however extensive the causative brain pathology is. Since WS remains an intractable epilepsy syndrome with limited treatment options, high-dose VB6 therapy is thought to be worth considering.