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.