Issues of Women with Epilepsy and Suitable Antiseizure Drugs.

Seizure aggravation in women with epilepsy (WWE) tends to occur at two specific times during the menstrual cycle: the perimenstrual phase and the ovulation period. Antiseizure drugs (ASDs), especially those that induce enzymes, can accelerate the metabolism of hormones in oral contraceptives, rendering them less effective. Estrogen in contraceptive pills increases the metabolism of lamotrigine. Physiological changes during pregnancy can significantly impact the pharmacokinetics of ASDs, potentially necessitating adjustments in dosage for women with epilepsy to maintain seizure control. The use of valproate in pregnant women is associated with the highest risk of major congenital malformations among ASDs. Risks of major congenital malformations associated with lamotrigine, levetiracetam, and oxcarbazepine were within the range reported in the general population. Exposure to valproate can lead to lower IQ in offspring. Reduced folic acid levels are linked to orofacial clefts, cardiovascular malformations, and urogenital and limb anomalies in WWE. Decreased folate levels are expected with the use of enzyme-inducing ASDs. However, a high dose of folate was associated with an increased risk of cancer in children of mothers with epilepsy. Most ASDs are generally considered safe for breastfeeding and should be encouraged. However, no single ASD is considered ideal for childbearing WWE. Lamotrigine and levetiracetam are relatively more suitable options for this situation.

Altered resting-state thalamo-occipital functional connectivity is associated with cognition in isolated rapid eye movement sleep behavior disorder.

OBJECTIVE: Isolated rapid eye movement sleep behavior disorder (iRBD) patients are at risk of cognitive impairments, however the underlying mechanism is still unclear. This study aimed to evaluate thalamo-cortical functional connectivity (FC) using resting-state functional magnetic resonance imaging (fMRI) and its correlation with cognitive dysfunction in patients with iRBD. METHODS: A total 37 polysomnographies (PSGs) confirmed iRBD patients and 15 age-sex matched controls underwent resting-state fMRI and comprehensive neuropsychological assessment. Thalamo-cortical FC was evaluated by using seed-to voxel analysis and was compared between the iRBD and controls. Correlation between the average value of significant clusters and cognitive function scores in iRBD were calculated. RESULTS: Compared to the control subjects, patients with iRBD patients showed cognitive decline in word list recognition (p = 0.016), and constructional recall (p = 0.044). The FC analysis showed increased FC between the left thalamus and occipital regions including the right cuneal cortex, left fusiform gyrus and lingual gyrus (cluster level p < 0.05, corrected for false discovery rate). The averaged thalamo-fusiform FC value positively correlated with word list recognition after adjusting for age and sex (adjusted r = 0.347, p = 0.041). CONCLUSION: Thalamic resting state FC is altered in iRBD patients and is associated with the cognitive function. Enhancement of the thalamo-occipital FC may reflect a compensatory mechanism for cognitive impairment in iRBD.

Increasing prevalence of antimicrobial resistance in urinary tract infections of neurological patients, Seoul, South Korea, 2007-2016.

OBJECTIVES: Urinary tract infection (UTI) is a common medical complication experienced by patients with neurologic diseases. In this study, we established the microbial etiologies of UTI, and resistances to antibiotics in UTI as well as determining which appropriate empirical antibiotics should be used to treat UTI in neurological patients. DESIGNS AND METHODS: We retrospectively reviewed microbial etiologies and antimicrobial resistance among patients experiencing UTI events in the neurology ward of Seoul National University Hospital from 2007 to 2016. RESULTS: The total number of UTI events observed was 301, and Klebsiella pneumoniae was the most common pathogen observed in UTIs. But in catheter-associated UTI (CAUTI), Enterococcus species were the most prevalent pathogens. Susceptibility to commonly-prescribed antibiotics decreased over 10 years, indicating increased antibiotic resistance in pathogens associated with UTI. ESBL-producing K. pneumoniae increased significantly, while increases of MDR K. pneumoniae, ESBL-producing E. coli, and VRE were not observed. CONCLUSIONS: The worldwide trend of increasing drug-resistant pathogens should be considered, and further studies on antibiotics resistance in UTI are needed. These data will greatly assist physicians when they select antibiotics to treat UTIs in neurological patients.

Rhythmical Photic Stimulation at Alpha Frequencies Produces Antidepressant-Like Effects in a Mouse Model of Depression.

Current therapies for depression consist primarily of pharmacological agents, including antidepressants, and/or psychiatric counseling, such as psychotherapy. However, light therapy has recently begun to be considered as an effective tool for the treatment of the neuropsychiatric behaviors and symptoms of a variety of brain disorders or diseases, including depression. One methodology employed in light therapy involves flickering photic stimulation within a specific frequency range. The present study investigated whether flickering and flashing photic stimulation with light emitting diodes (LEDs) could improve depression-like behaviors in a corticosterone (CORT)-induced mouse model of depression. Additionally, the effects of the flickering and flashing lights on depressive behavior were compared with those of fluoxetine. Rhythmical flickering photic stimulation at alpha frequencies from 9-11 Hz clearly improved performance on behavioral tasks assessing anxiety, locomotor activity, social interaction, and despair. In contrast, fluoxetine treatment did not strongly improve behavioral performance during the same period compared with flickering photic stimulation. The present findings demonstrated that LED-derived flickering photic stimulation more rapidly improved behavioral outcomes in a CORT-induced mouse model of depression compared with fluoxetine. Thus, the present study suggests that rhythmical photic stimulation at alpha frequencies may aid in the improvement of the quality of life of patients with depression.

Acquired encephalopathy associated with carnitine deficiency after cefditoren pivoxil administration.

We describe a 47-year-old woman who presented with palinopsia and subacute altered mental change after cefditoren pivoxil administration. The patient showed characteristic clinical manifestations of hypocarnitinemia, which affected her state of consciousness and she had radiologic findings that revealed metabolic encephalopathy with cytotoxic edema in the right occipital area and intracranial hemorrhages in right occipital and left frontal areas. Follow-up imaging after oral carnitine supplementation demonstrated complete resolution of the bilateral frontal subcortical T2 high-intensity lesions. Carnitine deficiency due to cefditoren pivoxil treatment may present as metabolic encephalopathy in adults. This possibility should be considered with the differential diagnosis of encephalopathies, and carnitine levels should be checked in patients treated with cefditoren pivoxil.

Assessment of language dominance by event-related oscillatory changes in an auditory language task: magnetoencephalography study.

The authors investigated the oscillatory changes induced by auditory language task to assess hemispheric dominance of language. Magnetoencephalography studies were conducted during word listening in 6 normal right-handed volunteers and 13 epilepsy patients who underwent Wada test. We carried out a time-frequency analysis of event-related desynchronization (ERD)/event-related synchronization (ERS) and intertrial coherence. We localized ERD/ERS on each subject's magnetic resonance images using beamformer. We compared ERD/ERS values between the left and right side of regions of interest in inferior frontal and superior temporal areas. We assessed the target frequency range that correlated best with the Wada test results. In all normal subjects, gamma ERD was lateralized to the left side in both the inferior frontal and superior temporal areas. In epilepsy patients, the concordance rate of gamma ERD and the Wada test results was 76.9% for the inferior frontal area and 69.2% for the superior temporal area. Gamma ERD can be considered as an indicator of language function, although it was not sufficient to replace the Wada test in the evaluation of epilepsy patients. The gamma ERD value of the inferior frontal area was more reliable for the assessment of language dominance compared with that obtained in the superior temporal area.

Thalamic changes in temporal lobe epilepsy with and without hippocampal sclerosis: a diffusion tensor imaging study.

OBJECTIVE: The seizure network may be different between temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) and without HS (TLE-HS). Chronic seizure activity may alter the diffusion properties of a seizure network. The thalamus is known to have an anatomical connection to the medial temporal area and to play a role in seizure modulation. This study aimed to evaluate differences in thalamic changes between TLE+HS and TLE-HS with diffusion tensor imaging (DTI). METHODS: Nine patients with TLE+HS and nine patients with TLE-HS were included in the study. All patients underwent surgery with good seizure outcomes. Hippocampal sclerosis was verified pathologically. Sixteen right-handed, normal subjects were enrolled as controls. DTI was acquired using 3.0 T MRI. The mean diffusivity (MD) and fractional anisotropy (FA) were calculated in the center of the bilateral thalamus with the DTIstudio program. RESULTS: The MD of bilateral thalami increased in both TLE groups compared to controls (p<0.05), while FA values did not differ from controls. The MD of the thalamus ipsilateral to the epileptogenic side was higher in the TLE+HS group than in the TLE-HS group (p=0.007). Onset age, seizure duration, seizure frequency and total seizure number were not correlated with FA and MD changes (p>0.05). CONCLUSION: Bilateral thalamic diffusion properties are altered in temporal lobe epilepsy. The presence of hippocampal sclerosis enhances the change ipsilaterally.

Region-specific plasticity in the epileptic rat brain: a hippocampal and extrahippocampal analysis.

PURPOSE: Recent evidence suggests that aberrant neuro/gliogenesis and/or inflammation play critical roles in epileptogenesis. Although the plastic and inflammatory changes have been described in the postseizure hippocampus, little data is available concerning extrahippocampal regions, notably in the piriform and entorhinal cortices, amygdala, and parts of the thalamus. In this study, we examined histological changes in whole epileptic rat brain, with respect to cell death, cell genesis, and inflammation. METHODS AND RESULTS: Experimental status epilepticus (SE) was induced using a lithium-pilocarpine injection. Neuronal death was evident in the amygdala, piriform, and entorhinal cortices, as well as the subfields of hippocampus. Microglial activation was observed in more extended limbic areas, such as, the hippocampus, entorhinal, perirhinal and piriform cortices, amygdala, thalamus, and hypothalamus, and a robust increase of cell genesis was noted in these damaged areas. The majority of newly generated cells in extrahippocampal areas proliferated in situ, and differentiated mainly into astrocytes or oligodendrocytes. In addition, stromal cell-derived factor-1alpha was found to be induced in close temporal and anatomical association with seizure-induced plasticity. DISCUSSION: These findings indicate that neuronal death, inflammation, and cell genesis are substantially associated throughout the entire brain and that they may influence the epileptogenic process and clinical manifestations.

Alteration of functional neuroanatomy of simple object memory in medial temporal lobe epilepsy patients.

Using H2 15O PET, we examined the neuroanatomy associated with a simple form of episodic memory in patients with right or left medial temporal lobe epilepsy and normal healthy controls. When line drawings of common objects were memorized and tested after a 30 min delay, no behavioral difference was found between the patient groups and the controls. However, the patients with epilepsy showed greater cortical activations than the control group on the side ipsilateral to the epileptic focus. rCBF in the anterior thalamic region was enhanced in patients relative to the control group. The results showed that long-term dysfunction of the medial temporal lobe might reinforce alternative memory pathways and recruit a distributed cortical network ipsilateral to their epilepsy focus.