A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated.

BACKGROUND: The presence of psychiatric comorbidity in some neurological disorders is common. A bi-directional influence between some psychiatric and neurological disorders has been discussed, but not widely studied. There is an absence of literature on the typology and rates of neurology consultations in different types of psychiatric inpatients.
METHODS: Cross-sectional study based on real world data on patients who had a neurological consultation during hospitalization on a psychiatric ward.
RESULTS: The most frequent reasons for visits to neurologists in our study were cluster \'Epilepsy/other types of non-epileptic seizures\' (n = 177, 36.44%), followed by cluster \'Movement disorders\' (n = 77, 20.48%), \'Cognitive disorder\' (n = 69, 18.35%), and finally cluster \'Neuropathy\' (n = 21, 5.59%). The most frequent type of psychiatric patient who required neurologic consultation presented a psychotic disorder (n = 100, 26.60%), follow by problem behavior (n = 82, 21.81%), bipolar disorder (n = 78, 20.78%), depressive disorder (n = 42, 11.17%) and autism spectrum disorder (n = 20, 5.32%). We found a statistically significant relationship between (problem behavior and intellectual disability) and neurologic consultation for epilepsy/other types of non-epileptic seizures, and between (depressive disorder, bipolar disorder, autism spectrum disorder and intellectual disability) and neurologic consultation for movement disorders.
CONCLUSIONS: This is the first study in the literature which analyzes the rates and typology of neurologic consultations in people hospitalized with psychiatric disorders. A deep knowledge of epilepsy, movement disorders and cognitive disorders should be required for health professionals to treat psychiatric inpatients appropriately. Patients with particular psychiatric disorders seem to require a higher number of neurologic consultations than others during their hospitalization.
BACKGROUND: Comorbilidad neurológica en pacientes psiquiátricos ingresados: evidencia sobre interconsultas de neurología en un centro español.
Introducción. La presencia de comorbilidad psiquiátrica en algunos trastornos neurológicos es frecuente. Se ha discutido sobre una influencia bidireccional entre algunos trastornos psiquiátricos y neurológicos, pero este hecho no se ha estudiado ampliamente. Existe escasa información en la bibliografía sobre la tipología y la prevalencia de las interconsultas de neurología en los diferentes tipos de pacientes psiquiátricos hospitalizados. Materiales y métodos. Estudio transversal basado en datos reales sobre pacientes que necesitaron una interconsulta de neurología durante su hospitalización en salud mental. Resultados. Los motivos más frecuentes que requirieron una interconsulta de neurología en nuestro estudio fueron el clúster ‘Epilepsia/otros tipos de crisis no epilépticas’ (n = 177; 36,44%), seguido del clúster ‘Trastornos del movimiento’ (n = 77; 20,48%), el clúster ‘Trastorno cognitivo’ (n = 69; 18,35%) y, por último, el clúster ‘Neuropatía’ (n = 21; 5,9%). El tipo más frecuente de paciente psiquiátrico que requirió consulta neurológica presentó un trastorno psicótico (n = 100; 26,6%), seguido de problemas de conducta (n = 82; 21,81%), trastorno bipolar (n = 78; 20,78%), trastorno depresivo (n = 42; 11,17%) y trastorno del espectro autista (n = 20; 5,32%). Se encontró una relación estadísticamente significativa entre problemas de conducta y discapacidad intelectual e interconsulta de neurología por epilepsia/otros tipos de crisis no epilépticas, y entre trastorno depresivo, trastorno bipolar, trastorno del espectro autista y discapacidad intelectual e interconsulta de neurología por trastornos del movimiento. Conclusiones. Éste es el primer estudio en la bibliografía que analiza la frecuencia y la tipología de las interconsultas de neurología en personas hospitalizadas con trastornos psiquiátricos. Debe requerirse a los profesionales que traten a pacientes de salud mental hospitalizados un conocimiento profundo en epilepsia, trastornos del movimiento y trastornos cognitivos. Algunos pacientes con determinados trastornos psiquiátricos parecen necesitar un mayor número de interconsultas de neurología que otros durante su hospitalización.

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UNASSIGNED: Seizure is one of the neurologic manifestations of coronavirus disease 2019 (COVID-19) infection. There are few studies focused on the outcome of hospitalized patients with COVID-19 and seizure.
UNASSIGNED: This was a subgroup analysis of patients with seizure based on a nationwide, multicenter, retrospective study of COVID-19 patients admitted in 37 hospitals in the Philippines.
UNASSIGNED: A total of 10,881 patients with COVID-19 infection were included. Among these, 27 (0.2 %) patients had pre-existing seizure/epilepsy and 125 (1.1 %) had new-onset seizure. The patients with pre-existing seizure/epilepsy had a mean age of 49 years and majority were males (63.0 %). The patients with new-onset seizure had a mean age of 57 years and majority were males (60.5 %). Among patients with pre-existing seizure/epilepsy, there were no significant differences in the proportion of severe/critical COVID-19 (p = 0.131), all-cause mortality (p = 0.177), full/partial neurologic recovery (p = 0.190), ventilator use (p = 0.106), length of intensive care unit stay (p = 0.276), and length of hospitalization (p = 0.591). Patients with new-onset seizure were 2.65 times more likely to have severe/critical COVID-19 infection (p < 0.001), 3.12 times more likely to die (p < 0.001), and 3.51 times more likely to require a ventilator (p < 0.001) than those without new-onset seizure. New-onset seizure, however, was not significantly associated with full/partial neurologic recovery (p = 0.184) and prolonged length of hospitalization (p = 0.050).
UNASSIGNED: Severe/critical COVID-19 infection, higher mortality rate, and use of a ventilator were significantly higher among patients with new-onset seizure but not among patients with pre-existing seizure/epilepsy.

Epilepsy, is a serious neurological condition, characterized by recurring, unprovoked seizures and affects over 50 million people worldwide. Epilepsy has an equal prevalence in males and females, and occurs throughout the life span. Women with epilepsy (WWE) present with unique challenges due to the cyclical fluctuation of sex steroid hormone concentrations during their life course. These shifts in sex steroid hormones and their metabolites are intricately intertwined with seizure susceptibility and affect epilepsy during the life course of women in a complex manner. Here we present a review encompassing neurosteroids-steroids that act on the brain regardless of their site of synthesis in the body; the role of neurosteroids in women with epilepsy through their life-course; exogenous neurosteroid trials; and future research directions. The focus of this review is on progesterone and its derived neurosteroids, given the extensive basic research that supports their role in modulating neuronal excitability.

Diagnosing a non-epileptic seizure is difficult in the absence of a video electroencephalogram. The expert commission of the international league against epilepsy proposes a diagnostic approach allowing the diagnosis to be made according to a degree of certainty with or in the absence of a video electroencephalogram. Our objective was to determine the hospital frequency of psychogenic non-epileptic seizures in the absence of video-electroencephalogram. Using the outpatient registry, we identified patients followed for epilepsy with two normal interictal electroencephalographies, between January 2020 and October 2021. A review of the patients\' medical records and an assessment of the validity of the diagnosis were carried out. Out of 64 patients evaluated with normal interictal electroencephalogram, 19 were included as suffering from psychogenic non-epileptic seizures, i.e. 26.68%. The average age was 23.94 +/- 9.4 years. Women represented 68.4%. Patients followed in neurology represented 84%. A history of childhood trauma was found in (47.4%). The first crisis was preceded by stressful events in 47.36%. Post-traumatic stress disorder was the most represented with 73.7% of cases. The average age was 20.95 +/- 9.8 years for the first crisis and the average duration of evolution of the crises was 3 years +/- 2 years. This study illustrates the possibility of making a presumptive diagnosis of psychogenic non-epileptic seizure in the absence of video-electroencephalogram.

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive inherited syndrome with heterogeneous symptoms, which makes it a challenge for early diagnosis. The mutation of VPS13A is considered intimately related to the pathogenesis of ChAc. To date, diverse mutation patterns of VPS13A, consisting of missense, nonsense, and frameshift mutations, have been reported. In this study, we first report a clinical case that was misdiagnosed as epilepsy due to recurrent seizures accompanied by tongue bite for 9 months, which was not rectified until seizures were controlled and involuntary orolingual movements with awareness became prominent and were confirmed to be orolingual dyskinesia. The patient was eventually diagnosed as ChAc based on whole-exome sequencing revealing novel homozygous c.2061dup (frameshift mutation) and c.6796A > T dual mutations in VPS13A. The patient from a family with consanguineous marriage manifested epileptic seizures at onset, including both generalized tonic-clonic seizures and absence but normal long-term electroencephalography, and gradually developed orofacial dyskinesia, including involuntary tongue protrusion, tongue biting and ulcers, involuntary open jaws, occasionally frequent eye blinks, and head swings. The first test of the peripheral blood smear was negative, and repeated checks confirmed an elevated percentage of acanthocytes by 15-21.3%. Structural brain MRI indicated a mildly swollen left hippocampus and parahippocampal gyrus and a progressively decreased volume of the bilateral hippocampus 1 year later, along with atrophy of the head of the caudate nucleus but no progression in 1 year. We deeply analyzed the reasons for long-term misdiagnosis in an effort to achieve a more comprehensive understanding of ChAc, thus facilitating early diagnosis and treatment in future clinical practice.

UNASSIGNED: Quantitative maps obtained with diffusion weighted (DW) imaging, such as fractional anisotropy (FA) -calculated by fitting the diffusion tensor (DT) model to the data,-are very useful to study neurological diseases. To fit this map accurately, acquisition times of the order of several minutes are needed because many noncollinear DW volumes must be acquired to reduce directional biases. Deep learning (DL) can be used to reduce acquisition times by reducing the number of DW volumes. We already developed a DL network named \"one-minute FA,\" which uses 10 DW volumes to obtain FA maps, maintaining the same characteristics and clinical sensitivity of the FA maps calculated with the standard method using more volumes. Recent publications have indicated that it is possible to train DL networks and obtain FA maps even with 4 DW input volumes, far less than the minimum number of directions for the mathematical estimation of the DT.
UNASSIGNED: Here we investigated the impact of reducing the number of DW input volumes to 4 or 7, and evaluated the performance and clinical sensitivity of the corresponding DL networks trained to calculate FA, while comparing results also with those using our one-minute FA. Each network training was performed on the human connectome project open-access dataset that has a high resolution and many DW volumes, used to fit a ground truth FA. To evaluate the generalizability of each network, they were tested on two external clinical datasets, not seen during training, and acquired on different scanners with different protocols, as previously done.
UNASSIGNED: Using 4 or 7 DW volumes, it was possible to train DL networks to obtain FA maps with the same range of values as ground truth - map, only when using HCP test data; pathological sensitivity was lost when tested using the external clinical datasets: indeed in both cases, no consistent differences were found between patient groups. On the contrary, our \"one-minute FA\" did not suffer from the same problem.
UNASSIGNED: When developing DL networks for reduced acquisition times, the ability to generalize and to generate quantitative biomarkers that provide clinical sensitivity must be addressed.

Objectives: We recently introduced a frameless, navigated, robot-driven laser tool for depth electrode implantation as an alternative to frame-based procedures. This method has only been used in cadaver and non-recovery studies. This is the first study to test the robot-driven laser tool in an in vivo recovery animal study. Methods: A preoperative computed tomography (CT) scan was conducted to plan trajectories in sheep specimens. Burr hole craniotomies were performed using a frameless, navigated, robot-driven laser tool. Depth electrodes were implanted after cut-through detection was confirmed. The electrodes were cut at the skin level postoperatively. Postoperative imaging was performed to verify accuracy. Histopathological analysis was performed on the bone, dura, and cortex samples. Results: Fourteen depth electrodes were implanted in two sheep specimens. Anesthetic protocols did not show any intraoperative irregularities. One sheep was euthanized on the same day of the procedure while the other sheep remained alive for 1 week without neurological deficits. Postoperative MRI and CT showed no intracerebral bleeding, infarction, or unintended damage. The average bone thickness was 6.2 mm (range 4.1-8.0 mm). The angulation of the planned trajectories varied from 65.5° to 87.4°. The deviation of the entry point performed by the frameless laser beam ranged from 0.27 mm to 2.24 mm. The histopathological analysis did not reveal any damage associated with the laser beam. Conclusion: The novel robot-driven laser craniotomy tool showed promising results in this first in vivo recovery study. These findings indicate that laser craniotomies can be performed safely and that cut-through detection is reliable.

UNASSIGNED: Padsevonil is an antiseizure medication candidate intended to benefit patients with drug-resistant epilepsy. Our investigations aimed at characterizing pharmacokinetics and drug-drug-interaction (DDI) profile of padsevonil.
UNASSIGNED: An overview of preclinical and clinical pharmacology studies conducted during padsevonil development is provided.
UNASSIGNED: In preclinical studies, cytochrome (CYP) 3A4 was identified as the main P450 isoform involved in padsevonil metabolism, with potential minor contribution from CYP2C19. Padsevonil was shown to be a time-dependent CYP2C19-inhibitor, weak CYP3A4-inducer, weak inhibitor of P-gp/OCT1/MATE2-K, and potent OCT2-inhibitor. Initial clinical pharmacology studies in healthy participants showed that padsevonil had (i) good absorption, (ii) clearance mediated mainly by metabolism, and (iii) time-dependent kinetics. A study in genotyped participants confirmed the role of CYP2C19 in clearance and time-dependent kinetics; the major contribution of CYP3A4 was confirmed in DDI studies with CYP3A4-inducers (carbamazepine, oxcarbazepine) and -inhibitor (erythromycin). Padsevonil did not affect pharmacokinetics of valproate/lamotrigine/levetiracetam/oxcarbazepine or oral contraceptives. In a cocktail clinical study, padsevonil showed moderate CYP2C19 inhibition (omeprazole) and weak CYP3A4 induction (oral midazolam). No specific effects on CYP1A2 (caffeine), CYP2C9 (S-warfarin), and CYP2D6 (dextromethorphan) were observed.
UNASSIGNED: The studies presented helped in understanding padsevonil disposition and risks of DDIs, which would inform dosing and prescribing.
UNASSIGNED: https://www.clinicaltrials.gov/identifiers are NCT04131517, NCT03480243, NCT03695094, NCT04075409.