Dose Of Valproate Research Articles

Risk factors, clinical correlates, and social functions of Chinese schizophrenia patients with drug-induced parkinsonism: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study.

Background: Drug-induced parkinsonism (DIP) is the most prevalent neurological side effect of antipsychotics in the Chinese population. Early prevention, recognition, and treatment of DIP are important for the improvement of treatment outcomes and medication adherence of schizophrenia patients. However, the risk factors of DIP and the impact on the clinical syndromes of schizophrenia remain unknown. Aim: The goal of this study was to explore the risk factors, clinical correlates, and social functions of DIP in Chinese schizophrenia patients. Methods: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study of the Chinese schizophrenia population with a baseline assessment was conducted from the year 2012 to 2018. Participants were recruited from four mental health centers in Shanghai and totaled 969 subjects. Sociodemographic data, drug treatment, and clinical variables were compared between the DIP group and the non-DIP group. Variables that correlated with the induction of DIP, and with p≤ 0.1, were included in the binary logistic model for analyzing the risk factors of DIP. First generation antipsychotics (FGA)/second generation antipsychotics (SGA) model and high and low/medium D2 receptor antipsychotics were analyzed respectively to control the bias of co-linearity. All risk factors derived from the a forementioned models and clinical variables with p≤ 0.1 were included in the multivariate analysis of clinical correlates and social function of DIP patients. The Positive and Negative Syndrome Scale (PANSS) model and the personal and social performance (PSP) model were analyzed separately to control for co-linearity bias. Results: Age (OR = 1.03, p< 0.001), high D2 receptor antagonist antipsychotic dose (OR = 1.08, p = 0.032), and valproate dose (OR = 1.01, p = 0.001) were the risk factors of DIP. FGA doses were not a significant contributor to the induction of DIP. Psychiatric symptoms, including more severe negative symptoms (OR = 1.09, p< 0.001), lower cognition status (OR = 1.08, p = 0.033), and lower excited symptoms (OR = 0.91, p = 0.002), were significantly correlated with DIP induction. Social dysfunction, including reduction in socially useful activities (OR = 1.27, p = 0.004), lower self-care capabilities (OR = 1.53, p< 0.001), and milder disturbing and aggressive behavior (OR = 0.65, p< 0.001), were significantly correlated with induction of DIP. Valproate dose was significantly correlated with social dysfunction (OR = 1.01, p = 0.001) and psychiatric symptoms (OR = 1.01, p = 0.004) of DIP patients. Age may be a profound factor that affects not only the induction of DIP but also the severity of psychiatric symptoms (OR = 1.02, p< 0.001) and social functions (OR = 1.02, p< 0.001) of schizophrenia patients with DIP. Conclusion: Age, high D2 receptor antagonist antipsychotic dose, and valproate dose are risk factors for DIP, and DIP is significantly correlated with psychiatric symptoms and social performance of Chinese schizophrenia patients. The rational application or discontinuation of valproate is necessary. Old age is related to psychotic symptoms and social adaption in Chinese schizophrenic patients, and early intervention and treatment of DIP can improve the prognosis and social performance of schizophrenia patients. Clinical Trial Registration: Identifier: NCT02640911.

Genetic generalized epilepsy: factors associated with drug resistance polytherapy

BackgroundDifferent studies investigating generalized genetic epilepsy (GGE) have shown that achieving 5 years of remission, early seizure remission, and needing antiseizure medication (ASM) monotherapy may predict favorable long-term outcomes.ResultsThis is a retrospective analytical cohort study. Records of patients with GGE diagnoses at a large epilepsy center in Cairo served as the data source. 630 patients (297 male patients (47.1%) and 333 female (52.9%)) were included, their median onset age was 13 years. The follow-up period of this study was at least 4 years. 418 patients (66.1%) were early remitters, 160 patients (25.4%) were late remitters, and 52 patients (8.3%) were intractable. In addition, 367 patients (58.3%) needed a single ASM to achieve a maximum remission period (monotherapy group), while 263 patients (41.7%) needed ASM polytherapy. Stepwise regression analysis revealed that absence seizures, clusters of seizures, seizure frequency before treatment, and dose of sodium valproate (VPA) until the first remission were independent predictors for polytherapy. Moreover, absence seizures, seizure frequency before treatment, VPA dose, and catamenial seizures in females were independent predictors of intractability.ConclusionThe majority of GGE have a favorable outcome, some clinical features could predict the need for polytherapy and failure of remission on treatment.

Lamotrigine (Sazar) in the treatment of epilepsy: four years of experience in Svt. Luka's Association of Medical institutions for the Diagnosis, Treatment, and Rehabilitation of Nervous System Diseases and Epilepsy

Aim. To assess the efficacy and tolerability of lamotrigine (Sazar) for various forms of epilepsy, based on long-term experience of Svt. Luka's Association of Medical Institutions for the Diagnosis, Treatment, and Rehabilitation of Nervous System Diseases and Epilepsy. We analyzed the data obtained during 4 years (from June 2018 to August 2022).Materials and methods. We evaluated the efficacy and tolerability of Sazar in 104 patients aged 3 to 37 years (87 children and 17 adults (12 women and 5 men)); their mean age was 9.7 years. The sample included 42 males and 62 females. All of them were treated at Svt. Luka's Association of Medical Institutions for the Diagnosis, Treatment, and Rehabilitation of Nervous System Diseases and Epilepsy.The sample included patients with structural and presumably structural focal epilepsy (n = 44), focal epilepsy of unknown etiology (n = 6), genetic and presumably genetic epilepsy and epileptic encephalopathies (n = 43), idiopathic epilepsy (n = 11).Sazar was used as a monotherapy in 38 patients, whereas 66 patients received it in combination with other antiepileptic drugs (AED) (Sazar + 1 AED in 48 patients; Sazar + 2 AED in 18 patients). Two patients initially receiving polytherapy were successfully transferred to Sazar monotherapy.The dose of Sazar varied between 75 and 400 mg/day. In the majority of patients, including all children, Sazar daily dose was split into 2 portions. Three adult patients received Cazar once a day either in the evening (n = 2) or in the morning (n = 1) at a dose of 200 mg/day. The follow-up time was between 6 months and over 4 years.Results and conclusion. Therapeutic remission was achieved in 47 out of 104 patients (45.2 %) receiving Sazar. As many as 35 patients (33.6 %) demonstrated an at least 50 % reduction in seizure frequency; 22 patients had no effect (21.2 %). None of the participants developed significant aggravation.Only 9 patients (8.6 %) discontinued Caser due to its initial low efficacy, while another 8 patients (7.6 %) stopped to receive Casar because it became ineffective after 6–12 months of treatment. In general, good therapeutic effect (remission or at least 50 % reduction in seizure frequency) was achieved in 82 out of 104 patients (78.8 %). Given the fact that this study included patients with severe epilepsy, we can conclude that treatment was very effective.Casar was most effective in patients with focal epilepsy (including structural, presumably structural, structural-genetic, and that of unidentified etiology) and idiopathic generalized epilepsy.The majority of the patients (n = 94; 90.4 %) demonstrated good tolerability of Casar. Casar-associated side effects were registered in 10 patients (9.6 %). Allergic skin rash was observed in 5 cases (4.8 %) and developed during the first 2 months of therapy. Allergic reactions accounted for 50 % of all side effects and were the only reason for Casar discontinuation due to poor tolerability.Two female patients of reproductive age started Sazar to reduce the valproate dose that caused severe menstrual disorders, weight gain, alopecia, and edema. Halving the dose of valproate (up to 750 mg/day) in combination with Casar significantly improved treatment tolerance. One patient gave birth to a healthy baby when she was receiving monotherapy with Sazar at a dose of 350 mg/day.Eight patients receiving Sazar reported a significant improvement in their mood and behavior (one patient that had earlier been diagnosed with depression discontinued antidepressants after Sazar initiation since she did not need them any longer). None of the patients reported any negative effects of Sazar on their memory, attention, mood, and behavior (as evaluated by patients and parents; in some cases, by a neuropsychologist).Patients’ adherence to treatment confirmed high Sazar efficacy and tolerability: 82 out of 104 patients (78.8 %) continued to receive the drug after 6 months of treatment and 69 patients (66.3 %) still continued it after 12 months of treatment. The follow-up period varied between 6 months and 4 years.Thus, our findings suggest high efficacy and good tolerability of long-term therapy with Sazar in patients with different forms of epilepsy.

Vestibular function in children with generalized epilepsy and treated with valproate

ABSTRACT Background Studies that evaluated vestibular function with epilepsy are fewer than auditory studies. We assessed vestibular function in children with epilepsy in inter-ictal period. Research design and methods This cross-sectional study included 35 children with generalized epilepsy (boys=15; girls=20; age=11.20±1.21 years; epilepsy duration=3.54±1.80 years) and treated with valproate (VPA) and 24 healthy children. Vestibular evaluation was conducted using videonystagmography (VNG) and cervical vestibular evoked myogenic potentials (cVEMPs). Results Dizziness was the vestibular symptom in 22.86% of cases. Vestibular dysfunctions (VDs) were found in 65.71%. Manifestations of peripheral VD (65.71%) included unilateral caloric weakness and reduced cVEMP amplitudes. Manifestations of central VD (28.57%) included oculomotor abnormalities, positional nystagmus with normal calorics, and prolonged cVEMPs latencies. Significant correlations were found between VDs and duration of epilepsy and its treatment [r = −0.368, P=0.01] and VPA dose [r = −0.286, P=0.02] and level [r = −0.355, P=0.01]. Logistic regression analysis showed that duration of epilepsy and its treatment [OR = 3.55 (95% CI = 2.54–6.50), P=0.001] were independently associated with VDs. Conclusions VDs are common in children with epilepsy. Bilateral peripheral VD was more common than central VD, suggesting an adverse effect of VPA. However, epilepsy cannot be excluded as a cause of central VD.

Valproate Targets Mammalian Gastrulation Impairing Neural Tissue Differentiation and Development of the Placental Source In Vitro.

The teratogenic activity of valproate (VPA), an antiepileptic and an inhibitor of histone deacetylase (HDACi), is dose-dependent in humans. Previous results showed that VPA impairs in vitro development and neural differentiation of the gastrulating embryo proper. We aimed to investigate the impact of a lower VPA dose in vitro and whether this effect is retained in transplants in vivo. Rat embryos proper (E9.5) and ectoplacental cones were separately cultivated at the air-liquid interface with or without 1 mM VPA. Embryos were additionally cultivated with HDACi Trichostatin A (TSA), while some cultures were syngeneically transplanted under the kidney capsule for 14 days. Embryos were subjected to routine histology, immunohistochemistry, Western blotting and pyrosequencing. The overall growth of VPA-treated embryos in vitro was significantly impaired. However, no differences in the apoptosis or proliferation index were found. Incidence of the neural tissue was lower in VPA-treated embryos than in controls. TSA also impaired growth and neural differentiation in vitro. VPA-treated embryos and their subsequent transplants expressed a marker of undifferentiated neural cells compared to controls where neural differentiation markers were expressed. VPA increased the acetylation of histones. Our results point to gastrulation as a sensitive period for neurodevelopmental impairment caused by VPA.

Supercritical solvent impregnation of sodium valproate nanoparticles on polymers: Characterization and optimization of the operational parameters

To improve the bioavailability and reduce the therapeutic dose and side effects of Sodium valproate (S-VPA), nanoparticles of this drug were loaded on the polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) polymers via the supercritical solvent impregnation (SSI) process. This process was carried out at different pressures (150–250 bar), temperatures (308–328 K), and impregnation times (60–180 min). The Box–Behnken design (BBD) method was applied to study the effect of operational parameters on the S-VPA/PVP and S-VPA/HPMC loadings and optimize the condition. Maximum loadings on both PVP (1.56%) and HPMC (1.5%) were achieved at 250 bar, 318 K, and 180 min. Moreover, the impregnated samples (S-VPA/PVP and S-VPA/HPMC) were investigated by the FTIR, DSC, SEM, DLS, and XRD analysis. The S-VPA nanoparticles with the mean particle size of 27 nm and 128 nm were uniformly impregnated on the PVP and HPMC polymers, respectively. The results confirmed the lower crystallinity of the impregnated S-VPA nanoparticles, leading to their higher solubility and bioavailability. Finally, Enhanced S-VPA solubility was approved by comparing the dissolution rate of the original and the impregnated S-VPA samples in the optimum conditions.

Seizure medication and planned pregnancy: balancing the risks and outcomes

ABSTRACT Introduction The therapeutic management of women with epilepsy (WWE) of childbearing age can be complicated by the need to balance maternal/fetal risks related to seizure occurrence during gestation with the potential teratogenic risks related to the use of anti-seizure medications (ASMs). Areas covered The authors review clinical evidence on seizure-related and ASM-related risks during pregnancy. Current regulatory indications are discussed, evaluating their impact on clinical practice, and ethical implications of pharmacological decisions are debated. Expert opinion If properly informed about the maternal/fetal risks carried by different pharmacological choices, WWE can become the final decision makers regarding their care in every phase of their life. Over the coming years, analysis of aggregated pregnancy registry data on the structural impact, on the fetus, of low doses of valproate and of newer ASMs, together with analysis of the main population study data on functional (cognitive and behavioral) outcomes, could lead to huge advances, making choosing an ASM a less complex process for the clinician and a less painful decision for the woman. Future objectives should include identification of the potential role of the pharmacogenomic profile of WWE in determining the risk of fetal malformations.

Dried Blood Spots as Matrix for Evaluation of Valproate Levels and the Immediate and Delayed Metabolomic Changes Induced by Single Valproate Dose Treatment

The immediate and delayed metabolic changes in rats treated with valproate (VPA), a drug used for the treatment of epilepsy, were profiled. An established approach using dried blood spots (DBS) as sample matrices for gas chromatography/mass spectrometry-based metabolomics profiling was modified using double solvents in the extraction of analytes. With the modified method, some of the previously undetectable metabolites were recovered and subtle differences in the metabolic changes upon exposure to a single dose of VPA between males and female rats were identified. In male rats, changes in 2-hydroxybutyric acid, pipecolic acid, tetratriacontane and stearic acid were found between the control and treatment groups at various time points from 2.5 h up to 24 h. In contrast, such differences were not observed in female rats, which could be caused by the vast inter-individual variations in metabolite levels within the female group. Based on the measured DBS drug concentrations, clearance and apparent volume of distribution of VPA were estimated and the values were found to be comparable to those estimated previously from full blood drug concentrations. The current study indicated that DBS is a powerful tool to monitor drug levels and metabolic changes in response to drug treatment.

Hematological Consequences of Valproic Acid in Pediatric Patients: A Systematic Review with a Mechanistic Approach.

Although Valproate (VPA) has several advantages in controlling seizures, it may cause serious hematological consequences. Hematotoxicity of VPA is particularly important in pediatrics because patients at this age are at a growing risk of leukemia. For a conclusive agreement about the toxicity of VPA, in this study, we systematically reviewed the literature in which the hematological consequences of VPA had been emphasized. A systematic literature search was performed in June 2021 on electronic databases to find original research on the association between VPA therapy and hematotoxicity in pediatric patients. For this purpose, the following search terms "hematotoxicity", "valproic acid" and "pediatrics" with different spellings and similar terms, were searched in the title, keywords, and abstracts of articles. The data were collected and used for qualitative data description. A total of 36 relevant articles with an overall 1381 study population were included. The results showed that VPA could cause severe hematotoxicity in children even at therapeutic doses. Neutropenia, thrombocytopenia, and bone marrow depression are the most common complications associated with VPA therapy. Also, findings showed that after discontinuation of VPA and starting other antiepileptic drugs or reducing the administered VPA dose, hematologic damages were entirely resolved, and all the hematological parameters improved during two weeks. This review showed that VPA therapy could cause hematotoxicity in children; hence, it is recommended to monitor hematological indices during VPA therapy. Also, according to the suggested mechanistic pathways of VPA side effects, a combination of VPA with antioxidants may reduce hematological side effects.

Clinical Evaluation of Levetiracetam in the Treatment of Epilepsy.

Objectives Epilepsy is a chronic neurological disorder that is characterized by episodes of seizure. Methods In this study, patients with status epilepticus in the Intensive Care Unit of the Department of Neurology of Qujing First People's Hospital were collected and treated with levetiracetam injection, continuous bedside EEG monitoring (cEEG) technology, and quantitative EEG (qEEG) technique. The inhibitory effects of different doses of levetiracetam injection and sodium valproate on abnormal discharge, the improvement of clinical symptoms, the incidence of adverse reactions, and prognosis were monitored, analyzed, and compared. Results Compared with the experimental group of sodium valproate, 1000 mg/d levetiracetam group and 1500 mg/d levetiracetam group had a high probability of successful symptom control and a short control time. The patients had a low recurrence rate and a long recurrence time, and the probability of abnormal discharge in EEG was low. Conclusions The recording results showed that levetiracetam could significantly inhibit the abnormal discharge of patients. Compared with sodium valproate, high-dose levetiracetam is a drug with a rapid effect, good effect, and long action time.

Achieving neurologically desirable outcomes to pregnancy in women with epilepsy

ObjectivesTo investigate possible factors that influenced whether pregnancy in women with epilepsy resulted in the desirable outcome of a live-born non-malformed infant and a mother whose pregnancy had been seizure free. ResultsThe desirable outcome, as defined, occurred in 46.3% of unselected pregnancies in the database of the Australian Register of Antiepileptic Drugs in Pregnancy (APR). The only factor investigated that had a statistically significant (P < 0.05) effect, increasing the chance of such a desirable outcome, was freedom from seizures in the pre-pregnancy year. However, anti-seizure medication (ASM) doses, particularly valproate doses, had been reduced prior to 15.6% of the pregnancies, and this may have concealed factors that otherwise may have adversely affected the desirable outcome rate. Analysis of data for monotherapy with the more commonly used ASMs appears to suggest that employing levetiracetam at the outset of antiseizure therapy may offer a better chance of a desirable outcome to future pregnancies than monotherapy with other ASMs, but this finding is not confirmed statistically. ConclusionsIn pregnancies where valproate use has already been minimized, seizure control throughout the pre-pregnancy year was associated with the best chance of a desirable outcome, as defined above. In most Australian women starting therapy for epilepsy initiating treatment with levetiracetam monotherapy may offer the best chance of such a desirable outcome to a future pregnancy, yet to be confirmed.

The effect of erythromycin and clarithromycin versus azithromycin on serum valproate concentration

IntroductionUnlike azithromycin, erythromycin and clarithromycin strongly inhibit CYP450, which metabolizes valproic acid. The aim of this study was to evaluate the impact of macrolide administration on serum valproate trough levels. MethodsThis retrospective cohort study included hospitalized adult patients who concomitantly received valproate with a macrolide. Patients who received a carbapenem, those who do not have a baseline and/or post-levels, and those who received different doses of valproate were excluded. The change in serum valproate trough level from baseline to after the occurrence of co-administration (post-level) was compared in patients who received either erythromycin or clarithromycin versus those who received azithromycin. ResultsA total of thirteen patients were included in the comparison. The mean ± SD for change in serum valproate trough levels was significantly higher in the erythromycin/clarithromycin group than the azithromycin group (209.1 ± 105.9 µmol/L [equivalent to 30.1 ± 15.2 mg/L] vs. 12.7 ± 52.1 µmol/L [equivalent to 1.8 ± 7.5 mg/L]; P = 0.002). ConclusionThis study found a significantly higher increase in serum trough levels of valproate after co-administration of erythromycin/clarithromycin versus azithromycin. Clinicians should consider avoiding co-administration of erythromycin and clarithromycin with valproate if possible or close monitoring of valproate levels with dose reduction.

Correlation studies on pathological changes in brain with neurotransmitters and behavioural changes in Balb/c mice

Aim: To determine the plasma neurotransmitters simultaneously and to find any correlation with pathological changes in the hippocampus and Purkinje cells and their relation with behavioral changes in Balb/c mice. Methodology: In the present study, both sexes of Balb /C mice were divided into two groups (4 males and 4 females; n = 8): Both the groups were given a single dose of either saline or sodium valproate (400mg kg-1) respectively through subcutaneous injection on PND 14. Behavioural tests were conducted on mice pups on various postnatal days till 40th day. On PND 41, blood samples were collected from all the animals for quantification of the neurotransmitters (serotonin, dopamine, and noradrenalin) in plasma, animals were sacrificed by cervical dislocation and whole brain was isolated for histological examination of the Purkinje cells and hippocampus. Results: Sodium valproate exposed animals showed loss of motor skill development (delayed negative geotaxic response), increased locomotor activity, increased anxiety, and retardation in water maze performance, and lower social interaction. Histopathological evolutions of cerebellum purkinje cells and hippocampus showed 40-50% atrophic cells in sodium valproate animals compared to control animals. Interpretation: The results of the present study indicate that Sodium valproate changes specific brain cell population in Balb/C mice, which might be the reason for the altered neurotransmitter levels, leading to behavioural changes in these animals.

Efficacy of levetiracetam, lamotrigine and sodium valproate on seizure attacks and EEG disorders in patients with juvenile myoclonic epilepsy: A double blind randomized clinical trial.

Background:Juvenile myoclonic epilepsy (JME) is one of the most important types of generalized idiopathic epilepsy. Patients generally respond quickly and perfectly to standard antiepileptic drugs but lifelong medication is necessary. Sodium valproate is the drug of choice in most references but it has some adverse reactions and some patients cannot tolerate the complications. Because of the need for life long treatment in this young aged group particularly child bearing women, we aimed to analyze the efficacy of these drugs to determine which has better efficacy with lower adverse effects.Methods:In this double-blind clinical trial 102 patients suffering from juvenile myoclonic epilepsy were randomly divided to three groups and treated with valproate, levetiracetam or lamotrigine and followed for 12 months at specified intervals.Results:Patients' mean age was 22.8 years and 28.4% of them were males and 71.6% were females. Effective terminal dose of sodium valproate, levetiracetam and lamotrigine were 1000, 1000 and 250mg, respectively. The rate of failure in controlling seizures and myoclonic jerks in lamotrigine group was meaningfully more than levetiracetam and sodium valproate (P=0.037).The general side effects of sodium valproate were much more; but there was not any significant difference between their effects on electroencephalogram (EEG) findings (P=0.81).Conclusion: Levetiracetam and sodium valproate have similar efficacy. But in the group of lamotrigine, rate of failure, myoclonus and drug adverse reactions were meaningfully more than sodium valproate and levetiracetam. According to our study, lamotrigine could not be a suitable treatment option for JME patients as a mono therapy. Levetiracetam can be a good alternative to sodium valproate, especially in women of childbearing age.

Analysis of gut microbiota in patients with epilepsy treated with valproate: Results from a three months observational prospective cohort study

BackgroundGrowing evidence implicates the potential effect of microbiota on the pathogenesis and course of epilepsy. However, the effects of valproate (VPA), a broad spectrum anti-epileptic drugs, on gut microbiota have not been investigated in humans. This study aimed to analyze fecal microbiota in patients with epilepsy treated with valproate. MethodsA total of 10 participants, who were newly diagnosed of cryptogenic epilepsy with treatment naïve and received 1000 mg daily doses of VPA, were recruited in our prospective study. Microbiota compositions were evaluated at baseline and after three months of VPA treatment using 16S rDNA sequencing. ResultsVPA treatment was associated with clinical improvements in all patients, but not changes in gut microbiota richness and complexity (Shannon: p = 0.82). Microbiome composition structure differences also revealed no statistical difference in dissimilarity (Adonis: p = 0.90). No statistical difference taxa were found between two groups. However, the ratio of phyla Firmicutes to Bacteriodetes (ANOVA: p = 0.037) markedly raised after three months of VPA-treatment. A correlation matrix based on the spearman correlation distance confirmed associations between specific fecal taxa and VPA-related clinical metabolic parameters, including drug concentration in the blood, total cholesterol, triglyceride, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase and weight gain. (p < 0.05) ConclusionsAmong those patients treated with VPA, characterization of the gut microbiota altered, and gut microbiota associated with weight gain and clinical biochemical indexes, suggesting that microbiome composition data might involve in the mechanisms of VPA induced metabolic disorder.

Pharmacological and non-pharmacological management of spinocerebellar ataxia: A systematic review.

Spinocerebellar ataxias (SCA) comprise a rare, genetic subgroup within the degenerative ataxias and are dominantly inherited, with up to 48 recognized genetic subtypes. While an updated review on the management of degenerative ataxia is published recently, an evidence-based review focussed on the management of SCA is lacking. Here, we reviewed the pharmacological and non-pharmacological management of SCA by conducting a systematic review on Medline Ovid and Scopus. Of 29,284 studies identified, 47 studies (pharmacological: n = 25; non-pharmacological: n = 22) that predominantly involved SCA patients were included. Twenty studies had a high risk of bias based on the Cochrane's Collaboration risk of bias tool. As per the European Federation of Neurological Societies 2004 guideline for therapeutic intervention, the remaining 27 studies were of Class I (n = 4) and Class II (n = 23) evidence. Only two therapies had Level A recommendations for the management of ataxia symptoms: riluzole and immediate in-patient neurorehabilitation. Ten therapies had Level B recommendations for managing ataxia symptoms and require further investigations with better study design. These include high dose valproate acid, branched-chain amino acid, intravenous trehalose; restorative rehabilitation using cycling regimen and videogame; and cerebellar stimulations using transcranial direct current stimulation and transcranial magnetic stimulation. Lithium and coaching on psychological adjustment received Level B recommendation for depressive symptoms and quality of life, respectively. Heterogeneous study designs, different genotypes, and non-standardized clinical measures alongside short duration and small sample sizes may hamper meaningful clinical translation. Therefore, rating of recommendations only serve as points of reference.

Malformation risk of new anti-epileptic drugs in women with epilepsy; observational data from the Kerala registry of epilepsy and pregnancy (KREP)

Objectives: We aim to report the major congenital malformation (MCM) rates for new and old anti-epileptic drugs (AED) exposures during the first trimester of pregnancy in women with epilepsy (WWE). Methods: We extracted relevant data on drug exposure and malformation rate from the records of a prospective observational registry (Kerala Registry of Epilepsy and Pregnancy) for all completed pregnancies between 1998 and 2019. A comprehensive and uniform criterion with detailed guideline was used for assessment of malformations. We employed generalised linear model to generate adjusted incidence rate ratios (aIRR) of MCM in AED exposed group as compared to AED unexposed group, after adjustment for age and educational status of mothers’ and epilepsy classification. Results: The unadjusted MCM rate was 6.2% for all the infants included in the study (148/2328); 4.7% for the unexposed group (16/340), and 6.6% for the exposed group (132/1988). The aIRR of MCM as compared to unexposed group was similar for all monotherapies; lamotrigine (0.50; 95% CI 0.07–3.68), levetiracetam (1.16; 0.43–3.11), oxcarbazepine (1.61; 0.62–4.21) valproate (1.71, 0.93–3.19), phenytoin (1.21, 0.51–2.90), carbamazepine (0.99, 0.54–1.82), and phenobarbitone (1.20, 0.52–2.74). However, the point estimates suggest least risk with lamotrigine and highest risk with valproate. Polytherapy with high-dose valproate carried significantly higher risk of MCM as compared to the unexposed group (aIRR=4.12; 2.18–7.79, p<0.001). The aIRR of GTCS during pregnancy was 1.63 (95% CI 1.12–2.37, p = 0.011) for monotherapy with new AEDs (lamotrigine, levetiracetam or oxcarbazepine) as compared to old AEDs (phenobarbitone, phenytoin, carbamazepine, or valproate). Conclusion: The MCM risk was significantly higher for polytherapy with high dose valproate. It did not differ substantially between different AED monotherapies although point estimate was lowest with lamotrigine. Pregnant women on new AEDs report higher likelihood of GTCS than women on old AEDs during pregnancy.

Treatment resistance in bipolar affective disorder with recurrent mania course-Role of periventricular leukomalacia.

A 34-year-old married female, educated up to grade 12, living as a homemaker in an urban area, presented to us for a clinical evaluation with a four-day history of manic symptoms along with auditory hallucinations and delusions of being pregnant. She had developed symptoms despite adherence to therapeutic doses of lithium, valproate, and quetiapine. She scored 27 on the Young Mania Rating Scale (YMRS) at the time of presentation. The evaluation included a detailed history, laboratory investigations, and neuroimaging of the brain.

Decreased fetal heart rate variability and maternal combined dose of sodium valproate and phenytoin.

A 32-year-old Japanese woman was admitted at 38 weeks' gestation with regular uterine contractions. She was diagnosed with frontal lobe epilepsy at the age of 17, and she had been treated with several anti-epileptic drugs (AEDs) since then but complied poorly due mainly to nausea and frequent seizure attacks.

Serotonin Syndrome Induced by a Single Dose of Venlafaxine and Magnesium Valproate.

Serotonin Syndrome Induced by a Single Dose of Venlafaxine and Magnesium Valproate.