Valproate Treatment Research Articles

Valproic-induced Fanconi syndrome: Clinical features, risk factors, diagnosis and management.

ObjectiveAlthough Fanconi syndrome (FS) induced by valproate (VPA) has occasionally been reported, the detailed clinical features of the disease remain unclear. The aim of this study was to elucidate the clinical features of patients with VPA-induced FS.MethodsWe searched Chinese and English databases for all original studies, clinical reports, and case reports on VPA-induced FS published before March 2022.ResultsA total of 29 articles including 54 patients (28 males and 24 females) were included. The patients had a median age of 7 years (range 2–34 years), had severely disabled (87.0%), tube feeding (64.8%), and received an average of 1.8 medications other than VPA. The median duration of VPA treatment was 4 years (range 0.7–15.5). Pathological fractures (25.9%), unexplained fever (11.1%), muscle weakness (9.3%), and edema (9.3%) were the most common symptoms, while 18 patients were diagnosed in incidental laboratory tests. Blood tests revealed hypokalemia (69.2%), hypophosphatemia (98.0%), and hypouricemia (93.3%). Urinalysis revealed glucosuria (96.1%), proteinuria (100.0%), generalized hyperaminoaciduria (100.0 %), β2 macroglobulin (100.0%). Decreased percent total reabsorption of phosphate (%TRP) found in 94.1% of patients, and increased fractional excretion of uric acid (FEUA) were found in 100% of patients. The median time to resolution of FS after discontinuation of drug therapy was 3 months (range 0.25–18).ConclusionsThe possibility of FS needs to be considered with long-term VPA administration, especially in young, tube-fed, severely disabled patients who are co-administered with anticonvulsants. Patients receiving VPA should have regular blood and urine tests. Abnormal laboratory values returned to normal levels after VPA discontinuation.

Integrative genomics reveals pathogenic mediator of valproate-induced neurodevelopmental disability.

Prenatal exposure to the anti-seizure medication sodium valproate (VPA) is associated with an increased risk of adverse postnatal neurodevelopmental outcomes, including lowered intellectual ability, autism spectrum disorder and attention-deficit hyperactivity disorder. In this study, we aimed to clarify the molecular mechanisms underpinning the neurodevelopmental consequences of gestational VPA exposure using integrative genomics. We assessed the effect of gestational VPA on foetal brain gene expression using a validated rat model of valproate teratogenicity that mimics the human scenario of chronic oral valproate treatment during pregnancy at doses that are therapeutically relevant to the treatment of epilepsy. Two different rat strains were studied-inbred Genetic Absence Epilepsy Rats from Strasbourg, a model of genetic generalized epilepsy, and inbred non-epileptic control rats. Female rats were fed standard chow or VPA mixed in standard chow for 2 weeks prior to conception and then mated with same-strain males. In the VPA-exposed rats maternal oral treatment was continued throughout pregnancy. Foetuses were extracted via C-section on gestational Day 21 (1 day prior to birth) and foetal brains were snap-frozen and genome-wide gene expression data generated. We found that gestational VPA exposure via chronic maternal oral dosing was associated with substantial drug-induced differential gene expression in the pup brains, including dysregulated splicing, and observed that this occurred in the absence of evidence for significant neuronal gain or loss. The functional consequences of VPA-induced gene expression were explored using pathway analysis and integration with genetic risk data for psychiatric disease and behavioural traits. The set of genes downregulated by VPA in the pup brains were significantly enriched for pathways related to neurodevelopment and synaptic function and significantly enriched for heritability to human intelligence, schizophrenia and bipolar disorder. Our results provide a mechanistic link between chronic foetal VPA exposure and neurodevelopmental disability mediated by VPA-induced transcriptional dysregulation.

Investigation into Antiepileptic Effect of Ganoderic Acid A and Its Mechanism in Seizure Rats Induced by Pentylenetetrazole.

Ganoderic acid A (GAA) exhibited neuron protection in in vitro epilepsy study, but no study has been done in vivo. Rats were administered (i.p.) pentylenetetrazole daily for 28 days to induce seizure. Rats with grade II or above of epileptic score were divided into three groups and given placebo, sodium valproate, or GAA treatment, respectively, for 7 days. The electrical signals of brain were monitored with electroencephalography (EGG); epileptic behavior was assessed using the Racine scale; morphological changes and apoptosis rate of cortical neurons were assessed with H&E staining and TUNEL staining, respectively. Protein expression of calcium-sensing receptor, p-ERK, p-JNK, and p-p38 in hippocampal tissue and Bcl-2, cleaved caspase-3, and Bax in cortical tissues was observed by Western blot and immunohistochemistry assay, respectively. After GAA treatment, apparent seizure-like EEG with significant arrhythmic disorder and spike waves was reduced or disappeared, and wave amplitude of EEG was reduced significantly. GAA showed similar effect with sodium valproate treatments on epilepsy. There were an apparent improvement of the epileptic behavior and a significant increase in the epileptic latency and shortening of the epileptic duration in the treatment group compared to control. GAA treatment ameliorated the nuclear pyknosis of neurons which appeared seriously in the epilepsy group. GAA treatment significantly reduced the cortical neuron apoptosis of epilepsy and the expression of calcium-sensing receptor, p-P38, p-JNK, cleaved caspase-3, and Bax but increased the expression of both p-ERK and Bcl-2. In conclusion, GAA treatment showed strong antiepileptic effect by decreasing apoptosis in cortical neuron and the expression of calcium-sensing receptor and stimulating the MAPK pathway.

A Longitudinal Study of the Association between the LEPR Polymorphism and Treatment Response in Patients with Bipolar Disorder.

Patients with bipolar disorder (BD) exhibit individual variability in the treatment outcome, and genetic background could contribute to BD itself and the treatment outcome. Leptin levels significantly change in BD patients treated with valproate (VPA), but whether LEPR polymorphisms are associated with treatment response is still unknown. This longitudinal study aimed to investigate the associations between LEPR polymorphisms and VPA treatment response in BD patients who were drug naïve at their first diagnosis of BD. The single-nucleotide polymorphisms (SNPs) of LEPR (rs1137101, rs1137100, rs8179183, and rs12145690) were assayed, and the LEPR polymorphism frequencies of alleles and genotypes were not significantly different between the controls (n = 77) and BD patients (n = 130). In addition, after the 12-week course of VPA treatment in BD patients, the LEPR polymorphisms showed significant effects on changes in disease severity. Moreover, considering the effect of the LEPR haplotype, the frequency of the CAGG haplotype in BD patients was higher than that in the controls (9.3 vs. 2.9%, p = 0.016), and the LEPR CAGG haplotype was associated with a better treatment response than the other haplotypes in BD patients receiving VPA treatment. Therefore, LEPR polymorphisms might serve as mediators involved in the therapeutic action of VPA treatment.

What are the effects of taking 300 pills of sodium valproate? - case report

INTRODUCTION: Sodium valproate is one of the most important antiepileptic drugs. It can be effective as a preventive treatment for migraine, it has also found use in the maintenance treatment of bipolar disorder and acute mania,it is sometimes used in the treatment of chronic neuropathic pain and fibromyalgia, in the treatment of schizophrenia borderline personality disorder and acquired brain injury, this drug is used off-label. Its overdose can be fatal.
 MATERIALS AND METHOD: Patient information was collected from hospital records available in the clinical toxicology department. In addition, we conducted a literature review on sodium valproate treatment, its toxicity, side effects and pharmacokinetics using PubMed.
 CASE REPORT: A 57-year-old patient with a history of depressive disorders was admitted to the Clinical Department of Toxicology and Cardiology in Lublin for intentional intoxication with the drug Absenor (sodium valproate). The patient had taken 3 packages of Absenor 500 mg (300 tablets in total) for suicidal purposes. The determined concentration of valproic acid was 841 µg/ml, and the patient's condition was very severe. Despite the treatment administered-multiple attempts at gastric lavage, administration of activated charcoal, performance of hemodialysis procedures, administration of infusion of catecholamines, the patient died on the fifth day of hospitalization.
 CONCLUSION: An overdose of sodium valproate can be fatal. Keep this in mind when ordering this drug for patients with a positive history of suicide attempts.

Effects of magnesium valproate adjuvant therapy on patients with dementia: A systematic review and meta-analysis.

Background:Current research has found contradictory results on the treatment of magnesium valproate (VPM) in patients with dementia (PwD).Objectives:Here, we conducted a meta-analysis to evaluate the efficacy and safety of VPM in the adjuvant treatment of PwD.Purpose:Current research has found contradictory results on the treatment of VPM in PwD. Here, we conducted a meta-analysis to evaluate the efficacy and safety of VPM in the adjuvant treatment of PwD.Methods:MEDLINE via PubMed, Cochrane Library, EBSCO, Embase, China National Knowledge (CNKI), and Wan Fang databases were researched to gather relevant data on magnesium valproate assistant therapy for patients with dementia (PwD) by using medical subject headings and term words.Results:After the final screening, 22 RCT studies (a total of 1899 participants) were included in this meta-analysis, which compared VPM adjuvant treatment with antidementia or psychotropic drug monotherapy. Significant differences were found in the scores on mini-mental state examination (P = .028), Alzheimer disease assessment scale cognitive subscale (P < .05), Bech-Rafaelsen Mania Rating Scale (P < .05), behavioral pathology in Alzheimer disease rating scale (P = .001), activities of daily living (P < .05), and Pittsburgh Sleep Quality Index (P < .05). Besides, the levels of inflammatory factors including IL-1β, IL-6, and TNF-α were significantly lower than those in the monotherapy group (P < .05). While there was no increase in the incidence of adverse events (P = .383), VPM as an assistant therapy is generally well tolerated in PwD.Conclusion:By meta-analysis, evidence was found to support VPM additional used for the treatment of cognitive function, psychiatric symptoms, or disease improvement in PwD. VPM may be a potential drug to aid in the treatment of dementia patients. However, there was lack of enough evidence to classification of dementia severity in our inclusion study. More research is still needed, including clinical trials evaluating VPM as a complementary therapy.

Risk factors and outcome of hyperammonaemia in people with epilepsy

BackgroundHyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear.ObjectiveTo identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes.MethodsWe carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 μmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia.ResultsWe reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment.ConclusionsDrug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.

Lumateperone-mediated effects on prefrontal glutamatergic receptor-mediated neurotransmission: A dopamine D1 receptor dependent mechanism

Lumateperone is a novel drug approved for the treatment of schizophrenia in adults and depressive episodes associated with bipolar depression in adults, as monotherapy and as adjunctive therapy with lithium or valproate treatment in the United States. Lumateperone simultaneously modulates key neurotransmitters, such as serotonin, dopamine, and glutamate, implicated in serious mental illness. In patients with schizophrenia, lumateperone was shown to improve positive symptoms along with negative and depressive symptoms, while also enhancing prosocial behavior. Moreover, in patients with bipolar I or II disorder, lumateperone improved depressive symptoms as well. To further understand the mechanisms related to lumateperone's clinical response, the aim of this study was to investigate the effect of lumateperone on dopaminergic- and glutamatergic signaling in the rat medial prefrontal cortex (mPFC). We used the conditioned avoidance response (CAR) test to determine the antipsychotic-like effect of lumateperone, electrophysiology in vitro to study lumateperone's effects on NMDA- and AMPA-induced currents in the mPFC, and the neurochemical techniques microdialysis and amperometry to measure dopamine- and glutamate release in the rat mPFC. Our results demonstrate that lumateperone; i) significantly suppressed CAR in rats, indicating an antipsychotic-like effect, ii) facilitated NMDA and AMPA receptor-mediated currents in the mPFC, in a dopamine D1-dependent manner, and iii) significantly increased dopamine and glutamate release in the rat mPFC. To the extent that these findings can be translated to humans, the ability of lumateperone to activate these pathways may contribute to its demonstrated effectiveness in safely improving symptoms related to neuropsychiatric disorder including mood alterations.

Neuroprotective effects of sodium valproate on hippocampal cell and volume, and cognitive function in a rat model of focal cerebral ischemia

Valproate (VPA) as a histone deacetylase (HDAC) inhibitor has shown neuroprotective effects in neurodegenerative diseases. This study evaluated whether VPA treatment ameliorated the synaptic plasticity dysfunction, hippocampal neuronal loss, and spatial memory deficits induced by cerebral ischemia in the middle cerebral artery occlusion (MCAO) model. Thirty-two male Sprague-Dawley rats were randomly divided into 4 groups control, sham, cerebral ischemia+vehicle (MCAO+V), and MCAO+VPA. The right common carotid artery was occluded for 1 hour. VPA (300 mg/kg) or vehicles were injected intraperitoneally on days 0,1,2 and 3 of the reperfusion. After 7 days of reperfusion the Morris water maze, passive avoidance, and open field tests were performed. Hippocampal synaptic plasticity in the CA1 area was recorded by field potential recording. We used the term neuronal Input-Output (I/O) function and paired-pulse ratio (PPR) to refer to basal synaptic transmission and presynaptic neurotransmitter release probability respectively. After that, the brains were removed for assaying stereological parameters of the CA1 neurons. Our results showed the VPA administration significantly reduced the total infarct volume, improved MCAO-induced spatial learning -memory, fear memory, and anxiety compared to the MCAO+V group. In addition, the field potential recording showed that VPA significantly ameliorated the impaired the long- term potentiation (LTP) induced by MCAO, without any effects on basal synaptic transmission and neurotransmitter release probability. Therefore, it seems that a decrease in total infarct volume and induction of long-term potentiation via postsynaptic mechanisms is responsible for improving MCAO-induced cognitive impairment.

Surgical treatment of a patient with live intracranial sparganosis for 17\xa0years

BackgroundThe incidence of sparganosis, especially intracranial live sparganosis is very low in China. Due to the lack of typical clinical manifestations, it is difficult to make a clear preoperative diagnosis of the disease, which often leads to delays the disease and serious consequences.Case presentationA 23-year-old man presented with a 17-year history of intermittent seizures and right extremity numbness and weakness. Magnetic resonance imaging (MRI) showed patchy, nodular and line-like enhancement. Enzyme-linked immunosorbent assay (ELISA) detected positive antibodies to Spirometra mansoni in peripheral blood and cerebrospinal fluid (CSF). In addition, during the operation, an ivory-colored live sparganosis was removed under the precise positioning of neuronavigation, and the patient was diagnosed with cerebral sparganosis. The patient began praziquantel and sodium valproate treatment after the operation, and was followed up for 3 months. There was no recurrence of epilepsy, and the weakness and numbness of the right limb improved.ConclusionNonspecific clinical manifestations often make the diagnosis of cerebral sparganosis difficult, and a comprehensive diagnosis should be made based on epidemiological history, clinical manifestations, ELISA results and imaging findings. Surgery is the preferred method for the treatment of cerebral sparganosis, and more satisfactory results can be achieved under the precise positioning of neuronavigation.

Roles of C-reactive protein polymorphisms and life event changes on cognitive function in bipolar patients receiving valproate.

IntroductionPatients with bipolar disorder (BD) exhibit an inflamed condition that is associated with metabolic disturbance and cognitive impairment. Whether inflammation, represented by C-reactive protein (CRP), is causally associated with BD and influences treatment outcome has not been established.MethodsWe examined whether CRP is a causal factor for the risk of BD in drug-naïve, depressed BD patients and investigated whether polymorphisms in CRP and life event changes influence cognitive function in BD patients receiving valproate (VPA) treatment.ResultsOur results showed that BD patients had significantly higher CRP levels and worse cognitive function than the controls, while the frequencies of CRP single nucleotide polymorphisms in BD patients and in controls were not different. In addition, the life event scale score was higher for BD patients than for controls. Furthermore, the genotypes of CRP polymorphisms and the interactions between polymorphisms of CRP and life event scale score had a significant influence on cognitive performance in BD patients after 12 weeks of VPA treatment.ConclusionOur study demonstrated the clinical utility of the application of functional genetics in clarifying the interactions among CRP, life event stress, and BD and suggested the important roles of CRP gene–environment interactions in developing treatment strategies for BD.

Effect of Sodium Valproate on Weight, Body Mass Index, Uric Acid, Vitamin D3, Blood Insulin, and Serum Lipid Profile in Children

Introduction: Due to the high prevalence of epilepsy and the use of sodium valproate as an antiepileptic drug by these patients, accurate recognition of its side effects and its effects on serum lipids profile, liver enzymes, uric acid level, and thyroid function tests, especially in cases that need long-term treatment seems essential. This study aimed to evaluate the effects of sodium valproate on weight, body mass index (BMI), vitamin D3, blood insulin, uric acid level, and serum lipids profile in children with newly diagnosed epilepsy. Materials and Methods: This prospective study was performed on 30 children between 3 and 8 years of age who suffered from newly diagnosed epilepsy and received sodium valproate as monotherapy. Data including demographic information (age, sex, height, weight, and waist and hip circumference of children), as well as clinical characteristics, such as liver enzymes (ALT, AST, ALK-P), serum lipids level (TG, TC, HDL-C, LDL-C), thyroid tests (TSH, T4), fasting blood sugar (FBS), uric acid level, 25 OH Vitamin D3 (Vit-D3), and blood insulin level of children before and six months after the consumption of sodium valproate, were examined. Results: The mean weight of children before and six months after the start of sodium valproate treatment was 18.54±2.99 and 21.13±3.93 (kg), respectively. This difference was statistically significant (P=0.005). Also, the mean weight Z-score of children before and after taking sodium valproate was -2.497 and -2.293, respectively, which was statistically significant too. In addition to weight gain, there was also a significant increase in the abdominal and hip circumference of children after taking valproate, whereas the increase in mean BMI before and after valproate administration was not statistically significant (P=0.114). However, mean weight gain, as well as the increase in the waist and hip circumference, had no relationship with gender (P&gt; 0.05). Also, sodium valproate significantly increased the ALT level (P=0.046). Moreover, sodium valproate did not affect other liver function markers (AST), thyroid hormones (TSH, T4), fasting blood sugar (FBS), uric acid level, 25 OH Vit-D3, and the children's blood insulin levels (P&gt; 0.05). Conclusion: According to the findings of this study, it can be concluded that sodium valproate is a good drug for children between 3 and 8 years of age, but it should be noted that taking this drug increases the chance of obesity in children. The main side effect of this drug is weight gain. Due to the significant increase in ALT enzyme, as observed in this study, it is recommended to check liver enzymes before, one, and six months after starting treatment as it can prevent the irreversible permanent side effects of this drug.

Does Valproate Treatment in Childhood Epilepsy Affect Nutritional Status and Biochemical Parameters?

Objective: Valproic acid is widely prescribed for the treatment of various neurological and neuropsychiatric disorders. This study aimed to determine the effect of valproic acid therapy, which is thought to have weight gain effect on nutritional status and some biochemical factors in children with epilepsy. Material and Methods: The study included 30 children and adolescents who received valproic acid monotherapy because of the diagnosis of epilepsy. Selected biochemical parameters before and 12 months after treatment were recorded retrospectively from the patient files. Valproic acid doses ranged from 11-40 mg/kg/day and plasma levels were maintained within the therapeutic limits throughout the study. The anthropometric measurements of the patients were recorded in the WHO Anthro program for children aged 1-5 years and the WHO Anthro-Plus program for children aged 5-18 years. Results: The epilepsy age of the patients was determined as 48.85±38.16 months; and they have been receiving valproic acid therapy at a dose of 25.00±10.75 mg/kg/day for 18.95±6.02 months. While no difference was found in terms of hunger VAS scores before and after treatment, VAS scores of appetite increased and satiety decreased (p<0.05). BMI-SDs, fasting insulin, HDL cholesterol and triglyceride levels increased after treatment (p<0.05). Conclusion: For this reason, it was thought that it is important to include a dietitian in multidisiplinary team for growth and weight monitoring in children receiving VPA therapy.

Oxcarbazepine versus sodium valproate in treatment of acute mania: a double-blind randomized clinical trial.

Oxcarbazepine as an anticonvulsant has been suggested as an effective drug in affective disorders. The present study was designed to compare the efficacy of oxcarbazepine and sodium valproate in the treatment of acute mania in the Iranian population. In a double-blind, randomized clinical trial, hospitalized bipolar patients in the acute manic phase who were admitted to Ibn-e-Sina psychiatric hospital in Mashhad city (north-eastern part of Iran) were enrolled. The diagnosis was confirmed using Structured Clinical Interview for DSM-IV-TR. Patients were then randomly allocated into two groups taking oxcarbazepine (900-2400 mg/day) and sodium valproate (about 20 mg/kg/day) for 6 weeks. Young Mania Rating Scale (YMRS), Clinical Global Impression Scale (CGI-S), and adverse effects of drugs were assessed at baseline and after 3 and 6 weeks. Mania symptoms based on mean scores of YMRS and CGI-S significantly decreased from baseline to endpoint in both treatments (P < 0.01). However, there was no significant difference between the two groups in terms of reduction of symptoms during times (P = 0.715 and P = 0.446, respectively) and adverse events (P > 0.05). This study confirmed the previous findings that indicate the efficacy of oxcarbazepine as same as sodium valproate. Moreover, its adverse effects resemble sodium valproate in the treatment of acutely manic patients.

Beneficial and Sexually Dimorphic Response to Combined HDAC Inhibitor Valproate and AMPK/SIRT1 Pathway Activator Resveratrol in the Treatment of ALS Mice.

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disorder. There is no cure and current treatments fail to slow the progression of the disease. Epigenetic modulation in the acetylation state of NF-kB RelA and the histone 3 (H3) protein, involved in the development of neurodegeneration, is a drugable target for the class-I histone deacetylases (HDAC) inhibitors, entinostat or valproate, and the AMP-activated kinase (AMPK)-sirtuin 1 pathway activator, resveratrol. In this study, we demonstrated that the combination of valproate and resveratrol can restore the normal acetylation state of RelA in the SOD1(G93A) murine model of ALS, in order to obtain the neuroprotective form of NF-kB. We also investigated the sexually dimorphic development of the disease, as well as the sex-sensibility to the treatment administered. We showed that the combined drugs, which rescued AMPK activation, RelA and the histone 3 acetylation state, reduced the motor deficit and the disease pathology associated with motor neuron loss and microglial reactivity, Brain-Derived Neurotrophic Factor (BDNF) and B-cell lymphoma-extra large (Bcl-xL) level decline. Specifically, vehicle-administered males showed earlier onset and slower progression of the disease when compared to females. The treatment, administered at 50 days of life, postponed the time of onset in the male by 22 days, but not in a significant way in females. Nevertheless, in females, the drugs significantly reduced symptom severity of the later phase of the disease and prolonged the mice’s survival. Only minor beneficial effects were produced in the latter stage in males. Overall, this study shows a beneficial and sexually dimorphic response to valproate and resveratrol treatment in ALS mice.

Mitochondrial DNA Copy Number Is Associated With Treatment Response and Cognitive Function in Euthymic Bipolar Patients Receiving Valproate.

BackgroundBipolar disorder (BD) is associated with cognitive impairment and mitochondrial dysfunction. However, the associations among mitochondrial DNA copy number (MCN), treatment response, and cognitive function remain elusive in BD patients.MethodsSixty euthymic BD patients receiving valproate (VPA) and 66 healthy controls from the community were recruited. The indices of metabolic syndrome (MetS) were measured. Quantitative polymerase chain reaction analysis of blood leukocytes was used to measure the MCN. Cognitive function was measured by calculating perseverative errors and completed categories on the Wisconsin Card Sorting Test (WCST). The VPA treatment response was measured using the Alda scale.ResultsBD patients had significantly higher MCN, triglyceride, and C-reactive protein (CRP) levels, waist circumference, and worse performance on the WCST than the controls. Regression models showed that BD itself and the VPA concentration exerted significant effects on increased MCN levels. Moreover, the receiver operating characteristic curve analysis showed that an MCN of 2.05 distinguished VPA responders from nonresponders, with an area under the curve of 0.705 and a sensitivity and specificity of 0.529 and 0.816, respectively. An MCN level ≥2.05 was associated with 5.39 higher odds of being a VPA responder (P = .006). BD patients who were stratified into the high-MCN group had a higher VPA response rate, better WCST performance, lower CRP level, and less MetS.ConclusionsThe study suggests a link between the peripheral MCN and cognitive function in BD patients. As an inflammatory status, MetS might modulate this association.

Who is prescribed valproate and how carefully is this treatment reviewed in UK mental health services? Data from a clinical audit.

Background:The licensed indications for valproate are narrow, yet this medication is commonly prescribed in mental health services.Objectives:To explore the target symptoms/behaviours for which valproate is prescribed and how well the efficacy and tolerability of this treatment are monitored in routine clinical practice.Design:An audit-based quality improvement (QI) programme in UK mental health services.Methods:Information on valproate prescribing was collected from clinical records using a bespoke data collection tool.Results:Sixty-four NHS mental health Trusts/healthcare organisations submitted data on valproate treatment for 5320 patients. Valproate was clearly prescribed for a licensed indication in 1995 (38%) patients, off-label in 1987 (37%) while the indication was uncertain/not available in 1338 (25%). Of the 919 patients started on valproate treatment within the past year, between a half and two-thirds had each of the relevant baseline physical health checks documented. In 539 (59%) of these patients, valproate was prescribed for an unlicensed indication; the prescription was recognised as off-label in 363 (67%), 20 (6%) of whom were documented as having had this explained to them. Of 631 patients prescribed valproate for between 3 months and a year, early on-treatment assessments of response and side effects were documented in 441 (70%) and 332 (53%), respectively. Of 4401 patients treated for more than a year, annual on-treatment reviews of clinical response and side effects were documented in 2771 (63%) and 2140 (49%), respectively.Conclusion:Our data suggest the majority of prescriptions for valproate in mental health services are not for a licensed indication. Furthermore, patients rarely receive an explanation that their valproate prescription is off-label, perhaps partly because the licensed indications are not widely understood by prescribers. Given the very limited evidence for efficacy for the off-label uses of valproate, failure to routinely conduct early on-treatment and annual reviews of the benefits and side effects of this medication may result in patients remaining on ineffective and poorly tolerated treatment by default.

Systematic review and meta-analysis of a variety of chemicals to treat migraine in the neurology department.

Migraine refers to a group of recurrent, chronic, neurological, and vascular diseases. Long-term recurrent migraine not only affects personal life and work, but also results in a huge economic burden on the family and society. Timely and accurate diagnosis of migraine and early and standardized treatment can effectively control migraine attacks. The treatment of migraine is to quickly stop the attack, relieve the associated symptoms, prevent recurrence, and restore normal life function as soon as possible. Literature retrieval was performed in the PubMed, Embase, and OVID-Medline English databases, and the retrieval period was from the establishment of the database to April 2021. Keywords such as migraine, chemical drugs, and therapeutic effect were used. A total of 13 studies involving 1,921 migraine patients were included. The results showed that there was a significant difference in incidence of adverse events in patients after treatment with chemical drugs and placebo [risk difference (RD) =0.11; 95% confidence interval (CI): 0.03 to 0.20; Z=2.70; P=0.007] and the frequency of headaches [mean difference (MD) =-1.31; 95% CI: -1.89 to -0.73; Z=4.40; P<0.0001]. The incidence of adverse events after topiramate treatment [odds ratio (OR) =3.63; 95% CI: 1.65 to 7.97; Z=3.21; P=0.001] and the frequency of headache [MD =-1.31; 95% CI: -1.87 to -0.75; Z=4.59; P<0.00001] was significantly different from the placebo group; The frequency of headache after sodium valproate treatment [MD =-0.92; 95% CI: -1.80 to -0.04; Z=2.05; P=0.04] was also significantly different from the placebo group. However, there was no significant difference in the incidence of adverse events and the frequency of headaches after flunarizine and placebo treatment. A total of 13 articles were included to evaluate the efficacy and tolerability of chemotherapeutic treatments for migraine. This study found that sodium valproate and propranolol were well tolerated for the prevention and treatment of migraine. The clinical manifestations were mainly unilateral temporal pulsing headache, some patients were accompanied by visual aura, fatigue, emotional and other triggers, and nearly half of the patients had a family history.

Effect of Sodium Valproate Treatment on the Cardiac Index in New Cases with Status Epilepticus

Background: Sodium valproate is an antiepileptic drug primarily used to treat status epilepticus [SE]; however, its effect on cardiac function is unclear. This study aimed to examine the effect of 6 months of sodium valproate treatment on the cardiac index in new cases with status epilepticus. Methods: In this cross-sectional study, 30 cases with status epilepticus [18 boys and 12 girls] who were admitted to the Pediatric Intensive Care Unit of Hazrat-e Rasool Hospital were enrolled. Information on basic demographic and clinical data of all children, such as age, weight, gender, blood pressures, and underlying diseases, was recorded. Echocardiography and electrocardiogram [ECG] were performed for all cases before and after the treatment. Results: There were no abnormalities in ECG parameters [including PR, QRS, and QT intervals] after 6 months of treatment with sodium valproate. No significant differences were found in echocardiographic parameters, including blood pressure, pulmonary artery pressure [PAP], right ventricular [RV] size, diastolic dysfunction,], Tie index, end-diastolic volume [EDV], ejection fraction [EF], and TAPSE before and after study [p&gt;0.05]. Conclusion: Administration of sodium valproate over 6 months is not associated with a serious adverse effect on heart function in children with status epilepticus.

Subacute combined degeneration of spinal cord, optic atrophy and thrombocytopenia without anemia secondary to B12 deficiency

Long-standing vitamin B12 deficiency can lead to neurological manifestations such as optic atrophy and subacute combined degeneration of the cord without causing significant anemia. In addition, folic acid supplementation could mask the hematological manifestations of vitamin B12 deficiency and delay the presentation of neurological manifestations We present a case of a 32-year-old vegan woman on long-term sodium valproate and folic acid treatment presenting with progressive weakness of bilateral lower limbs for three months and reduced vision in both eyes for two weeks duration. Further evaluation revealed optic atrophy, combined degeneration of the spinal cord, macrocytosis, thrombocytopenia, and severely deficient serum B12 levels. With B12 replacement therapy, the patient’s overall wellbeing improved.