The effect of protocatechuic acid on neuropathic pain and possible mechanism.

OBJECTIVES: The goal of the research is to investigate the protocatechuic acid (PCA) potential action, a phenolic acid derivative, on pain induced by neuropathy and to determine its efficacy on activation of KATP type channels and A1 receptors. MATERIALS AND METHODS: Neuropathic pain by cause of sciatic nerve damage was induced in Sprague-Dawley rats. Anti-allodynic and anti-hyperalgesic effects were evaluated with von Frey apparatus and Hargreave's plantar test apparatus, respectively. The effects of PCA at the doses of 75, 150 and 300 mg/kg, carbamazepine at the doses of 50 and 100 mg/kg, combination of low effective doses of PCA and carbamazepine were tested. Pretreatments 3 µg/kg DPCPX as adenosine A1 receptor antagonist and 60.7 nmol glibenclamide as KATP channel blocker were applied for mechanistic studies. RESULTS: PCA showed anti-allodynic and anti-hyperalgesic effects without impairing locomotor activity. In addition, the combination treatment was found to be more effective than the separate individual treatments of drugs. KATP channel activation related with A1 receptor stimulation makes a significant contribution to the anti-allodynia and anti-hyperalgesia induced by PCA. CONCLUSIONS: It can be said that PCA has similar effects with carbamazepine, which is used in clinical practice, and that PCA can take place as an adjuvant drug in neuropathic pain with the combination group. In addition, it is seen that the undesirable effects that drugs can cause alone can be avoided and a more effective treatment potential can be created with multiple mechanisms.

Birth outcomes in pregnant women with epilepsy: A Nationwide multicenter study from Türkiye.

OBJECTIVE: The present study was aimed at investigating the effects of anti-seizure medications (ASMs), patient demographic characteristics, and the seizure type and frequency on the development of congenital malformations (CMs) in the infants of pregnant women with epilepsy (PWWE). METHODS: PWWE followed up at the neurology outpatient clinic of 21 centers between 2014 and 2019 were included in this prospective study. The follow-up of PWWE was conducted using structured, general pregnant follow-up forms prepared by the Pregnancy and Epilepsy Study Committee. The newborns were examined by a neonatologist after delivery and at 1 and 3 months postpartum. RESULTS: Of the infants of 759 PWWE, 7.2% had CMs, with 5.6% having major CMs. Polytherapy, monotherapy, and no medications were received by 168 (22.1%), 548 (72.2 %), and 43 (5.7 %) patients, respectively. CMs were detected at an incidence of 2.3% in infants of PWWE who did not receive medication, 5.7% in infants of PWWE who received monotherapy, and 13.7% in infants of PWWE who received polytherapy. The risk of malformation was 2.31-fold (95% confidence interval (CI): 1.48-4.61, p < .001) higher in infants of PWWE who received polytherapy. Levetiracetam was the most frequently used seizure medication as monotherapy, with the highest incidence of CMs occurring with valproic acid (VPA) use (8.5%) and the lowest with lamotrigine use (2.1%). The incidence of CMs was 5% at a carbamazepine dose <700 mg, 10% at a carbamazepine dose ≥700 mg, 5.5% at a VPA dose <750 mg, and 14.8% at a VPA dose ≥750 mg. Thus the risk of malformation increased 2.33 times (p = .041) in infants of PWWE receiving high-dose ASMs. SIGNIFICANCE: Birth outcomes of PWWE receiving and not receiving ASMs were evaluated. The risk of CMs occurrence was higher, particularly in infants of PWWE using VPA and receiving polytherapy. The incidence of CMs was found to be lower in infants of PWWE receiving lamotrigine.

Acupuncture for the treatment of trigeminal neuralgia: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Few systematic reviews have examined the effects of acupuncture on trigeminal neuralgia. This review aims to provide up-to-date evidence on the efficacy of acupuncture for managing pain in patients with trigeminal neuralgia. METHODS: Eleven databases were searched from inception until November 2022 for relevant articles Two researchers independently conducted study selection, data extraction, and evaluation. The present review solely targeted randomized controlled trials (RCTs). The Cochrane risk of bias assessment tool 2.0 was employed to assess the risk of bias. Data were compiled using RevMan 5.4.1 software, and the quality of the evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Thirty studies involving 2295 patients were included in this review. Compared with carbamazepine, acupuncture led to improvements in pain scores (15 RCTs, mean difference (MD) - 1.40, 95% confidence interval (CI)-1.82 to -0.98 [95% prediction interval, -3.137,0.343], p < 0.00001, low certainty of evidence (CoE)), response rates (29 RCTs, risk ratio (RR) 1.20, 95% CI 1.15 to 1.25 [95% prediction interval, 1.067, 1.346], p < 0.00001, low CoE), frequency of pain attacks (2 RCTs, MD -2.53, 95% CI -4.11 to -0.96, P = 0.002, low CoE), and adverse effects (13 RCTs, risk difference (RD) -0.15, 95% CI -0.19 to -0.11 [95% prediction interval, -0.193, -0.108], P < 0.00001, very low CoE). CONCLUSION: Although the quality of evidence is low, compared with carbamazepine, acupuncture may improve trigeminal neuralgia-related pain. Further rigorously designed studies are warranted to confirm the effects of acupuncture on patients with trigeminal neuralgia.

Efficacy and safety of different antidepressants and anticonvulsants in central poststroke pain: A network meta-analysis and systematic review.

OBJECTIVE: To evaluate the efficacy and safety of different antidepressants and anticonvulsants in the treatment of central poststroke pain (CPSP) by network meta-analysis and provide an evidence-based foundation for clinical practice. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, APA PsycINFO, Wanfang, VIP and other databases were searched by computer to find clinical randomized controlled studies (RCTs) on drug treatment of CPSP. The retrieval time limit was from the establishment of each database to July 2022. The quality of the included RCTs was evaluated using the bias risk assessment tool recommended by Cochrane. Stata 14.0 was used for network meta-analysis. RESULTS: A total of 13 RCTs, 1040 patients and 9 drugs were finally included. The results of the network meta-analysis showed that the effectiveness ranking as rated by the visual analog scale (VAS) was gabapentin > pregabalin > fluoxetine > lamotrigine > duloxetine > serqulin > amitriptyline > carbamazepine > vitamin B. Ranking according to the numerical rating scale (NRS) was pregabalin > gabapentin > carbamazepine. Ranking derived from the Hamilton depression scale (HAMD) was pregabalin > duloxetine > gabapentin > amitriptyline. CONCLUSION: All nine drugs can relieve the pain of CPSP patients to different degrees; among them pregabalin and gabapentin have the most significant effect, and gabapentin and pregabalin also have the most adverse reactions. In the future, more multicenter, large sample, double-blind clinical randomized controlled trials need to be carried out to supplement and demonstrate the results of this study.

Impact of carbamazepine on vitamin D levels: A meta-analysis.

PURPOSE: There are longstanding concerns about the impact of enzyme-inducing anti-seizure medications (ASMs) on vitamin D, an important molecule in both bone metabolism and inflammation pathways. The relationship between chronic use of carbamazepine and vitamin D levels has been studied, but no comprehensive review to inform practitioners and policymakers is currently available. We performed a meta-analysis on studies that measured 25-hydroxyvitamin D (25OHD) levels in persons taking carbamazepine to determine whether this drug significantly reduces circulating 25OHD. PRINCIPAL RESULTS: From a literature search of the terms "carbamazepine" and "vitamin D", we identified 12 studies that measured 25OHD levels in persons on carbamazepine monotherapy groups and controls. Persons taking carbamazepine had significantly lower 25OHD levels than persons not taking carbamazepine. The average 25OHD levels of carbamazepine-treated patients across all studies was 21.8 ng/mL (IQR 15.4,26.0) whereas 25OHD levels of control subjects was 28.0 ng/mL (IQR 20.8,30.4). The weighted difference of means was 4.00 ng/mL of 25OHD. Neither age nor sex nor duration of carbamazepine therapy had a significant impact on this finding. The effect was similar irrespective of whether the comparator group consisted of healthy controls or epilepsy patients taking non-inducing medications. MAJOR CONCLUSIONS: Carbamazepine use is associated with a reduction of 25OHD levels. In combination with other literature establishing the problematic metabolic effects of carbamazepine, this meta-analysis provides additional evidence in favor of the use of alternative ASMs as first-line agents. At minimum, vitamin D supplementation should be strongly considered for patients prescribed carbamazepine.

Serum folate levels in children on long-term anti-seizure medication in a Nigerian tertiary center-Implications for practice and public health.

BACKGROUND: Epilepsy is the most common childhood neurological disorder in Nigeria. Treatment of epilepsy is long-term and sometimes lifelong with anti-seizure medications. There are conflicting reports on the effect of anti-seizure medications on serum folate. There is therefore a need to determine the effect of a commonly used anti-seizure medication's on serum folate levels of children. This would provide an evidence-based consideration for folic acid supplementation in children on anti-seizure medication as has been suggested by some studies. STUDY OBJECTIVES: To determine whether serum folate levels were lower in children taking long-term carbamazepine or sodium valproate, compared to a control group. METHODS: Serum folic acid levels were measured from well-nourished children between the ages of 1-17 years on carbamazepine and sodium valproate monotherapy and their age/sex-matched controls, using spectrophotometry. RESULTS: The mean serum folate levels of patients on carbamazepine (43) and sodium valproate (22) were 0.032 mg/l ± 0.009 and 0.028 mg/l ± 0.008, respectively. The mean folate levels of the controls were 0.046 mg/l ± 0.03 (p = 0 001). No statistically significant difference was observed between the serum folate levels of children on the two anti-seizure medications, that is, carbamazepine and valproate. CONCLUSION: The children on treatment with carbamazepine and sodium valproate for more than 6 months had statistically significantly lower serum levels of folic acid compared to the standard reference range and controls. The serum folate levels of children on carbamazepine were not statistically different from those on sodium valproate.

Pharmacokinetic Drug-Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients.

Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug-drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.

Alcohol Withdrawal Syndrome: Outpatient Management.

Approximately one-half of patients with alcohol use disorder who abruptly stop or reduce their alcohol use will develop signs or symptoms of alcohol withdrawal syndrome. The syndrome is due to overactivity of the central and autonomic nervous systems, leading to tremors, insomnia, nausea and vomiting, hallucinations, anxiety, and agitation. If untreated or inadequately treated, withdrawal can progress to generalized tonic-clonic seizures, delirium tremens, and death. The three-question Alcohol Use Disorders Identification Test-Consumption and the Single Alcohol Screening Question instrument have the best accuracy for assessing unhealthy alcohol use in adults 18 years and older. Two commonly used tools to assess withdrawal symptoms are the Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised, and the Short Alcohol Withdrawal Scale. Patients with mild to moderate withdrawal symptoms without additional risk factors for developing severe or complicated withdrawal should be treated as outpatients when possible. Ambulatory withdrawal treatment should include supportive care and pharmacotherapy as appropriate. Mild symptoms can be treated with carbamazepine or gabapentin. Benzodiazepines are first-line therapy for moderate to severe symptoms, with carbamazepine and gabapentin as potential adjunctive or alternative therapies. Physicians should monitor outpatients with alcohol withdrawal syndrome daily for up to five days after their last drink to verify symptom improvement and to evaluate the need for additional treatment. Primary care physicians should offer to initiate long-term treatment for alcohol use disorder, including pharmacotherapy, in addition to withdrawal management.

Management of bone metabolism in epilepsy.

BACKGROUND AND PURPOSE: Many systemic problems arise due to the side effects of antiepileptic drugs (AEDs) used in epilepsy patients. Among these adverse effects are low bone mineral density and increased fracture risk due to long-term AED use. Although various studies have supported this association with increased risk in recent years, the length of this process has not been precisely defined and there is no clear consensus on bone density scanning, intervals of screening, and the subject of calcium and vitamin D supplementation. In this study, in accordance with the most current recommendations, our applications and data, including the detection of possible bone mineralization disorders, treatment methods, and recommendations to prevent bone mineralization disorders, were evaluated in epilepsy patients who were followed up at our outpatient clinic. It was aimed to draw attention to the significance of management of bone metabolism carried out with appropriate protocols. METHODS: Epilepsy patients were followed up at the Antalya Training and Research Hospital Department of Neurology, Epilepsy Outpatient Clinic who were at high risk for osteoporosis (use of valproic acid [VPA] and enzyme-inducing drugs, using any AED for over 5 years, and postmenopausal women) and were evaluated using a screening protocol. According to this protocol, a total of 190 patients suspected of osteoporosis risk were retrospectively evaluated. Four patients were excluded from the study due to secondary osteoporosis. RESULTS: Of the 186 patients who were included in the study, 97 (52.2%) were women and 89 (47.8%) were men. Prevalence of low bone mineral density (BMD) was 42%, in which osteoporosis was detected in 11.8% and osteopenia in 30.6% of the patients. Osteoporosis rate was higher at the young age group (18-45) and this difference was statistically significant (p=0.018). There was no significant difference between male and female sexes according to osteoporosis and osteopenia rates. Patients receiving polytherapy had higher osteoporosis rate and lower BMD compared to patients receiving monotherapy. Comparison of separate drug groups according to osteoporosis rate revealed that osteoporosis rate was highest in patient groups using VPA+ carbamazepine (CBZ) (29.4%) and VPA polytherapy (19.4%). Total of osteopenia and osteoporosis, or low BMD, was highest in VPA polytherapy (VPA+ non-enzyme-inducing AED [NEID]) and CBZ polytherapy (CBZ+NEID) groups, with rates of 58.3% and 55.1%, respectively. In addition, there was no significant difference between drug groups according to bone metabolism markers, vitamin D levels, and osteopenia-osteoporosis rates. CONCLUSION: Assuming bone health will be affected at an early age in epilepsy patients, providing lifestyle and diet recommendations, avoiding polytherapy including VPA and CBZ when possible, and evaluating bone metabolism at regular intervals are actions that should be applied in routine practice.

Clinico-laboratory characteristics and outcome of patients with eucalyptus oil-induced/provoked seizures: A case series and systematic review of the published patients.

Seizures triggered by skin application, inhalation or ingestion of over-the-counter medications containing eucalyptus oil are known. We report five children who suffered likewise. We made a systematic search for all reported cases and performed a pooled analysis to provide a comprehensive estimate of the type of seizures, their management and outcome. In 110 cases (49 children), inhalational use was the most predominant, generalised tonic-clonic (the commonest semiology) and levetiracetam was the most common anti-convulsant treatment used. Most cases had an uneventful recovery. Adults were less likely to have prolonged and multiple seizures, requiring intensive care or mechanical ventilation.

Effect of carbamazepine on emotional intelligence and mindfulness in patients with partial epilepsy.

OBJECTIVE: To assess the effectiveness of carbamazepine on emotional intelligence and mindfulness in patients with epilepsy. METHODS: The repeated-measure case-control study was conducted at the Nishter Hospital, Multan, Bahawal Victoria Hospital, Bahawalpur, and Civil Hospital, Bahawalpur, Pakistan, from April 2017 to March 2018, and comprised of patients with partial epilepsy and healthy controls. Baseline data was collected using BarOn Emotional Quotient Inventory and Cognitive and Affective Mindfulness Scale-Revised. Subsequent data was collected twice in titration and maintenance phases during carbamazepine therapy for patients, while the controls were on no medication. Data was analysed using SPSS 20. RESULTS: Of the 80 subjects, 40(50%) were cases with a mean age of 37.92±9.09 years, and 40(50%) were controls with a mean age of 37.80±9.00 years. The patients had significantly lower emotional intelligence and mindfulness compared to the controls (p<0.001). Patients showed improved emotional intelligence and mindfulness after the therapy compared to their baseline scores (p<0.05). CONCLUSIONS: Carbamazepine was found to be effective in improving emotional intelligence and mindfulness in patients with epilepsy.

Epilepsy in Morocco: Realities, pitfalls and prospects.

The World Health Organization (WHO) estimates that about 50 million people of all ages have epilepsy and nearly 85% of whom live in low- and middle-income (LMICs) countries. In Morocco, epilepsy is one of the major neurological health conditions, with an estimated prevalence of 1.1%. The management of patients is difficult due to multiple factors. The lack of neurologists whose number is currently 180, the uneven distribution of neurologists who are concentrated in large cities, 43% of whom are in Rabat and Casablanca alone; the low involvement of general practitioners in the management of epilepsy; the frequent consultation of traditional healers; and the low coverage of social security all contribute to the treatment gap. The management of epilepsy has advanced considerably since the early nineties. Several factors contributed to this progress: the increasing number of neurologists compared to previous years, the creation of well-equipped new academic centers, and small units of general neurology, in addition to the disuse of several antiepileptic drugs. However, much work remains to be done against the use of many forms of traditional practices and the low involvement of general practitioners in the management of epilepsy. This is the first study on epilepsy conducted in Morocco.

Antiseizure drug efficacy and tolerability in established and novel drug discovery seizure models in outbred vs inbred mice.

OBJECTIVE: Initial identification of new investigational drugs for the treatment of epilepsy is commonly conducted in well-established mouse acute and chronic seizure models: for example, maximal electroshock (MES), 6 Hz, and corneal kindling. Comparison of the median effective dose (ED50) of approved antiseizure drugs (ASDs) vs investigational agents in these models provides evidence of their potential for clinical efficacy. Inbred and outbred mouse strains exhibit differential seizure susceptibility. However, few comparisons exist of the ED50 or median behaviorally impairing dose (TD50) of prototype ASDs in these models in inbred C57Bl/6 vs outbred CF-1 mice, both of which are often used for ASD discovery. METHODS: We defined the strain-related ED50s and TD50s of several mechanistically distinct ASDs across established acute seizure models (MES, 6 Hz, and corneal-kindled mouse). We further quantified the strain-related effect of the MES ED50 of each ASD on gross behavior in a locomotor activity assay. Finally, we describe a novel pharmacoresistant corneal-kindling protocol that is suitable for moderate-throughput ASD screening and demonstrates highly differentiated ASD sensitivity. RESULTS: We report significant strain-related differences in the MES ED50 of valproic acid (CF-1 ED50: 90 mg/kg [95% confidence interval (CI) 165-214] vs C57Bl/6: 276 mg/kg [226-366]), as well as significant differences in the ED50 of levetiracetam in the pharmacoresistant 6 Hz test (CF-1: 22.5 mg/kg [14.7-30.2] vs C57Bl/6: >500 mg/kg [CI not defined]). There were no differences in the calculated TD50 of these ASDs between strains. Furthermore, the MES ED50 of phenobarbital significantly enhanced locomotor activity of outbred CF-1, but not C57Bl/6, mice. SIGNIFICANCE: Altogether, this study provides strain-related information to differentiate investigational agents from ASD standards-of-care in commonly employed preclinical discovery models and describes a novel kindled seizure model to further explore the mechanisms of drug-resistant epilepsy.

Electroacupuncture therapy for change of pain in classical trigeminal neuralgia.

INTRODUCTION: Classical trigeminal neuralgia (CTN) is a kind of trigeminal neuralgia which is due to neurovascular compression. The common neurological treatment CTN drug called carbamazepine is the main measure, although it usually has side effects and a high-rate of relapse. As a critical alternative therapy, electroacupuncture (EA) has been shown to benefit for neuropathic pain. The aims of this study are to observe the therapeutic effect and safety of EA for CTN, to evaluate whether EA has the advantage over carbamazepine in the analgesia of CTN. Furthermore, we would to establish a standardized, effective, and convenient therapy program of EA. METHODS AND ANALYSIS: One hundred twenty patients diagnosed with CTN will be randomized for a 4-week intervention. The interventions will be different according to the four groups (EA + carbamazepine group, sham EA + carbamazepine group, EA + placebo group and sham EA + placebo group). EA therapy will be performed in specific acupoints with a dilute wave (2/100 Hz) for 60 minutes. Carbamazepine tablets will be taken orally with 0.1 g each time, thrice daily. Sham EA and placebo intervention will not receive EA and drug treatment. The main outcomes are the change from baseline intensity of pain at 6 months (pain evaluation by visual analogue score) and the change from baseline brief introduction of 2-week pain to evaluate pain comprehensively. The data management and statistical analysis will be conducted by third party statisticians. Incidence of adverse events will be investigated. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Clinical Trial Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University (NO. ZSLL-KY-2017-033) and Jiaxing Hospital of Traditional Chinese Medicine (NO. 2018-JZLK-002). The results will be disseminated by presentation at peer-reviewed journals.

Bilateral calcaneal insufficiency fractures due to chronic carbamazepine use for trigeminal neuralgia: A case report.

Stress fractures of calcaneus are uncommon cause of heel pain. Stress fractures could be seen in risc groups such as metabolic diseases/medications causing poor bone quality and exposing repetitive microtrauma. Anti-epileptic drug (AED) use is related with poor bone quality and increased fracture risc. Although carbamazepine-induced stress fracture is a well-known entity and there are case reports in other bones such as the femoral neck, bilateral calcaneal insufficiency fractures is an extraordinary location. To the best of our knowledge, this is the first case reporting an insufficiency fracture involving calcaneus in the relevant literature. Due to the rarity of both conditions, we decided to present and discuss this patient. When patients receiving AED treatment present with heel pain without previous plantar fasciitis history or traumatic event, insufficiency fractures should be kept in mind. This case highlights the importance of screening adverse effect of CBZ on bone metabolism in patients with long CBZ use. We report here a 41-year-old lady suffering from bilateral heel pain without trauma history. Her complaining did not respond to analgesics and stretching exercises of plantar fascia. In her past medical history she reported ongoing carbamazepine (CBZ) use over 8 years for trigeminal neuralgia. She had had low bone mineral density; defined as osteopenia. Both calcaneus MRI revealed bilateral stress fractures of calcaneum. She had been advised immobilization for 6 weeks, vitamin D and calcium supplements. CBZ has been stopped by neurology specialist and she had undergone microvascular decompression surgery for intractable pain of trigeminal neuralgia. She is doing well with full recovery from heel pain and trigeminal neuralgia at the end of one year. CBZ use causes poor bone quality through vitamin D metabolism. Heel pain without traumatic event, objective findings of plantar fasciitis and calcaneal spur syndrome in an CBZ using patient insufficiency fracture of calcaneus should be remembered and evaluated rigorously.

Longterm Antiepileptic Therapy and Bone Health: Implications for Patients with Brain Tumors.

OBJECTIVE: The objective of our study was to investigate the effects of carbamazepine (CBZ) and lamotrigine (LTG) treatment on bone metabolism in epileptic patients. PATIENTS AND METHODS: A cross-sectional study was performed on normal controls (N=30) and 100 patients with symptomatic epilepsy caused by a primary brain tumor, divided into two groups according to the treatment: LTG monotherapy group (N=50) and CBZ monotherapy group (N=50). For each participant serum levels of 25-OHD and osteocalcin (OCLN) were measured, and bone mineral density (BMD) was evaluated by the dual-energy X-ray absorptiometry method. RESULTS: There was no statistically significant difference in the average values of vitamin D in serum between the CBZ and LTG groups (Vitamin D CBZ 17.03±12.86 vs. Vitamin D LTG 17.97±9.15; F=0.171, P=0.680). There was no statistically significant difference in the average values of OCLN between the CBZ and LTG groups (OCLN CBZ 26.06±10.87 vs. OCLN LTG 27.87±28.45; F=0.171, P=0.674). The BMD value was lower in both groups using antiepileptic agents compared to the controls, but when comparing the CBZ group to the LTG group, a statistically significant difference was only observed for the Z score (T-score CBZ: 0.08± 1.38 vs. T-score LTG: 0.37± 1.02; F=1.495, P=0.224; Z score CBZ: -0.05±1.17 vs. Z. score CBZ: 0.38±0.96; F=4.069, P=0.046) (Table 3). CONCLUSION: The choice of antiepileptic agents for treating seizures in patients with brain tumors should be carefully evaluated in relation to their impact on bone health. These patients could benefit from supplementation and regular measurement of biochemical markers of bone turnover and BMD.

Electrophysiological and Neurochemical Assessment of Selenium Alone or Combined with Carbamazepine in an Animal Model of Epilepsy.

The present study aims to evaluate the efficacy of selenium (Se) alone or combined with carbamazepine (CBZ) against the adverse effects induced by the chemoconvulsant pentylenetetrazole (PTZ) in the cortex of adult male rats. Electrocorticogram (ECoG) and oxidative stress markers were implemented to evaluate the differences between treated and untreated animals. Animals were divided into five groups: control group that received i.p. saline injection, PTZ-treated group that received a single i.p. injection of PTZ (60 mg/kg) for induction of seizures followed by a daily i.p. injection of saline, Se-treated group that received an i.p. injection of sodium selenite (0.3 mg/kg/day) after PTZ administration, CBZ-treated group that received orally CBZ (80 mg/kg/day) after PTZ administration, and combination (Se plus CBZ)-treated group that received an oral administration of CBZ (80 mg/kg/day) followed by an i.p. injection of sodium selenite (0.3 mg/kg/day) after PTZ administration. Quantitative analyses of the ECoG indices and the neurochemical parameters revealed that Se and CBZ have mitigated the adverse effects induced by PTZ. The main results were decrease in the number of epileptic spikes, restoring the normal distribution of slow and fast ECoG frequencies and attenuation of most of the oxidative stress markers. However, there was an increase in lipid perioxidation marker in combined treatment of CBZ and Se. The electrophysiological and neurochemical data proved the potential of these techniques in evaluating the treatment's efficiency and suggest that supplementation of Se with antiepileptic drugs (AEDs) may be beneficial in ameliorating most of the alterations induced in the brain as a result of seizure insults and could be recommended as an adjunct therapy with AEDs.

Language impairment in children aged 5 and 8 years after antiepileptic drug exposure in utero - the Norwegian Mother and Child Cohort Study.

BACKGROUND AND PURPOSE: The purpose was to examine the consequences of antiepileptic drug (AED) exposure during pregnancy on language abilities in children aged 5 and 8 years of mothers with epilepsy. METHODS: The study population included children of mothers with and without epilepsy enrolled in the Norwegian Mother and Child Cohort Study 1999-2008. Mothers prospectively provided information on epilepsy diagnosis, AED use during pregnancy and the child's language abilities at age 5 and 8 years, in questionnaires with validated language screening tools. AED concentrations in gestation week 17-19 and in the umbilical cord were measured. RESULTS: The study population included 346 AED-exposed and 388 AED-unexposed children of mothers with epilepsy, and 113 674 children of mothers without epilepsy. Mothers of 117 and 121 AED-exposed children responded to the questionnaires at age 5 and 8 years, respectively. For AED-exposed children, the adjusted odds ratio for language impairment was 1.6 [confidence interval (CI) 1.1-2.5, P = 0.03] at age 5 years and 2.0 (CI 1.4-3.0, P < 0.001) at age 8 years, compared to children of mothers without epilepsy. Children exposed to carbamazepine monotherapy had a significantly increased risk of language impairment compared to control children at age 8 years (adjusted odds ratio 3.8, CI 1.6-9.0, P = 0.002). Higher maternal valproate concentrations correlated with language impairment at age 5 years. Periconceptional folic acid supplement use protected against AED-associated language impairment. CONCLUSION: Foetal AED exposure in utero is associated with an increased risk of language impairment in children aged 5 and 8 years of mothers with epilepsy. Periconceptional folic acid use had a protective effect on AED-associated language impairment.

Anti-epileptic drug and folic acid usage during pregnancy, seizure and malformation outcomes: Changes over two decades in the Kerala Registry of Epilepsy and Pregnancy.

BACKGROUND: This study was carried out to determine changes over time in use of folic acid, anti-epileptic drugs (AED), seizures during pregnancy and malformation rate over two decades in women with epilepsy enrolled in the Kerala registry of Epilepsy and Pregnancy (KREP). METHODS: All completed pregnancies with known outcome between 1998 and 2017 (n = 1962) were analyzed for the use of folic acid and AEDs in the first trimester, seizure count for the entire pregnancy and the presence of major congenital malformation (MCM). The results were presented for three epochs (1998-2004, 2005-2011 and 2012-2017). RESULTS: There was significant increase (p = .001) in the use of folic acid 5 mg/day or more in pre-pregnancy month (43.9 to 81 %) and first trimester (52.7 to 86.6 %). Occurrence of seizures during pregnancy had declined significantly (57.2 to 32.9 %, p = 0.001) over time. Those who were off AEDs during pregnancy declined from 17.4 to 8.5 % (p = .001). Newer AEDs - lamotrigine, levetiracetam, oxcarbazepine and topiramate) were increasingly preferred in the last seven years instead of older AEDs (phenobarbitone, phenytoin and clonazepam). There was no significant change in the use of carbamazepine or valproate. MCM rates did not show any significant change (7.5 to 7.3 %). CONCLUSION: Seizure control and high dose folic acid usage during pregnancy had improved over two decades. Despite the changes in the AED usage over time the MCM rates had remained unchanged probably due to continued use of valproate, increased use of topiramate and clobazam that are associated with higher MCM rates and lack of reduction in polytherapy.

Sodium Channels in Human Pain Disorders: Genetics and Pharmacogenomics.

Acute pain is adaptive, but chronic pain is a global challenge. Many chronic pain syndromes are peripheral in origin and reflect hyperactivity of peripheral pain-signaling neurons. Current treatments are ineffective or only partially effective and in some cases can be addictive, underscoring the need for better therapies. Molecular genetic studies have now linked multiple human pain disorders to voltage-gated sodium channels, including disorders characterized by insensitivity or reduced sensitivity to pain and others characterized by exaggerated pain in response to normally innocuous stimuli. Here, we review recent developments that have enhanced our understanding of pathophysiological mechanisms in human pain and advances in targeting sodium channels in peripheral neurons for the treatment of pain using novel and existing sodium channel blockers.