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.

Retrospective analysis of effectiveness of fingolimod in real life setting in Turkey (REFINE).

BACKGROUND: During multiple sclerosis (MS) treatment different modes of action such as lateral (interferon beta to glatiramer acetate or glatiramer acetate to interferon beta) or vertical (interferon beta/glatiramer acetate to fingolimod) drug switch can be performed. This study aims to investigate the clinical effectiveness of switching from the first-line injectable disease modifying treatments (iDMTs) to fingolimod (FNG) compared to switching between first-line iDMTs. METHODS: This is a multicenter, observational and retrospective study of patients with relapsing-remitting MS who had lateral and vertical switch. The observation period included three key assessment time points (before the switch, at switch, and after the switch). Data were collected from the MS patients' database by neurologists between January 2018 and June 2019. The longest follow-up period of the patients was determined as 24 months after the switch. RESULTS: In 462 MS patients that were included in the study, both treatments significantly decreased the number of relapses during the postswitch 12 months versus preswitch one year while patients in the FNG group experienced significantly fewer relapses compared to iDMT cohort in the postswitch 12 months period. FNG cohort experienced fewer relapses than in the iDMT cohort within the postswitch 2 year. The mean time to first relapse after the switch was significantly longer in the FNG group. DISCUSSION: The present study revealed superior effectiveness of vertical switch over lateral switch regarding the improvement in relapse outcomes. Patients in the FNG cohort experienced sustainably fewer relapses during the follow-up period after the switch compared the iDMT cohort. Importantly, switching to FNG was more effective in delaying time to first relapse when compared with iDMTs.

Analysis of Vitamin D Receptor Polymorphisms in Patients with Familial Multiple Sclerosis.

OBJECTIVE: Genetic and environmental factors are important in the development of the multiple sclerosis (MS). Vitamin D shows its effects on the immune system with the vitamin D receptor (VDR) in the nucleus. Single nucleotide polymorphisms (SNPs) in the VDR gene can lead to alterations in vitamin D functions and metabolism.Taq I, Apa I, Fok I and Bsm I polymorphisms and MS associations have been investigated in many studies. VDR gene polymorphism has not been previously studied in patients with familial MS. AIM: We aimed to investigate the relationship between familial MS patients present in Turkish population and VDR genotypes Taq I, Apa I and Fok I polymorphisms. METHODS: 29 patients with a family history of MS and 120 healthy control subjects were included in the present study. We studied present VDR genotypes Taq I, Apa I and Fok I polymorphisms. RESULTS: We observed a significant difference between controls and patient group only in Taq I polymorphism (p: 0.025). Homozygousity of G allele was not seen in the patients whereas in controls frequency of that genotype was p:0.208. When gender was considered males show significant difference for GG genotype. There were no significant association for the Apa I and Fok I polymorphisms. CONCLUSION: Although our findings suggest association between VDR Taq I polymorphism and the familial MS, additional studies are needed to establish detailed relationships.

A Rare Presentation of Cranial Polyneuropathy Without Rash Caused by Varicella Zoster Virus.

INTRODUCTION: Varicella Zoster Virus (VZV) is associated with many disorders of the central and peripheral nervous systems including neuralgia, meningitis, meningoencephalitis, cerebellitis, vasculopathy, myelopathy, Ramsay-Hunt syndrome, and polyneuritis cranialis. Cranial nerves V, VI, VII, VIII, IX, X, XI, and/or XII may be affected. The neurological disorders caused by VZV usually present with rash, but may rarely present without rash. CASE REPORT: We herein present a case of polyneuritis cranialis without rash caused by VZV affecting cranial nerves VII, VIII, IX, and X. After excluding other causes of the condition, we diagnosed VZV infection based on VZV DNA in the CSF and an elevated anti-VZV IgG level in serum. The patient responded well to antiviral therapy. CONCLUSION: VZV infection should be kept in mind during the differential diagnosis of polyneuritis cranialis; it is important to note that VZV re-activation may occur without rash.

Hesperidin, a Citrus Flavonoid, Has the Ameliorative Effects Against Experimental Autoimmune Encephalomyelitis (EAE) in a C57BL/J6 Mouse Model.

The aim of this study was determined the effects of Hesperidin (HP) on neuronal damage in brain tissue caused by Experimental allergic encephalomyelitis (EAE), an established model of multiple sclerosis in C57BL/J6 mice. To explore 40 mice were equally divided into four groups: (1) Control, (2) EAE, (3) HP, and (4) HP + EAE. 14 days after induction of EAE with MOG35-55 and pertussis toxin, the mice treated with HP at the doses of 50 mg/kg/day for 7 days subcutaneously. To our results HP treatment prevents the oxidative stress caused by EAE via a decrease in lipid peroxidations and increase in elements of the antioxidant defense systems in brain tissue. Also, EAE elevate the IL-17, express the pro-inflammatory cytokines, and caspase-3-like immunreactivity, show apoptosis, staining in EAE mice brain and increased the incidence of histopathological damage. However, immonohistochemical and histological changes were reversed with HP. Moreover, elevated TNF-α and IL-1ß levels, a result of EAE, were decreased in serum and neurological deficits as clinical signs were reversed with HP treatment in EAE mice, given HP. In conclusion, HP treatment effectively prevents oxidative, immunological and histological damage in the brain caused by EAE. It was thought that the beneficial effects of HP are likely a result of its strong antioxidant and anti-inflammatory properties.

Hesperidin protects brain and sciatic nerve tissues against cisplatin-induced oxidative, histological and electromyographical side effects in rats.

In the present study, the beneficial effect of hesperidin (HP), a citrus flavonoid, on cisplatin (CP)-induced neurotoxicity was investigated. A total of 28 rats were equally divided into four groups; the first group was kept as control. In the second and third groups, CP and HP were given at the doses of 7 and 50 mg/kg/day, respectively. In the fourth group, CP and HP were given together at the same doses. The results indicated that although CP caused significant induction of lipid peroxidations and reduction in the antioxidant defense system potency in the brain and sciatic nerve, HP prevented these effects of CP. Besides, CP led to histopathological damage, mainly apoptosis, as well as electromyographical (EMG) changes in sciatic nerve. On the other hand, HP treatment reversed histopathological and EMG effects of CP. In conclusion, CP had severe dose-limiting neurotoxic effects and these effects of CP can be prevented by HP treatment. Thus, it appears that coadministration of HP with CP may be a useful approach to attenuate the negative effects of CP on the nervous system.

Familial Pompe Disease.

INTRODUCTION: Pompe disorder is a rare glycogen storage disorder that is due to a deficiency of the lysosomal alpha glycosidase enzyme. The heart, skeletal muscle, liver and nervous system can be affected from the lysosomal glycogen accumulation. Symptoms such as muscle weakness, hypotony, myopathy and respiratory failure develop. The onset may be at the infantile, adolescent or adult period depending on the enzyme level. The CK level is high in almost all patients. The diagnosis is made with enzyme level measurement and genetic analysis. CASE REPORT: We present a family with Pompe disease consisting of the asymptomatic mother and two siblings who presented with muscle weakness and respiratory failure and who had been followed-up with a diagnosis of muscular dystrophy for a long time.

Fish oil protects the peripheral and central nervous systems against cisplatin-induced neurotoxicity.

OBJECTIVE: The protective effects of fish oil (FO) on cisplatin (CP)-induced central and peripheral neurotoxicity were investigated in rats. METHODS: Rats (n = 28) were divided equally into four groups, the first group was kept as a control. In the second and third groups, CP and FO were given at doses of 7 mg/kg and 1 softgel/rat/day, respectively. In the fourth group, CP and FO were given together at the same doses. RESULTS: Although CP caused significant oxidative damage, via induction of lipid peroxidation and reduction in the antioxidant defense system potency, FO treatment largely reversed these effects. CP also resulted in histopathological damage, such as apoptosis, and electromyographical changes in the sciatic nerve. FO treatment partially prevented the histopathological and electromyographical effects of CP. DISCUSSION: CP has severe central and peripheral neurotoxic effects in rats and these effects were largely prevented by FO treatment. Thus, it appears that co-administration of FO with CP may be a useful approach to attenuate the negative effects of CP on the nervous system.

The Turkish experience of COVID-19 infection in people with NMOSD and MOGAD: A milder course?

BACKGROUND: COVID-19 is a multisystemic infection with variables consequences depending on individual and comorbid conditions. The course and outcomes of COVID-19 during neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are not clearly known. OBJECTIVE/METHODS: The aim of this study was to examine the features and outcomes of COVID-19 infection in NMOSD and MOGAD patients. The patients' demographic and clinical factors, disease modifying treatment (DMT) used and disease information of COVID-19 infection were recorded. Conditions leading to hospitalization and severe exposure to COVID-19 infection were also analyzed. RESULTS: The study included 63 patients from 25 centers. Thirty-two patients (50.8%) belong to AQP-4 seropositive group, 13 (20.6%) and 18 (28.6%) were in MOG-positive and double-seronegative groups, respectively. Risk factors for severe COVID-19 infection and hospitalization were advanced age, high disability level and the presence of comorbid disease. Disease severity was found to be high in double-seronegative NMOSD and low in MOGAD patients. No statistically significant effect of DMTs on disease severity and hospitalization was found. CONCLUSION: In NMOSD and MOGAD patients, advanced age, high disability and presence of comorbid disease pose risks for severe COVID-19 infection. There was no direct significant effect of DMTs for COVID-19 infection.

Neuropathic Pain Frequency in Neurology Outpatients: A Multicenter Study.

INTRODUCTION: Neuropathic pain is common, but the frequency of misdiagnosis and irrational treatment is high. The aim of this study is to evaluate the rate of neuropathic pain in neurology outpatient clinics by using valid and reliable scales and review the treatments of patients. METHODS: The study was conducted for 3 months in eleven tertiary health care facilities. All outpatients were asked about neuropathic pain symptoms. Patients with previous neuropathic pain diagnosis or who have neuropathic pain symptoms were included and asked to fill painDETECT and douleur neuropathic en 4 questions (DN4) questionnaire. Patients whose DN4 score is higher than 3 and/or painDETECT score higher than 13 and/or who are on drugs for neuropathic pain were considered patients with neuropathic pain. The frequency of neuropathic pain was calculated and the treatments of patients with neuropathic pain were recorded. RESULTS: Neuropathic pain frequency was 2.7% (95% CI: 1.5-4.9). The most common cause was diabetic neuropathy. According to painDETECT, the mean overall pain intensity was 5.7±2.4, being lower among patients receiving treatment. Pharmacological neuropathic pain treatment was used by 72.8% of patients and the most common drug was pregabalin. However, 70% of those receiving gabapentinoids were using ineffective doses. Besides, 4.6% of the patients were on medications which are not listed in neuropathic pain treatment guidelines. CONCLUSION: In our cohort, the neuropathic pain severity was moderate and the frequency was lower than the literature. Although there are many guidelines, high proportion of patients were being treated by ineffective dosages or irrational treatments.

Is there a relationship between Toxoplasma gondii infection and idiopathic Parkinson's disease?

Idiopathic Parkinson's disease defines a group of Parkinson's disease (PD) of which the aetiology is unknown but an underlying brain disease is suspected. We selected patients of this subgroup of PD and investigated the seropositivity rate for anti-Toxoplasma IgG antibody by Sabin-Feldman dye test (SFDT). By measuring seropositivity in PD patients, we searched for a probable relationship between Toxoplasma gondii infection and idiopathic PD incidence. Fifty patients diagnosed with idiopathic PD and 50 healthy volunteers were included in the study. Blood samples were taken from all 100 participants and anti-T. gondii antibody titres were investigated using SFDT. Anti-T. gondii antibodies were detected at a titre of >or=1/16 in 25 of the 50 patients (50%) and in 20 of the control group (40%). No higher antibody titre was found in the control group. In conclusion, despite the emerging literature on a possible relationship between T. gondii infection and neurological disease, and the high anti-T. gondii seropositivity found in our PD patients, we did not detect any statistically significant association between T. gondii and idiopathic PD.

A case of high grade glioma following treatment of relapsing-remitting multiple sclerosis with fingolimod.

Multiple sclerosis is a major cause of neurological disability, especially in young adults. There have been several case reports of an increased risk of cancer after long-term treatment for multiple sclerosis. Fingolimod is an immunomodulating agent used in the treatment of relapsing-remitting multiple sclerosis. The side effects commonly associated with fingolimod are cardiac side effects, macular edema, and elevated liver enzyme levels. Increased risks of infection and cancer have also been reported. High grade glioma is an aggressive primary brain tumor. There has been one case report of high grade glioma during fingolimod treatment. Here, we report the case of a 58-year-old woman diagnosed with glioblastoma multiforme after one year of fingolimod treatment for multiple sclerosis.

Can T2 blackout effect be a marker of iron accumulation in brains of multiple sclerosis patients?

OBJECTIVE: T2 blackout (TBO) effect, which is a common finding in the brains of multiple sclerosis (MS) patients and older population that are imaged for other reasons on diffusion weighted imagings (DWI) and apparent diffusion coefficient (ADC) map show the existence of paramagnetic materials in the tissue. Because iron is known to accumulate in especially deep gray matter (DGM) structures in MS brains, we aimed to investigate the relationship between TBO and clinico-radiological parameters that may be iron-related in MS. METHODS: We retrospectively reviewed the latest MR images of MS patients on 3 Tesla MR scanner between 2018 and 2019. TBO existence and severity on DWI-ADC was assessed by two radiologists and its correlation with several outcomes of MS was investigated. RESULTS: No significant relationship was found between TBO and gender, subtype of MS whereas TBO was positively correlated with parameters such as black-hole lesions, cortical atrophy, duration of disease, age and extended disability status scale (EDSS) score. CONCLUSIONS: TBO shows correlation with the conditions which were revealed to be associated with iron accumulation in the brain of MS patients in the literature. Therefore, we concluded that TBO and its severity in DGM may represent iron accumulation in MS brains. ADVANCES IN KNOWLEDGE: TBO effect as a frequent imaging finding in daily practice may be used as predictor of the disease course of MS due to possible effects of iron accumulation in brain and thereby may be useful in modifying treatment strategies.

Two New Cases and Literature Review of CLIPPERS Syndrome with Long-Term Follow-up.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder of the central nervous system. The pathophysiology of CLIPPERS is unknown. The disease has characteristic radiological lesions located in the pons, bulbus, and cerebellum. Here we report two new cases and review the literature on CLIPPERS syndrome. A 35-year-old woman presented with a 2-month history of progressive double vision, vertigo, gait ataxia, nausea, and vomiting. The second case was that of a 40-year-old Iraqi man who presented with a 3-month history of vertigo, headache, and gait ataxia. Diagnosis of CLIPPERS was established based on findings of punctate, nodular enhancing lesions in the pons and bulbus in the first case and in the cerebellum in the second. Our patients responded well to steroid therapy and remained relapse-free for 2 years. CLIPPERS is a rare autoimmune disorder with characteristic radiological findings. Long-term immunosuppressive therapy is necessary for treatment.

Listeria monocytogenes rhombencephalitis in a patient with multiple sclerosis during fingolimod therapy.

OBJECTIVE: To describe a case of Listeria monocytogenes rhombencephalitis in a patient receiving fingolimod. METHODS: This is a case study. RESULTS: Our patient developed acute rhombencephalitis with hydrocephalus induced with Listeria monocytogenes while on fingolimod. Shunt surgery was performed for the hydrocephalus and patient recovered partially after medical and surgical therapy. CONCLUSION: We describe the first probable case of fingolimod-associated Listeria monocytogenes rhombencephalitis in a patient with multiple sclerosis. Clinicians should be aware of listeriosis and implement measures for its prevention.

Neurological autoantibodies in drug-resistant epilepsy of unknown cause.

BACKGROUND: Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. AIMS: To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. METHODS: Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were determined. RESULTS: Serum antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive patients. CONCLUSION: Autoimmune factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

Cerebrospinal Fluid Dynamics in Patients with Multiple Sclerosis: The Role of Phase-Contrast MRI in the Differential Diagnosis of Active and Chronic Disease.

Objective: Multiple sclerosis (MS) is an inflammatory disease characterized by demyelinating plaques in the white matter. Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a new hypothesis for the etiopathogenesis of MS disease. MS-CCSVI includes a significant decrease of cerebrospinal fluid (CSF) flow through the cerebral aqueduct secondary to an impaired venous outflow from the central nervous system. This study aimed to determine whether CSF flow dynamics are affected in MS patients and the contributions to differential diagnosis in active and chronic disease using phase-contrast magnetic resonance imaging (PC-MRI). Materials and Methods: We studied 16 MS patients with chronic plaques (group 1), 16 MS patients with active plaques-enhanced on MRI (group 2), and 16 healthy controls (group 3). Quantitatively evaluation of the CSF flow was performed from the level of the cerebral aqueduct by PC-MRI. According to heart rates, 14-30 images were obtained in a cardiac cycle. Cardiac triggering was performed prospectively using finger plethysmography. Results: No statistically significant difference was found between the groups regarding average velocity, net forward volume and the average flow (p > 0.05). Compared with the controls, group 1 and group 2, showed a higher peak velocity (5.5 ± 1.4, 4.9 ± 1.0, and 4.3 ± 1.3 cm/sec, respectively; p = 0.040), aqueductal area (5.0 ± 1.3, 4.1 ± 1.5, and 3.1 ± 1.2 mm2, respectively; p = 0.002), forward volume (0.039 ± 0.016, 0.031 ± 0.013, and 0.021 ± 0.010 mL, respectively; p = 0.002) and reverse volume (0.027 ± 0.016, 0.018 ± 0.009, and 0.012 ± 0.006 mL, respectively; p = 0.000). There were no statistical significance between the MS patients with chronic plaques and active plaques except for reverse volume. The MS patients with chronic plaques showed a significantly higher reverse volume (p = 0.000). Conclusion: This study indicated that CSF flow is affected in MS patients, contrary to the hypothesis that CCSVI-induced CSF flow decreases in MS patients. These findings may be explained by atrophy-dependent ventricular dilatation, which may occur at every stage of MS.

The association between vitamin D receptor polymorphisms and multiple sclerosis in a Turkish population.

BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS). Genetic and environmental factors are important in disease development. Many studies have investigated the relationship between MS and VDR polymorphisms. VDR gene polymorphism has not been previously studied in Turkish MS patients. We aimed to investigate the relationship between MS and VDR genotypes Taq I, Apa I and Fok I polymorphisms in a Turkish population. METHODS: 167 MS patients and 146 healthy control subjects were included in the present study. MS and the VDR TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) polymorphisms were investigated. RESULTS: The study enrolled 167 patients (121 females, 46 males) with MS and 146 healthy individuals (88 females, 58 males). The frequency of only the Fok I polymorphism differed significantly between the two groups (p = 0.002). The TaqI (rs731236) and ApaI (rs7975232) genotype distributions were not significantly different between MS patients and healthy controls (p = 0.626 and p = 0.990, respectively). Also there were no significant gender difference between patients and controls for Taq I and Apa I. CONCLUSION: In conclusion, we found a significant association between MS and the FokI polymorphism in our region of Turkey. However, the results may be different in other populations. More epidemiological and genetic studies are needed to explain the association between genetic factors and MS.

Effects of phenytoin and lamotrigine treatment on serum BDNF levels in offsprings of epileptic rats.

The role of brain-derived neurotrophic factor (BDNF) is to promote and modulate neuronal responses across neurotransmitter systems in the brain. Therefore, abnormal BDNF signaling may be associated with the pathophysiology of schizophrenia. Low BDNF levels have been reported in brains and serums of patients with psychotic disorders. In the present study, we investigated the effects of antiepileptic drugs on BDNF in developing rats. Pregnant rats were treated with phenytoin (PHT), lamotrigine (LTG) and folic acid for long-term, all through their gestational periods. Experimental epilepsy (EE) model was applied in pregnant rats. Epileptic seizures were determined with electroencephalography. After birth, serum BDNF levels were measured in 136 newborn rats on postnatal day (PND) 21 and postnatal day 38. In postnatal day 21, serum BDNF levels of experimental epilepsy group were significantly lower compared with PHT group. This decrease is statistically significant. Serum BDNF levels increased in the group LTG. This increase compared with LTG+EE group was statistically significant. In the folic acid (FA) group, levels of serum BDNF decreased statistically significantly compared to the PHT group. On postnatal day 38, no significant differences were found among the groups for serum BDNF levels. We concluded that, the passed seizures during pregnancy adversely affect fetal brain development, lowering of serum BDNF levels. PHT use during pregnancy prevents seizure-induced injury by increasing the levels of BDNF. About the increase level of BDNF, LTG is much less effective than PHT, the positive effect of folic acid on serum BDNF levels was not observed. LTG increase in BDNF is much less effective than PHT, folic acid did not show a positive effect on serum BDNF levels. Epilepsy affects fetal brain development during gestation in pregnant rats, therefore anti-epileptic therapy should be continued during pregnancy.