Antiepileptic Therapy Research Articles

Clinical case of religious delusion in a combination of schizoaffective disorder and epilepsy

IntroductionDespite existing observations of religious delusions in epilepsy in classical psychiatric literature, such clinical cases are rare in current practice.ObjectivesTo reveal features of disease progression, interference of combined mental pathology, treatment specifics, markers of possible harmful behavior.MethodsPsychopathological, Multichannel eyes closed resting EEG in interictal period.ResultsPatient N, 39 years old, manifested her illness at age 13 with affective bipolar disorder; phases lasted several months each. From age 19, rare recurrent generalized convulsive paroxysms preceded by an aura; non-convulsive paroxysms were observed. The patient was uncritical of paroxysms and discontinued anticonvulsive therapy. At age 29 and 30 she suffered two psychotic attacks (lasting several weeks) with sensory delusions of meaning, staging, persecution, megalomaniacal ideas of apocalyptic content (ideas that she was responsible for possible outbreak of nuclear war, coming of the Apocalypse, her son was the antichrist). Delusional behavior (tried to take the naked infant out into the cold, throwing him out of the window). Anticonvulsive therapy accompanied by antipsychotic medications. Schizoaffective disorder and epilepsy diagnosed. From age 35, acute psychotic attacks with apocalyptic delirium preceded by the same aura lasted maximum one day, followed by partial amnesia. Epileptiform polyspikes (up to 150 μV) registered in the right temporal-central EEG leads.ConclusionsPresence of religious delusion in combined schizoaffective disorder and epilepsy, requires special approach: combination of anticonvulsants and antipsychotics. Religiosity of patient should be taken into account as well.DisclosureNo significant relationships.

The Value of Shunt Surgery or Prophylactic Antiepileptic Therapy or Both in the Development of Dementia at Early Stages in Patients With Ventricular Dilatation.

The primary purpose of the current study was to determine the value of the shunt surgery and/or prophylactic antiepileptic therapy, in patients after mild traumatic brain injury (mTBI) with ventricular dilatation (VD) and incipient cognitive impairment, in the prevention of cognitive deterioration and probably in the development of dementia.Based on the following criteria: a) mTBI b) VD detected in CT scan during admission, and c) the presence of one of the following: i) dizziness, ii) headache, and iii) seizures, admitted to the Emergency Department between January 2010 and January 2020, we enrolled 127 of 947 eligible subjects.The subjects were divided into five groups: Group A (control group): only VD illustration in CT scan, Group B: incipient dementia, who had a more insidious onset presenting with cognitive dysfunctions at indefinite ages, Group C: shunt system (SH)/antiepileptic drugs (AEDs) presenting with cognitive dysfunction and urinary incontinence or gait disturbances or both, that were treated as idiopathic normal-pressure hydrocephalus (iNPH) with the surgical placement of an SH and AED therapy (standard AED phenytoin (1000 mg loading dose followed by 300 mg) daily), and Group D: AED, presenting with cognitive dysfunctions at indefinite ages and one or two episodes of seizures in the past, treated with AED from the very first moment of initiation with a standard AED phenytoin (1000 mg loading dose followed by 300 mg) daily.Overall, improvement in daily activities was achieved in 14.1% (18 of 127 patients), recording a significantly higher performance in group D (5.5%) rather than in groups A (1.5%), B (3.1%), and C (3.9%), (p < 0.05). We concluded that changes in VD (ΔVD) were associated with improvement in mRS (ΔmRS ≥ 1) - daily activities and mental status. ΔVD was also independently associated with reduced daily activities during the long-term follow-up. Interestingly, therapeutic shunting and AED in patients with a history of epilepsies may have a positive impact on the development of mental status impairment. This is a novel observation that has to be confirmed by more extensive multicenter studies in the future.

Effects of Long-Term Treatment with Different Types of Anti-Epileptic Drugs on Vitamin D2 and Osteoprotegrin Serum Levels in Iraqi Patients

Epilepsy is a chronic neurological illness had been described as repeated seizures associated with abnormal neurological activities in the brain. Epilepsy affects nearly fifty million people worldwide, with 85 percent of them living in developing countries. Vitamin D2 (VD2) is ergocalciferol (made from ergosterol). Genetic disorders related to vitamin D metabolism are dysfunction of generally loss osteoid mineralization the leading cause to bone disorders including: rickets or osteomalacia. Osteoprotegerin (OPG) is an osteoclastogenesis inhibitory factor (OCIF), OPG has essential role in bone metabolism and bone mass level. The aim of the present study is to investigate the effects of long-term treatment with anti-epileptic drugs (old Vs new antiepileptics) on vitamin D2 and osteoprotegrin levels among Iraqi epileptic patients. The study included fifty-one epileptic outpatients, whom attending the Consultant Clinic of Baghdad Teaching Hospital at the Medical City –Complex for the period from October/2021 to December/2021. The selected patients were on antiepileptic drugs for more than 2years, hence were grouped according to their antiepileptic therapy into: Group-1: 24 epileptic patients on old antiepileptic drugs (Carbamazepine or Valproate). Group-2: 27 epileptic patients on new antiepileptic drugs (Levetiracetam), to be compared with Group-3: 28 apparently healthy control subjects, with age and sex matching to that of patients. Serum was obtained from their blood specimens to measure: serum VD2 and OPG concentrations among the study groups participants, using specific ELISA Kits. Data analysis revealed that the mean vitamin D2 levels were not significantly different between group -1 (old antiepileptic drugs) and group-2 (new antiepileptic drugs), whereas, both of the patients groups expressed significantly lower values than the control group. However, serum osteoprotegrin levels were significantly elevated in group-1 compared to group-2. Furthermore, both of the epileptic patients groups had significantly higher values compared to the healthy subjects group. Keywords: Osteomalacia, antiepileptic drugs, Vitamin D2, Osteoprotegrin.

Comparison between the effects of older versus newer generations of antiepileptic drugs on bone metabolism in adult Iraqi patients: an observational study

Background: Metabolic bone disorder is a significant endocrine system disorder that encompasses any disorder that alters the natural skeleton's mineralization process. Epilepsy is a prevalent central nervous system disorder that can cause biochemical abnormalities involving bone metabolism in the epileptic patients. The present study aimed to investigate the effects of chronic use of older compared to the newer generations of antiepileptic drugs on bone metabolism-related biomarkers. Methods: The study included fifty-one epileptic outpatients who attended the Consultation Clinic of Baghdad Teaching Hospital at the Medical City Complex from October/2021 to December/2021. The selected patients were on antiepileptic drugs for more than 2 years, hence were grouped according to their antiepileptic therapy into: Group-1: 24 epileptic patients on old antiepileptic drugs (Carbamazepine or Valproate). Group-2: 27 epileptic patients on new antiepileptic drugs (Levetiracetam), compared with Group-3: 28 healthy control subjects. Serum was obtained from their blood specimens to measure: calcium and inorganic phosphate by colorimetric assays, parathyroid hormone, and level of bone alkaline phosphatase activity. Results: Data analysis revealed that the median value of serum parathyroid hormone levels was significantly elevated in the epileptic patients' groups compared to the healthy control group. However, group-2 (new generation antiepileptic drugs) presented higher values. Whereas serum calcium and inorganic phosphate levels showed non-significant variation for all the studied groups. Furthermore, serum bone alkaline phosphatase activity exhibited significantly higher values in the patients compared to the healthy subjects group, with more significant elevation among those on old generation antiepileptic drugs (Carbamazepine or Valproate). Conclusion: Epileptic individuals who had been on AEDs for more than two years had increased parathyroid hormone levels, which were boosted by the newer antiepileptic drug Levetiracetam. Furthermore, BAP serum levels were considerably greater in epileptic patients than in healthy control participants, with larger values generated by older antiepileptic medications.

Overexpression of BDNF in the ventrolateral periaqueductal gray regulates the behavior of epilepsy-migraine comorbid rats.

ObjectiveTo investigate the effects of brain‐derived neurotrophic factor (BDNF) overexpression in the ventrolateral periaqueductal gray (vlPAG) on behavioral changes in epilepsy–migraine comorbid rats.MethodWe used an adeno‐associated virus (AAV)‐mediated vector to supplement BDNF in the vlPAG area prior to the establishment of a pilocarpine‐nitroglycerin (Pilo‐NTG) combination‐induced comorbid model of epilepsy and migraine. Seizure‐ and migraine‐related behaviors were analyzed. Cell loss and apoptosis in vlPAG were detected through hematoxylin‐eosin (HE) and TUNEL staining. Immunofluorescence staining analyses were employed to detect expressions of BDNF and its receptor, tyrosine kinase B (TrkB), in vlPAG. Immunohistochemical staining was conducted to detect expressions of c‐Fos and calcitonin gene‐related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and trigeminal ganglion (TG).ResultsComparing to control group, AAV–BDNF injected comorbid group showed lower pain sensitivity, scratching head, and spontaneous seizures accompanied by the downregulation of c‐Fos labeling neurons and CGRP immunoreactivity in the TNC and TG. However, these changes were still significantly higher in the comorbid group than those in both epilepsy and migraine groups under the same intervention.ConclusionThese data demonstrated that supplying BDNF to vlPAG may protect structural and functional abnormalities in vlPAG and provide an antiepileptic and analgesic therapy.

Investigating the Link Between the Gut Microbiome and Epilepsy in Zebrafish

Epilepsy is the fourth most common neurological disorder affecting over 50 million people worldwide. Recent research indicates that modulation of the gut microbiome can alter the course of the disease in animal models as well as in humans. The gut microbiome is an ecosystem of fungi, viruses, and bacteria that is influenced by an individual’s genetics, diet, and lifestyle. The impact that the gut‐brain axis may have on epilepsy is not well understood. Dietary modifications are often used as treatment options for epileptic patients that are unresponsive to other anticonvulsant therapies. In fact, current research indicates that ketogenic diets are associated with a decrease in microbial diversity and diminished seizure activity. It is not known whether this dietary modification works through the gut‐brain axis. Zebrafish are a commonly used animal model to study human disease, including epilepsy and gut microbiome mechanisms. The aim of this study is to validate the use of zebrafish to study the interactions between the gut‐brain axis and epilepsy, as well as further explore the mechanism by which the microbiome alters the course of the disease. We hypothesize that antibiotic‐treated fish will experience diminished seizure responses to Pentylenetetrazol (PTZ) due to a decrease in intestinal bacterial abundance. Zebrafish were treated with broad‐spectrum antibiotics to alter the diversity of the microbiome. Fish were then given PTZ to induce a seizure‐like state. Seizure activity was recorded and evaluated using EthoVision tracking system and software. Intestinal and brain tissue were harvested for bacterial DNA and RNA respectively. Bacterial abundance was significantly decreased in antibiotic treated fish. Seizure activity was significantly increased in PTZ‐treated fish and was surprisingly augmented in antibiotic‐treated fish (n= 5, p &lt; 0.05). In addition, we observed an increase in glutamate along with a decrease in GABA receptor expression in PTZ‐treated fish; these results were reversed in fish treated with both antibiotics and PTZ. Collectively these results indicate that zebrafish are an effective model for studying gut‐brain communication involving epilepsy and modulating the gut microbiome may influence seizure activity in PTZ‐treated fish.

Ex Vivo and In Vivo Studies of the Lysophospholipids Edelfosine and Mitelfosine to Develop Novel Anti‐Epileptic Therapies

Epilepsy is a chronic neurological disorder characterized by repeated seizures. Today, most anti‐epileptic therapies are a combination of anticonvulsant drugs that work on the excitability of neurons by inhibiting sodium and calcium channels, enhancing GABAergic transmission, inhibiting glutamate transmission or have several combined actions. However, these drugs have detrimental side effects, such as congenital disabilities and psychiatric comorbidities such as mood disorders, depression, and anxiety. In addition, ~35% of adults and ~15% of children epilepsy patients are resistant to these available therapies. Thus, it is critical to study new drugs against epileptic seizures that target neuronal mechanisms different from those used by classical anticonvulsants. Edelfosine (Ef) is a lysophospholipid that works as a phospholipase‐C‐β3 (PLCβ3) inhibitor. PLCβ3 is an effector of the G protein coupled to muscarinic acetylcholine receptors that produces inositol triphosphate and diacylglycerol increasing the release of calcium (Ca+2) from the calcium‐storing organelles. This cytoplasmic Ca2+ regulates several signaling cascades including opening of ion channels that leads neurons to excitotoxic death. Thus, Ef utilizes a neuroprotective mechanism against excitotoxicity that does not act directly on ion channels. This makes Ef a superior drug against muscarinic hyperstimulation. Unfortunately, Ef is not effective within the brain due to the blood‐brain barrier's (BBB) high selectivity, which does not allow its entry. Our project aims to deliver therapeutic concentrations of Ef to the brain to diminish neuronal excitotoxicity. Our first studies test the ex vivo effect of Ef in rat hippocampal slices after two different muscarinic hyperstimulation (excitotoxic insults). Our results showed that Ef could decrease brain excitotoxicity from both insults by inhibiting the PLCβ3 enzyme. This ex vivo preliminary data demonstrates for the first time in a brain model that exposure of hippocampal slices to Ef induced a significant recovery after a muscarinic hyperstimulation insult. For the next studies, we developed two non‐BBB‐targeted serum albumin (SA)‐based drug delivery system (DDS) loading Ef and the Ef analog, mitelfosine (Mf). We characterized the particle physical properties of these Ef‐SA DDS and Mf‐SA DDS using dynamic light scattering and circular dichroism. For both DDS, SA showed characteristic structural changes compared to the native SA, demonstrating the capacity of SA to load these two lysophospholipids. We also performed a short in vivo experiment for four days administrating these DDS to determine their safety in mice. From these in vivo preliminary results, we concluded that Ef‐SA DDS and Mf‐SA DDS showed no sign of toxicity and did not affect the weight, grooming or mobility. Future experiments will focus on the development of BBB‐targeted Ef‐SA DDS and Mf‐SA DDS and their in vivo effect in an epilepsy mouse model.

THE EVALUATION OF ANTI-EPILEPTIC DRUGS DOSAGE IN MALNOURISHED CHILDREN: CASES IN INDONESIAN COMMUNITY OF EPILEPSY

Anti-epileptic drug (AED) has a narrow therapeutic index of drugs that a slight increase in dosage showed toxic effects. The therapeutic response is difficult to predict in malnutrition status because the patient with nutritional deficiency have more complicated problems likes hypoalbuminemia, macronutrient and micronutrients deficiency that affected the levels of AEDs. The nutritional deficiency could be a direct and indirect cause of ineffective AEDs therapy and also recurrent epilepsy. This study aims to describe the use of antiepileptic drugs in Indonesian children with poor nutritional status. The research design was observational studies with cross sectional random sampling to evaluate the AED doses of malnutrition status in children. All information was collected by spreading electronic forms and interviewing the parents by phone. The data were analyzed descriptively. Total of 8 malnourished children mostly included in the range of ages from &gt;2 to 12 years (n=5; 62.50%) with means 3,9±2,7 years. The study showed valproic acid was bigger used in monotherapy (n=5; 62,50%) than polytherapy with carbamazepine or sodium phenytoin and phenobarbital. The means estimation of valproic acid monotherapy concentration in females’ group (n=2; 33,33%) showed sub-therapeutics level were Cssmin 26,09±0,57 mg/L and Cssmax 64,17±1,39 mg/L, also the means in males’ group (n=2; 33,33%) of valproic acid monotherapy were Cssmin 22.07±2,71 mg/L and Cssmax 54.27±6.66 mg/L. All of them included in good clinical outcome of free seizure &gt; 6 months.

Online Consultation as A Rescue Measure for Children with Neurological and Neurodevelopmental Disorders in the COVID-19 Era

Background: A covid-19 pandemic is an unprecedented event, which has a profound impact on the lives of children with neurological and neurodevelopmental disorders besides other people. In Bangladesh, the effects of the Covid-19 pandemic on children with neurological and neurodevelopmental disorders have not been adequately studied. Aim of the study: The aim of this study was to assess the diseases status of children with neurological and neurodevelopmental disorders during the Covid-19 pandemic. Methods: This voluntary prospective observational study was conducted during the period from June 2020 to August 2020 with an attachment of the department Paediatric Neuroscience, Bangladesh Shishu Hospital &amp; Institute, Dhaka, Bangladesh, and Neurogen Health Care, Dhaka, Bangladesh. A total of 78 children with at least one symptom of neurological and/or neurodevelopmental disorders were included as the study subjects of this study. Both previously diagnosed and newly recruited patients were accumulated as the study subjects. Both physical and online (With telephonic communication) consultation and follow-up were arranged for all the patients during the study period. All data were collected, processed, and analyzed by using MS Office and SPSS version 23 programs as per need. Results: In this study, the mean (±SD) age of the participants was 9.87±2.59 years. The male-female ratio was 1.4:1. The majority of the participants were from rural areas (55) and only 2 were from Covid-19 affected. About half of the participants (49%) were with epilepsy. Besides this, ‘impairment in social interaction, communication and behavior problem’, CP with global developmental delay, syndromic child, and ‘hyperactivity and inattention were found in 22%, 13%, 10%, and 6% participants respectively. The majority of the patients (53%) of this study were under antiepileptic therapies. Besides this, 9%, 13%, 5%, 14%, and 6% of participants were taking Immunosuppressive therapies, physical or occupational therapies, psychotherapy, combination therapy, and some other therapies respectively. Conclusion: Epilepsy is the most common disorder among children with neurological and neurodevelopmental disorders who saught for online consultation. Online consultation followed by subsequent physical consultation may be considered as an effective approach in managing patients with neurological and neurodevelopmental disorders during any pandemic situation like Covid-19.

Current Aspects of Antiepileptic Therapy in Pregnant Women

Achieving a high quality of life in patients with epilepsy is of paramount importance not only for neurologists, but also for allied professionals who guide patients through the subsequent stages of treatment after diagnosis. This is of particular relevance to patients in the gestational period. Literature suggests that 13% of women experience an exacerbation of epilepsy during pregnancy, which is due to a reduction in plasma levels of antiepileptic drugs (PEPs) due to increased metabolism. However, 14% of women have seizures exclusively during pregnancy.

A relation between the quality of life of patients with epilepsy and adherence to treatment as well as retention on therapy

Objective: to demonstrate the mutual influence of the quality of patients’s life during epilepsy, adherence to received anticonvulsant therapy and retention on therapy.Material and methods. We conducted an analytical review of studies published by foreign authors in recent years (published within 2016–2021 were considered of top priority), devoted to the influence of various factors on adherence to therapy in patients with epilepsy. A search for relevant publications was conducted in English-language databases (PubMed/MEDLINE, ClinicalKey) by using key words and phrases: “epilepsy AND quality of life AND adherence to therapy”, “epilepsy AND quality of life AND retention on therapy”, “epilepsy AND adherence to therapy”, “compliance AND epilepsy AND quality of life”, “adherence to therapy AND retention on therapy AND epilepsy”, “nonadherence to therapy AND epilepsy AND quality of life”. After the selection procedure, 22 scientific publications were included in the review.Results. Factors that have a negative impact on adherence to therapy have been identified (comorbid cognitive impairment, the combination of lack of control over seizures and the presence of adverse events after drug administration, depression and anxiety, the need to change the lifestyle for taking the drug, concern about the potential negative consequences of taking the drug, recent uncontrolled seizures, lack of professional implementation, high frequency of taking the drug, problems with doctor-patient relationship, insufficient social support), and factors that have a positive impact (emotional support from the doctor, establishing doctor-patient partnership).Conclusion. There is a relationship between the patient's quality of life and adherence to therapy. Patient adherence to therapy is important for the effectiveness of epilepsy treatment and, along with the severity of epilepsy, is a significant factor affecting the quality of patients’ life during epilepsy. An opportunity for long-term retention on anticonvulsant therapy also has a cross-correlation with quality of life.

The potential interaction between antiepileptic drugs and nutraceuticals used in pediatrics with epilepsy

Background: The trend of using nutraceuticals in Indonesia increases every year. This study aims to describe nutraceuticals consumed in pediatrics with epilepsy as additional antiepileptic therapy and analyze their potential drug interactions.&#x0D; Methods: This research was a cross-sectional study with total sampling method which was carried out in the period of June to July 2020. Inclusion criteria were children with epilepsy aged 0-17 years who were members of the Indonesian Epilepsy Community, had a doctor's diagnosis of epilepsy, received oral antiepileptic medication, and took nutraceutical products/food supplements. Data were analyzed descriptively based on data obtained through electronic data filling sheets and interviews.&#x0D; Results: There were 106 participants from the Indonesian Epilepsy Community in total, with 14 children (13.2 %) using nutraceutical supplements. They were male (n=8; 57.1%), 2-12 years old (n=10; 71.4%), and good nutritional status (n=10; 71.4%). Most nutraceuticals consumed were dietary supplements containing vitamins (n=10; 71.4%). Of the eight potential drug interactions identified, 25% (n=2) were significant interactions, and 75% (n=6) were minor interactions. The potential for major interactions occurred in administering nutraceutical products containing vitamin D with the antiepileptic drug phenytoin and phenobarbital.&#x0D; Conclusion: In this study, nutraceuticals and antiepileptic drugs had a little clinically meaningful interaction effect.

Modern aspects of anticonvulsant pharmacotherapy in newborns

Proper treatment of neonatal seizures is crucial for reducing long-term neurological disorders. None of the currently used drugs to treat neonatal seizures has sufficient evidentiary base to make an unambiguous conclusion about its effectiveness. There are no results of large-scale studies that allow choosing an anticonvulsant drug for starting therapy and an alternative to it, in case the drug of choice is ineffective. The review summarizes the data on the effectiveness of anticonvulsants of different pharmacologic classes and considers their benefits, drawbacks, and possible mechanisms of variability in effectiveness when used in newborns. The review also analyzes approaches to the duration of the anticonvulsant therapy and discusses the problems and prospects of clinical trials for increasing the effectiveness and safety of anticonvulsant therapy in newborns.

Neurocognitive Outcome and Seizure Freedom After Awake Surgery of Gliomas.

ObjectivesGliomas are often diagnosed due to epileptic seizures as well as neurocognitive deficits. First treatment choice for patients with gliomas in speech-related areas is awake surgery, which aims at maximizing tumor resection while preserving or improving patient’s neurological status. The present study aimed at evaluating neurocognitive functioning and occurrence of epileptic seizures in patients suffering from gliomas located in language-related areas before and after awake surgery as well as during their follow up course of disease.Materials and MethodsIn this prospective study we included patients who underwent awake surgery for glioma in the inferior frontal gyrus, superior temporal gyrus, or anterior temporal lobe. Preoperatively, as well as in the short-term (median 4.1 months, IQR 2.1-6.0) and long-term (median 18.3 months, IQR 12.3-36.6) postoperative course, neurocognitive functioning, neurologic status, the occurrence of epileptic seizures and number of antiepileptic drugs were recorded.ResultsBetween 09/2012 and 09/2019, a total of 27 glioma patients, aged 36.1 ± 11.8 years, were included. Tumor resection was complete in 15, subtotal in 6 and partial in 6 patients, respectively. While preoperatively impairment in at least one neurocognitive domain was found in 37.0% of patients, postoperatively, in the short-term, 36.4% of patients presented a significant deterioration in word fluency (p=0.009) and 34.8% of patients in executive functions (p=0.049). Over the long-term, scores improved to preoperative baseline levels. The number of patients with mood disturbances significantly declined from 66.7% to 34.8% after surgery (p=0.03). Regarding seizures, these were present in 18 (66.7%) patients prior to surgery. Postoperatively, 22 (81.5%) patients were treated with antiepileptic drugs with all patients presenting seizure-freedom.ConclusionsIn patients suffering from gliomas in eloquent areas, the combination of awake surgery, regular neurocognitive assessment - considering individual patients´ functional outcome and rehabilitation needs – and the individual adjustment of antiepileptic therapy results in excellent patient outcome in the long-term course.

Sublingual Administration of Tacrolimus and Cases of Significant Nephrotic and Neurologic Toxicity

<h3>Introduction</h3> This topic warrants consideration due to the popularity of sublingual administration of tacrolimus and the possibility of deleterious effects. There are significantly different characteristics of sublingual tacrolimus compared to oral administration. In bypassing enterohepatic circulation, a greater proportion of circulating tacrolimus may be available in a 'free' form, unbound to proteins and blood cells. This is similar to a rapid intravenous delivery of calcineurin inhibitor which has noted toxicities. <h3>Case Report</h3> (Case 1) A 49 year old male underwent heart transplant without induction, sublingual tacrolimus was started and after two days of trough levels of 5ng/mL or below, the dose was increased to 4mg SL bid, levels increased from to 17.8 ng/mL. While creatinine increased from 1.7 mcg/dL (POD#2) to a peak of 5.1 mcg/dL on POD#6. The patient was otherwise quite stable. Tacrolimus was held temporarily then converted to oral administration. The creatinine eventually recovered to a value of 1.5mg/dL. The average tacrolimus trough level (while receiving oral dosing) during this period of creatinine recovery was 5.9 ng/ML. (Case 2) 64 year old man with ICM received a heart transplant with uneventful operative course and no induction. He received tacrolimus 1mg orally pre-operatively. Then he received 2mg Of the drug sublingually twice daily until POD # 2. On POD#3 he experienced a generalized tonic-clonic seizure that terminated with anticonvulsant therapy. The tacrolimus trough levels rose quickly after the initial tacrolimus sublingual dosing postoperatively, measured at 11.4 ng/mL on POD#2. Neurology recommended a switch to cyclosporine (goal trough level 200-250ng/mL). The patient remained on levetiracetam for 14 days, no further epileptic activity was observed. Renal function during this episode from a creatinine of 1.4 mg/dL on POD#1 to 4.2 mg/dL on POD#3. <h3>Summary</h3> The molecular size of tacrolimus allows for passage into the glomerulus when in the free form. This may also facilitate blood/brain barrier transport. The presented cases provide cause for consideration of possible toxicity of tacrolimus given sublingually, particularly in patients whose levels rise rapidly. Through rapid absorption, the drug may not have sufficient time to bind to proteins and cells before it reaches end organs in which toxicity occurs.

A case of primary antiphospholipid antibody syndrome with intermittent cerebral venous sinus thrombosis manifested with recurrent epilepsy

Antiphospholipid syndrome (APS) is an acquired autoimmune clinical disorder characterized by persistently raised levels of anti-phospholipid antibodies and clinical feature of hypercoagulability (recurrent vascular thrombosis and pregnancy morbidities). Primary APS is idiopathic in nature though secondary APS is associated with other connective tissue diseases like SLE. Here, we present an instance of primary APS with recurrent cerebral venous sinus thrombosis in a youthful unmarried female who clinically presented with generalized epilepsy. Level of anti-cardiolipin (aCL) and anti-beta 2 GP1 antibodies were found elevated on two occasions 12 weeks apart. The patient was treated with anticoagulation therapy along with anti-epileptic therapy and she responded well to the therapy. This case report highlights that clinicians should always suspect APS in female patients who had history of seizures and ischemic or thrombotic lesions on brain imaging, irrespective of presence of pregnancy comorbidities. Keywords: antiphospholipid syndrome; cerebral venous; sinus thrombosis; epilepsy

Hematological consequences of antiepileptic drug therapy among children with epilepsy

Hematological consequences of antiepileptic drug therapy among children with epilepsy

Status epilepticus caused by canine distemper virus in a striped hyena (Hyaena hyaena)

AbstractA 6‐month‐old free‐living female striped hyena (Hyaena hyaena) was referred to the Veterinary Teaching Hospital of Ferdowsi University of Mashhad, Mashhad, Iran with lethargy and seizures. The general and neurological examinations revealed normal heart rate, polypnoea, abnormal respiratory sounds, decreased consciousness and no postural reactions in limbs. The animal had generalised seizures every 20 minutes, lasting about 1 minute. To control seizures, 10 mg diazepam (0.7 mg/kg) was injected intravenously four times every 2 minutes. With this treatment, the animal's seizures stopped. Based on characteristic clinical signs, lymphopaenia, and positive rapid kit and RT‐PCR results, canine distemper virus (CDV) was confirmed. The animal developed general seizures again 12 hours after referral and died during the seizures. This is the first case report of status epilepticus due to CDV in a striped hyena that did not respond to anticonvulsant therapies and caused the death of the animal.

Serum Calcium, Vitamin D3 and Bone Specific Alkaline Phosphatase Levels in Nigerian Children Treated with Antiepileptic Drugs: A Comparative Study

Background and Aim of the Study: Studies have shown that serum 25-hydroxycholecalciferol, calcium and bone-specific alkaline phosphatase (B-ALP) are altered in children on antiepileptic drugs (AEDs), and these could result in poor bone mineralization. The study aimed to determine the serum 25-hydroxycholecalciferol, calcium, and B-ALP levels among children on AEDs attending the paediatric neurology clinic of the University of Port Harcourt Teaching Hospital (UPTH).&#x0D; Methods: This cross-sectional analytical study was carried out from January 2018 to April 2019 on 100 children on AEDs and 100 age- and gender-matched healthy controls, aged 1.5 - 17 years. Data on socio-demography, AED regimen, and clinical examination findings of the subjects, their serum 25-hydroxycholecalciferol, calcium, and B-ALP levels were obtained and entered into a proforma. Data obtained were analysed using IBM SPSS version 20. Statistical significance was set at p-value of &lt; 0.05.&#x0D; Results: The subjects had significantly lower mean serum 25-hydroxycholecalciferol and calcium and higher mean serum B-ALP levels than the controls, respectively. The mean serum 25-hydroxycholecalciferol was significantly lower in children on AED polytherapy. There was negative correlation between the duration of drug therapy and all serum biochemical indices but this was only significant for serum 25-hydroxycholecalciferol level (p = 0.027). Age significantly impacted negatively on serum 25-hydroxycholecalciferol, p = 0.036 and calcium levels, p = 0.009, but not on B-ALP (p = 0.392).&#x0D; Conclusion: Children on antiepileptic drugs in UPTH had lower mean serum 25-hydroxycholecalciferol and calcium levels but higher mean serum BALP level than healthy controls, as well as inverse relationship between duration of AED therapy and 25, hydroxycholecalciferol, calcium and B-ALP. We therefore recommend children with epilepsy on antiepileptic drugs have their serum 25-hydroxycholecalciferol, calcium and B-ALP levels monitored to enable early detection of any abnormalities.

EFFECT OF DIFFERENT ANTICONVULSANTS ON LIVER ENZYME ACTIVITIES IN PATIENTS WITH SEIZURE DISORDER

Background: Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures, which has transient signs and/or symptoms of abnormal, synchronous neuronal activity in the brain. Antiepileptic drugs (AEDs) used for the prevention of seizure have been found to be an inducer of liver enzyme activity. So, the purpose of this study was to see the effect of antiepileptic drugs on hepatic enzymes activity. Methods: An observational study was carried out in Kathmandu Medical College from October 2020 to April 2021 at neurology department. Sixty-seven seizure patients aged 19-89 years were included in the study. Liver function test was performed before medication, followed up and monitored for three and six months. Paired sample t-test was used to compare the means by using SPSS version 15. Results: Among carbamazepine (CBZ) and sodium valproate (VPA) treated cases, 4.5% and 9.1% respectively showed raised Alanine aminotransferase (ALT) activity whereas, 13.6% and 4.5% respectively showed raised Alkaline Phosphatase (ALP) activity. ALT activity was higher in VPA treated patient compared to CBZ treated patient. However, ALP activity was raised in CBZ treated patient compared to VPA treated patients. No, change in liver enzyme activities was observed in patient treated with Levetiracetam Conclusions: Anticonvulsant drugs used during the treatment have mild to moderate hepatotoxicity. Liver enzyme activity more than two to three-fold may increase. Levetiracetam has minimal hepatic metabolism while sodium valproate is more hepatotoxic. Therefore, routine screening of hepatic enzymes is recommended to the patients under antiepileptic therapy.