Standard Anticonvulsant Therapy Research Articles

Case study of use of EpiTapp® app in structural focal epilepsy as component of rehabilitation program

Introduction. In 2022, new clinical guidelines ‘Epilepsy and status epilepticus in adults and children’ were released, according to which it is recommended for adult patients with epilepsy to include behavioral methods in the form of self-management programs in addition to standard antiepileptic therapy as rehabilitation measures in comprehensive care for patients with epilepsy in order to improve the quality of life, cognitive functions and adherence to treatment. Considering the urgency of this problem and the opportunities offered by new clinical guidelines, there has been interest in a more detailed study of the EpiTapp® technique as an element of a self-management program in addition to standard antiepileptic therapy as a comprehensive care, using the example of a patient with structural focal epilepsy (SFE).Objective. To present a clinical case of using the EpiTapp® application as part of a self-management program in addition to standard antiepileptic therapy as a comprehensive care for an adult patient with SFE.Materials and methods. The study used the author's technique of brush tapping (RF patent No. 2606489 dated 10.01.2017). Patient A. used the EpiTapp® application in addition to the antiepileptic therapy she received, as a part of rehabilitation program for self-management of epileptic seizures, on an outpatient basis.Results. The analysis of the diary of observation of epileptic seizures showed that in 93 % of cases, patient A. managed to stop the incipient motor focal seizure (FS) and prevent its transformation into a bilateral tonic-clonic seizure. Thus, against the background of regular use of the EpiTapp® method, the patient's frequency of FS decreased by 55.8 % by visit 4 compared to visit 2. Patient A. rated the effectiveness and safety of the EpiTapp® application by 95 %.Conclusions. Thus, the use of the EpiTapp® application allowed a woman with difficult-to-treat SFE to gain control over epileptic seizures without changing the regimen and dose of antiepileptic therapy.

Comorbid disorders in posttraumatic and post-success epilepsy. Possibilities of therapy

In the article, the authors substantiate the methods of treatment of the most common cause of symptomatic epilepsy in adults, namely traumatic and ischemic. The complexity of treatment is the need to take into account the location and magnitude of brain damage, the severity of the pathological process, risk factors for the most symptomatic epilepsy, the presence of comorbid pathology. Also, the large number of side effects from taking antiepileptic drugs, encourages the discovery of new treatments.A method of treating post-traumatic epilepsy (PTE), in which, in addition to standard anticonvulsant therapy, other drugs were prescribed, such as: ethylmethylhydroxypyridine succinate, nootropic heptapeptide ACTH 4-10, Magnerot, ethylmethylhydroxypyridine succinate, Semax 0.1% solution.Fifteen patients with PTE and 19 patients with post-stroke epilepsy (PIE) were examined. In the process of examination of patients with PTE, the main neurological syndromes that accompany epilepsy are identified and are often combined with each other. At PIE in the anamnesis all patients had various cardiovascular pathology: cerebral atherosclerosis, arterial hypertension, diabetes mellitus, ischemic heart disease, etc.During treatment, in addition to controlling seizures, the number of complaints of cephalgia decreased, the signs of clinical depression and subjective experiences decreased. Positive changes in bioelectrogenesishave been registered. The state of short-term and long-term memory, stability of attention has improved. A positive effect was obtained from the treatment of seizures and comorbid pathology.The alternating effect of the proposed drugs on the background of anticonvulsant therapy leads to a significant reduction in the number and duration of epileptic seizures.

Cannabis for Pediatric Epilepsy.

Epilepsy is a chronic disease characterized by recurrent unprovoked seizures. Up to 30% of children with epilepsy will be refractory to standard anticonvulsant therapy, and those with epileptic encephalopathy can be particularly challenging to treat. The endocannabinoid system can modulate the physiologic processes underlying epileptogenesis. The anticonvulsant properties of several cannabinoids, namely Δ-tetrahydrocannabinol and cannabidiol (CBD), have been demonstrated in both in vitro and in vivo studies. Cannabis-based therapies have been used for millennia to treat a variety of diseases including epilepsy. Several studies have shown that CBD, both in isolation as a pharmaceutical-grade preparation or as part of a CBD-enriched cannabis herbal extract, is beneficial in decreasing seizure frequency in children with treatment-resistant epilepsy. Overall, cannabis herbal extracts appear to provide greater efficacy in decreasing seizure frequency, but the studies assessing cannabis herbal extract are either retrospective or small-scale observational studies. The two large randomized controlled studies assessing the efficacy of pharmaceutical-grade CBD in children with Dravet and Lennox-Gastaut syndromes showed similar efficacy to other anticonvulsants. Lack of data regarding appropriate dosing and pediatric pharmacokinetics continues to make authorization of cannabis-based therapies to children with treatment-resistant epilepsy challenging.

Neurosteroid and benzodiazepine combination therapy reduces status epilepticus and long-term effects of whole-body sarin exposure in rats.

ObjectiveOur objective was to evaluate the protective efficacy of the neurosteroid pregnanolone (3α‐hydroxy‐5β pregnan‐20‐one), a GABAA receptor‐positive allosteric modulator, as an adjunct to benzodiazepine therapy against the chemical warfare nerve agent (CWNA) sarin (GB), using whole‐body exposure, an operationally relevant route of exposure to volatile GB.MethodsRats implanted with telemetry transmitters for the continuous measurement of cortical electroencephalographic (EEG) activity were exposed for 60 minutes to 3.0 LCt50 of GB via whole‐body exposure. At the onset of toxic signs, rats were administered an intramuscular injection of atropine sulfate (2 mg/kg) and the oxime HI‐6 (93.6 mg/kg) to increase survival rate and, 30 minutes after seizure onset, treated subcutaneously with diazepam (10 mg/kg) and intravenously with pregnanolone (4 mg/kg) or vehicle. Animals were evaluated for GB‐induced status epilepticus (SE), spontaneous recurrent seizures (SRS), impairment in spatial memory acquisition, and brain pathology, and treatment groups were compared.ResultsDelayed dual therapy with pregnanolone and diazepam reduced time in SE in GB‐exposed rats compared to those treated with delayed diazepam monotherapy. The combination therapy of pregnanolone with diazepam also prevented impairment in the Morris water maze and reduced the neuronal loss and neuronal degeneration, evaluated at one and three months after exposure.SignificanceNeurosteroid administration as an adjunct to benzodiazepine therapy offers an effective means to treat benzodiazepine‐refractory SE, such as occurs following delayed treatment of GB exposure. This study is the first to present data on the efficacy of delayed pregnanolone and diazepam dual therapy in reducing seizure activity, performance deficits and brain pathology following an operationally relevant route of exposure to GB and supports the use of a neurosteroid as an adjunct to standard anticonvulsant therapy for the treatment of CWNA‐induced SE.

PND74 - COST UTILITY MODEL OF BRIVARACETAM IN THE ADJUNCTIVE TREATMENT FOR PARTIAL-ONSET EPILEPTIC SEIZURES IN SPAIN

Brivaracetam was authorized in Spain in 2016 for treatment as adjunctive therapy for partial onset seizures with or without secondary generalization in adults over 16 years of age with epilepsy. This study aims to assess the cost effectiveness of standard antiepileptic drug therapy plus Brivaracetam compared with the third-generation anti-epileptic drugs used as standard of care from the perspective of the Spanish healthcare payer. The treatment pathway of a hypothetical cohort of patients over 2 years (8 trimesters) was simulated using a Markov model. Data about health state probabilities, seizure frequency and utility values were taken from trials or from the literature. Effectiveness measures, including the probability of changing the health status (reducing the number of seizures), and the QALYs of each health status were analysed throught studies review and real data literature. Unit costs were taken from national references and price references was 2016. Deterministic and probabilistic sensitivity analyses were conducted. Brivaracetam treatment was dominant again Eslicarbazepine and and Lacosamide, and cost-utility again Zonisamine using a willingness to pay of 20,000 Euros per quality adjusted life-year. Probabilistic Sensitive Analysis supports the result of base case. In patients with difficult-to-treat epilepsy, standard anti-epileptic drug therapy plus Brivaracetam appears to be a cost-utility option in Spain.

Akut izoniazid intoksikasyonu: Olgu sunumu

Isoniazid is a bactericidal antituberculosis drug, used commonly for treatment and prophylaxis of tuberculosis. Acute isoniazid intoxication is characterized by a clinical triad consisting of metabolic acidosis with a high anion gap resistant to treatment with sodium bicarbonate, seizures which may be fatal and refractory to standard anticonvulsant therapy, and coma. Pyridoxine, in a dose equivalent to the amount of isoniasid ingested, is the only effective antidote. Here, we reported a 14 years old female patient with the diagnosis of isoniasid intoxcication, successfully treated in our intensive care unit.

Vitamin and Cofactor Responsive Encephalopathies and Seizures

Early diagnosis and treatment vitamin and/or cofactor responsive encephalopathies and seizures is critical for both seizure control and cerebral development and to prevent the kindling of intractable seizures with secondary brain injury. Recognition of these specific disorders is key to their management given their essential requirement for specific cofactors and their reduced responsiveness to standard anticonvulsant therapy. The overall goals of this review are; (1) To provide recognition of the clinical phenotypes of selected treatable metabolic etiologies of early-onset encephalopathies with seizures; (2) To highlight the appropriate diagnostic investigations for each, and (3) To outline the effective treatment strategies. Each condition will be described followed by an approach to vitamin-responsive infantile-onset seizure management. A list of vitamin/cofactor responsive neurological conditions is provided in Table 1.

Cirrhosis associated with pyridoxal 5'-phosphate treatment of pyridoxamine 5'-phosphate oxidase deficiency.

We report the case of an 8-year-old boy with pyridoxamine 5'-phosphate oxidase (PNPO) deficiency. He developed seizures at 24h of age that were refractory to standard anticonvulsant therapy and a trial of pyridoxine but responded to pyridoxal phosphate (PLP) at 28days of life. Genetic testing identified compound heterozygous mutations in the PNPO gene. Management of encephalopathic episodes required escalation of PLP dose to 100 mg/kg/day by 2 years of age. Routine blood tests at this time showed significantly deranged liver function tests (LFTs). A wedge liver biopsy showed early cirrhosis with marked elevation of pyridoxal and pyridoxic acid levels in the liver sample. Despite extensive investigation, no cause other than PLP therapy could be identified for the cirrhosis. The PLP dose was weaned to 50mg/kg/day before episodes of encephalopathy recurred. Concurrent with the reduction of his PLP dose, LFTs showed improvement. However, at 8 years of age, there is persistent evidence of hepatic fibrosis and early portal hypertension. We hypothesise that hepatic toxicity due to PLP or its degradation products is the cause of cirrhosis in this boy. Until further evidence becomes available, we would suggest that people with PNPO deficiency are treated with the minimum dose of PLP required to prevent episodes of encephalopathy.

Convulsive Seizures with a Therapeutic Dose of Isoniazid

An 86-year-old woman who had been treated for tuberculous peritonitis and pulmonary tuberculosis, exhibited a disturbance of consciousness and tonic-clonic convulsions seven days after the administration of the antituberculous drug isoniazid. As her serum vitamin B6 level was remarkably low, she was diagnosed with convulsive seizures due to vitamin B6 deficiency associated with isoniazid treatment. Seizures refractory to standard anticonvulsant therapy were controlled with the administration of pyridoxine. Most reported cases of isoniazid-induced convulsive seizures occurred as a result of an overdose due to attempted suicide. This report presents a case of convulsive seizures that occurred in association with the short-term administration of a therapeutic dose of isoniazid.

Clinical Pharmacology of Midazolam in Neonates and Children: Effect of Disease—A Review

Midazolam is a benzodiazepine with rapid onset of action and short duration of effect. In healthy neonates the half-life (t 1/2) and the clearance (Cl) are 3.3-fold longer and 3.7-fold smaller, respectively, than in adults. The volume of distribution (Vd) is 1.1 L/kg both in neonates and adults. Midazolam is hydroxylated by CYP3A4 and CYP3A5; the activities of these enzymes surge in the liver in the first weeks of life and thus the metabolic rate of midazolam is lower in neonates than in adults. Midazolam acts as a sedative, as an antiepileptic, for those infants who are refractory to standard antiepileptic therapy, and as an anaesthetic. Information of midazolam as an anaesthetic in infants are very little. Midazolam is usually administered intravenously; when minimal sedation is required, intranasal administration of midazolam is employed. Disease affects the pharmacokinetics of midazolam in neonates; multiple organ failure reduces the Cl of midazolam and mechanical ventilation prolongs the t 1/2 of this drug. ECMO therapy increases t 1/2, Cl, and Vd of midazolam several times. The adverse effects of midazolam in neonates are scarce: pain, tenderness, and thrombophlebitis may occur. Respiratory depression and hypotension appear in a limited percentage of infants following intravenous infusion of midazolam. In conclusion, midazolam is a safe and effective drug which is employed as a sedative, as antiepileptic agent, for infants who are refractory to standard antiepileptic therapy, and as an anaesthetic.

Cost Effectiveness of Lacosamide in the Adjunctive Treatment of Patients with Refractory Focal Epilepsy in Belgium

Lacosamide is an anti-epileptic drug, indicated as adjunctive therapy for patients with focal seizures with or without secondary generalization. This study aims to assess the cost effectiveness of standard anti-epileptic drug therapy plus lacosamide 300 mg/day compared with standard therapy alone from the perspective of the Belgian healthcare payer. The treatment pathway of a hypothetical cohort of 1000 patients over 2 years was simulated using a decision tree. Data about health state probabilities, seizure frequency and utility values were taken from lacosamide trials or from the literature. Effectiveness measures included the number of seizures avoided and the number of quality-adjusted life-years gained. Unit costs were taken from national references. Resource use was estimated by a panel of eight neurologists with extensive experience in epilepsy. The price year was 2008. Deterministic and probabilistic sensitivity analyses were conducted. Over a 24-month period, standard anti-epileptic drug therapy plus lacosamide led to a reduction of seven seizures, an increase of 0.038 quality-adjusted life-years and a cost decrease of &U20AC;3619 per patient compared with standard therapy alone. Using a willingness to pay of &U20AC;30 000 per quality-adjusted life-year, the net monetary benefit of standard anti-epileptic drug therapy plus lacosamide amounted to &U20AC;4754. The probability of standard anti-epileptic drug therapy plus lacosamide being cost effective was 97.3%, 99.8%, 99.9% and 100% at 6, 12 , 18 and 24 months, respectively. In patients with difficult-to-treat epilepsy, standard anti-epileptic drug therapy plus lacosamide appears to be a cost-effective option in Belgium.

Kombinationstherapie bei Epilepsie

Use of Monotherapy is acknowledged as the standard anticonvulsant therapy although no more than about 65% of patients become seizure-free with a single antiepileptic drug. Therefore, up to 50% of patients with epilepsy are treated at least intermittently with more than one antiepileptic drug. The percentage of patients achieving complete seizure control with combination therapy after ineffective monotherapy is small. Monotherapy and combination therapy are not always contrary to each other; many anticonvulsants have different modes of action and are effectively a combination therapy in one drug. Combinations of anticonvulsants with differing mechanisms of action are called "rational polypharmacy". A superior efficacy of these combinations over combinations of anticonvulsants with identical or similar mechanisms of action have not been proved by randomised trials. Add-on trials with lacosamide and the combination of lamotrigine and valproic acid, however, suggest a superior tolerability and/or efficacy of combinations with differing mechanisms of action. Treatment with drug combinations should take into account, above all, efficacy and safety, interactions, and costs of each antiepileptic drug as well as comorbidity.

Short-course of prednisolone in solitary cysticercus granuloma: A randomized, double-blind, placebo-controlled trial

To determine the effect of administration of a short course of prednisolone on seizure and radiologic outcome in patients with solitary cysticercus granuloma (SCG). One hundred forty-eight subjects presenting with new-onset seizures (<15 days duration) and with SCG demonstrated on imaging studies were randomly allocated to either treatment with prednisolone (40-60 mg/day for 2 weeks) or placebo in addition to standard antiepileptic drug therapy. The subjects were followed up for seizure recurrence for 9 months. Repeat computed tomography (CT, at 3 months) and magnetic resonance imaging (MRI, at 6 months) to evaluate resolution and calcification of the lesion. There was no difference in the proportion of subjects with seizure recurrence during the follow-up period in the treatment (n = 16, 21.9%) and control (n = 19, 25.33%) groups (p = 0.7). However, generalized seizures occurred in a significantly lesser proportion of subjects in the treatment group (n = 3, 15.79%) in comparison to the control group (n = 12, 60.00%) (p = 0.015). There were no significant differences in the proportion of subjects with complete resolution of the SCG on repeat CT at 3 months [treatment group (27, 46.7%) and control group (23, 39.8%); p = 0.453] and repeat MRI at 6 months [treatment group (28, 46.7%) and control group (21, 38.9%); p = 0.402]. The administration of a short course of prednisolone does not offer significant improvement in seizure control, although a benefit in terms of reducing the likelihood of generalized seizures is possible. Furthermore, it does not improve the chances of resolution of the SCG on follow-up imaging studies.

Emergency Management of Pediatric Convulsive Status Epilepticus

To perform a multicenter study examining the presentations and emergency management of children with convulsive status epilepticus (CSE) to sites within the Paediatric Research in Emergency Departments International Collaborative. Retrospective review of children presenting to emergency departments (EDs) with convulsive seizures of at least 10 minutes' duration. Eight sites within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand participated. Patients were identified through a search of ED electronic records for the period January 2000 to December 2004. Data were obtained from 542 eligible episodes of CSE. Demographics and seizure history were similar across all sites. One third of children with CSE presented with their first seizure. A preexisting diagnosis that predisposed to seizures was present in 59%. Median duration of seizures before hospitalization was 45 minutes, and median duration of treatment in ED before termination was 30 minutes. Prehospital duration did not seem to influence the timing of key ED interventions such as the administration of second-line anticonvulsants or progression to rapid sequence induction (RSI) of anesthesia and intubation. Convulsive status epilepticus was terminated after first-line treatment in 42%, second-line treatment in 35%, and RSI in 22%. One third of the patients had persistent seizure activity beyond 40 minutes of ED treatment. Marked variation in the use of RSI for refractory seizures was observed between sites. Convulsive status epilepticus is an important neurological emergency, with many children experiencing prolonged seizures in both the prehospital and hospital phases. Persistent seizure activity beyond 40 minutes contrasts with current published guidelines. There is a need to adopt a widely accepted approach to the management of children who fail to respond to standard anticonvulsant therapy.

Refractory Status Epilepticus in Suspect Encephalitis

The California Encephalitis Project (CEP) is a program designed to determine causes of encephalitis. We sought to determine whether there are any distinguishing characteristics of patients with encephalitis who develop refractory status epilepticus from those who do not. Data from all patients in the CEP were retrospectively reviewed and analyzed. Diagnostic testing was performed for a panel of infectious agents and medical information collected using a standardized form. Encephalitis patients were subdivided into three categories: (i) patients with status epilepticus unresponsive to standard antiepileptic therapy who required general anesthetic coma for management (Group I), (ii) patients with seizures or status epilepticus responsive to standard antiepileptic therapy (Group II), and (iii) patients without seizures (Group III). Supplementary information was requested on Group I patients. Of 1,151 patients; 43 (4%) were classified as Group I, 459 (40%) as Group II, and 649 (56%) as Group III. Compared to Groups II and III, Group I patients were younger (median age = 10.0 years), more likely to have fever (93%), prodromal respiratory (57%) or gastrointestinal illness (64%), and less likely to have CSF pleocytosis (47%) or abnormal neuroimaging (16%). A causative infectious agent was verified in three of the Group I patients; and a putative agent in nine others. Supplementary information on Group I revealed that 28% died within 2 years and 56% were neurologically impaired or undergoing rehabilitation. Encephalitis and refractory status epilepticus occur most commonly in the pediatric age group, an infectious etiology is usually not established, and outcomes are generally poor.

The cognitive effects of oxcarbazepine versus carbamazepine or valproate in newly diagnosed children with partial seizures

To investigate the effect of oxcarbazepine against standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in children and adolescents (aged 6 to <17 years) with newly diagnosed partial seizures. A multicentre, open-label, randomised, active-control, three-arm, parallel-group, 6-month study. The primary cognitive variable, the Computerized Visual Searching Task (CVST), assessed mental information processing speed and attention. Secondary variables included additional tests assessing psychomotor speed, alertness, memory and learning, and non-verbal intelligence. Of 112 patients randomised, 99 completed the study. The dropout rate was 11.6%; 13 patients discontinued due to adverse events (n=5) or unsatisfactory therapeutic effect (n=8). Mean CVST time decreased in all groups, indicating an improvement of mental processing speed and no cognitive impairment in any treatment group. No statistically significant difference was observed between oxcarbazepine and combined carbamazepine/valproate. Analysis of secondary variables did not show statistically significant differences between oxcarbazepine, carbamazepine and valproate. Analysis of intelligence test results showed that the number of correct answers increased at end point in all groups. The percentage of patients remaining seizure free throughout treatment was comparable across all groups (oxcarbazepine 58%; carbamazepine 46%; valproate 54%; carbamazepine/valproate 50%). The most common adverse events were fatigue and headache for oxcarbazepine, fatigue and rash for carbamazepine, and headache, increased appetite and alopecia for valproate. Oxcarbazepine treatment over 6 months does not display any differential effects on cognitive function and intelligence in children and adolescents with newly diagnosed partial seizures relative to standard antiepileptic drug therapy. No impairment in cognitive function was observed in any treatment group over a 6-month period.

Cognitive Function During Oxcarbazepine Treatment for Partial Seizures

The effect of oxcarbazepine compared to standard antiepileptic drug therapy (carbamazepine and valproate) on cognitive function in 112 children and adolescents (ages 6 to 16 years) with newly diagnosed partial seizures was investigated in a multicenter, open-label, randomized, active-control group study at University Hospital, Bern, Switzerland; University of Maastricht, The Netherlands; and other European centers.

Effects of oxcarbazepine on cognitive function in children and adolescents with partial seizures

The authors investigated the effect of oxcarbazepine on cognitive function in children and adolescents (6 to younger than 17 years of age) with newly diagnosed partial seizures in an open-label comparison with standard antiepileptic drug therapy (carbamazepine and valproate). No differences in cognitive tests were observed between oxcarbazepine and carbamazepine/valproate over a 6-month treatment period.

Struggling with Rasmussen's Syndrome

Struggling with Rasmussen's Syndrome

Seizures, Metabolic Acidosis and Coma Resulting from Acute Isoniazid Intoxication

Isoniazid is an anti-tuberculosis drug, used commonly for treatment and prophylaxis of tuberculosis. Acute isoniazid intoxication is characterized by a clinical triad consisting of metabolic acidosis resistant to treatment with sodium bicarbonate, seizures which may be fatal and refractory to standard anticonvulsant therapy, and coma. Treatment requires admission to the intensive care unit for ventilatory support, management of seizures and metabolic acidosis. Pyridoxine, in a dose equivalent to the amount of isoniazid ingested, is the only effective antidote. We report the successful treatment of two isoniazid intoxication cases: the case of a child developing an accidental acute isoniazid intoxication and an adult case of isoniazid intoxication with the intent of suicide.