Use Of Antiepileptic Drugs Research Articles

Opioid Prescribing for Proximal Row Carpectomy versus Four-Corner Arthrodesis.

Background Proximal row carpectomy (PRC) and four-corner arthrodesis (4-CA) represent motion-sparing procedures for addressing degenerative wrist pathologies. While both procedures demonstrate comparable functional outcomes, postoperative pain presents a surgical challenge that often necessitates the use of opioids. Objectives The aim of this study was to (1) compare opioid prescribing patterns surrounding PRC and 4-CA, (2) identify risk factors predisposing patients to increased perioperative and prolonged postoperative opioids, and (3) examine the association between opioids and perioperative health care utilization. Patients and Methods PearlDiver Patients Records Database was used to retrospectively identify patients undergoing primary PRC and 4-CA between 2010 and 2018. Patient demographics, comorbidities, prescription drug usage, and perioperative health care utilization were evaluated. Perioperative opioid prescriptions and post-operative opioid prescriptions were recorded. Logistic regression analysis evaluated the association of patient risk factors. Results There was no significant difference in perioperative (PRC [odds ratio {OR}: 0.84, p = 0.788]; 4-CA [OR: 0.75, p = 0.658]) or prolonged postoperative opioid prescriptions (PRC [OR: 0.95, p = 0.927]; 4-CA [OR: 0.99, p = 0.990]) between PRC and 4-CA. Chronic back pain and use of benzodiazepines or anticonvulsants were associated with increased risks of prolonged postoperative opioids. Prolonged postoperative opioids presented increased risks of emergency department visits (OR: 2.09, p = 0.019) and hospital readmissions (OR: 10.2, p = 0.003). Conclusion No significant differences exist in the prescription of opioids for PRC versus 4-CA. Both procedures have high amounts of prolonged postoperative opioid use, which is associated with increased risks of emergency department visits and hospital readmissions. Level of Evidence This is a level III, retrospective comparative study.

Sleep duration and quality among U.S. adults with epilepsy: National Health Interview Survey 2013, 2015, and 2017

BackgroundEpilepsy is associated with a high prevalence of sleep disturbance. However, population-based studies on the burden of sleep disturbance in people with epilepsy are limited. This study assessed sleep duration and sleep quality by epilepsy status in the general U.S. adult population aged ≥ 18 years. MethodsWe pooled data of cross-sectional National Health Interview Surveys in 2013, 2015, and 2017 to compare the prevalence of sleep duration and quality among those without epilepsy (N = 93,126) with those with any epilepsy (a history of physician-diagnosed epilepsy) (N = 1774), those with active epilepsy (those with a history of physician-diagnosed epilepsy who were currently taking medication to control it, had one or more seizures in the past year, or both) (N = 1101), and those with inactive epilepsy (those with a history of physician-diagnosed epilepsy who were neither taking medication for epilepsy nor had had a seizure in the past year) (N = 673). We also compared these measures between those with active and those with inactive epilepsy. The prevalences were adjusted for sociodemographics, behaviors, and health covariates, with multivariable logistic regression. We used Z-tests to compare prevalences of sleep duration and quality at the statistical significance level of 0.05. ResultsAdults with any epilepsy reported significantly higher adjusted prevalences of short sleep duration (<7 h) (36.0% vs. 31.8%) and long sleep duration (>9 h per day) (6.7% vs. 3.7%) but a lower prevalence of healthy sleep duration (7–9 h per day) (57.4% vs.64.6%) than those without epilepsy. In the past week, adults with any epilepsy reported significantly higher adjusted prevalences than adults without epilepsy of having trouble falling asleep (25.0% vs. 20.3%), staying asleep (34.4% vs. 26.3%), nonrestorative sleep (adults did not wake up feeling well rested) (≥3days) (50.3% vs. 44.3%), and taking medication to help themselves fall asleep or stay asleep (≥1 times) (20.9% vs. 13.5%). However, adults with active epilepsy did not differ from adults with inactive epilepsy with respect to these sleep duration and quality measures. ConclusionsAdults with epilepsy reported more short or long sleep duration and worse sleep quality than those without epilepsy. Neither seizure occurrence nor antiepileptic drug use accounted for these differences in sleep duration and quality. Careful screening for sleep complaints as well as identifying and intervening on the modifiable risk factors associated with sleep disturbances among people with epilepsy could improve epilepsy outcomes and quality of life.

Perampanel dosage in plasma samples: development and validation of a novel HPLC method with combined UV-Fluorescence detection

Therapeutic drug monitoring (TDM) is a recognized method to improve the quality of use of antiepileptic drugs, such as perampanel (PRP). It is the first compound in the class of selective non-competitive antagonists of AMPA receptors approved in 2012 in Europe and United States for adjunctive therapy of partial seizures. Although several studies have recently underlined that a general reference range for PRP plasmatic concentration might be difficult to propose, TDM of this drug is important in specific clinical situations, as hepatic or renal impairment or co-administration with enzyme-inducing antiepileptics. Several methods have been described in literature for the determination of PRP in different biological matrices, which include the use of liquid chromatography methods coupled with ultraviolet, fluorescence, mass or tandem-mass spectrometry detection. Here we describe the development and validation of a novel method for the measurement of PRP in plasma samples, based on a HPLC-UV/FL double detection approach and using ketoprofen as internal standard. PRP concentration in a small subset of plasma samples of treated patients was evaluated using both our approach and a commercially available CE-IVD LC–MS/MS method. The results obtained were compared, and confirmed the possibility to use our method as an alternative to LC–MS/MS in clinical routine.

A Review of Studies on the Use of New Non-Gabapentinoid Anticonvulsants and Muscle Relaxants in the Control of Acute Postoperative Pain

Postoperative pain management in any type of surgery is an important issue for patients. The pain relief contributes to decreased hospital costs, shorter hospital stay, and elevated patient consent. Correspondingly, in this review article we assessed the postoperative pain management efficacy of new non-gabapentinoid anticonvulsants and muscle relaxant drugs in pre-clinical and clinical studies. The scientific databases, including PubMed, Embase, Scopus, and Google Scholar, were searched using relevant keywords: surgery, postoperative pain, analgesia, non-gabapentinoid anticonvulsants, and muscle relaxants. New anticonvulsants reduce postoperative pain, length of stay at postoperative anesthesia care unit, and analgesic requirement after surgeries. Their mechanisms include the inhibition of glutamate release, blocking the N-type calcium channels of afferent neurons, inhibition of supraspinal 5-hydroxytryptamine-3 receptor, and prevention of cyclin-dependent kinase 5-mediated collapsin response mediator protein 2 phosphorylation. Also, muscle relaxants show the same effects by downregulation the Cacna1a, Cacna1b, and Runt-related transcription factor 1 genes of dorsal root ganglia, inhibition the release of glutamate, aspartate or substance P from the terminals of primary afferent C and Aδ fibers, expression of Neurokinin 1 receptor in the spinal dorsal horn, agonistic effect on α2-adrenoceptor, and stimulation of acetylcholine release in the spinal cord. With respect to the concerns regarding opioid abuse, muscle relaxants and non-gabapentinoid anticonvulsant drugs can be regarded as a safe option for postoperative pain control.

Understanding new-onset refractory status epilepticus from an immunological point of view.

New-onset refractory status epilepticus (NORSE) is unexpected onset of refractory status epilepticus in individuals with no preexisting relevant neurologic condition. The etiologies remain largely cryptogenic; treatment is challenging after failure to control seizures despite use of multiple antiepileptic drugs and anesthetic agents. Frequent fever and other infectious prodromes, elevated proinflammatory cytokine/chemokine levels, and limbic or multifocal brain lesions indicate active inflammation in NORSE. Among identified causes, autoimmune encephalitis is the most common and accounts for more than one-third of all known NORSE cases, followed by infection-related etiologies. Although more evidence is needed, anti-cytokine therapies with tocilizumab and anakinra along with other immunotherapeutic agents used in autoimmune encephalitis can aid in alleviating or hindering the inflammatory cascade and controlling seizures.

Management of Depressed Skull Fractures: Selective Conservative Management of Non Missile Injuries

Objective: To determine the outcomes of management of depressed skull fractures. Study Design: Descriptive Study Place and Duration of Study: Department of Neurosurgeries, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences Gambat and Chandka Medical College Hospital, Larkana from 1st March 2020 to 28th February 2021. Methodology: Eighty patients of both sexes were enrolled in this study. Patients were aged between 12-70 years of age. Patient’s detailed demographics age, sex and body mass index were recorded. Diagnosis of skull fractures from closed head injury patients were undergone for CT scan Depressed fracture of more than 5 mm, cosmetically disfiguring fractures and fracture over the sinuses were operated. All the patients were given prophylactic antibiotics and anticonvulsants. Patients were followed for 4-months. Outcomes were assessed by Glasgow Coma Scale (GCS). Results: Fifty five (68.8%) patients were males and thirty five (31.2%) were females with mean age was 18.21±7.32 years and mean body mass index was 20.04±3.14 kg/m2. Road traffic accident (56.25%) was the most common cause of the injury followed by fall from the height 25 (31.25%). The compound fractures have 48 (60%) and simple fractures were 32 (40%). Surgery was done among 70 (87.5%) cases and 10 (12.5%) patients were conservatively treated. Among these 50 (62.5%) patients were completely recovered. Cerebrospinal fluid leak was the most common complication and was found in 13 (16.25%) cases. Conclusion: The use of antibiotics and anticonvulsants had effective results during peri-operative periods to avoid infection and epilepsy. The initial stage of operation is particularly necessary when the fracture is larger than 5mm. Cerebrospinal fluid leaks occur after surgery as the most common complication. Keywords: Depressed skull fracture, Non-missile injuries, Cerebrospinal fluid

Clinical predictors of drug-resistant epilepsy in children

Background/aimIn up to 20% of epilepsy patients, seizures may not be controlled despite the use of antiepileptic drugs, either alone or in combination. These individuals are considered to have drug-resistant epilepsy. Drug-resistant epilepsy is usually associated with intellectual disability, psychiatric comorbidity, physical injury, sudden unexpected death, and low quality of life. Early detection and prediction of drug-resistant epilepsy are essential in determining the patient’s most appropriate treatment option. This retrospective study aimed to determine the clinical, electroencephalographic, and radiological factors associated with medically intractable childhood seizures.Materials and methods Data regarding 177 patients diagnosed with drug-resistant epilepsy were compared with 281 patients with drug-responsive epilepsy. Results Univariate analysis showed that age at seizure onset, having mixed seizure types, history of status epilepticus, history of neonatal seizures, history of both having febrile and afebrile seizures, daily seizures at the onset, abnormality on the first electroencephalogram, generalized epileptic abnormality on electroencephalogram, abnormal neurodevelopmental status, abnormal neuroimaging, and having symptomatic etiology were significant risk factors for the development of drug-resistant epilepsy (p < 0.05). In multivariable analysis, having mixed seizure types, history of status epilepticus, having multiple seizures in a day, intellectual disability, symptomatic etiology, and neuroimaging abnormality remained significant predictors for developing drug-resistant epilepsy.ConclusionsIn the course of childhood epilepsy, some clinical features may predict the outcome. Early identification of patients with high risk for drug-resistant epilepsy will help plan the appropriate treatment option. Further prospective studies should confirm these findings.

Lamotrigine induced Steven Johnson syndrome: A case report in Al Batool teaching hospital in Diyala governorate

Background: Steven Johnson syndrome (SJS) is a rare disease that is characterized by acute cutaneous manifestation represented by eruptions of the skin and the mucosal membranes. SJS is an immune-mediated disease, a hypersensitive reaction, characterized by hyperpigmentation of the mucous membranes, rash on the skin and multiple bullae and erosions scattered all over the body especially the face, trunk, and the extremities. Many studies reported that the incidence rate of the SJS was about 1.2 – 6 cases/ million each year and it is more common among males while the toxic epidermal necrolysis (TEN) is more common among females. In addition to the cutaneous manifestations.SJS might show multiple systemic manifestations including the liver, lungs and kidneys. In this case we reported the development of Steven Johnson syndrome in relation to the use of lamotrigine antiepileptic drug.

Post-stroke epilepsy and antiepileptic drug use in men and women.

Evidence-based recommendations for choice of antiepileptic drug (AED) in post-stroke epilepsy (PSE) are lacking. The aim of this study was to describe the use and persistence of AEDs when initiating treatment in men and women with PSE. An observational study based on individual-level patient data from a regional healthcare register in Stockholm, Sweden, was conducted. Adults (≥18years) with a stroke diagnosis 2012-2016, a dispensed prescription of any AED within two years after the stroke, and with an epilepsy-related diagnosis were identified. Multinomial logistic regression and logistic regression were used to identify factors associated with choice of AED and discontinuation within 90days, respectively. Of 9652 men and 9844 women with a stroke diagnosis, 287 men and 273 women had PSE and were dispensed AED. More than 60% of both men and women with PSE were treated with levetiracetam. Carbamazepine was the second most common drug followed by lamotrigine and valproic acid. There were significant differences in AED choice depending on for instance sex, age and renal impairment. Levetiracetam had the highest persistence in both men and women. Choice of AED, oral anticoagulant use and percutaneous endoscopic gastrostomy (PEG) showed an association with the persistence to therapy. We conclude that in both men and women with PSE, levetiracetam was the most used AED for initiation of treatment and also had the highest persistence.

Anti-seizure activity of African medicinal plants: The identification of bioactive alkaloids from the stem bark of Rauvolfia caffra using an in vivo zebrafish model

Ethnopharmacological relevanceEpilepsy is one of the major chronic diseases that does not have a cure to date. Adverse drug reactions have been reported from the use of available anti-epileptic drugs (AEDs) which are also effective in only two-thirds of the patients. Accordingly, the identification of scaffolds with promising anti-seizure activity remains an important first step towards the development of new anti-epileptic therapies, with improved efficacy and reduced adverse effects. Herbal medicines are widely used in developing countries, including in the treatment of epilepsy but with little scientific evidence to validate this use. In the search for new epilepsy treatment options, the zebrafish has emerged as a chemoconvulsant-based model for epilepsy, mainly because of the many advantages that zebrafish larvae offer making them highly suitable for high-throughput drug screening. Aim of the studyIn this study, 20 medicinal plants traditionally used in South Africa to treat epilepsy were screened for anti-epileptic activity using a zebrafish larvae model. Materials and methodsToxicity triaging was conducted on 120 crude extracts, 44 fractions and three isolated compounds to determine the maximum tolerated concentration (MTC) of each extract, fraction or compound. MTC values were used to guide the concentration range selection in bioactivity studies. The effectiveness of crude extracts, fractions and isolated compounds from Rauvolfia caffra Sond. in suppression of pentylenetetrazole (PTZ) induced seizure-like behaviour in a 6-dpf zebrafish larvae model was measured using the PTZ assay. ResultsFollowing a preliminary toxicity triage and bioactivity screen of crude extracts from 20 African plants used traditionally for the treatment and management of epilepsy, the methanolic extract of Rauvolfia caffra Sond. was identified as the most promising at suppressing PTZ induced seizure-like behaviour in a zebrafish larvae model. Subsequent bioactivity-guided fractionation and spectroscopic structural elucidation resulted in the isolation and identification of two tryptoline derivatives; a previously unreported alkaloid to which we assigned the trivial name rauverine H (1) and the known alkaloid pleiocarpamine (2). Pleiocarpamine was found to reduce PTZ-induced seizures in a dose-dependent manner. ConclusionsAccordingly, pleiocarpamine represents a promising scaffold for the development of new anti-seizure therapeutic compounds. Furthermore, the results of this study provide preliminary evidence to support the traditional use of Rauvolfia caffra Sond. in the treatment and management of epilepsy. These findings warrant further studies on the anti-epileptic potential of Rauvolfia caffra Sond. using other models.

Pharmacological management of seizures in patients with COVID-19: a systematic review

Background: Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported to exhibit neurological symptoms such as seizures and impaired consciousness. Our study reviews reported cases to assess the pharmacological approach to managing seizures in SARS-CoV-2 patients and associated outcomes. Methods: A systematic review of case reports on the incidence of seizures following coronavirus disease 2019 (COVID-19) among patients that reported use of antiepileptic drugs (AEDs) in management was performed by using the PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines. Databases used included EMBASE, PubMed, SCOPUS, and Google Scholar. Data was presented as qualitative and descriptive data. Results: In total, 67 articles were selected for full-text assessment, of which 19 were included in the final review. Patients had a median age of 54 years, most of whom were male. Remdisivir, dexamethasone, Laminavir, hydroxychloroquine, azithromycin, and Lopinavir-ritonavir were common agents used in the management of COVID-19. Most patients presented with either generalized tonic-clonic seizures or status epilepticus. Most patients received levetiracetam as drug choice or as part of their regimen. Other AEDs commonly prescribed included midazolam and sodium valproate. Some patients received no antiepileptic drug therapy. Most of the patients who died had more than one comorbidity. Also, most of the patients who died received COVID-19 treatment drugs. None of the patients who received midazolam as drug choice or as part of their regimen developed recurrent seizures in contrast to patients who received levetiracetam and sodium valproate as drug choice or as part of their regimen. Interestingly, none of the patients who received no AEDs suffered recurrent seizures or died. Conclusions: Standard guidelines for managing seizures in COVID-19 patients may be required. A limitation of this review is that it involved the use of case reports with no controls and a small number of patients.

Cyclophosphamide‐induced posterior reversible encephalopathy syndrome: A case report

AbstractPosterior reversible encephalopathy syndrome (PRES) is an acute neurological disorder of vascular origin characterized by headache, seizures, encephalopathy, visual disturbances, and focal neurological deficits. Characteristic clinical findings along with T2 or fluid‐attenuated inversion recovery (FLAIR) hyperintensities on magnetic resonance imaging (MRI) in the bilateral parieto‐occipital region help confirm the diagnosis. In addition to common risk factors such as eclampsia, preeclampsia, renal failure, sepsis, and autoimmune diseases, PRES has also been reported in patients receiving chemotherapeutic drugs. We report a case of a 65‐year‐old woman with multiple myeloma who developed PRES following the administration of cyclophosphamide. Although our patients had multiple risk factors for PRES, such as renal insufficiency, bortezomib, cyclophosphamide, and steroids, a comprehensive clinical evaluation pointed toward cyclophosphamide as the cause of PRES. Active treatment to lower blood pressure, the use of antiepileptic drugs, and the withdrawal of cyclophosphamide led to rapid and complete recovery with no residual neurological dysfunction.

Stevens-Johnson syndrome and toxic epidermal necrolysis: literature review

Egle Janusonyte1 1Vilnius University, Faculty of Medicine, Vilnius, Lithuania Abstract Background and aim. Stevens-Johnson syndrome and toxic epidermal necrolysis are rare life-threatening conditions caused by a delayed hypersensitivity skin reaction manifesting through large body surface area epidermal detachment. This condition can occur at any stage of life. In up to 80 % of cases, it develops due to medication such as antibiotics and antiepileptic drugs use, however, it can also be induced by infections. It is crucial to urgently provide supportive care to the patient and to consider possible immunomodulatory therapy measures currently debated on in clinical communities, as well as to transfer the patient to burns treatment unit, if possible. The aim of this literature review is to provide an overview of most recent data in terms of treatment and care as well as possible complications and prognosis in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Materials and methods. The literature review was conducted through the PubMed search system with combination of the terms ‘Stevens-Johnson syndrome’, ‘toxic epidermal necrolysis’, ‘supportive treatment’, and ‘immunomodulatory therapy’. In total, 38 publications were overviewed, the majority of the publications analysed were published over past 10 years with additionally reviewed first historical descriptions of these conditions as well as international classification that is still used. Results. Following extensive literature review, the aetiology, diagnostics, supportive and immunomodulatory treatment recommendations are introduced, most common complications and prognosis are described. Keywords. Stevens-Johnson syndrome; toxic epidermal necrolysis; supportive treatment; immunomodulatory therapy. https://doi.org/10.53453/ms.2021.06.15

CO4 Predictors of Inpatient Relapse in Multiple Sclerosis Patients Using First-Line Disease Modifying Therapies: A Machine Learning Study of Real World Data

Relapse among multiple sclerosis (MS) patients is associated with disability progression and worsening outcomes. This study aims to identify characteristics of inpatient MS relapse using claims data and machine learning techniques. MS patients with a new prescription or administration of a disease modifying therapy (DMT) were identified based on ICD-9/10 diagnosis codes in de-identified Optum® Clinformatics® Data Mart from 2000-2019. The first DMT date was the index date with >=2 MS diagnoses required in the preceding 6 months (baseline). Inpatient relapse was defined as an inpatient visit with a primary MS diagnosis code during the 12 months following the index date. Features included demographics, comorbidities, concomitant medications, healthcare resource utilization (HRU), DMT route of administration and proportion of days covered (PDC) for DMTs. Five-fold cross validation was used to tune and evaluate traditional and regularized logistic regression, XGBoost, support vector machine, random forest and feed-forward neural network models. The best model was selected using the area under the ROC curve (AUC) and accuracy, recall, precision, F1-score and specificity were assessed. Inpatient relapse was observed for 984 (5.2%) patients of 18,820 patients (mean age=44.2 years; females=75.8%). The XGBoost model had the best AUC (AUC=79.3%; accuracy=74.3%; recall=69.7%; precision=13.1%, F1=0.22, specificity=74.5%). Predictors of inpatient relapse included MS related HRU measures (previous IP or ER visit with MS diagnosis, number of MS related encounters, utilization of home care services and durable medical equipment), epilepsy/convulsions, paralysis, urinary tract infections, potential medication side effects (nausea and vomiting), use of muscle relaxants, anticonvulsants and antidepressants. Factors protective of relapse were increased PDC, older age, DMTs administered as infusion, Caucasian race and being female. Our study identified demographic and clinical predictors of inpatient MS relapse with high predictive accuracy. Our findings can potentially be utilized to better manage patients at high risk of relapse.

The long-term efficacy of cannabidiol in the treatment of refractory epilepsy.

Cannabidiol (CBD) has been shown to reduce seizures among patients with refractory epilepsies of various etiologies in recent clinical trials and an expanded access program (EAP). Most studies report efficacy over short time periods (<1year), with little published on longer term efficacy. Here, we investigate the efficacy of CBD for a treatment period of up to 60months (median = 45.5months). We conducted a retrospective review of patient-reported seizure logs and medical records for 54 subjects with refractory epilepsy who enrolled in the Massachusetts General Hospital's open-label EAP for CBD as a new treatment for epilepsy. We analyzed the effect of CBD on seizure frequencies and concomitant antiepileptic drug (AED) use at 1year after starting treatment and the most recent study visit. Our results indicate that CBD maintains its efficacy for controlling seizures from Year 1 to the most recent study visit. The percentage of seizure responders remained similar at these time points (41.7%-42.6%), and the seizure response rate was also maintained (p=.12). Efficacy was also seen over a broad dose range, and up to 50mg/kg/day. CBD was particularly effective for controlling seizures in the setting of tuberous sclerosis complex and for reducing epileptic spasms and absence seizures. Although CBD use did not lead to an overall decrease in concomitant AEDs, most subjects reduced the dose of at least one concomitant AED compared to baseline. CBD was generally well tolerated, with drowsiness and diarrhea as the primary adverse reactions. This study demonstrates CBD does not lose its efficacy in controlling seizures over a treatment period of up to 60months. Taken alongside other results on the efficacy and tolerability of CBD in the treatment of refractory epilepsies, our results provide evidence that CBD is an effective, safe, and well-tolerated AED for long-term use.

Reporting of drug reaction with eosinophilia and systemic symptoms from 2002 to 2019 in the US Food and Drug Administration Adverse Event Reporting System

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced severe cutaneous adverse reaction that is often overlooked owing to its overlap with other infectious and inflammatory illnesses; however, early identification and treatment are important to preventing associated morbidity and mortality.1,2 Historically, anticonvulsant use in association with DRESS syndrome was cited as early as the 1930s, with initial descriptions involving drug-associated hypersensitivity.2 In the 1950s, the term “drug-induced pseudolymphoma” described syndromes of cutaneous symptoms with organ involvement and other systemic features.

TSC1 and TSC2: Tuberous Sclerosis Complex and Its Related Epilepsy Phenotype

AbstractTuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by a multisystemic involvement. In TSC, reduced function of TSC1 and TSC2 genes products (hamartin and tuberin, respectively) leads to an hyperactivation of the mechanistic target of rapamycin (mTOR) pathway and to a consequent cell growth dysregulation. In TSC patients, neurological and neuropsychiatric manifestations, especially epilepsy and neuropsychiatric comorbidities such as autism or intellectual disability, represent the most disabling features. In particular, epilepsy occurrs up to 80% of patients, is often drug resistant and is frequently associated with neurological impairment. Due to the burden of this morbidity, different treatment strategies have been proposed with the purpose to make patients epilepsy free, such as the use of different antiepileptic drugs like vigabatrin, carbamazepine, valproic acid, and levetiracetam. More recently, a mTOR inhibitor (i.e. everolimus) has showed promising results in terms of seizures reduction.

Sudden unexpected death in epilepsy: Experience of neurologists in Saudi Arabia

ImportanceSudden unexpected death in epilepsy (SUDEP) may account for up to 17% of all deaths in epilepsy. However, it is unknown if neurologists discuss this risk with patients. ObjectiveThis study aimed to examine the understanding and practices of SUDEP by neurologists in Saudi Arabia. MethodsAn electronic web-based survey was sent to 125 neurologists using the mailing list of the Saudi Neurology Society. The survey questions included respondents’ demographics, frequency of SUDEP discussion, reasons for discussing/not discussing SUDEP, and perceived patient reactions. Respondents’ knowledge of the SUDEP risk factors was examined using 12 items from the currently available literature. Logistic regression analyses were applied to examine the factors that influence the frequency of SUDEP discussions and perceived patient reactions. ParticipantsThe participants were neurologists who had completed postgraduate training, devoted >5% of their time to clinical care, and had at least one patient with epilepsy in their independent neurology clinic. ResultsA total of 60 respondents met the eligibility criteria and completed the surveys. Of them, 25% discussed SUDEP most of the time, 65% sometimes or rarely, and 10% never discussed it. Of those who discussed SUDEP with their patients, 63.3% did it if the patient was at high risk. Poor compliance with antiepileptic drugs (AEDs) was the most common patient factor highlighted (81.7%). The perceived patients’ reactions were variable, with positive reactions (motivation to comply and appreciation) being the most frequent. The majority of respondents (78.3%) had incomplete understanding of the published SUDEP risk factors, with SUDEP knowledge scores ≤2.5 (≤50% of the possible total score). The most identified risk factors were frequent generalized tonic-clonic seizures (83.3%), long duration of epilepsy (53.3%), lack of use or sub-therapeutic levels of AEDs (50%), and AED polytherapy (50%). No association was found between how often SUDEP was discussed and other factors, including training in epilepsy, ≥10 years in practice, seeing ≥100 patients, and having SUDEP cases in the past two years. It was found that patients positively reacted to discussion on SUDEP if neurologists had a good understanding of the SUDEP risk factors (χ2 = 5.773, p = 0.016). ConclusionsNeurologists in Saudi Arabia do not often discuss SUDEP with patients that have epilepsy. Moreover, when they do, they stress a more individualized approach despite having only a limited understanding of the SUDEP risk factors. Our findings suggest that more guidance should be provided to practitioners on how best to counsel their patients about SUDEP.

THE EFFECT OF ANTICONVULSANT DRUGS ON SERUM THYROID-STIMULATING HORMONE

Objective: Antiepileptic (AED) drugs are an integral component of the management of seizure disorder; however, they have a wide spectrum of adverse effects. It is important to be aware of these side effects as they have a major impact on the quality of life and are sometimes partially reversible after drug discontinuation. Among them, the influence of AED on thyroid function is an important one. However, there is only limited data available. The objective of this study is to evaluate the effect of AED on thyroid-stimulating hormone (TSH).&#x0D; Methods: A cross-sectional study of 1-year duration (march 2017 – march 2018) was conducted among 150 epileptic patients receiving phenytoin, carbamazepine, and sodium valproate for more than 6 months in a tertiary care center in central Kerala. Serum levels of TSH of patients on AED were compared with that of 50 healthy age- and sex-matched control groups. Data regarding the same were analyzed using SPSS version 16 with the Chi-square test, ANOVA, and independent t-test.&#x0D; Results: A total of 150 epileptic patients with a mean age of 35.54 + 10.72, including 66 males (44%) and 84 females (56%) were enrolled in this study. Fifty adults of mean age 36.5+ 8.4 and male to female ratio 1.10:1 formed the control group. It was found that the mean TSH value of patients on phenytoin (3.97+ 1.47), carbamazepine (3.57+ 1.44), and sodium valproate 3.03 + 1.41 significantly higher than that of the control group (1.91 + 0.72). On comparing the mean serum TSH of the drug group significant difference noted between phenytoin and sodium valproate treated group. Among the 12 patients develop subclinical hypothyroidism 65% taking drugs for more than 5 years.&#x0D; Conclusion: There is a positive correlation between the use of anticonvulsants and thyroid dysfunction and the association increases with the duration of therapy. The clinicians should be encouraged for regular monitoring of thyroid function test to impart a better quality of life to the patients.

Factors Associated With Inadequate Response to Bisphosphonate Therapy in Patients With Osteoporosis in Real-Life Clinical Practice: a Single-Center Retrospective Analysis of 300 Patients

Introduction: Bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA) is a useful tool to monitor response to osteoporosis treatment in clinical practice. Despite bisphosphonates therapy, some patients may exhibit bone loss during treatment for different reasons. These patients may have greater fracture risk than responders and may have unrecognized secondary causes that require further attention and treatment. Objectives: To identify factors associated with inadequate response (IR) to bisphosphonates therapy in patients with osteoporosis in real-life clinical practice. Methods: This is a single-center case-control study of patients with osteoporosis treated with bisphosphonates as recommended. Baseline and follow-up (12–24 months/apart) DXA scans were performed on same device (GE-Lunar Prodigy). IR was defined as loss of BMD greater than the least significant change (LSC) on the follow-up DXA. Clinical, biochemical and densitometric parameters of patients with IR were compared to responders using t-test or Mann-Whitney test (continuous), or chi-square test (categorical variables), as appropriated. We used logistic regression to assess the association magnitude between exposures and IR. Results: From 300 patients included from 2014 to 2018 (13% males, mean age 68 ±10 years), 198(66%) were treated with oral bisphosphonates and 102(34%) with zoledronic acid (ZA). IR was observed in 44(15%) patients. All parameters were similar at baseline, except for greater prevalence of oral bisphosphonates (82% vs 63%, p=0.016) and anticonvulsants use (18% vs 7%, p=0.015) in patients with IR compared to responders. Additionally, patients with IR exhibited a lower % change in CTX following therapy in comparison to responders (median -37% [IQR -68; -16%] vs -57% [-74; -32], p=0.029, respectively), and higher serum CTX levels after treatment (median 236pg/mL [IQR 162; 344] vs 165pg/mL [119; 254], p=0.004). The likelihood of IR was greater with oral bisphosphonates then with ZA (OR 2.61, IC95% 1.16–5.81, p=0.002), and with anticonvulsants use (OR 2.94. IC95% 1.19–7.25, p=0.019). The association with IR persisted for both variables (p≤0.01), when accounted simultaneously in the same model, along with age and gender. Conclusion: Inadequate bisphosphonate response was present in 15% of individuals, which was independently associated with anticonvulsant use and particularly among those on oral bisphosphonate therapy rather than ZA. This knowledge may help to clinically identify potential modifiable factors related to unresponsiveness and to optimize treatment accordingly.