Single Seizure Research Articles

Audiogenic Seizures in the Streptozotocin-Induced Rat Alzheimer's Disease Model.

Alzheimer's disease (AD) is a neurodegenerative and progressive disorder with no cure and constant failures in clinical trials. The main AD hallmarks are amyloid-β (Aβ) plaques, neurofibrillary tangles, and neurodegeneration. However, many other events have been implicated in AD pathogenesis. Epilepsy is a common comorbidity of AD and there is important evidence indicating a bidirectional link between these two disorders. Some studies suggest that disturbed insulin signaling might play an important role in this connection. To understand the effects of neuronal insulin resistance in the AD-epilepsy link. We submitted the streptozotocin (STZ) induced rat AD Model (icv-STZ AD) to an acute acoustic stimulus (AS), a known trigger of seizures. We also assessed animals' performance in the memory test, the Morris water maze and the neuronal activity (c-Fos protein) induced by a single audiogenic seizure in regions that express high levels of insulin receptors. We identified significant memory impairment and seizures in 71.43% of all icv-STZ/AS rats, in contrast to 22.22% of the vehicle group. After seizures, icv-STZ/AS rats presented higher number of c-Fos immunopositive cells in hippocampal, cortical, and hypothalamic regions. STZ may facilitate seizure generation and propagation by impairment of neuronal function, especially in regions that express high levels of insulin receptors. The data presented here indicate that the icv-STZ AD model might have implications not only for AD, but also for epilepsy. Finally, impaired insulin signaling might be one of the mechanisms by which AD presents a bidirectional connection to epilepsy.

P300 event-related potentials in people with epilepsy: clinico-neurophysiologic study

BackgroundThere is increasing evidence that prolonged or recurrent seizures can cause or exacerbate cognitive impairment (CI) in memory, attention, orientation, and visuospatial and abstraction disabilities, all of which can jeopardize educational progress and achievement throughout life. The objectives of our study are to assess the cognitive functions in people with epilepsy (PwE) using P300 event-related potentials (ERPs), and correlate each P300 components with six explanatory variables (epilepsy type, seizure type, NHS3 score- seizure severity, disease duration, age at first seizure, and the number of anticonvulsant medications).MethodsOne hundred and two PwE [52 with focal epilepsy and 50 with generalized epilepsy, as classified by the International League Against Epilepsy in 2017]. They underwent electroencephalography (EEG) and P300. The Montreal Cognitive Assessment (MoCA) scale was used to assess baseline cognitive functions.ResultsEpileptic patients showed significant latency prolongation and amplitude reduction of P300 as compared to non-epileptic population. Longer P300 latency and lower amplitude were seen in patients with abnormal EEG records. P300 latency was longer in patients using poly-therapy. P300 components correlated well with age at presentation and disease duration but not with NHS3. According to epilepsy type, 50.98% of PwE had focal epilepsy and 49.02% had generalized epilepsy, 85.29% of them had abnormal EEG recording. Considering seizure type, 47.06% had a generalized tonic–clonic seizure, 38.24% had a focal to bilateral tonic–clonic seizure, 20.59% had a myoclonic seizure, 12.75% had a focal with impaired awareness seizure, 3.92% had a focal aware seizure, and 2.94% had an absence seizure. Seventy-seven PwE had one type of seizure, while 25 had more than one type of seizure. The NHS3 score was higher in those with a single seizure type than in those with multiple seizure types.ConclusionAll seizure types had an abnormal P300 component, indicating cognitive function deficits. P300 may be a promising objective method for assessing cognitive function in PwE. The number of antiepileptic drugs used, the presence of EEG abnormalities, the age at presentation, and the duration of the disease are the factors that best correlate with cognitive impairment (CI).

Risk of Recurrence in Patients with an Unprovoked Tonic-Clonic Seizure and Generalized Epileptiform Discharges on EEG.

The decision to initiate treatment in patients with a first unprovoked seizure remains controversial. Studies have reported a recurrence rate ranging from 21-50%, but most have included patients with different etiologies, EEG findings, and seizure types. This study aimed to determine the risk of recurrence in patients with a first unprovoked generalized tonic-clonic (GTC) seizure with evidence of generalized spike-wave discharges (GSWD) on EEG and compare the efficacy of antiseizure medications (ASM) in preventing recurrence. This prospective study included consecutive patients who presented with a single GTC seizure, evidence of GSWD on EEG, and a follow-up period of at least one year. All patients underwent extensive evaluation, including a 3-hour sleep-deprived video-EEG recording and an epilepsy protocol brain MRI. Treatment with ASM was recommended for all patients. The decision regarding the specific ASM to be used was left to the treating physician's discretion. A total of 57 patients with a median age of 19 years were included. A total of 41 patients agreed to be started on an ASM while 16 declined. Seizure recurred in 6/41 (14.6%) patients in the treated group compared to 11/16 (68.8%) in the untreated group (P = 0.00006). Valproate was significantly more efficacious than levetiracetam or lamotrigine (P = 0.04). Of the 15 patients who discontinued ASM treatment after remaining seizure free for an average of 30 months, 6 (40%) experienced a seizure recurrence. Patients with a first unprovoked GTC seizure and evidence of GSWD on EEG have a high risk of recurrence if left untreated. Valproate is the most efficacious ASD for preventing recurrence in this population. A sizeable proportion of patients can be successfully tapered off medication after a period of seizure freedom. This study provides valuable information for guiding treatment decisions in this patient population.

Seizure After Ischemic Stroke; A Diagnostic and Management Challenge in a Resource Limited Setting: A Case Report

Background: Poststroke seizures occur in 6-8% of the adult population that suffer an ischaemic stroke. This pathological process increases metabolic stress and cell death, the extent of vascular obstruction in the brain, the mortality rate and long term morbidity. Poststroke seizures represent one of the most important complications of stroke that must be recognised and treated in a timely fashion. These are classified as either early or late depending on the time of onset after stroke. Case Report: A 51 year old woman presented to the Emergency Department of RSUD Dr Murjani following a generalised tonic-clonic seizure 3 hours prior that had lasted for two minutes. On arrival the patient subsequently had two further generalised tonic-clonic seizures with a one hour interval between. Whole body stiffness and a fixed upward gaze were observed. A non-contrast CT Head displayed a diffuse infarct of the left frontotemporoparietooccipital lobes. The patient had a history of stroke one year previously and a second stroke one month ago with resultant persistent weakness of the right upper and lower limbs. This patient was diagnosed with poststroke seizure of late onset and treated in hospital with diazepam 10mg and phenytoin 100mg three times per day. Discussion: Poststroke seizure is described as either early-onset (occurring in the first week after a stroke) or late-onset (occurring after the first week). Based on the International League Against Epilepsy (ILAE) definition, a single unprovoked late-onset poststroke seizure occurring more than seven days after a stroke is considered as epilepsy with a high risk (>60%) of recurrent seizures that may occur for up to ten years thereafter. Hence this risk factor must be identified and treated correctly to prevent significantly increased morbidity for the patient

Diagnostic Accuracy of Ambulatory EEG vs Routine EEG in Patients With First Single Unprovoked Seizure.

To evaluate the diagnostic accuracy of the ambulatory EEG (aEEG) at detecting interictal epileptiform discharges (IEDs)/seizures compared with routine EEG (rEEG) and repetitive/second rEEG in patients with a first single unprovoked seizure (FSUS). We also evaluated the association between IED/seizures on aEEG and seizure recurrence within 1 year of follow-up. We prospectively evaluated 100 consecutive patients with FSUS at the provincial Single Seizure Clinic. They underwent 3 sequential EEG modalities: first rEEG, second rEEG, and aEEG. Clinical epilepsy diagnosis was ascertained based on the 2014 International League Against Epilepsy definition by a neurologist/epileptologist at the clinic. An EEG-certified epileptologist/neurologist interpreted all 3 EEGs. All patients were followed up for 52 weeks until they had either second unprovoked seizure or maintained single seizure status. Accuracy measures (sensitivity, specificity, negative and positive predictive values, and likelihood ratios), receiver operating characteristic (ROC) analysis, and area under the curve (AUC) were used to evaluate the diagnostic accuracy of each EEG modality. Life tables and the Cox proportional hazard model were used to estimate the probability and association of seizure recurrence. Ambulatory EEG captured IED/seizures with a sensitivity of 72%, compared with 11% for the first rEEG and 22% for the second rEEG. The diagnostic performance of the aEEG was statistically better (AUC: 0.85) compared with the first rEEG (AUC: 0.56) and second rEEG (AUC: 0.60). There were no statistically significant differences between the 3 EEG modalities regarding specificity and positive predictive value. Finally, IED/seizure on the aEEG was associated with more than 3 times the hazard of seizure recurrence. The overall diagnostic accuracy of aEEG at capturing IED/seizures in people presenting with FSUS was higher than the first and second rEEGs. We also found that IED/seizures on the aEEG were associated with an increased risk of seizure recurrence. This study provides Class I evidence supporting that, in adults with First Single Unprovoked Seizure (FSUS), 24-h ambulatory EEG has increased sensitivity when compared with routine and repeated EEG.

Invasive Fungal Infection of the Duramater as the Presenting Manifestation of Disseminated Sarcoidosis (P10-10.005)

<h3>Objective:</h3> To describe a case of invasive fungal infection of the duramater which was the presenting manifestation of Disseminated sarcoidosis <h3>Background:</h3> Invasive Central nervous system fungal infections are usually encountered in the setting of immunosuppressive conditions, craniospinal trauma or instrumentation. It is rare for a treatment naïve patient with sarcoidosis to develop fungal infection of the duramater. <h3>Design/Methods:</h3> We describe the case of a young male who was found to have nodular thickening of the duramater due to Invasive CNS fungal infection. <h3>Results:</h3> We had a 27 year old man who had no prior comorbidities who presented with a single seizure. On evaluation, he was found to have nodular thickening of the Duramater. Differentials of infective, inflammatory, histiocytic and malignant conditions were considered. He underwent detailed evaluation and PET-CT revealed generalized lymphadenopathy. Biopsy from the dural thickening revealed septate hyphae and fungal culture showed Acremonium species. There were granulomas found on histopathologic examination of the dural as well as subcarinal lymphnode biopsy. He was treated with Voriconazole for 24 weeks followed by treatment of sarcoidosis. <h3>Conclusions:</h3> Sarcoidosis may be associated with immunodeficiency due to its effects on the lymphocytes, bone marrow and other organs such as the thymus. There have been several reports of patients with sarcoidosis being predisposed to infections such as Progressive multifocal leukoencephalopathy, fungal infections, tuberculosis and other bacterial infections. These infections may occur de-novo in the absence of immunosuppressant drugs or corticosteroids which have been traditionally used in the management of sarcoidosis with organ threatening or life threatening symptoms. Infections that occur as the first manifestation of an underlying autoimmune condition are challenging to diagnose. Appropriate diagnosis is essential to ensure optimum treatment of both conditions. <b>Disclosure:</b> Dr. Elavarasi has stock in Pfizer. Dr. Elavarasi has stock in PGHL. The institution of Dr. Elavarasi has received research support from All India Institute of Medical Sciences, New Delhi. The institution of Dr. Elavarasi has received research support from Indian Council for Medical Research. Dr. SINGH has nothing to disclose. Dr. CHHATTERPAL has nothing to disclose. Dr. Wig has nothing to disclose. Dr. Mittal has nothing to disclose. Mehar Chand Sharma has nothing to disclose. Dr. DAS has nothing to disclose. Ajay Garg has nothing to disclose. Dr. Jagdevan has nothing to disclose. Dr. Shamim has nothing to disclose. Dr. Tripathi has nothing to disclose. Dr. Vibha has nothing to disclose. Rajesh Kumar Singh has nothing to disclose.

State of the Art and Challenges in Epilepsy-A Narrative Review.

Epilepsy is a common condition worldwide, with approximately 50 million people suffering from it. A single seizure does not mean epilepsy; almost 10% of the population can have a seizure during their lifetime. In particular, there are many other central nervous system disorders other than epilepsy in which seizures occur, either transiently or as a comorbid condition. The impact of seizures and epilepsy is, therefore, widespread and easily underestimated. It is estimated that about 70% of patients with epilepsy could be seizure-free if correctly diagnosed and treated. However, for patients with epilepsy, quality of life is influenced not only by seizure control but also by antiepileptic drug-adverse reactions, access to education, mood, employment, and transportation.

Prognosis of adults and children following a first unprovoked seizure.

Prognosis of adults and children following a first unprovoked seizure.

Acute symptomatic epileptic seizures and epilepsy after stroke

Acute symptomatic epileptic seizures occur within 7 days after the stroke onset. Acute symptomatic epileptic seizures occur in 6.3% of stroke cases: ischemic stroke 4.2%, cerebral infarction with hemorrhagic transformation 12.5%, intracerebral hemorrhage 16.2%. Cumulative risk of subsequent unprovoked epileptic seizure after the first acute symptomatic seizure at follow-up for 10 years is 18.7 %. In acute symptomatic epileptic seizure secondary prevention with antiepileptic drugs usually is not indicated. If antiepileptic drug treatment is initiated after a single acute symptomatic seizure, it should be discontinued after the acute period of the disease. The 10-years risk of subsequent unprovoked epileptic seizures after the single unprovoked epileptic seizure in stroke patients is 71.5%. In this situation the epilepsy diagnosis is reasonable and antiepileptic drug treatment should be initiated. The incidence of epilepsy after acute ischemic or hemorrhagic stroke is identical 1012%. The choice of the group of antiepileptic drugs should be based on clinical guidelines for patients with focal forms of epilepsy. Pharmacokinetic interactions between antiepileptic drugs and oral anticoagulants, antiplatelet agents, antihypertensive drugs, and other xenobiotics should be minimized. Thus antiepileptic drugs that induce or inhibit microsomal liver enzymes should also be avoided.

PSAT210 A Case of Asymptomatic Severe Hypocalcemia: Consideration of Genetic Causes

Abstract Calcium sensing receptor (CaSR) activating mutations are a rare etiology of calcium dyscrasias in the general population. Of these, hypocalciuric hypocalcemia and autosomal dominant hypocalcemia (ADH) type 1 are the most common subtypes, with a prevalence of 74.1 and 3.9 per 100,000, respectively. Although rare, these mutations should be considered in patients with a family history of hypocalcemia, particularly if asymptomatic, as the treatment goals and replacement strategies differ from typical primary hypoparathyroidism, with which they are often mistaken. We present a case of a 41-year-old male with a history of treated vitamin D deficiency and anxiety who presented to endocrinology clinic for severe asymptomatic hypocalcemia (serum calcium 6.0-7.0). Family history pertinent for a mother, sister, and brother also with hypocalcemia, and brother with single childhood hypocalcemic seizure at age 4. Patient reported being on and off calcium, calcitriol, and ergocalciferol for years and has never had any symptoms regardless of his regimen or serum calcium. Specifically, he had no personal history of paresthesia, muscle cramping, or kidney stones. No family history of osteoporosis, fracture, kidney stone, or renal disease. Laboratory evaluation over the last 30 years most pertinent for serum calcium 6.0-9.5 on varying supplement/medication regimens, low-normal PTH, initially elevated and now normal serum phosphorous, low-normal serum magnesium, and 24h urinary calcium quite variable but as high as &amp;gt;300mg/d (when serum calcium within normal limits). Genetic testing revealed a heterozygous DNA sequence change detected on exon 7 of the CaSR gene, which has been previously found to be a pathogenic cause of ADH. Activating mutations of the CaSR (typically ADH type 1) clinically present as hypocalcemia, low or low-normal PTH, hyperphosphatemia, hypomagnesemia, and increased urinary calcium. When starting the evaluation for these mutations, it is important to note that there are two types of ADH. Type 1 mutations occur as an activating mutation at the CaSR causing hypersensitivity to calcium, while type 2 activating mutations occur at a different locale (G alpha 11 subunit). Despite mutations at different sites, each type leads to a similar gain-of-function mutation and a very similar clinical presentation. The clinical significance of differentiating these diagnoses from primary hypoparathyroidism (PHP) lies in the goals of treatment and in the adverse effects of over-supplementation of calcium in ADH. In PHP, patients generally have symptomatic hypocalcemia, and calcium can and should be supplemented to prevent adverse events of chronic hypocalcemia. Contrastingly, in CaSR mutation conditions, mild and even significant hypocalcemia is well tolerated. If patients’ serum calcium is normalized, they often experience significant hypercalciuria and renal manifestations therein, such has nephrocalcinosis and nephrolithiasis. Therefore, treatment of patients with CaSR activating mutations should be aimed at relieving hypocalcemia symptoms, if any are present. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

The Brain Protein Acylation System Responds to Seizures in the Rat Model of PTZ-Induced Epilepsy.

Abnormal energy expenditure during seizures and metabolic regulation through post-translational protein acylation suggest acylation as a therapeutic target in epilepsy. Our goal is to characterize an interplay between the brain acylation system components and their changes after seizures. In a rat model of pentylenetetrazole (PTZ)-induced epilepsy, we quantify 43 acylations in 29 cerebral cortex proteins; levels of NAD+; expression of NAD+-dependent deacylases (SIRT2, SIRT3, SIRT5); activities of the acyl-CoA-producing/NAD+-utilizing complexes of 2-oxoacid dehydrogenases. Compared to the control group, acylations of 14 sites in 11 proteins are found to differ significantly after seizures, with six of the proteins involved in glycolysis and energy metabolism. Comparing the single and chronic seizures does not reveal significant differences in the acylations, pyruvate dehydrogenase activity, SIRT2 expression or NAD+. On the contrary, expression of SIRT3, SIRT5 and activity of 2-oxoglutarate dehydrogenase (OGDH) decrease in chronic seizures vs. a single seizure. Negative correlations between the protein succinylation/glutarylation and SIRT5 expression, and positive correlations between the protein acetylation and SIRT2 expression are shown. Our findings unravel involvement of SIRT5 and OGDH in metabolic adaptation to seizures through protein acylation, consistent with the known neuroprotective role of SIRT5 and contribution of OGDH to the Glu/GABA balance perturbed in epilepsy.

Seizure Semiology Over Time in Adult Diffuse Glioma

Abstract AIMS Patients with gliomas often present with generalised seizures, but subsequently develop focal seizures on treatment. The occurrence of a single generalised seizure at onset precludes the return of a driving licence, even if a patient continues to have only focal aware seizures. We investigated seizure semiology over time, to determine how many patients with ongoing seizures may be safe to drive. METHOD We analysed clinical data of patients with histologically-confirmed IDH-mutant diffuse gliomas, diagnosed between 2004-2015. Seizures were classified as: 1 – focal / 2 - generalised; A – aware / B – unaware; M – motor / N – non-motor. Seizure type at diagnosis and last follow-up was recorded. RESULTS 189 patients were identified, of whom 140 presented with seizures (74%). 115 of these patients had a full data set. 59 (51%) presented with generalised seizures. 10% had only a single seizure at presentation, 55 % had further seizures then became seizure-free and 35% continued to have seizures at last follow-up. Of the 40 patients who continued to have seizures, 7 (17.5%) had 1AN, 16 (40%) had 1AM, 1 (2.5%) had 1BN and 5 (12.5%) had 1BM. 11 (27.5%) had generalised seizures. Of the 7 patients with 1AN seizures at last follow-up, 4 initially presented with a generalised seizure, 1 with 1AN, 1 with 1AM and 1 with 1BM. CONCLUSION Almost two thirds of patients became seizure-free and, of those that continued to have seizures, 57.5% developed only focal aware seizures. Current driving regulations may be unduly restrictive for patients with gliomas.

Photobiomodulation regulates adult neurogenesis in the hippocampus in a status epilepticus animal model

Status epilepticus (SE) refers to a single seizure that lasts longer than typical seizures or a series of consecutive seizures. The hippocampus, which is vulnerable to the effects of SE, has a critical role in memory storage and retrieval. The trisynaptic loop in the hippocampus connects the substructures thereof, namely the dentate gyrus (DG), CA3, and CA1. In an animal model of SE, abnormal neurogenesis in the DG and aberrant neural network formation result in sequential neural degeneration in CA3 and CA1. Photobiomodulation (PBM) therapy, previously known as low-level laser (light) therapy (LLLT), is a novel therapy for the treatment of various neurological disorders including SE. However, the effects of this novel therapeutic approach on the recovery process are poorly understood. In the present study, we found that PBM transformed SE-induced abnormal neurogenesis to normal neurogenesis. We demonstrated that PBM plays a key role in normal hippocampal neurogenesis by enhancing the migration of maturing granular cells (early neuronal cells) to the GCL, and that normal neurogenesis induced by PBM prevents SE-induced hippocampal neuronal loss in CA1. Thus, PBM is a novel approach to prevent seizure-induced neuronal degeneration, for which light devices may be developed in the future.

Approach to initial management of canine generalised epileptic seizures in primary-care veterinary practices in the United Kingdom.

To investigate how primary care clinicians in the UK approach initial management of canine generalised epileptic seizures, including factors potentially associated with prescription and choice of anti-seizure drugs. Electronic health records concerning 3,150,713 consultations (917,373 dogs) were collected from 224 veterinary practices by the Small Animal Veterinary Surveillance Network. Free-text clinical narratives were reviewed to identify those consistent with generalised epileptic seizure activity, including only those recording the first presentation for seizures. Dogs older than 6 years were excluded. Five hundred and seventeen cases were included. Sixty-seven dogs (13.0%) received anti-seizure drugs at first presentation; this was significantly more likely in dogs presented withcluster seizures (odds ratio 13.8, 95% confidence interval 7.3 to 26.1). Phenobarbital (n=36) and imepitoin (n=29) were the most frequently chosen anti-seizure drugs. Presentation for a single epileptic seizure occurred in 321 dogs; seven were prescribed anti-seizure drugs. Eighty-six dogs were presented with cluster seizures; 38 were prescribed anti-seizure drugs, most frequently imepitoin (n= 19) and phenobarbital (n=17). Of the dogs presenting with a single seizure and at least 6-month follow-up (n=165), 33 (20%) did not have subsequent seizures recorded. Primary care clinicians rarely prescribed anti-seizure drugs following a single epileptic seizure in accordance with International Veterinary Epilepsy Task Force recommendations. Less than half of dogs initially presenting with cluster seizures were prescribed anti-seizure drugs. Imepitoin was frequently selected in the treatment of cluster seizures despite no authorisation for this purpose. These findings may ultimately contribute to improved cohesion in the management of canine epileptic seizures between primary care and referral institutions.

Influence of methadone on the anticonvulsant efficacy of valproate sodium gabapentin against maximal electroshock seizure in mice by regulation of brain MDA TNF-α.

Methadone is the most frequently used opioid therapy worldwide, with controversial effects on oxidative stress homeostasis. This study investigated the effects of intraperitoneal (i.p.) co-administration of methadone (0.1, 0.3, 1, and 3 mg/kg) and valproate sodium (300 mg/kg) or gabapentin (50 mg/kg) in the mice maximal electroshock (MES)-induced seizure model. The adverse effect of drugs was assessed using the chimney test. The levels of tumor necrosis factor-alpha (TNF-α) and malondialdehyde (MDA) contents were measured in mice brains after a single seizure. Administration of methadone alone resulted in a significant reduction in the duration of hind limb extension (HLE) than that in the control group. Methadone pretreatment at doses of 0.1 and 0.3 mg/kg i.p. decreased, and at doses of 1 and 3 mg/kg i.p. had an increasing effect on anticonvulsant efficacy of gabapentin. Pretreatment with all doses of methadone significantly decreased the valproate anticonvulsive efficacy. At doses of 1 and 3 mg/kg i.p. methadone per se increased brain MDA levels after MES-induced seizure. Administration of methadone (0.3 mg/kg i.p.) enhanced and at 3 mg/kg decreased gabapentin effect on brain MDA level, but their co-treatment did not lead to further increase in MDA. Methadone at 0.3–3 mg/kg enhanced the effect of sodium valproate on MDA levels in the brain, but at all doses significantly potentiated its effect on brain TNF-α levels. The drugs did not produce any side effects on motor coordination in experimental animals. In conclusion, methadone showed different effects on anticonvulsant actions of gabapentin and valproate through regulation of brain levels of MDA and TNF-α.

Prevalence and Risk Factors for Pharmacoresistance in Children With Focal Cortical Dysplasia-Related Epilepsy.

Focal cortical dysplasia (FCD) is the most common cause of surgically remediable epilepsy in children. Little is known about the risk factors for the timing and development of pharmacoresistance in this population. This study sought to evaluate the prevalence and risk factors for pharmacoresistance in pediatric FCD-related epilepsy. In this retrospective single-center cohort design, patients were identified from search of centralized radiology report database and a central epilepsy surgical database. Inclusion criteria consisted of 3T MRI-confirmed FCD from January, 2011, to January, 2020; ages 0 days to 22 years at MRI; and at least 18 months of documented follow-up after MRI, unless had single seizure or incidentally discovered FCD. Records were excluded if there was dual pathology (except for mesial temporal sclerosis), hemimegalencephaly, or tuberous sclerosis complex present in imaging or history. One hundred forty-three patients with confirmed FCD met the inclusion criteria. One hundred twenty-four children had epilepsy (87% of patients with FCD) with median age at seizure onset 2.7 years (IQR 0.75-6 years, range 0-17 years). Twelve children (8.5%) had a single lifetime seizure (provoked or unprovoked) or recurrent provoked seizures. Seven children (4.9%) had incidental FCD. Ninety-two patients (74%) of those with epilepsy met criteria for pharmacoresistance. Of children with epilepsy of all types, 93 children (75%) were seizure-free at the last visit; 82 patients underwent epilepsy surgery, of whom 59 (72%) achieved seizure freedom. Seven percent (9/124) achieved seizure freedom with a second ASM and 5.6% (7/124) with a third or more ASMs. Failure of only 1 antiseizure medication is associated with enormous increased incidence and earlier development of pharmacoresistance (OR 346; 95% CI 19.6-6,100); Cox regression showed FCD lobar location, pathologic subtype, and age at seizure onset are not. Failure of 1 antiseizure medication is associated with substantial risk of pharmacoresistance. These data support an operational redefinition of pharmacoresistance, for surgical planning, in FCD-related epilepsy to the failure of 1 antiseizure medication and support early, potentially curative surgery to improve outcomes in this patient population.

Quantitative evaluation of the composition of synthetic cannabinoid receptor agonists (SCRA) in infused papers and herbal materials seized in Brazilian prisons

This study describes the identification and quantification of synthetic cannabinoid receptor agonists (SCRA) in infused paper and herbal material samples, seized in prisons located in São Paulo state, Brazil. The selected samples (23 infused paper and 3 herbal material samples) were previously analyzed by the São Paulo State Police, in a qualitative analysis by gas chromatography–mass spectrometry (GC–MS) using full-scan and library search for identification. Afterward, these samples were analyzed by liquid chromatography-tandem mass spectrometry in a triple quadrupole (LC-MS/MS) system operating in MRM mode for determination of the majority and the possible minority SCRA present in the samples. For the LC-MS/MS analysis the samples were extracted with methanol and diluted in a proportion of 1:1000 and 1:10,000. All substances identified by GC-MS were also identified by LC-MS/MS, but not the opposite, showing GC-MS full-scan method employed were unable to detect those SCRA presented in lower concentration levels. The presence of a single SCRA in the samples was observed in 11 samples (27.5%), while in 29 samples (72.5%) two or more SCRA were identified. The SCRA most frequently detected in the samples were MDMB-4en-PINACA and ADB-BUTINACA, present in 72% and 70% of the samples, respectively. The concentration of SCRA shown great variability, ranging from 0.2 μg/infused paper to 3000 μg/infused paper. In cases with more than one SCRA detected, the minority compounds did not exceed the concentration of 50 μg/infused paper. Comparing two different samples of a single seizure it was possible to identify the same substances but in different concentration levels, or different compositions (mixtures). The highest concentration of SCRA present in the infused papers was for the cases involving MDMB-4en-PINACA as the major compound, reaching until 3000 μg/infused paper, but this SCRA was also found as minority in other cases, with concentrations as low as 0.9 μg/infused paper. Among all samples, 4F-MDMB-BUTICA was detected in only one case, at a concentration of 125 μg/infused paper. For the three samples of plant material, ADB-BUTINACA appears as the major compound, with the presence of other minor SCRA ranging from 0.2 to 5 μg/mg. These results shows that the studied samples did not present homogeneity in the composition and concentration levels, even when comparing a single case, but it seems that some SCRA are commonly found together. The presence of different SCRA in the same sample may contribute to the increase in the toxicity of these compounds, which reinforces the need to obtain quantitative and qualitative data from the seized samples.

Application of Machine Learning Methods for Epilepsy Risk Ranking in Patients with Hematopoietic Malignancies Using.

Machine learning methods to predict the risk of epilepsy, including vascular epilepsy, in oncohematological patients are currently considered promising. These methods are used in research to predict pharmacoresistant epilepsy and surgical treatment outcomes in order to determine the epileptogenic zone and functional neural systems in patients with epilepsy, as well as to develop new approaches to classification and perform other tasks. This paper presents the results of applying machine learning to analyzing data and developing diagnostic models of epilepsy in oncohematological and cardiovascular patients. This study contributes to solving the problem of often unjustified diagnosis of primary epilepsy in patients with oncohematological or cardiovascular pathology, prescribing antiseizure drugs to patients with single seizure syndromes without finding a disease associated with these cases. We analyzed the hospital database of the V.A. Almazov Scientific Research Center of the Ministry of Health of Russia. The study included 66,723 treatment episodes of patients with vascular diseases (I10–I15, I61–I69, I20–I25) and 16,383 episodes with malignant neoplasms of lymphoid, hematopoietic, and related tissues (C81–C96 according to ICD-10) for the period from 2010 to 2020. Data analysis and model calculations indicate that the best result was shown by gradient boosting with mean accuracy cross-validation score = 0.96. f1-score = 98, weighted avg precision = 93, recall = 96, f1-score = 94. The highest correlation coefficient for G40 and different clinical conditions was achieved with fibrillation, hypertension, stenosis or occlusion of the precerebral arteries (0.16), cerebral sinus thrombosis (0.089), arterial hypertension (0.17), age (0.03), non-traumatic intracranial hemorrhage (0.07), atrial fibrillation (0.05), delta absolute neutrophil count (0.05), platelet count at discharge (0.04), transfusion volume for stem cell transplantation (0.023). From the clinical point of view, the identified differences in the importance of predictors in a broader patient model are consistent with a practical algorithm for organic brain damage. Atrial fibrillation is one of the leading factors in the development of both ischemic and hemorrhagic strokes. At the same time, brain infarction can be accompanied both by the development of epileptic seizures in the acute period and by unprovoked epileptic seizures and development of epilepsy in the early recovery and in a longer period. In addition, a microembolism of the left heart chambers can lead to multiple microfocal lesions of the brain, which is one of the pathogenetic aspects of epilepsy in elderly patients. The presence of precordial fibrillation requires anticoagulant therapy, the use of which increases the risk of both spontaneous and traumatic intracranial hemorrhage.

Large Vertex Encephaloceles: Management and Outcomes.

Complex vertex and posterior encephaloceles containing brain tissue have uncertain prognosis and high operative risk. Patients may not be offered operative intervention depending on local and regional specialist expertise. The authors present their experience treating 5 such pediatric patients. This is a retrospective review of the surgical assessment, planning, and technique of cranial repairs, as well as surgical outcomes and developmental follow-up regarding adaptive functioning for patients presenting for second opinion for encephalocele of the cranial vertex after having been deemed too high risk at another institution. Five consecutive patients presented between January 2014 and June 2016. One patient was not offered repair. Of 4 patients who underwent reconstruction, average age at time of repair was 2.7 months (range, 0.9-6.7). One presented with ruptured encephalocele, whereas the remaining 3 underwent drainage of the encephalocele (average volume of 1200mL) at time of surgical resection. Operative time averaged 3.7 hours (range, 2.2-5.3). There were no deaths. One patient had a single seizure postoperatively. Two patients required placement of permanent shunt for hydrocephalus. Two patients completed developmental evaluations, both of whom exhibited delays in adaptive functioning relative to same-aged peers. Patients with large, complex encephalocele warrant evaluation by an experienced high-volume tertiary care pediatric craniofacial center. The decision to proceed with surgical management should include an interdisciplinary team of surgeons, anesthesiologists, neurologists, and social work. Further study of developmental outcomes in both operated and unoperated patients is necessary to better understand risks and benefits of reconstruction.

Risk Factors and Incidence of Epilepsy after Severe Traumatic Brain Injury.

We determined the incidence of post-traumatic epilepsy after severe traumatic brain injury. Of 392 patients surviving to discharge, cumulative incidence of post-traumatic epilepsy was 25% at 5 years and 32% at 15 years, an increase compared with historical reports. Among patients with one late seizure (>7 days post-trauma), the risk of seizure recurrence was 62% after 1 year and 82% at 10 years. Competing hazards regression identified age, decompressive hemicraniectomy, and intracranial infection as independent predictors of post-traumatic epilepsy. Patients with severe traumatic brain injury and a single late post-traumatic seizure will likely require long-term antiseizure medicines. ANN NEUROL 2022;92:663-669.