Good Seizure Control Research Articles

Long-term Outcome of Seizure Control and Neurologic Performance After Limited Hippocampal Radiofrequency Thermocoagulation for Mesial Temporal Lobe Epilepsy

Limited hippocampal radiofrequency thermocoagulation (RFTC) for patients with mesial temporal lobe epilepsy was associated with good short-term seizure control and few complications. We aimed to demonstrate the neuropsychologic outcomes and assess the prognostic factors of long-term seizure control in these patients. We included all patients with mesial temporal lobe epilepsy who underwent limited hippocampal RFTC from January 2016 to December 2020. Clinical data of age, sex, seizure control before and after operation were all corrected. Pre- and postoperative neuropsychologic function including full-scale intelligence quotient (FSIQ), memory quotient, and the Mini-Mental State Examination was used. Thirty-one patients (17 female and 14 male) with a mean epilepsy duration of 22.3 years and seizure frequency of 5.7 times per month were included. The intraoperative seizure rate was 19.3%, and a higher preoperative seizure frequency (P= 0.001) and longer duration of epilepsy (P= 0.042) were associated with the occurrence of intraoperative seizures. The postoperative FSIQ scores were significantly better than preoperative scores (mean 92.1 vs. 89.7, P= 0.014). Nine patients (29%) who underwent limited hippocampal RFTC were seizure-free at 1 year of follow-up. Responders represented 58% (n= 18) of patients at 1 year. The mean follow-up period was 34.7 ± 13.3 months. Five patients remained seizure free and 13 patients are still responders at the last follow-up visits. Long-term seizure frequency was 2.32 ± 2.86 times per month. Limited hippocampal RFTC is a safe stereotactic minimal invasive procedure with good neuropsychologic outcome and acceptable efficacy of seizure reduction in appropriately selected patients.

Quality of epilepsy care in a rural and deprived Scottish population.

Epilepsy is among the commonest neurological disorders globally. Appropriate prescription and good adherence to anticonvulsants can achieve seizure freedom rates of 70%. Scotland is an affluent nation with free at point-of-access health care but there remain significant healthcare inequalities, particularly associated with deprivation. Anecdotally, epileptics in rural Ayrshire rarely engage with healthcare services. We describe the prevalence and management of epilepsy in a deprived and rural Scottish population. Electronic records were used to obtain the following for patients with coded diagnoses of 'Epilepsy' or 'Seizures' within a general practice list of 3500 patients: demographics; diagnosis; seizure types; date and level (primary, secondary) of last review; last seizure date; anticonvulsant prescription; adherence; and any clinic discharge due to non-attendance. 92 patients were coded as above. 56 had a current diagnosis of epilepsy (prev 16.1/100,000). 69% had good adherence. 56% had good seizure control, with adherence associated with control. Of the 68% managed by primary care, 33% were uncontrolled and 13% had had an epilepsy review in the previous year. 45% of patients referred to secondary care were discharged for non-attendance. We demonstrate a high prevalence of epilepsy, low anticonvulsant adherence and sub-optimal rates of seizure freedom. These may be linked to poor attendance at specialist clinics. Management in primary care is challenging as evidenced by low review rates and high rates of ongoing seizures. We propose that the synergistic factors of uncontrolled epilepsy, deprivation and rurality make it difficult to attend clinics, with resultant health inequalities.

Glioma features and seizure control during long-term follow-up.

An epileptic seizure is a common presenting symptom of glioma, or epilepsy may develop later during the disease. Epileptic seizures affect the quality of life in patients with glioma. Good seizure control during 6-12months follow-up has been associated with gross total resection, radiation therapy and chemotherapy of gliomas. Little is known about seizure control during long-term follow-up and about factors which may affect the prognosis of epilepsy in glioma patients. We identified retrospectively all adult patients with diffuse glioma (grade 2-4) associated epilepsy (n=123) living in Helsinki, who received treatment at Helsinki University Hospital neuro-oncology center during 2013-2015. We excluded patients with histopathological diagnosis prior to 2005. Data was collected from medical records for five years after diagnosis of glioma, or until death. In this patient cohort 49 (39.8%) had grade 2 glioma, 19 (15.4%) had grade 3 glioma and 55 (44.7%) had grade 4 glioma. 29 (23.6%) of tumors were astrocytomas, 24 (19.5%) were oligoastrocytomas, 15 (12.2%) were oligodendrogliomas and 55 (44.7%) were glioblastomas. A seizure was the presenting symptom in 87 (70.7%) of the patients. The majority, 68 (57.6%) patients were seizure-free for at least 12months at some point during follow-up and 47 (39.8%) patients were seizure-free during the last year of follow-up. Survival for five years from glioma diagnosis (p<0.001), lower grade of tumor (p<0.001), IDH mutation (p<0.001), epilepsy as first symptom (p<0.001), younger age (p<0.001) and lack of progression (p = 0.021) correlated with seizure freedom at the end of follow-up. When the results were analyzed separately in survivors and deceased patients, only progression correlated negatively with seizure freedom at the end of follow-up in surviving patients (p = 0.008). In 5-year survivors, longer seizure-free periods were achieved by patients without progression of glioma (p = 0.040) vs patients with progression, or without focal aware (p 0.003) or focal impaired awareness seizures (p = 0.002) vs patients with only focal to bilateral tonic-clonic seizures. In deceased patients, progression (p<0.001) and lower grade of glioma (p = 0.003) correlated positively and focal aware seizures negatively (p = 0.021) with a longer seizure-free period. In all patients, freedom of seizures at the end of follow-up was less likely for patients who had focal aware (p = 0.015) than for patients without focal aware seizures. There are differences in seizure-free times in patients with grade 2-4 glioma and epilepsy. The results suggest that the prognosis of glioma may be the most important factor influencing the prognosis of epilepsy.

Neurosurgery in feline epilepsy, including clinicopathology of feline epilepsy syndromes

Feline epilepsy is treated with antiseizure medications, which achieves fair to good seizure control. However, a small subset of feline patients with drug-resistant epilepsy requires alternative therapies. Furthermore, approximately 50 % of cats with epileptic seizures are diagnosed with structural epilepsy with or without hippocampal abnormality and may respond to surgical intervention. The presence of hippocampal pathology and intracranial tumors is a key point to consider for surgical treatment. This review describes feline epilepsy syndrome and epilepsy-related pathology, and discusses the indications for and availability of neurosurgery, including lesionectomy, temporal lobectomy with hippocampectomy, and corpus callosotomy, for cats with different epilepsy types.

Therapeutic drug monitoring of levetiracetam: Method validation using high-performance liquid chromatography-ultraviolet detector technique and usefulness in patient care setting.

To develop and validate a modified HPLC-UV method for the estimation of serum levetiracetam levels and to assess the usefulness of serum levetiracetam estimation in epileptic patients. Modification of a previously existing HPLC-UV method was performed using liquid- liquid phase extraction and processing using reverse phase analytic HPLC-UV detector technique followed by method validation. Serum samples of patients attending our hospital's Therapeutic Drug Monitoring Outpatient Department services were analyzed for levetiracetam levels using the study method. Data of the past 6 years (2015-2020) were descriptively analyzed. The modified HPLC-UV method was validated as per ICH Q2 (R1) 2005 guidelines. Usefulness of levetiracetam estimation was assessed in 1383 patients (635 children, 683 adults, 40 elderly, and 25 pregnant women). Levetiracetam levels were within the therapeutic range (TR) in 520 children, 543 young adults, 35 elderly patients, and nine pregnant women. In 112 of 232 patients with low levetiracetam levels, poor compliance was elicited. Of 641 patients on polytherapy, 446 patients had levetiracetam values within TR, whereas 29 had values above and 166 patients had values less than TR. Sodium valproate, phenytoin sodium, and carbamazepine affected levetiracetam levels when given concomitantly. Levetiracetam dose was adjusted in 61 patients with abnormal levels for better clinical response. Good seizure control was noted in 913 (82.47%) patients whose levels were within TR, whereas 136 (58.62%) patients with low levels reported an increase in seizure frequency. The modified HPLC-UV method is simple, rapid, efficient, and reliable for assaying serum levetiracetam.

Is Hippocampal Resection Necessary for Low-Grade Epilepsy-Associated Tumors in the Temporal Lobe?

Low-grade epilepsy-associated tumors (LEATs) are common in the temporal lobe and can cause drug-resistant epilepsy. Complete resection of LEATs is sufficient for seizure relief. However, hippocampal resection might result in postoperative cognitive impairment. This study aimed to clarify the necessity of hippocampal resection for seizure and cognitive outcomes in patients with temporal lobe LEATs and a normal hippocampus. The study included 32 patients with temporal lobe LEATs and without hippocampal abnormalities. All patients underwent gross total resection as treatment for drug-resistant epilepsy at our tertiary epilepsy center from 2005 to 2020, followed by at least a 12-month follow-up period. Seizure and cognitive outcomes were compared between patients who underwent additional hippocampal resection (Resected group) and those who did not (Preserved group). Among the participants, 14 underwent additional hippocampal resection and 28 (87.5%) achieved seizure freedom irrespective of hippocampal resection. The seizure-free periods were not different between the two groups. Additional hippocampal resection resulted in a significantly negative impact on the postoperative verbal index. In conclusion, additional hippocampal resection in patients with temporal lobe LEATs without hippocampal abnormalities is unnecessary because lesionectomy alone results in good seizure control. Additional hippocampal resection may instead adversely affect the postoperative language function.

Early Epilepsy Surgery in Benign Cerebral Tumors: Avoid Your 'Low-Grade' Becoming a 'Long-Term' Epilepsy-Associated Tumor.

Epilepsy surgery in low-grade epilepsy-associated neuroepithelial tumors (LEAT) is usually evaluated in drug-resistant cases, often meaning a time delay from diagnosis to surgery. To identify factors predicting good postoperative seizure control and neuropsychological outcome, the cohort of LEAT patients treated with resective epilepsy surgery at the Epilepsy Center Frankfurt Rhine-Main, Germany between 2015 and 2020 was analyzed. Thirty-five patients (19 males (54.3%) and 16 females, aged 4 to 40 years (M = 18.1), mean follow-up 33 months) were included. Following surgery, 77.1% of patients remained seizure-free (Engel IA/ILAE 1). Hippocampus and amygdala resection was predictive for seizure freedom in temporal lobe epilepsy. In total, 65.7% of all patients showed cognitive deficits during presurgical workup, decreasing to 51.4% after surgery, predominantly due to significantly less impaired memory functions (p = 0.011). Patients with presurgical cognitive deficits showed a tendency toward a longer duration of epilepsy (p = 0.050). Focal to bilateral tonic-clonic seizures (p = 0.019) and young age at onset (p = 0.018) were associated with a higher likelihood of cognitive deficits after surgery. Therefore, we advocate early epilepsy surgery without requiring proof of drug-resistance. This refers especially to lesions associated with the non-eloquent cortex.

Clinical and electroencephalographic features of epilepsy in patients with triple X syndrome: A case series

PurposeTriple X syndrome, is an often undiagnosed chromosomal abnormality with an incidence of 1/1000 females. Main associated disorders are urogenital malformations, premature ovarian failure or primary amenorrhea, gastrointestinal problems, psychiatric disorders and epilepsy. To date, triple X is not related to a specific epileptic syndrome. Therefore, the purpose of this clinical series is to analyze seizure semiology, electroencephalogram features and the long-term outcome of 13 patients with epilepsy and triple X syndrome. MethodsWe retrospectively evaluated the long-term seizure outcome in patients with triple X syndrome who had been referred to 11 Epilepsy Centers in Italy. A close electroclinical follow-up was made for at least 2 years and outcomes were reported. ResultsOur case series confirms that epilepsy is not an occasional finding but part of the phenotypic spectrum of this syndrome. The seizure semiology shows an higher prevalence of focal seizures in 62% of patients. EEG findings of focal epileptic activity were reported in 85% of patients. Anti-seizure medications were successful in all our patients whom in most cases were responsive to monotherapy. ConclusionAccording to our case series most successful drugs were VPA and LEV. Long term prognosis of epilepsy in our case series was good. Our experience suggests that all triple X patients achieve good seizure control and in 69% of cases normalization of the EEG.

Association between serum vitamin D status and the anti-seizure treatment in Chinese children with epilepsy.

ObjectiveTo compare the serum 25-OH-VitD levels, the major marker of vitamin D (VitD) status, between healthy children and children with epilepsy before initiation of and during anti-seizure medications (ASMs) treatment and to evaluate the potential influence factors on 25-OH-VitD levels. Another major aim was to assess the potential role of VitD supplementation.MethodsFor comparison, we finally enrolled and collected data from 6,338 healthy children presenting to Health Care Department and 648 children visiting primary care pediatricians with symptoms of epilepsy in Children’s Hospital of Nanjing Medical University from January 2019 to June 2021. The demographic and biochemical characteristics of each child were extracted from the hospital information system.ResultsSerum 25-OH-VitD levels in 648 children with epilepsy were significantly lower than those of 6,338 healthy children (P < 0.0001), and the percentage of VitD insufficiency and deficiency status in pediatric patients was 49.19%. Of note, the serum 25-OH-VitD levels in children with newly diagnosed epilepsy before receiving any ASMs treatment were also significantly lower than those in healthy controls. Interestingly, ASMs therapy, alone or in combination, did not consistently reduce baseline serum VitD levels in children with epilepsy. The lower serum VitD levels in pediatric patients than those in healthy children might be related to the disease itself, rather than the ASMs treatment. As expected, VitD supplementation substantially increased the serum 25-OH-VitD levels (P < 0.0001). More critically, children with epilepsy receiving VitD supplementation achieved good seizure control in our study.SignificanceIn this retrospective study, the childhood epilepsy before initiation of and during ASMs treatment decreased the serum 25-OH-VitD concentrations, suggesting a clear association between epileptic disease and the risk of VitD deficiency. ASMs coadministration and long-term valproic acid treatment did not worse VitD-deficiency status, but in the small group receiving VitD supplementation, there was a significant improvement in reduction of seizure frequency. Therefore, pediatric clinicians are urged to raise public awareness of epilepsy-associated VitD deficiency.

Childhood Absence Epilepsy Associated With Concomitant Centrotemporal Spikes.

ObjectivesThe coexistence of generalized epileptiform discharges of 3Hz spike-and-wave complexes, which are the hallmark of childhood absence epilepsy (CAE), and centrotemporal spikes, which are characteristic of benign epilepsy with centrotemporal spikes (BECTs) in the same or subsequent EEGs appears to be very rare. Only a few published reports have shown a possible concomitance of CAE and BECTs electrographic changes. The study aimed to analyze electrographic and clinical features of patients with CAE who had concomitant or subsequent EEG features of BECTs.MethodDuring a five-year analysis period (2014-2018), 277 children with BECTs and 93 children with CAE were diagnosed and treated at the pediatric neurology unit of Sultan Qaboos University Hospital (SQUH) in Muscat, Oman. Nine patients were identified to have overlapping EEG findings of both epileptic syndromes. We then analyzed the nine children's clinical features, outcomes, and EEG findings in detail.ResultsThe clinical onset of all our patients aged 5-14 years (six boys, three girls) was characterized by the absence of seizures, either typical (seven children) or atypical (two children). Six out of nine patients presented with concomitant electrographic features of both syndromes, whereas three patients experienced the EEG pattern of two syndromes at different times. All nine children were treated with valproate as the first-line medication, with reasonable seizure control. However, three patients required a second add-on medication. Despite good seizure control, six of our patients had poor school performance and five children had comorbid conditions such as ADHD and learning disability.ConclusionThe coexistence of CAE and BECTS is described in the literature albeit rare. This overlap is mostly in electrographic features with or without the clinical features seen in both syndromes.

Robot-Assisted Radiofrequency Ablation Combined with Thermodynamic Simulation for Epilepsy Reoperations.

Repeat craniotomies to treat recurrent seizures may be difficult, and minimally invasive radiofrequency ablation is an alternative therapy. On the basis of this procedure, we aimed to develop a more reliable methodology which is helpful for institutions where real-time image monitoring or electrophysiologic guidance during ablation are not available. We used simulation combined with a robot-assisted radiofrequency ablation (S-RARFA) protocol to plan and execute brain epileptic tissue lesioning. Trajectories of electrodes were planned on the robot system, and time-dependent thermodynamics was simulated with radiofrequency parameters. Thermal gradient and margin were displayed on a computer to calculate ablation volume with a mathematic equation. Actual volume was measured on images after the ablation. This small series included one pediatric and two adult patients. The remnant hippocampus, corpus callosum, and irritative zone around arteriovenous malformation nidus were all treated with S-RARFA. The mean error percentage of the volume ablated between preoperative simulation and postoperative measurement was 2.4 ± 0.7%. No complications or newly developed neurologic deficits presented postoperatively, and the patients had little postoperative pain and short hospital stays. In this pilot study, we preliminarily verified the feasibility and safety of this novel protocol. As an alternative to traditional surgeries or real-time monitoring, S-RARFA served as successful seizure reoperation with high accuracy, minimal collateral damage, and good seizure control.

Expanding the genetic and clinical characteristics of Protocadherin 19 gene mutations

BackgroundPCDH19-related epilepsy is a rare X-linked type of epilepsy caused by genomic variants of the Protocadherin 19 (PCDH19) gene. The clinical characteristics of PCDH19-related epilepsy are epileptic and non-epileptic symptoms with highly variable severity among patients.Case presentationWe present a case of a 4-year old female with PCDH19-related epilepsycaused by new variants in the PCDH19 gene. Our patient was admitted for the first time at the age of 12 months for seizure clusters arising under condition of apyrexia. The electroencephalography (EEG) showed frontal paroxysmal activity. The genetic analysis identified the two variants c.1006G > A (p.Val336Met) and c.1014C > A (p.Asp338Glu) in the gene PCDH19. The patient was treated with Carbamazepine and Clonazepam achieving the disappearance of seizures. During the follow-up, the neurological examination was persistently normal with neither cognitive impairment nor behavior disturbances. From 2 years of age EEG controls were persistently normal.ConclusionThis patient presents two novel variants of the PCDH19 gene associated with a mild form of epilepsy with normal cognitive development with an apparently better prognosis. According to our experience, the dual therapy with Carbamazepine and Clonazepam has led to a good control of seizures.

Association between serum vitamin D levels and age in patients with epilepsy: a retrospective study from an epilepsy center in Saudi Arabia.

BACKGROUND: Vitamin D deficiency has been linked to various medical conditions such as bone loss, decreased mineralization, endocrine disorders, and central nervous system disorders, including epilepsy. Vitamin D deficiency is prevalent among patients with epilepsy (PWE). However, the specific association between vitamin D levels and age in PWE is unclear.OBJECTIVES: Identify the relation between vitamin D level and age in PWE and evaluate factors that may play a role in seizure control.DESIGN: Retrospective analytical medical record reviewSETTING: Outpatient epilepsy research clinic in Saudi ArabiaPATIENTS AND METHODS: Between November 2016 and April 2020, we selected eligible PWE aged older than 14 years whose vita-min D levels were recorded at least once after reviewing 1550 patient electronic files. We analyzed data on serum vitamin D level by age and other factors, vitamin D supplement use, seizure classification, and conducted a multivariate logistic regression to assess associations with seizure control.MAIN OUTCOME MEASURES: Relationships between vitamin D levels and age and factors that might affect seizure control.SAMPLE SIZE: 524 patientsRESULTS: The prevalence of low serum vitamin D levels was high (86.8%). The median vitamin D level in all patients was low (38 nmol/L), and was lower in young PWE than in adult PWE (P<.01). Only 146 patients received vitamin D supplements. High vitamin D levels were associated with a 40% seizure reduction.CONCLUSION: Vitamin D deficiency is underestimated in PWE in Saudi Arabia, and is more prevalent among young adults and patients on polytherapy than in other PWE. Patients with high vitamin D levels had good seizure control compared with those with low levels. The effect of vitamin D supplements on seizure control should be further investigated in randomized control trials.LIMITATIONS: Retrospective study and no categorization by presence of supplementation.CONFLICT OF INTEREST: None.

The Concept of «Peritumoral Zone» in Diffuse Low-Grade Gliomas: Oncological and Functional Implications for a Connectome-Guided Therapeutic Attitude.

Diffuse low-grade gliomas (DLGGs) are heterogeneous and poorly circumscribed neoplasms with isolated tumor cells that extend beyond the margins of the lesion depicted on MRI. Efforts to demarcate the glioma core from the surrounding healthy brain led us to define an intermediate region, the so-called peritumoral zone (PTZ). Although most studies about PTZ have been conducted on high-grade gliomas, the purpose here is to review the cellular, metabolic, and radiological characteristics of PTZ in the specific context of DLGG. A better delineation of PTZ, in which glioma cells and neural tissue strongly interact, may open new therapeutic avenues to optimize both functional and oncological results. First, a connectome-based “supratotal” surgical resection (i.e., with the removal of PTZ in addition to the tumor core) resulted in prolonged survival by limiting the risk of malignant transformation, while improving the quality of life, thanks to a better control of seizures. Second, the timing and order of (neo)adjuvant medical treatments can be modulated according to the pattern of peritumoral infiltration. Third, the development of new drugs specifically targeting the PTZ could be considered from an oncological (such as immunotherapy) and epileptological perspective. Further multimodal investigations of PTZ are needed to maximize long-term outcomes in DLGG patients.

Effect of Early Surgical Intervention for Brain Tumors Associated with Epilepsy on the Improvement in Memory Performance.

We evaluated the effect of early surgical intervention on the change in memory performance of patients with low-grade brain tumors associated with epilepsy. Twenty-three adult patients with low-grade brain tumors and epilepsy who underwent surgery at our institution between 2010 and 2019 were included. The Wechsler Memory Scale-Revised (WMS-R) was used to assess cognitive memory performance. Memory performance before and after surgery was retrospectively evaluated. In addition, the relationships among preoperative memory function, postoperative seizure outcome, preoperative seizure control, temporal lobe lesion, and change in memory function were examined. There were statistically significant improvements from median preoperative to postoperative WMS-R subscale scores for verbal memory, general memory, and delayed recall (p<0.001, p<0.001, and p=0.0055, respectively) regardless of preoperative sores and tumor location. Good postsurgical seizure control was associated with significant improvements in postoperative WMS-R performance. Our results indicated that early surgical intervention might improve postoperative memory function in patients with low-grade brain tumors and epilepsy.

EP028: Neurological manifestations in PMM2 related congenital disorders of glycosylation (CDG): Insights into clinico-radiological characteristics and recommendations for follow-up

PMM2-CDG is the most common N-linked glycosylation disorder. Neurological involvement is one of the major clinical features in individuals with PMM2-CDG. Understanding the neurological phenotype is essential as many treatments are on the horizon, and their ability to modify the neurological manifestations are yet to be understood. Prospective neurologic evaluation of patients with PMM2-CDG to systematically explore the neurologic phenotype, predict severity and to derive recommendations for clinical practice and research. Patients with biochemical and molecular confirmation of PMM2-CDG who were recruited along with other CDG to the Frontiers of Congenital Disorders of Glycosylation (FCDGC) natural history study were evaluated for neurological manifestations as a part of standard care. Thirty-two patients were included (7 females and 25 males). Mean age at diagnosis was 7 months (range 4 months to 32 years). Various diagnosis like spinal muscular atrophy, Prader-Willi syndrome and congenital muscular dystrophy were considered initially, before suspecting CDG. Mean age at assessment at our clinic was 11.42 years (range of 2 to 34 years). Only two patients were walking unassisted, the rest required assistance to walk. Socio-adaptive and language domains were relatively preserved when compared to motor development. Retinopathy was present in 10 (31%) and hearing loss requiring aids was seen in 6 (19%) patients. Cerebellar ataxia was the most common finding (97%) followed by myopathy (78%), neuropathy (78%), movement disorder (50%) and spasticity (19%). Seizures were present in 69% of patients with mean age at onset being 3 years (range 3 months to 24 years). Eleven of them both febrile and afebrile seizures, 4 had only febrile and 7 only afebrile seizures. Status epilepticus requiring hospital admission was seen in 28%. Antiepileptics tried were levetiracetam, oxcarbazepine, carbamazepine, phenytoin, clobazam, clonazepam and lacosamide. Three had medically refractory seizures, 3 with initially refractory seizures were currently under control, 16 had good seizure control from beginning. Total of 7 stroke like episodes (SLE) were seen in 6 patients, with precipitating factor being seizures in 4, infection in 2 and an accidental fall in one. Most of them recovered in a day. Two patients had normal imaging, whereas all others revealed progressive cerebellar atrophy. Mean score in Nijmegen Pediatric CDG rating scale was 23.1(range of 14 to 33). Statistically significant correlation was seen with seizures and SLE (p=0.004). No statistical significance was seen with head circumference, clinical features, imaging findings, Nijmegen scores or transferrin values with the severity of involvement, seizures, or SLE. Cerebellar ataxia is the most common neurological sign in PMM2-CDG. Patients with seizures are prone to develop SLE. Adequate seizure control might prevent SLE and progressive neurologic deterioration. Transferrin profile and Nijmegen scoring does not appear to correlate with neurological involvement or severity.

Cerebral creatine deficiency disorders – A clinical, genetic and follow up study from India

IntroductionCerebral creatine deficiency syndromes (CCDS) are a group of potentially treatable neurometabolic disorders. The clinical, genetic profile and follow up outcome of Indian CCDS patients is presented. Materials and methodsThis was a retrospective cohort of CCDS patients seen over six-years. Diagnosis was based either on low creatine peak on proton magnetic resonance spectroscopy (MRS) and/or genetic evaluation. ResultsThirteen patients were eligible [8 creatine transporter deficiency (CTD), 4 guanidinoacetate methyltransferase (GAMT) deficiency and 1 could not be classified]. The mean (±SD) age at diagnosis was 7.2(±5.0) years.Clinical manifestations included intellectual disability (ID) with significant expressive speech delay in all. Most had significant behavior issues (8/13) and/or autism (8/13). All had history of convulsive seizures (11/13 had epilepsy; 2 patients only had febrile seizures) and 2/13 had movement disorder. Constipation was the commonest non-neurological manifestation (5/13 patients).Cranial MRI was normal in all CTD patients but showed globus pallidus hyperintensity in all four with GAMT deficiency. MRS performed in 11/13 patients, revealed abnormally low creatine peak. A causative genetic variant (novel mutation in nine) was identified in 12 patients.Three GAMT deficiency and one CTD patient reported neurodevelopmental improvement and good seizure control after creatine supplementation. ConclusionIntellectual disability, disproportionate speech delay, autism, and epilepsy, were common in our CCDS patients. A normal structural neuroimaging with easily controlled febrile and/or afebrile seizures differentiated CTD from GAMT deficiency patients who had abnormal neuroimaging and often difficult to control epilepsy and movement disorder.

Epilepsy-Related Mortality in Children and Young Adults in Denmark

Background and Objectives Mortality is increased in epilepsy, but the important issue is that a proportion of epilepsy-related death is potentially preventable by optimized therapy and therefore needs to be identified. A new systematic classification of epilepsy-related mortality has been suggested to identify these preventable deaths. We applied this classification to an analysis of premature mortality in persons with epilepsy who were &lt;50 years of age. Methods The study was a population-based retrospective cohort of all Danish citizens with and without epilepsy 1 to 49 years of age during 2007 to 2009. Information on all deaths was retrieved from the Danish Cause of Death Registry, autopsy reports, death certificates, and the Danish National Patient Registry. The primary cause of death in persons with epilepsy was evaluated independently by 3 neurologist, 1 neuro-pediatrician, and 2 cardiologists. In case of uncertainty, a pathologist was consulted. All deaths were classified as either epilepsy related or not epilepsy related, and the underlying causes or modes of death were compared between persons with and without epilepsy. Results During the study period, 700 deaths were identified in persons with epilepsy, and 440 (62.9%) of these were epilepsy related, 169 (38%) directly related to seizures and 181 (41%) due to an underlying neurologic disease. Sudden unexpected death in epilepsy accounted for 80% of deaths directly related to epilepsy. Aspiration pneumonia was the cause of death in 80% of cases indirectly related to epilepsy. Compared with the background population, persons with epilepsy had a nearly 4-fold increased all-cause mortality (adjusted mortality hazard ratio 3.95 [95% confidence interval [CI] 3.64–4.27], p &lt; 0.0001) and a higher risk of dying of various underlying causes, including alcohol-related conditions (hazard ratio 2.91 [95% CI 2.23–3.80], p &lt; 0.0001) and suicide (hazard ratio 2.10 [95% CI 1.18–3.73], p = 0.01). Discussion The newly proposed classification for mortality in persons with epilepsy was useful in an unselected nationwide cohort. It helped in classifying unnatural causes of death as epilepsy related or not and in identifying potentially preventable deaths. The leading causes of premature mortality in persons &lt;50 years of age were related to epilepsy and were thus potentially preventable by good seizure control.

Omega-3 supplementation in children with ADHD and intractable epilepsy

BackgroundOmega-3 may have a role in the treatment of drug- resistant epilepsy. ObjectivesTo evaluate omega-3 supplementation in seizure control in children with attention deficit hyperactivity disorder (ADHD) and intractable epilepsy. Patients and MethodsSixty children with ADHD and intractable epilepsy were enrolled. They were randomly assigned in a double-blind fashion in a 1:1 ratio into the omega-3 supplementation group or the placebo group in addition to risperidone and antiepileptic drugs. All patients were assessed for the frequency and severity of the epileptic attacks at baseline, monthly, and at 6 months from the beginning of the study; 30 children received omega-3 and the other 30 children received placebo. ResultsAt baseline, the median number of seizures per month was 5 in both groups. After one month, this median decreased to 3 and became 2 after two months of supplementation with omega-3 in the supplementation group while it remained 5 in the control group. After 3 months and till the end of the study, this median decreased to 0 while it remained 5 in the control group throughout the study period.Children who were supplemented with omega-3 showed a significant decrease in the monthly frequency of seizure attacks after six months of supplementation compared to the baseline before supplementation (P < 0.05) There was no significant decrease in the severity of the seizures attacks among our patients with omega-3 supplementation (P > 0.05). ConclusionOmega 3 may help in achieving good seizure control in children with ADHD and intractable epilepsy.

Brain tumour related epilepsy with co-existing non epileptic attacks: Characteristics of a clinically challenging cohort

Abstract Aims The co-existence of non-epileptic attacks (NEAD) in patients with brain tumour related epilepsy (BTRE) is poorly described. Non epileptic attacks (NEAD) co-occur in up to 30% of patients with epilepsy PWE. Adverse life events are associated with development of NEAD; their co-occurrence in those with BTRE is potentially un-surprising. We sought to characterise the evolution of symptoms in this cohort. Method Clinical trajectories of patients with BTRE and co-existing NEAD were characterised. The diagnosis of NEAD was based on the epilepsy specialist’s observation of attacks and /or capture of attacks on video. Some patients had additional video EEG correlate. Patients had been referred because of persisting symptoms in spite of escalating antiepileptic therapy. Results Of eight patients, six were initially misdiagnosed with escalating seizures. One patient developed NEAD de novo following tumour biopsy, the remaining patients developed NEAD following onset of BTRE. Onset of NEAD was not temporally linked with the diagnosis of a brain tumour. In five patients, NEAD onset occurred when seizures were controlled (&amp;lt; 1 seizure/ month). All patients reported fear of developing uncontrolled seizures as being associated with their symptoms and identified their NEAD as more disabling than their epilepsy. Patients were eventually managed with polytherapy -two found adjunctive clobazam helpful and four were offered antidepressant/ anxiolytic medication. Behavourial strategies including mindfulness were also discussed. At time of last follow up, seven patients had on-going NEAD symptoms in spite of good seizure control. Conclusion NEAD can co-occur with BTRE and should be considered in those with rapidly escalating symptoms in spite of antiepileptic therapy and radiologically stable lesions. Both making the diagnosis of NEAD and providing ongoing support is challenging. These patients require a multidisciplinary approach with support from allied specialties including neuropsychiatry and neuropsychology.