Frequency Of Epileptic Seizures Research Articles

Impact of Epilepsy-Based Progressive Muscle Relaxation Exercises on Epileptic Seizure Frequency, Sleep Quality, and Stress Severity among Children

Impact of Epilepsy-Based Progressive Muscle Relaxation Exercises on Epileptic Seizure Frequency, Sleep Quality, and Stress Severity among Children

The Frequency of Catamenial Epilepsy in Female Epileptic Patients of Reproductive Age Group Presented to the Tertiary Care Hospital.

Background and aimCatamenial epilepsy is the type of seizures during the reproductive phase of menstruation due to hormonal changes during the different phases of menstruation. This study aims to evaluate the frequency of epileptic seizures in women during the menstruation cycle and its management.Material and methodsThis study was conducted at the neurology department of Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan. The study's duration was six months, from the 22nd of January 2020 to the 22nd of July 2020. The sample size for catamenial epilepsy in female epileptic patients of reproductive age was 78%. After approval by the ethical committee of JPMC, data collection started. Data was collected and analyzed in the Statistical Package for the Social Sciences (SPSS, version 22; IBM Inc., Armonk, USA). Mean, and the standard deviation was calculated for age, duration of epilepsy, duration of antiepileptic, and antiepileptic drug. A Chi-square test was applied, and p≤0.05 was considered a statistically significant difference.ResultsA total of 184 female patients of reproductive age were selected for this study. The mean duration of epilepsy was 15.96 ± 8.85 months. The mean duration of antiepileptic drugs was 11.16 ± 7.53 months. In 73 patients (39.7%), EEG showed increased seizure activity during particular phases of the menstrual cycle. Catamenial epilepsy was seen in 73 patients (39.7%). The stratification according to age, duration of epilepsy, duration of antiepileptic drugs, the antiepileptic drug was done to observe the effect of these modifiers on catamenial epilepsy.ConclusionCatamenial epilepsy is relatively common epilepsy. The physician should evaluate patients when the seizures are refractory to the treatment. The females should manage a seizure diary, which will be beneficial in the management of epilepsy. In women with epilepsy, catamenial epilepsy should be considered in the diagnosis when the seizures are refractory to optimal treatment.

Correlates of psychological distress in epileptic patients during the COVID-19 outbreak

IntroductionFollowing the severe consequences of the coronavirus disease 2019 (COVID-19) outbreak, on March 9th, 2020 the Italian Government implemented extraordinary measures to limit viral transmission, including restrictive quarantine measures. Psychological distress represents the seizure-precipitating factor most often reported by patients with epilepsy. To date, no studies have analyzed the role played by the different dimensions of psychological distress quarantine-induced in patients with epilepsy. Materials and MethodsWe included a total of 40 patients, 18 suffered from generalized, and 22 from focal epilepsy. The patients previously seen in the outpatient clinic during the pre-lockdown period between January and February 2020 were reevaluated after the lockdown period. Psychological distress was evaluated by using the three subscales of Impact of Event Scale-Revised (IES-R). Finally, we employed logistic regression analyses to explore the demographic and clinical features associated to high scores on IES-R. ResultsPatients with higher scores on IES-R Intrusion and IES-R Avoidance subscales demonstrated an increased number of epileptic attacks compared to prelockdown period. Multivariate logistic regression analyses showed that a specific subgroup of patients (i.e., older, female with more anxious symptoms) are at higher risk of increased seizure frequency. ConclusionsOur study confirmed that the frequency of epileptic seizures increased during lockdown when compared to pre-lockdown period. The early identification of patients more vulnerable to worsening is crucial to limit the risk of requiring hospital or clinical treatment during the COVID-19 outbreak.

Relationship of serum ATPase activity and the levels of neuron- specific enolase, S100B and B-cell lymphoma/leukemia-2 with cognitive function after epileptic seizure.

To analyze the relationship of serum ATPase activity and the levels of neuron-specific enolase (NSE), S100B protein and B-cell lymphoma/leukemia (Bcl)-2 with cognitive function in patients after epileptic seizure. A total of 65 epilepsy patients were enrolled as the epilepsy group from the hospital between May 2017 and February 2019. A control group was formed by 30 healthy volunteers at the same period and in the same area whose basic data matched with those of the epileptic patients. Cognitive function was evaluated using the Montreal Cognitive Assessment Form (MoCA). Time and frequency of epileptic seizures were recorded in epileptic group. Within 6 hours following the attack, blood tests were carried out to measure the hydrolysis rates of serum adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), phosphodiesterase (PDE) activity, and levels of serum NSE, S100B and Bcl-2. The relationship of these indexes with the time of epileptic seizure and MoCA total score was analyzed. The epilepsy group included 18 cases (27.69%) with cognitive dysfunction. The time and frequency of epileptic seizure in the patients with cognitive dysfunction was significantly higher than that of patients without cognitive dysfunction, while the total MoCA score was significantly lower with cognitive dysfunction than that without (P<0.05). The total MoCA score of epileptic patients with and without cognitive dysfunction was significantly lower than that of the control group (P<0.05). The hydrolysis rates of ATP, ADP and AMP, PDE activity, and serum NES, S100B and Bcl-2 levels in patients with cognitive dysfunction were significantly higher than those without cognitive dysfunction (P<0.05). The above serum indexes of the patients were significantly higher than those of people in the control group (P<0.05). Spearman's correlation analysis showed that hydrolysis rates of serum ATP, ADP and AMP, PDE activity, and serum NES, S100B and Bcl-2 levels were positively correlated with time and frequency of epileptic seizure (P<0.05), and negatively correlated with total MoCA score (P<0.05). The cognitive function of epilepsy patients is significantly decreased compared with that of healthy individuals. Serum ATPase activity, along with serum NES, S100B and Bcl-2 levels, is associated with time and frequency of epileptic seizure and cognitive function after attack.

Compassionate use of everolimus for refractory epilepsy in a patient with MTOR mosaic mutation

The MTOR gene encodes the mechanistic target of rapamycin (mTOR), which is a core component of the PI3K-AKT-mTOR signaling pathway. Postzygotic MTOR variants result in various mosaic phenotypes, referred to in OMIM as Smith-Kinsgmore syndrome or focal cortical dysplasia. We report here the case of a patient, with an MTOR mosaic gain-of-function variant (p.Glu2419Lys) in the DNA of 41% skin cells, who received compassionate off-label treatment with everolimus for refractory epilepsy. This 12-year-old-girl presented with psychomotor regression, intractable seizures, hypopigmentation along Blaschko's lines (hypomelanosis of Ito), asymmetric regional body overgrowth, and ocular anomalies, as well as left cerebral hemispheric hypertrophy with some focal underlying migration disorders. In response to the patient's increasingly frequent epileptic seizures, everolimus was initiated (after approval from the hospital ethics committee) at 5 mg/day and progressively increased to 12.5 mg/day. After 5 months of close monitoring (including neuropsychological and electroencephalographic assessment), no decrease in seizure frequency was observed. Though the physiopathological rationale was good, no significant clinical response was noticed under everolimus treatment. A clinical trial would be needed to draw conclusions, but, because the phenotype is extremely rare, it would certainly need to be conducted on an international scale.

Atypical duration of epileptic and psychogenic nonepileptic events

ObjectivesWe aimed to estimate the frequency of epileptic seizures (ES) and psychogenic nonepileptic seizures (PNES) with atypical duration in our epilepsy monitoring unit (EMU), in order to raise awareness of atypical durations of both types of events. Materials & methodsWe retrospectively reviewed all consecutive video-electroencephalogram (vEEG) recordings in our medical center's EMU from January 2013 to December 2017 and identified patients with seizures with atypical duration. Short PNES were defined as those lasting fewer than 2 min and long ES as those lasting for more than 5 min. ResultsThe files of 830 adult (age >16 years) patients were reviewed, of whom 26 patients (3.1%, mean age: 33.3 ± 9.8 years, 12 females) were diagnosed as having an unusual seizure duration. Among 432 patients with ES during monitoring, fourteen patients [3.2% (95% confidence interval (CI): 1.5%–5.0%), mean age: 33.0 ± 12.2, 5 females [had long ES durations (exceeding 5 min). In 64% of patients with long ES, the events were provoked by antiepileptic drug (AED) withdrawal during vEEG, 62% had focal lesion on brain imaging, and 64% had a frontotemporal or a temporal seizure focus. Among 223 patients diagnosed with PNES, 12 patients [5.4% (95% CI: 2.2%–8.6%), mean age: 33.6 ± 6.6, 7 females] had short PNES durations (less than 2 min) and demonstrated motor (9/12, 75%), altered responsiveness (6/12, 50%), and vocalization (5/12, 42%) as the most prominent clinical features. ConclusionsThe data from our case files highlight two main considerations in the diagnosis of paroxysmal events: prolonged event can be due to ES, while short events can be psychogenic.

ERGO2: A Prospective, Randomized Trial of Calorie-Restricted Ketogenic Diet and Fasting in Addition to Reirradiation for Malignant Glioma

ERGO2 is the first randomized clinical trial on a calorically restricted ketogenic diet (KD) and intermittent fasting (KD-IF) in addition to reirradiation for recurrent malignant gliomas. Fifty patients were randomized 1:1 to reirradiation combined with either a calorically unrestricted diet or KD-IF. The KD-IF schedule included 3 days of KD (21-23 kcal/kg/d), followed by 3 days of fasting and again 3 days of KD. Primary endpoint was progression-free survival (PFS) at 6 months (PFS6). Secondary endpoints were PFS, local PFS, overall survival (OS), frequency of epileptic seizures, rate of ketosis and quality of life. Four patients quit the trial before treatment and 3 patients stopped KD-IF prematurely. Of the 20 patients who completed KD-IF, 17 patients developed ketosis at day 6 and glucose levels declined significantly. KD-IF was well-tolerated with a modest weight loss of -2.1 ± 1.8 kg. No severe adverse events attributable to the diet occurred. PFS6 was not significantly different between the 2 groups (KD-IF: 20%; calorically unrestricted diet: 16%). Similarly, no difference in PFS, local PFS6, or OS was observable. Explorative analysis revealed that patients in the KD-IF group who had a glucose level of less than the median (83.5 mg/dL) on day 6 had significantly longer PFS and OS compared with those above the median (P < .05). KD-IF is feasible and effective in inducing ketosis in heavily pretreated patients with recurrent glioma. However, the short schedule reported here failed to increase the efficacy of reirradiation. CLINICALTRIALS. NCT01754350.

Clinical Characteristics of Anti-GABA-B Receptor Encephalitis.

Objective: Anti-GABA-B (gamma aminobutyric acid-B) receptor encephalitis is an autoimmune disease mediated by GABA-B-related antibodies. To fully understand the disease, we collected clinical data from patients with GABA-B receptor encephalitis and conducted an analysis to draw conclusions.Methods: All patients with GABA-B receptor encephalitis from the Neurology Department of Beijing Tiantan Hospital, affiliated with Capital Medical University, from August 2015 to September 2019 were accepted as study subjects. The clinical data of the patients were analyzed retrospectively and included the general demographic characteristics, clinical manifestations, and auxiliary examinations, including laboratory results, electroencephalograms (EEGs), brain magnetic resonance imaging (MRI), and positron emission tomography (PET-CT) results, as well as treatments.Results: From August 2015 to September 2019, 14 cases of anti-GABA-B receptor encephalitis were diagnosed. Among these patients, middle-aged and elderly men were the main demographic, with an average age of 52 years; moreover, the onset of the disease was relatively sudden, and the time from onset to diagnosis was ~1 month. The main clinical symptoms were frequent epileptic seizures, cognitive dysfunction, and mental behavioral disorders. In seven (50%) patients, the leukocyte in cerebrospinal fluid (CSF) were increased. Five (36%) patients had elevated cerebrospinal fluid protein. In most patients, the oligoclonal bands (83%) of CSF were positive, and 24 h IgG levels (92%) were increased. Anti-Hu or anti-Yo antibodies were positive in two (14%) patients. Tumor markers in 10 (71%) patients indicated that neuron-specific enolase, gastrin-releasing precursor, non-small cell lung cancer-related antigen, or carcinoembryonic antigen levels were increased. EEG results often indicated slow waves, sharp waves, or spike waves in temporal areas. Brain MRI always showed high T2 signals in the medial temporal lobe, hippocampus, and amygdala and swelling in the medial temporal lobe and hippocampus. PET-CT scans almost showed abnormal metabolism in the hippocampus and temporal lobe. Three (21%) patients who underwent systemic PET-CT showed hypermetabolism in pulmonary parenchymal nodules and enlargement of mediastinal lymph nodes. All patients underwent high-dose hormone therapy or immunoglobulin immunotherapy. After treatment, the symptoms of epilepsy, cognitive disorders, and mental behavioral disorders improved to varying degrees. However, one patient died of lung cancer.Conclusion: Anti-GABA-B receptor encephalitis mainly occurred in middle-aged and elderly men, and the disease onset was relatively sudden. Before disease onset, some patients experienced fever and non-specific respiratory symptoms, which mainly manifested as frequent epileptic seizures, cognitive dysfunction, and abnormal mental behavior. MRI and PET-CT revealed abnormal signals and local metabolism, respectively, in the temporal lobe. Moreover, the disease has a close relationship with lung cancer, which requires long-term follow-up observation.

Epilepsy surgery reduced seizure frequency for patients with severe motor and intellectual disorders

IntroductionLittle is known about epilepsy surgery for patients with severe motor and intellectual disorders (SMIDs). We hypothesized that epilepsy surgery could reduce epileptic seizure frequency in these patients. The purpose of this study was to compare pre- and postoperative seizure frequency in patients with SMIDs. MethodsA total of 288 surgeries were performed for pediatric patients, including those with SMIDs, from 2009 to 2018. Inclusion criteria were as follows: Oshima classification 1 (intelligence quotient <20 and bedridden), ≥2 years old, proven ictal events evaluated by long-term video electroencephalography, and ≥1-year follow-up. Seizure frequency and the number of antiseizure medications (ASMs) were compared between pre- and postepilepsy surgery. Patients' respiratory and feeding conditions were also examined to determine comorbidities. ResultsNineteen patients (5 girls, 14 boys; age: 2 to 12 years) fulfilled the inclusion criteria. One patient underwent focus resection, 2 patients underwent total corpus callosotomy, and 16 patients underwent vagus nerve stimulation therapies. Of 19 patients, 16 (84.2%) had daily seizures, and 3 (15.8%) had weekly seizures before surgery. Epilepsy surgery significantly reduced seizure frequency (p = 0.029). Five patients (26.3%) had status epilepticus (SE) before surgery, which disappeared in all but one after surgery (p = 0.046). The number of ASMs did not change between before and after surgery (p = 0.728). ConclusionEpilepsy surgery reduced the frequency of epileptic seizures and improved SE even among patients with compromised respiratory function and compromised food intake.

Extended-release vinpocetine: a possible adjuvant treatment for focal onset epileptic seizures.

Extended-release vinpocetine is effective to control focal onset epileptic seizures with a low rate of adverse events. A clinical study was performed to evaluate the efficacy and tolerability of vinpocetine as an adjuvant treatment in patients with this condition. A double-blind clinical study of parallel groups was conducted, in which 87 patients with a diagnosis of focal epilepsy treated with one to three antiepileptic drugs were recruited. Patients were randomized to receive vinpocetine (n = 41) or placebo (n = 46) adjuvant to their treatment. Patients entered the baseline phase (4 weeks), the titration phase (4 weeks) and the evaluation phase (8 weeks), maintaining stable doses of vinpocetine and their respective antiepileptic drug treatment. Vinpocetine was more effective than placebo in reducing seizures at the end of the evaluation phase (p < 0.0001). Sixty-nine percent of the vinpocetine-treated patients had a 50% reduction in seizures compared to 13% of placebo-treated patients. No significant differences in the presence of adverse effects in patients treated with vinpocetine compared to those treated with placebo were observed. The most frequent adverse events observed with vinpocetine were headache (7.9%) and diplopia (5.2%). As an adjuvant treatment, vinpocetine (2 mg/kg/day) effectively reduced the frequency of epileptic seizures and proved to be well tolerated. Vinpocetine has a wide safety profile and well-known adverse events, which are transient and with no sequelae.

Features of the structure of epileptic syndrome and cognitive disorders in patients with cerebral arteriovenous malformation

To assess the frequency, structure of epileptic syndrome and cognitive impairment in patients with cerebral AVM (PAVM). The main group consisted of 78 PAVM: average age of 36.2. The results of the study:1 subgroup- a right-hemisphere localization - 41(53%); 2 subgroup - a left-hemisphere localization – 37(47%). Of these, 33%frontal lobe; 12% the temporal lobe;17% area central convolutions; 28% the parietal and the occipital lobe;10% - subcortical structures. In all cases evaluated, the frequency of epileptic seizures: frequent 11%; moderate 50%; rare 28%; seizures were not observed in 11% cases. The structure of epileptic syndrome was presented in the following seizures: partial sensorimotor in 29%; vegetative-visceral - 40%; mixed: complex partial; secondary generalized - 31%. Changes in EEG in 14% cases, changes were not observed; moderate diffuse changes at the level of diencephalic structures –23%; paroxysmal activity of malformations with an interest in diencephalic structures of the brain-41%;the formation of a mirror focus –10%, moderate irritative changes of EEG –7%; the presence of the pattern of epileptiform activity-5%. Cognitive impairment of varying severity degree were identified in PAVM: mild cognitive disorders – 21%; mild cognitive impairment – 64%; dementia from mild to severe, severity – 13%. The duration and frequency of the epileptic syndrome of the complex structure aggravate the course of cognitive impairment, thereby reducing quality of life of PAVM. A comprehensive assessment of cognitive disorders, structure and frequency of epileptic syndrome can be a diagnostic criterion of the results of the immediate outcomes of endovascular treatment of AVM.

Psychosocial problem of people with epilepsy in Ulaanbaatar of Mongolia

Background Epilepsy is a common neurological disease, which need to health care and public health service topicality that is a very important for people with epilepsy (PWE). Purpose To investigate psychosocial problem of the people with epilepsy. Method 77 patients were included in our study. In order to identify psychosocial problems we used the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI) and a ten-item measure of felt stigma for this cross-sectional study. Result There were 46.8% female, 44.2% were married, 75.3% unemployment. The frequencies of anxiety symptoms in PWE were 31.2% very anxiety, 32.5% anxiety and 36.4% not anxiety, the rates of depressive symptoms in PWE were 18.2% very depressed, 19.5% depressed and 62.3% not depressed, respectively. All of the 62.3% PWE felt stigma. Considering the age, psychological problem, some of the variables of the participants, the age of the people with epilepsy was associated with depression and the stigma scores, negatively. (r= -0.2 p=0.05; r = -0.2 p=0.05). There are relationships between stigma and anxiety, depression, social-interaction of the attitude scores in PWE. (r= 0.5 p= 0.01; r= 0.5 p= 0.01; r=0.4 p= 0.01). Whereas that the correlation statistic did not indicate a relationship between the duration of the epilepsy and anxiety, depression, stigma and social-interaction’s scores Conclusion This reveals that it has positive relationship with social-interaction and attitude. Frequency of epileptic seizures induces the anxiety and depression of the people with epilepsy and thus worsens their stigmatization.

Interventions for treating brain arteriovenous malformations in adults.

Brain arteriovenous malformations (AVMs) are the single most common cause of intracerebral haemorrhage in young adults. Brain AVMs also cause seizure(s) and focal neurological deficits (in the absence of haemorrhage, migraine or an epileptic seizure); approximately one-fifth are incidental discoveries. Various interventions are used in an attempt to eradicate brain AVMs: neurosurgical excision, stereotactic radiosurgery, endovascular embolization, and staged combinations of these interventions. This is an update of a Cochrane Review first published in 2006, and last updated in 2009. To determine the effectiveness and safety of the different interventions, alone or in combination, for treating brain AVMs in adults compared against either each other, or conservative management, in randomized controlled trials (RCTs). The Cochrane Stroke Group Information Specialist searched the Cochrane Stroke Group Trials Register (last searched 7 January 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1) in the Cochrane Library, MEDLINE Ovid (1980 to 14 January 2019), and Embase OVID (1980 to 14 January 2019). We searched international registers of clinical trials, the contents pages of relevant journals, and bibliographies of relevant articles (November 2009). We also contacted manufacturers of interventional treatments for brain AVMs (March 2005). We sought RCTs of any intervention for brain AVMs (used alone or in combination), compared against each other or against conservative management, with relevant clinical outcome measures. One author screened the results of the updated searches for potentially eligible RCTs for this updated review. Both authors independently read the potentially eligible RCTs in full and confirmed their inclusion according to the inclusion criteria. We resolved disagreement by discussion. We assessed the risk of bias in included studies and applied GRADE. We included one trial with 226 participants: A Randomized trial of Unruptured Brain Arteriovenous Malformations (ARUBA), comparing intervention versus conservative management for unruptured brain AVMs (that had never bled). The quality of evidence was moderate because we found just one trial that was at low risk of bias other than a high risk of performance bias due to participants and treating physicians not being blinded to allocated treatment. Data on functional outcome and death at a follow-up of 12 months were provided for 218 (96%) of the participants in ARUBA. In this randomized controlled trial (RCT), intervention compared to conservative management increased death or dependency (modified Rankin Scale score ≥ 2, risk ratio (RR) 2.53, 95% confidence interval (CI) 1.28 to 4.98; 1 trial, 226 participants; moderate-quality evidence) and the proportion of participants with symptomatic intracranial haemorrhage (RR 6.75, 95% CI 2.07 to 21.96; 1 trial, 226 participants; moderate-quality evidence), but there was no difference in the frequency of epileptic seizures (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 226 participants; moderate-quality evidence). Three RCTs are ongoing. We found moderate-quality evidence from one RCT including adults with unruptured brain AVMs that conservative management was superior to intervention with respect to functional outcome and symptomatic intracranial haemorrhage over one year after randomization. More RCTs will help to confirm or refute these findings.

OS6.5 ERGO2: A prospective randomized trial of a 9-day schedule of calorically restricted ketogenic diet and fasting or standard diet in addition to re-irradiation for malignant glioma

Abstract BACKGROUND Ketogenic diet (KD) and fasting have anticancer effects in tumor models, possibly due to a differential stress response with sensitization of tumor cells and protection of normal tissue. We therefore set up ERGO2 (NCT01754350), the first randomized clinical trial of calorically-restricted KD and intermittent fasting (KD-IF) in addition to re-irradiation for recurrent malignant gliomas. MATERIAL AND METHODS Patients were randomized 1:1 to re-irradiation combined with either calorically unrestricted diet (standard diet, SD) or KD-IF. The KD-IF schedule included 3 days of KD (21–23 kcal/kg/d), followed by 3 days of fasting and again 3 days of KD. The primary endpoint was progression-free survival (PFS) rate at 6 months (PFS6). Secondary endpoints were PFS, local control, overall survival (OS), frequency of epileptic seizures, rate of ketosis and quality of life. RESULTS 50 patients were included. Four patients quit the trial before treatment and three patients stopped KD-IF prematurely. Of the 20 patients who completed KD-IF, 17 patients developed ketosis at day 6, and glucose levels declined significantly. KD-IF was well-tolerated with a modest weight loss of -2.1±1.8 kg. No severe adverse events attributable to the diet occurred. There was no difference in PFS6 between the two groups (KD-IF: 20%, SD: 16%). Similarly, no difference in PFS, local PFS6 and OS were observable. Explorative analysis revealed that among patients of the KD-IF group, those who achieved ketosis of at least 1.5 mmol/l had significantly longer PFS compared to those with lesser or no ketosis. CONCLUSION KD-IF is feasible and effective in inducing ketosis in heavily pretreated patients with recurrent glioblastoma. However, the short schedule reported here failed to increase the efficacy of re-irradiation.

Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR-135a-5p, as well as those between miR-135a-5p and 3' untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual-luciferase reporter gene assay. The expression of miR-135a-5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR-135a-5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv-shGAS5 and Lv-miR-135a-5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR-135a-5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR-135a-5p. After the treatment of Lv-shGAS5 and Lv-miR-135a-5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR-135a-5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.

KINESITHERAPEUTIC APPROACH IN CHILD CEREBRAL PALSY

Child Cerebral Palsy (CCP) is a non-progressive, chronic brain injury that can occur during pregnancy - prenatal period, during childbirth - perinatal period or postnatal period. It is characterized by a disorder of muscle tone, disturbance of balance, coordination, speech, hearing, etc. Also, some children may experience some degree of cognitive and intellectual deficiency. Damage mainly occurs at the upper motor neuron affecting the cerebellum. This disorder of the central nervous system leads to disruption of the normal development of motor functions, muscle tone, and coordination. Children's cerebral palsy is a disease that very often leads to severe disability, and to successfully battle with the consequences and serious disabilities, early detection, and the onset of treatment is needed from the first days of the child's life. The treatment of CCP is complex in which, besides medical, pedagogical and social rehabilitation, kinesitherapy is included. The aim of the study is to evaluate the effect of the kinesitherapeutic approach and the specialized kinesitherapeutic method in children with CP. Material and Methods: The study was conducted with 8 children with CP due to premature birth and complications at birth and with spastic diplexia after periventricular leucomalation, the leg being more affected than the hand and with no signs of cortical damage and spastic hemiplegia.The study excludes patients with severe and frequent epileptic seizures and serious cognitive problems. For the purpose of the study, a set of diagnostic methods was applied, and the results were scored at the beginning, 3rd month, and 6th month of treatment initiation and were applied to a working datasheet. Were Evaluated: the functionality of a modified test Chedoke-McMaster (Chedoke-McMaster Stroke Assessment), muscle tone with a modified scale of Ashworth and the balanace capabilities with test Berg (Berg Balanace Ssale-BBS). Results: The specialized kinesitherapeutic methodology permanently stabilizes the functional opportunities for rehabilitation and balanced opportunities for children with CP. Conclusion: The complete and in-depth analysis of the tangible results gives us reason to assert that the applied kinesitherapy has both an early and a late therapeutic effect that is related to the duration of administration, the structure of performance and the purpose of the included kinesitherapeutic means.

Quality of Life in Chronic Ketogenic Diet Treatment: The GLUT1DS Population Perspective.

Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare, genetically determined neurological disorder, for which Ketogenic Diet (KD) represents the gold standard life-long treatment. The aim of this study is to investigate health related quality of life in a well characterized cohort of patients affected by GLUT1DS treated with KD, evaluating factors that can influence patients’ and parents’ quality of life perception. Methods: This is a double center exploratory research study. A postal survey with auto-administrable questionnaires was conducted among 17 subjects (aged 3–22 years) with diagnosis of GLUT1DS, receiving a stable KD treatment for more than 1 year. The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales was adopted. Clinical variables analyzed in relation to quality of life were frequency of epileptic seizures and movement disorder since KD introduction, presence of intellectual disability (ID), and KD ratio. Results: Quality of life global scores were impaired both in parents’ and children’s perspectives, with a significant concordance. Taking into consideration subscales, the average was 64.17 (range 10–100) for physical functioning, 74.23 (range 30–100) for emotional functioning, 62.64 (range 10–100) for social functioning, and 56 (range 15–92) for school functioning. Conclusions: In patients with GLUT1DS the quality of life perception is comparable to that of other patients with chronic disease. In our sample, the presence of movement disorder seems to be a crucial element in quality of life perception.

A Single-Arm Open-Label Clinical Trial on the Efficacy and Safety of Sirolimus for Epileptic Seizures Associated with Focal Cortical Dysplasia Type II: A Study Protocol.

Epileptic seizures are core symptoms in focal cortical dysplasia (FCD), a disease that often develops in infancy. Such seizures are refractory to conventional antiepileptic drugs (AED) and temporarily disappear in response to AED in only 17% of patients. Currently, surgical resection is an important option for the treatment of epileptic seizures in FCD. In 2015, Korean and Japanese groups independently reported that FCD is caused by somatic mosaic mutation of the MTOR gene in the brain tissue. Based on these results we decided to test a novel treatment using sirolimus, an mTOR inhibitor, for epileptic seizures in patients with FCD type II. A single arm open-label clinical trial for FCD type II patients is being conducted in order to evaluate the efficacy and safety of sirolimus. The dose of sirolimus is fixed for the first 4 weeks and dose adjustment is achieved to maintain a blood level of 5 to 15 ng/mL during 8 to 24 weeks after initiation of administration, and it is kept within this level during a maintenance therapy period of 12 weeks. Primary endpoint is a reduction in the rate of incidence of focal seizures (including focal to bilateral tonic-clonic seizures) per 28 days during the maintenance therapy period from the observation period. To evaluate the frequency of epileptic seizures, registry data will be used as an external control group. We hope that the results of this trial will lead to future innovative treatments for FCD type II patients.

Clinical phenotype of autism spectrum disorders in children of preschool and school age, burdened epileptic seizures

Background. Clinical polymorphism and polymorphism are inherent in the clinical phenotype of children with autism spectrum disorders (ASD). There is a consensus, relatively high, between 5% and 38% of the prevalence of epilepsy in ASD. There are reasons to believe that ASD with epilepsy and specific epileptic activity on EEG and ASD with hyperkinetic symptoms without signs of epileptic process can be determined by different variants of genetic polymorphism or by different variants of gene expression, determined by different influences.&#x0D; Objective – to study the features of the clinical phenotype of ASD in preschool and school-age children with epileptic seizures and specific epileptic activity on EEG.&#x0D; Materials and methods. In the Department of Mental Disorders of Children and Adolescents of the Institute of Psychiatry of the Ministry of Health of Ukraine 116 children aged 2-10 years with ASD were examined. The study group was divided into three subgroups: subgroup A – 23 children with a history of epileptic seizures, subgroup B – 35 children with specific forms of epileptic activity on EEG without epileptic seizures, subgroup C – 19 children with ASD having specific epileptic activity for EEG repetitive involuntary movements (motor stereotypes, motor tics) and vocalizations (vocal tics). The control group consisted of 39 children with ASD non a history of seizures and specific epileptic activity on the EEG. The follow-up of children with ASD in the comparison groups was performed for 1-1.5 years. We used such research methods: clinical-psychopathological, psychodiagnostic, psychometric, statistical.&#x0D; Results. In children with ASD and comorbid epileptic seizures, disorders of social reciprocity are of crucial diagnostic importance. Communication disorders and recurrent, stereotyped behaviors, movements, and interests in children in this group are significantly less common than in comparison groups. Incidents of repetitive stereotypes in these children are associated with sensory impairments and autostimulations. Children with ASD, complicated by severe and frequent epileptic seizures, are characterized by impaired social reciprocity and communication against the background of regression or stagnation of speech and motor skills development.&#x0D; Disorders of communication and repetitive behavior in ASD in children of different ages are represented by different monoqualitative syndrome (phenotypes). Younger children less than 6 years of age are dominant in stereotypical movements, while children aged 6-8 years have repetitive behaviors associated with the overriding interests.&#x0D; Two subtypes of clinical phenotypes of ASD were identified: the variant with symptoms, which more closely determined the stereotypical sensor and motor behavior and the variant with symptoms of insistence on equality, with the overriding interests of preservation, identity. Movement stereotypes predominated in children with ASD without epileptic seizures and without epileptic activity on EEG. In children with ASD and epileptic activity on EEG, motor stereotypes and repetitive identity-preserving behavior were equally common.&#x0D; Conclusions. Disorders of social reciprocity, communication, repetitive behavior, in particular stereotyped movements are diagnostically significant signs of ASD, in particular ASD complicated by epileptic seizures, ASD with specific epileptic activity on EEG.&#x0D; According to the results of a long 1-1.5 years’ prospective study, it was established that the clinical phenotype of ASD with epileptic seizures, ASD without epileptic seizures with specific epileptic activity on EEG and RAS without epileptic seizures and changes in EEG are characterized by differing clinical picture and course.&#x0D; Qualitative communication disorders and stereotypical movements in addition to ASD are observed in other psychiatric disorders, including Tourette disorder, obsessive-compulsive disorders, and intellectual disability. Expressed repeated identity-preserving behavior is the basis for dual diagnosis of ASD and obsessive-compulsive disorder. Motor and vocal tics may be the basis for dual diagnosis of ASD and Tourette’s disorder.&#x0D; The presence of age-related pathoplasty of clinical manifestations of ASD in the comparison groups was established.

Attention deficit hyperactivity disorder (ADHD) in children with epilepsy.

Attention deficit hyperactivity disorder (ADHD) is a common comorbidity of childhood epilepsy. ADHD symptoms in children with epilepsy have been studied since 1970s in western countries. However, relative studies are still rather limited in China. To study the incidence rate of ADHD in children with epilepsy, and further analyze the relationship of epilepsy and ADHD in China. 206 children (age 6-16) with epilepsy and 58 healthy controls underwent assessment instruments (DSM-IV ADHD, ADHD Rating Scale-IV, and SNAP-IV Rating Scale). The prevalence of comorbid ADHD was significantly higher in children with epilepsy (24.76%) than that in controls (5.17%), and inattentive subtype (ADHD-I, 14.1%) was the most prevalent. ADHD in childhood epilepsy was associated with younger age, early first onset age, and high frequency of epileptic seizures. There was no significant difference of ADHD incidence rate regarding the seizure type and abnormal electroencephalogram (EEG) discharges. The ADHD comorbidity rate in children treated with antiepileptic drugs (AEDs) (27.6%) was higher than that without AEDs therapy (14.0%); multiple AEDs were associated with a higher rate of ADHD comorbidity as compared with single AEDs. The incidence of comorbid ADHD in epileptic children treated with traditional single AEDs was significantly higher than those treated with novel single AEDs. Children with epilepsy have more attention problems as compared with healthy controls. ADHD in childhood epilepsy is associated with male sex, younger age, early first onset age, high frequency of epileptic seizures, and multiple AEDs.