Resistant Epilepsy Research Articles

Targeting p-glycoprotein efflux transporter via the selective cox2 inhibitor celecoxib improves levetiracetam clinical response in epilepsy

One of the major drug efflux transporters of concern in drug resistant epilepsy (DRE) is P-glycoprotein (P-gp). P-gp's reported overexpression in epileptic foci resected from patients intensifies its intimate link to DRE. The principal aim of the study was to assess the importance of P-gp as a potential therapeutic target in epilepsy. Can expression modulation of P-gp by celecoxib boost the antiepileptic effect of the P-gp substrate; levetiracetam?

Selection of children with drug resistant epilepsy who are candidates for epilepsy surgery: pre and post-operative evaluation

Abstract Objective To select patients with drug resistant epilepsy following up in Pediatrics Neurology Outpatient Clinic of Children's Hospital, Ain Shams University who are candidates for epilepsy surgery and to detect outcome of epilepsy surgery in such children as regards seizures control. Methods This prospective study was conducted over a period of 36 months and comprises of 3 stages. Stage 1 includes selection of candidates for epilepsy surgery and preoperative evaluation. Evaluation included clinical assessment, video EEG, MRI epilepsy protocol. Stage 2 include surgery phase where decision of surgery was made by a multidisciplinary team. Stage 3 includes post-operative evaluation as regards Seizures frequency, Seizures Severity using Chalfont score, Engel Epilepsy Surgery Outcome Scale and the International League Against Epilepsy (ILAE) outcome classification. Data was tabulated and analyzed with SSPS package for windows. Results 17 patients underwent epilepsy surgery. Results revealed significant decrease in seizures frequency and severity at 6 and 12 months after surgery. As regards Engel Epilepsy Surgery Outcome Scale 11 (64.7%) patients were class I at 12 months. As regards the ILAE outcome classification 10 (58.8%) patients are class 1 at 12 months. Conclusions epilepsy surgery can be a hope for patients with drug resistant epilepsy who are well selected and evaluated preoperatively. New studies on larger number and for longer duration are recommended.

The “newest” AEDS - are they gamechangers?

The newest ASMs: Are they gamechangers? Much has been written recently about the failure of several decades worth of newly approved antiseizure medicines (ASMs) to be able to reduce the number of treatment resistant epilepsy patients, despite the approval of over a dozen new therapies. Recent studies have suggested that the likelihood that epilepsy will be resistant to anti-seizure medicines has changed very little over the last several decades. Clinicians turned to surgery and devices as the best tools for providing a substantial seizure reduction. However, in the last several years there appears to finally be evidence that substantial progress is possible from ASMs. Some of this turnaround has arisen from a renewed interest in treatment of orphan epilepsies associated with developmental and epileptic encephalopathy (DEE). One example of a “gamechanging” ASM is fenfluoramine, which has been approved for the treatment of Dravet syndrome. Cenobamate, recently approved for use in focal epilepsy, also performed extremely well, both in short-term randomized placebo-controlled trials, and in long-term follow-up studies, where observed seizure freedom rates of over 20% at the highest dose far surpass the seizure freedom rates seen with devices such as the responsive neurostimulator and the deep brain stimulator. These recent drug approvals have provided an excellent demonstration that we should not count out the benefits of anti-seizure medications in the fight to eliminate treatment resistant epilepsy. The next few years will bring trials of disease modifying treatments including precision therapies targeted at epilepsies caused by specific gene mutations.

Feasibility of transcutaneous auricular vagus nerve stimulation in treatment of drug resistant epilepsy: A multicenter prospective study

BackgroundTranscutaneous auricular vagus nerve stimulation (ta-VNS) is a new non-invasive technique developed as treatment option for drug resistant epilepsy. A few studies have been carried out showing that the efficacy and tolerability of ta-VNS is comparable with traditional implanted VNS but the feasibility of the therapy has been poorly described. This study aimed to explore potential clinical benefits of ta-VNS and to evaluate adaptation, compliance, as well as the usability of the device from a service design perspective. MethodsA prospective, multicenter, clinical, investigator-initiated trial was conducted using the NEMOS® ta-VNS device. After eight weeks baseline, all subjects started ta-VNS with individually adjusted currents for four hours per day for six-months (first endpoint) followed by optional 12 months follow-up (second endpoint). The primary outcome was six months retention rate of ta-VNS therapy. Secondary outcomes included the user retention rate at 12 months follow-up, compliance, changes in scores of psychometric measures. For the study of feasibility, a service design questionnaire on medical devices used in the home was developed. ResultsIn total 37 subjects had been included in the study after 45 months where the study was prematurely terminated due to recruitment problems and due to a high drop-out rate. Twenty-two subjects (59 %) completed the first six months of the study and in total six subjects (16 %) completed the following 12 months follow-up. The reasons for discontinuation were a mixture of medical and practical issues of which the majority were related to a combination of both. Those, who managed to continue to use ta-VNS throughout the study, gave generally higher scores for the device usability and compatibility with lifestyle. The study turned out to be inadequately powered to reach any conclusion in terms of the clinical benefits of ta-VNS but present an example of difficulties that are encountered in conducting high-quality studies with digital devices. ConclusionThe feasibility of ta-VNS therapy showed to be relatively modest which is most likely due to practical usability issues and lifestyle fits. The results of this study stress the importance of generating data based on patients experiences at an early stage during the development phase and when designing clinical trials on medical devices that depend on patient’s active participation and motivation.

Evaluation of drug-resistant focal epilepsy in the western Indian adult population

Despite the best possible pharmacotherapy, 30% of persons with epilepsy will remain drug resistant. Drug resistant Epilepsy (DRE) has many different presentations and causes; hence evaluation may help to understand and manage appropriately. To study a cohort of adult patients with refractory focal epilepsy, focusing on clinical semiology, risk factors, imaging and video EEG findings. This is a prospective observational study done in adult neurology department of tertiary care hospital, from 2013 to 2016. The primary inclusion criteria were patients with drug refractory focal seizure (as per ILAE definition 2010), with age more than 12 years. Detailed clinical data, long term EEG monitoring, MRI and minimum follow up of 6 months were collected. Of 120 patients of DRE, 72% were in the age group of 12-30 yrs. Febrile seizure (26%) and head injury (17%) were the most significant antecedent history. Focal seizures with dyscognitive features were present in 87%. 16 patients had abnormal neurological examination. The most common radiological finding was mesial temporal sclerosis and gliosis. After complete evaluations, 30% of the patients were found to have pseudo-resistance. The evaluation led to modification of treatment in more than three-fourth of the patients. Early age of onset, history of febrile seizures, past history of head injury, focal dyscognitive type of seizures and structural lesion on imaging are common factors in patients with DRE. Pseudo- resistance due to wrong diagnosis and inadequate AEDs were responsible for one third of cases.

Risk of seizure clusters and status epilepticus following rapid and ultra-rapid medication discontinuation during intracranial EEG monitoring

ObjectiveAnti-seizure medications (ASMs) are discontinued in the course of intracranial EEG (iEEG) monitoring for presurgical evaluation. The ASM withdrawal facilitates an emergence of seizures but may also precipitate seizure clusters (SC) and status epilepticus (SE). The aim of this study was to compare the rates of SC and SE during the ultra-rapid withdrawal (URW) and rapid withdrawal (RW) of ASMs during iEEG. MethodsWe performed a retrospective observational study of all consecutive patients with drug resistant epilepsy who completed iEEG at our comprehensive epilepsy center from 2012-2018. SC was defined as three or more seizures in 24 h with a return to baseline between the events. SE was defined as ≥ 5 min of clinical seizure or ≥ 10 min of ictal electrographic activity or series of seizures with no return to the neurological baseline between the events. ResultsOf 107 patients who completed iEEG with intracranial grid or strip electrodes, 46 (43%) were male. Median age at the time of iEEG was 35.4 years (interquartile range [IQR], 26.4 - 44.9). Ninety patients (84.1%) had all AEDs held on admission, while 16 patients (15%) underwent a rapid taper. The median time to first seizure was 15.1 (8.2 - 22.6) h. Sixty-two patients (57.9%) developed SC, while 10 (9.4%) developed SE. Twenty-six patients (36.1%) with these complications required intravenous lorazepam or other rescue ASMs, while the remaining patients had spontaneous resolution of seizures; intubations were not required. While there were differences in the proportions in patients who experienced SC, SE, or neither in the URW and RW groups, these differences were not significant at the 0.05 alpha level. SignificanceUltra-rapid and rapid ASM withdrawal are accompanied by SC and SE the majority of which terminate spontaneously. These data support the use of either approach of the medication taper for seizure provocation in iEEG.

Using Dictyostelium to Advance Our Understanding of the Role of Medium Chain Fatty Acids in Health and Disease.

Ketogenic diets have been utilized for many years to improve health, and as a dietary approach for the treatment of a range of diseases, where the mechanism of these low carbohydrate and high fat diets is widely considered to be through the production of metabolic products of fat breakdown, called ketones. One of these diets, the medium chain triglyceride ketogenic diet, involves high fat dietary intake in the form of medium chain fatty acids (MCFAs), decanoic and octanoic acid, and is commonly used in endurance and high intensity exercises but has also demonstrated beneficial effects in the treatment of numerous pathologies including drug resistant epilepsy, cancer, and diabetes. Recent advances, using Dictyostelium discoideum as a model, have controversially proposed several direct molecular mechanisms for decanoic acid in this diet, independent of ketone generation. Studies in this model have identified that decanoic acid reduces phosphoinositide turnover, diacylglycerol kinase (DGK) activity, and also inhibits the mechanistic target of rapamycin complex 1 (mTORC1). These discoveries could potentially impact the treatment of a range of disorders including epilepsy, cancer and bipolar disorder. In this review, we summarize the newly proposed mechanisms for decanoic acid, identified using D. discoideum, and highlight potential roles in health and disease treatment.

Psychiatric disorders, depression and quality of life in patients with psychogenic non-epileptic seizures and drug resistant epilepsy living in Argentina

ObjectivesPsychiatric disorders are frequently found in both patients with PNES and DRE, making the differential diagnosis even more complex. The aim of this study was to analyze and compare psychiatric aspects and the quality of life in patients with psychogenic non-epileptic seizures (PNES) and drug resistant epilepsy (DRE). MethodsPatients admitted to video-electroencephalograpy (VEEG) unit with confirmed PNES and DRE were included. Demographical characteristics, psychiatric diagnosis according to SCID I and II of DSM IV, pharmacological treatment, general functioning measured with GAF (Global assessment of functionality), quality of life (QoL) using QlesQSF (Quality of Life Enjoyment and Satisfaction Questionnaire Short Form) and depression severity using BDI II (Beck depression inventory), were compared between the groups. Non-parametric tests, chi square test, and logistic regression were used for statistical analysis. Results148 patients consecutively admitted to VEEG were included (DRE n = 97; PNES n = 51). Somatization disorder (RR: 13.02, 95% CI: 1.23–137.39, p = 0.03) and a history of trauma (RR: 8.66, 95% CI: 3.21–23.31, p = 0.001) were associated with PNES. The QlesQ score and the GAF score were lower with a higher prevalence of suicide attempts in the PNES group (p < 0.01). A negative correlation was observed between the severity of depression and the quality of life (DRE r = - 0.28, p = 0.013; PNES r = - 0.59, p = 0.001). ConclusionsHigher psychiatric comorbidity with poorer QoL were found in PNES patients compared to DRE. However, depression comorbidity negatively affected the QoL in both groups. Future studies based on illness perception will be orientated to complete this analysis.

Early-onset eyelid stereotypies are a frequent and distinctive feature in Dravet syndrome

Dravet syndrome (DS) is a severe infantile-onset epilepsy syndrome featuring drug resistant epilepsy, global developmental delay and intellectual disability. In addition to ataxia and progressive crouch gait, Parkinsonism has recently been reported as characteristic in young adults with DS. We describe 5 patients out of a series of 23 patients with DS who present between 12 and 24 months of age with repetitive episodes of eyelid closure, sometimes as fast as eye blinking or flickering. Consistent lack of any EEG correlate in serial video-EEG ruled out an epileptic origin. We propose that this movement disorder, namely ‘eyelid stereotypies’, might be an early motor trait of SCN1A-associated DS.

Treatment outcomes in drug resistant juvenile myoclonic epilepsy: Valproate resistance may not be the end of the road

ObjectiveTo determine treatment responses to various antiseizure medicines (ASMs) in patients with drug resistant juvenile myoclonic epilepsy (DRJME) MethodsWe reviewed records of all JME patients attending epilepsy clinics at 5 centers during a 5-year period. We used International Consensus Criteria to diagnose JME and International League Against Epilepsy Criteria to define drug resistance and sustained seizure freedom. We only used broad spectrum medicines which included valproate, lamotrigine, topiramate, levetiracetam, clobazam, phenobarbitone, clonazepam, and zonisamide. We considered an ASM successful if patient achieved seizure freedom within 3 months of attaining maintenance dose. ResultsWe studied 116 patients (61 males) with DRJME. At terminal followup, 82 (70.7%) patients had achieved sustained seizure freedom with a mean followup of 3.2 ± 1.3 years after last dose change. In patients where valproate failed as first- or second-line ASM (n=70; 60.3%), 49(70%) became seizure-free. In this group, 33(67%) patients became seizure-free after addition of lamotrigine. Success rate of lamotrigine and valproate combination was 69% as compared to 9% with all other combinations (p = 0.001). In patients who were not exposed to valproate as initial therapy (n=46), 33 (71.7%) became seizure-free, 30 (91%) after adding valproate. At last follow-up, 75 (90%) seizure-free patients were receiving valproate including 45 (55%) patients with a combination of valproate and lamotrigine. Only one of 24 patients became seizure-free after failing valproate and lamotrigine combination. ConclusionSeizure freedom can be achieved in two-thirds of patients with DRJME. A combination of valproate and lamotrigine is the most effective duotherapy.

Unilateral Blinking: Insights from Stereo-EEG and Tractography

To study the neuroanatomical correlate of involuntary unilateral blinking in humans, using the example of patients with focal epilepsy. Patients with drug resistant focal epilepsy undergoing presurgical evaluation with stereotactically implanted EEG-electrodes (sEEG) were recruited from the local epilepsy monitoring unit. Only patients showing ictal unilateral blinking or unilateral blinking elicited by direct electrical stimulation were included (n = 16). MRI and CT data were used for visualization of the electrode positions. In two patients, probabilistic tractography with seeding from the respective electrodes was additionally performed. Three main findings were made: (1) involuntary unilateral blinking was associated with activation of the anterior temporal region, (2) tractography showed widespread projections to the ipsilateral frontal, pericentral, occipital, limbic and cerebellar regions and (3) blinking was observed predominantly in female patients with temporal lobe epilepsies. Unilateral blinking was found to be associated with an ipsilateral activation of the anterior temporal region. We suggest that the identified network is not part of the primary blinking control but might have modulating influence on ipsilateral blinking by integrating contextual information.

Advances in Brain Imaging Techniques for Patients With Intractable Epilepsy.

Intractable epilepsy, also known as drug resistance or refractory epilepsy, is a major problem affecting nearly one-third of epilepsy patients. Surgical intervention could be an option to treat these patients. Correct identification and localization of epileptogenic foci is a crucial preoperative step. Some of these patients, however, have no abnormality on routine magnetic resonance imaging (MRI) of the brain. Advanced imaging techniques, therefore, can be helpful to identify the area of concern. Moreover, a clear delineation of certain anatomical brain structures and their relation to the surgical lesion or the surgical approach is essential to avoid postoperative complications, and advanced imaging techniques can be very helpful. In this review, we discuss and highlight the use of advanced imaging techniques, particularly positron emission tomography (PET)–MRI, single-photon emission computed tomography, functional MRI, and diffusion tensor imaging–tractography for the preoperative assessment of epileptic patients.

Factors Affecting Vagus Nerve Stimulation Outcomes in Epilepsy.

Epilepsy as a common neurological disease is mostly managed effectively with antiepileptic medications. One-third of patients do not respond to medical treatments requiring alternative therapies. Vagus nerve stimulation (VNS) has been used in the last decades for the treatment of medically resistant epilepsy. Despite the extensive use of VNS in these patients, factors associated with clinical outcomes of VNS remain to be elucidated. In this study, we evaluated factors affecting VNS outcomes in epileptic patients to have a better understanding of patients who are better candidates for VNS therapy. Several databases including PubMed, Scopus, and Google Scholar were searched through June 2020 for relevant articles. The following factors were assessed in this review: previous surgical history, age at implantation and gender, types of epilepsy, duration of epilepsy, age at epilepsy onset, frequency of attacks, antiepileptic drugs, VNS parameters, EEG findings, MRI findings, and biomarkers. Literature data show that nonresponder rates range between 25% and 65%. Given the complexity and diversity of factors associated with response to VNS, more clinical studies are needed to establish better paradigm for selection of patients for VNS therapy.

Cognitive impairments in patients with treatment resistant epilepsy and complex rehabilitation

Background. The study of features of comorbid pathology in patients with epilepsy is of particular interest due to the high prevalence of this pathology and a significant impact on the quality of life of patients and their social adaptation. Aim. The aim of the research was to detect versatile cognitive impairments and affective disorders in epilepsy, and to study the results of cognitive training and psychoeducation. Materials and methods. The theoretical analysis of modern scientific researches in the field of cognitive and affective impairments during epilepsy was carried out. We studied the features of clinical and psychopathological manifestations in patients, suffering from epilepsy. The study covered 146patients (85 men and 61 women) who were in inpatient care. The following psychodiagnostic techniques were used: the MOCA test, the Toronto Cognitive Assessment (TorCA), the MiniMult test, the Münsterberg test, the quality of life scale, the Hamilton scale of depression and anxiety. Results. This publication offers the results of a study of cognitive and affective disorders the quality of life in patients who suffer from epilepsy and the results of online cognitive training and psychoeducation. We found cognitive decline in 88% of patients with epilepsy and improvement of cognitive functions by methods of non-pharmacological correction. Conclusions. Affective and cognitive disorders significantly affects the quality of life of patients, their ability to work and socialization. The conducted research showed that compared to the control group of healthy persons, patients with epilepsy showed improvement in their cognitive decline, anxiety and depressive disorders. Cognitive online training appeared to be effective for the patients with epilepsy.

Deep brain stimulation in patients with long history of drug resistant epilepsy and poor functional status: Outcomes based on the different targets

BackgroundDeep brain stimulation (DBS) is a widely used surgical procedure for the treatment of patients with drug resistant epilepsy (DRE) and several anatomical target have been described. Indications for DBS includes patients with focal, partial seizure and those for which resective or disconnective surgery are contraindicated, such as involvement of eloquent cortex or significant comorbidities. Despite the SANTE trial has clearly indicated the efficacy of DBS of anterior nucleus of the thalamus (ANT), specific indications regarding the best anatomical target and outcome in patients with severe disability are lacking. Here we described our case series of patients underwent DBS of three different target including ANT, centromedian thalamic nucleus (CMN) and subthalamic nucleus (STN). MethodSix patients with DRE have been treated with DBS of ANT (n = 3), STN (n = 2) and CMN (n = 1). Outcome has been expressed as seizures frequency reduction and patients functional status after surgery with a follow-up of 5–11 years. ResultsFour out of six patients show no reduction of seizures frequency after DBS implant with one case of increasing atypical absence. Two cases, one ANT and one CMN, show a significant reduction of seizures frequency of 50–60%. No patients improve relative to functional outcome and one showed psychiatric symptoms worsening. ConclusionsFor patients with DRE and severe functional disability, DBS may reduce seizure frequency in some cases, but it does not improve functional outcome.

MiR-485's anti-drug resistant epilepsy effects by regulating SV2A/PSD-95 and targeting ABCC1 and neuronal signaling-transduction proteins in hippocampus of rats.

AimDrug‐resistant epilepsy (DRE), most subsequently developing refractory epilepsy, causes a significant burden to the society. microRNAs have been demonstrated as key regulators and therapeutic targets in epilepsy. Accordingly, the aim of the present study was to test whether miR‐485 could be a potential target for DRE.Methods and resultsAn in vivo DRE model was developed in Sprague–Dawley rats by lithium chloride‐pilocarpine and screened by antiepileptic drugs. We found that miR‐485‐5p in hippocampus was significant downregulated at early stage and recovered to normal level at late stage of DRE. Overexpression of miR‐485‐5p in dentate gyrus (DG) of hippocampus in DRE rats could significantly decrease the frequency of seizures and the numbers of epileptiform spikes of hippocampal DG neuron, and could specifically decrease SV2A expression without affecting PSD‐95 expression in DG. Furthermore, miR‐485‐5p overexpression could significantly downregulate the expression of efflux transporter related to multidrug resistance (ABCC1) in hippocampus at late stage of DRE. Finally, a specific expression pattern of neuronal signaling‐transduction proteins (LRP4, MDM4, p53, and TMBIM1) for DRE was observed, and miR‐485‐5p overexpression could modulate these proteins’ expression levels toward normal in hippocampus both at early and late stage of DRE.ConclusionCollectively, these results suggest that miR‐485 was a potential target for anti‐DRE, and this effects might be partially via miR‐485‐5p/homeostatic‐synaptic plasticity‐molecule axis and/or targeting efflux transporter (ABCC1) and other neuronal signaling‐transduction proteins (LRP4, MDM4, p53, and TMBIM1).

Neuropathological spectrum of drug resistant epilepsy: 15-years-experience from a tertiary care centre

Neuropathology of drug resistant epilepsy (DRE) has direct bearing on the clinical outcome. Classification of the most common pathologies, hippocampal sclerosis (HS) and focal cortical dysplasia (FCD) have undergone several revisions and studies on the surgical pathology of DRE employing the updated ILAE classification are scarce. Here, we report the neuropathological spectrum of 482 surgically treated cases of DRE from a single institute using the latest ILAE classifications along with clinicoradiologic correlation. Majority of the cases (324, 67.2%) had temporal lobe epilepsy (TLE), with 158 (32.8%) having extratemporal seizure focus. Among TLE, HS was most common (n = 208, 64.2%), followed by neoplasms (42, 13%), FCD (26, 8%) and dual pathology (23, 7%). Less frequent were vascular malformations (cavernoma-3, arteriovenous malformation-1), mild malformation of cortical development (mMCD, 3), gliotic lesions (5), cysticercosis (2), double pathology (2) and polymicrogyria (1). Among extratemporal epilepsies, FCD was most common (46, 29.1%), followed by neoplasms (29, 18.3%), gliotic lesions (27, 17.1%), Rasmussen encephalitis (18, 11.4%), hypothalamic hamartoma (12, 7.6%), malformations of cortical development (10, 6.3%) and vascular malformations (6, 3.8%). Less frequent were double pathology (2, cysticercosis + FCD type IIb, DNET + FCD type IIb), mMCD (2), cysticercosis (1) and dual pathology (1). No underlying pathology was detected in 12 cases (2.5%). Radiopathological concordance was noted in 83%. In 36 cases (7.5%), histopathology detected an unsuspected second pathology that included FCD type III (n = 16) dual pathology (n = 18) and double pathology (n = 2). Further, in four MRI negative cases, histopathology was required for a conclusive diagnosis.

Self-esteem mediates mental health outcomes in young people with epilepsy.

To evaluate the extent to which self-esteem mediates the impacts of epilepsy-specific and environmental factors on mental health outcomes in young people with epilepsy. A prospective cohort of 480 young people with epilepsy and their families participated in five visits over 28months. We collected data on clinical seizure burden, cognitive comorbidity, peer and parental support, self-esteem, and self-reported mental health symptoms. We used structural equation modeling to specify and test relationships among these constructs simultaneously. Direct, indirect, and total effects were estimated with confidence intervals constructed through bias-corrected bootstrapping. Self-esteem mediated the effects of clinical seizure burden ( =0.23, 95% confidence interval [0.05, 0.42]) and peer support ( =-0.15, 95% CI [-0.28, -0.03]) on mental health. There were no mediating effects of parental support ( =-0.07, 95% CI [-0.14, 0.00]) or cognitive comorbidity ( =-0.01, 95% CI [-0.02, 0.01]) on mental health. We found evidence that self-esteem mediates the impact that both clinical seizure burden and peer support have on mental health outcomes, indicating that assessment of and interventions targeting self-esteem may be appropriate for young people with epilepsy. Supporting self-esteem could mitigate negative influences on mental health, whether from resistant epilepsy or low peer support.

P 20. Stimulus-dependent behavioural disorder in patients with ANT-DBS for Epilepsy

Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) is as an effective and safe treatment option for patients with resistant epilepsy. A SANTE Study reported that there was a gradual improvement in selected neuropsychological test results in patient with DBS in ANT. Among those improvements there were reported a number of psychiatric adverse affects. However little is studied about immediate neuropsychological effects of DBS in ANT. Recently demonstrated Voges B. et. al (2015) a stimulus- and voltage-dependent effect interrupting sleep and leading to the occurrence of neuropsychiatric symptoms (npS) (e.g. depression, mood instability, disturbed sleep) during ATN-DBS. We here present one patient with a voltage-independent developing of npS during ANT-DBS. The 45-year-old right-handed female patient with mental retardation with autistic spectrum disorder presented with focal not lesional refractory epilepsy. The average seizure frequency was 6.1 per day with a range of 1 to 16 seizures daily. After failure of 13 AED“s, a DBS-ANT was initiated at the age of 44. Follow up simultaneous EEG- video recording from 26 surface electrode contacts after beginning to stimulate with standard parameters (unipolar cyclic (1min ON/5min OFF) stimulation with 5 V stimulation amplitude, 120 Hz stimulation frequency and a pulse width of 90 μs) there were seen a directly dependence of neuropsychiatric symptoms (stereotypical movements with sitting down, torso wiggling (Body rocking) with or without singing) and impulse onset. In video-EEG monitoring we determined, that the duration of npS was also the same as impulse lasts. A clinical response to stimulation was 84 %. We improve adverse effects changing the programming settings: the amplitude was gradually reduced to two volts, the stimulation frequency 120 Hz and a pulse width of 90 μs where the same. Actual case report devoted to immediate complex behavioural disorder, which does not fulfil criteria for a complex focal seizure, and is strongly associated with unipolar bilateral stimulation of ANT. The actual clinical presentation of the DBS induced behavioural disorder semiologically coincide with the term “stereotypic movement disorder”. We hypothesize that impaired function of ARAS lead to reduced behavioural suppression of impulse mediated behaviour in the patient with mental retardation. We analysed her video-EEG before she was being stimulated and noticed, that she already had a typical body movement (body rocking) but much less frequently. Obviously a DBS of ANT had had a strong influence on behavioural disorder of our patient and was reversible after adjusting the stimulation parameters.

Diagnosis, treatment and postsurgical complications in a dog with epileptic seizures and a naso-ethmoidal meningoencephalocele

BackgroundNaso-ethmoidal meningoencephalocele is usually a congenital anomaly consisting of a protrusion of cerebral tissue and meninges into the ethmoidal labyrinth. The condition is a rare cause of structural epilepsy in dogs. We report the clinical presentation, surgical intervention, postoperative complications and outcome in a dog with drug resistant epilepsy secondary to a meningoencephalocele.Case presentationA 3.3-year-old male neutered Tamaskan Dog was referred for assessment of epileptic seizures secondary to a previously diagnosed left-sided naso-ethmoidal meningoencephalocele. The dog was drug resistant to medical management with phenobarbital, potassium bromide and levetiracetam. Surgical intervention was performed by a transfrontal craniotomy with resection of the meningoencephalocele and closure of the dural defect. Twenty-four hours after surgery the dog demonstrated progressive cervical hyperaesthesia caused by tension pneumocephalus and pneumorrhachis. Replacement of the fascial graft resulted in immediate resolution of the dog’s neurological signs. Within 5 months after surgery the dog progressively developed sneezing and haemorrhagic nasal discharge, caused by sinonasal aspergillosis. Systemic medical management with oral itraconazole (7 mg/kg orally q12h) was well-tolerated and resulted in resolution of the clinical signs. The itraconazole was tapered with no relapsing upper airway signs. The dog’s frequency of epileptic seizures was not affected by surgical resection of the meningoencephalocele. No treatment adjustments of the anti-epileptic medication have been necessary during the follow-up period of 15 months.ConclusionsSurgical resection of the meningoencephalocele did not affect the seizure frequency of the dog. Further research on prognostic factors associated with surgical treatment of meningoencephaloceles in dogs is necessary. Careful monitoring for postsurgical complications allows prompt initiation of appropriate treatment.