Cognitive Neurorehabilitation in Epilepsy Patients via Virtual Reality Environments: Systematic Review.

OBJECTIVE: Epilepsy patients could possibly benefit from the remuneration observed in the use of virtual reality (VR) and virtual environments (VEs), especially in cognitive difficulties associated with visuospatial navigation (memory, attention, and processing speed). AIM: Research questions under consideration in the present systematic review are associated to VEs' efficiency as a cognitive rehabilitation practice in epilepsy and the particular VR methods indicated for epilepsy patients. To meet criteria, studies included participants suffering from any form of epilepsy and a methodological design with a structured rehabilitation program/model. Data were collected online, using academic databases. RESULTS: Fourteen studies were included in the literature review and 6 in the statistical analysis. ROBINS-I protocol was implemented to assess the risk of bias. An inverse variance analysis (random effects) of pooled estimates of differences was implemented, in the form of continuous data. Despite the heterogeneity of the studies, all of them agree on the beneficial aspects of VR and VEs in cognitive rehabilitation in relation to visuospatial memory, attention, and information processing speed. CONCLUSION: We suggest that patients suffering from epilepsy may benefit from the use of VR cognitive rehabilitation interventions, concerning visuospatial memory, attention, and information processing speed. However, further investigation is needed in order to gain a better understanding of the mechanisms involved in cognitive rehabilitation via VEs and establish efficient and dynamic rehabilitation protocols.

Chronic hematoma superimposed to a large frontotemporal arachnoid cyst: evidence against crowding of audioverbal memory.

We report a patient with a chronic subdural/epidural hematoma superimposed to a large arachnoid cyst occupying the left frontotemporal region. Both were discovered accidentally because of a trigeminal neuralgia and concomitant subjective memory complaints. Patient's sudden selective audioverbal memory impairment probably links to a primary cortical tone deregulation and expressed through deficits of arousal-mediating structures subtly impacted by the hematoma's progression. This case illustrates that in early-onset asymmetrical brain damage (usually left), language, audioverbal memory in particular, should not always come to dominate intact hemisphere function. A severity-threshold may exist below which inter-hemispheric reorganization of audioverbal memory is unlikely.

Understanding frontal lobe function in epilepsy: Juvenile myoclonic epilepsy vs. frontal lobe epilepsy.

AIM: To compare neuropsychological function in juvenile myoclonic epilepsy (JME) and frontal lobe epilepsy (FLE) since frontal circuitry is involved in both conditions. By drawing on previously theory-guided hypotheses and findings, a particular emphasis is placed on the way different cognitive-pathophysiological mechanisms act upon to produce frontal dysfunction in JME (frontal-executive and attention-related problems: vigilance, reaction times, processing speed, and response inhibition) and in FLE (reflecting the coproduct of the functional deficit zone), respectively. METHODS: A total of 16 patients with JME, 34 patients with FLE, and 48 normal controls, all matched for age and education, were administered a comprehensive battery of tests to assess frontal-executive functions, as well as attention, memory, and learning domains. Participants did not take medications other than antiepileptics or have a psychiatric history. RESULTS: Patients with FLE overall showed worse neuropsychological performance compared to both JME and HCs. With respect to JME, patients with FLE did significantly worse in measures of verbal and nonverbal executive function, short-term-, and long-term- auditory-verbal memory and learning, immediate and delayed episodic recall, visual attention and motor function, visuo-motor coordination and psychomotor speed, speed of visual information processing, and vocabulary. Patients with JME performed significantly worse compared to FLE only in associative semantic processing, while the former outperformed all groups in vocabulary, visuomotor coordination, and psychomotor speed. CONCLUSION: We suggest that selective impairments of visual- and mostly auditory-speed of information processing, vigilance, and response inhibition may represent a salient neuropsychological feature in JME. These findings suggest the existence of an aberrantly working executive-attention system, secondary to pathological reticulo-thalamo-cortical dynamics. Contrariwise, cortically (frontal and extra-frontal) and subcortically induced malfunction in FLE is determined by the functional deficit zone i.e., the ensemble of cortical and subcortical areas that are functionally abnormal between seizures.

Telemetric intracranial pressure monitoring: our experience with 22 patients investigated for intracranial hypertension.

INTRODUCTION: We present the application of the Raumedic® P-tel telemetric device that monitors Intracranial Pressure (ICP) over long periods, in 22 patients, with suspected intracranial hypertension. METHODS: A telemetric device (Raumedic®, Neurovent® P-tel) was surgically implanted in 22 patients aged between 21 and 65 years. Among the patients, the inconclusive diagnosis of benign intracranial hypertension was set in 10, the possible diagnosis of postoperative hydrocephalus in 3, and the possible diagnosis of aqueduct stenosis in 2. Additionally, shunt malfunction and Normal Pressure Hydrocephalus (NPH) were investigated in 1 and 3 patients, respectively. Finally, 3 patients presented ventricular dilatation of unknown origin. All the individuals underwent a 3-day ICP recording within the nursing unit. Three more recordings were obtained over a period of 2-6 months at the outpatient base. RESULTS: Analysis of the data excluded the diagnosis of intracranial hypertension in 12 patients. Elevated ICP values were confirmed in 10 patients. Subsequently, 7 of them underwent shunts' implantation, while 2 refused further neurosurgical treatment and 1 was treated with acetazolamide. Additionally, 1 patient who demonstrated normal ICP values, thus confirmed with NPH, underwent VP shunt implantation, while another 2 with similar characteristics refused further surgery. In our series the overall clinical complication rate after P-tel implantation was insignificant. CONCLUSIONS: The telemetric device is safely implanted via a rather simple procedure. In selected patients, it could provide long-term ICP recordings, which are necessary to confirm diagnosis and guide to the appropriate treatment.

Circulating miR-146a and miR-134 in predicting drug-resistant epilepsy in patients with focal impaired awareness seizures.

OBJECTIVE: Epilepsy is one of the most prevalent neurologic disorders, causing serious psychological problems and reducing quality of life. Although 20 different antiepileptic drugs (AEDs) have been approved by the US Food and Drug Administration (FDA), 30% of patients have drug-resistant epilepsy (DRE). Considering the role of miR-146a and miR-134 in neuroinflammation and dendritic functionality, respectively, the aim of this study was the clinical evaluation of circulating miR-146a and miR-134 as novel noninvasive molecular markers for the prognosis of refractory epilepsy. METHODS: The study included 162 patients with focal impaired awareness seizures. Total RNA was extracted from serum samples spiked with synthetic cel-miR-39-3p for normalization purposes. First-strand complementary DNA (cDNA) synthesis was performed using microRNA-specific stem-loop primers, and hsa-miR-134/146a levels were quantified by quantitative polymerase chain reaction (qPCR). DRE was used as clinical end point event. Internal validation was performed by bootstrap analysis, and decision curve analysis was used to evaluate the clinical benefit on disease prognosis. RESULTS: The circulating levels of both miR-134 and miR-146a were elevated in patients with drug-resistant seizures. The receiver-operating characteristic (ROC) curve and logistic regression analysis demonstrated that patients with increased circulating miR-134/146a levels are at significantly higher risk for developing DRE, independently of temporal lobe sclerosis, epilepsy duration, familial history, age at first seizure, age, body mass index (BMI), smoking behavior, and gender. Finally, decision curve analysis highlighted that the evaluation of circulating miR-134/146a led to superior clinical benefit for DRE prognosis and patients' risk stratification. SIGNIFICANCE: Elevated serum miR-134/146a levels are associated with a higher risk for AED-resistant epilepsy and could constitute novel noninvasive molecular markers to improve disease early prognosis and support precision medicine.

Pharmacokinetic and pharmacodynamic modeling of levetiracetam: investigation of factors affecting the clinical outcome.

This study aimed to evaluate the pharmacokinetics and pharmacodynamics of oral levetiracetam therapy in drug refractory adult epileptic outpatients, as well as factors affecting them. Concentration-time data were collected at steady state, while seizure recurrence was monitored for 13 months. Non-linear mixed effects modeling was applied, and covariates assessed included weight, height, age, daily dose and creatinine clearance.Plasma concentrations of levetiracetam were best described by a one-compartment pharmacokinetic model (V/F = 34.7 L) with first-order absorption (ka = 0.616 h-1) and clearance (CL/F = 3.26 L/h). Patient's CrCL was found to significantly affect levetiracetam clearance (beta = 0.795). Time to seizure occurrence followed an exponential distribution and the mean time to seizure occurrence was estimated Te = 22.08 days. Seizure rate per month followed a Poisson distribution, while mean seizure rate per month was estimated λ = 1.33. Daily dose significantly affected the mean estimated time to seizure (beta = -2.2) and the mean monthly seizure rate (beta = 2.27) in a reverse way. Using discrete time Markov chains, it was shown that the transition probability from focal seizures to focal to bilateral tonic-clonic is significantly altered in relation to patient's CrCL.Simulations showed that dose should be adjusted in relation to CrCL, while low doses of levetiracetam are more effective for seizure control. Modeling and simulation in every-day clinical practice may provide significant information for the optimization of seizure control using well-known agents.

Emotional asymmetries in refractory medial temporal and frontal lobe epilepsy: Their impact on predicting lateralization and localization of seizures.

BACKGROUND: Emotional disturbances have been reported in patients with epilepsy. Although conflicting results emanate from relevant studies, depressive symptoms are seen more often in temporal lobe epilepsy (TLE) whereas, hypomanic/manic symptoms usually accompany frontal lobe epilepsy (FLE); the above psychiatric symptoms are especially seen in refractory epilepsy. However, neocortical TLE and medial TLE are considered as distinct epileptic syndromes, and there is limited literature on comparison of affective traits in medial TLE (MTLE) and FLE. AIM: In the present study, we sought to investigate affective traits among epilepsy surgery candidates suffering refractory left medial TLE (LMTLE), right medial TLE (RMTLE), left FLE (LFLE), and right FLE (RFLE). RESULTS: Our results revealed that patients with MTLE scored significantly higher than the ones with FLE in depression, anxiety, asthenia, and melancholia as measured by the Symptoms Rating Scale for Depression and Anxiety (SRSDA), while patients with FLE scored significantly higher in mania than those with MTLE. Moreover, patients with MTLE scored significantly higher than their FLE counterparts on the anxiety scale of the State Trait Personality Inventory (STPI)-trait version. When laterality of the seizure focus was taken into account, no differences were found among both patients with MTLE and patients with FLE, with exception for the Trail Making Test part B (TMT-B) in which patients with RMTLE performed significantly worse than patients with LMTLE. Seizure frequency was higher for FLE. CONCLUSIONS: We provide evidence for an anterior-frontal versus a posterior-medial temporal cerebral functional asymmetry with regard to the manifestation of manic and depressive emotional traits in FLE and MTLE, respectively. Our results are mainly discussed within the frame of their contribution in localizing and to a lesser extent in lateralizing seizures foci in epilepsy surgery candidates. We suggest that this is of great importance in the context of preoperative monitoring of epilepsy surgery, especially when neuropsychologists are called upon to provide anatomical information in defining the functional deficit zone.

Potential implications of Luria's work for the neuropsychology of epilepsy and epilepsy surgery: A perspective for re-examination.

The pioneeristic work of Alexander Romanovic Luria into the field of human neuropsychology offered eminent contributions to clinical praxis by providing theory guided methods and instruments for the study of higher cortical functions. However, lots of this knowledge corpus either remains untranslated and thus inaccessible, or in some cases selectively overlooked by academic authorities and consequently not passed to the future generations of experts. Although Luria was not exclusively devoted to the study of epilepsy, his theories and clinical approaches actually penetrate the whole neuropathology spectrum. His holistic and systemic approach to the brain sounds nowadays more than opportune and consistent with the network approach of the modern neuroimaging era. As to epilepsy, the logic underlying the Lurian approach (cognitive functions organized into complex functional systems with intra- and/or inter-hemispheric distribution, as opposed to the modularistic view of the brain) seems consistent with our current knowledge in epileptology with respect to epileptic networks, as well as the modern construct of the functional deficit zone. These contributions seem to be highly promising for the neuropsychology of epilepsy and epilepsy surgery, since they provide clinicians with valuable methods and theories to assist them in the localization -and lateralization- of cognitive deficits. Consequently they are of great applicability in the context of the preoperative neuropsychological monitoring of patients candidates for epilepsy surgery, where neuropsychologist are called upon to provide surgeons with anatomical data.

Combined GSTP1 and NQO1 germline polymorphisms in the susceptibility to Multiple Sclerosis.

Germline polymorphisms of detoxification genes could influence susceptibility to Multiple Sclerosis (MS). Glutathione-S-transferases (GSTs) and NAD(P)H: quinone oxidoreductase 1 (NQO1) are detoxifying enzymes involved in biotransformation of metabolites preventing cells from oxidative damage. In order to evaluate the possible contribution of the A313G GSTP1 inactivating polymorphism, alone and in combination with the C609T NQO1 genetic variant in MS susceptibility, we performed a case-control study consisting of 254 MS patients and 370 healthy donors. Genotypes were investigated using a new Real-Time PCR and PCR-RFLP assays. The GSTP1 polymorphism was evaluated in relation to patients' characteristics (clinical subtypes, age and gender) and the NQO1 gene status. GSTP1 genotype distribution was similar between cases and controls. Higher frequency of GSTP1 heterozygotes was observed in patients with relapsing remitting disease (RRMS) (p = 0.019), especially in those presenting a benign form (EDSS ≤ 2 after 10-15 years from the disease onset). Interestingly, genotype distribution analysis of combined GSTP1 and NQO1 polymorphisms revealed significantly higher frequency of GSTP1 heterozygous (A/G) and NQO1 variant genotypes (C/T and T/T) in patients as compared to the controls (p = 0.031). The increased incidence of combined GSTP1 and NQO1 variant genotypes in MS patients may suggest that defective function of detoxification enzymes might be an important determinant of susceptibility and clinical manifestation of the disease. Moreover, the results suggest a possible role for the GSTP1 heterozygous background in the development of RRMS.

Transcranial direct current stimulation efficacy in trigeminal neuralgia.

Trigeminal neuralgia is a severe, disabling pain and its deafferentation remains a challenge for health providers. Transcranial direct current stimulation is a non-invasive stimulation technique which finds new utility in managing pain. Therefore, the introduction of alternative, non-invasive, safe, and effective methods should be considered in treating patients with trigeminal neuralgia unresponsive to conventional treatment.

Paradigm shift in Parkinson's disease: using continuous telemonitoring to improve symptoms control. Results from a 2-years journey.

Introduction: Conventional care in Parkinson's disease (PD) faces limitations due to the significant time and location commitments needed for regular assessments, lacking quantitative measurements. Telemonitoring offers clinicians an opportunity to evaluate patient symptomatology throughout the day during activities of daily living. Methods: The progression of PD symptoms over a two-year period was investigated in patients undergoing traditional evaluation, supplemented by insights from ambulatory measurements. Physicians integrated a telemonitoring device, the PDMonitor®, into daily practice, using it for informed medication adjustments. Results: Statistical analyses examining intra-subject changes for 17 subjects revealed a significant relative decrease of -43.9% in the device-reported percentage of time spent in "OFF" state (from 36.2 to 20.3%). Following the 24-month period, the majority of the subjects improved or exhibited stable symptom manifestation. In addition to positively impacting motor symptom control, telemonitoring was found to enhance patient satisfaction about their condition, medication effectiveness, and communication with physicians. Discussion: Considering that motor function is significantly worsened over time in patients with PD, these findings suggest a positive impact of objective telemonitoring on symptoms control. Patient satisfaction regarding disease management through telemonitoring can potentially improve adherence to treatment plans. In conclusion, remote continuous monitoring paves the way for a paradigm shift in PD, focusing on actively managing and potentially improve symptoms control.

Implantable Subcutaneous Peripheral Nerve Stimulation Improves Degenerative Ataxia.

Degenerative cerebellar ataxias have no pharmacological or rehabilitation evidence-based treatment so far. Patients remain highly symptomatic and disabled despite receiving the best medical treatment available. This study investigates the clinical and neurophysiologic outcomes of the use of subcutaneous cortex stimulation (in keeping with the established protocol of peripheral nerve stimulation applied in chronic intractable pain) in degenerative ataxia. We report a case of a 37-year-old right-handed man who developed moderate degenerative cerebellar ataxia at the age of 18 years. His symptoms progressively worsened and impaired his daily activities. We observed clinical improvement for at least one month following an initial two-week trial of parietal transcranial direct current stimulation. Although preoperative non-invasive transcranial neuromodulation application does not predict invasive cortex stimulation outcome, we pursued a long-lasting effect by implanting parietal and occipital subcutaneous electrodes. At 12 months following permanent implantation, the patient exhibited amelioration of his symptoms and a change in neurophysiologic parameters. Central neuromodulation based on peripheral stimulation is considered part of neurosurgical clinical practice for the treatment of a variety of neurological disorders. The underpinning neurophysiological mechanism that explains the effectiveness of the method has not been fully elucidated. We believe that further studies are warranted to investigate these promising results in such devastating conditions.

Effectiveness of the Combination of Probiotic Supplementation on Motor Symptoms and Constipation in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) reflects the second most common neurodegenerative disorder and is associated with high morbidity and mortality. Besides the motor features, non-motor symptoms, such as constipation, are very common. There is accumulating evidence that neuroinflammation is associated with the PD pathological processes. Alterations of gut microbiota and microbial metabolites have been linked to the pathogenesis of PD. Previous research has shown that probiotic supplementation has beneficial effects on motor and non-motor symptoms and especially on constipation. AIM: In this study, we examine the effectiveness of a combination of probiotic supplementation (butyrate triglyceride 302.86 mg, Crocus sativus L. 30 mg, and vitamin D3 100 mcg), on constipation and motor symptoms in PD. METHODS: The present study is a retrospective study that examined the existing medical records of patients with diagnosed PD, having chronic constipation and used the probiotic supplementation for its management. A total of 41 existing medical records were screened. Medical records were excluded in the case of participation in another study for PD, suffering from irritable bowel syndrome, organic constipation, long-term laxative use changes in the standard dopaminergic treatment, Mini-Mental Status Examination (MMSE) score<24, hospitalization and antibiotic medication, and diarrheal syndrome. Nine medical records were excluded, and a final number of 32 medical records was finally examined. All 32 patients had evaluations carried out at baseline and three months after supplement administration. A stool diary questionnaire, the Unified Parkinson's Disease Rating Scale III (UPDRS III), and the Schwab and England and the Hoehn and Yahr scales were used for the evaluation. RESULTS: The median defecation frequency was significantly improved. The supplementation administration significantly improved UPDRS III by 7.7% (from 35.72±15.51 to 32.97±15.71, p = 0.005) at month three, as compared to baseline. A positive effect was also seen in the Schwab and England scale. There was no effect on the Hoehn and Yahr scale. CONCLUSION: The enteric microbiome composition is altered in PD, and there is accumulating evidence that probiotic supplementation could alleviate disease symptoms in neuroinflammatory disorders.

Epilepsy and the "dark" literature of the Greek novelist Demosthenes Voutyras: an outstanding epileptic personality.

BACKGROUND: The role of temporal lobe epilepsy (TLE) in determining personality traits and neurobehavioral symptoms, collectively known as the interictal behavioral syndrome (also known as Geschwind syndrome or "Gastaut-Geschwind syndrome"), as well as the syndrome's association with the particular artistic expression of many epileptic litterateurs are well known in neurology and psychiatry. A deepening of emotionality along with a serious, highly ethical, and spiritual behavior have been described as positive personality changes among patients with chronic mesial-TLE. OBJECTIVES: Our narrative-based clinical hypothesis aims at contributing to the ongoing debate on the association between TLE and artistic expression, as well as the latter's supposed implication for epileptology in general and the neuropsychology of epilepsy in particular. METHODS: Through an analysis of the biography, language, and literary work of Greek novelist Demosthenes Voutyras, we hypothesize that his mystical and dark writing style could be attributed to medial temporal interictal dynamics. CONCLUSIONS: We suggest that the psycholiterary profile of Voutyras is consistent with the idiosyncratic characteristics of the temporal lobe personality, while a non-dominant temporal lobe contribution has been proposed.

ANTECEDENTES: O papel da epilepsia do lobo temporal (ELT) na determinação de traços de personalidade e sintomas neurocomportamentais, coletivamente conhecidos como síndrome comportamental interictal (também conhecida como síndrome de Geschwind ou "síndrome de Gastaut-Geschwind"), bem como a associação da síndrome com o expressão de muitos literatos epilépticos são bem conhecidos em neurologia e psiquiatria. Um aprofundamento da emotividade juntamente com um comportamento sério, altamente ético e espiritual tem sido descrito como mudanças positivas de personalidade em pacientes com ELT mesial crônica. OBJETIVOS: A nossa hipótese clínica narrativa visa contribuir para o debate em curso sobre a associação entre ELT e a expressão artística, bem como a suposta implicação desta última para a epilepsia em geral e a neuropsicologia da epilepsia em particular. MéTODOS: Através de uma análise da biografia, linguagem e obra literária do romancista grego Demóstenes Voutyras, levantamos a hipótese de que seu estilo de escrita místico e sombrio poderia ser atribuído à dinâmica interictal temporal medial. CONCLUSõES: Sugerimos que o perfil psicoliterário de Voutyras é consistente com as características idiossincráticas da personalidade do lobo temporal, enquanto uma contribuição do lobo temporal não dominante foi proposta.

Combined Invasive Peripheral Nerve Stimulation in the Management of Chronic Post-Intracranial Disorder Headache: A Case Report.

The introduction of ventricular shunts dramatically changed the outcome and quality of life of hydrocephalic patients. However, shunt surgery continues to be associated with numerous adverse events. Headache is one of the most common complications after shunt operation. It is often of prolonged duration, the symptoms resemble those of migraine, and pain does not respond to medication. We propose invasive peripheral nerve stimulation as a potential solution in the treatment of patients suffering from chronic headache associated with shunted hydrocephalus. A young woman presented with daily holocephalic headache with diffuse pain exacerbated by lying down. Imaging revealed panventricular enlargement and possible aqueduct stenosis. When a ventriculoperitoneal shunt was placed, clinical symptoms resolved. Nevertheless, she gradually exacerbated after a second valve replacement due to wound infection. Imaging revealed decompressed ventricles and appropriate shunt placement. The diagnosis of chronic post-intracranial disorder headache was set. Therefore, occipital nerve stimulation was applied and, considering that the patient did not have a total response, bilateral parietal stimulation was added. Three months after the combined PNS, she experienced total remission of headache. Combined PNS eases refractory headaches much more than occipital nerve stimulation alone and could be considered as a solution for shunted hydrocephalus-associated headache.

Arousal deregulation in the co-shaping of neuropsychological dysfunction in frontal and mesial temporal lobe epilepsy.

OBJECTIVE: Our work aims to investigate the role of physiological arousal in the expression of neuropsychological deficits in frontal lobe epilepsy (FLE) and mesial temporal lobe epilepsy (mTLE), by drawing on the Lurian theory of brain function. METHODS: For this study a total of 43 patients with focal onset epilepsy has been taken; twenty-four patients with FLE, 19 patients with mTLE and 26 healthy controls, all matched for age and education. Participants underwent a comprehensive neuropsychological assessment including various cognitive domains, such as attention, episodic memory, speed of information processing, response inhibition and mental flexibility, working memory, verbal fluency (phonological & semantic). RESULTS: There were no significant differences between FLE and mTLE patients in terms of neuropsychological performance. However, both FLE and mTLE patients showed significantly worse performance in several cognitive domains than HCs. The results seem to support our hypothesis that aberrant physiological arousal, as reflected in patients' worse performance in vigilance and attention, response inhibition, and processing speed, along with other disease-specific variables, may co-determine neuropsychological dysfunction and/or impairment in both FLE and mTLE. CONCLUSION: Identifying a differential arousal-related neuropsychological affection in FLE and mTLE, among the known deleterious effects of the functional deficit zone and other disease-related variables, may further our understanding of the underlying cognitive-pathophysiological mechanisms in focal epilepsy syndromes.

Adaptive immersive Virtual Environments as a treatment for depersonalization disorder.

Depersonalization is a dissociative disorder associated to a profound disruption of self-awareness in the form of emotional numbing and feelings of disembodiment. The salient feature of depersonalization is a breakdown in the familiarity of one's psychological and somatic self (and surroundings when derealization is also present), in spite of being aware of the unreality of the change. At an early stage of research it was realized that people inclined to dissociation find it harder to tolerate discontinuity in perceptual environments, possibly due to a rigid perceptual attitude. Consequently, perceptual discontinuity experienced during momentary immersion into a VE would be expected to increase symptoms of dissociation among individuals prone to develop them. It has been put forward that a tendency toward immersion or absorption, linking to imaginative processes underlying the dissociative experience, significantly relates to the level of change in virtual reality-induced dissociative symptoms. Consequently, it has been implied that increased tolerability of perceptual discontinuities and a more flexible perceptual attitude in people suffering depersonalization/derealization disorder may be of help. We propose the use of adaptive immersive virtual environments to the treatment of depersonalization. In particular, we propose that implementation of biofeedback electrical stimulation to detect somato-sensory processing bias may contribute to selectively targeting deranged neurocognitive processing components, and as an indirect consequence promote, to some extent, the diagnostic process. Psychophysiological approaches may be of help in the treatment of depersonalization via additional series of afferent inputs - virtual reality (VR) stimuli - to alter the receptive fields of the affected proprioceptive systems and reorganize them. The aim of this paper is to stimulate future research towards the development of potential virtual rehabilitation programs based on biofeedback, electrical stimulation and concurrent measurement of galvanic skin response and EEG targeting selective somatosensory stimulation in patients with depersonalization. Our research hypotheses might constitute a starting point for the development of new treatment tools for depersonalization in particular and depersonalization/derealization disorder in general.

Long-Term Neuropsychological Outcomes Following Temporal Lobe Epilepsy Surgery: An Update of the Literature.

We present an update of the literature concerning long-term neuropsychological outcomes following surgery for refractory temporal lobe epilepsy (TLE). A thorough search was conducted through the PubMed and Medline electronic databases for studies investigating neuropsychological function in adult patients undergoing resective TLE surgery and followed for a mean/median > five years period. Two independent reviewers screened citations for eligibility and assessed relevant studies for the risk of bias. We found eleven studies fulfilling the above requirements. Cognitive function remained stable through long-term follow up despite immediate post-surgery decline; a negative relation between seizure control and memory impairment has emerged and a possible role of more selective surgery procedures is highlighted.

Α Multicenter Retrospective Study Evaluating Brivaracetam in the Treatment of Epilepsies in Clinical Practice.

Brivaracetam (BRV) is the latest approved antiepileptic drug. The aim of the study was to evaluate the efficacy and tolerability of BRV in everyday clinical practice. In this retrospective, observational, multicenter study, data from epilepsy patients receiving BRV from January 2018 to July 2019 were analyzed. Patients with age ≥16 suffering from any type of epilepsy and having at least one follow up encounter after dose titration were included. 156 consecutive patients were included in the study. The mean age was 40 (16-84 years) and the mean duration of epilepsy was 21 years. Of the 156 patients, 81% were diagnosed with focal-onset seizures, 16% with generalized seizures, while 3% suffered from unclassified seizures. Nine patients received BRV as monotherapy as a switching therapy. At the first follow up visit, seizure cessation was achieved in 56 (36%) patients and the rate of ≥50% responders was 36%. Twenty four patients (15%) remained unchanged; six patients (4%) were recorded with increased seizure frequency, while the remaining 9% had a response of less than 50%. Twenty-six patients (17%) showed clinically significant adverse events, but none were life threatening. Brivaracetam seems to be an effective, easy to use and safe antiepileptic drug in the clinical setting.