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.

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.

Neuropsychology of epilepsy surgery and theory-based practice: an opinion review.

The present review attempts to discuss how some of the central concepts from the Lurian corpus of theories are relevant to the modern neuropsychology of epilepsy and epilepsy surgery. Through the lenses of the main Lurian concepts (such as the qualitative syndrome analysis), we discuss the barriers to clinical reasoning imposed by quadrant-based views of the brain, or even atheoretical, statistically-based and data-driven approaches. We further advice towards a systemic view inspired by Luria's clinical work and theorizing, given their importance towards our clinical practice, by contrasting it to the modular views when appropriate. Luria provided theory-guided methods of assessment and rehabilitation of higher cortical functions. Although his work did not specifically address epilepsy, his theory and clinical approaches actually apply to the whole neuropathology spectrum and accounting for the whole panorama of neurocognition. This holistic and systemic approach to the brain is consistent with the network approach of the neuroimaging era. As to epilepsy, the logic of cognitive functions organized into complex functional systems, contrary to modular views of the brain, heralds current knowledge of epilepsy as a network disease, as well as the concept of the functional deficit zone.

A presente revisão tenta discutir como alguns dos conceitos centrais do corpus de teorias lurianas são relevantes para a moderna neuropsicologia da epilepsia e cirurgia da epilepsia. Através das lentes dos principais conceitos lurianos (como a análise qualitativa de síndromes), discutimos as barreiras ao raciocínio clínico impostas por visões do cérebro baseadas em quadrantes, ou mesmo abordagens ateóricas, baseadas em estatísticas e orientadas por dados. Aconselhamos ainda uma visão sistêmica inspirada na clínica e na teorização de Luria, dada sua importância para nossa prática clínica, contrastando-a com as visões modulares quando apropriado. Luria forneceu métodos teóricos de avaliação e reabilitação de funções corticais superiores. Embora seu trabalho não abordasse especificamente a epilepsia, sua teoria e abordagens clínicas na verdade se aplicam a todo o espectro da neuropatologia e respondem por todo o panorama da neurocognição. Essa abordagem holística e sistêmica do cérebro é consistente com a abordagem de rede da era da neuroimagem. Quanto à epilepsia, a lógica das funções cognitivas organizadas em sistemas funcionais complexos, ao contrário das visões modulares do cérebro, anuncia o conhecimento atual da epilepsia como uma doença em rede, bem como o conceito de zona de déficit funcional.

Neuropsychology of epilepsy surgery and theory-based practice: an opinion review / Neuropsicologia da cirurgia de epilepsia e prática teórica: uma revisão de opinião

Abstract The present review attempts to discuss how some of the central concepts from the Lurian corpus of theories are relevant to the modern neuropsychology of epilepsy and epilepsy surgery. Through the lenses of the main Lurian concepts (such as the qualitative syndrome analysis), we discuss the barriers to clinical reasoning imposed by quadrant-based views of the brain, or even atheoretical, statistically-based and data-driven approaches. We further advice towards a systemic view inspired by Luria's clinical work and theorizing, given their importance towards our clinical practice, by contrasting it to the modular views when appropriate. Luria provided theory-guided methods of assessment and rehabilitation of higher cortical functions. Although his work did not specifically address epilepsy, his theory and clinical approaches actually apply to the whole neuropathology spectrum and accounting for the whole panorama of neurocognition. This holistic and systemic approach to the brain is consistent with the network approach of the neuroimaging era. As to epilepsy, the logic of cognitive functions organized into complex functional systems, contrary to modular views of the brain, heralds current knowledge of epilepsy as a network disease, as well as the concept of the functional deficit zone.

Resumo A presente revisão tenta discutir como alguns dos conceitos centrais do corpus de teorias lurianas são relevantes para a moderna neuropsicologia da epilepsia e cirurgia da epilepsia. Através das lentes dos principais conceitos lurianos (como a análise qualitativa de síndromes), discutimos as barreiras ao raciocínio clínico impostas por visões do cérebro baseadas em quadrantes, ou mesmo abordagens ateóricas, baseadas em estatísticas e orientadas por dados. Aconselhamos ainda uma visão sistêmica inspirada na clínica e na teorização de Luria, dada sua importância para nossa prática clínica, contrastando-a com as visões modulares quando apropriado. Luria forneceu métodos teóricos de avaliação e reabilitação de funções corticais superiores. Embora seu trabalho não abordasse especificamente a epilepsia, sua teoria e abordagens clínicas na verdade se aplicam a todo o espectro da neuropatologia e respondem por todo o panorama da neurocognição. Essa abordagem holística e sistêmica do cérebro é consistente com a abordagem de rede da era da neuroimagem. Quanto à epilepsia, a lógica das funções cognitivas organizadas em sistemas funcionais complexos, ao contrário das visões modulares do cérebro, anuncia o conhecimento atual da epilepsia como uma doença em rede, bem como o conceito de zona de déficit funcional.

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.

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.

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.

Epilepsy and the "dark" literature of the Greek novelist Demosthenes Voutyras: an outstanding epileptic personality / Epilepsia e a literatura "sombria" do romancista grego Demosthenes Voutyras: uma personalidade epilética notável

Abstract 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.

Resumo 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.

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.

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.

The Greek Collaborative Long COVID Study: Non-Hospitalized and Hospitalized Patients Share Similar Symptom Patterns.

Long COVID-19 syndrome refers to persisting symptoms (>12 weeks) after the initial coronavirus infection and is estimated to affect 3% to 12% of people diagnosed with the disease globally. Aim: We conducted a collaborative study with the Long COVID patient organization in Greece, in order to estimate the characteristics, symptoms, and challenges these patients confront. Methods: Data were collected from 208 patients using unstructured qualitative free-text entries in an anonymized online questionnaire. Results: The majority of respondents (68.8%) were not hospitalized and reported lingering symptoms (66.8%) for more than six months. Eighteen different symptoms (fatigue, palpitations, shortness of breath, parosmia, etc.) were mentioned in both hospitalized and community patients. Awareness of Long COVID sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still not included inthe management plan of Long COVID patients. Conclusions: Patients infected with coronavirus with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Long COVID syndrome appears to be a multi-systemic entity and a multidisciplinary medical approach should be adopted in order to correctly diagnose and successfully manage these patients.

Selective impairment of auditory attention processing in idiopathic generalized epilepsies: Implications for their cognitive pathophysiology.

The neuropsychological characteristics of Idiopathic Generalized Epilepsies (IGEs) as a wide syndrome encompassing different clinical entities have been as yet not well understood. We have studied neuropsychological performance in patients suffering Juvenile Myoclonic Epilepsy (JME) and Generalized Tonic Clonic Seizures (IGE-GTCS-only) to provide indirect-cognitive evidence on the pathophysiology of IGE-related neuropsychological dysfunction. Greater arousal-related impairments were expected for the auditory modality, by drawing on previous anatomo-clinical and neuro-evolutionary accounts. We have studied neurocognitive functioning in 26 IGE patients, suffering either JME (n = 16) or IGE-GTCS-only (n = 10), and their healthy counterparts consisted of 26 (18 females) demographically matched participants. IGE patients (JME and IGE-GTCS-only) did worse with respect to HC (healthy controls) in visual- and auditory- speed of information processing (reaction time), auditory-vigilance and -response inhibition, visuo-motor coordination, visual working memory and motor speed, delayed visual recall, immediate- and delayed verbal episodic recall, lexical access and retrieval, semantic associative processing, auditory-verbal memory span and verbal learning. Although both IGE-GTCS-only and JME patients delayed episodic recall was defective, the former did significantly worse. We believe that IGE patients' neuropsychological derailments represent indirect-secondary manifestations of a primary cortical tone deregulation inherent to IGEs' pathophysiology. In particular, IGE patients' worse-dissociated performance in auditory TOVA-also seen previously in TBI and schizophrenia-may implicate a grater vulnerability of the auditory information processing system, as well as a possibly shared cognitive pathophysiological component between IGE and the above nosologies.

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.

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.

Spastic paraplegia preceding PSEN1-related familial Alzheimer's disease.

INTRODUCTION: We investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 (PSEN1) related familial Alzheimer's disease (AD). METHODS: We performed whole exome sequencing (WES) in 60 probands with hereditary spastic paraplegia (HSP) phenotype that was negative for variants in known HSP-related genes. Where PSEN1 mutation was identified, brain biopsy was performed. We investigated the link between HSP and AD with PSEN1 in silico pathway analysis and measured in vivo the stability of PSEN1 mutant γ-secretase. RESULTS: We identified a PSEN1 variant (p.Thr291Pro) in an individual presenting with pure SP at 30 years of age. Three years later, SP was associated with severe, fast cognitive decline and amyloid deposition with diffuse cortical plaques on brain biopsy. Biochemical analysis of p.Thr291Pro PSEN1 revealed that although the mutation does not alter active γ-secretase reconstitution, it destabilizes γ-secretase-amyloid precursor protein (APP)/amyloid beta (Aßn) interactions during proteolysis, enhancing the production of longer Aß peptides. We then extended our analysis to all 226 PSEN1 pathogenic variants reported and show that 7.5% were associated with pure SP onset followed by cognitive decline later in the disease. We found that PSEN1 cases manifesting initially as SP have a later age of onset, are associated with mutations located beyond codon 200, and showed larger diffuse, cored plaques, amyloid-ring arteries, and severe CAA. DISCUSSION: We show that pure SP can precede dementia onset in PSEN1-related familial AD. We recommend PSEN1 genetic testing in patients presenting with SP with no variants in known HSP-related genes, particularly when associated with a family history of cognitive decline.

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.

Fatigue and cognitive functions in epilepsy: A review of the literature.

Epilepsy is a common neurological disorder affecting people of all ages and inducing cognitive impairments. While research has advanced in terms of neuropsychological enquiries of the various epileptic syndromes, the understanding of more complex and ill-defined phenomena such as fatigue is still unclear for epilepsy. It is suggested that fatigue is not just physical, but there can also be a cognitive element to it. Although studies in other conditions have been able to identify a relationship between fatigue and particular cognitive components, similar evidence is sparse in patients with epilepsy. This review is an attempt to gather, analyze, integrate, and critically discuss available information on fatigue and its rapport with various aspects of epilepsy, particularly focusing on cognition. Future directions are discussed urging researchers to target cognitive components of fatigue.