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Although a large array of biomarkers have been investigated in Friedreich's ataxia (FRDA) trials, the optimal biomarker for assessing disease progression or therapeutic benefit has yet to be identified. We searched PubMed, MEDLINE, and EMBASE databases up to June 2023 for any original study (with ≥ 5 participants and ≥ 2 months' follow-up) reporting the effect of therapeutic interventions on any clinical, cardiac, biochemical, patient-reported outcome measures, imaging, or neurophysiologic biomarker. We also explored the biomarkers' ability to detect subtle disease progression in untreated patients. The pooled standardized mean difference (SMD) was calculated using a random-effects model. The study's protocol was registered in PROSPERO (CRD42022319196). In total, 43 studies with 1409 FRDA patients were included in the qualitative synthesis. A statistically significant improvement was observed in Friedreich Ataxia Rating Scale scores [combining Friedreich Ataxia Rating Scale (FARS) and modified FARS (mFARS): SMD = - 0.32 (- 0.62 to - 0.02)] following drugs that augment mitochondrial function in a sensitivity analysis. Left ventricular mass index (LVMI) was improved significantly [SMD = - 0.34 (- 0.5 to - 0.18)] after 28.5 months of treatment with drugs that augment mitochondrial function. However, LVMI remained stable [SMD = 0.05 (- 0.3 to 0.41)] in untreated patients after 6-month follow-up. None of the remaining biomarkers changed significantly following any treatment intervention nor during the natural disease progression. Nevertheless, clinical implications of these results should be interpreted with caution because of low to very low quality of evidence. Further randomized controlled trials of at least 24 months' duration using a biomarker toolbox rather than a single biomarker are warranted.
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PURPOSE: Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial fibrillation (AF) and increase in stroke and death risk. We sought to perform a systematic review with a meta-analysis to evaluate the prevalence of AHREs detected by CIEDs, their association with stroke risk, development of clinical AF, and mortality among patients without a documented history of AF. METHODS: We searched several databases, ClinicalTrials.gov, references of reviews, and meeting abstract books without any language restrictions up to 9 September 2020. We studied patients with CIEDs in whom AHREs were detected. Exclusion criterion was AF history. Our primary outcome was the risk of ischemic stroke in patients with AHREs. RESULTS: We deemed eligible eight studies for the meta-analysis enrolling a total of 4322 patients with CIED and without a documented AF history. The overall AHRE incidence ratio was estimated to be 17.56 (95% CI, 8.61 to 35.79) cases per 100 person-years. Evidence of moderate certainty suggests that patients with documented AHREs were 4.45 times (95% CI 2.87-6.91) more likely to develop clinical AF. Evidence of low confidence suggests that AHREs were associated with a 1.90-fold increased stroke risk (95% CI 1.19-3.05). AHREs were not associated with a statistically significant increased mortality risk. CONCLUSION: The present systematic review and meta-analysis demonstrated that among patients without a documented history of AF, the detection of AHREs by CIEDs was associated with significant increased risk of clinical AF and stroke. REGISTRATION NUMBER (DOI): Available in https://doi.org/10.17605/OSF.IO/ZRF6M .
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Fibrilação Atrial , Desfibriladores Implantáveis , Acidente Vascular Cerebral , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Desfibriladores Implantáveis/efeitos adversos , Átrios do Coração , Humanos , Incidência , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Apolipoprotein E (APOE) ε4 allele is a major genetic risk factor for Alzheimer disease and mild cognitive impairment (MCI). Computer-based training programs can improve cognitive performance in elderly populations. However, the effects of computer-based interventions on MCI APOE ε4 carriers have never been studied before. OBJECTIVE: The effects of different web-based interventions and the APOE isoform-specific differences in training outcomes are investigated. METHODS: Using a quasi-experimental study design, 202 participants with MCI aged 60 years and older took part in three different intervention programs (physical and cognitive [Long-Lasting Memories, or LLM], cognitive [Active Control, or AC], or physical intervention [Physical Training Control, or PTC]) via an innovative information and communication technologies exergaming platform. Participants in each interventional group were subdivided into APOE ε4 carriers and non-APOE ε4 carriers. All participants underwent an extensive neuropsychological evaluation before and after the training, blood tests, and brain imaging. RESULTS: All interventions resulted in multiple statistically significant cognitive benefits after the intervention. Verbal learning (California Verbal Learning Test: immediate recall test score-LLM: P=.04; AC: P<.001), working memory (digit span forward and backward test scores-AC: P=.03; PTC: P=.02 and P=.006, respectively), and long-term memory (California Verbal Learning Test: delayed recall test score-LLM: P=.02; AC: P=.002; and PTC: P=.02) were improved. There was no statistically significant difference among the intervention effects. APOE ε4 presence moderates intervention effects as the LLM intervention improved only their task-switching processing speed (Trail Making Test, Part B: P=.03) and the PTC intervention improved only the working memory (digit span backward: P=.03). No significant performance alteration was noted for the APOE ε4+ cognitive AC training group. CONCLUSIONS: None of the applied interventions could be identified as the optimal one; it is suggested, however, that combined cognitive and physical training and physical training via exergaming may be more effective for the high-risk MCI ΑPOE ε4+ subgroup.
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Apolipoproteínas E/genética , Disfunção Cognitiva/terapia , Intervenção Baseada em Internet/estatística & dados numéricos , Testes Neuropsicológicos/normas , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Fatores de RiscoRESUMO
OBJECTIVE: Electrical source imaging (ESI) is a well-established approach to localizing the epileptic focus in drug-resistant focal epilepsy. So far, ESI has been used primarily on interictal events. Emerging evidence suggests that ictal ESI is also feasible and potentially useful. We aimed to investigate the diagnostic accuracy of ESI on ictal events using high-density electroencephalography (EEG). METHODS: We performed ictal ESI on 14 patients (9 with temporal lobe epilepsy) admitted for presurgical evaluation who presented seizures during a long-term (≥18 h) high-density EEG recording (13 with 256 electrodes and one with 128 electrodes), and subsequently 8 of them underwent epilepsy surgery (postoperative follow-up >1 year). Artifact-free EEG epochs at ictal οnset were selected for further analysis. The predominant ictal rhythm was identified and filtered (±1 Hz around the main frequency). ESI was computed for each time point using an individual head model and a distributed linear inverse solution, and the average across source localizations was localized. For validation, results were compared with the resection area and postoperative outcome. RESULTS: Ictal ESI correctly localized the epileptic seizure-onset zone in the resection area in five of six postoperatively seizure-free patients. Interictal and ictal ESI were concordant in 9 of 14 patients and partially concordant in additional 4 of 14 patients (93%). Divergent solutions were found in only one of the 14 patients (7%). SIGNIFICANCE: Ictal ESI is a promising localization technique in focal epilepsy.
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Mapeamento Encefálico/métodos , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/métodos , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/fisiopatologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Processamento de Sinais Assistido por Computador , Adolescente , Adulto , Algoritmos , Criança , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons/métodos , Cuidados Pré-Operatórios , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Resultado do Tratamento , Adulto JovemRESUMO
We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.
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Transtornos Cognitivos , Epilepsia/cirurgia , Testes Neuropsicológicos/normas , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/etiologia , Epilepsia/complicações , Epilepsia/epidemiologia , Europa (Continente)/epidemiologia , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Humanos , Cooperação Internacional , NeuroimagemRESUMO
BACKGROUND: Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS. OBJECTIVE: The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP. METHODS: Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients. RESULTS: MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally. CONCLUSION: PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc.
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Córtex Cerebral/fisiologia , Estimulação Elétrica , Eletrocorticografia , Potencial Evocado Motor/fisiologia , Estimulação Magnética Transcraniana , Adulto , Córtex Cerebral/fisiopatologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsias Parciais/fisiopatologia , Humanos , Masculino , Músculo Esquelético/fisiologia , Adulto JovemRESUMO
BACKGROUND: Paclitaxel-based regimens are frequently associated with the development of peripheral neuropathy. The autonomous nervous system (ANS) effects, however, of this chemotherapeutic agent remain unexplored. METHODS: We investigated a group of 31 female patients with ovarian cancer receiving treatment with paclitaxel and carboplatin, as well as a group of 16 healthy age- and gender-matched healthy volunteers. All study participants completed a questionnaire and were assessed neurophysiologically at three time points (baseline, 3-4 months and 6-8 months following the onset of chemotherapy). The evaluation of the ANS included assessment of the adrenergic cardiovascular function (orthostatic hypotension-OH), parasympathetic heart innervation (30/15 ratio) and sympathetic skin response (SSR). RESULTS: At the 3-4 months ANS assessment, 19.2 % of the patients had systolic OH and the same percentage had diastolic OH, but at the 6-8 months evaluation no patient had systolic OH and only 13.8 % had diastolic OH. The values of the 30/15 ratio were significantly reduced at both time points, whereas the SSR was not affected. CONCLUSIONS: Combined paclitaxel and carboplatin chemotherapy is associated with significant effects on the parasympathetic heart innervation and occasionally with effects on the adrenergic cardiovascular reaction. The SSR remained unaffected. Physicians should be alert to the possibility of these treatment-emergent side effects, so as to monitor ANS parameters and introduce treatment modifications accordingly. Our findings however, should be validated in larger cohorts.
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Antineoplásicos/efeitos adversos , Doenças do Sistema Nervoso Autônomo/induzido quimicamente , Sistema Nervoso Autônomo/efeitos dos fármacos , Carboplatina/efeitos adversos , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
PURPOSE OF REVIEW: The aim is to critically review recent advances emerging from the application of transcranial magnetic stimulation (TMS) as a research and clinical tool in the field of epilepsy. RECENT FINDINGS: A number of TMS-electromyography (EMG) and TMS-electroencephalography (EEG) studies have identified distinct changes of cortical excitability associated with specific epilepsy syndromes and in asymptomatic siblings of patients with epilepsy. Pharmaco-TMS studies have shed additional light on the effects of traditional and recently introduced antiepileptic drugs on excitatory and inhibitory brain microcircuits as well as cortical plasticity mechanisms. In addition, stronger evidence has emerged that TMS may serve as a biomarker with prognostic (i.e. predicting response to pharmacologic or surgical interventions) and diagnostic potential (for instance aiding in the noninvasive localization of the epileptogenic zone). Finally, the role of repetitive TMS in the therapeutic management of drug-resistant epilepsies and refractory status epilepticus has been further defined and is expected to become more prominent by the optimization of the stimulation parameters. SUMMARY: TMS has provided important insight into the pathophysiological substrate of human epilepsies and emerges as a valuable tool with diagnostic, prognostic and therapeutic potential. The recent advent of TMS-EEG can be reasonably expected to contribute further significant advances to the field of epilepsy.
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Córtex Cerebral/fisiologia , Epilepsia/diagnóstico , Epilepsia/terapia , Estimulação Magnética Transcraniana , Animais , Anticonvulsivantes/uso terapêutico , Córtex Cerebral/patologia , HumanosRESUMO
The occurrence of epileptiform discharges (ED) in electroencephalographic (EEG) recordings of patients with epilepsy signifies a change in brain dynamics and particularly brain connectivity. Transcranial magnetic stimulation (TMS) has been recently acknowledged as a non-invasive brain stimulation technique that can be used in focal epilepsy for therapeutic purposes. In this case study, it is investigated whether simple time-domain connectivity measures, namely cross-correlation and partial cross-correlation, can detect alterations in the connectivity structure estimated from selected EEG channels before and during ED, as well as how this changes with the application of TMS. The correlation for each channel pair is computed on non-overlapping windows of 1 s duration forming weighted networks. Further, binary networks are derived by thresholding or statistical significance tests (parametric and randomization tests). The information for the binary networks is summarized by statistical network measures, such as the average degree and the average path length. Alterations of brain connectivity before, during and after ED with or without TMS are identified by statistical analysis of the network measures at each state.
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Encéfalo/fisiopatologia , Conectoma/métodos , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Potenciais Evocados , Rede Nervosa/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Adulto , Interpretação Estatística de Dados , Feminino , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
We describe the case of a patient with bilateral thalamic lesions due to brain infarcts in the paramedian thalamic artery territories. The patient demonstrated symptoms of apathy (e.g., loss of initiative and interest in others, poor motivation, flattened affect). Neuropsychological assessment 3 and 5 years post-infarct revealed severe deficits in verbal and non-verbal immediate and delayed memory, attention, and executive functioning, with minimal improvement over time. Also, he demonstrated difficulties in social cognition (i.e., perception of facial expressions of others and of sarcasm). These findings are discussed and interpreted in light of current theories regarding the neurobiological substrate of apathy.
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Apatia/fisiologia , Infarto Cerebral/complicações , Transtornos Cognitivos/etiologia , Percepção Social , Tálamo/irrigação sanguínea , Tálamo/patologia , Adulto , Humanos , Masculino , Testes NeuropsicológicosRESUMO
BACKGROUND: The therapeutic landscape of spinal muscular atrophy (SMA) was dramatically transformed with the introduction of three disease-modifying therapies (DMTs). A systematic review was performed to assess available evidence regarding quantitative therapeutic biomarkers used in SMA patients older than 11 years under treatment with DMTs. METHODS: Latest literature search in MEDLINE, EMBASE, Cochrane databases and gray literature resources was performed in June 2021. Studies reporting only motor function or muscle strength scales or pulmonary function tests were excluded. Primary outcome was the change from baseline score of any serum, cerebrospinal fluid (CSF) or neurophysiologic biomarker examined. RESULTS: Database and gray literature search yielded a total of 8050 records. We identified 14 records published from 2019 until 2021 examining 18 putative serum, CSF or neurophysiologic biomarkers along with routine CSF parameters in 295 SMA nusinersen-treated type 2-4 patients older than 11 years of age. There is evidence based on real-world observational studies suggesting that serum creatinine, creatine kinase activity levels along with CSF Αß42, glial fibrillary acidic protein concentration as well as ulnar compound motor action potential amplitude and single motor unit potential amplitude changes may depict therapeutic response in this population. CONCLUSION: This systematic review explored for the first-time biomarkers used to monitor therapeutic efficacy in SMA adolescents and adults treated with DMTs. Research in this area is in its early stages, and our systematic review can facilitate selection of quantitative therapeutic biomarkers that may be used as surrogate measures of treatment efficacy in future trials. PROTOCOL REGISTRATION: PROSPERO CRD42021245516.
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Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Humanos , Adulto , Adolescente , Atrofia Muscular Espinal/tratamento farmacológico , Biomarcadores , Resultado do TratamentoRESUMO
Technological advancements have facilitated the availability of reliable and thorough genetic analysis in many medical fields, including neurology. In this review, we focus on the importance of selecting the appropriate genetic test to aid in the accurate identification of disease utilizing currently employed technologies for analyzing monogenic neurological disorders. Moreover, the applicability of comprehensive analysis via NGS for various genetically heterogeneous neurological disorders is reviewed, revealing its efficiency in clarifying a frequently cloudy diagnostic picture and delivering a conclusive and solid diagnosis that is essential for the proper management of the patient. The feasibility and effectiveness of medical genetics in neurology require interdisciplinary cooperation among several medical specialties and geneticists, to select and perform the most relevant test according to each patient's medical history, using the most appropriate technological tools. The prerequisites for a comprehensive genetic analysis are discussed, highlighting the utility of appropriate gene selection, variant annotation, and classification. Moreover, genetic counseling and interdisciplinary collaboration could improve diagnostic yield further. Additionally, a sub-analysis is conducted on the 1,502,769 variation records with submitted interpretations in the Clinical Variation (ClinVar) database, with a focus on neurology-related genes, to clarify the value of suitable variant categorization. Finally, we review the current applications of genetic analysis in the diagnosis and personalized management of neurological patients and the advances in the research and scientific knowledge of hereditary neurological disorders that are evolving the utility of genetic analysis towards the individualization of the treatment strategy.
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Doenças do Sistema Nervoso , Neurologia , Humanos , Medicina de Precisão , Testes Genéticos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/terapia , Bases de Dados Factuais , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: The use of patient-reported outcomes (PRO) in clinical practice is gaining increasing attention. This study aimed to provide a critical assessment of the current state-of-the-art and beliefs about the use of PRO in the management of people with epilepsy across some European countries. METHODS: Structured interviews were conducted with European experts to collect insights about (I) the personal experience with PRO; (II) the value and impact of PRO in the decision-making process at the national level; and (III) the interest for and use of PRO by national health authorities. RESULTS: Nine neurologists (Austria, Belgium, Czechia, Denmark, France, Greece, Italy, Poland, and United Kingdom), three health economists (Portugal, Romania, and Sweden), and one epidemiologist (Slovakia) participated. They all stated that PRO are collected at their own countries in the context of clinical trials and/or specific projects. During everyday clinical practice, PRO are collected routinely/almost routinely in Austria and Sweden and only at the discretion of the treating physicians in Czechia, Denmark, France, Greece, and Portugal. There was complete consensus about the favorable impact that the PRO can have in terms of clinical outcomes, healthcare resources utilization, and general patient satisfaction. Only participants from Portugal and Sweden answered that the PRO are perceived as very important by the National Health Authorities of their respective countries. CONCLUSIONS: Differences exist in attitudes and perspectives about PRO in epilepsy across Europe. An active plan is warranted to harmonize the measurement of PRO and ensure they can be relevant to people with epilepsy and health services.
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Epilepsia , Medidas de Resultados Relatados pelo Paciente , Humanos , Europa (Continente) , Itália , Polônia , Epilepsia/terapiaRESUMO
Anxiety in epilepsy has recently become a focus of interest for a number of reasons. Epidemiological studies have established that anxiety disorders are twice as common in patients with epilepsy compared to the general population, while in referral centres their prevalence is even higher. In addition, it has been recently appreciated that anxiety exerts a significant negative impact on the quality of life of patients with epilepsy of any age. With regard to the pathogenesis of anxiety in epilepsy, a number of theories have been put forward including those based on psychodynamics, learning-cognition, and neurobiology. From a clinical point of view, anxiety may occur as a comorbid disorder with epilepsy or be directly linked with epilepsy as a preictal, ictal, postictal or interictal phenomenon. The treatment of anxiety in patients with epilepsy requires a comprehensive, multidisciplinary, clinical assessment. Regarding pharmacological therapies, it should be recognised that some drugs prescribed for anxiety disorders are associated with a high risk of seizures, whereas some antiepileptic drugs possess anxiolytic properties that could be of use in the management of epileptic patients with anxiety. The correct diagnosis and successful treatment of anxiety is expected to have significant benefits for the quality of life of epileptic patients.
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Epilepsia , Qualidade de Vida , Anticonvulsivantes/uso terapêutico , Ansiedade , Epilepsia/tratamento farmacológico , Humanos , Convulsões/diagnósticoRESUMO
The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has reached technological maturity and has been an object of significant scientific interest for over two decades. Ιn parallel, accumulating evidence highlights the potential of TMS-EEG as a useful tool in the field of clinical neurosciences. Nevertheless, its clinical utility has not yet been established, partly because technical and methodological limitations have created a gap between an evolving scientific tool and standard clinical practice. Here we review some of the identified gaps that still prevent TMS-EEG moving from science laboratories to clinical practice. The principal and partly overlapping gaps include: 1) complex and laborious application, 2) difficulty in obtaining high-quality signals, 3) suboptimal accuracy and reliability, and 4) insufficient understanding of the neurobiological substrate of the responses. All these four aspects need to be satisfactorily addressed for the method to become clinically applicable and enter the diagnostic and therapeutic arena. In the current review, we identify steps that might be taken to address these issues and discuss promising recent studies providing tools to aid bridging the gaps.
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Neurociências , Estimulação Magnética Transcraniana , Eletroencefalografia/métodos , Laboratórios , Reprodutibilidade dos Testes , Estimulação Magnética Transcraniana/métodosRESUMO
The aim of the present study was to evaluate the effect of information processing speed on the functioning of specific working memory components, i.e. phonological loop, visuospatial sketchpad, central executive and episodic buffer. Cognitive tasks that assess working memory ("word lists recall" for the phonological loop, "block recall" for the spatial component of visuospatial sketchpad, "listening recall" for the central executive and "immediate story recall" for the episodic buffer) and information processing speed (symbol digit modalities test- oral form) were administered to 38 patients with multiple sclerosis. Results showed that the central executive and episodic buffer components were significantly related to information processing speed. However, when age was included in the regression model, information processing speed significantly predicted only the episodic buffer scores. Further research on the relationship between the episodic buffer and information processing speed is recommended.
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Memória de Curto Prazo , Esclerose Múltipla , Cognição , Humanos , Rememoração Mental , Esclerose Múltipla/complicações , Testes NeuropsicológicosRESUMO
OBJECTIVE: In epilepsy patients, Transcranial Magnetic Stimulation (TMS) may result in the induction and modulation of epileptiform discharges (EDs). We hereby investigate the modulatory effects of TMS on brain connectivity in Genetic Generalized Epilepsy (GGE) and explore their potential as a diagnostic biomarker in GGE. METHODS: Patients with GGE (n=18) and healthy controls (n=11) were investigated with a paired-pulse TMS-EEG protocol. The brain network was studied at local and at global levels using Coherence as an EEG connectivity measure. Comparison of patients vs controls was performed in a time-resolved manner by analyzing comparatively pre- vs post-TMS brain networks. RESULTS: There was statistically significant TMS-induced modulation of connectivity at specific frequency bands within groups and difference in TMS-induced modulation between the two groups. The most significant difference between patients and controls related to connectivity modulation in the γ band at 1-3 sec post-TMS (p=0.004). CONCLUSIONS: TMS modulates the healthy and epileptic brain connectivity in different ways. Our results indicate that TMS-EEG connectivity analysis can be a basis for a diagnostic biomarker of GGE. SIGNIFICANCE: The analysis identifies specific time periods and frequency bands of interest of TMS-induced connectivity modulation and elucidates the effect of TMS on the healthy and epileptic brain connectivity.
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Encéfalo/fisiopatologia , Epilepsia Generalizada/diagnóstico , Rede Nervosa/fisiopatologia , Adolescente , Adulto , Eletroencefalografia , Epilepsia Generalizada/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
Transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) is a technique for studying cortical excitability and connectivity in health and disease, allowing basic research and potential clinical applications. A major methodological issue, severely limiting the applicability of TMS-EEG, relates to the contamination of EEG signals by artifacts of biologic or non-biologic origin. To solve this problem, several methods, based on independent component analysis (ICA), principal component analysis (PCA), signal space projection (SSP), and other approaches, have been developed over the last decade. This article is divided into two parts. In the first part, we review the theoretical background of the currently available TMS-EEG artifact removal methods. In the second part, we formally introduce the mathematics underpinnings of the cleaning methods. We classify them into spatial and temporal filters based on their properties. Since the most frequently used TMS-EEG cleaning approach are spatial filter methods, we focus on them and introduce beamforming as a unified framework of the most popular spatial filtering techniques. This unifying approach enables the comparative assessment of these methods by highlighting their differences in terms of assumptions, challenges, and applicability for different types of artifacts and data. The different properties and challenges of the methods discussed are illustrated with both simulated and recorded data. This article targets non-mathematical and mathematical audiences. Accordingly, those readers interested in essential background information on these methods can focus on Section 2. Whereas theory-oriented readers may find Section 3 helpful for making informed decisions between existing methods and developing the methodology further.
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Artefatos , Estimulação Magnética Transcraniana , Eletroencefalografia/métodos , Análise de Componente Principal , Estimulação Magnética Transcraniana/métodosRESUMO
The FDA cleared deep transcranial magnetic stimulation (Deep TMS) with the H7 coil for obsessive-compulsive disorder (OCD) treatment, following a double-blinded placebo-controlled multicenter trial. Two years later the FDA cleared TMS with the D-B80 coil on the basis of substantial equivalence. In order to investigate the induced electric field characteristics of the two coils, these were placed at the treatment position for OCD over the prefrontal cortex of a head phantom, and the field distribution was measured. Additionally, numerical simulations were performed in eight Population Head Model repository models with two sets of conductivity values and three Virtual Population anatomical head models and their homogeneous versions. The H7 was found to induce significantly higher maximal electric fields (p<0.0001, t = 11.08) and to stimulate two to five times larger volumes in the brain (p<0.0001, t = 6.71). The rate of decay of electric field with distance is significantly slower for the H7 coil (p < 0.0001, Wilcoxon matched-pairs test). The field at the scalp is 306% of the field at a 3 cm depth with the D-B80, and 155% with the H7 coil. The H7 induces significantly higher intensities in broader volumes within the brain and in specific brain regions known to be implicated in OCD (dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and pre-supplementary motor area (pre-SMA)) compared to the D-B80. Significant field ≥ 80 V/m is induced by the H7 (D-B80) in 15% (1%) of the dACC, 78% (29%) of the pre-SMA, 50% (20%) of the dlPFC, 30% (12%) of the OFC and 15% (1%) of the IFG. Considering the substantial differences between the two coils, the clinical efficacy in OCD should be tested and verified separately for each coil.
Assuntos
Córtex Motor , Transtorno Obsessivo-Compulsivo , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Cabeça , Humanos , Córtex Motor/fisiologia , Transtorno Obsessivo-Compulsivo/terapia , Estimulação Magnética TranscranianaRESUMO
BACKGROUND: Rapidly progressive dementias (RPDs) are dementias that progress subacutely over a time period of weeks to months. Primary Sjögren's syndrome (pSS) is an autoimmune disease that can affect any organ system and may present with a wide range of clinical features that may mimic a plethora of medical conditions and, in rare cases, may manifest as RPD. We describe a unique case of pSS, in which rapidly progressive dementia (RPD) was the first disease manifestation, and the patient's radiological and electroencephalogram findings were compatible with Creutzfeldt- Jakob disease (CJD). CASE PRESENTATION: Here, we report a 58-year-old woman who presented with cognitive impairment rapidly deteriorating over the last 6 months prior to admission. Brain MRI and EEG were indicative of CJD. However, CSF 14-3-3 and tau/phospho tau ratio were within normal limits and therefore alternative diagnoses were considered. Blood tests were significant for positive antinuclear antibodies, anti-ENA, and anti-SSA and a lip biopsy was consistent with pSS. The patient was started on intravenous steroids followed by oral prednisone taper, which prevented further deterioration. CONCLUSION: This rare case expands the spectrum of neurological manifestations in pSS and highlights the importance of considering pSS in the differential diagnosis of RPDs in order to avoid misdiagnosis and provide appropriate treatment in a timely fashion.