Neurobiology of Tourette\u27s syndrome: the autoimmune post-streptococcal hypothesis

CONTEXTO: A síndrome de Tourette (ST) caracteriza-se pela presença de tiques motores e pelo menos um tique fônico. Algumas semelhanças clínicas com a coréia reumática ou de Sydenham (CS) incentivaram a formulação da hipótese da existência de um grupo de transtornos neuropsiquiátricos associados a processo auto-imune decorrente de infecção estreptocócica (PANDAS). OBJETIVO: Revisar a literatura quanto às evidências em relação à hipótese de que mecanismos auto-imunes pós-estreptocócicos estão envolvidos na etiopatogênese da ST. MÉTODOS: Revisão sistemática na base de dados MedLine com os termos "Tourette", "tic", "PANDAS", "antibodies", "streptococcal" e "rheumatic". RESULTADOS: Retornaram 238 artigos da busca. Selecionaram-se 53 trabalhos, os quais tiveram suas referências bibliográficas também revisadas. São apresentados os resultados de estudos que avaliaram aspectos imunes na ST, incluindo anticorpos antiestreptocócicos e antinúcleos da base, e sua terapêutica imunebaseada, discutindo a validade do conceito de PANDAS. CONCLUSÕES: As evidências ainda não são satisfatórias no que tange a uma base auto-imune pós-estreptocócica para a ST. Um aprimoramento dos métodos investigativos e na seleção das amostras pode trazer maiores contribuições à questão.BACKGROUND: Tourette\u27s syndrome (TS) is characterized by the presence of motor tics and at least one phonic tic. Some clinical similarities with Sydenham\u27s chorea (SC) lead to the hypothesis of a new group of disorders associated with an autoimmune process due to a streptococcal infection (PANDAS). Objective: To review the literature in search of evidence on the existence of post-streptococcal autoimmune mechanisms involved with the etiopathogenesis of TS. METHODS: A systematic review with the terms "Tourette", "tic", "PANDAS", "antibodies", "streptococcal" and "rheumatic" was carried on using the MedLine. RESULTS: The search found 238 articles. Fifty and three articles were selected which also had their references reviewed. The results of studies that investigated autoimmune aspects of TS, including anti-streptococcal and anti-basal ganglia anti-bodies, and immune-based therapy, were presented and discussed. DISCUSSION: The evidences to date are not satisfactory regarding a post-streptococcal auto-immune process in ST. The improvement on investigative methods and sample selection might contribute to this question

Neurological Disorders Depression Inventory for Epilepsy (NDDI-E): brazilian version of a screening instrument

INTRODUCTION: Depression is the most common psychiatric comorbidity in epilepsy, being its identification frequently neglected in most epilepsy centers. OBJECTIVE: To evaluate the performance of the Brazilian version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) in a group of patients from a specialized center. METHODS: The recently validated Brazilian version of the NDDI-E was applied to a group of 142 outpatients with epilepsy. We used the MINI-Plus as a gold standard to diagnosis major depressive episode. Results: Forty patients (28.2%) were depressed at the time of evaluation. The ROC curve analysis indicated that the cutoff at 15 (>15) represented the greatest dichotomy between depressed and nondepressed (sensitivity 70.0%, specificity of 87.3%, positive predictive value of 68.3% and negative predictive value of 88.1%). The use of lower cutoff points may eventually be adopted to provide greater sensitivity to the instrument. CONCLUSION: The Brazilian version of NDDI-E is a sensitive and practical tool that can help in tracking depression in epilepsy in order to reduce its underdiagnosis.INTRODUÇÃO: Depressão é a comorbidade psiquiátrica mais frequente na epilepsia, sendo sua identificação frequentemente negligenciada nos centros especializados. OBJETIVO: Avaliar o desempenho da versão brasileira do Inventário de Depressão em Transtornos Neurológicos para a Epilepsia (IDTN-E) em um grupo de pacientes atendidos em um serviço especializado. MÉTODOS: A versão brasileira do ITDN-E foi aplicada em um grupo de 142 pacientes com epilepsia. Foi utilizado o MINI-Plus como padrão ouro para o diagnóstico de episódio depressivo maior. Resultados: Quarenta pacientes (28,2%) apresentavam o diagnóstico de depressão no momento da avaliação. A análise da curva ROC indicou que o ponto de corte em 15 (>15) para o IDTN-E representa dicotomização ótima entre deprimidos e não deprimidos (sensibilidade de 70,0%, especificidade de 87,3%, valor preditivo positivo de 68,3% e valor preditivo negativo de 88,1%). A utilização de pontos de corte inferiores pode eventualmente ser adotada para proporcionar uma maior sensibilidade ao instrumento. CONCLUSÃO: A versão brasileira do IDTN-E é um instrumento sensível e prático que pode auxiliar o rastreamento da depressão na epilepsia, diminuindo o seu subdiagnóstico.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Hospital Felício Rocho Centro Universitário de Belo HorizonteUniversidade Federal de São Paulo (UNIFESP) Departamento de Neurologia e NeurocirurgiaUniversidade Federal de São Paulo (UNIFESP) Departamento de PsiquiatriaUniversidade Federal de Minas Gerais Faculdade de MedicinaUniversidade Federal de Minas Gerais Instituto de Ciências BiológicasUniversidade Federal de Minas Gerais Hospital das Clínicas Serviço de NeurologiaHospital Felício Rocho Núcleo Avançado de Tratamento das EpilepsiasUniversidade Federal de Minas Gerais Hospital das ClínicasUNIFESP, Depto. de Neurologia e NeurocirurgiaUNIFESP, Depto. de PsiquiatriaSciEL

Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAM-D) in patients with epilepsy

OBJECTIVE: To determine cutoff points of highest sensitivity and specificity on the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAM-D) for depression diagnosis in epilepsy. METHODS: Seventy-three patients from a referral center for the treatment of epilepsy underwent neuropsychiatric evaluation. We collected clinical and socio-demographic data, and applied the following instruments: Structured Clinical Interview (MINI-PLUS) for psychiatric diagnosis according to DSM-IV, HAM-D and BDI. RESULTS: At assessment, 27.4% of the patients were depressed and 37% met diagnostic criteria for lifetime major depression. The ROC curve analysis indicated that a score > 16 on the BDI (94.4% sensitivity, 90.6% specificity) and > 16 on the HAM-D (95% sensitivity, 75.5% specificity) revealed great dichotomy between depressed and nondepressed patients. Both instruments showed a negative predictive value exceeding 95%. CONCLUSION: The frequency of major depression is elevated in patients with epilepsy. BDI and HAM-D can help physicians in the identification of depression in epilepsy, reducing its underdiagnosis.OBJETIVO: Determinar os pontos de melhor sensibilidade e especificidade do Inventário de Depressão de Beck (BDI) e da Escala de Avaliação de Depressão de Hamilton (HAM-D) no diagnóstico de depressão associada à epilepsia. MÉTODOS: Setenta e três pacientes de um centro de referência no tratamento da epilepsia foram submetidos à avaliação neuropsiquiátrica. Foram colhidos dados clínicos e sociodemográficos, sendo utilizados os seguintes instrumentos: entrevista clínica estruturada (MINI-PLUS) para diagnóstico psiquiátrico conforme o DSM-IV, HAM-D e BDI. RESULTADOS: No momento da entrevista, 27,4% dos pacientes estavam deprimidos e 37% preenchiam critérios para diagnóstico de depressão maior ao longo da vida. A análise da curva ROC indicou que o ponto de corte em 16 (> 16) para o BDI (sensibilidade de 94,4%, especificidade de 90,6%) e em 16 (> 16) para a HAM-D (sensibilidade de 95%, especificidade de 75,5%) representou dicotomização ótima entre deprimidos e não deprimidos. Ambos os instrumentos apresentaram um valor preditivo negativo superior a 95%. CONCLUSÃO: A frequência de depressão maior é elevada em pacientes com epilepsia. BDI e a HAM-D podem auxiliar o clínico na identificação da depressão associada à epilepsia, diminuindo seu subdiagnóstico.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Universidade Federal de Minas Gerais Serviço de Neurologia Hospital das ClínicasHospital Felício Rocho Núcleo Avançado de Tratamento das EpilepsiasUniversidade Federal de São Paulo (UNIFESP) Departamento de Neurologia e NeurocirurgiaUniversidade Federal do Estado de São Paulo Laboratório Interdisciplinar de Neurociências ClínicasUniversidade Federal de Minas GeraisUNIFESP, Depto. de Neurologia e NeurocirurgiaSciEL

Translation and cross-cultural adaptation of the Interictal Dysphoric Disorder Inventory (IDDI)

INTRODUCTION: Interictal dysphoric disorder (IDD) is a behavioral syndrome described mainly in epileptic patients. The pleomorphic and unspecific nature of its symptoms makes difficult its recognition. The Interictal Dysphoric Disorder Inventory (IDDI) is an instrument specifically created to evaluate IDD symptoms and to facilitate its diagnosis. PURPOSE: Translation and cross-cultural adaptation of the Interictal Dysphoric Disorder Inventory (IDDI). METHODS: Twenty-one patients regularly accompanied in the outpatient epilepsy clinic of Universidade Federal de São Paulo (UNIFESP) - UNIFESP answered the questionnaire. The original version in English for translation was obtained with one of the authors (Marco Mula). Later, two independent native English-speaking teachers fluent in Portuguese translated this consensus version back into English. Comparison of the back-translation with the original English version showed only a few discrepancies and the English and Portuguese versions were considered conceptually equivalents. RESULTS: Seventeen female (81%) and four male (19%) answered the questionnaire. The mean age was of 32.3 years and seven had primary school, four had completed secondary and two, higher education. After patients had answered the 21 questionnaires, only three of them did not understand question D of the Appendix section, which had to be rewritten. CONCLUSION: Brazilian patients easily understood the questions of IDDI. We believe that after finishing validation of its psychometric properties this instrument will be very helpful to evaluate the IDD in Brazilian people with epilepsy.INTRODUÇÃO: O transtorno disfórico interictal (TDI) se constitui em uma síndrome comportamental descrita principalmente em pacientes com epilepsia. A apresentação pleomófica e inespecífica dos seus sintomas, no entanto, dificulta seu diagnóstico. O Interictal Dysphoric Disorder Inventory (IDDI) é um instrumento recentemente criado com a finalidade de facilitar o diagnóstico do TDI entre os pacientes com epilepsia. OBJETIVO: Tradução e adaptação cultural do Interictal Dysphoric Disorder Inventory (IDD) MÉTODOS: Vinte e um pacientes em acompanhamento regular no ambulatório de Epilepsia do Departamento de Neurologia e Neurocirurgia da Universidade Federal de São Paulo (UNIFESP) - UNIFESP responderam ao questionário. A versão original foi obtida com um dos autores da escala (Marco Mula) que concedeu a versão original em inglês para a tradução. Dois professores de inglês nativos fizeram a retrotradução. As versões em português e a retrotraduzida foram comparadas à original e após consenso foi obtida a versão final. RESULTADOS: Dos pacientes entrevistados, 17 (81%) eram do sexo feminino, com média de idade de 32,3 anos. Sete completaram o ensino fundamental, enquanto quatro completaram o ensino médio e dois, o ensino superior. Após a aplicação dos 21 questionários apenas a questão D do Apêndice não foi compreendida por três pacientes, tendo sido reescrita. CONCLUSÃO: o ITDI demonstrou-se uma escala de fácil aplicação na população brasileira, constituindo-se de grande utilidade para a avaliação do TDI em pacientes com epilepsia.Universidade Federal de São Paulo (UNIFESP) Departamento de Neurologia e NeurocirurgiaUniversidade Federal de São Paulo (UNIFESP) Departamento de PsiquiatriaUniversidade Federal de Minas Gerais Hospital das Clínicas Unidade de NeuropsiquiatriaUNIFESP, Depto. de Neurologia e NeurocirurgiaUNIFESP, Depto. de PsiquiatriaSciEL

Determinants of quality of life in Brazilian patients with myasthenia gravis

OBJECTIVES: The aims of the current study were 1) to evaluate the reliability and validity of the Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale and 2) to investigate the quality of life of Brazilian patients with myasthenia gravis and its determinants. METHODS: This cross-sectional study included 69 patients with myasthenia gravis who underwent neurological evaluation and completed questionnaires regarding quality of life (the 36-item Short Form of the Medical Outcomes Study and the 15-item Myasthenia Gravis Quality of Life Scale), anxiety and depressive symptoms. RESULTS: The Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale showed high internal consistency and good concurrent validity with the 36-item Short Form of the Medical Outcomes Study and its subscales. Determinants of quality of life in Brazilian patients with myasthenia gravis included the current status of myasthenia gravis as assessed by the Myasthenia Gravis Composite, the current prednisone dose and the levels of anxiety and depression. CONCLUSION: The Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale is a valid instrument. Symptom severity, prednisone dosage and anxiety and depression levels impact the quality of life of patients with myasthenia gravis

Cross-cultural adaptation of the neurobehavior inventory (NBI) for Brazil

OBJETIVO: Realizar a adaptação transcultural de instrumento para avaliação das alterações comportamentais tipicamente descritas em portadores de epilepsia do lobo temporal (ELT), o Inventário Neuro-Comportamental (NBI) para a população brasileira. MÉTODOS: Inicialmente, foi feita a tradução do instrumento original para o português. Esta versão foi revisada e retrotraduzida para o inglês. A seguir, a versão retrotraduzida foi comparada à versão original em inglês, sendo corrigidas as divergências no texto em português. Em um segundo momento, 15 pacientes do Ambulatório de Epilepsia do Hospital das Clínicas da UFMG portadores de ELT responderam ao inventário. À aplicação do questionário, eventuais dificuldades e os itens mal compreendidos foram analisados pelos autores. RESULTADOS: Na versão final para o português, os itens 11, 14, 17, 61 e 75 foram modificados. Sete pacientes (46,7%) eram do sexo feminino, com idade entre 26 e 65 anos. A maioria dos pacientes (93,3%) apresentou uma pontuação total elevada. Os domínios mais comumente alterados foram hiperreligiosidade, detalhismo e crença na predestinação pessoal (73,3% dos pacientes em cada um deles). CONCLUSÃO: A versão em português do NBI pode ser um instrumento útil para avaliar alterações comportamentais na ELT aplicada ao contexto clínico dos pacientes brasileiros.PURPOSE: To perform the cross-cultural adaptation of an instrument designed to measure behavioral changes typically described in temporal lobe epilepsy (TLE), the Neurobehavior Inventory (NBI), for Brazilian population. METHODS: At first the original instrument was translated to Portuguese-Brazilian language. This version was revised and translated back into English. Later, both English versions were compared and the divergences were corrected in the Portuguese text. The second step consisted of the application of the inventory to 15 TLE patients from the Epilepsy Program, Federal University of Minas Gerais. The authors analyzed eventual difficulties and misunderstandings in the application of the questionnaire. RESULTS: In the final Portuguese version, the questions 11, 14, 17, 61 and 75 were considered difficult to understand and were modified. Seven (46.7%) subjects were women, with 26 to 65 years. Most of the patients (93.3%) had a high total score level. Religious convictions, interest in details and sense of personal destiny were the most common altered domains (73.3% of the patients in each one of them). CONCLUSION: The Portuguese-Brazilian version of the NBI may be a useful instrument to evaluate TLE behavioral alterations in the Brazilian clinical context

Electronic Structure and Coexistence of Superconductivity with Magnetism in RbEuFe4As4

In the novel stoichiometric iron-based material RbEuFe4As4, superconductivity coexists with a peculiar long-range magnetic order of Eu 4f states. Using angle-resolved photoemission spectroscopy, we reveal a complex three-dimensional electronic structure and compare it with density functional theory calculations. Multiple super-conducting gaps were measured on various sheets of the Fermi surface. High-resolution resonant photoemission spectroscopy reveals magnetic order of the Eu 4f states deep into the superconducting phase. Both the absolute values and the anisotropy of the superconducting gaps are remarkably similar to the sibling compound without Eu, indicating that Eu magnetism does not affect the pairing of electrons. A complete decoupling between Fe-and Eu-derived states was established from their evolution with temperature, thus unambiguously demonstrating that superconducting and a long-range magnetic orders exist independently from each other. The established electronic structure of RbEuFe4As4 opens opportunities for the future studies of the highly unorthodox electron pairing and phase competition in this family of iron-based superconductors with doping.We thank Matthew Watson for his critical reading of the manuscript. We thank Diamond Light Source for access to beamline I05 (Proposal No. SI15074 and No. SI19041) that contributed to the results presented here. Work was done using equipment from the LPI Shared Facility Center. K.S.P. and V.M.P. acknowledge support by the Russian Scientific Foundation (RSF Project No. 21-12-00394). A.V.S. and A.S.U. acknowledge support by the Russian Foundation for Basic Research (Project No. 21-52-12043). E.V.C. acknowledges funding by Saint Petersburg State University project for scientific investigations (ID No. 73028629). S.V.E. acknowledges support from the government research assignment for ISPMS SB RAS (Project FWRW-2019-0032). R.V. acknowledges funding by the Deutsche Forschungsgemeinschaft (DFG) TRR 288 (Project A05). V.B. thanks the Goethe University Frankfurt for computational resources and Daniel Guterding for providing the FS plotting software. K.K. thanks M. Valvidares, J. Herrero, H. B. Vasili, S. Agrestini, and N. Brookes for their support during the XMCD experiment at ALBA via IHR Proposal 2019063615. D.V.V. also acknowledges support from the Spanish Ministry of Economy (MAT-2017-88374-P

Cognitive Impairment Following Acute Mild Traumatic Brain Injury

Patients with mild traumatic brain injury (mTBI) may present cognitive deficits within the first 24 h after trauma, herein called “acute phase,” which in turn may lead to long-term functional impairment and decrease in quality of life. Few studies investigated cognition in mTBI patients during the acute phase. The objectives of this study were to investigate the cognitive profile of patients with mTBI during the acute phase, compared to controls and normative data, and whether loss of consciousness (LOC), previous TBI and level of education influence cognition at this stage. Fifty-three patients with mTBI (aged 19–64 years) and 28 healthy controls participated in the study. All patients were evaluated at bedside within 24 h post-injury. Demographic and clinical data were registered. Cognitive function was assessed with the Mini-mental state examination (MMSE), the Frontal Assessment Battery (FAB), Digit Span (working memory), and the Visual Memory Test/Brief Cognitive Battery (for episodic memory). The clinical sample was composed mainly by men (58.5%). The mean age was 39 years-old and 64.3% of the patients had more than 8 years of education. The most common causes of mTBI were fall from own height (28.3%), aggression (24.5%), and fall from variable heights (24.5%). Compared to controls, mTBI patients exhibited significantly worse performance on MMSE, FAB, naming, incidental memory, immediate memory, learning, and delayed recall. Compared to normative data, 26.4% of patients had reduced global cognition as measured by the MMSE. Episodic memory impairment (13.2%) was more frequent than executive dysfunction (9.4%). No significant differences were found in cognitive performance when comparing patients with or without LOC or those with or without history of previous TBI. Patients with lower educational level had higher rates of cognitive impairment (VMT naming−28.6 vs. 4.2%; VMT immediate memory−32 vs. 4.2%; VMT learning−39.3 vs. 4.2%, all p < 0.05). In sum, we found significant cognitive impairment in the acute phase of mTBI, which was not associated with LOC or history of TBI, but appeared more frequently in patients with lower educational level

Long-lived spin waves in a metallic antiferromagnet

Collective spin excitations in magnetically ordered crystals, called magnons or spin waves, can serve as carriers in novel spintronic devices with ultralow energy consumption. The generation of well-detectable spin flows requires long lifetimes of high-frequency magnons. In general, the lifetime of spin waves in a metal is substantially reduced due to a strong coupling of magnons to the Stoner continuum. This makes metals unattractive for use as components for magnonic devices. Here, we present the metallic antiferromagnet CeCo2P2, which exhibits long-living magnons even in the terahertz (THz) regime. For CeCo2P2, our first-principle calculations predict a suppression of low-energy spin-flip Stoner excitations, which is verified by resonant inelastic X-ray scattering measurements. By comparison to the isostructural compound LaCo2P2, we show how small structural changes can dramatically alter the electronic structure around the Fermi level leading to the classical picture of the strongly damped magnons intrinsic to metallic systems. Our results not only demonstrate that long-lived magnons in the THz regime can exist in bulk metallic systems, but they also open a path for an efficient search for metallic magnetic systems in which undamped THz magnons can be excited.This work was supported by the German Research Foundation (DFG) through Grants No. KR3831/5-1, No. LA655/20-1m, Fermi-NEst, GRK1621, TRR288 (No. 422213477) project A03, and SFB1143 (No. 247310070). D.V.V. acknowledges support from the Spanish Ministry of Science and Innovation, project PID2020-116093RB-C44, funded by MCIN/AEI/10.13039/ 501100011033. A.E. acknowledges funding by Fonds zur Förderung der wissenschaftlichen Forschung (FWF) grant I 5384. Part of the calculations were performed at Rechenzentrum Garching of the Max Planck Society (Germany). The authors acknowledge the ESRF for beamtime on beamline ID32.Peer reviewe