Guillain-Barré syndrome and checkpoint inhibitor therapy: insights from pharmacovigilance data.

Background There are increasing reports of cases of Guillain-Barré syndrome (GBS), as an adverse event of an immune checkpoint inhibitor (ICI) but postmarket data on the incidence of this remains scarce. This study sought to conduct a comprehensive review of GBS events arising as a secondary outcome of ICI treatments in real-world patients, using the Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Data covering the period from the third quarter of 2003 to the second quarter of 2023 were extracted from the FAERS database. GBS cases (associated with the usage of avelumab, atezolizumab, ipilimumab, nivolumab and pembrolizumab) were subjected to disproportionality analysis to detect potential signals. Results A total of 2208 reports of GBS were identified within the FAERS database, with 242 of these cases (10.9%) being associated with ICIs. All five drugs exhibited a disproportionality in the reporting of adverse events, with the highest observed for avelumab (reporting OR, ROR: 29.8), followed by atezolizumab (ROR: 17.0), ipilimumab (ROR: 16.0), pembrolizumab (ROR: 11.9) and nivolumab (ROR: 8.2). Conclusion These checkpoint inhibitors are associated with a statistically significant disproportionate number of reports of GBS as an adverse event, with avelumab being the ICI with the highest association. The present pharmacovigilance study serves as a valuable tool, offering a more comprehensive and nuanced perspective on GBS associated with ICIs. This study contributes to a deeper comprehension of this rare adverse drug effect.

Intermediate conduction velocity in two cases of Charcot-Marie-Tooth disease type 1A.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1A (CMT1A) is the most prevalent hereditary neuropathy worldwide and classically has slow nerve conduction velocity (NCV), in most cases below 38 m/s. Two unrelated patients with motor NCVs in the upper limbs above 38 m/s are reported. METHOD: Case report. RESULTS: Two genetically confirmed CMT1A patients are presented, from two unrelated families (one of British origin and the other of Brazilian origin). Both individuals had upper limb motor NCVs above 38 m/s, with values ranging from 41.9 to 45 m/s in the median nerve and from 42 to 42.3 m/s in the ulnar nerve. They presented with a very mild phenotype, with CMT Neuropathy Score version 2 (CMTNSv2) of 6 and 5, respectively. In contrast, affected family members within both kinships exhibited a classical phenotype with more severe disease manifestation (CMTNSv2 ranging from 12 to 20) and motor NCVs below 30 m/s. CONCLUSION: These cases, although very rare, highlight the importance of testing PMP22 duplication in patients with intermediate conduction velocities.

Charcot-Marie-Tooth disease: from historical landmarks in Brazil to current care perspectives.

Hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease (CMT), traditionally refers to a group of genetic disorders in which neuropathy is the main or sole feature. Its prevalence varies according to different populations studied, with an estimate between 1:2,500 to 1:10,000. Since the identification of PMP22 gene duplication on chromosome 17 by Vance et al., in 1989, more than 100 genes have been related to this group of disorders, and we have seen advances in the care of patients, with identification of associated conditions and better supportive treatments, including clinical and surgical interventions. Also, with discoveries in the field of genetics, including RNA interference and gene editing techniques, new treatment perspectives begin to emerge. In the present work, we report the most import landmarks regarding CMT research in Brazil and provide a comprehensive review on topics such as frequency of different genes associated with CMT in our population, prevalence of pain, impact on pregnancy, respiratory features, and development of new therapies.

A neuropatia sensitivo-motora hereditária, também conhecida como doença de Charcot-Marie-Tooth (CMT), tradicionalmente se refere a um grupo de doenças genéticas em que a neuropatia é a principal ou única manifestação. Sua prevalência varia de acordo com as diferentes populações estudadas, com estimativa entre 1:2.500 a 1:10.000. Desde a identificação da duplicação do gene PMP22 no cromossomo 17, por Vance et al., em 1989, mais de 100 genes foram relacionados a esse grupo de doenças e temos visto avanços no atendimento aos pacientes, com identificação de condições associadas e melhores tratamentos de suporte, incluindo intervenções clínicas e cirúrgicas. Além disso, com as descobertas no campo da genética, incluindo técnicas de interferência de RNA e de edição genética, novas perspectivas de tratamento começaram a surgir. No presente trabalho, relatamos os marcos mais importantes sobre a pesquisa de CMT no Brasil e fornecemos uma revisão abrangente sobre tópicos como frequência de diferentes genes associados à CMT em nossa população, prevalência de dor, impacto na gravidez, alterações respiratórias e desenvolvimento de novas terapias.

Molecular mimicry between Zika virus and central nervous system inflammatory demyelinating disorders: the role of NS5 Zika virus epitope and PLP autoantigens.

BACKGROUND: Evidence indicates a strong link between Zika virus (ZikV) and neurological complications. Acute myelitis, optic neuritis, polyneuropathy, and encephalomyelitis that mimic inflammatory idiopathic demyelination disorders (IIDD) after ZikV infection have been reported in Brazil. OBJECTIVE: The present study aims to investigate the possible occurrence of molecular mimicry between ZikV antigens and Multiple Sclerosis (MS) autoantigens, the most frequent IIDD of the central nervous system (CNS). METHODS: A retrospective cohort study with 305 patients admitted due to suspected arbovirus infection in Rio de Janeiro was performed, all subjects were submitted to neurological examination, and a biological sample was collected for serologic and molecular diagnostic. Bioinformatics tools were used to analyze the peptides shared between ZikV antigens and MS autoantigens. RESULTS: Of 305 patients, twenty-six were positive for ZikV and 4 presented IDD patterns found in MS cases. Sequence homology comparisons by bioinformatics approach between NS5 ZikV and PLP MS protein revealed a homology of 5/6 consecutive amino acids (CSSVPV/CSAVPV) with 83% identity, deducing a molecular mimicry. Analysis of the 3D structures revealed a similar conformation with alpha helix presentation. CONCLUSIONS: Molecular mimicry between NS5 Zika virus antigen and PLP MS autoantigens emerge as a possible mechanism for IDD spectrum in genetically susceptible individuals.

ANTECEDENTES: Evidências indicam uma forte ligação entre o vírus Zika (ZikV) e complicações neurológicas. Mielite aguda, neurite óptica, polineuropatia e encefalomielite que mimetizam distúrbios inflamatórios de desmielinização idiopáticos (DDII) após infecção por ZikV têm sido relatadas no Brasil. OBEJTIVO: O presente estudo tem como objetivo investigar a possível ocorrência de mimetismo molecular entre antígenos do ZikV e autoantígenos da Esclerose Múltipla (EM), a DDII mais frequente do sistema nervoso central (SNC). MéTODOS: Foi realizado um estudo de coorte retrospectivo com 305 pacientes internados por suspeita de infecção por arbovírus no Rio de Janeiro, todos os indivíduos foram submetidos a exame neurológico e coleta de amostra biológica para diagnóstico sorológico e molecular. Ferramentas de bioinformática foram usadas para analisar os peptídeos compartilhados entre antígenos do ZikV e autoantígenos da EM. RESULTADOS: Dos 305 pacientes, vinte e seis foram positivos para ZikV e 4 apresentaram padrão IDD encontrado em casos de EM. As comparações de homologia de sequência por abordagem de bioinformática entre a proteína NS5 ZikV e PLP EM revelaram uma homologia de 5/6 aminoácidos consecutivos (CSSVPV/CSAVPV) com 83% de identidade, deduzindo um mimetismo molecular. A análise das estruturas 3D revelou uma conformação semelhante com apresentação em alfa-hélice. CONCLUSõES: O mimetismo molecular entre o antígeno NS5 do vírus Zika e o autoantígeno PLP da EM surge como um possível mecanismo para o espectro IDD em indivíduos geneticamente suscetíveis.

Brazilian consensus for diagnosis, management and treatment of hereditary transthyretin amyloidosis with peripheral neuropathy: second edition.

Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ∼ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ∼ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.

Shared Molecular Signatures Across Zika Virus Infection and Multiple Sclerosis Highlight AP-1 Transcription Factor as a Potential Player in Post-ZIKV MS-Like Phenotypes.

Zika virus (ZIKV) is an arbovirus of the Flaviviridae genus that has rapidly disseminated from across the Pacific to the Americas. Robust evidence has indicated a crucial role of ZIKV in congenital virus syndrome, including neonatal microcephaly. Moreover, emerging evidence suggests an association between ZIKV infection and the development of an extensive spectrum of central nervous system inflammatory demyelinating diseases (CNS IDD), such as multiple sclerosis-like clinical phenotypes. However, the underlying mechanisms of host-pathogen neuro-immune interactions remain to be elucidated. This study aimed to identify common transcriptional signatures between multiple sclerosis (MS) and ZIKV infection to generate molecular interaction networks, thereby leading to the identification of deregulated processes and pathways, which could give an insight of these underlying molecular mechanisms. Our investigation included publicly available transcriptomic data from MS patients in either relapse or remission (RR-MS) and datasets of subjects acutely infected by ZIKV for both immune peripheral cells and central nervous system cells. The protein-protein interaction (PPI) analysis showed upregulated AP-1 transcription factors (JUN and FOS) among the top hub and bottleneck genes in RR-MS and ZIKV data. Gene enrichment analysis retrieved a remarkable presence of ontologies and pathways linked to oxidative stress responses, immune cell function, inflammation, interleukin signaling, cell division, and transcriptional regulation commonly enriched in both scenarios. Considering the recent findings concerning AP-1 function in immunological tolerance breakdown, regulation of inflammation, and its function as an oxidative stress sensor, we postulate that the ZIKV trigger may contribute as a boost for the activation of such AP-1-regulated mechanisms that could favor the development of MS-like phenotypes following ZIKV infection in a genetically susceptible individual.

Molecular mimicry between Zika virus and central nervous system inflammatory demyelinating disorders: the role of NS5 Zika virus epitope and PLP autoantigens / Mimetismo molecular entre o vírus Zika e os distúrbios inflamatórios desmielinizantes do sistema nervoso central: o papel do epítopo NS5 do vírus Zika e dos autoantígenos PLP

Abstract Background Evidence indicates a strong link between Zika virus (ZikV) and neurological complications. Acute myelitis, optic neuritis, polyneuropathy, and encephalomyelitis that mimic inflammatory idiopathic demyelination disorders (HDD) after ZikV infection have been reported in Brazil. Objective The present study aims to investigate the possible occurrence of molecular mimicry between ZikV antigens and Multiple Sclerosis (MS) autoantigens, the most frequent HDD of the central nervous system (CNS). Methods A retrospective cohort study with 305 patients admitted due to suspected arbovirus infection in Rio de Janeiro was performed, all subjects were submitted to neurological examination, and a biological sample was collected for serologic and molecular diagnostic. Bioinformatics tools were used to analyze the peptides shared between ZikV antigens and MS autoantigens. Results Of 305 patients, twenty-six were positive for ZikV and 4 presented IDD patterns found in MS cases. Sequence homology comparisons by bioinformatics approach between NS5 ZikV and PLP MS protein revealed a homology of 5/6 consecutive amino acids (CSSVPV/CSAVPV) with 83% identity, deducing a molecular mimicry. Analysis of the 3D structures revealed a similar conformation with alpha helix presentation. Conclusions Molecular mimicry between NS5 Zika virus antigen and PLP MS autoantigens emerge as a possible mechanism for IDD spectrum in genetically susceptible individuals.

Resumo Antecedentes Evidências indicam uma forte ligação entre o vírus Zika (ZikV) e complicações neurológicas. Mielite aguda, neurite óptica, polineuropatia e encefalomielite que mimetizam distúrbios inflamatórios de desmielinização idiopáticos (DDII) após infecção por ZikV têm sido relatadas no Brasil. Obejtivo O presente estudo tem como objetivo investigar a possível ocorrência de mimetismo molecular entre antígenos do ZikV e autoantígenos da Esclerose Múltipla (EM), a DDII mais frequente do sistema nervoso central (SNC). Métodos Foi realizado um estudo de coorte retrospectivo com 305 pacientes internados por suspeita de infecção por arbovirus no Rio de Janeiro, todos os indivíduos foram submetidos a exame neurológico e coleta de amostra biológica para diagnóstico sorológico e molecular. Ferramentas de bioinformática foram usadas para analisar os peptídeos compartilhados entre antígenos do ZikV e autoantígenos da EM. Resultados Dos 305 pacientes, vinte e seis foram positivos para ZikV e 4 apresentaram padrão IDD encontrado em casos de EM. As comparações de homologia de sequência por abordagem de bioinformática entre a proteína NS5 ZikV e PLP EM revelaram uma homologia de 5/6 aminoácidos consecutivos (CSSVPV/CSAVPV) com 83% de identidade, deduzindo um mimetismo molecular. A análise das estruturas 3D revelou uma conformação semelhante com apresentação em alfa-hélice. Conclusões O mimetismo molecular entre o antígeno NS5 do vírus Zika e o autoantígeno PLP da EM surge como um possível mecanismo para o espectro IDD em indivíduos geneticamente suscetíveis.

Brazilian consensus for diagnosis, management and treatment of hereditary transthyretin amyloidosis with peripheral neuropathy: second edition / Consenso brasileiro para o diagnóstico, manejo e tratamento da polineuropatia amiloidótica familiar associada à transtirretina: segunda edição

Abstract Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ~ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.

Resumo Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ~ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.

Neurodevelopmental outcomes in a cohort of children with congenital Zika syndrome at 12 and 24 months of age.

BACKGROUND: Early child development is a critical stage of life that influences social, educational and health outcomes worldwide. A few years after Zika epidemic, families of children born with congenital Zika syndrome (CZS) continue to face uncertainties when it comes to the development of their children. The present study sought to analyse the developmental trajectories of a subset of children born with CZS in the first 24 months of life. METHODS: Thirty-five children with CZS were assessed with the Bayley-III Scales at 12 and 24 months of age from November 2016 to December 2018 in a rehabilitation centre in Brazil. Inclusion criteria included children with established diagnosis of CZS. Exclusion criteria included the presence of arthrogryposis, prematurity, irregular follow-up, clinical complications or other causes of microcephaly. Children born with CZS who evolved with cerebral palsy (CP) were classified according to the Gross Motor Function Classification System (GMFCS) at 2 years of age. RESULTS: At 12 months of age mean composite scores on the Bayley cognitive, communication and motor scores were 57.71 (SD 7.11), 57.94 (SD 14.34) and 49.26 (7.20), respectively. At 24 months of age, composite scores were 57.43 (SD 7.11), 53.60 (SD 12.29) and 48.83 (7.76). In addition, 31 (88.57%) out of 34 children diagnosed with CP were classified as GMFCS levels IV and V. CONCLUSION: Zika virus congenital infection is a risk factor for functional impairments across all developmental domains having a direct and substantial negative impact in early child development.

Charcot-Marie-Tooth disease: from historical landmarks in Brazil to current care perspectives / Doença de Charcot-Marie-Tooth: dos marcos históricos no Brasil até as perspectivas atuais de cuidado

Abstract Hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease (CMT), traditionally refers to a group of genetic disorders in which neuropathy is the main or sole feature. Its prevalence varies according to different populations studied, with an estimate between 1:2,500 to 1:10,000. Since the identification of PMP22 gene duplication on chromosome 17 by Vance et al., in 1989, more than 100 genes have been related to this group of disorders, and we have seen advances in the care of patients, with identification of associated conditions and better supportive treatments, including clinical and surgical interventions. Also, with discoveries in the field of genetics, including RNA interference and gene editing techniques, new treatment perspectives begin to emerge. In the present work, we report the most import landmarks regarding CMT research in Brazil and provide a comprehensive review on topics such as frequency of different genes associated with CMT in our population, prevalence of pain, impact on pregnancy, respiratory features, and development of new therapies.

Resumo A neuropatia sensitivo-motora hereditária, também conhecida como doença de Charcot-Marie-Tooth (CMT), tradicionalmente se refere a um grupo de doenças genéticas em que a neuropatia é a principal ou única manifestação. Sua prevalência varia de acordo com as diferentes populações estudadas, com estimativa entre 1:2.500 a 1:10.000. Desde a identificação da duplicação do gene PMP22 no cromossomo 17, por Vance et al., em 1989, mais de 100 genes foram relacionados a esse grupo de doenças e temos visto avanços no atendimento aos pacientes, com identificação de condições associadas e melhores tratamentos de suporte, incluindo intervenções clínicas e cirúrgicas. Além disso, com as descobertas no campo da genética, incluindo técnicas de interferência de RNA e de edição genética, novas perspectivas de tratamento começaram a surgir. No presente trabalho, relatamos os marcos mais importantes sobre a pesquisa de CMT no Brasil e fornecemos uma revisão abrangente sobre tópicos como frequência de diferentes genes associados à CMT em nossa população, prevalência de dor, impacto na gravidez, alterações respiratórias e desenvolvimento de novas terapias.

Chronic inflammatory demyelinating polyneurophaty: assessment of the cognitive function and quality of life.

BACKGROUND: Studies were carried out with the objective of evaluating the quality of life (QoL) of patients affected by chronic inflammatory demyelinating polyradiculopathy (CIDP). However, the cognitive issue is still little addressed. OBJECTIVES: To assess the QoL and cognitive impairment of patients with CIDP and to analyze whether there is a correlation between these parameters. METHODS: Seven patients with CIDP and seven paired controls were subjected to: mini-mental state examination (MMSE); Montreal cognitive assessment (MoCA); digit symbol replacement/symbol copy test (DSST); fatigue severity scale (FSS); Beck depressive inventory-I (BDI-I), and a short-form of health survey (SF-36). RESULTS: The mean age of the participants was 50 years (71.4% male). The MMSE and MoCA had no statistical difference between the groups. Patients showed superior results in the memory domain in the MoCA (5 vs. 2, p = 0.013). In the DSST, we observed a tendency for patients to be slower. There was a strong negative correlation between fatigue levels and vitality domain (SF-36). There was no significant correlation between depression levels and QoL, and there was no correlation between depression and the results obtained in the cognitive tests. The patients presented higher levels of depression (15.28 vs. 3.42, p < 0.001). A total of 57% had severe fatigue, 28.8% self-reported pain, and 57.1% complained of cramps. CONCLUSION: There was no cognitive impairment in these patients. However, there was a tendency of slower processing speed. To better evaluate the alterations found, a study with a larger number of individuals would be necessary. Chronic inflammatory demyelinating polyradiculopathy affects the QoL of patients in different ways.

ANTECEDENTES: Estudos foram realizados com o objetivo de avaliar a qualidade de vida (QV) de pacientes acometidos pela polirradiculopatia desmielinizante inflamatória crônica (PDIC). No entanto, a questão cognitiva ainda é pouco abordada. OBJETIVOS: Avaliar a QV e o comprometimento cognitivo em pacientes com PDIC bem como se existe correlação entre esses parâmetros. MéTODOS: Sete pacientes com PDIC e sete controles pareados foram submetidos a: miniexame do estado mental (MEEM); avaliação cognitiva de Montreal (MoCA); teste de substituição de símbolo de dígito/cópia de símbolo (DSST); escala de gravidade da fadiga (FSS); Beck depressive inventory-I (BDI-I) e um short-form of health survey (SF-36). RESULTADOS: A média de idade dos pacientes foi de 50 anos (71,4% do sexo masculino). O MMSE e o MoCA não apresentaram diferença estatística entre os grupos. Os pacientes apresentaram resultados superiores no domínio memória do MoCA (5 vs. 2, p = 0,013). No DSST, observamos uma tendência de os pacientes serem mais lentos. Houve forte correlação negativa entre os níveis de fadiga e o domínio vitalidade (SF-36). Não houve correlação significativa entre níveis de depressão e QV. Não houve correlação entre depressão e os resultados obtidos nos testes cognitivos. Níveis elevados de depressão foram observados nos pacientes (15,28 vs. 3,42, p < 0,001). Um total de 57% apresentou fadiga intensa, 28,8% dor autorreferida, e 57,1% queixam-se de câimbras. CONCLUSãO: Não há comprometimento cognitivo nos pacientes estudados. Observamos somente uma tendência de lentificação na velocidade de processamento. Para melhor avaliar as alterações encontradas, será necessário estudo com um número maior de indivíduos. A PDIC afeta de diferentes formas o nível de QV de seus portadores.

Chronic inflammatory demyelinating polyneurophaty: assessment of the cognitive function and quality of life / Polineuropatia desmielinizante inflamatória crônica: avaliação da função cognitiva e qualidade de vida

Abstract Background Studies were carried out with the objective of evaluating the quality of life (QoL) of patients affected by chronic inflammatory demyelinating polyradiculopathy (CIDP). However, the cognitive issue is still little addressed. Objectives To assess the QoL and cognitive impairment of patients with CIDP and to analyze whether there is a correlation between these parameters. Methods Seven patients with CIDP and seven paired controls were subjected to: mini-mental state examination (MMSE); Montreal cognitive assessment (MoCA); digit symbol replacement/symbol copy test (DSST); fatigue severity scale (FSS); Beck depressive inventory-I (BDI-I), and a short-form of health survey (SF-36). Results The mean age of the participants was 50 years (71.4% male). The MMSE and MoCA had no statistical difference between the groups. Patients showed superior results in the memory domain in the MoCA (5 vs. 2, p = 0.013). In the DSST, we observed a tendency for patients to be slower. There was a strong negative correlation between fatigue levels and vitality domain (SF-36). There was no significant correlation between depression levels and QoL, and there was no correlation between depression and the results obtained in the cognitive tests. The patients presented higher levels of depression (15.28 vs. 3.42, p < 0.001). A total of 57% had severe fatigue, 28.8% self-reported pain, and 57.1% complained of cramps. Conclusion There was no cognitive impairment in these patients. However, there was a tendency of slower processing speed. To better evaluate the alterations found, a study with a larger number of individuals would be necessary. Chronic inflammatory demyelinating polyradiculopathy affects the QoL of patients in different ways.

Resumo Antecedentes Estudos foram realizados com o objetivo de avaliar a qualidade de vida (QV) de pacientes acometidos pela polirradiculopatia desmielinizante inflamatória crônica (PDIC). No entanto, a questão cognitiva ainda é pouco abordada. Objetivos Avaliar a QV e o comprometimento cognitivo em pacientes com PDIC bem como se existe correlação entre esses parâmetros. Métodos Sete pacientes com PDIC e sete controles pareados foram submetidos a: miniexame do estado mental (MEEM); avaliação cognitiva de Montreal (MoCA); teste de substituição de símbolo de dígito/cópia de símbolo (DSST); escala de gravidade da fadiga (FSS);Beck depressive inventory-I (BDI-I) e um short-form of health survey (SF-36). Resultados A média de idade dos pacientes foi de 50 anos (71,4% do sexo masculino). O MMSE e o MoCA não apresentaram diferença estatística entre os grupos. Os pacientes apresentaram resultados superiores no domínio memória do MoCA (5 vs. 2, p = 0,013). No DSST, observamos uma tendência de os pacientes serem mais lentos. Houve forte correlação negativa entre os níveis de fadiga e o domínio vitalidade (SF-36). Não houve correlação significativa entre níveis de depressão e QV. Não houve correlação entre depressão e os resultados obtidos nos testes cognitivos. Níveis elevados de depressão foram observados nos pacientes (15,28 vs. 3,42, p < 0,001). Um total de 57% apresentou fadiga intensa, 28,8% dor autorreferida, e 57,1% queixam-se de câimbras. Conclusão Não há comprometimento cognitivo nos pacientes estudados. Observamos somente uma tendência de lentificação na velocidade de processamento. Para melhor avaliar as alterações encontradas, será necessário estudo com um número maior de indivíduos. A PDIC afeta de diferentes formas o nível de QV de seus portadores.

Corneal confocal microscopy in patients with distal symmetric polyneuropathy compared to controls.

BACKGROUND: Diabetic neuropathy (DN) is a very common clinical condition throughout the world. The diagnostic tests currently recommended have low sensitivity, such as electromyography, or are invasive, such as skin biopsy. New techniques have been developed to identify the early involvement of the peripheral nerve. With the advent of corneal confocal microscopy (CCM), a reduction in corneal innervation in patients with DN has been observed. OBJECTIVE: To compare, through CCM, diabetic patients with symptomatic distal symmetric polyneuropathy (DSP) and controls. METHODS: In the present study, through CCM, we compared the morphological changes in the sub-basal epithelial corneal plexus of 35 diabetic patients with symptomatic DSP with 55 controls. Moreover, we sought to determine a pattern of change regarding the severity stages of DSP, comparing the clinical, laboratory, and nerve-conduction (NC) variables. RESULTS: Differences between the control and diabetic groups were observed for the following variables, respectively: age (44.9 ± 13.24 years versus 57.02 ± 10.4 years; p < 0.001); fiber density (29.7 ± 10.2 versus 16.6 ± 10.2; p < 0.001); number of fibers (4.76 ± 1.30 versus 3.14 ± 1.63; p < 0.001); number of Langerhans cells (4.64 ± 8.05 versus 7.49 ± 10.3; p = 0.035); tortuosity (p < 0.05); and thickness (p < 0.05). Furthermore, inverse relationships were found regarding fiber density and age (p < 0.01) and fiber density and the severity of the disease (p < 0.05). A positive relationship between the conduction velocity of the fibular nerve and fiber density (p < 0.05) was also observed. CONCLUSION: Corneal confocal microscopy proved to be a fast, noninvasive and reproducible method for the diagnosis, staging, and monitoring of diabetic DSP.

ANTECEDENTES: A neuropatia diabética (ND) é condição clínica muito frequente no mundo inteiro. Os testes diagnósticos atualmente preconizados são pouco sensíveis, como a eletroneuromiografia, ou invasivos, como a biópsia de pele. Novas técnicas de investigação complementares têm sido desenvolvidas a fim de identificar o acometimento precoce do nervo periférico. Com o advento da microscopia confocal de córnea (MCC), observou-se redução da inervação da córnea em pacientes com ND. OBJETIVO: Comparar, por meio da MCC, pacientes diabéticos com polineuropatia simétrica distal (PSD) sintomática e controles. MéTODOS: Neste estudo, por meio da MCC, comparamos as alterações morfológicas do plexo sub-basal epitelial da córnea de 35 pacientes diabéticos com PSD sintomática com 55 indivíduos controles. Além disso, buscamos determinar um padrão de alteração entre os estágios de gravidade da PSD, comparando variáveis clínicas, laboratoriais e de neurocondução. RESULTADOS: Diferenças entre os grupos controle e diabéticos foram verificadas com relação às seguintes variáveis, respectivamente: idade (44,9 ± 13,24 anos versus 57,02 ± 10,4 anos; p < 0,001); densidade das fibras (29,7 ± 10,2 versus 16,6 ± 10,2; p < 0,001); número de fibras (4,76 ± 1,30 versus 3,14 ± 1,63; p < 0,001); número de células de Langerhans (4,64 ± 8,05 versus 7,49 ± 10,3; p = 0,035); tortuosidade (p < 0,05), e espessura (p < 0,05). Além disso, relações inversamente proporcionais foram verificadas entre a densidade das fibras e a idade (p < 0,01), e entre a densidade das fibras e a gravidade da doença (p < 0,05). Observou-se ainda uma relação positiva entre a velocidade de condução do nervo fibular e a densidade das fibras (p < 0,05). CONCLUSãO: A MCC constitui um método rápido, não invasivo e reprodutível para o diagnóstico, o estadiamento, e o acompanhamento da PSD diabética.

HIV-associated painful neuropathy: where are we?

BACKGROUND: After the advent of combination antiretroviral therapy, infection with the human immunodeficiency virus (HIV) ceased to be a devastating disease, but sensory neuropathy resulting from the permanence of the virus and the side effects of treatment have worsened the morbidities of these patients. OBJECTIVE: To investigate the quality of life of 64 HIV-positive patients: 24 with painful neuropathy (case group) and 40 without painful neuropathy (control group). The impact of other factors on quality of life was also assessed. METHODS: To assess painful neuropathy, the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale, Douleur Neuropathique 4 (DN4) questions and Neuropathy Disability Score (NDS) were used. The Short Form Health Survey (SF-36) scale was used to assess quality of life. Factors related or unrelated to HIV were obtained through the medical history and analysis on medical records. RESULTS: The quality of life of patients with neuropathic pain was worse in six of the eight domains of the SF-36 scale. The number of clinical manifestations related to HIV, length of time with detectable viral load since diagnosis, length of time since the diagnosis of HIV infection and length of time of HAART use had a negative impact on quality of life. Higher levels of CD4, education and family income had a positive impact. CONCLUSIONS: Painful neuropathy related to HIV is a factor that worsens the quality of life of patients infected with this virus and should be included in the clinical evaluation.

Corneal confocal microscopy in patients with distal symmetric polyneuropathy compared to controls / Microscopia confocal de córnea em pacientes com polineuropatia simétrica distal comparados a controles

Abstract Background Diabetic neuropathy (DN) is a very common clinical condition throughout the world. The diagnostic tests currently recommended have low sensitivity, such as electromyography, or are invasive, such as skin biopsy. New techniques have been developed to identify the early involvement of the peripheral nerve. With the advent of corneal confocal microscopy (CCM), a reduction in corneal innervation in patients with DN has been observed. Objective To compare, through CCM, diabetic patients with symptomatic distal symmetric polyneuropathy (DSP) and controls. Methods In the present study, through CCM, we compared the morphological changes in the sub-basal epithelial corneal plexus of 35 diabetic patients with symptomatic DSP with 55 controls. Moreover, we sought to determine a pattern of change regarding the severity stages of DSP, comparing the clinical, laboratory, and nerve-conduction (NC) variables. Results Differences between the control and diabetic groups were observed for the following variables, respectively: age (44.9 ± 13.24 years versus 57.02 ± 10.4 years; p< 0.001); fiber density (29.7 ± 10.2 versus 16.6 ± 10.2; p< 0.001); number of fibers (4.76 ± 1.30 versus 3.14 ± 1.63; p< 0.001); number of Langerhans cells (4.64 ± 8.05 versus 7.49 ± 10.3; p= 0.035); tortuosity (p< 0.05); and thickness (p< 0.05). Furthermore, inverse relationships were found regarding fiber density and age (p< 0.01) and fiber density and the severity of the disease (p< 0.05). A positive relationship between the conduction velocity of the fibular nerve and fiber density (p< 0.05) was also observed. Conclusion Corneal confocal microscopy proved to be a fast, noninvasive and reproducible method for the diagnosis, staging, and monitoring of diabetic DSP.

Resumo Antecedentes A neuropatia diabética (ND) é condição clínica muito frequente no mundo inteiro. Os testes diagnósticos atualmente preconizados são pouco sensíveis, como a eletroneuromiografia, ou invasivos, como a biópsia de pele. Novas técnicas de investigação complementares têm sido desenvolvidas a fim de identificar o acometimento precoce do nervo periférico. Com o advento da microscopia confocal de córnea (MCC), observou-se redução da inervação da córnea em pacientes com ND. Objetivo Comparar, por meio da MCC, pacientes diabéticos com polineuropatia simétrica distal (PSD) sintomática e controles. Métodos Neste estudo, por meio da MCC, comparamos as alterações morfológicas do plexo sub-basal epitelial da córnea de 35 pacientes diabéticos com PSD sintomática com 55 indivíduos controles. Além disso, buscamos determinar um padrão de alteração entre os estágios de gravidade da PSD, comparando variáveis clínicas, laboratoriais e de neurocondução. Resultados Diferenças entre os grupos controle e diabéticos foram verificadas com relação às seguintes variáveis, respectivamente: idade (44,9 ± 13,24 anos versus 57,02 ± 10,4 anos; p< 0,001); densidade das fibras (29,7 ± 10,2 versus 16,6 ± 10,2; p< 0,001); número de fibras (4,76 ± 1,30 versus 3,14 ± 1,63; p< 0,001); número de células de Langerhans (4,64 ± 8,05 versus 7,49 ± 10,3; p= 0,035); tortuosidade (p< 0,05), e espessura (p < 0,05). Além disso, relações inversamente proporcionais foram verificadas entre a densidade das fibras e a idade (p< 0,01), e entre a densidade das fibras e a gravidade da doença (p< 0,05). Observou-se ainda uma relação positiva entre a velocidade de condução do nervo fibular e a densidade das fibras (p< 0,05). Conclusão A MCC constitui um método rápido, não invasivo e reprodutível para o diagnóstico, o estadiamento, e o acompanhamento da PSD diabética.

Interleukin-31 and soluble CD40L: new candidate serum biomarkers that predict therapeutic response in multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease that affects the central nervous system (CNS), varying from relatively benign to severely disabling. Although the roles of several cytokines and chemokines in MS are well established, their roles in MS lesions and evolution remain a matter of debate. Soluble CD40L (sCD40L) is a ligand that induces lymphocyte proinflammatory activity by stimulating the activation and maturation of B cells, promoting isotype switching and affinity hypermutation. Circulating sCD40L levels reflect activation of the CD40-CD40L complex. The interaction between CD40 and CD40L is of fundamental importance, suggesting their role in MS pathogenesis. Interleukin-31 (IL-31) is a proinflammatory cytokine that plays a role in allergies, autoimmune diseases, and is a major factor in several chronic inflammatory diseases. IL-31 triggers the JAK-STAT pathway in several different cell types, to induce proliferation and tissue remodeling in fibroblasts, epithelial cells, and endothelial cells. Some studies have described a correlation between these two cytokines and decreased serum levels of sCD40L and IL-31 after MS treatment, accompanied by a lower inflammatory response. In this review, we emphasize the possible correlation and positive feedback between IL31 and sCD40L in the MS proinflammatory response. We also describe the justification for this hypothesis and whether it is possible to investigate these cytokines as biomarkers of MS.

Influence of Islamic religion and spirituality on the well-being and quality of life of cancer patients: a meta-analysis and a hypothetical model of cerebral mechanisms / Influência da religião e da espiritualidade islâmica no bem-estar e na qualidade de vida de pacientes com câncer: uma metanálise e um modelo hipotético de mecanismos cerebrais

OBJECTIVE: To systematically analyze quantitative data about the effects of religion/spirituality and the well-being/quality of life of cancer patients. The second aim was to hypothesize a neurophysiological model of the association between religion/spirituality and the brain. METHODS: This study met the PRISMA Statement and was registered at PROSPERO database. Randomized and Controlled trials investigating religion/spirituality and well-being/quality of life of cancer patients were included. Based on neuroimaging and neurophysiology studies, a neuroanatomical model was developed to hypothesize the relationship between neuroscience and religion/spirituality. RESULTS: A large effect size was found on the improvement of well-being/quality of life (SMD = 3.90 [2.43-5.38], p < 0.01). Heterogeneity was high among studies (I2 = 98%, p < 0.01). Specific regions of the brain, such as the temporal lobes, amygdalae and hippocampus, regions from the limbic system, were hypothesized to take part in the religion/spirituality phenomena and the well-being/quality of life improvement. CONCLUSION: Religion/spirituality intervention, mainly the Islamic, promotes an improvement on wellbeing/quality of life of cancer patients.

OBJETIVO: Analisar sistematicamente dados quantitativos sobre os efeitos da religião/espiritualidade e o bem-estar/qualidade de vida de pacientes com câncer. O segundo objetivo foi levantar a hipótese de um modelo neurofisiológico da associação entre religião/espiritualidade e o cérebro. MÉTODOS: Este estudo seguiu as recomendações do PRISMA e foi registrado no PROSPERO. Estudos randomizados e controlados investigando religião/espiritualidade e o bem-estar/qualidade de vida de pacientes com câncer foram incluídos. Com base em estudos de neuroimagem e neurofisiologia, um modelo neuroanatômico foi desenvolvido para hipotetizar relações entre neurociência e religião/espiritualidade. RESULTADOS: Um tamanho de efeito grande foi encontrado na melhoria do bem-estar/qualidade de vida (SMD = 3,90 [2,43-5,38], p < 0,01). A heterogeneidade foi alta entre os estudos (I2 = 98%, p < 0,01). Regiões específicas do cérebro, como lobos temporais, amídalas e hipocampo, regiões do sistema límbico, foram hipotetizadas como participantes dos fenômenos religião/espiritualidade e melhoria do bem-estar/qualidade de vida. CONCLUSÃO: A intervenção religiosa/espiritual, principalmente islâmica, promove melhora no bem-estar/qualidade de vida em pacientes com câncer.

HIV-associated painful neuropathy: where are we? / Neuropatia dolorosa associada ao HIV: onde estamos?

ABSTRACT Background: After the advent of combination antiretroviral therapy, infection with the human immunodeficiency virus (HIV) ceased to be a devastating disease, but sensory neuropathy resulting from the permanence of the virus and the side effects of treatment have worsened the morbidities of these patients. Objective: To investigate the quality of life of 64 HIV-positive patients: 24 with painful neuropathy (case group) and 40 without painful neuropathy (control group). The impact of other factors on quality of life was also assessed. Methods To assess painful neuropathy, the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale, Douleur Neuropathique 4 (DN4) questions and Neuropathy Disability Score (NDS) were used. The Short Form Health Survey (SF-36) scale was used to assess quality of life. Factors related or unrelated to HIV were obtained through the medical history and analysis on medical records. Results: The quality of life of patients with neuropathic pain was worse in six of the eight domains of the SF-36 scale. The number of clinical manifestations related to HIV, length of time with detectable viral load since diagnosis, length of time since the diagnosis of HIV infection and length of time of HAART use had a negative impact on quality of life. Higher levels of CD4, education and family income had a positive impact. Conclusions: Painful neuropathy related to HIV is a factor that worsens the quality of life of patients infected with this virus and should be included in the clinical evaluation.

RESUMO Antecedentes: Após o advento da terapia antirretroviral combinada a infecção pelo vírus da imunodeficiência humana (HIV) deixou de ser uma doença devastadora, porém a neuropatia sensitiva consequente à permanência do vírus e ao efeito colateral do tratamento piora a morbidade desses pacientes. Objetivo: Investigar a qualidade de vida de 64 pacientes com HIV, 24 com neuropatia dolorosa (grupo caso) e 40 sem neuropatia dolorosa (grupo controle). Avaliou-se também o impacto de outros fatores relacionados e não relacionados ao HIV na qualidade de vida. Métodos: Para avaliação da neuropatia dolorosa foram utilizadas as escalas Leeds Assessment of Neuropathic Symptoms and Signs (LANSS), Douleur Neuropathique 4 (DN4) e Escore de Comprometimento Neuropático (ECN). Para avaliação da qualidade de vida foi utilizada a escala Short Form Health Survey (SF-36). Fatores relacionados e não relacionados ao HIV foram obtidos através da anamnese e análise de prontuário. Resultados: A qualidade de vida dos pacientes com dor neuropática foi pior em 6 dos 8 domínios da escala SF-36. O número de manifestações clínicas relacionadas ao HIV, tempo de carga viral detectável desde o diagnóstico, tempo de diagnóstico da infecção pelo vírus e tempo de uso de TARVC impactaram negativamente na qualidade de vida. Maior nível de CD4, da escolaridade e da renda familiar impactaram positivamente. Conclusões: A neuropatia dolorosa relacionada ao HIV é fator de piora da qualidade de vida dos pacientes infectados por esse vírus devendo ser incluída na avaliação clínica desses pacientes.

Primary neural leprosy: clinical, neurophysiological and pathological presentation and progression.

Disability in leprosy is a direct consequence of damage to the peripheral nervous system which is usually worse in patients with no skin manifestations, an underdiagnosed subtype of leprosy known as primary neural leprosy. We evaluated clinical, neurophysiological and laboratory findings of 164 patients with definite and probable primary neural leprosy diagnoses. To better understand the disease progression and to improve primary neural leprosy clinical recognition we compared the characteristics of patients with short (≤12 months) and long (>12 months) disease duration. Positive and negative symptoms mediated by small-fibres were frequent at presentation (∼95%), and symptoms tend to manifest first in the upper limbs (∼68%). There is a consistent phenotypic variability between the aforementioned groups. Deep sensory modalities were spared in patients evaluated within the first 12 months of the disease, and were only affected in patients with longer disease duration (∼12%). Deep tendon reflexes abnormalities were most frequent in patients with longer disease duration (P < 0.001), as well as motor deficits (P = 0.002). Damage to large fibres (sensory and motor) is a latter event in primary neural leprosy. Grade-2 disability and nerve thickening was also more frequent in cases with long disease duration (P < 0.001). Primary neural leprosy progresses over time and there is a marked difference in clinical phenotype between patients with short and long disease duration. Patients assessed within the first 12 months of symptom onset had a non-length-dependent predominant small-fibre sensory neuropathy, whilst patients with chronic disease presented an asymmetrical all diameter sensory-motor neuropathy and patchily decreased/absent deep tendon reflexes.

A Brazilian multicentre study on the clinical and epidemiological profiles of 1116 patients with amyotrophic lateral sclerosis and its phenotypic variants.

Objective: We conducted a multicentre, cross-sectional analysis of Brazilian patients with amyotrophic lateral sclerosis (ALS) and its phenotypic variants. We describe and compare their clinical and epidemiological data. Methods: We collected data from 1,116 patients who visited seven rehabilitation hospitals in the SARAH network from 1 January 2009 to 20 March 2020. This representative sample of patients was from 308 cities in 25 states from the country's five regions. Results: The median age at onset was 55 years, and we found a significant linear correlation between the age at onset and the Municipal Human Development Index (MHDI) but not survival time. We found a four-year difference using a cutoff value of 0.750 (p < 0.001). There was a male predominance, with a 1.2:1 sex ratio. The median time from onset to diagnosis was 17.6 months, and the most common phenotypic presentations were spinal-onset and bulbar-onset ALS (62.7% and 14.7%, respectively). In total, 12.9% of the patients had familial ALS, likely due to the overrepresentation of ALS type 8 patients in our population. Conclusions: In general, our numbers are consistent with most international series and with those of other Brazilian cohorts. When patients were analyzed according to their MHDI a considerable delay in symptom onset was found, suggesting the possibility of an environmental effect on these patients. Brazil has a longer diagnostic delay which is similar to other less-developed countries. This is a substantial concern and should be a priority for health authorities and neurology societies.