Molecular Mimicry between SARS-CoV-2 Proteins and Human Self-Antigens Related with Autoimmune Central Nervous System (CNS) Disorders.

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induces the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted to the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions that share a high identity between SARS-CoV-2 antigens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG, and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals.

The clinical-radiological paradox in multiple sclerosis: myth or truth?

BACKGROUND: Multiple sclerosis (MS) is an inflammatory, degenerative, demyelinating disease that ranges from benign to rapidly progressive forms. A striking characteristic of the disease is the clinical-radiological paradox. OBJECTIVES: The present study was conducted to determine whether, in our cohort, the clinical-radiological paradox exists and whether lesion location is related to clinical disability in patients with MS. METHODS: Retrospective data from 95 patients with MS (60 women and 35 men) treated at a single center were examined. One head-and-spine magnetic resonance imaging (MRI) examination from each patient was selected randomly, and two independent observers calculated lesion loads (LLs) on T2/fluid attenuation inversion recovery sequences manually, considering the whole brain and four separate regions (periventricular, juxtacortical, posterior fossa, and spinal cord). The LLs were compared with the degree of disability, measured by the Kurtzke Expanded Disability Status Scale (EDSS), at the time of MRI examination in the whole cohort and in patients with relapsing-remitting (RR), primarily progressive, and secondarily progressive MS. RESULTS: High LLs correlated with high EDSS scores in the whole cohort (r = 0.34; p < 0.01) and in the RRMS group (r = 0.27; p = 0.02). The EDSS score correlated with high regional LLs in the posterior fossa (r = 0.31; p = 0.002) and spinal cord (r = 0.35; p = 0.001). CONCLUSIONS: Our results indicate that the clinical-radiological paradox is a myth and support the logical connection between lesion location and neurological repercussion.

ANTECEDENTES: A esclerose múltipla (EM) é uma doença inflamatória, degenerativa e desmielinizante que varia de formas benignas a rapidamente progressivas. Uma característica marcante da doença é o paradoxo clínico-radiológico. OBJETIVOS: O presente estudo foi realizado para determinar, se na nossa amostragem, o paradoxo clínico-radiológico existe e se a localização das lesões está relacionada à incapacidade clínica em pacientes com EM. MéTODOS: Foram examinados retrospectivamente dados de 95 pacientes com EM (60 mulheres e 35 homens) atendidos em um único centro. Um exame de ressonância magnética de cada paciente foi selecionado aleatoriamente, e dois observadores independentes calcularam as cargas lesionais (CLs) em sequências T2 e FLAIR manualmente, considerando todo o cérebro e quatro regiões separadamente (periventricular, justacortical, fossa posterior e medula espinhal). As CLs foram comparadas com o grau de incapacidade, medido pela Escala de Status expandido de incapacidade (EDSS, na sigla em inglês) de Kurtzke, no momento do exame de ressonância magnética (RM) em toda a coorte e em pacientes com as formas surto remissão (SR), primariamente progressiva (PP), e secundariamente progressiva (SP) da EM. RESULTADOS: Cargas lesionais elevadas foram correlacionadas com altos índices de EDSS considerando toda a coorte (r = 0.34; p < 0.01) e no grupo SR (r = 0.27; p = 0.02). O EDSS foi correlacionado com CLs altas na fossa posterior (r = 0.31; p = 0.002) e na medula (r = 0.35; p = 0.001). CONCLUSõES: Nossos resultados indicam que o paradoxo clínico-radiológico é um mito e apoiam a conexão lógica entre a localização da lesão e a repercussão neurológica.

The clinical-radiological paradox in multiple sclerosis: myth or truth? / O paradoxo clínico radiológico na esclerose múltipla: mito ou verdade?

Abstract Background Multiple sclerosis (MS) is an inflammatory, degenerative, demyelinating disease that ranges from benign to rapidly progressive forms. A striking characteristic of the disease is the clinical-radiological paradox. Objectives The present study was conducted to determine whether, in our cohort, the clinical-radiological paradox exists and whether lesion location is related to clinical disability in patients with MS. Methods Retrospective data from 95 patients with MS (60 women and 35 men) treated at a single center were examined. One head-and-spine magnetic resonance imaging (MRI) examination from each patient was selected randomly, and two independent observers calculated lesion loads (LLs) on T2/fluid attenuation inversion recovery sequences manually, considering the whole brain and four separate regions (periventricular, juxtacortical, posterior fossa, and spinal cord). The LLs were compared with the degree of disability, measured by the Kurtzke Expanded Disability Status Scale (EDSS), at the time of MRI examination in the whole cohort and in patients with relapsing-remitting (RR), primarily progressive, and secondarily progressive MS. Results High LLs correlated with high EDSS scores in the whole cohort (r = 0.34; p< 0.01) and in the RRMS group (r = 0.27; p= 0.02). The EDSS score correlated with high regional LLs in the posterior fossa (r = 0.31; p= 0.002) and spinal cord (r = 0.35; p= 0.001). Conclusions Our results indicate that the clinical-radiological paradox is a myth and support the logical connection between lesion location and neurological repercussion.

Resumo Antecedentes A esclerose múltipla (EM) é uma doença inflamatória, degenerativa e desmielinizante que varia de formas benignas a rapidamente progressivas. Uma característica marcante da doença é o paradoxo clínico-radiológico. Objetivos O presente estudo foi realizado para determinar, se na nossa amostragem, o paradoxo clínico-radiológico existe e se a localização das lesões está relacionada à incapacidade clínica em pacientes com EM. Métodos Foram examinados retrospectivamente dados de 95 pacientes com EM (60 mulheres e 35 homens) atendidos em um único centro. Um exame de ressonância magnética de cada paciente foi selecionado aleatoriamente, e dois observadores independentes calcularam as cargas lesionais (CLs) em sequências T2 e FLAIR manualmente, considerando todo o cérebro e quatro regiões separadamente (periventricular, justacortical, fossa posterior e medula espinhal). As CLs foram comparadas com o grau de incapacidade, medido pela Escala de Status expandido de incapacidade (EDSS, na sigla em inglês) de Kurtzke, no momento do exame de ressonância magnética (RM) em toda a coorte e em pacientes com as formas surto remissão (SR), primariamente progressiva (PP), e secundariamente progressiva (SP) da EM. Resultados Cargas lesionais elevadas foram correlacionadas com altos índices de EDSS considerando toda a coorte (r = 0.34; p< 0.01) e no grupo SR (r = 0.27; p= 0.02). O EDSS foi correlacionado com CLs altas na fossa posterior (r = 0.31; p= 0.002) e na medula (r = 0.35; p= 0.001). Conclusões Nossos resultados indicam que o paradoxo clínico-radiológico é um mito e apoiam a conexão lógica entre a localização da lesão e a repercussão neurológica.

Magnetic resonance imaging evaluation of spinal cord lesions: what can we find? - Part 2. Inflammatory and infectious injuries.

Diseases involving the spinal cord include a heterogeneous group of abnormalities, including those of inflammatory, infectious, neoplastic, vascular, metabolic, and traumatic origin. Making the clinical differentiation between different entities is often difficult, magnetic resonance imaging being the diagnostic method of choice. Although the neuroimaging findings are not pathognomonic, many are quite suggestive, and the radiologist can assist in the diagnosis and, consequently, in the therapeutic guidance. In this second part of our article, the objective is to review the magnetic resonance imaging findings of the main inflammatory and infectious spinal cord injuries.

As doenças que envolvem a medula espinal incluem um grupo heterogêneo de anomalias, englobando causas inflamatórias, infecciosas, neoplásicas, vasculares, metabólicas e traumáticas. Muitas vezes a diferenciação clínica entre as diversas entidades é difícil, sendo a ressonância magnética a modalidade de escolha na investigação diagnóstica. Apesar de os achados de neuroimagem não serem patognomônicos, muitos são bastante sugestivos, podendo o radiologista auxiliar no diagnóstico e, consequentemente, na orientação terapêutica. O objetivo desta segunda parte do artigo é revisar os achados de ressonância magnética das principais lesões medulares inflamatórias e infecciosas.

Magnetic resonance imaging evaluation of spinal cord lesions: what can we find? - Part 1. Neoplastic, vascular, metabolic, and traumatic injuries.

Diseases involving the spinal cord include a heterogeneous group of abnormalities, including those of inflammatory, infectious, neoplastic, vascular, metabolic, and traumatic origin. Making the clinical differentiation between different entities is often difficult, magnetic resonance imaging being the diagnostic method of choice. Although the neuroimaging findings are not pathognomonic, many are quite suggestive, and the radiologist can assist in the diagnosis and, consequently, in the therapeutic guidance. In this first part of our article, the objective is to review the magnetic resonance imaging findings of the main neoplastic, vascular, metabolic, and traumatic spinal cord injuries.

As doenças que envolvem a medula espinal incluem um grupo heterogêneo de anomalias, englobando causas inflamatórias, infecciosas, neoplásicas, vasculares, metabólicas e traumáticas. Muitas vezes a diferenciação clínica entre as diversas entidades é difícil, sendo a ressonância magnética a modalidade de escolha na investigação diagnóstica. Apesar de os achados de neuroimagem não serem patognomônicos, muitos são bastante sugestivos, podendo o radiologista auxiliar no diagnóstico e, consequentemente, na orientação terapêutica. O objetivo desta primeira parte do artigo é revisar os achados de ressonância magnética das principais lesões medulares neoplásicas, vasculares, metabólicas e traumáticas.

Preliminary comparative study of cortical thickness in HIV-infected patients with and without working memory deficit.

PURPOSE: Changes in cerebral cortical regions occur in HIV-infected patients, even in those with mild neurocognitive disorders. Working memory / attention is one of the most affected cognitive domain in these patients, worsening their quality of life. Our objective was to assess whether cortical thickness differs between HIV-infected patients with and without working memory deficit. METHODS: Forty-one adult HIV-infected patients with and without working memory deficit were imaged on a 1.5 T scanner. Working memory deficit was classified by composite Z scores for performance on the Digits and Letter-Number Sequencing subtests of the Wechsler Adult Intelligence Scale (third edition; WAIS-III). Cortical thickness was determined using FreeSurfer software. Differences in mean cortical thickness between groups, corrected for multiple comparisons using Monte-Carlo simulation, were examined using the query design estimate contrast tool of the FreeSurfer software. RESULTS: Greater cortical thickness in left pars opercularis of the inferior frontal gyrus, and rostral and caudal portions of the left middle frontal gyrus (cluster 1; p = .004), and left superior frontal gyrus (cluster 2; p = .004) was observed in HIV-infected patients with working memory deficit compared with those without such deficit. Negative correlations were found between WAIS-III-based Z scores and cortical thickness in the two clusters (cluster 1: ρ = -0.59; cluster 2: ρ = -0.47). CONCLUSION: HIV-infected patients with working memory deficit have regions of greater thickness in the left frontal cortices compared with those without such deficit, which may reflect increased synaptic contacts and/or an inflammatory response related to the damage caused by HIV infection.

Magnetic resonance imaging evaluation of spinal cord lesions: what can we find? - Part 2. Inflammatory and infectious injuries / Avaliação por ressonância magnética das lesões intramedulares: o que podemos encontrar? - Parte 2. Lesões inflamatórias e infecciosas

Abstract Diseases involving the spinal cord include a heterogeneous group of abnormalities, including those of inflammatory, infectious, neoplastic, vascular, metabolic, and traumatic origin. Making the clinical differentiation between different entities is often difficult, magnetic resonance imaging being the diagnostic method of choice. Although the neuroimaging findings are not pathognomonic, many are quite suggestive, and the radiologist can assist in the diagnosis and, consequently, in the therapeutic guidance. In this second part of our article, the objective is to review the magnetic resonance imaging findings of the main inflammatory and infectious spinal cord injuries.

Resumo As doenças que envolvem a medula espinal incluem um grupo heterogêneo de anomalias, englobando causas inflamatórias, infecciosas, neoplásicas, vasculares, metabólicas e traumáticas. Muitas vezes a diferenciação clínica entre as diversas entidades é difícil, sendo a ressonância magnética a modalidade de escolha na investigação diagnóstica. Apesar de os achados de neuroimagem não serem patognomônicos, muitos são bastante sugestivos, podendo o radiologista auxiliar no diagnóstico e, consequentemente, na orientação terapêutica. O objetivo desta segunda parte do artigo é revisar os achados de ressonância magnética das principais lesões medulares inflamatórias e infecciosas.

Magnetic resonance imaging evaluation of spinal cord lesions: what can we find? - Part 1. Neoplastic, vascular, metabolic, and traumatic injuries / Avaliação por ressonância magnética das lesões intramedulares: o que podemos encontrar? - Parte 1. Lesões neoplásicas, vasculares, metabólicas e traumáticas

Abstract Diseases involving the spinal cord include a heterogeneous group of abnormalities, including those of inflammatory, infectious, neoplastic, vascular, metabolic, and traumatic origin. Making the clinical differentiation between different entities is often difficult, magnetic resonance imaging being the diagnostic method of choice. Although the neuroimaging findings are not pathognomonic, many are quite suggestive, and the radiologist can assist in the diagnosis and, consequently, in the therapeutic guidance. In this first part of our article, the objective is to review the magnetic resonance imaging findings of the main neoplastic, vascular, metabolic, and traumatic spinal cord injuries.

Resumo As doenças que envolvem a medula espinal incluem um grupo heterogêneo de anomalias, englobando causas inflamatórias, infecciosas, neoplásicas, vasculares, metabólicas e traumáticas. Muitas vezes a diferenciação clínica entre as diversas entidades é difícil, sendo a ressonância magnética a modalidade de escolha na investigação diagnóstica. Apesar de os achados de neuroimagem não serem patognomônicos, muitos são bastante sugestivos, podendo o radiologista auxiliar no diagnóstico e, consequentemente, na orientação terapêutica. O objetivo desta primeira parte do artigo é revisar os achados de ressonância magnética das principais lesões medulares neoplásicas, vasculares, metabólicas e traumáticas.

Possível associação entre doença desmielinizante e neoplasias oligodendrogliais: relato de caso / Possible association between demyelinating disease and oligodendroglial tumors: a case report

Desde o primeiro relato de doença desmielinizante associada a tumores cerebrais por Scherer em 1938, inúmeros outros relatos de casos foram publicados fazendo associação desta doença com diferentes tumores primários do sistema nervoso central. Nosso trabalho descreve o caso de uma paciente de 23 anos com duas lesões encefálicas biopsiadas, mostrando inicialmente processo inflamatório desmielinizante que no seguimento desenvolve um oligodendroglioma anaplásico. A partir deste caso, realizamos uma revisão da literatura dessa associação específica, primeiramente publicada por Barnard e Jellinek em 1967, e ressaltamos a importância da diferenciação entre a forma desmielinizante tumefativa de uma neoplasia cerebral verdadeira. (AU)

Since the first report of demyelinating disease associated with brain tumors by Scherer in 1938, several other case reports have been published making association of this disease with different primary tumors of the central nervous system. Our paper describes the case of a 23 year old patient with two brain lesions, biopsied, initially showing a demyelinating inflammatory process that in the follow up develops an anaplastic oligodendroglioma. From this case, we conducted a literature review of this specific association, first published by Barnard and Jellinek in 1967, and emphasize the importance of difference in a tumefactive demyelinating lesions between of true brain neoplasm. (AU)

Regional Cerebral Gray Matter Volume in HIV-Positive Patients with Executive Function Deficits.

PURPOSE: To evaluate whether human immunodeficiency virus (HIV)-positive patients with and without executive functions deficits and healthy control subjects differ on cortical thickness and subcortical brain structures volume in vivo. METHODS: In total, 34 HIV-positive patients with executive functions deficits were compared with 13 HIV-positive patients without executive functions deficits and 19 gender-, age-, and education-matched control subjects. Executive functions impairments were classified by performance on the Wisconsin card sorting test. T1 3-dimensional magnetization prepared rapid gradient echo-weighted imaging was performed using a 1.5 Tesla (magnetic resonance) MR scanner. FreeSurfer software was used to perform cortical reconstruction and volumetric segmentation of subcortical gray matter structures. RESULTS: HIV-positive patients with executive functions deficits had smaller volumes in the right and left caudate compared with the HIV-positive patients without executive functions deficits and control groups. In addition, HIV-positive patients with executive functions deficits had smaller volumes in their left accumbens, right putamen, and globus pallidum compared with the control group. No significant differences in cortical thickness were observed between the groups. CONCLUSION: HIV-positive patients with executive functions deficits have reduced volumes of several subcortical structures, primarily in the caudate nucleus.

Novel microduplications at Xp11.22 including HUWE1: clinical and molecular insights into these genomic rearrangements associated with intellectual disability.

Recently, we defined a minimal overlapping region for causal Xp11.22 copy number gains in males with intellectual disability (ID), and identified HECT, UBA and WWE domain-containing protein-1 (HUWE1) as the primary dosage-sensitive gene, whose overexpression leads to ID. In the present study, we used this minimal interval to search for HUWE1 copy number variations by quantitative polymerase chain reaction in a large cohort of Brazilian males with idiopathic ID. We detected two unrelated sporadic individuals with syndromic ID carrying unique overlapping duplications encompassing HUWE1. Breakpoint junction analysis showed a simple tandem duplication in the first patient, which has probably arisen by microhomology-mediated break-induced repair mechanism. In the second patient, the rearrangement is complex having an insertion of an intrachromosomal sequence at its junction. This kind of rearrangement has not been reported in Xp11.22 duplications and might have emerged by a replication- or recombination-based mechanism. Furthermore, the presence of infantile seizures in the second family suggests a potential role of increased KDM5C expression on epilepsy. Our findings highlight the importance of microduplications at Xp11.22 to ID, even in sporadic cases, and reveal new clinical and molecular insight into HUWE1 copy number gains.

A novel method for intraoral access to the superior head of the human lateral pterygoid muscle.

BACKGROUND: The uncoordinated activity of the superior and inferior parts of the lateral pterygoid muscle (LPM) has been suggested to be one of the causes of temporomandibular joint (TMJ) disc displacement. A therapy for this muscle disorder is the injection of botulinum toxin (BTX), of the LPM. However, there is a potential risk of side effects with the injection guide methods currently available. In addition, they do not permit appropriate differentiation between the two bellies of the muscle. Herein, a novel method is presented to provide intraoral access to the superior head of the human LPM with maximal control and minimal hazards. METHODS: Computational tomography along with digital imaging software programs and rapid prototyping techniques were used to create a rapid prototyped guide to orient BTX injections in the superior LPM. RESULTS: The method proved to be feasible and reliable. Furthermore, when tested in one volunteer it allowed precise access to the upper head of LPM, without producing side effects. CONCLUSIONS: The prototyped guide presented in this paper is a novel tool that provides intraoral access to the superior head of the LPM. Further studies will be necessary to test the efficacy and validate this method in a larger cohort of subjects.

Síndrome de Parry-Romberg: achados nas sequências avançadas de ressonância magnética - relato de caso / Parry-Romberg syndrome: findings in advanced magnetic resonance imaging sequences - case report

Síndrome de Parry-Romberg é uma doença rara caracterizada por atrofia hemifacial progressiva associada a outras alterações sistêmicas, dentre elas, neurológicas. Atualmente, são poucos os trabalhos que exploraram sequências avançadas em ressonância magnética nesta enfermidade. Neste artigo, relatamos o caso de um paciente com 45 anos e descrevemos os achados de ressonância magnética estrutural e em sequências avançadas, correlacionando com dados fisiopatológicos.

Parry-Romberg syndrome is a rare disease characterized by progressive hemifacial atrophy associated with other systemic changes, including neurological symptoms. Currently, there are few studies exploring the utilization of advanced magnetic resonance sequences in the investigation of this disease. The authors report the case of a 45-year-old patient and describe the findings at structural magnetic resonance imaging and at advanced sequences, correlating them with pathophysiological data.