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Introdução: A Síndrome da Pessoa Rígida é uma doença neuroimunológica rara do sistema nervoso central caracterizada por espasmos dolorosos e rigidez progressiva que envolvem os músculos proximais dos membros e axiais do tronco. A forma clássica tem início insidioso com piora gradual ao longo do tempo e muitas vezes leva à incapacidade permanente. Objetivo: Analisar os estudos publicados na literatura científica que utilizaram a reabilitação fisioterapêutica como proposta de tratamento dos sintomas motores na Síndrome da Pessoa Rígida. Método: Trata-se de uma revisão integrativa da literatura realizada no período de julho a dezembro de 2022 nas bases de dados PubMed, SciELO, LILACS e BVS. Resultados: Foram encontrados 12 artigos publicados entre o período de 2002 a 2021, que discorriam sobre o tratamento fisioterapêutico nesta população. O número escasso de estudos se dá pela raridade da patologia que dificulta a realização de ensaios clínicos robustos. Os artigos selecionados eram relatos de casos de um ou mais indivíduos, com enfoque nas intervenções realizadas de acordo com cada queixa funcional apresentada, sendo estas a dor, fraqueza muscular, hipomobilidade articular, rigidez, instabilidade postural, alterações na marcha e limitações nas atividades de vida diária. Conclusão: A reabilitação fisioterapêutica faz parte do tratamento sintomatológico e tem como finalidade, auxiliar na manutenção da funcionalidade e qualidade de vida, minimizando as repercussões motoras que são desencadeadas pela síndrome.

Introduction: Stiff Person Syndrome is a rare neuroimmunological disease of the central nervous system characterized by painful spasms and progressive rigidity involving the proximal muscles of the limbs and axial muscles of the trunk. The classic form has an insidious onset with gradual worsening over time and often leads to permanent disability. Objective: To analyze the studies published in the scientific literature that used hysiotherapeutic rehabilitation as a proposal for treating motor symptoms in Stiff Person Syndrome. Method: This is an integrative review of the literature carried out from July to December 2022 in the PubMed, SciELO, LILACS and VHL databases. Results: 12 articles published between 2002 and 2021 were found, which discussed physiotherapeutic treatment in this population. The scarce number of studies is due to the rarity of the pathology, which makes it difficult to carry out robust clinical trials. The selected articles were case reports of one or more individuals, focusing on interventions carried out according to each functional complaint presented, these being pain, muscle weakness, joint hypomobility, stiffness, postural instability, changes in gait and limitations in walking activities. daily life. Conclusion: Physiotherapy rehabilitation is part of symptomatological treatment and aims to help maintain functionality and quality of life, minimizing the motor repercussions that are triggered by the syndrome.

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Leukodystrophies represent a large and complex group of inherited disorders affecting the white matter of the central nervous system. Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare leukodystrophy which still needs the proper identification of diagnostic, prognostic, and monitoring biomarkers. The aim of this study was to determine the diagnostic and prognostic value of chitinases and neurofilament light chain as biomarkers for ALSP. A cross-sectional study was performed to analyze cerebrospinal fluid levels of chitinases (chitotriosidase and chitinase 3-like 2) and neurofilament light chain in five different groups: (i) normal health individuals; (ii) patients with definitive diagnosis of ALSP and genetic confirmation; (iii) asymptomatic patients with CSF1R variants; (iv) patients with other adult-onset leukodystrophies; and (v) patients with amyotrophic lateral sclerosis (external control group). Chitinase levels showed a statistical correlation with clinical assessment parameters in ALSP patients. Chitinase levels were also distinct between ALSP and the other leukodystrophies. Significant differences were noted in the levels of chitinases and neurofilament light chain comparing symptomatic (ALSP) and asymptomatic individuals with CSF1R variants. This study is the first to establish chitinases as a potential biomarker for ALSP and confirms neurofilament light chain as a good biomarker for primary microgliopathies.

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Background: Acute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and prognostic value of serum neurofilament light chain (NfL) as potential biomarker for AHP. Methods: We conducted a cross-sectional observational study to evaluate NfL levels in patients with AHP. They were divided in different groups: normal health individuals; patients with definitive diagnosis of AHP during acute episodes; patients with AHP and infrequent attacks; patients with AHP and recurrent attacks; asymptomatic individuals with positive genetic testing and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels elevated 4 or more times ("high excretors"); asymptomatic individuals with exclusive positive genetic test; control group with Hereditary Amyloidosis related to Transthyretin with Polyneuropathy (ATTRv-PN). Results: During acute attacks, serum NfL levels were 68 times higher compared to normal controls and disclosed a strong correlation with ALA and PBG levels; also exhibited elevated levels in patients with chronic symptoms regardless of the number of disease attacks compared to healthy controls, and at similar levels to patients with ATTRv-PN, which is a model of progressive neuropathy. Conclusion: This study represents the first to establish NfL as a biomarker for AHP, disclosing NfL as a sensitive biomarker for axonal damage and chronic symptom occurrence. This study not only underscores that neurological damage associated with the disease in any patient, irrespective of the number of attacks, but also reinforces the progressive and profoundly debilitating nature of acute and chronic symptoms observed in individuals with AHP.

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Juvenile Amyotrophic Lateral Sclerosis is a genetically heterogeneous neurodegenerative disorder, which is frequently misdiagnosed due to low clinical suspicion and little knowledge about disease characteristics. More than 20 different genetic loci have been associated with both sporadic and familial juvenile Amyotrophic Lateral Sclerosis. Currently, almost 40% of cases have an identifiable monogenic basis; type 6, associated with FUS gene variants, is the most prevalent globally. Despite several upper motor neuron-dominant forms being generally associated with long-standing motor symptoms and slowly progressive course, certain subtypes with lower motor neuron-dominant features and early bulbar compromise lead to rapidly progressive motor handicap. For some monogenic forms, there is a well-established genotypic-phenotypic correlation. There are no specific biochemical and neuroimaging biomarkers for the diagnosis of juvenile Amyotrophic Lateral Sclerosis. There are several inherited neurodegenerative and neurometabolic disorders which can lead to the signs of motor neuron impairment. This review emphasizes the importance of high clinical suspicion, assessment, and proper diagnostic work-up for juvenile Amyotrophic Lateral Sclerosis.

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BACKGROUND: Porphyrias are a rare group of disease due to inherited defects of heme synthesis with important systemic manifestations and great burden of disease for patients and families due to the exceptional course of disease with disabling chronic symptoms interposed by life-threatening acute attacks. Unfortunately, the porphyrias are usually underrecognized reflecting a lack of medical and disease awareness as well as few studies about natural history in large cohorts of patients. The main aim of this article is present consistent data about natural history and burden of disease in a large Brazilian cohort. METHODS: We conducted a national cross-sectional registry with retrospective clinical data of Brazilian patients with porphyria collected with Brazilian patients Association with Porphyria in collaboration with a tertiary care center for rare diseases. RESULTS: A cohort of 172 patients was analyzed in which 148 (86%) patients had the diagnosis of acute hepatic porphyria [AHP] that needed a mean of 62.04 medical visits and 9.6 years to achieve a definitive diagnosis. About AHP cohort, the most common first clinical manifestation were abdominal pain in 77 (52%) patients and acute muscle weakness in 23 (15.5%) with 73 (49.3%) patients presenting only one attack during disease course and 37 (25%) exhibiting 4 or more attacks in the last year. Of note, 105 patients with AHP reported chronic manifestations and the scores for quality of life are lower when compared with general healthy population. CONCLUSIONS: Brazilian patients with AHP had a higher prevalence of chronic disabling manifestations and a poor quality of life like other cohorts and a higher proportion of patients with recurrent attacks than previously reported.

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Autoimmune diseases have been progressively recognized as a potential complication of primary immunodeficiency, especially for some genetic subtypes of common variable immunodeficiency. Although often associated with other autoimmune disorders, autoimmune myasthenia gravis is occasionally identified as a neuromuscular complication of primary immunodeficiency. We report the case of a Brazilian woman with common variable immunodeficiency-8 due to an LRBA variant, in which myasthenia gravis was identified in association with anti-acetylcholine receptor antibody. Marked clinical improvement occurred after intravenous immunoglobulin therapy.

Doenças autoimunes foram progressivamente reconhecidas como complicações potenciais das imunodeficiências primárias, especialmente para alguns subtipos genéticos das imunodeficiências comuns variáveis. Embora se associe comumente a outras doenças autoimunes, a Miastenia gravis autoimune adquirida foi raramente associada como complicação neuromuscular de imunodeficiências primárias. É descrito neste artigo o caso de paciente brasileira do sexo feminino com diagnóstico de Imunodeficiência Comum Variável tipo 8 por variante no gene LRBA, na qual foi identificada Miastenia gravis em associação a anticorpos antirreceptor de acetilcolina. Ela evoluiu com marcante melhora clínica após a introdução de terapêutica com imunoglobulina endovenosa.

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Charcot-Marie-Tooth's disease (CMT) represents the most common inherited neuropathy. Most patients are diagnosed during late stages of disease course during adulthood. We performed a review of clinical, neurophysiological, and genetic diagnoses of 32 patients with genetically defined childhood-onset demyelinating CMT under clinical follow-up in a Brazilian Center for Neuromuscular Diseases from January 2015 to December 2019. The current mean age was 33.1 ± 18.3 years (ranging from 7 to 71 years) and mean age at defined genetic diagnosis was 36.1 ± 18.3 years. The mean age at onset was 6.1 ± 4.4 years. The most common initial complaint was bilateral pes cavus. The genetic basis included PMP22 duplication (CMT1A) ( n = 18), GJB1 (CMTX1) ( n = 5), MPZ (CMT1B) ( n = 3), FIG4 (CMT4J) ( n = 3), SH3TC2 (CMT4C) ( n = 1), PLEKHG5 (CMTRIC) ( n = 1), and PRX (CMT4F) ( n = 1). Almost all patients ( n = 31) presented with moderate or severe compromise in the CMT neuropathy score 2 with the highest values observed in CMT1B. Medical history disclosed obstructive sleep apnea ( n = 5), aseptic meningitis ( n = 1/ MPZ ), akinetic-rigid parkinsonism ( n = 1/ FIG4 ), and overlapping chronic inflammatory demyelinating polyneuropathy ( n = 1/ MPZ ). Motor conduction block was detected in three individuals ( PMP22 , FIG4 , MPZ ). Acute denervation occurred in seven patients. Nonuniform demyelinating patterns were seen in four individuals (two CMT1A, one CMT1B, and one CMTX1). Abnormal cerebral white matter findings were detected in CMT1A and CMTX1, while hypertrophic roots were seen in CMT1A, CMT1B, and CMTX1. Our study emphasizes a relative oligogenic basis in childhood-onset demyelinating CMT and atypical findings may be observed especially in MPZ , PMP22 , and GJB1 gene variants.