Progressive multiple sclerosis: The treatment gap

Humphries, Courtney

doi:10.1038/nature11108

Cited by 15 publications

(6 citation statements)

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“…Logistic regression models were used with stepwise variable selection to model the probabilities of early ALs and PVI. Factors within the models included the time interval from birth to onset, onset to progression and from progression to death, gender, >2 relapses in the first 2 years after onset, MS being progressive in last illness, a high grade of PVI (none/minimal [0-1] vs significant presence [2][3][4][5]), and the presence of early active plaques found in the standardized assessment.…”

Section: Discussionmentioning

confidence: 99%

“…I nflammation is thought to be the fundamental driver of the pathology in multiple sclerosis (MS) at all stages of the disease course, giving rise to demyelination and axonal and neuronal loss, and this combined pathology results in the characteristic symptoms experienced by people with MS. [1][2][3] In individuals, the manifestations are highly variable but are characterized by two dominant clinical events: relapses, that is, transient periods of neurological deterioration with variable recovery; and progression, characterized by the gradual accumulation of disability that leads to the major personal and societal cost of MS. 4 Relapses have proven amenable to therapy, but progression has thus far been resistant to treatment, leading to a major unmet need. 5 Thus, despite extensive pathological evidence for inflammation in progressive MS, 1,6 no immunomodulatory treatment that has been shown to suppress relapses and gadolinium magnetic resonance imaging (MRI) activity has had a major impact on the progressive course. 7,8 This may be due to the dominant type of intrathecal compartmentalized inflammation in progression being "hidden" behind the blood-brain barrier or due to alternative mechanisms, such as cortical pathology and slowly expanding lesions.…”

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confidence: 99%

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High Levels of Perivascular Inflammation and Active Demyelinating Lesions at Time of Death Associated with Rapidly Progressive Multiple Sclerosis Disease Course: A Retrospective Postmortem Cohort Study

Nicholas,

Magliozzi,

Marastoni

et al. 2024

Annals of Neurology

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ObjectiveAnalysis of post‐mortem multiple sclerosis (MS) tissues combined with in‐vivo disease milestones suggest that while perivascular white matter infiltrates associate with demyelinating activity in the initial stages; leptomeningeal immune cell infiltration, enriched in B cells and associated with cortical lesions, contribute to disease progression. We systematically examine the association of inflammatory features and white matter demyelination at post‐mortem with clinical milestones.MethodsIn 269 MS brains; 20 sites were examined using immunohistochemistry for active lesions (ALs) and perivenular inflammation (PVI). In a subset of 22 a detailed count of CD20+ B cells and CD3+ T cells in PVIs was performed.ResultsALs were detected in 22%, whereas high levels of PVI were detected in 52% of cases. ALs were present in 35% of cases with high levels of PVI. Shorter time from onset of progression to death associated with increased prevalence and higher levels of PVI (both p<0.0001). Shorter time from onset of progression to wheelchair use associated with higher prevalence of ALs (OR 0.921, 95% CI (0.858, 0.989), p=0.0230) and higher level of PVI (0.932, (0.886, 0.981), p=0.0071). High levels of PVI were associated with meningeal inflammation and increased cortical demyelination and significantly higher levels of B lymphocytes within the PVI.InterpretationALs, a feature of early disease stage, persist up to death in a subgroup with high levels of PVI. These features link to a rapid progressive phase and higher levels of meningeal inflammation and B‐cell infiltrates, supporting the hypothesis that chronic inflammation drives progression in MS.This article is protected by copyright. All rights reserved.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

High Levels of Perivascular Inflammation and Active Demyelinating Lesions at Time of Death Associated with Rapidly Progressive Multiple Sclerosis Disease Course: A Retrospective Postmortem Cohort Study

Nicholas,

Magliozzi,

Marastoni

et al. 2024

Annals of Neurology

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“…However, this process usually results in incomplete myelinization or the production of low-quality myelin. This failure in remyelination precedes a progressive axon degeneration aggravating the neurological symptoms in MS patients, such as mobility and sensory impairment, fatigue, and temporary loss of vision, among many others leading to progressive disease [ 1 , 5 , 6 , 9 , 10 , 11 ]. Thus, primary demyelination leads to neurodegeneration, causing devastating neurological damage and disability in MS patients.…”

Section: Multiple Sclerosismentioning

confidence: 99%

Neurodegeneration in Multiple Sclerosis: The Role of Nrf2-Dependent Pathways

et al. 2022

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Multiple sclerosis (MS) encompasses a chronic, irreversible, and predominantly immune-mediated disease of the central nervous system that leads to axonal degeneration, neuronal death, and several neurological symptoms. Although various immune therapies have reduced relapse rates and the severity of symptoms in relapsing-remitting MS, there is still no cure for this devastating disease. In this brief review, we discuss the role of mitochondria dysfunction in the progression of MS, focused on the possible role of Nrf2 signaling in orchestrating the impairment of critical cellular and molecular aspects such as reactive oxygen species (ROS) management, under neuroinflammation and neurodegeneration in MS. In this scenario, we propose a new potential downstream signaling of Nrf2 pathway, namely the opening of hemichannels and pannexons. These large-pore channels are known to modulate glial/neuronal function and ROS production as they are permeable to extracellular Ca2+ and release potentially harmful transmitters to the synaptic cleft. In this way, the Nrf2 dysfunction impairs not only the bioenergetics and metabolic properties of glial cells but also the proper antioxidant defense and energy supply that they provide to neurons.

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“…O acompanhamento por fisioterapeutas e terapeutas ocupacionais auxiliam na recuperação de surtos e manutenção da independência funcional dos pacientes. O acompanhamento emocional e cognitivo feito por psicólogos e neuropsicólogos permite cuidar da preservação da autoestima e minimizar os déficits cognitivos que surgem em decorrência das lesões (Humphries, 2012). Outras intervenções podem ser igualmente benéficas para as pessoas com esclerose múltipla e seus familiares.…”

Section: Samira Maria Fiorotto and Sabrina Martins Barrosounclassified

Relato de Experiência em Acompanhamento Cognitivo com um Paciente com Esclerose Múltipla

Fiorotto

Barroso

2015

Psicol. cienc. prof.

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Resumo: A Esclerose Múltipla (EM) é uma doença crônica e autoimune, caracterizada por desmielinização, inflamação e neurodegeneração do Sistema Nervoso Central. Entre 30 e 50% dos indivíduos com EM apresentam comprometimento cognitivo. O processo de reabilitação cognitiva visa capacitar o paciente a conviver, reduzir e/ou superar os déficits cognitivos decorrentes da doença. Este trabalho relata a experiência de uma estagiária de Psicologia ao participar de um projeto de extensão universitária de acompanhamento cognitivo a um paciente com EM. Inicialmente o paciente foi submetido à avaliação neuropsicológica, identificando funções cognitivas preservadas e déficits. Foram observados déficits na recordação tardia, compreensão léxica, compreensão aritmética e aprendizagem numérica. Posteriormente, o paciente recebeu acompanhamento cognitivo semanal pelo período de seis meses. Após o período do acompanhamento, foi feita a reavaliação neuropsicológica. Observou-se melhora significativa na capacidade de recordação tardia e na aprendizagem aritmética, que deixaram de consistir em déficits. Além disso, houve abrandamento do déficit na compreensão aritmética. Os demais resultados permaneceram sem alterações. O trabalho mostra o impacto positivo que o acompanhamento cognitivo pode trazer ao paciente com EM e como a experiência de extensão pode auxiliar na formação dos estudantes de Psicologia. Palavras-chave: Esclerose Múltipla. Terapia Cognitiva. Esclerose Múltipla, Reabilitação.Abstract: Multiple sclerosis (MS) is a chronic, autoimmune disease characterized by demyelination, inflammation, and neurodegeneration of the central nervous system. Between 30% and 50% of individuals with MS have cognitive impairment. Thus, the process of cognitive rehabilitation aims to enable the patient to live, reduce, and/or overcome the cognitive deficits of the disease. This study reports the experience of an undergraduate psychology extension project that implemented cognitive monitoring with a patient suffering from MS. Initially, the patient submitted to a neuropsychological assessment that identified deficits and preserved cognitive functions. The evaluation also showed deficits in long-term memory, lexical comprehension, arithmetic understanding, and learning. Subsequently, the patient received weekly cognitive monitoring for a period of six months. After the monitoring period, the patient made a neuropsychological reassessment in which a significant improvement in long-term memory and arithmetic understanding was found. Although the other results remained unchanged, this study shows that cognitive monitoring can have a positive impact on patients with MS. It also shows how the experience of an extension project can assist in the training of psychology students. Keywords: Multiple Sclerosis. Cognitive Therapy. Multiple Sclerosis, Reahabilitation.Resumen: La esclerosis múltiple (EM) es una enfermedad crónica, autoinmune, caracterizada por la desmielinización, la inflamación y la neurodegeneración del sistema nervioso central. Entre el...

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Progressive multiple sclerosis: The treatment gap

Cited by 15 publications

References 0 publications

High Levels of Perivascular Inflammation and Active Demyelinating Lesions at Time of Death Associated with Rapidly Progressive Multiple Sclerosis Disease Course: A Retrospective Postmortem Cohort Study

High Levels of Perivascular Inflammation and Active Demyelinating Lesions at Time of Death Associated with Rapidly Progressive Multiple Sclerosis Disease Course: A Retrospective Postmortem Cohort Study

Neurodegeneration in Multiple Sclerosis: The Role of Nrf2-Dependent Pathways

Relato de Experiência em Acompanhamento Cognitivo com um Paciente com Esclerose Múltipla

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