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Chronic traumatic encephalopathy neuropathology might not be inexorably progressive or unique to repetitive neurotrauma.

In the 20th century, chronic traumatic encephalopathy (CTE) was conceptualized as a neurological disorder affecting some active and retired boxers who had tremendous exposure to neurotrauma. In recent years, the two research groups in the USA who have led the field have asserted definitively that CTE is a delayed-onset and progressive neurodegenerative disease, with symptoms appearing in midlife or decades after exposure. Between 2005 and 2012 autopsy cases of former boxers and American football players described neuropathology attributed to CTE that was broad and diverse. This pathology, resu

Regulated cell death in autoimmune diseases: molecular mechanisms and therapeutic opportunities.

Autoimmune diseases develop from a breakdown in immune tolerance and arise through complex interactions among genetic susceptibility, enviro … such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis, sjögren's syndrome, systemic sclerosis, type 1 diabetes, ulcerative colitis, dermatomyositis, ankylosing spondylitis, Chronic Dermatitis, antiphospholipid syndrome, Nephritis, and ANCA-associated vasculitis. These pathways do not function independe …

Воздействие когнитивной реабилитации и физических упражнений на структуру мозга при прогрессивном множественном склерозе: результаты испытания CogEx.

Ранее мы демонстрировали повышенный объем кортикальной серой материи (GM) у участников судебных процессов по делу CogEx, которые проводили когнитивную реабилитацию (CR). Здесь мы изучаем комбинированное воздействие CR и аэробных упражнений (EX) на региональные изменения в объемах мозга и целостности белых веществ (WM). Семьдесят три пациента были произвольно разбиты на четыре группы, которые получили комбинацию CR и EX или их фальшивые версии: CR + EX, CR + EX-sham, EX + CR-sham и CR-sham + EX-sham. Для включения в программу требуется диагностика прогрессивного множественного склероза (ПМС) и

Совпадение в аннотации оригинала
BACKGROUND: We previously showed increased cortical grey matter (GM) volume in CogEx trial participants who performed cognitive rehabilitati … am versions: CR + EX, CR + EX-sham, EX + CR-sham, and CR-sham + EX-sham. A diagnosis of progressive multiple sclerosis (PMS) and impaired information processing speed were required for inclusion. Participants attended a 12-week intervention twice/week. Assessments were performed at baseline, week-12 (W12), and nine months post-baseline (M9). Structural MRI scans wer …

Safety assessment of switching from fingolimod to siponimod: An Italian multicenter prospective study.

INTRODUCTION: Safety concerns have been raised regarding fingolimod to siponimod transition in people with Secondary Progressive Multiple Sclerosis (SPMS). OBJECTIVE: To explore factors associated with the choice of switching from fingolimod to siponimod and the safety of this sequencing. METHODS: We conducted a prospective observational study that included patients who had a confirmed diagnosis of SPMS at the time of study entry and had been treated with fingolimod for at least two years. Upon enrollment, patients either continued fingolimod (comparator group) or transitioned to siponimod (…

Cannabinoids in multiple sclerosis: A neurophysiological analysis.

OBJECTIVES: To investigate the action of cannabinoids on spasticity and pain in secondary progressive multiple sclerosis, by means of neurophysiological indexes. MATERIAL AND METHODS: We assessed 15 patients with progressive MS (11 females) using clinical scales for spasticity and pain, as well as neurophysiological variables (H/M ratio, cutaneous silent period or CSP). Testing occurred before (T0) and during (T1) a standard treatment with an oral spray containing delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Neurophysiological measures at T0 were compared with those of 14 healthy…

Ocrelizumab Treatment in Patients with Primary Progressive Multiple Sclerosis: Short-term Safety Results from a Compassionate Use Programme in Germany.

OBJECTIVES: In January 2018, the European Union (EU) approved ocrelizumab in relapsing multiple sclerosis (RMS) and as the first disease-modifying therapy (DMT) for patients with primary progressive multiple sclerosis (PPMS) with efficacy proven in a phase 3 randomised controlled trial. Eleven months prior to the European regulatory approval, a compassionate use programme (CUP) made ocrelizumab available to 489 patients with PPMS in Germany, thereby for the first time providing a therapeutic option to patients with PPMS who could not participate in ocrelizumab studies. Here, we report real-wor…

Strabismus surgery for internuclear ophthalmoplegia with exotropia in multiple sclerosis.

BACKGROUND: Internuclear ophthalmoplegia (INO) is a disabling condition affecting up to 40% of patients with multiple sclerosis (MS). Management of bilateral internuclear ophthalmoplegia (BINO) with exotropia in MS has been controversial because of the uncertain course of MS. Diplopia associated with INO severely impacts the patient's quality of life and, therefore, treatment should be considered. METHODS: Three patients (ages 28, 62, and 82 years) who had BINO with exotropia and disabling diplopia secondary to MS underwent bilateral medial rectus resections with either unilateral or bilatera…

[A case of primary progressive multiple sclerosis with onset of memory impairment].

We report a 52-year-old woman with primary progressive multiple sclerosis (PPMS) presenting with chronic progressive memory impairment. From a couple of years prior to admission, she had developed impairment of her short-term memory. For example, she forgot her nephew's name, and spoke the same phrases again and again. She also sometimes forgot to turn off her gas stove and forgot things she bought in shops. Moreover, her mental activity gradually decreased and she became apathetic. However, she did not note her memory impairment, and had no hallucinations. She was admitted to our hospital on …

Циклоксигеназы-1 и циклоксигеназы-2, измеряемые с помощью позитронной томографии, не изменяются в мозгах людей со стабильным множественным склерозом.

Множественный склероз (MS) — хроническое воспалительное заболевание, затрагивающее центральную нервную систему, которое включает в себя иммунную демиэлизацию и аксонное дегенерацию. Технологии клинической съемки играют важнейшую роль в диагностике и оценке прогнозов в отношении MS. Магнитные резонансные изображения чаще всего используются для визуализации обезвоживания и выявления острых и хронических активных повреждений, которые являются ключевыми показателями клинического курса болезни. Предыдущие исследования также выявили эффективность белка транслокатора 18-kDa (TSPO) позитрона выбросов

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system that involves immune-mediated demyelination and axonal degeneration. Clinical imaging techniques play a critical role in diagnosing and assessing the prognosis of MS. Magnetic resonance imaging has been most frequently used to visualize demyelination and detect acu…

Chronic traumatic encephalopathy neuropathologic change in former Australian rugby players.

AIMS: We applied the 2021 consensus criteria for both chronic traumatic encephalopathy neuropathological change and traumatic encephalopathy syndrome in a small case series of six former elite-level Australian rugby code players. METHODS: Neuropathological assessment of these cases was carried out at the Sydney and Victorian Brain Banks. Clinical data were collected via clinical interviews and health questionnaires completed by the participants and/or their next of kin, and neuropsychological testing was conducted with participants who were capable of completing this testing. RESULTS: All ca

Патогенетическое участие аутоматики и митофагии в первичном прогрессивном мультиклерозе.

Первичный прогрессивный множественный склероз (ППМС) влияет на поднабор пациентов, страдающих НР, и характеризуется непрерывным развитием с самого начала. Молекулярные механизмы, лежащие в основе РРМС, плохо понимаются, а возможности лечения ограничены, при этом отсутствуют конкретные маркеры для раннего обнаружения и мониторинга. В ходе этого исследования изучалась роль автофагии и митофагии в РРМС. Мы обнаружили, что автофагичные маркеры (ATG5 и ATG7) и митофагиевые маркеры (Parkin and Optineurin) были значительно сокращены в сыворотке пациентов, получающих ПУПМ, по сравнению с лицами, осуще

Совпадение в аннотации оригинала
Primary progressive multiple sclerosis (PPMS) affects a subset of MS patients and is characterised by continuous progression from the onset. The molecular mechanisms underlying PPMS are poorly understood, and therapeutic options are limited, with no specific markers for early detection and monitoring. This study investigated the roles of autophagy and mitoph…

Cerebrospinal fluid insulin-like growth factor 1 is low in acute and chronic white-matter diseases of children.

Insulin-like growth factor 1 increases both the number of oligodendrocytes and the amount of axonal myelin produced. The aim of this study was to see whether insulin-like growth factor 1 played a role in white-matter diseases of children. We studied insulin-like growth factor 1 in the cerebrospinal fluid of children with various white-matter diseases: (1) children with acute demyelinating events: acute disseminated encephalomyelitis (n = 5), acute transverse myelitis in multiple sclerosis (n = 1), and infarct of the medial cerebral artery causing secondary white-matter changes (n = 1), and (2)…

Misfolding protein pathology detected in a chronic mouse model of multiple sclerosis.

Multiple sclerosis (MS) is one of the most common causes of neurological disability in young adults. The pathobiology of MS includes both autoimmune inflammation and underlying degeneration, with the current challenge being to better understand and treat MS progression. The cuprizone (CPZ) mouse model is commonly used to study de- and remyelination. Despite initial robust myelin repair after toxin withdrawal, mice display progressive callosal atrophy, myelin loss, and gliosis. We tested the hypothesis that this delayed demyelination is due to a progressive degenerative proteopathy. Male C57BL/…

Vidofludimus calcium for the treatment of multiple sclerosis: development rationale, mechanism of action, and early trial data.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune condition of the central nervous system associated with progressive disability. Safe and well tolerated treatments targeting both inflammatory and neurodegenerative processes are needed to address the spectrum of MS pathophysiology. AREAS COVERED: Vidofludimus calcium is a potent, orally available direct activator of nuclear receptor-related 1 (Nurr1) protein and selective dihydroorotate dehydrogenase (DHODH) inhibitor. The article explores the chemistry, mechanisms of action, and pharmacokinetics of vidofludimus calcium. Furthermore, pre…

От патогенеза к точной медицине: выявление иммунного дисбаланса в множественных склерозах.

Множественный склероз (MS) — хроническое нервно-воспалительное и нейродегенеративное заболевание, которое по-прежнему является одной из основных причин нетравматической инвалидности у молодых людей. Срочная необходимость проведения исследований в области НР никогда не была еще более острой, поскольку масштабы распространения и распространения ВИЧ/СПИДа в мире растут, а пациенты по-прежнему сталкиваются с задержками в диагностике, неполным реагированием на терапию и ограниченными возможностями для прогрессивных заболеваний. Достигнутый в последнее время прогресс в определении стадий заболеваний

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that remains a leading cause of non-traumatic disability in young adults. The urgency to advance MS research has never been greater, as global incidence and prevalence are rising, and patients continue to face delays in diagnosis, incomplete response to therapies, and limite…

Effect of optic neuritis on progressive axonal damage in multiple sclerosis patients.

OBJECTIVE: The objective of this research was to study the effect of optic neuritis (ON) on axonal damage in multiple sclerosis (MS) patients. Specifically, we compared changes over 2 years in the retinal nerve fibre layer (RNFL) between affected and contralateral eyes in MS patients with a prior history of ON. METHODS: Thirty-four patients with one unilateral definitive episode of ON were included and underwent a complete ophthalmic examination, optical coherence tomography (OCT), scanning laser polarimetry, visual evoked potentials (VEP) and pattern electroretinogram (pERG). All patients we…

Selective GPR17 antagonism enhances structural and functional recovery in animal models of demyelination.

Myelination, driven by differentiation of oligodendrocyte precursor cells, is critical for metabolic and structural support and efficient axonal signal transmission in neurons. Loss of myelin is a hallmark of multiple sclerosis and other devastating demyelinating disorders. As demyelination persists, neurons become increasingly vulnerable, leading to neurodegeneration and chronic disability. Restoring myelin through endogenous repair mechanisms offers a promising therapeutic approach to mitigate progressive neuronal loss. One key regulator of myelination is the G protein-coupled receptor 17, G…

Multiple sclerosis and Natalizumab.

Natalizumab (NTZ), defined as "the first of a new class of drugs known as elective adhesion molecule inhibitors" was developed at the beginning of 2003 to treat relapsing-remitting multiple sclerosis (MS) and was approved in the United States in November 2004. In February 2005, the production of NTZ was suspended by Producer Firms on account of the occurrence of two serious adverse events: two patients who had been taking NTZ manifested a progressive multifocal leukoencephalopathy; the patients showed progressive neurologic deterioration, initially believed to be a worsening of the pre-existin…

Epigenetic insights into multiple sclerosis disease progression.

Multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system, is today a leading cause of unpredictable lifelong disability in young adults. The treatment of patients in progressive stages remains highly challenging, alluding to our limited understanding of the underlying pathological processes. In this review, we provide insights into the mechanisms underpinning MS progression from a perspective of epigenetics, that refers to stable and mitotically heritable, yet reversible, changes in the genome activity and gene expression. We fir…

Varicella zoster virus in progressive forms of multiple sclerosis.

OBJECTIVE: The apparent association between varicella zoster virus (VZV) and multiple sclerosis (MS) has been described. In patients with relapse/remission (R/R) MS we have found high loads of VZV DNA in lymphocytes and in cerebrospinal fluid (CSF), as well as abundant viral particles in CSF visualized by electron microscopy at the time of relapse. Both, the molecular and the ultrastructural evidence of VZV became negative in the same patients at the time of remission. METHODS: In the present study we analyzed the presence of VZV in patients with progressive forms of MS; DNA from VZV was sear…