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Effect of Fingolimod on Neural Stem Cells: A Novel Mechanism and Broadened Application for Neural Repair.

Inflammatory demyelination and axonal damage of the CNS are hallmarks of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Fingolimod (FTY720), the first FDA-approved oral medication for MS, suppresses acute disease but is less effective at the chronic stage, and whether it has a direct effect on neuroregeneration in MS and EAE remains unclear. Here we show that FTY720, at nanomolar concentrations, effectively protected survival of neural stem cells (NSCs) and enhanced their development into mature oligodendrocytes (OLGs) in vitro, primarily through…

[Analysis of clinical features for 8 patients with autoimmune dementia].

OBJECTIVE: To explore the clinical features and therapeutic profiles of autoimmune dementia. METHODS: Eight hospitalized patients with autoimmune dementia during March 2011 and May 2013 were recruited and retrospectively analyzed for clinical features, as well as therapeutic and prognosis profiles. RESULTS: There were 3 males and 5 females with a onset age range of 45-72 years. Their onsets varied from acute (n = 3), subacute (n = 1) to chronic (n = 4).Six of them had a fluctuating course. The diagnoses were multiple sclerosis (n = 3), paraneoplastic limbic encephalitis (n = 2) and Hashimoto…

Relapsing optic neuritis: a multicentre study of 62 patients.

BACKGROUND: Optic neuritis (ON) may be the first symptom of a central nervous system demyelinating, systemic or infectious disease but few p … ONCLUSION: RON is likely a separate entity corresponding to an autoimmune disease that differs from multiple sclerosis (MS), NMO and vasculitis. We provide a new classification system based on a better understanding of RON which could allow an improved management by early treatment of poor prognosis forms.

Comparison of the clinical courses of the opticospinal and conventional forms of multiple sclerosis in Japan.

We evaluated the clinical courses of 216 patients with multiple sclerosis (MS) diagnosed according to the recommended diagnostic criteria of McDonald et al (10). Sixty-five patients clinically displaying selective involvement of the optic nerves and spinal cord were classified as opticospinal MS (OS-MS), while the other 151 showing disseminated involvement of the central nervous system were classified as conventional MS (C-MS). The disease duration did not differ significantly between the two subtypes (11.2 years vs. 11.5 years). In addition to a higher age of onset, female preponderance and h…

Lower Motor Neuron Disease Misclassified As Inflammatory Myopathy in a Young Woman With Myositis-Specific Antibodies.

A 30-year-old woman presented with slowly progressive neck and proximal limb weakness over three years. Initial evaluation showed moderate creatine kinase elevation, anti-Mi-2β and anti-glycyl-tRNA synthetase (EJ) positivity, and electrophysiological and muscle biopsy findings interpreted as inflammatory myopathy. She was diagnosed with polymyositis and received multiple immunosuppressive therapies without clinical improvement. Despite normalization of creatine kinase, weakness and muscle wasting progressed. Re-evaluation revealed profound generalized atrophy, hyporeflexia, widespread limb and

Digital Pathology Identifies Associations between Tissue Inflammatory Biomarkers and Multiple Sclerosis Outcomes.

BACKGROUND: Multiple sclerosis (MS) is a clinically heterogeneous disease underpinned by inflammatory, demyelinating and neurodegenerative processes, the extent of which varies between individuals and over the course of the disease. Recognising the clinicopathological features that most strongly associate with disease outcomes will inform future efforts at patient phenotyping. AIMS: We used a digital pathology workflow, involving high-resolution image acquisition of immunostained slides and opensource software for quantification, to investigate the relationship between clinical and neuropatho…

Перепрофилирование многочисленных методов склерозовой терапии с помощью микробной иммунодуляции и эпигенетического контроля.

Множественный склероз (MS) — хроническое аутоиммунное расстройство, отмеченное иммунной демиэлизацией и нейродегенерацией в центральной нервной системе. В настоящем Обзоре рассматриваются иммунологические, молекулярные и эпигенетические основы MS с уделением особого внимания участию клеток T и B, дисрегулированным каналам подачи сигналов (например, TGF-β, Akt, Wnt) и роли смерти клеток в прогрессировании заболеваний. Эпигенетические механизмы, такие, как метилация ДНК и модификации гистона, еще больше модифицируют иммунную реакцию. В то время как нынешняя терапия в целом подавляет иммунитет, н

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disorder marked by immune-driven demyelination and neurodegeneration in the central nervous system. This Review explores the immunological, molecular, and epigenetic underpinnings of MS, emphasizing T and B cell involvement, dysregulated signaling pathways (e.g., TGF-β, Akt, Wnt), and the role of cell death in …

Intravenous immunoglobulin therapy for scleromyxedema: a case report and review of literature.

Scleromyxedema is a chronic, idiopathic disorder characterized by cutaneous dermal mucin deposition in association with increased dermal collagen and absence of thyroid disease. The clinical features involve sclerosis of skin with numerous, 2-3 mm, firm, waxy, papules in a symmetrical distribution pattern. The skin lesions may progress to widespread and indurated plaques resulting in patient disability via decreased mobility, sclerodactyly and microstomia. Abnormalities in the muscular, neurologic, rheumatologic, pulmonary, renal and cardiovascular systems may accompany the cutaneous lesions.

[Use of immunoglobulins G in the treatment of nervous system diseases].

Short term and long term beneficial effects of IgG administration have been studied in 4 groups of neuro-immunological diseases: Polymyositis, dermatomyositis and myasthenia. Peripheral neuropathies (myelinopathies), primarily in Guillain-Barré syndrome and in chronic inflammatory polyneuropathy. Children intractable Epilepsy. Multiple Sclerosis. Actual results are in favor of an objective and marked improvement (after 1 or 2 months) in the first 2 groups using intravenous IgG. In M.S. patients, the short term treatment of bouts (especially: optic neuritis) seems promising. Results of the only…

B-Cell Depletion as Evidence for Shared Neuroimmune Pathways in Combined Central and Peripheral Demyelination: A Case Report and Literature Review.

Combined central and peripheral demyelination (CCPD) is a rare neuroimmunological condition involving inflammatory demyelination of both the central nervous system (CNS) and peripheral nervous system (PNS). We report a chronic progressive CCPD case initially diagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP) and treated with conventional CIDP-directed immunotherapies, with subsequent development of multiple sclerosis (MS)-like CNS demyelination. An extensive diagnostic evaluation excluded alternative infectious, metabolic, paraneoplastic, and antibody-mediated etiologies aff…

The cGAS-STING Pathway Drives Astrocyte-Mediated Demyelination in Multiple Sclerosis Through Clusterin Secretion.

BACKGROUND: Multiple sclerosis (MS) is a chronic neuroinflammatory disorder characterized by oligodendrocyte injury and demyelination. The disease progresses from peripheral immune attacks to compartmentalized central nervous system (CNS) inflammation, culminating in irreversible neurodegeneration. Although current immunotherapies suppress peripheral relapses, they inadequately address compartmentalized CNS inflammation and progressive neurodegeneration. METHODS: We reanalyzed published single-nucleus RNA-seq datasets from human MS lesions. Primary astrocytes, oligodendrocytes, and organotypi…

Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis.

Given the abnormalities in B-cell activity occurring in the central nervous system (CNS) of patients with multiple sclerosis (MS), we have explored the possibility that CNS inflammation induced in mouse models of experimental autoimmune encephalomyelitis (EAE) triggers expression of molecules that control the development and functional organization of lymphoid follicles, the sites where B-cell responses are initiated. By reverse transcription-polymerase chain reaction (RT-PCR), we find that gene expression of CXCL13, a chemokine involved in B-cell recruitment into lymphoid follicles, and BAFF,…

[Blood levels of soluble ICAM-1 in patients with multiple sclerosis].

INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The Intercellular Adhesion Molecule plays a fundamental part in the migration of T cells to the inflammed tissues. It is known that there is an increase in the expression of endothelial cells and other cells found in lesions of the central nervous system of MS patients. ICAM-I may be detected in its soluble form in serum and it is of interest to understand its behaviour in this liquid since it is easily accessible. MATERIAL AND METHODS: We studied the concentration of soluble ICAM-I in the s…

Myeloid ATP Citrate Lyase Regulates Macrophage Inflammatory Responses In Vitro Without Altering Inflammatory Disease Outcomes.

Macrophages are highly plastic, key regulators of inflammation. Deregulation of macrophage activation can lead to excessive inflammation as seen in inflammatory disorders like atherosclerosis, obesity, multiple sclerosis and sepsis. Targeting intracellular metabolism is considered as an approach to reshape deranged macrophage activation and to dampen the progression of inflammatory disorders. ATP citrate lyase (Acly) is a key metabolic enzyme and an important regulator of macrophage activation. Using a macrophage-specific Acly-deficient mouse model, we investigated the role of Acly in macropha…

Early recognition of chronic rejection in a face allotransplant patient with alopecia.

The features of chronic rejection (CR) in full-face vascularized composite allotransplantation (VCA) are not well-known. Herein, we report a full-face transplant patient that experienced two episodes of acute rejection (AR) and three episodes of AR/CR over the course of 6-years. The patient noticed a small, round patch of hair loss in his beard 9 months after the second AR episode, which occurred 21 months post-transplantation. Biopsy of the alopecic patch showed lichen-planopilaris-like features, which were suggestive of early CR. Despite an increase in immunosuppressive dosages, the alopecia

Dementia in the Forensic Setting: Diagnoses Obtained Using a Condensed Protocol at the Office of Chief Medical Examiner, New York City.

Individuals with dementia may come to forensic autopsy, partly because of non-natural deaths (e.g. fall-related), and/or concerns of abuse/neglect. At the New York City Office of Chief Medical Examiner (NYC OCME), brains from such cases are submitted for neurodegenerative disease (ND) work-up. Seventy-eight sequential cases were evaluated using a recently published condensed protocol for the NIA-AA guidelines for the neuropathologic assessment of Alzheimer disease (AD), a cost-cutting innovation in diagnostic neuropathology. ND was identified in 74 (94.9%) brains; the most common were AD (n = 

Systemic sclerosis complicated with localized scleroderma-like lesions induced by Köbner phenomenon.

BACKGROUND: Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities. OBJECTIVE: We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology. METHODS: Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized. RESULTS: SSc patients wi

[Recent advances in the treatment the nervous system disorders with interferon-alpha].

INTRODUCTION: The interferons (IFN) have had considerable effect on the course of relapses and the natural course of the disability of patients with multiple sclerosis (MS). However, the effects of IFN in other neurological disorders are little known. OBJECTIVES: To review the literature on the experimental and clinical applications of the IFN in disorders of the nervous system excluding MS. DEVELOPMENT: We reviewed studies of the applications of the IFN in viral diseases (experimental and human rabies, herpes zoster, herpes virus, non-herpetic meningoencephalitic viruses, HTLV-I myelopathy,…

Maintenance of chronic neuroinflammation in multiple sclerosis via interferon signaling and CD8 T-cell-mediated cytotoxicity.

Chronic neuroinflammation and neurodegeneration are critical but unresolved drivers of disability accumulation in progressive multiple sclerosis (MS). Chronic active white matter lesions, identifiable radiologically as paramagnetic rim lesions (PRL), indicate progression-relevant chronic neuroinflammation. Using single-cell transcriptomics (scRNAseq) and T-cell receptor sequencing (scTCR-seq), we profiled cerebrospinal fluid (CSF) and blood immune cells of 34 radiologically characterized adults with MS (17 untreated, 6 treated with B-cell-depletion) and 5 healthy controls. Coupled with proteom…

CAR Treg therapies for neurodegenerative diseases.

Regulatory T cells (Tregs) promote immune tolerance by recognizing non-foreign self-antigens. Consequently, Tregs suppress chronic immune re … eg therapies can treat Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. In each case, a Treg-based approach transforms a neurotoxic, inflammatory environment through neurotrophic responses. By doing so, CAR Tregs may restore brain balance and slow disease progression. This review highlights ongoing efforts to develop C …