Clinicopathological features of inflammatory demyelinating diseases in biopsy.
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ABSTRACT:
SUBMITTER: Wei J
PROVIDER: S-EPMC7213618 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
Publications
Clinicopathological features of inflammatory demyelinating diseases in biopsy.
Wei Jia J Xu Wei-Wei WW Wang Ke-Jie KJ Fu Yong-Juan YJ Piao Yue-Shan YS Lu De-Hong DH
Chinese medical journal 20200501 9
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Project description:BackgroundNeuromyelitis optica spectrum disorder (NMOSD) stands out among CNS inflammatory demyelinating diseases (CIDDs) due to its unique disease characteristics, including severe clinical attacks with extensive lesions and its association with systemic autoimmune diseases. We aimed to investigate whether characteristics of B cell receptors (BCRs) differ between NMOSD and other CIDDs using high-throughput sequencing.MethodsFrom a prospective cohort, we recruited patients with CIDDs and categorized them based on the presence and type of autoantibodies: NMOSD with anti-aquaporin-4 antibodies, myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) with anti-myelin oligodendrocyte glycoprotein antibodies, double-seronegative demyelinating disease (DSN), and healthy controls (HCs). The BCR features, including isotype class, clonality, somatic hypermutation (SHM), and the third complementarity-determining region (CDR3) length, were analyzed and compared among the different disease groups.ResultsBlood samples from 33 patients with CIDDs (13 NMOSD, 12 MOGAD, and 8 DSN) and 34 HCs were investigated for BCR sequencing. Patients with NMOSD tended to have more activated BCR features compare to the other disease groups. They showed a lower proportion of unswitched isotypes (IgM and IgD) and a higher proportion of switched isotypes (IgG), increased clonality of BCRs, higher rates of SHM, and shorter lengths of CDR3. Notably, advanced age was identified as a clinical factor associated with these activated BCR features, including increased levels of clonality and SHM rates in the NMOSD group. Conversely, no such clinical factors were found to be associated with activated BCR features in the other CIDD groups.ConclusionsNMOSD patients, among those with CIDDs, displayed the most pronounced B cell activation, characterized by higher levels of isotype class switching, clonality, SHM rates, and shorter CDR3 lengths. These findings suggest that B cell-mediated humoral immune responses and characteristics in NMOSD patients are distinct from those observed in the other CIDDs, including MOGAD. Age was identified as a clinical factor associated with BCR activation specifically in NMOSD, implying the significance of persistent B cell activation attributed to anti-aquaporin-4 antibodies, even in the absence of clinical relapses throughout an individual's lifetime.
| S-EPMC10548735 | biostudies-literature
Project description:Myelin oligodendrocyte glycoprotein (MOG), a member of the immunoglobulin (Ig) superfamily, is a myelin protein solely expressed at the outermost surface of myelin sheaths and oligodendrocyte membranes. This makes MOG a potential target of cellular and humoral immune responses in inflammatory demyelinating diseases. Due to its late postnatal developmental expression, MOG is an important marker for oligodendrocyte maturation. Discovered about 30 years ago, it is one of the best-studied autoantigens for experimental autoimmune models for multiple sclerosis (MS). Human studies, however, have yielded controversial results on the role of MOG, especially MOG antibodies (Abs), as a biomarker in MS. But with improved detection methods using different expression systems to detect Abs in patients' samples, this is meanwhile no longer the case. Using cell-based assays with recombinant full-length, conformationally intact MOG, several recent studies have revealed that MOG Abs can be found in a subset of predominantly pediatric patients with acute disseminated encephalomyelitis (ADEM), aquaporin-4 (AQP4) seronegative neuromyelitis optica spectrum disorders (NMOSD), monophasic or recurrent isolated optic neuritis (ON), or transverse myelitis, in atypical MS and in N-methyl-d-aspartate receptor-encephalitis with overlapping demyelinating syndromes. Whereas MOG Abs are only transiently observed in monophasic diseases such as ADEM and their decline is associated with a favorable outcome, they are persistent in multiphasic ADEM, NMOSD, recurrent ON, or myelitis. Due to distinct clinical features within these diseases it is controversially disputed to classify MOG Ab-positive cases as a new disease entity. Neuropathologically, the presence of MOG Abs is characterized by MS-typical demyelination and oligodendrocyte pathology associated with Abs and complement. However, it remains unclear whether MOG Abs are a mere inflammatory bystander effect or truly pathogenetic. This article provides deeper insight into recent developments, the clinical relevance of MOG Abs and their role in the immunpathogenesis of inflammatory demyelinating disorders.
| S-EPMC5420591 | biostudies-literature
Project description:Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disease that mainly affects the peripheral nerves and nerve roots and typically presents with distal dominant motor and sensory disturbances as clinical symptoms. Central nervous system (CNS) demyelination with inflammation occurs infrequently in patients with CIDP. Here, we present a unique autopsy report of CIDP causing severe demyelination along the entire spinal cord. A Japanese woman exhibited progressive muscle weakness, muscle atrophy, sensory disturbances, and tremors in her upper and lower extremities, which began in her 60s. A nerve conduction study revealed a marked prolongation of distal latencies and very low or no compound muscle action potential amplitudes, and cerebrospinal fluid protein levels were prominently elevated. Following the diagnosis of CIDP, a combination of methylprednisolone pulse therapy, high-dose intravenous immunoglobulin therapy, and plasma exchange mildly improved her symptoms. The patient died of septic shock at the age of 74 years. Neuropathological examination revealed demyelinating lesions with inflammation in the peripheral regions of the anterior, lateral, and posterior funiculi along the entire spinal cord (from the cervical to the sacral cord), and axons and neurons were well preserved in these lesions. The nerve roots in the cervical and lumbar plexuses, cauda equina, sciatic nerve, and sural nerve showed prominent swelling and edema with infiltration of inflammatory cells. Many onion bulbs were visible in the fascicles of the sciatic and sural nerves. Our results suggest that demyelination with inflammation can occur in the CNS and peripheral nervous system in CIDP, especially in patients with specific conditions, such as severe intrathecal inflammation.
| S-EPMC11655328 | biostudies-literature
Project description:Current treatments for central nervous system (CNS) inflammatory demyelinating diseases (IDDs) include corticosteroids, plasma exchange, intravenous immunoglobulin, and immunosuppressant drugs. However, some patients do not respond well to traditional therapies. In recent years, novel drugs, such as monoclonal antibodies, targeting the complement component C5, CD19 on B cells, and the interleukin-6 (IL-6) receptor, have been used for the treatment of patients with refractory CNS IDDs. Among these, tocilizumab and satralizumab, humanized monoclonal antibodies against the IL-6 receptor, have shown beneficial effects in the treatment of this group of diseases. In this review, we summarize current research progress and prospects relating to anti-IL-6 therapies in CNS IDDs.
| S-EPMC9647084 | biostudies-literature
Project description:BackgroundDistinguishing between central nervous system lymphoma (CNSL) and CNS infectious and/or demyelinating diseases, although clinically important, is sometimes difficult even using imaging strategies and conventional cerebrospinal fluid (CSF) analyses. To determine whether detection of genetic mutations enables differentiation between these diseases and the early detection of CNSL, we performed mutational analysis using CSF liquid biopsy technique.MethodsIn this study, we extracted cell-free DNA from the CSF (CSF-cfDNA) of CNSL (N = 10), CNS infectious disease (N = 10), and demyelinating disease (N = 10) patients, and performed quantitative mutational analysis by droplet-digital PCR. Conventional analyses were also performed using peripheral blood and CSF to confirm the characteristics of each disease.ResultsBlood hemoglobin and albumin levels were significantly lower in CNSL than CNS infectious and demyelinating diseases, CSF cell counts were significantly higher in infectious diseases than CNSL and demyelinating diseases, and CSF-cfDNA concentrations were significantly higher in infectious diseases than CNSL and demyelinating diseases. Mutation analysis using CSF-cfDNA detected MYD88L265P and CD79Y196 mutations in 60% of CNSLs each, with either mutation detected in 80% of cases. Mutual existence of both mutations was identified in 40% of cases. These mutations were not detected in either infectious or demyelinating diseases, and the sensitivity and specificity of detecting either MYD88/CD79B mutations in CNSL were 80% and 100%, respectively. In the four cases biopsied, the median time from collecting CSF with the detected mutations to definitive diagnosis by conventional methods was 22.5 days (range, 18-93 days).ConclusionsThese results suggest that mutation analysis using CSF-cfDNA might be useful for differentiating CNSL from CNS infectious/demyelinating diseases and for early detection of CNSL, even in cases where brain biopsy is difficult to perform.
| S-EPMC10501233 | biostudies-literature
Project description:ObjectivesSerum synaptic proteins levels may change with age-related neurodegeneration, affecting their clinical implications as a disease biomarker. We aimed to investigate neuronal and astroglial markers in patients with multiple sclerosis (MS) and aquaporin-4 antibody-seropositive neuromyelitis optica spectrum disorders (NMOSD) to compare the clinical implications of these markers according to age.MethodsUsing single-molecule array assays, we measured neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in sera from consecutive patients with MS (n = 117) and NMOSD (n = 63). For each disease, we assessed correlations between these markers and disease severity (Expanded Disability Status Scale [EDSS]) scores according to three age groups (≤44, 45-54, and ≥55 years).ResultsAlthough serum GFAP levels were significantly higher in patients with NMOSD than those with MS, levels of both serum markers revealed significant positive correlations with EDSS scores in both diseases. In MS patients, the degrees of correlation between serum NfL (or GFAP) levels and EDSS scores were similar across all age groups. However, in NMOSD patients, positive GFAP-EDSS correlations were distinctively stronger in the youngest than in the oldest group. Conversely, there were no positive NfL-EDSS correlations in NMOSD in the youngest group, but there were significant in the oldest group.InterpretationThe degrees to which serum NfL and GFAP levels reflect disease severity vary significantly with patient age in NMOSD, but not in MS. These findings suggest that the pathological processes and progression differ between the diseases; hence, serum biomarker levels may need to be interpreted differently according to patient age and disease type.
| S-EPMC7317646 | biostudies-literature
Project description:ObjectiveTo assess whether patients with acute inflammatory demyelinating polyneuropathy (AIDP) associated with SARS-CoV-2 show characteristic electrophysiological features.MethodsClinical and electrophysiological findings of 24 patients with SARS-CoV-2 infection and AIDP (S-AIDP) and of 48 control AIDP (C-AIDP) without SARS-CoV-2 infection were compared.ResultsS-AIDP patients more frequently developed respiratory failure (83.3% vs. 25%, P=0.000) and required intensive care unit (ICU) hospitalization (58.3% vs. 31.3%, P=0.000). In C-AIDP, distal motor latencies (DMLs) were more frequently prolonged (70.9% vs. 26.2%, P=0.000) whereas in S-AIDP distal compound muscle action potential (dCMAP) durations were more frequently increased (49.5% vs. 32.4%, P=0.002) and F waves were more often absent (45.6% vs. 31.8%, P=0.011). Presence of nerves with increased dCMAP duration and normal or slightly prolonged DML was elevenfold higher in S-AIDP (31.1% vs. 2.8%, P=0.000);11 S-AIDP patients showed this pattern in 2 nerves.ConclusionIncreased dCMAP duration, thought to be a marker of acquired demyelination, can also be oserved in critical illness myopathy. In S-AIDP patients, an increased dCMAP duration dissociated from prolonged DML, suggests additional muscle fiber conduction slowing, possibly due to a COVID-19-related hyperinflammatory state. Absent F waves, at least in some S-AIDP patients, may reflect α-motor neuron hypoexcitability because of immobilization during the ICU stay. These features should be considered in the electrodiagnosis of SARS-CoV-2 patients with weakness, to avoid misdiagnosis.
| S-EPMC7891083 | biostudies-literature
Project description:The present study reported on the histomorphological observations and immunohistochemical features of five cases of gastric inflammatory myofibroblastic tumor (IMT). Loosely arranged fat fusiform myofibroblast-fibroblasts and diffusely or patchily distributed inflammatory cells, which formed a diverse morphological structure, were observed. In the mucous vascular structure, mucoid or collagenous areas, fibromatosis- or scar-like lesions were generally <10 mm in size and both had diffuse or patchy plasma cells, lymphocytes and other inflammatory-cell infiltration backgrounds. The immunophenotype was vimentin- and smooth muscle actin-positive with pan-cytokeratin, desmin and calponin expression and CD34-positive foci; furthermore, three cases were positive for anaplastic lymphoma kinase expression. Gastric IMT is rare, with unique histopathological changes and corrosion-like invasion of the smooth muscle of the stomach wall, blood vessels, nerves and adipose tissue. It should be differentiated from a variety of spindle cell tumor types and tumor-like lesions.
| S-EPMC8290396 | biostudies-literature
Project description:Various vaccines have been developed in response to the SARS-CoV-2 pandemic, and the safety of vaccines has become an important issue. COVID-19 vaccine-related central nervous system inflammatory demyelinating diseases (CNS IDDs) have been reported recently. We present one case of AstraZeneca vaccine-related myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease and a literature review of another 78 patients published from January 2020 to October 2022. Patients were divided into three vaccine types (viral vector, mRNA, and inactivated vaccines) for further analyses. Among 79 patients with COVID-19 vaccine-related CNS IDDs, 49 (62%) cases received viral vector vaccines, 20 (25.3%) received mRNA vaccines, and 10 (12.7%) received inactivated vaccines. Twenty-seven cases (34.2%) were confirmed with autoantibodies, including fifteen patients (19%) with anti-MOG, eleven (13.9%) with anti-aquaporin 4 (AQP4), and one (1.3%) with both antibodies. Significantly, more males developed CNS IDDs post viral vector vaccines compared to mRNA and inactivated vaccines. Patients receiving mRNA vaccines were older than those receiving other types. Furthermore, mRNA and inactivated vaccines correlated more with anti-AQP4 antibodies, while viral vector vaccines showed higher MOG positivity. This research suggests potential associations between COVID-19 vaccine-related CNS IDDs and gender, age, and autoantibodies, contingent on vaccine types. Protein sequence analysis implies similarities between the S protein and AQP4/MOG. Further studies may elucidate the mechanisms of CNS IDDs, aiding vaccine selection for specific types.
| S-EPMC10969393 | biostudies-literature
Project description:ObjectivesTo describe lesional diffusion-weighted imaging characteristics in a cohort of patients with biopsy-proven CNS inflammatory demyelinating disease (IDD) and compare diffusion characteristics of ring-enhancing CNS IDD lesions vs abscesses and tumors.MethodsForty prebiopsy apparent diffusion coefficient (ADC) maps were reviewed from 30 patients with CNS IDD. Lesions were analyzed for size, T2-weighted (T2W) hypointense rim, enhancement, and ADC pattern. ADC patterns of CNS IDD ring-enhancing lesions were compared with a published cohort of 35 patients with ring-enhancing tumors and abscesses.ResultsIDD lesions displayed a spectrum of peripheral ADC patterns at the lesion edge: restricted diffusion (low ADC), 33%; increased diffusion (high ADC), 60%; and normal diffusion (homogeneously isointense), 7%. Of biopsied lesions, 93% enhanced (ring, 52%; heterogeneous, 34%; homogeneous, 7%). A hypointense T2W rim was observed in 53%. A ring pattern on ADC (isointense or dark) was associated with T2W hypointense rims (p = 0.02) but not with ring enhancement. On serial imaging, 4 of 7 (57%) patients demonstrated changes in ADC patterns. Peripheral restriction was more common in IDD (p = 0.006) than in tumors or abscesses, whereas central restriction was only observed in abscesses. Restricted lesions in the same stage were more common in the non-IDD cohort (42% vs 20%), with a uniform restricted pattern seen only in abscesses.ConclusionsIn ring-enhancing lesions, peripheral diffusion restriction is more common in IDD than in tumors/abscesses, whereas central restriction is more common among abscesses. Rapid ADC pattern changes in IDD probably reflect dynamic lesion evolution and may distinguish IDD from tumors.
| S-EPMC3359505 | biostudies-literature