Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.
Humans ; Multiple Sclerosis/pathology* ; Remyelination/physiology* ; Myelin Sheath/pathology* ; Inflammation/drug therapy* ; Homeostasis

Multiple sclerosis (MS) is regarded as a chronic inflammatory disease that leads to demyelination and eventually to neurodegeneration. Activation of innate immune cells and other inflammatory cells in the brain and spinal cord of people with MS has been well described. However, with the innovation of technology in glial cell research, we have a deep understanding of the mechanisms of glial cells connecting inflammation and neurodegeneration in MS. In this review, we focus on the role of glial cells, including microglia, astrocytes, and oligodendrocytes, in the pathogenesis of MS. We mainly focus on the connection between glial cells and immune cells in the process of axonal damage and demyelinating neuron loss.
Humans ; Multiple Sclerosis ; Neuroglia ; Inflammation/pathology* ; Brain/pathology* ; Spinal Cord/pathology*

PURPOSE: To describe a technique for urodynamic diagnosis of detrusor sphincter dyssynergia (DSD) using urethral pressure measurements and examine potential associations between urethral pressure and bladder physiology among patients with DSD. METHODS: Multiple sclerosis (MS) and spinal cord injured (SCI) patients with known DSD diagnosed on videourodynamics (via electromyography or voiding cystourethrography) were retrospectively identified. Data from SCI and MS patients with detrusor overactivity (DO) without DSD were abstracted as control group. Urodynamics tracings were reviewed and urethral pressure DSD was defined based on comparison of DSD and control groups. RESULTS: Seventy-two patients with DSD were identified. Sixty-two (86%) had >20 cm H₂O urethral pressure amplitude during detrusor contraction. By comparison, 5 of 23 (22%) of control group had amplitude of >20 cm H₂O during episode of DO. Mean duration of urethral pressure DSD episode was 66 seconds (range, 10–500 seconds) and mean urethral pressure amplitude was 73 cm H₂O (range, 1–256 cm H₂O). Longer (>30 seconds) DSD episodes were significantly associated with male sex (81% vs. 50%, P=0.013) and higher bladder capacity (389 mL vs. 219 mL, P=0.0004). Urethral pressure amplitude measurements during DSD were not associated with significant urodynamic variables or neurologic pathology. CONCLUSIONS: Urethral pressure amplitude of >20 cm H2O during detrusor contraction occurred in 86% of patients with known DSD. Longer DSD episodes were associated with larger bladder capacity. Further studies exploring the relationship between urethral pressure measurements and bladder physiology could phenotype DSD as a measurable variable rather than a categorical observation.
Ataxia* ; Diagnosis* ; Electromyography ; Humans ; Male ; Multiple Sclerosis ; Pathology ; Phenotype ; Physiology ; Retrospective Studies ; Spinal Cord ; Spinal Cord Injuries ; Urinary Bladder ; Urodynamics*

BACKGROUNDNeuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice.

METHODSData including the patients' serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables.

RESULTSTotally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (Δ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = -3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; Δ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; Δ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups.

CONCLUSIONThe different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

Adolescent ; Adult ; Aquaporin 4 ; blood ; cerebrospinal fluid ; Autoantibodies ; blood ; cerebrospinal fluid ; Demyelinating Diseases ; blood ; cerebrospinal fluid ; pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multiple Sclerosis ; blood ; cerebrospinal fluid ; pathology ; Myelin-Oligodendrocyte Glycoprotein ; blood ; cerebrospinal fluid ; Neuromyelitis Optica ; blood ; cerebrospinal fluid ; pathology ; Retrospective Studies ; Young Adult

Balo's concentric sclerosis is regarded as a rare variant of multiple sclerosis. Traditionally, Balo's concentric sclerosis was a post-mortem diagnosis, but the recent introduction of brain magnetic resonance imaging (MRI) scans may allow noninvasive access without biopsy. Brain MRI findings of Balo's concentric sclerosis is characteristic concentric configuration of alternating bands of white matter of different pathology, with relatively preserved myelination alternating with regions of demyelination in the cerebral white matter. We report a case of Balo's concentric sclerosis with recurrent optic neuritis.
Biopsy ; Brain ; Demyelinating Diseases ; Diagnosis ; Diffuse Cerebral Sclerosis of Schilder* ; Humans ; Magnetic Resonance Imaging ; Multiple Sclerosis ; Myelin Sheath ; Optic Neuritis* ; Pathology

Magnetic resonance (MR) images can be used to detect lesions in the brains of patients with multiple sclerosis (MS). An automatic method is presented for segmentation of MS lesions using multispectral MR images in this paper. Firstly, a Pd-w image is subtracted from its corresponding T1-w images to get an image in which the cerebral spinal fluid (CSF) is enhanced. Secondly, based on kernel fuzzy c-means clustering (KFCM) algorithm, the enhanced image and the corresponding T2-w image are segmented respectively to extract the CSF region and the CSF-MS lesions combinatoin region. A raw MS lesions image is obtained by subtracting the CSF region from CSF-MS region. Thirdly, based on applying median filter and thresholding to the raw image, the MS lesions were detected finally. Results were tested on BrainWeb images and evaluated with Dice similarity coefficient (DSC), sensitivity (Sens), specificity (Spec) and accuracy (Acc). The testing results were satisfactory.
Algorithms ; Brain ; pathology ; Humans ; Image Enhancement ; Magnetic Resonance Imaging ; Multiple Sclerosis ; diagnosis ; Sensitivity and Specificity

Multiple sclerosis (MS) is a common inflammatory demyelinating disorder of central nervous system, and the disease burder could be well evaluated by conventional magnetic resonance imaging (MRI), including T2-weighted, fluid-attenuatd inversion recovery, and postcontrast T1-weighted sequences. We investigated the perfusion state of MS plaques using brain perfusion imaging in a 12-year-old boy with MS.
Child ; Humans ; Magnetic Resonance Imaging ; Male ; Multiple Sclerosis ; pathology ; Spin Labels

Alzheimer Disease ; Diabetic Neuropathies ; pathology ; Glaucoma ; pathology ; Humans ; Multiple Sclerosis ; pathology ; Nerve Fibers ; pathology ; Ophthalmoscopy ; Optic Nerve ; pathology ; Parkinson Disease ; pathology ; Retinal Neurons ; pathology ; Tomography, Optical Coherence

Hereditary sclerosing poikiloderma (HSP) is a very rare disease. The clinical features are principally widespread poikiloderma and linear hyperkeratotic and sclerotic bands. We report an 18-yr-old male who presented reticular hyperpigmented lesions on the trunk and extremities since 2-yr-old. Also, linear sclerosing bands appeared on both antecubital and popliteal fossae after yr. Histopathologic finding showed dense sclerotic collagen fibers with telangiectasia in the upper dermis and fragmentations of damaged elastic fibers in the elastic stain, consistent with HSP. We report the first Korean case of HSP.
Abnormalities, Multiple ; Adolescent ; Elastic Tissue/pathology ; Fingers/abnormalities ; Humans ; Hyperpigmentation/pathology ; Male ; Micrognathism/pathology ; Rothmund-Thomson Syndrome/*diagnosis/pathology ; Sclerosis/pathology ; Skin Diseases/diagnosis/pathology