Short-term safety of inactivated SARS-Cov-2 vaccines in Chinese patients with central nervous system inflammatory demyelinating diseases.

Objective: This study aims to evaluate the short-term safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in Chinese patients with central nervous system inflammatory demyelinating diseases (CNS IDDs). Methods: A web-based survey was conducted among patients with CNS IDDs from April 15 to 19, 2022 in China. In total, 645 patients with CNS IDDs were identified, including 425 patients with multiple sclerosis (MS), 194 with neuromyelitis optica spectrum disorder (NMOSD), and 26 with other CNS IDDs. The questionnaire consisted of demographic data, clinical records, history of SARS-CoV-2 vaccination, and vaccination-related symptoms within one month after vaccination. The demographic data, clinical information, and relapse rates between vaccinated and non-vaccinated patients were compared. Results: Among 645 patients with CNS IDDs, 78 were vaccinated and 567 were non-vaccinated with the vaccination rate of 12.1 %. Compared to non-vaccinated group, a lower percentage of patients on DMDs therapy (41.0 % vs. 71.8 %, P < 0.001) and an increased proportion of patients with other vaccination in past 3 years (17.9 % vs. 4.8 %, P < 0.001) were observed in vaccinated group. Six patients experienced a relapse within 30 days of a vaccination. Additionally, vaccine-associated relapse rates in vaccinated patients did not significantly differ from these in non-vaccinated patients among 2020, 2021, and from January 1 to October 1, 2022. Conclusions: No increased risk of vaccination-associated relapses among Chinese patients with CNS IDDs indicated that inactivated SARS-CoV-2 vaccines appear to be safe for this population.

Rituximab at lower dose for neuromyelitis optica spectrum disorder: a multicenter, open-label, self-controlled, prospective follow-up study.

Objective: To address a novel lower-dose rituximab (RTX) therapy strategy based on our clinical experience and assess its efficacy and safety in neuromyelitis optica spectrum disorder (NMOSD). Methods: A multicenter, open-label, self-controlled, prospective follow-up study. Totally, 108 NMOSD patients were enrolled and a lower-dose RTX strategy was applied including 100 mg weekly for 3 weeks and then reinfusions every 6 months. Annualized relapse rate (ARR), the expanded disability status scale (EDSS) score and length of spinal cord lesions were included to evaluate the efficacy. Side effects were recorded to assess the safety profile. Results: Of 108 patients, 80 (74.1%) initiated low-dose RTX therapy immediately after acute attack treatment and 33 (30.6%) initiated it after the first attack. During a median treatment period of 35.5 (22.0-48.8) months, significant decreases were observed in median ARR (1.1 [0.8-2.0] versus 0 [0-0.2], p < 0.001), EDSS score (3.5 [2.5-4.0] versus 2.0 [1.0-3.0], p < 0.001) and spinal cord lesion segments (5.0 [4.0-8.0] versus 3.0 [1.0-6.0], p < 0.001). The cumulative risk of relapses significantly decreased during the post- versus pre-RTX period (HR 0.238, 95%CI 0.160-0.356, p < 0.001) and on early therapy initiated within 24 months after disease onset versus delayed therapy (HR 0.506, 95%CI 0.258-0.994, p = 0.041). No serious side effects were recorded and all the subjects did not discontinue treatment due to RTX-related side effects. Conclusion: Our research provided evidence supporting the lower-dose RTX strategy in treating NMOSD and reopened the issues of optimal dosage and therapy initiation timing.

Late-Onset Anti-GABAB Receptor Encephalitis: Clinical Characteristics and Outcomes Differing From Early-Onset Patients.

BACKGROUND AND OBJECTIVES: Existing evidence indicates anti-GABAB receptor encephalitis (GABABR-E) seems to occur more commonly later in life, yet the age-associated differences in clinical features and outcomes are not well determined. This study aims to explore the demographic, clinical characteristics, and prognostic differences between late-onset and early-onset GABABR-E and identify predictors of favorable long-term outcomes. METHODS: This is an observational retrospective study conducted in 19 centers from China. Data from 62 patients with GABABR-E were compared between late-onset (aged 50 years or older) and early-onset (younger than 50 years) groups and between groups with favorable outcomes (modified Rankin scale (mRS) ≤ 2) and poor outcomes (mRS >2). Logistic regression analyses were applied to identify factors affecting long-term outcomes. RESULTS: Forty-one (66.1%) patients experienced late-onset GABABR-E. A greater proportion of males, a higher mRS score at onset, higher frequencies of ICU admission and tumors, and a higher risk of death were demonstrated in the late-onset group than in the early-onset group. Compared with poor outcomes, patients with favorable outcomes had a younger onset age, a lower mRS score at onset, lower frequencies of ICU admission and tumors, and a greater proportion with immunotherapy maintenance for at least 6 months. On multivariate regression analysis, age at onset (OR, 0.849, 95% CI 0.739-0.974, p = 0.020) and the presence of underlying tumors (OR, 0.095, 95% CI 0.015-0.613, p = 0.013) were associated with poorer long-term outcomes, whereas immunotherapy maintenance for at least 6 months was associated with favorable outcomes (OR, 10.958, 95% CI 1.469-81.742, p = 0.020). DISCUSSION: These results demonstrate the importance of risk stratification of GABABR-E according to age at onset. More attention should be paid to older patients especially with underlying tumors, and immunotherapy maintenance for at least 6 months is recommended to achieve a favorable outcome.

Efficacy and safety of repeated low-dose rituximab therapy in relapsing-remitting multiple sclerosis: A retrospective case series study.

BACKGROUND: Rituximab (RTX) is an extensively used off-label drug for multiple sclerosis (MS), whereas the induction and maintenance regimens vary widely among studies. Few data are available on efficacy and safety of repeated low-dose RTX therapy in MS patients. OBJECTIVE: This study aimed to evaluate the efficacy and safety of repeated low-dose RTX therapy for relapsing-remitting MS (RRMS), the most common form of MS affecting approximately 85% of patients. METHODS: Nine RRMS patients were enrolled and the medical records were retrospectively reviewed. RTX at 100 mg per week for three consecutive weeks was used as induction therapy. Maintenance therapy was reinfusions of RTX at 100 mg every 6 months during the first year, followed by 100 mg every 6 to 12 months. Main outcome measures included annualized relapse rate (ARR), expanded disability status scale (EDSS) score, and T2 lesion burden on MRI for evaluating the efficacy of low-dose RTX regimen. Meanwhile, adverse events (AEs) were recorded to assess the safety of repeated RTX infusions. RESULTS: All patients were females with an average onset age of 25.4 ± 6.7 years. The median disease duration before the first RTX infusion was 56 (range, 3-108) months and the median follow-up period was 30 (range, 15-40) months. No relapses were recorded in all patients after RTX therapy. Repeated low-dose RTX therapy resulted in a dramatic reduction of median ARR (pre-RTX vs post-RTX, 1.1 vs 0, p = 0.012), median EDSS score (2.0 vs 0, p = 0.007), and the number of T2 lesions on MRI (35.6 ± 18.0 vs 29.4 ± 18.1, p = 0.001). A total of 35 episodes of AEs occurred during repeated low-dose RTX therapy, and all of them were mild and transient. CONCLUSION: Repeated low-dose RTX therapy is cost-effective for RRMS patients and shows a good safety profile. It may be a promising option for those having no access or poor response to first-line disease-modified drugs (DMDs), particularly in low- or middle-income countries.

Coexistence of Myelin Oligodendrocyte Glycoprotein Immunoglobulin G and Neuronal or Glial Antibodies in the Central Nervous System: A Systematic Review.

BACKGROUND: Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) has been considered a diagnostic marker for patients with demyelinating disease, termed "MOG-IgG associated disorder" (MOGAD). Recently, the coexistence of MOG-IgG and other neuronal or glial antibodies has attracted extensive attention from clinicians. In this article, we systematically review the characteristics of MOG-IgG-related antibody coexistence syndrome. METHODS: Two authors independently searched PubMed for relevant studies published before October 2021. We also manually searched the references of each related article. The appropriateness of the included studies was assessed by reading the titles, abstracts, and full texts if necessary. RESULTS: Thirty-five relevant publications that met our inclusion criteria were finally included, of which fourteen were retrospective studies and twenty-one were case reports. A total of 113 patients were reported to show the coexistence of MOG-IgG and neuronal or glial antibodies. Additionally, 68.14% of patients were double positive for MOG-IgG and N-Methyl-D-Aspartate Receptor-IgG (NMDAR-IgG), followed by 23.01% of patients who were double positive for MOG-IgG and aquaporin4-IgG (AQP4-IgG). Encephalitis was the predominant phenotype when MOG-IgG coexisted with NMDAR-IgG, probably accompanied by imaging features of demyelination. Patients with dual positivity for MOG-IgG and AQP4-IgG experienced more severe disease and more frequent relapses. The coexistence of MOG-IgG and antibodies other than NMDAR-IgG and AQP4-IgG was extremely rare, and the clinical presentations were diverse and atypical. Except for patients who were double positive for MOG-IgG and AQP4-IgG, most patients with multiple antibodies had a good prognosis. CONCLUSIONS: MOG-IgG may coexist with neuronal or glial antibodies. Expanded screening for neuronal or glial antibodies should be performed in patients with atypical clinical and radiological features.

Association between serum low-density neutrophils and acute-onset and recurrent Guillain-Barré syndrome.

BACKGROUND AND AIM: Guillain-Barré syndrome (GBS) is one of the most common causes of acute flaccid paralysis. A timely assessment of this disease condition and its treatments are of vital importance to patients diagnosed with GBS. The purpose of this study is to investigate the variation trend of neutrophils along with disease courses and assess the prognostic value of serum low-density neutrophils (LDNs) in the acute-onset and recurrence of GBS. METHODS: A total of 176 GBS patients were recruited. Patients were evaluated with Medical Research Council (MRC) sum score and the Hughes Functional Grading Scale score upon admission. Peripheral blood samples were collected for routine testing. Flow cytometry analysis was performed to identify LDNs. All patients were followed up to collect disease condition data. RESULTS: The total neutrophil ratios and counts were significantly higher in patients with acute-onset GBS compared to healthy controls (HCs). These counts/ratios decreased during remission and re-elevated in recurrent GBS patients. However, no correlation was observed between the total neutrophil counts/ratios and the MRC sum score. The LDNs collected from different GBS courses were identified using flow cytometry. The counts and ratios were significantly higher in acute-onset GBS and recurrent GBS compared to HCs and patients in remission. The LDN counts/ratios displayed a negative correlation with the MRC sum scores in acute-onset GBS and recurrent GBS. CONCLUSION: Our findings suggest that LDN counts/ratios are positively correlated with the acute-onset and recurrence of GBS and its severity. Therefore, LDNs might serve as an accessible prognostic indicator for disease progression monitoring.

Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis.

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.

Possible coexistence of MOG-IgG-associated disease and anti-Caspr2 antibody-associated autoimmune encephalitis: a first case report.

Myelin oligodendrocyte glycoprotein antibody-associated disease has been proposed as a separate inflammatory demyelinating disease of the central nervous system (CNS) since the discovery of pathogenic antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG). Antibodies targeting contactin-associated protein-like 2 (Caspr2), a component of voltage-gated potassium channel (VGKC) complex, have been documented to be associated with a novel autoimmune synaptic encephalitis with a low incidence. Herein, we reported an adult female with initial presentation of decreased vision in the right eye and subsequent episodes of neuropsychiatric disturbance including hypersomnia, agitation, apatheia, and memory impairment. Magnetic resonance imaging (MRI) revealed multiple lesions scattered in brain, brainstem, and cervical and thoracic spinal cord, showing hypointensity on T1-weighted images, hyperintensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Heterogenous patchy or ring-like enhancement was observed in the majority of lesions. The detection of low-titer MOG-IgG exclusively in cerebrospinal fluid (CSF; titer, 1:1) and Caspr2-IgG in both serum and CSF (titers, 1:100 and 1:1) led to a possible diagnosis of coexisting MOG-IgG-associated disease (MOGAD) and anti-Caspr2 antibody-associated autoimmune encephalitis. The patient was treated with immunosuppressive agents including corticosteroids and immunoglobulin, and achieved a sustained remission. To the best of our knowledge, this is the first report on the possible coexistence of MOGAD and anti-Caspr2 antibody-associated autoimmune encephalitis, which advocates for the recommendation of a broad spectrum screening for antibodies against well-defined CNS antigens in suspected patients with autoimmune-mediated diseases of the CNS.

T Follicular Helper-Like Cells Are Involved in the Pathogenesis of Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) have been proved to be T cell-mediated autoimmune diseases. Recent researches indicate that humoral immunity is also involved in the pathogenesis of these disorders. T follicular helper (Tfh) cells are critical for B cell differentiation and antibody production. However, the role of Tfh cells in MS and EAE remains unclear. Here, we found elevated frequencies of CD4+CXCR5+PD-1+ Tfh-like cells in both MS patients and EAE. In EAE mice, Tfh-like cells, together with B cells, were found in the ectopic lymphoid structures in spinal cords. Moreover, Tfh-like cells promoted the antibody production via IL-21/IL-21R and CD40 ligand/CD40 interaction and the synergy effect of STAT3 and non-canonical NF-κB signaling pathway inside B cells. Moreover, adoptive transfer of Tfh-like cells could increase the severity and delay the remission of EAE. In conclusion, our data indicate that Tfh-like cells contribute to the pathogenesis of EAE.

Role of perforin secretion from CD8+ T-cells in neuronal cytotoxicity in multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is the most prevalent autoimmune disease of the central nervous system, and is characterized by inflammation and myelin damage. The immune system initiates the autoimmune response, although the mechanisms of neuronal damage have not been elucidated. The purpose of the present study was to investigate autoreactive CD4+ and CD8+ T lymphocytes, in conjunction with other inflammatory cells and cytokines in active MS lesions. METHODS: EAE animal models was established by plantar injections of MBP (200 µg per rat). Purified CD4+ or CD8+ T-cells were isolated from heparinized peripheral blood (EAE animals and control animals) via negative selection. To examine effects of presence of autoreactive CD4+ and CD8+ T lymphocytes, we carried out ELISA, Western blot analysis and TUNEL. In addition, we examined the direct effects of various factors on neuronal cell death using MTT assay. RESULTS: The data revealed that CD8+ T-cells were more toxic to neurons compared to CD4+ T-cells, in both the MBP and EAE conditions. Bax was greater increased when neurons were co-cultured with CD8+ T-cells in the MBP group. There is a significant increase in IL-17 secretion by CD4+ T-cells in both the MBP group and EAE group. Neuronal viability were affected by Perforin (1.5 µg/mL). CONCLUSION: The present study extends previous research by demonstrating the role of CD8+ T-cells in MS and supports perforin secretion by CD8+ T-cells as a potential therapeutic factor. Furthermore, we determined that CD4+ T-cells can enhance CD8+ T-cell neuronal cytotoxicity via induction of intense inflammation.

Melatonin Suppresses Neuropathic Pain via MT2-Dependent and -Independent Pathways in Dorsal Root Ganglia Neurons of Mice.

Melatonin (Mel) and its receptors (MT1 and MT2) have a well-documented efficacy in treating different pain conditions. However, the anti-nociceptive effects of Mel and Mel receptors in neuropathic pain (NP) are poorly understood. To elucidate this process, pain behaviors were measured in a dorsal root ganglia (DRG)-friendly sciatic nerve cuffing model. We detected up-regulation of MT2 expression in the DRGs of cuff-implanted mice and its activation by the agonist 8-M-PDOT (8MP). Also, Mel attenuated the mechanical and thermal allodynia induced by cuff implantation. Immunohistochemical analysis demonstrated the expression of MT2 in the DRG neurons, while MT1 was expressed in the satellite cells. In cultured primary neurons, microarray analysis and gene knockdown experiments demonstrated that MT2 activation by 8MP or Mel suppressed calcium signaling pathways via MAPK1, which were blocked by RAR-related orphan receptor alpha (RORα) activation with a high dose of Mel. Furthermore, expression of nitric oxide synthase 1 (NOS1) was down-regulated upon Mel treatment regardless of MT2 or RORα. Application of Mel or 8MP in cuff-implanted models inhibited the activation of peptidergic neurons and neuro-inflammation in the DRGs by down-regulating c-fos, calcitonin gene-related peptide [CGRP], and tumor necrosis factor-1α [TNF-1α] and interleukin-1ß [IL-1ß]. Addition of the MT2 antagonist luzindole blocked the effects of 8MP but not those of Mel. In conclusion, only MT2 was expressed in the DRG neurons and up-regulated upon cuff implantation. The analgesic effects of Mel in cuff-implanted mice were closely associated with both MT2-dependent (MAPK-calcium channels) and MT2-independent (NOS1) pathways in the DRG.

Intracranial lesion as onset symptom in a patient with early undifferentiated connective tissue disease: a case report.

BACKGROUND: Undifferentiated connective tissue disease (UCTD) is widely considered to be a distinct clinical entity, and now divided into two subgroups: stable UCTD and early UCTD. The most frequent onset symptoms of UCTD include arthralgias, arthritis, Raynaud's phenomenon, mucocutaneous involvement, and sicca symptoms. However, Neurologic involvement is rare, and intracranial lesion as onset symptom in a patient with early UCTD has not yet been reported. CASE PRESENTATION: A 51-year-old Chinese female experienced progressive left leg weakness for 14 days before hospitalizing in our department. The lesion on right parietal lobe was initially detected by brain magnetic resonance imaging. Although the patient declined a cerebral biopsy, the possibility of stroke, cerebral venous sinus thrombosis, NMOSD, MS, autoimmune encephalitis, intracranial infections, and malignant tumors as cause of the lesion was excluded by intracranial angiogram, CSF study, MRI enhancement and MRS examination. Moreover, immunologic studies showed high titer of antinuclear antibody, increased erythrocyte sedimentation rate and C-reactive protein. These results led to a diagnosis of early UCTD with central nerve system (CNS) involvement. After low dose corticosteroid and azathioprine therapy, the patient's symptoms, abnormalities in immunologic tests and cerebral radiologic examinations were all greatly improved within a short duration. CONCLUSIONS: This is the first report of intracranial lesion as onset symptom in a patient with early UCTD. Our case suggested that central nerve system (CNS) involvement could be the onset symptom in early UCTD, and should be recognized quickly with exclusion of other causative factors in the differential diagnosis. Prompt and adequate treatment with low-dose steroid and immunosuppressive drugs could improve the prognosis of both early UCTD and CNS involvement.

Increased Circulating T Follicular Helper Cells Are Inhibited by Rituximab in Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune disease of the central nervous system. The existence of autoantibody targeting aquaporin-4 (AQP4-Ab) indicates the involvement of humoral immunity in the pathogenesis of this disease. Rituximab (RTX), a monoclonal antibody against CD20, has been used to treat NMOSD by depleting circulating B cells and overall satisfactory outcome has been achieved. Although T follicular helper cells have been proved to regulate B cell activation and antibody production, the role of these cells in NMOSD and the impact of RTX treatment on these cells remain less understood. In this study, we found that frequencies of circulating T follicular helper (cTfh) cells and B cells together with the related cytokines, IL-21 and IL-6, were closely correlated with disease activity of NMOSD. Furthermore, B cell depletion with RTX treatment inhibited the expansion of cTfh cells, and these effects were achieved through eliminating IL-6-producing B cells and blocking the direct contact between cTfh cells and B cells. These findings imply the complicated cross talk between cTfh cells and B cells and may provide a novel therapeutic target for NMOSD.

[Myeloid-derived Gr-1⁺ CD11b⁺ suppressor cells are involved in immunoregulation of experimental autoimmune encephalomyelitis].

OBJECTIVE: To explore the change in the number and role of Gr-1⁺ CD11b⁺ myeloid-derived suppressor cells (MDSCs) in experimental autoimmune encephalomyelitis (EAE). METHODS: Totally 30 healthy female C57BL/6 mice were randomly divided into two groups: EAE-induced group (n=15) and control group (n=15). EAE was induced by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55), and pathological changes in spinal cords were revealed by HE staining and Luxol fast blue (LFB) staining. The number of Gr-1⁺ CD11b⁺ MDSCs in spleens and spinal cords of the two groups was respectively compared by flow cytometry and immunofluorescent staining. The effect of Gr-1⁺ CD11b⁺ MDSCs from EAE mice on the proliferation of CD4⁺ T cells and CD8⁺ T cells was evaluated by in vitro co-culture system. RESULTS: Twelve of 15 immunized mice (80%) developed EAE. HE staining showed an extensive infiltration of inflammatory cells in the spinal cords of the EAE mice. LFB staining revealed multiple demyelinated lesions in the above inflammatory infiltration. The immunofluorescent histochemistry suggested that many Gr-1⁺ CD11b⁺ MDSCs were present in spinal cords of the EAE mice, but no positive cells were observed in the control group. The mass of spleen in the EAE mice was significantly higher than that of the control mice [(146.5 ± 12.4) mg vs (67.2 ± 8.7) mg, P<0.01], and the proportion of splenic Gr-1⁺ CD11b⁺ MDSCs in EAE mice significantly increased (P<0.01 vs controls). Consistent with the results of immunofluorescent staining, a significantly increased proportion of Gr-1⁺ CD11b⁺ MDSCs in spinal cords of EAE mice was observed with flow cytometry. In vitro co-culture analysis revealed that Gr-1⁺ CD11b⁺ MDSCs from spinal cords of the EAE mice markedly suppressed the proliferation of CD4⁺ T cells and CD8⁺ T cells. CONCLUSION: EAE induces an expansion and aggregation of Gr-1⁺ CD11b⁺ MDSCs in spleens and spinal cords. These cells suppress T cell proliferation in vitro and are involved in the immunoregulation of EAE.

Diffusion tensor imaging characterization of occult brain damage in relapsing neuromyelitis optica using 3.0T magnetic resonance imaging techniques.

Studies of relapsing neuromyelitis optica (RNMO) using advanced MRI techniques are limited compared with those done on multiple sclerosis (MS). The present study used diffusion tensor imaging (DTI) to investigate whether occult brain damage exists in RNMO patients. DTI scans using a 3.0T MRI scanner were performed in 24 clinically confirmed RNMO patients whose conventional brain MRI results were normal, and also in 24 age- and sex-matched healthy control subjects. DTI data were processed to generate fractional anisotropy (FA) and mean diffusivity (MD) maps, and region of interest (ROI) analyses were performed to obtain these parameters in white matter (including medulla oblongata, cerebral peduncle, optic radiation, genu of corpus callosum, splenium of corpus callosum, and internal capsule) and gray matter (including thalamus and putamen). Regional measures from patients at stable and acute phases were compared with healthy controls. Both acute and stable NMO patients had a higher average FA in ROIs of the thalamus and putamen. Acute NMO patients had significantly higher average MDs than controls in the genu of corpus callosum and optic radiation, and significantly lower average MDs in the medulla oblongata. Stable NMO patients had increased MDs in the genu of corpus callosum and optic radiation, but lower MDs in the medulla oblongata, internal capsule and thalamus. The DTI findings confirm the presence of occult tissue damage in normal-appearance white and gray matter, especially deep gray matter, in RNMO patients. This study adds further to the evidence that DTI is suitable as a tool for characterizing subtle brain tissue damage.

Cognitive function, depression, fatigue, and activities of daily living in patients with neuromyelitis optica after acute relapse.

The status of fatigue, depression, and activities of daily living and their relationships with cognitive function in patients with neuromyelitis optica (NMO) after acute relapse has never been observed. This study investigated cognitive function, fatigue, depression, activities of daily living, and the relationships among them in NMO patients. Twenty-two NMO patients without visible lesions on conventional brain MRI after acute relapse, 22 depression patients, and 22 healthy comparison subjects received several scales to assess cognitive function, fatigue, and depression. Every NMO patient completed a survey of activities of daily living. Between-group comparisons and correlational analyses were applied to examine the differences and the relationships among them. We found that NMO patients had significantly impaired memory, decreased information processing speed, and damaged attention. Some impaired cognitive domains were significantly correlated with fatigue and depression, and activities of daily living were correlated with these impaired cognitive domains, fatigue, depression, and disability. These results confirm cognitive deficits in memory, information processing speed, and attention exist in NMO patients without visible brain lesions after acute relapse. Fatigue and depression may affect cognitive function and increase the negative impact of cognitive deficits on the activities of daily living in patients with NMO.

Cognitive impairment and whole brain diffusion in patients with neuromyelitis optica after acute relapse.

The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive tests to assess cognitive function. Head diffusion tensor imaging (DTI) of all patients with NMO were collected with a 3-T MR system. Correlations of cognitive test scores and whole brain FA and MD were examined by voxel-based analysis. Region-of-interest analysis was applied to the significantly correlated regions which the most frequently appeared. We found that NMO patients without visible brain lesions had significantly impaired learning and memory, decreased information processing speed, and damaged attention compared with normal control subjects. These impaired cognitive domains were significantly correlated with FA and MD in local regions of corpus callosum, anterior cingulate and medial frontal cortex. In corpus callosum of NMO patients, mean FA was significantly lower and mean MD higher than normal control subjects. Our findings suggest that cognitive impairments in learning and memory, information processing speed and attention occur in NMO patients without visible brain lesions during acute relapse. The impairments in immediate and short-term memory in NMO patients may be due to information encoding deficits in the process of information acquisition. The corpus callosum of such patients may have local microscopic damages that play a role in cognitive impairments during acute relapse.