FCGR3A-V158F gene polymorphism: A potential predictor for rituximab dosing optimization in Chinese patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Rituximab (RTX), an anti-CD20 monoclonal antibody, has shown promise in managing neuromyelitis optica spectrum disorders (NMOSD) by depleting B cells and reducing relapses. However, there is no consensus on the optimal RTX dosing regimen, and genetic factors, such as FCGR3A-V158F polymorphism, may influence treatment outcomes. This study investigates how FCGR3A-V158F genotypes influence RTX efficacy in Chinese NMOSD patients under varying dosing regimens and aims to optimize treatment protocols. METHODS: We conducted a retrospective analysis of 25 Chinese NMOSD patients treated with RTX, grouped into standardized and low-dosage regimens. FCGR3A-V158F genotypes were determined, and treatment responses were evaluated, including relapse rates, time to first relapse (TFR), B-cell depletion, dose adjustments, and treatment retention. RESULTS: Among all patients, 15 received standardized dosages, while 10 received varied induction doses (500 mg to 1200 mg) in low-dose regimens. For FCGR3A-V158F genotypes, 15 had the FF genotype, and 10 were V carriers (3 VV genotype, 7 VF genotype). Regardless of dosing, FF genotype patients had a higher relapse rate post-RTX treatment compared to V carriers (P < 0.05). None of the 3 VV genotype patients in either dose group experienced relapses post-RTX. In both dose groups, FF genotype patients had significantly shorter TFR and required more RTX dose adjustments post-RTX treatment compared to V carriers in the standardized dosage group (P < 0.05). FF genotype patients in the low dosage group were more likely to experience insufficient B-cell depletion, had lower treatment retention rates, and more discontinuations than V carriers in the standardized dosage group (P < 0.05). Insufficient B-cell depletion significantly predicted clinical relapses after RTX treatment (P < 0.05). In survival analysis, FF genotype patients, regardless of dosing, experienced earlier relapses post-RTX treatment (P < 0.05). CONCLUSIONS: This study highlights the importance of RTX dosage selection in NMOSD treatment, particularly for FCGR3A-FF genotype patients. Standard-dose RTX therapy with vigilant monitoring of peripheral blood B-cell levels is recommended for these individuals to optimize treatment efficacy.

Therapeutic efficacy and safety of plasmapheresis in elderly patients with neuromyelitis optica spectrum disorder: a single-center observational study.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a devastating autoimmune disorder with cycles of escalating relapse. Rates of diagnosis in the elderly are increasing. Therapeutic decision-making is more challenging in elderly patients due to multiple comorbidities and high risk of drug-induced side effects. Objective: This retrospective study assessed the efficacy and safety of standard plasma exchange (PLEX) treatment in an elderly population with NMOSD. Design: Seventy-six patients with NMOSD who received PLEX were apportioned to two groups as either elderly (⩾60 years, n = 26) or young (<60 years) at the time of the first procedure. Methods: Therapeutic response was judged according to functional recovery at 6 months, as reflected by Expanded Disability Status Scale (EDSS) and visual outcome scale (VOS) scores. Results: The mean age of the 26 elderly patients was 67.7 ± 7.9 years (range 60-87 years); the population was predominantly female (88.5%). PLEX sessions were generally well tolerated among the elderly. Compared with the young patients, the elderly had significantly more comorbidities and concomitant medications. Twenty-four (96.0%) elderly patients showed functional improvement at 6 months after PLEX, of which 15 (60.0%) experienced moderate-to-marked improvement. Six months after the initial PLEX treatment, the patients overall experienced a significant improvement in EDSS and VOS scores. Logistic regression showed that severe optic neuritis attack was a significant independent prognostic factor associated with poor PLEX response. The groups were comparable regarding overall or serious adverse events. The rate of transient hypotension was significantly higher in the elderly compared with the young. Conclusion: PLEX is an effective and safe therapy for elderly patients with NMOSD and should be considered a treatment option during NMOSD attacks. In the elderly, preventive measures against hypotension are recommended before PLEX.

Successful treatment of rituximab-unresponsive elderly-onset neuromyelitis optica spectrum disorder and hypogammaglobulinemia with ofatumumab plus intravenous immunoglobulin therapy in a patient with mutant FCGR3A genotype: A case report.

Background: Elderly-onset neuromyelitis optica spectrum disorder (NMOSD) is a rare entity that poses a therapeutic challenge. We report a case of elderly-onset NMOSD with mutant FCGR3A genotype who was successfully treated with ofatumumab after multiple episodes of relapse. Case Report: The patient was a 67-year-old woman who was diagnosed with NMOSD with high disease activity. She experienced six episodes of relapse over a period of 2 years despite immunosuppressant therapy with intravenous rituximab (RTX), oral steroids, mycophenolate mofetil, and tacrolimus. At the last relapse, she was unable to walk and developed immunosuppressant-induced hypogammaglobulinemia. Based on the insufficient B cell depletion and FCGR3A-FF genotype carrier, the patient was diagnosed as RTX non-responder. After subcutaneous ofatumumab plus intravenous immunoglobulin replacement therapy, she was able to walk independently, and experienced no further relapse. Ofatumumab was well-tolerated, and sufficiently depleted the circulating B cells. Conclusion: Ofatumumab might be an effective alternative in RTX-unresponsive NMOSD, and seems to be safe in elderly patients.

Area Postrema Syndrome: A Rare Feature of Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids.

Background: The area postrema syndrome (APS) is a unique diagnostic criterion for neuromyelitis optica spectrum disorders (NMOSD). However, APS has rarely been reported in cases of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Case presentation: A 36-year-old woman presented with APS and clinical features of diffuse central nervous system involvement during the early stage of the disease. Owing to the absence of serum aquaporin 4 antibodies, she was initially misdiagnosed as a case of seronegative NMOSD. However, the distinct neuroimaging characteristics [symmetrical small punctuate gadolinium enhancing lesions (pepper-like)], typical clinical/radiological relapse, and intense steroid-dependence in this case, prompted us to correct the diagnosis as probable CLIPPERS. To prevent relapse, long-term oral steroids and an immunosuppressive agent were administered. Conclusions: CLIPPERS may present as APS, and should be considered in the differential diagnosis of NMOSD.

Questioning the existence of monophasic neuromyelitis optica spectrum disorder by defining a novel long-term relapse-free form from a large Chinese population.

OBJECTIVE: To clarify the existence of monophasic neuromyelitis optica spectrum disorders (NMOSD) and to identify predictive factors of long-term relapse-free form. METHODS: We retrospectively analyzed 289 Chinese patients with NMOSD. Selected subjects were divided into three groups based on the time interval between disease onset and the first relapse, if any. Clinical and imaging data were acquired from each patient's medical record and evaluated as predictive factors for NMOSD. RESULTS: In total, none of the participating patients exhibited a monophasic form of NMOSD. Rather, 241 patients were selected for relapse tendency analysis; 143 (59.3%) patients relapsed within the first year, 66 (27.4%) during 1-5 years, and 32 (13.3%) beyond 5 years. Such onset symptoms as optic neuritis (ON) and non-longitudinally extensive transverse myelitis (LETM) were independent prognostic factors for a prolonged remission interval (P < 0.05). The relapse rate was bi-modal for ON patients in the first year (47.9%) and beyond 5 years (24.0%) after disease onset, respectively. However, most TM and area postrema syndrome (APS) patients experienced an attack within the first year (61.3% for TM and 76.9% for APS). A survival analysis showed that attacks with APS (P < 0.0001) and TM (P < 0.05) have a significantly higher risk of early relapse than with ON and that seropositive aquaporin-4 antibody may shorten the relapse interval for all onset symptoms (P < 0.0001). CONCLUSIONS: Our study indicated that the monophasic form of NMOSD may not exist when a sufficient follow-up period is considered. Onset phenotypes with ON, non-APS, or non-LETM attacks had a lower risk of early relapse.

Clinical utility of AQP4-IgG titers and measures of complement-mediated cell killing in NMOSD.

OBJECTIVE: To investigate whether aquaporin-4-immunoglobulin G (AQP4-IgG) titers and measures of complement-mediated cell killing are clinically useful to predict the occurrence of relapse, relapse severity, and/or disability in neuromyelitis optica spectrum disorder (NMOSD). METHODS: We studied 336 serial serum specimens from 82 AQP4-lgG-seropositive patients. NMOSD activity at blood draw was defined as preattack (24 [7.1%], drawn within 30 days preceding an attack), attack (108 [32.1%], drawn on attack onset or within 30 days after), or remission (199 [59.2%], drawn >90 days after attack onset and >30 days preceding a relapse). For each specimen, we documented the attack type and severity and immunotherapy status. Complement-mediated cell killing was quantitated by flow cytometry using an M23-AQP4 cell-based assay. RESULTS: The estimated logarithmic means of AQP4-IgG titers in preattack, attack, and remission samples were 3.302, 3.657, and 3.458, respectively, p = 0.21. Analyses of 81 attack/remission pairs in 42 patients showed no significant titer differences (3.736 vs 3.472, p = 0.15). Analyses of 13 preattack/attack pairs in 9 patients showed no significant titer differences (3.994 vs 3.889, p = 0.67). Of 5 patients who converted to seronegative status, 2 continued to have attacks. Titers for major and minor attacks (n = 70) were not significantly different (3.905 vs 3.676, p = 0.47). Similarly, measures (titers) of complement-mediated cell killing were not significantly associated with disease course, attack severity, or disability at 5 years. CONCLUSIONS AND RELEVANCE: AQP4-IgG titer and complement-mediated cell killing lack significant prognostic or predictive utility in NMOSD. Although titers may drop in the setting of immunotherapy, seroconversion to negative status does not preclude ongoing clinical attacks. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with NMOSD, AQP4-IgG titers and measures of complement-mediated cell killing activity do not predict relapses, relapse severity, or disability.

Reduced sarcolemmal aquaporin 4 expression can support the differential diagnosis of neuromyelitis optica spectrum disorders.

This study aimed to investigate the underlying pathological muscle damage in neuromyelitis optica spectrum disorder (NMOSD) patients without muscular symptoms. We prospectively enrolled 15 patients with aquaporin 4 (AQP4) antibody seropositive NMOSD and 16 patients with non-NMOSD diseases as a control group. Biceps biopsy samples from 18 patients were examined. Six NMOSD patients exhibited inflammatory lesions/edema in lower muscles on muscle MRI. On histopathological examination, NMOSD samples showed significantly decreased IgG-targeting AQP4 expression on sarcolemma compared with non-NMOSD samples in terms of the area of positive staining and integrated optical density. Muscle biopsy can support the differential diagnosis of NMOSD.

[Clinical and genetic analysis of a patient with Krabbe disease presented as peripheral neuropathy].

OBJECTIVE: To explore the clinical, electrophysiological and imaging features of a patient with Krabbe disease caused by GALC mutation. METHODS: A comprehensive analysis including clinical investigation and genetic testing was carried out. RESULTS: The patient presented with peripheral neuropathy with electrophysiological anomaly suggestive of asymmetric demyelinating neuropathy. Brain imaging revealed leukoencephalopathy. Genetic analysis has identified compound heterozygous mutations in exons 5 and 11 of the GALC gene, namely c.461C>A and c.1244G>A. CONCLUSION: Krabbe disease is a group of disorders featuring substantial phenotypic heterogeneity. Genetic and enzyme testing has become indispensable for accurate diagnosis for this disease.

Regulatory effect of miR-421 on humeral fracture and heterotopic ossification in elderly patients.

The present study aimed to investigate the role of miR-421 and bone morphogenetic protein-2 (BMP-2) in the bone tissues and blood of elderly patients with humeral fractures and heterotopic ossification. A total of 38 patients with humeral fractures, including 16 patients who received surgery within 1-7 days of fracture and 22 patients who received surgery within 8-14 days of fracture, were enrolled. An additional 18 patients who had heterotopic ossification and 26 patients who had humeral fracture and not heterotopic ossification were also included. Bone tissues and blood were collected. Reverse transcription-quantitative polymerase chain reaction was performed to determine the miR-421 and BMP-2 mRNA expression levels in the samples. Western blotting and ELISA were performed to detect BMP-2 protein levels in bone tissues and blood, respectively. Dual-luciferase reporter assays were performed to verify whether BMP-2 is the direct target gene of miR-421. Compared with the patients who received surgery 1-7 days after fracture, the patients who accepted the surgery 8-14 days after fracture had significantly increased levels of BMP-2 mRNA and protein in their bone tissues and blood (P<0.05). Contrastingly, the expression level of miR-421 decreased in the samples from patients who accepted the surgery 8-14 days after fracture compared with the level in those who received surgery 1-7 days after fracture (P<0.05). Compared with the patients without heterotopic ossification, the patients with heterotopic ossification had increased BMP-2 mRNA and protein expression levels in their bone tissues and blood, whereas the expression of miR-421 was significantly decreased (P<0.05). The dual-luciferase reporter assay demonstrated that BMP-2 was the direct target gene of miR-421. The upregulation of BMP-2 may be associated with the downregulation of miR-421. miR-421 may regulate the recovery of humeral fracture and heterotopic ossification through BMP-2. The results of the present study may provide a theoretical basis for the diagnosis and treatment of humeral fracture and heterotopic ossification.

Early identification of anti-NMDA receptor encephalitis presenting cerebral lesions in unconventional locations on magnetic resonance imaging.

To facilitate the diagnosis of anti-NMDAR encephalitis presenting with brain lesions in unconventional locations (BLUL) on MRI, we retrospectively analyzed forty-five Chinese patients. Eighteen (40.0%) of their MRI initially exhibited one or more BLUL. These locations predominantly included cerebral gray matter (cortex, basal ganglia and thalamus), as well as white matter and brainstem. Due to these BLUL, thirteen (72.2%) patients were originally misdiagnosed with other diseases and developed poor clinical and imaging outcomes. Therefore, anti-NMDAR encephalitis has unpredictable MRI findings that easily obscure its diagnosis and cause serious sequelae. Anti-NMDAR antibody tests are highly recommended in patients with BLUL.

Dose effects of mycophenolate mofetil in Chinese patients with neuromyelitis optica spectrum disorders: a case series study.

BACKGROUND: Neuromyelitis optica (NMO) spectrum disorder (NMOSD) is a devastating autoimmune inflammatory disorder of the central nervous system, which can result in blindness or paralysis. Currently, there is a dire need for new treatment options in the clinic. Several case series have shown that mycophenolate mofetil (MMF) may be an effective treatment for NMOSD patients. The dosing of MMF in the treatment of NMOSD has been poorly studied. Therefore, we evaluated the efficacy, tolerability, influential factors and optimal dosage of MMF in Chinese patients with NMOSD. METHODS: A case series of 109 NMO or NMOSD (limited forms of NMO with seropositive AQP4-IgG) patients were retrospectively analyzed and followed up. Out of the 109 patients, 86 patients had received MMF for 6 months or longer and were included for efficacy assessment. RESULTS: When comparing the annualized relapse rate (ARR) of MMF treatment with that of pre-MMF treatment period, MMF was found to significantly reduce ARR in 75 (87%) patients (p < 0.0001). The median pre-treatment Expanded Disability Status Scale (EDSS) score in remission decreased from 3 (range, 0-8.5) to 2.5 (range, 0-8) at the last follow-up (p = 0.006), yet no significant difference was found in the visual score. The higher doses of MMF (1750 mg/d to 2000 mg/d) significantly lowered the relapse risks compared with lower doses (1000 mg/d or less, p < 0.0001) or moderate doses (1250 to 1500 mg/d, p = 0.031). Coexisting with systemic autoimmune diseases (HR, 2.418; p = 0.0345) and attack number before MMF initiation (HR, 1.117; p = 0.02) were important risk factors for relapses. MMF was generally well tolerated with adverse effects occurring in 21 patients (19%). While four patients decreased their daily doses because of the adverse effects, only one patient stopped MMF treatment. CONCLUSIONS: MMF is generally effective and well tolerated in Chinese NMOSD patients. High-dose MMF was more potent than the lower dose for NMOSD patients, with 1750 mg of daily MMF being the recommended dosage for Chinese patients with NMOSD. MMF treatment reduces the frequency of relapses and improves the quality of life for patients with this debilitating disease.

Plasma Exchange for Neuromyelitis Optica Spectrum Disorders in Chinese Patients and Factors Predictive of Short-term Outcome.

PURPOSE: The purposes of this article were to evaluate the short-term outcome of plasma exchange (PLEX) for neuromyelitis optica spectrum disorders (NMOSDs) in Chinese patients and to identify the factors predictive of a favorable response to therapy. METHODS: We retrospectively analyzed data from 29 Chinese patients with NMOSD. All patients received 2 to 7 sessions of PLEX every other day. Expanded Disability Status Scale (EDSS) scores were estimated at baseline, at relapse, and before and at follow-up after PLEX. Patients were assigned to 1 of 2 groups according to treatment responses of marked to moderate improvement and mild to no improvement. FINDINGS: Twenty-four of 29 patients (82.8%) showed functional improvement at 1 month after PLEX, 9 of whom experienced moderate to marked improvement. Early PLEX initiation and a lower baseline EDSS score were independent prognostic factors (both, P < 0.05). In addition, relapse symptoms of nonoptic neuritis and acute transverse myelitis plus circumventricular organs, seronegativity for aquaporin-4 antibodies, shorter initial therapy-PLEX interval, and no prior optic neuritis attacks were predictive factors significantly associated with a favorable response to treatment (all, P < 0.05). The delay time pre-PLEX was inversely correlated with reduction in EDSS score. The percentage reductions in EDSS score in groups receiving PLEX on days ≤15 and days 16 to 30 were significantly greater than those in the groups treated on days 31 to 60 and days 61 to 90 (all, P < 0.05). Most PLEX sessions were generally well tolerated. IMPLICATIONS: PLEX is an effective therapy for NMOSD in the Chinese population, and early PLEX initiation was associated with a favorable response. We recommend an optimum PLEX time of 30 days from the time of disease onset. Further long-term prospective, multicenter studies that include a larger sample of patients with NMOSD treated with PLEX are necessary.

Etiological, clinical, and radiological features of longitudinally extensive myelopathy in Chinese patients.

Longitudinally extensive myelopathy (LEM) is a rare spinal syndrome, and was mostly assessed in western populations. In order to investigate the etiological, clinical, and radiological features of LEM in Chinese patients, we retrospectively analyzed eighty-nine (40 men and 49 women, median age 45.9±15.7years) patients with LEM hospitalized in China-Japan Friendship Hospital. LEM comprised autoimmune inflammatory myelitis (n=53), metabolic and compressive disorders (n=13), vascular diseases (n=10), neoplastic diseases (n=7), infectious diseases (n=4), and syringomyelia (n=2). Neuromyelitis optica spectrum disorders (NMOSD) was the most common cause of transverse myelopathy identified in LEM (38/89 [42.7%]) characterized by intractable vomiting and hiccups and painful tonic spasms. Subacute combined degeneration and anterior spinal artery syndrome accounted for the largest non-transverse LEM, which selectively affected the spinal dorsal and/or lateral columns and the spinal anterior region, respectively. Radicular pain was common in anterior spinal artery syndrome. Postrema (n=15, 39.5%) and cervical (n=31, 81.6%) lesions were significantly increased in NMOSD versus non-NMOSD (n=7, 13.7% and n=34, 66.7%, respectively, p<0.05]. Axial T2-weighted MRI indicated that 46 (51.7%) patients exhibited complete lesions; 43 (48.3%) patients exhibited non-transverse lesions, mainly unilateral or symmetrical tract lesions. Twenty-four (51.1%) LEM patients exhibited distinct gadolinium contrast enhancement. In this Chinese cohort, LEM was primarily attributed to NMOSD. While the etiological distribution in the non-NMOSD group was different from western populations, clinical and imaging features may facilitate a differential diagnosis.

A case report of SPG11 mutations in a Chinese ARHSP-TCC family.

BACKGROUND: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a complicated form of hereditary spastic paraplegia, characterized by progressive spastic paraplegia, weakness of the lower extremities and is usually accompanied by mental retardation. Mutations in the Spastic Paraplegia gene 11 (SPG11) account for a large proportion of ARHSP-TCC cases worldwide. CASE PRESENTATION: We describe a Chinese family with ARHSP-TCC. Two daughters of this family presented with a spastic gait and cognitive impairment. Brain imaging of the index patient revealed a thin corpus callosum. We performed detailed physical and auxiliary examinations and were able to exclude acquired causes of spastic paraplegia. To determine the causative mutation, we took a candidate gene approach and screened the coding sequence and some flanking intronic sequence of SPG11 by direct Sanger sequencing. We identified two novel compound heterozygous mutations in SPG11 in affected individuals (c.1551_1552delTT, p.Cys518SerfsTer39 and c.5867-1G > T (IVS30-1G > T), p.Thr1956ArgfsTer15). Bioinformatic analysis predicts that these mutations would lead to a loss of protein function due to the truncation of the SPG11 protein. CONCLUSIONS: The results of this case report indicate a broader approach to include screening for SPG11 mutations in ARHSP-TCC patients. Our findings enrich the phenotypic spectrum of SPG11 mutations.

Differentiation of neuromyelitis optica spectrum disorders from ultra-longitudinally extensive transverse myelitis in a cohort of Chinese patients.

This study aimed to differentiate neuromyelitis optica spectrum disorders (NMOSD) from other causes in cases of ultra-longitudinally extensive transverse myelitis (uLETM). We retrospectively analyzed thirty-three Chinese patients with uLETM hospitalized in the China-Japan Friendship Hospital. The patients were divided into NMOSD (n=21) and non-NMOSD (n=12) groups. The NMOSD group exhibited significantly more comorbidity compared with the non-NMOSD group; moreover, the NMOSD group uniquely exhibited intractable vomiting and hiccups (IVH). The prevalence rates of cervicothoracic, area postrema (AP), and other circumventricular organ (CVO) lesions were significantly increased in the NMOSD group compared with the non-NMOSD group. Moreover, uLETM was strongly associated with NMOSD. These novel findings indicate that CVO lesions, including AP, and particularly when combined with clinical IVH, may represent a useful discriminator to differentiate NMOSD.

[Serum uric acid level and clinical relevance analysis in autoimmune myelopathy].

OBJECTIVE: To quantify serum uric acid (UA) levels in autoimmune myelopathy (AMs) patients and analyze the clinical relevance. METHODS: Blood samples from hospitalized patients with AMs (n = 69) in acute phase and other neurological disorders (n = 50) between September 2009 and December 2013 and healthy subjects (n = 50) were used to detect UA level by enzymatic calorimetric method.Expanded disability status scale (EDSS) and spinal MRI-T2 imaging were used for clinical and imaging severity evaluations.And serum AQP4 anitbody and other antibodies were tested. RESULTS: Serum UA level in AMs patients ((223 ± 76) µmol/L) was lower than in controls ((325 ± 53) µmol/L and (324 ± 48) µmol/L, P < 0.001); for clinical relevance analysis, serum UA levels in females ((208 ± 64) µmol/L), age ≥ 40 years ((185 ± 64) µmol/L), EDSS score ≥ 4.5 ((179 ± 59) µmol/L), transverse lesion ((179 ± 56) µmol/L) and neuromyelitis optica/spectrum disorders ((199 ± 70) µmol/L) were lower than in males ((252 ± 88) µmol/L, P < 0.05), age < 40 years ((266 ± 66) µmol/L, P < 0.001), EDSS score < 4.5 ((257 ± 70) µmol/L, P < 0.001), non-transverse lesion ((274 ± 64) µmol/L, P < 0.001) and multiple sclerosis ((261 ± 69) µmol/L, P < 0.05). An inverse correlation existed between UA level and involved spinal segments (r = -0.665, P < 0.001); status of serum antibodies and associated diseases showed no significant differences. CONCLUSION: Serum UA level is low and shows strong relevance with clinical and imaging severity in AMs patients. And UA is recommended as a biomarker of AMs.

Short myelitis lesions in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders.

IMPORTANCE: Short transverse myelitis (STM; <3 vertebral segments) is considered noncharacteristic of neuromyelitis optica (NMO) spectrum disorders (NMOSDs). Nonappreciation of the potential for STM to occur in NMOSD may lead to increased disability from delay in diagnosis and appropriate treatment. OBJECTIVES: To determine the frequency of short lesions at the initial myelitis manifestation of NMOSD and to compare the demographic, clinical, and radiological characteristics of aquaporin-4-IgG (AQP4-IgG) seropositive and seronegative STM. DESIGN, SETTING, AND PARTICIPANTS: We reviewed the records and images of patients at the Mayo Clinic who were identified as AQP4-IgG positive from 1996 to 2014. Inclusion criteria were first STM episode, magnetic resonance imaging performed 90 days or less from symptom onset, spinal cord T2-hyperintense lesion less than 3 vertebral segments, AQP4-IgG seropositivity, and a final diagnosis of NMO or NMOSD. Patients with an initial longitudinally extensive transverse myelitis were excluded (n = 151). Patients with STM who were seronegative for AQP4-IgG among an Olmsted County population-based cohort of inflammatory demyelinating disorders of the central nervous system were used as a control group. MAIN OUTCOMES AND MEASURES: Delay to diagnosis in months, clinical and radiological characteristics, and disability measured by ambulatory status. RESULTS: Twenty-five patients who were AQP4-IgG seropositive with an initial STM represented 14% of initial myelitis episodes among patients with NMOSD. The STM episode was defined as the first manifestation of NMOSD in 10 patients (40%) preceded by optic neuritis in 13 patients (52%) and preceded by a nausea and vomiting episode in 2 patients (8%). In comparison with the excluded patients with NMOSD who had an initial longitudinally extensive transverse myelitis, delay to diagnosis/treatment was greater when initial lesions were short (P = .02). In AQP4-IgG-positive STM cases, subsequent myelitis episodes were longitudinally extensive in 92%. Attributes more common in patients with AQP4-IgG-positive STM than in 27 population-based patients with AQP4-IgG-negative STM included the following: nonwhite race/ethnicity; tonic spasms; coexisting autoimmunity; magnetic resonance imaging (central cord lesions, T1 hypointensity, and a brain inconsistent with multiple sclerosis); and cerebrospinal fluid (oligoclonal bands lacking). CONCLUSIONS AND RELEVANCE: Short transverse myelitis is not uncommon in NMOSD and, when it is present, delays diagnosis and treatment. Clinical and radiological characteristics identified in this study may help select patients with STM who are at the highest risk for an NMOSD. Short transverse myelitis does not exclude consideration of AQP4-IgG testing or NMOSD diagnosis.

[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's encephalopathy (n = 1), microscopic polyangiitis (n = 1) and unclassified autoimmune encephalopathy (n = 1). Progressive memory loss without delirium was the main symptom.In addition, 3 patients suffered epilepsy, 2 with intractable hyponatremia, 4 with positive serum autoimmune or paraneoplastic antibodies, 7 with inflammatory cerebrospinal fluid, 4 with abnormal electroencephalography (EEG) and 8 with various changes on brain magnetic resonance imaging (MRI). Two patients had concurrent Hashimoto's thyroiditis and another with small cell lung cancer. All patients improved after treatment with immunological and antineoplastic therapies. CONCLUSION: Autoimmune dementia has complex causes with a rapidly progressive and fluctuating course. The coexisting conditions include epilepsy, hyponatremia, organ-specific autoimmunity, inflammatory spinal fluid with abnormal EEG and brain MRI findings.Immunotherapy is recommended.

Aquaporin 4 IgG serostatus and outcome in recurrent longitudinally extensive transverse myelitis.

IMPORTANCE: Studies focused on recurrent longitudinally extensive transverse myelitis (rLETM) are lacking. OBJECTIVES: To determine the aquaporin 4 (AQP4) IgG detection rate using recombinant human APQ4-based assays in sequential serum specimens collected from patients with rLETM categorized as negative by first-generation tissue-based indirect immunofluorescence (IIF) assay and to define the clinical characteristics and motor disability outcomes in AQP4-IgG-positive rLETM. DESIGN, SETTING, AND PARTICIPANTS: A search of the Mayo Clinic computerized central diagnostic index (October 1, 2005, through November 30, 2011), cross-linked with the Neuroimmunology Laboratory database, identified 48 patients with rLETM, of whom 36 (75%) were positive and 12 (25%) negative for neuromyelitis optica (NMO) IgG (per IIF of serial serum specimens). Stored serum specimens from "seronegative" patients were retested with recombinant human AQP4-based assays, including enzyme-linked immunosorbent, transfected cell-based, and fluorescence-activated cell-sorting assays. Control patients included 140 AQP4-IgG-positive patients with NMO, of whom a subgroup of 20 initially presented with 2 attacks of transverse myelitis (rLETM-onset NMO). MAIN OUTCOMES AND MEASURES: AQP4-IgG serostatus, clinical characteristics, and Expanded Disability Status Scale score. RESULTS: Six patients with negative IIF results were reclassified as AQP4-IgG positive, yielding an overall AQP4-IgG seropositivity rate of 89%. Fluorescence-activated cell-sorting, cell-based, and enzyme-linked immunosorbent assays improved the detection rate to 89%, 85%, and 81%, respectively. The female to male ratio was 2:3 for AQP4-IgG-negative rLETM and 5:1 for AQP4-IgG-positive patients. The AQP4-IgG-positive patients with rLETM or rLETM-onset NMO were similar in age at onset, sex ratio, attack severity, relapse rate, and motor disability. From Kaplan-Meier analyses, 36% of AQP4-IgG-positive patients with rLETM are anticipated to need a cane to walk within 5 years after onset. For patients with rLETM-onset NMO, the median time from onset to first optic neuritis attack (54 months) was similar to the median disease duration for AQP4-IgG-positive patients with rLETM (59 months). The median number of attacks was 3 for AQP4-IgG-positive patients with rLETM (range, 2-22), and the first optic neuritis attack for those with rLETM-onset NMO followed a median of 3 myelitis attacks (range, 2-19). Immunosuppressant therapy reduced the relapse rate in both AQP4-IgG-positive and AQP4-IgG-negative patients with rLETM. CONCLUSIONS AND RELEVANCE: Recombinant antigen-based assays significantly increase AQP4-IgG detection in patients with rLETM, and AQP4-IgG-negative adults with rLETM are rare. Evolution to NMO can be anticipated in AQP4-IgG-positive patients. Early initiation of immunotherapy may result in a more favorable motor outcome.

[Longitudinally extensive spinal cord lesion: etiology and imaging features].

OBJECTIVE: To explore the etiologies and imaging features of longitudinally extensive spinal cord lesion (LESCL). METHODS: The etiologies and magnetic resonance (MR) imaging features of 51 hospitalized LESCL patients from January 2011 to August 2013 were reviewed and retrospectively analyzed. RESULTS: Among them, the causes were neuromyelitis optica spectrum disorder (NMOSD, n = 25), isolated longitudinally extensive transverse myelitis (n = 6), subacute combined degeneration (n = 4), multiple sclerosis (MS, n = 3), paraneoplastic myelopathy (n = 3), anterior spinal artery syndrome (n = 3), acute disseminated encephalomyelitis (n = 2), spinal dural arteriovenous fistula (n = 2), intramedullary spinal cord metastasis (n = 1), myelopathic leukemia (n = 1) and syringomyelus (n = 1). For MR imaging, at least one lesion of each patient presented continuously longitudinal profile and whole-length spinal cord was involved in 11 patients. CONCLUSION: LESCL may be caused by various diseases. And the imaging features may aid its diagnosis despite a lack of specificity.