Longitudinally Extensive Transverse Myelitis Patients Research Articles

Etiology and Factors Related Outcomes of Longitudinally Extensive Transverse Myelitis in Thailand

Objective This study aimed to evaluate the clinical features, etiology, and prognosis of longitudinally extensive transverse myelitis (LETM) patients in Thailand. Background LETM has various etiology and is different in each region. Proper investigations are essential to reduce misdiagnosis and delay in treatments, which affect clinical recovery and prognosis. In Thailand, there is no clinical study on the etiology of LETM. Therefore, our study aimed to evaluate the clinical features, etiology, and prognosis of LETM patients in Thailand. Design/Methods Patients diagnosed with LETM at University Hospital between January 2015 and October 2021 were included. Patient demographics, clinical presentations, Expanded Disability Status Scale (EDSS), imagings, laboratory testing, cerebrospinal fluid profiles, final diagnosis, and treatments were recorded. Factors related to outcomes of LETM were analyzed. Results A total of 40 patients, there were 21 females (52.5%), the mean age of onset was 48.4 years (SD = 15.8). NMOSD was the most common etiology of LETM (n = 15), followed by infection (n = 5), SLE (n = 5), idiopathic causes (n = 4), CIS (n = 3), MS (n = 1), spinal dural AVF (n = 2), ADEM (n = 2), either 1 had spinal cord infarction, schwannoma, and vitamin B12 deficiency. Most patients in this study had severe LETM (n = 31). Complete cord had significantly poorer outcome (p-value = 0.003), while dorsolateral and anterior cord had better outcome (p-value = 0.046, 0.046). Conclusions NMOSD was the most common etiology of LETM, and a history of prior attacks led to the diagnosis of NMOSD. Complete cord lesion on axial spinal cord MRI was sensitive to NMOSD but not specifically. Factors related to the prognosis of LETM included completed cord lesions on MRI axial view trended to have a poor outcome, and dorsolateral and anterior cord lesions had a better prognosis.

Longitudinally Extensive Transverse Myelitis: A Retrospective Study Differentiating Neuromyelitis Optica Spectrum Disorder From Other Etiologies.

BackgroundLongitudinally extensive transverse myelitis (LETM) is characterized by contiguous immune-mediated inflammatory lesion of the spinal cord extending more than three vertebral segments. Neuromyelitis optica spectrum disorder (NMOSD) is the most common and important cause of LETM. This study aims to evaluate the demographic profile, clinical presentations, neuroimaging features, laboratory parameters, and etiologies of LETM and differentiates NMOSD from other etiologies of LETM.MethodologyThis retrospective cross-sectional study was conducted at the Department of Neurology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal. After receiving clearance from the ethical committee, a retrospective chart review was conducted and records of all the inpatient LETM cases admitted from March 2018 to June 2020 were obtained. From the patient records, the following information was extracted: the demographic profile, clinical presentations, neuroimaging features, cerebrospinal fluid analysis, serum anti-aquaporin-4 (AQP4) immunoglobulin G status, hemogram, infectious disease profile, inflammatory markers, and auto-immune panels. Descriptive analysis of data was performed with SPSS statistics 23.0 version (IBM Corp, Armonk, NY, USA).ResultsIn our study, the mean age of LETM patients was 36.58 years, and 12 out of 19 (63.15%) patients were young, with an age less than 40 years. A total of 13 (68.40%) patients were male, with a male-to-female ratio of 2.16. Seven (36.80%) patients had a clinical diagnosis of NMOSD with anti-AQP4 antibody-positive status, four (21.10%) had unknown etiology, three (15.8%) had post-infectious transverse myelitis, and three (15.80%) had a diagnosis of idiopathic transverse myelitis. There was a single case (5.30%) of cervical spondylotic myelopathy and leukemic transverse myelitis each. The common presenting symptoms of LETM were bladder dysfunction, paraparesis, quadriparesis, and visual impairment. Visual involvement, either unilateral or bilateral, was common in NMOSD and LETM of unknown etiology category. Similarly, brain lesion was common in patients with NMOSD and LETM of unknown etiology category.Conclusion LETM is a heterogeneous disorder with diverse etiologies and clinical presentations. NMOSD is an important cause of LETM that predominantly affects females. Optic neuritis can be seen in LETM of various etiologies, but it is more common in anti-AQP4-positive NMOSD patients. Brain lesions in LETM are common in anti-AQP4-positive NMOSD.

Frequency and characteristics of short versus longitudinally extensive myelitis in adults with MOG antibodies: A retrospective multicentric study

Objectives: We aim to (1) determine the frequency and distinctive features of short myelitis (SM) and longitudinally extensive transverse myelitis (LETM) in a cohort of adults with myelin oligodendrocyte glycoprotein (MOG)-antibody (Ab)-associated myelitis and (2) determine baseline prognostic factors among MOG-Ab-positive patients whose disease started with myelitis. Material and Methods: We retrospectively analyzed clinical and paraclinical variables from a multicentric French cohort of adults with MOG-Ab-associated myelitis. At last follow-up, patients were classified into two groups according to the severity of the Expanded Disability Status Scale (EDSS) as ⩽2.5 or ⩾3.0. Results: Seventy-three patients with at least one episode of myelitis over disease course were included; among them, 28 (38.4%) presented with SM at the time of the first myelitis. Motor and sphincter involvement was less frequently observed in SM (51.9% and 48.2%, respectively) than in LETM patients (83.3% and 78.6%, respectively), p = 0.007 and p = 0.017; 61% of LETM patients displayed brain lesions compared to 28.6% in the SM group, p = 0.008, and the thoracic segment was more frequently involved in the LETM (82.2%) than in the SM group (39.3%), p < 0.001. EDSS at last follow-up was higher in LETM (median 3.0 (interquartile range: 2.0–4.0)) compared to SM patients (2.0, (1.0–3.0)), p = 0.042. Finally, a higher EDSS at onset was identified as the only independent risk factor for EDSS ⩾3.0 (odds ratio, 1.40, 95% confidence interval (CI): 1.01–1.95, p = 0.046). Conclusion: SM in MOG-Ab-associated disease is not rare. The severity at onset was the only independent factor related to the final prognosis in MOG-Ab-associated myelitis.

Prevalence and risk factors of deep venous thrombosis in patients with longitudinally extensive transverse myelitis: one center data from China

ObjectiveDeep venous thrombosis (DVT) is a severe complication in longitudinally extensive transverse myelitis (LETM) patients. It may interfere with LETM treatment and delay the recovery of the spinal dysfunction. However, there is less data about the prevalence and risk factors of DVT in patients with LETM. We analyzed data retrospectively to ascertain the prevalence of DVT and the clinical risk factors for DVT.MethodsClinical data on 255 LETM patients were collected from medical records. All patients were performed color Doppler ultrasound(US) to screen DVT in both lower extremities when admitted. Clinical characteristics of LETM patients with DVT were compared with those without DVT using corresponding statistical methods. Multivariate logistic regression was performed to identify risk factors related to DVT.ResultsDVT were found in 11.8% patients with LETM. Univariate analysis showed that age, muscle force and elevated baseline D-dimer were risk factors for DVT. After multivariate logistic regression, age, dyslipidemia, segments of lesions, and elevated baseline D-dimer remained significant independent risk factors.ConclusionsDVT is common in patients with LETM and related to patient’s age, dyslipidemia, segments of lesions, and elevated baseline D-dimer. Early recognition of DVT and thrombosis prophylaxis are appropriate in patients with LETM.

Etiologic spectrum and functional outcome of the acute inflammatory myelitis.

Clinical, neuroimaging, and laboratory features are not specific enough to establish the etiological diagnosis of the acute inflammatory myelitis (AIM). Longitudinally extensive transverse myelitis (LETM) seen on magnetic resonance imaging (MRI) has been associated with a poor functional prognosis. The aim of this study was to assess the functional outcomes of a first AIM event comparing patients with LETM vs. no LETM on MRI and to report the differential diagnosis. Clinical, radiological, biochemical aspects were collected, and Winner-Hughes Functional Disability Scale (WHFDS) was performed after 3 and 6months. Centromedullary lesions were associated with LETM, lateral lesions with partial lesion (PL), and brain MRI lesions with multiple sclerosis and acute encephalomyelitis disseminated. LETM patients were associated with a worse functional outcome as the need of a wheelchair after 3 and 6months (OR=7.61 p=0.01; OR 4.8 p=0.04, respectively), a walker or cane (OR=11.0 p=0.002, OR=4.3 p=0.03, respectively). In addition, we found a correlation between LETM and acute complete transverse myelitis and PL with acute partial transverse myelitis (83.3 and 90.9%, respectively; p<0.0001). In conclusion, AIM is a heterogeneous syndrome from an etiological point of view and LETM patients had worse functional prognosis compared with PL after 3 and 6months.

Longitudinally extensive transverse myelitis: A retrospective analysis of sixty-four patients at tertiary care center of North-West India

ObjectivesTo evaluate the demographic profile, clinical presentations, laboratory parameters and etiologies of longitudinally extensive transverse myelitis (LETM) patients in Indian population. Patients and methodsLETM is characterized by contiguous inflammatory lesions of spinal cord extending to three or more vertebral segments. Neuromyelitis optica (NMO) is the most common cause of LETM. In clinical practice, both LETM and NMO are thought to be synonymous with each other because of their very frequent association. Other causes of LETM are infective, neoplastic, autoimmune diseases and connective tissue disorders. All other causes should be ruled out before making the diagnosis of NMO in LETM patients. We conducted a retrospective study from August 2010 to February 2016 and analyzed various demographic profile, clinical presentations, laboratory parameters and etiologies in sixty-four patients of LETM. ResultsIn our series, majority of the patients presented with acute bladder dysfunction and paraparesis. Twenty-one patients (32.81%) were clinically diagnosed as NMO, out of which thirteen patients were found to have positive serum NMO antibody. Other etiologies of LETM in our series were multiple sclerosis [9 patients], acute disseminated encephalomyelitis (ADEM) [6 patients], postinfectious [5 patient], subacute combined degeneration (SCD) [4 patient], tuberculous myelitis [4 patients], spinal arteriovenous malformation (AVM) [3 patient] and systemic lupus erythematosus (SLE) [3 patient], respectively. In nine patients, cause could not be ascribed despite thorough investigations. ConclusionLETM is a heterogeneous disorder with a varied clinical feature, etiologies and outcome. Even the LETM patients who presented with optic neuritis do not necessarily have NMO. Therefore, the diagnosis of NMO should be made only after excluding other causes of LETM. The presence of NMO-Ab (Aquaporin 4-Ab) predicts the increased risk of recurrence of LETM or conversion to NMO.

Quantitative analysis of aquaporin-4 antibody in longitudinally extensive transverse myelitis

Aquaporin-4 (AQP-4) antibody-positive longitudinally extensive transverse myelitis (LETM) is referred to as a neuromyelitis optica (NMO) spectrum disorder. We conducted an exploratory investigation of correlations between AQP-4 antibody serum levels, as determined by a fluorescent immunoprecipitation assay, and clinical characteristics in LETM. Expanded Disability Status Scores (EDSS) scores and number of segments of spinal cord involved were positively correlated to AQP-4 antibody levels. However, serum AQP-4 antibody levels were not correlated with the time to next attack or the conversion time of LETM to NMO, although seropositive LETM patients demonstrated a high conversion rate to NMO (78.1%).

A recurrent longitudinally extensive transverse myelitis with Aquaporin-4(AQP4) antibody after herpes zoster

Longitudinally extensive transverse myelitis (LETM) is a syndrome that involves three or more vertebral segments in the spinal cord lesion, and it is one of the characteristic features of neuromyelitis optica (NMO) differentiating it from multiple sclerosis. Many studies proved the importance of aquaporin-4 (AQP4) antibody, which plays a vital role in the pathogenesis of NMO. Recent reports suggest that recurrent LETM patients with positive anti-AQP4 antibody titers have a higher chance of converting to NMO, and they are now termed as NMO spectrum disorders (NMOSD). The specific role of AQP4 antibody in NMO is yet to be elucidated but there are reports to bring up the pathogenesis in relation with infectious events. Interestingly, parainfectious NMOSD tends to spare the optic nerve unlike classic NMOSD. Here we report a young woman who was once diagnosed as herpes zoster-related LETM, but later developed as recurrent LETM with positive AQP4 antibody titers, which renders the diagnosis of parainfectious LETM without optic neuritis.

Distinctive clinical and neuroimaging characteristics of longitudinally extensive transverse myelitis associated with aquaporin-4 autoantibodies

Longitudinally extensive transverse myelitis (LETM) is a characteristic feature of Neuromyelitis Optica (NMO), but it can also occur in several other inflammatory diseases of the central nervous system (CNS). An IgG autoantibody that binds to aquaporin-4 (AQP4), the predominant water channel of the CNS, is a reliable biomarker of the NMO spectrum disorders, and if detected predicts the recurrence of the myelitis. In this study, we compared the clinical and neuroimaging characteristics of AQP4-IgG+ and AQP4-IgG- LETM patients. Thirty-seven first-ever LETM patients were retrospectively evaluated and divided into two groups according to the presence of AQP4 autoantibodies. AQP4-IgG was detected in the serum and in the cerebrospinal fluid of sixteen patients. The female to male ratio was higher in AQP4-IgG+ patients. Intractable nausea and vomiting and paroxysmal tonic spasms often accompanied the LETM in AQP4-IgG+ patients. T2-weighted spinal cord MRI revealed that inflammatory lesions extending into the brainstem and involving the central grey matter occurred more frequently in AQP4-IgG+ LETM patients. Hypointense lesions on T1-weighted spinal cord MRI were detected more frequently in the seropositive group, and their presence correlated with attack severity. In conclusion, this study provides clinical and spinal cord neuroimaging clues that can help distinguishing AQP4-IgG+ LETM patients.

Clinical and immunological follow-up of B-cell depleting therapy in CNS demyelinating diseases

The aim of this observational study was to analyze clinical and immunological effects of rituximab treatment in neuromyelitis optica (NMO) and longitudinally extensive transverse myelitis (LETM) patients. We report on four NMO and two recurrent LETM patients who were treated with rituximab. Overall, B-cell depletion resulted in profound clinical stabilization in all patients. Rituximab did not affect titers of antibodies to aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein, immunoglobulin (Ig) isotypes and IgG subtype distribution, even after long-term B-cell depletion. Relapses were not associated with re-emerging B-cells, serum levels of B-cell activating factor (BAFF) or AQP4-IgG titers. BAFF serum levels increased following rituximab treatment.

Distinct features between longitudinally extensive transverse myelitis presenting with and without anti-Aquaporin 4 antibodies

Objectives: Longitudinally extensive transverse myelitis (LETM) with spinal cord lesions spanning three or more vertebral segments is a key feature of neuromyelitis optica (NMO). However, the role of anti-aquaporin 4 (anti-AQP4) antibody, a sensitive biomarker of NMO, in the conversion of LETM to NMO remains uncertain. Methods: Thirty first-ever LETM patients were retrospectively analysed and divided into two groups according to the presence of anti-AQP4 antibodies. Results: Eighteen (60%) patients presented with anti-AQP4 antibodies. Fifteen (83.33%) anti-AQP4 (+) LETM patients converted to NMO, while only three of 12 (25%, p = 0.002) anti-AQP4 (-) LETM patients progressed to NMO, over a mean follow-up period of 5.63 years. Seven (38.89%) anti-AQP4 (+) and one (8.33%) anti-AQP4 (-) LETM patients received interferon-β1a treatment, respectively. Anti-AQP4 (+) LETM patients demonstrated a higher immunogamma globulin (IgG) index (0.68 ± 0.43 versus 0.47 ± 0.19, p = 0.018), annual relapse rate (0.72 ± 0.31 versus 0.42 ± 0.17, p = 0.01) and Kurtzke Expanded Disability Status Scale (4.28 ± 2.22 versus 2.67 ± 2.26, p = 0.031), than anti-AQP4 (-) LETM patients. In spinal magnetic resonance imaging (MRIs), more than half (58.33%) of the anti-AQP4 (+) LETM patients were observed to have central grey matter-predominant involvement in the axial view, while peripheral white matter-predominant involvement (51.85%) was the most common pattern observed in the anti-AQP4 (-) LETM patients. Conclusion: Anti-AQP4 (+) LETM demonstrated a high conversion rate to NMO (83.33%), suggesting that anti-AQP4 (+) LETM may represent an early, isolated syndrome of NMO spectrum disorder. The greater number of patients receiving interferon-β treatment in anti-AQP4 (+) LETM may contribute to its high annual relapse rate.

Clinical characteristics, prognosis, and seropositivity to the anti-aquaporin-4 antibody in Korean patients with longitudinally extensive transverse myelitis

Longitudinally extensive transverse myelitis (LETM) is a syndrome with extensive spinal cord lesions spanning three or more vertebral segments on spinal cord MRI. Although many reports have indicated that LETM is a characteristic feature of neuoromyelitis optica (NMO) in Western countries, the clinical characteristics and risk for development of NMO in Korean patients with LETM is not clear. We retrospectively investigated the clinical, laboratory, radiological features, and prognosis of Korean patients with a first-ever episode of idiopathic LETM. Patients were classified into four subgroups, depending on their clinical course: monophasic LETM, recurrent LETM, NMO, and classic multiple sclerosis (MS). We compared various clinical, laboratory, and radiological features between groups. Of 20 patients with first-ever LETM, 15 (75%) were men, and 13 (65%) experienced clinical relapse over a mean follow-up period of 58 months. Three of 20 patients (two with NMO, one with recurrent myelitis) were seropositive for anti-AQP4 antibodies. The predominance of men in the monophasic and recurrent LETM groups compared to the NMO group was remarkable. In conclusion, Korean patients with LETM are predominantly male and have low seropositivity for anti-AQP4 antibody, which distinguishes them from LETM patients in Western countries. Patients with LETM and seropositivity for anti-AQP4 antibody have a high risk of relapse. The male predominance and the relatively low seropositive rate for anti-AQP4 suggests that rather than being a limited form of NMO, recurrent LETM is a new clinical entity in Koreans.

Minor salivary gland inflammation in Devic’s disease and longitudinally extensive myelitis

Devic’s disease is often considered as a variant of multiple sclerosis (MS). However, evidence suggests that Devic’s disease may be distinct from MS. Devic’s disease can coexist with connective tissue diseases, particularly Sjögren’s disease, but this association is rare with MS. Diagnosis of Sjögren’s disease in patients with neurological symptoms is often difficult. During early stages of Sjögren’s disease, patients may not fulfill all criteria for Sjögren’s disease. A high percentage of patients with Sjögren’s disease have inflammatory infiltrates in minor salivary glands, and this may be a reliable indicator of early or subclinical disease. We show high prevalence (80%) of salivary gland inflammation in Devic’s disease and longitudinally extensive transverse myelitis (LETM). We diagnosed 16 patients with Devic’s disease, and 2 of these satisfied criteria for Sjögren’s disease as did 2 of 9 patients with LETM. Anti-SSA/B titers were infrequently elevated. Although most did not satisfy criteria for Sjögren’s disease. 9 of 12 Devic’s disease patients and 7 of 8 LETM patients had severe salivary gland inflammation. Thus: (1) patients with Devic’s disease or with LETM who have positive labial biopsies but do not satisfy criteria for Sjögren’s disease could have subclinical Sjögren’s diseases. Alternatively, (2) as patients with Devic’s disease have elevated titers of several autoantibodies, so there may exist a set of antibodies that react with antigens in minor salivary glands and cause inflammation. Minor salivary gland biopsy is more sensitive than anti-SSA/B serology in providing histological evidence for possible Sjögren’s disease with CNS lesions.