Transverse Myelitis Consortium Working Group Research Articles

Longitudinally extensive transverse myelitis in childhood: Clinical features, treatment approaches, and long-term neurological outcomes

AimLongitudinally extensive transvers myelitis (LETM) is a rare and disabling condition in childhood. The aim of the present study was to share experiences from our center regarding the treatment features and clinical and radiologic course in our LETM patients in light of the literature data. Material and methodThe study was designed as cross-sectional and included children who followed for LETM at our pediatric neurology clinic between 2010 and 2019. ATM was diagnosed according to the diagnostic criteria report from the Transverse Myelitis Consortium Working Group. LETM was defined as the presence of spinal cord lesions spanning a length of 3 or more consecutive vertebral segments. The patients’ medical records were examined in terms of demographic characteristics, presenting symptoms, history of infection prior to and during LETM, prodromal history, neurological examination, laboratory and radiological findings, clinical course, and treatment. The Barthel Index was used to assess the physical independence in activities of daily living of patients with LETM who were followed for at least one year. ResultsA total of 15 (8 girl) patients were included in the study. The patients were between 1 and 17 years of age. Presenting symptoms included inability to walk in 12 patients, incontinence in 9 patients, low back pain in 4 patients, abdominal pain in 2 patients, and inability to use the arms in 2 patients. In Barthel Index assessment of physical independence in activities of daily living, 8 patients were evaluated as completely independent, 3 patients as moderately dependent, and 2 patients as slightly dependent. When the 4 patients with motor area impairment and moderate dependency according to the Barthel Index were examined, it was noted that all of them had been admitted 4 days after the onset of symptoms and that 2 (13.3%) had cervicothoracic involvement and 2 (13.3%) had involvement of the entire cord. ConclusionShorter delay from symptom onset to initiation of immunomodulatory therapy as well as effective rehabilitation resulted in favorable outcomes, with the most noticeable improvement in the areas of motor function and incontinence.

Frequency and etiology of acute transverse myelitis in Southern Finland

Objective: Acute transverse myelitis is a relatively rare, frequently debilitating but potentially treatable emergency. The objective of this study was to evaluate the incidence and etiology of acute transverse myelitis in two major hospital districts in Southern Finland. Methods: We identified all patients with acute transverse myelitis admitted to Turku University Hospital and Päijät-Häme Central hospital during nine years. The two hospitals serve a catchment area of 673,000 people in Southern Finland. Acute transverse myelitis was diagnosed according to the 2002 Transverse Myelitis Consortium Working Group. Patient files were reviewed for details of the clinical presentation and disease outcome, for laboratory findings and for neuroimaging. Charts were re-evaluated after an average of 7.7 years for confirmation of the acute transverse myelitis etiology. Results: In total 63 patients fulfilled the Transverse Myelitis Consortium Working Group diagnostic criteria for acute transverse myelitis. The frequency of the condition was hence 1.04 cases/ 100,000 inhabitants/ year. In the studied cohort, 7/63 (11%) patients had idiopathic transverse myelitis after initial evaluation and in 4/63 (6.3%) patients the idiopathic transverse myelitis remained the final diagnosis after follow-up and re-evaluation. Of the disease-associated myelitis cases MS or clinically isolated syndrome was the largest group, explaining 41% of all myelitis cases. The mean follow-up time before a patient was diagnosed with MS was 1.7 ± 2.2 years. Other etiologies included acute disseminated encephalomyelitis (ADEM), neurosarcoidosis, neuromyelitis optica (NMO), systemic autoimmune diseases and infectious diseases. Conclusions: In more than half of the acute transverse myelitis cases the final diagnosis is other than MS. Careful diagnostic work-up is needed for correct early treatment and best long-term outcome.

Clinical, laboratory features, and prognostic factors in adult acute transverse myelitis: an Italian multicenter study.

We compared the clinical, laboratory, and radiological features of different subgroups of acute transverse myelitis (ATM) diagnosed according to the criteria established by the Transverse Myelitis Consortium Working Group (TMCWG) as well as of non-inflammatory acute transverse myelopathies (NIATM) to identify possible short- and long-term prognostic factors. A multicenter and retrospective study comprising 110 patients with ATM and 15 NIATM admitted to five Italian neurological units between January 2010 and December 2014 was carried out. A significantly higher frequency of isolated sensory disturbances at onset in ATM than in NIATM patients (chi-square = 14. 7; P = 0.005) and a significantly higher frequency of motor symptoms in NIATM than ATM (chi-square = 12.4; P = 0.014) was found. ATM patients with high disability at discharge had more motor-sensory symptoms without (OR = 3.87; P = 0.04) and with sphincter dysfunction at onset (OR = 7.4; P = 0.0009) compared to those with low disability. Higher age (OR = 1.08; P = 0.001) and motor-sensory-sphincter involvement at onset (OR = 9.52; P = 0.002) were significantly associated with a high disability score at discharge and after a median 1-year follow-up. The diagnosis of ATM may prevail respect to that of NIATM when a sensory symptomatology at onset occurs. In ATM, patients older and with motor-sensory involvement with or without sphincter impairment at admission could experience a major risk of poor prognosis both at discharge and at longer time requiring a timely and more appropriate treatment.

Vaccine Induced Acute Transverse Myelitis: Case Report

Acute transverse myelitis is a focal inflammatory disorder of the spinal cord [1]. One of the main etiologic factors include, multiple sclerosis, post-infectious and post-traumatic events although autoimmune phenomenon is the most common cause [2].Transverse Myelitis (TM) due to etiology other than Multiple Sclerosis has shown spinal cord involvement of two or more segments [3]. Annually millions of active immunization with vaccines is carried out globally with little transverse myelitis caused because of the adverse reactions due to these vaccinations [4,5]. In order to improve accuracy of reporting, research and diagnosis, the Transverse Myelitis Consortium Working Group (TMCWG) has produced criteria for the diagnosis of ATM [6].Here we report a case of TM in adult, diagnosed as TM consistent with the TMCWG criteria and probably this is the first ever been reported case from Nepal.

Vaccine Induced Acute Transverse Myelitis: A Case Report

Acute transverse myelitis is a focal infl ammatory disorder of the spinal cord. One of the main etiologic factors include, multiple sclerosis, post-infectious and post-traumatic events although autoimmune phenomenon is the most common cause. Transverse Myelitis (TM) due to etiology other than Multiple Sclerosis has shown spinal cord involvement of two or more segments. Annually millions of active immunization with vaccines is carried out globally with few transverse myelitis caused because of the adverse reactions due to these vaccinations. In order to improve accuracy of reporting, research and diagnosis, the Transverse Myelitis Consortium Working Group (TMCWG) have produced criteria for the diagnosis of ATM. Here we report a case of TM in adult, diagnosed as TM consistent with the TMCWG criteria and probably this is the first ever been reported case from Nepal. Nepal Journal of Neuroscience. Vol. 13, No. 2, 2016, Page: 89-91

Pediatric transverse myelitis.

Pediatric acute transverse myelitis (ATM) is an immune-mediated CNS disorder and contributes to 20% of children experiencing a first acquired demyelinating syndrome (ADS). ATM must be differentiated from other presentations of myelopathy and may be the first presentation of relapsing ADS such as neuromyelitis optica (NMO) or multiple sclerosis (MS). The tenets of the diagnostic criteria for ATM established by the Transverse Myelitis Consortium Working Group can generally be applied in children; however, a clear sensory level may not be evident in some. MRI lesions are often centrally located with high T2 signal intensity involving gray and neighboring white matter. Longitudinally extensive ATM occurs in the majority. Asymptomatic lesions on brain MRI are seen in more than one-third and predict MS or NMO. The role of antibodies such as myelin oligodendrocyte glycoprotein in monophasic and relapsing ATM and their significance in therapeutic approaches remain unclear. ATM is a potentially devastating condition with variable outcome and presents significant cumulative demands on health and social care resources. Children generally have a better outcome than adults, with one-half making a complete recovery by 2 years. There is need for standardization of clinical assessment and investigation protocols to enable international collaborative studies to delineate prognostic factors for disability and relapse. There are no robust controlled trials in children or adults to inform optimal treatment of ATM, with one study currently open to recruitment. This review provides an overview of current knowledge of clinical features, investigative workup, pathogenesis, and management of ATM and suggests future directions.

Cytokines and matrix metalloproteinases in the cerebrospinal fluid of patients with acute transverse myelitis: an outcome analysis.

Role of cytokines as well as matrix metalloproteinases (MMPs) is well defined in various central nervous system inflammatory diseases. However, the role of these cytokines and MMPs in acute transverse myelitis is inadequately studied. Patients with acute transverse myelitis, fulfilling the inclusion and exclusion criteria defined by Transverse Myelitis Consortium Working Group, were enrolledalong with age and sex matchedcontrols. A detailed clinical evaluation and magnetic resonance imaging of patients was done. Cerebrospinal fluid (CSF) samples both from patients and controls were collected. CSF samples were analyzed for cytokines [interleukin (IL)-6, IL-8, IL-10 and IL-17)] and matrix metalloproteinases (MMP-2, MMP-9). Patients were followed up for 3months. Disability was assessed using modified Barthel index (MBI). CSF levels of all cytokines IL-6, IL-8, IL-10, MMP-2 and MMP-9, except IL-17, were significantly higher in patients with acute transverse myelitis (p<0.001). CSF IL-6 and IL-8 were significantly associated with severity of the disease (MBI≤12). After 3months, quadriparesis (p=0.001, odd's ratio 19.5, 95% CI 2.34-62.39) and long-segment myelitis (p=0.035, odd's ratio 4.37, 95% CI 1.17-5.95) were significantly associated with poor outcome. Among cytokines and MMPs, IL-6 levels at baseline correlated significantly with the MBI at 3months (Spearmen's ρ=-0.335, p=0.01). In conclusion, both anti-inflammatory and pro-inflammatory cytokines, MMP-2, and MMP-9 are elevated in the acute phase of transverse myelitis. Possibly, IL-6 plays a role in determining the disability.

Systemic lupus erythematosus-associated acute transverse myelitis: manifestations, treatments, outcomes, and prognostic factors in 20 patients.

Transverse myelitis is a rare complication of systemic lupus erythematosus (SLE). This retrospective multicentre study identifies the prognostic factors in a relatively large patient series. Twenty patients fulfilled the SLE criteria of the ACR classification and the Transverse Myelitis Consortium Working Group. A severe neurological flare was defined as muscle strength grade <3/5 in more than half the muscle groups at the motor neurological level. Inability to run or another significant ambulation-unrelated disability was considered as 'unfavourable neurological outcome'. Myelitis was the first SLE symptom in 12 patients; in the eight others, it occurred 8.6 years (median delay) after SLE onset. Eleven patients presented severe neurological impairments. The treatment included corticosteroids in all patients associated with intravenous cyclophosphamide in 11 and/or hydroxychloroquine in 14. Unfavourable outcomes were observed in 53% of the patients at six months and in 28% at end of follow-up (median: 5.9 years). An initial severe neurological impairment and no cyclophosphamide use were associated with unfavourable neurological outcomes at six months and at end of follow-up, respectively. Transverse myelitis may reveal SLE or occur more than 10 years after SLE diagnosis. The initial severity of the neurological flare (with paraplegia) is the main prognostic marker. The study provides arguments for cyclophosphamide use.

Prognostic Indicators of Acute Transverse Myelitis in 39 Children

BackgroundThe Transverse Myelitis Consortium Working Group has proposed new diagnostic criteria for acute transverse myelitis. The purpose of the present study is to evaluate the relations between clinical variables and functional prognosis using new criteria. MethodsWe reviewed 39 Chinese cases meeting the new criteria, recorded clinical epidemiological data, and followed activities of daily living measuring scale (Modified Barthel Index). ResultsThirty-nine children met new criteria for definite acute transverse myelitis in the past 14 years between 1995 and 2008. Mean follow-up time was 102.7 months. Conversion to multiple sclerosis occurred in two patients (5.1%). Those children with a short time to maximal deficits, long time of peak neurological impairment and initial time of treatment, increased protein levels of the cerebrospinal fluid, and secondary infection were more likely to have residual neurological deficits, resulting in lower qualities of life (P = 0.005, P = 0.003, P = 0.011, P = 0.0012, P = 0.000, respectively). ConclusionsA short time to maximal deficits, long time of peak neurological impairment and initial time of treatment, increased protein levels of cerebrospinal fluid, and secondary infection played important roles in predicting poor prognosis.

Idiopathic acute transverse myelitis: outcome and conversion to multiple sclerosis in a large series

BackgroundIn 2002, the Transverse Myelitis Consortium Working Group (TMCWG) proposed the diagnostic criteria for idiopathic acute transverse myelitis (IATM) to delimit and unify this group of patients. This study aimed to describe the conversion rate to multiple sclerosis (MS) and variables associated with conversion, and to analyze functional outcome and prognostic factors associated with functional recovery in patients who fulfilled the current TMCWG criteria for definite and possible IATM.MethodsEighty-seven patients diagnosed with IATM between 1989 and 2011 were retrospectively reviewed. Two patients with positive neuromyelitis optica IgG serum antibodies were excluded. Epidemiological, clinical, laboratory, magnetic resonance imaging (MRI) data and outcome of 85 patients were analyzed.ResultsEleven (13%) patients converted to MS after a median follow-up of 2.9 years (interquartile range 1.0-4.8). Early-age onset of symptoms was related to conversion to MS. Only 9.4% of patients with IATM were unable to walk unassisted at the end of follow-up. Urinary sphincter dysfunction (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.04-10.92) and longitudinally extensive transverse myelitis (LETM) on MRI (OR 12.34, 95% CI 3.38-45.00) were associated with a poorer outcome (Rankin ≥ 2).ConclusionsAt least 13% of patients who fulfill the TMCWG criteria for definite and possible IATM will convert to MS. Functional recovery in IATM is poorer in patients with urinary sphincter dysfunction at admission or LETM on MRI.

Acute transverse myelitis in Buenos Aires, Argentina. A retrospective cohort study of 8 years follow-up

IntroductionEpidemiological studies on acute transverse myelitis (ATM) in South America are scarce. The aim of our study was to describe demographic, clinical and para-clinical features of patients with ATM in a health care organisation in Buenos Aires. A further objective was to determine the aetiologies of ATM. MethodsAll patients diagnosed with ATM between June 1, 2002 and June 30, 2010 were retrospectively identified, using the Transverse Myelitis Consortium Working Group (TMCWG) criteria. ResultsA total of 40 patients diagnosed with ATM (24 females, 60%) were included. The mean follow-up was 57±8 months. The principal cause of myelitis found was ATM secondary to demyelinating disease (55%). Idiopathic ATM was diagnosed in 15 (37.5%) cases in the sample. The majority of patients had an extensive cord lesion (50%) detectable with spinal MRI. ConclusionThere are few epidemiological studies concerning ATM in Argentina, and we believe that it is important to be aware of the manner in which this condition manifests itself in this region. We would therefore be able to compare them with studies previously published in other countries.

Mielitis transversa aguda en Buenos Aires, Argentina. Estudio de una cohorte retrospectiva de 8 años de seguimiento

IntroductionEpidemiological studies on acute transverse myelitis (ATM) in South America are scarce. The aim of our study was to describe demographic, clinical and para-clinical features of patients with ATM in a health care organisation in Buenos Aires. A further objective was to determine the aetiologies of ATM. MethodsAll patients diagnosed with ATM between June 1, 2002 and June 30, 2010 were retrospectively identified, using the Transverse Myelitis Consortium Working Group criteria. ResultsA total of 40 patients diagnosed with ATM, (24 females, 60%) were included. The mean follow-up was 57±8 months. The principal cause of myelitis found was ATM secondary to demyelinating disease (55%). Idiopathic ATM was diagnosed in 15 (37.5%) cases in the sample. The majority of patients had an extensive cord lesion (50%) detectable with spinal MRI. ConclusionThere are few epidemiological studies concerning ATM in Argentina, and we believe that it is important to be aware of the manner in which this condition manifests itself in this region. We would therefore be able to compare them with studies previously published in other countries.

Acute transverse myelitis and antiphospholipid antibodies in lupus. No evidence for anticoagulation

Current views suggest that prothrombotic properties of antiphospholipid antibodies (aPL) have a role in the development of acute transverse myelitis (ATM) in patients with systemic lupus erythematosus (SLE). Consequently, empiric anticoagulation may be included in these patients' treatment. We performed a systemic review of the literature to explore the clinical value of the presence of aPL in patients with lupus myelitis and the possible effectiveness of anticoagulation. We analyzed clinical and laboratory data extracted from published cases of SLE-associated ATM, fulfilling the Transverse Myelitis Consortium Working Group diagnostic criteria, that provided information on aPL. We report on a total of 70 patients. aPL, detected upon ATM onset in 54% of patients, neither predicted the involvement of the thoracic part of the spine, which has been postulated to reflect a predominantly thrombosis-induced injury, nor correlated with relapsing ATM, additional lupus CNS manifestations, or worse clinical outcome. An unfavorable outcome could be predicted by paralysis (P=0.02) and abnormal CSF findings at presentation (P=0.02). Whilst all patients received major immunosuppressive regimens, severe neurologic impairment (estimated Expanded Disability Status Scale score>7) was found primarily in aPL-negative patients (P=0.03). Anticoagulation was more frequently applied in aPL-positive patients (P=0.04), but any additional therapeutic effect was not evident. Detection of circulating aPL at ATM onset appears unreliable to suggest a thrombotic cause and perhaps not enough to dictate therapeutic anticoagulation. Registry creation of ATM in patients with SLE is needed to obtain more definite answers on the role of aPL in this condition.

606: Incidence, prognostic features and clinical outcomes of idiopathic acute transverse myelitis in Canterbury, New Zealand

Acute transverse myelitis (ATM) manifests as sensory, motor or autonomic dysfunction due to inflammation of the spinal cord. Common causes of inflammation include post radiation myelopathy, cord infarction, infections, multiple sclerosis or related to systemic disease. Recent diagnostic criteria for acute transverse myelitis by the Transverse Myelitis Consortium Working Group propose a definition for “idiopathic” ATM. Signs, symptoms, time course of progression and evidence for inflammation consistent with ATM are specified for inclusion criteria.

Idiopathic acute transverse myelitis: a clinical study and prognostic markers in 45 cases

Objective The Transverse Myelitis Consortium Working Group has proposed new diagnostic criteria for idiopathic acute transverse myelitis (ATM). We reviewed patients admitted to our center diagnosed with myelitis with two objectives: (i) to evaluate the usefulness of these criteria in distinguishing between myelitis as the first episode of multiple sclerosis (MS) and idiopathic ATM; and (ii) to analyse the clinical and laboratory variables that may be used as functional prognostic markers. Methods We selected patients who met the criteria. We recorded clinical epidemiological data, patients treated with methylprednisolone, maximal disability reached and disability at final follow-up. We also recorded cerebrospinal fluid (CSF) data and the number of levels affected in the spinal magnetic resonance imaging (MRI). Results Twenty-four patients fulfilled the criteria for definite ATM and 21 for possible ATM. Five patients converted to MS. Mean follow-up time was 3.5 years. There was an association between younger patients and female patients with conversion to MS. The highest Rankin score reached and increased CSF glucose levels were associated with a poor outcome. In multivariate analysis, only the admission Rankin score was associated with outcome. Conclusions (i) About 10% of patients who met the criteria may convert to MS; and (ii) admission Rankin score was the only independent prognostic factor found.

Acute transverse myelitis

Acute noncompressive myelopathies were first recognized in the 19th century, and early pathologic studies identified both inflammatory and vascular etiologies.1–3 The terms acute transverse myelitis (ATM) and acute transverse myelopathy have been used interchangeably to describe a syndrome characterized by anterior and posterior (hence transverse) spinal cord impairment resulting in weakness, a sensory level, and autonomic dysfunction. Possible causes include vascular, infectious, neoplastic, collagen vascular, iatrogenic, and autoimmune etiologies.4 In addition, the syndrome can occur as part of CNS demyelinating disease such as neuromyelitis optica (NMO) or, uncommonly, typical multiple sclerosis (MS). Once such recognized causes are excluded, the question remains as to whether there exists a unique disease entity “idiopathic ATM.” Based on expert opinion, the Transverse Myelitis Consortium Working Group (TMCWG) proposed diagnostic criteria for idiopathic ATM.5 The clinical requirements include bilateral sensory, motor, or autonomic dysfunction referable to the spinal cord, with a clearly defined sensory level that progresses to the nadir over 4 to 21 days from onset. Neuroimaging, preferably MRI, is used to eliminate structural causes. …

Diagnostic Criteria of Acute Transverse Myelitis

Inclusion and exclusion criteria for the diagnosis of acute transverse myelitis (ATM), as a basis for multicenter clinical trials, are proposed by a Transverse Myelitis Consortium Working Group.