Showing papers on "Myelitis published in 2019"

Clinical, Radiologic, and Prognostic Features of Myelitis Associated With Myelin Oligodendrocyte Glycoprotein Autoantibody

Abstract: Importance Recognizing the characteristics of myelin oligodendrocyte glycoprotein autoantibody (MOG-IgG) myelitis is essential for early accurate diagnosis and treatment. Objective To evaluate the clinical, radiologic, and prognostic features of MOG-IgG myelitis and compare with myelitis with aquaporin-4–IgG (AQP4-IgG) and multiple sclerosis (MS). Design, Setting, and Participants We retrospectively identified 199 MOG-IgG–positive Mayo Clinic patients from January 1, 2000, through December 31, 2017, through our neuroimmunology laboratory. Fifty-four patients met inclusion criteria of (1) clinical myelitis; (2) MOG-IgG positivity; and (3) medical records available. We excluded 145 patients without documented myelitis. Myelitis of AQP4-IgG (n = 46) and MS (n = 26) were used for comparison. Main Outcomes and Measures Outcome variables included modified Rankin score and need for gait aid. A neuroradiologist analyzed spine magnetic resonance imaging of patients with MOG-IgG and control patients blinded to diagnosis. Results Of 54 included patients with MOG-IgG myelitis, the median age was 25 years (range, 3-73 years) and 24 were women (44%). Isolated transverse myelitis was the initial manifestation in 29 patients (54%), and 10 (19%) were initially diagnosed as having viral/postviral acute flaccid myelitis. Cerebrospinal fluid–elevated oligoclonal bands occurred in 1 of 38 (3%). At final follow-up (median, 24 months; range, 2-120 months), 32 patients (59%) had developed 1 or more relapses of optic neuritis (n = 31); transverse myelitis (n = 7); or acute disseminated encephalomyelitis (n = 1). Clinical features favoring MOG-IgG myelitis vs AQP4-IgG or MS myelitis included prodromal symptoms and concurrent acute disseminated encephalomyelitis. Magnetic resonance imaging features favoring MOG-IgG over AQP4-IgG or MS myelitis were T2-signal abnormality confined to gray matter (sagittal line and axial H sign) and lack of enhancement. Longitudinally extensive T2 lesions were of similar frequency in MOG-IgG and AQP4-IgG myelitis (37 of 47 [79%] vs 28 of 34 [82%];P = .52) but not found in MS. Multiple spinal cord lesions and conus involvement were more frequent with MOG-IgG than AQP4-IgG but not different from MS. Wheelchair dependence at myelitis nadir occurred in one-third of patients with MOG-IgG and AQP4-IgG but never with MS, although patients with MOG-IgG myelitis recovered better than those with AQP4-IgG. Conclusions and Relevance Myelitis is an early manifestation of MOG-IgG–related disease and may have a clinical phenotype of acute flaccid myelitis. We identified a variety of clinical and magnetic resonance imaging features that may help clinicians identify those at risk in whom MOG-IgG should be tested.

Neuromyelitis optica spectrum disorders.

Abstract: Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon antibody-mediated disease of the central nervous system. Long segments of spinal cord inflammation (myelitis), severe optic neuritis, and/or bouts of intractable vomiting and hiccoughs (area postrema syndrome) are classic presentations of the disease and may alert the clinician to the diagnosis. Untreated, approximately 50% of NMOSD patients will be wheelchair users and blind, and a third will have died within 5 years of their first attack. Unlike multiple sclerosis, a progressive clinical course is very unusual and the accrual of disability is related to relapses. Approximately 75% of patients have antibodies against aquaporin-4, a water channel expressed on astrocytes. Relapses are treated aggressively to prevent residual disability with high-dose steroids and often plasma exchange. Relapse prevention is crucial and achieved with long-term immunosuppression. In this article we review the pathogenesis, clinical features, diagnosis and management of NMOSD.

Brain and cord imaging features in neuromyelitis optica spectrum disorders.

Abstract: Objectives To validate imaging features able to discriminate neuromyelitis optica spectrum disorders from multiple sclerosis with conventional magnetic resonance imaging (MRI). Methods In this cross-sectional study, brain and spinal cord scans were evaluated from 116 neuromyelitis optica spectrum disorder patients (98 seropositive and 18 seronegative) in chronic disease phase and 65 age-, sex-, and disease duration-matched multiple sclerosis patients. To identify independent predictors of neuromyelitis optica diagnosis, after assessing the prevalence of typical/atypical findings, the original cohort was 2:1 randomized in a training sample (where a multivariate logistic regression analysis was run) and a validation sample (where the performance of the selected variables was tested and validated). Results Typical brain lesions occurred in 50.9% of neuromyelitis optica patients (18.1% brainstem periventricular/periaqueductal, 32.7% periependymal along lateral ventricles, 3.4% large hemispheric, 6.0% diencephalic, 4.3% corticospinal tract), 72.2% had spinal cord lesions (46.3% long transverse myelitis, 36.1% short transverse myelitis), 37.1% satisfied 2010 McDonald criteria, and none had cortical lesions. Fulfillment of at least 2 of 5 of absence of juxtacortical/cortical lesions, absence of periventricular lesions, absence of Dawson fingers, presence of long transverse myelitis, and presence of periependymal lesions along lateral ventricles discriminated neuromyelitis optica patients in both training (sensitivity = 0.92, 95% confidence interval [CI] = 0.84-0.97; specificity = 0.91, 95% CI = 0.78-0.97) and validation samples (sensitivity = 0.82, 95% CI = 0.66-0.92; specificity = 0.91, 95% CI = 0.71-0.99). MRI findings and criteria performance were similar irrespective of serostatus. Interpretation Although up to 50% of neuromyelitis optica patients have no typical lesions and a relatively high percentage of them satisfy multiple sclerosis criteria, several easily applicable imaging features can help to distinguish neuromyelitis optica from multiple sclerosis. ANN NEUROL 2019;85:371-384.

Clinical Subpopulations in a Sample of North American Children Diagnosed With Acute Flaccid Myelitis, 2012-2016

Abstract: Importance Acute flaccid myelitis (AFM) is an emerging poliolike illness of children whose clinical spectrum and associated pathogens are only partially described. The case definition is intentionally encompassing for epidemiologic surveillance to capture all potential AFM cases. Defining a restrictive, homogenous subpopulation may aid our understanding of this emerging disease. Objective To evaluate the extent to which the US Centers for Disease Control and Prevention (CDC) case definition of AFM incorporates possible alternative diagnoses and to assess the plausibility of a case definition that enriches the biological homogeneity of AFM for inclusion in research studies. Design, Setting, and Participants Retrospective case analysis of children younger than 18 years diagnosed as having AFM between 2012 and 2016 using the CDC case definition. Group 1 included patients recruited from the United States and Canada based on the CDC case definition of AFM. Group 2 included patients referred to the Johns Hopkins Transverse Myelitis Center for evaluation of suspected AFM. Patients’ records and imaging data were critically reviewed by 3 neurologists to identify those cases with definable alternative diagnoses, and the remaining patients were categorized as having restrictively defined AFM (rAFM). Clinical characteristics were compared between patients with rAFM (cases) and those with alternative diagnoses, and a case description distinguishing these AFM groups was identified. Interrater reliability of this description was confirmed for a subset of cases by a fourth neurologist. Data were analyzed between May 2017 and November 2018. Main Outcomes and Measures Proportion of patients with possible alternative diagnosis. Results Of the 45 patients who met the CDC AFM case definition and were included, the mean age was 6.1 years; 27 were boys (60%); and 37 were white (82%), 3 were Asian (7%), 1 was Hispanic (2%), and 4 were mixed race/ethnicity (9%). Of the included patients, 34 were classified as having rAFM, and 11 had alternate diagnoses (including transverse myelitis, other demyelinating syndromes, spinal cord stroke, Guillain-Barre syndrome, Chiari I myelopathy, and meningitis). Factors differing between groups were primarily asymmetry of weakness, lower motor neuron signs, preceding viral syndrome, symptoms evolving over hours to days, absence of sensory deficits, and magnetic resonance imaging findings. A case description was able to reliably define the rAFM group. Conclusions and Relevance We present an approach for defining a homogeneous research population that may more accurately reflect the pathogenesis of the prototypical poliomyelitis-like subgroup of AFM. The definition of rAFM forms a blueprint for inclusion criteria in future research efforts, but more work is required for refinement and external validation.

Acute Flaccid Myelitis in the United States: 2015–2017

Abstract: BACKGROUND: Acute flaccid myelitis (AFM) is a neurologic condition characterized by flaccid limb weakness. After a large number of reports of AFM in 2014, the Centers for Disease Control and Prevention began standardized surveillance in the United States to characterize the disease burden and explore potential etiologies and epidemiologic associations. METHODS: Persons meeting the clinical case criteria of acute flaccid limb weakness from January 1, 2015, through December 31, 2017, were classified as confirmed (spinal cord gray matter lesions on MRI) or probable (white blood cell count >5 cells per mm3 in cerebrospinal fluid [CSF]). We describe clinical, radiologic, laboratory, and epidemiologic findings of pediatric patients (age ≤21 years) confirmed with AFM. RESULTS: Of 305 children reported from 43 states, 193 were confirmed and 25 were probable. Of confirmed patients, 61% were male, with a median age of 6 years (range: 3 months to 21 years; interquartile range: 3 to 10 years). An antecedent respiratory or febrile illness was reported in 79% with a median of 5 days (interquartile range: 2 to 7 days) before limb weakness. Among 153 sterile-site specimens (CSF and serum) submitted to the Centers for Disease Control and Prevention, coxsackievirus A16 was detected in CSF and serum of one case patient and enterovirus D68 was detected in serum of another. Of 167 nonsterile site (respiratory and stool) specimens, 28% tested positive for enterovirus or rhinovirus. CONCLUSIONS: AFM surveillance data suggest a viral etiology, including enteroviruses. Further study is ongoing to better characterize the etiology, pathogenesis, and risk factors of this rare condition.

Comparison of Clinical Outcomes of Transverse Myelitis Among Adults With Myelin Oligodendrocyte Glycoprotein Antibody vs Aquaporin-4 Antibody Disease

Abstract: Importance Recognizing the differences between transverse myelitis (TM) associated with myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) disease vs aquaporin-4 (AQP4)-Ab disease and prognosticating patients within each group may be an important factor for better clinical treatment for these respective patients. Objectives To compare the clinical and radiological findings of the first TM episode in patients with MOG-Ab disease vs patients with AQP4-Ab disease and to assess factors associated with worse outcomes and relapse risk. Design, Setting, and Participants This retrospective cross-sectional study used data collected from the Oxford Neuromyelitis Optica Service database, a national service that serves the south of England, including detailed clinical data, and high-quality imaging from within 4 weeks of the first TM episode from patients with MOG-Ab disease or AQP4-Ab disease and a confirmed history of TM from April 2018 to January 2019. Data analyses were conducted from February 2019 to April 2019. Main Outcomes and Measures Onset features of each condition measured using the Expanded Disability Status Scale (EDSS) score, time to an EDSS score of 6, time to relapse, and residual sphincter dysfunction at least 6 months after the first TM episode and at last follow-up. Results The total cohort included 115 adult patients, including 46 patients with MOG-Ab disease and 69 patients with AQP4-Ab disease. Patients with AQP4-Ab disease, compared with patients with MOG-Ab disease, tended to be older at onset of disease (mean [SD] age, 48.5 [14.9] years vs 33.7 [1.2] years) and female (57 [83%] women vs 24 [52%] women). Transverse myelitis occurred at onset of disease for 32 patients (70%) with MOG-Ab disease and 57 patients (78%) with AQP4-Ab disease. Onset severity did not differ between groups. An acute disseminated encephalomyelitis–like presentation occurred at the time of the TM in 4 patients (9%) with MOG-Ab disease but no patients with AQP4-Ab disease. Compared with patients with AQP4-Ab disease, patients with MOG-Ab disease were more likely to have short cord lesions (22 patients [48%] vs 10 patients [15%];P Conclusions and Relevance This study found that in patients who experienced a TM episode, short and multiple lesions at onset were more common in those with MOG-Ab disease than among those with AQP4-Ab disease. The presence of a brainstem lesion at the time of a TM episode in patients with MOG-Ab disease was associated with a worse recovery. In patients with AQP4-Ab disease, those 50 years and older at disease onset had more disability, and those younger than 50 years at disease onset had more relapses.

Glial fibrillary acidic protein IgG related myelitis: characterisation and comparison with aquaporin-4-IgG myelitis

Abstract: IgG directed against the α-isoform of glial fibrillary acidic protein (GFAP-IgG) predicts a distinct corticosteroid-responsive meningoencephalomyelitis termed autoimmune GFAP astrocytopathy, when detected on cerebrospinal fluid (CSF).1 Optic disc oedema and tremor are common accompaniments. The MRI hallmark is a striking linear perivascular enhancement radially oriented around the ventricles (radial enhancement), while the myelitis component is generally associated with a longitudinally extensive T2 lesion on spinal cord MRI, similar to that typically encountered in aquaporin-4-IgG (AQP4-IgG) related myelitis.1–3 We compared the clinical, laboratory and MRI features of GFAP-IgG and AQP4-IgG related myelitis. ### Patient ascertainment We retrospectively identified GFAP-IgG seropositive patients seen at the Mayo Clinic ( 1 January 2000 to 31 December 2017). Inclusion criteria were as follows: (1) serum/CSF demonstrating GFAP pattern by indirect immunofluorescence with GFAPα specificity confirmed by cell-based assay, as previously described;1 (2) first myelitis episode; (3) serum sample negative for myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) and AQP4-IgG using previously described methodology4 5; (4) adequate clinical data available. Nine patients with GFAP-IgG myelitis were included in a prior report.1 Two patients with dual positivity in serum for AQP4-IgG and GFAP-IgG were excluded. Medical records were reviewed and compared with 41 patients from a previously identified cohort of AQP4-IgG seropositive patients at the first episode of clinical myelitis who tested negative for GFAP-IgG (41 tested) and MOG-IgG (13 tested).5 Improvement was defined as subjective improvement reported by the patient with objective improvement confirmed by the physician. ### Neuroimaging All available MRI sequences obtained within 4 months of myelitis onset were reviewed by one neurology investigator (ES/EPF) and one neuroradiologist (TJK/KNK/PPM) as described previously.5 Consensus was achieved in situations of disagreement. ### Statistical analysis Wilcoxon rank-sum test or χ2/Fisher’s exact test was used as appropriate for comparison (JMP 8.0 software). Fifty-four patients with myelitis were included: GFAP-IgG positive, …

Persistent MOG-IgG positivity is a predictor of recurrence in MOG-IgG-associated optic neuritis, encephalitis and myelitis.

Abstract: Background:MOG-IgG-associated optic neuritis, encephalitis and myelitis (MONEM) is a recently recognized group of inflammatory central nervous system (CNS) disorders distinct from multiple sclerosi...

Long-term disability in neuromyelitis optica spectrum disorder with a history of myelitis is associated with age at onset, delay in diagnosis/preventive treatment, MRI lesion length and presence of symptomatic brain lesions.

Abstract: Background Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system (CNS) that preferentially targets the spinal cord and optic nerves. Increasing disability is accrued with each inflammatory attack. Disability has been shown to be an independent predictor of poor quality of life in those with NMOSD. Factors associated with increasing disability need further systematic investigation. Methods We performed a multi-center retrospective chart analysis of aquaporin-4 (AQP4) seropositive NMOSD patients with a history of myelitis seen at five large referral centers for patients with NMOSD worldwide for whom thorough records including relapse history and corresponding imaging were available. Potential contributors to long-term disability were extracted including demographics, radiographic findings, and clinical characteristics. Multivariable regression modeling was conducted to determine correlates of disability in patients with NMOSD, as measured by the Expanded Disability Status Scale (EDSS). Results One hundred eighty-two AQP4 seropositive patients (88% female) were included in this analysis. Multiple regression modeling revealed that older age at disease onset, delay in diagnosis/preventive treatment, length of longest acute myelitis lesion and presence of symptomatic brain/brainstem lesions were associated with increased disability when holding other variables constant. Conclusion While age at onset is a factor that cannot be controlled in NMOSD, we can reduce the delay in diagnosis/preventive treatment and reduce future relapses in the brain/brainstem and spinal cord. Delay in diagnosis/preventive treatment and imaging variables that contributed to increased disability support the need for improved measures for early, accurate diagnosis and management of NMOSD, and aggressive treatment of acute relapses.

Acute Flaccid Myelitis Associated with Enterovirus D68 in Children, Argentina, 2016

Abstract: After a 2014 outbreak of severe respiratory illness caused by enterovirus D68 in the United States, sporadic cases of acute flaccid myelitis have been reported worldwide. We describe a cluster of acute flaccid myelitis cases in Argentina in 2016, adding data to the evidence of association between enterovirus D68 and this polio-like illness.

Acute Flaccid Myelitis: A Clinical Overview for 2019

Abstract: Acute flaccid myelitis (AFM) is characterized by flaccid paralysis of one or more limbs, often following a viral illness, with magnetic resonance imaging findings consistent with inflammation of the spinal cord gray matter. It is unclear whether all patients with AFM will have full recovery of neurologic function. Since 2014, there have been several clusters of AFM in the United States, with a 3-fold increase in reported AFM cases recorded in 2018 compared with the previous year. Epidemiological evidence supports a temporal association between respiratory enteroviral illness, particularly with enteroviruses D68 and A71, and clustering of AFM cases. However, causality has yet to be established. Treatment of AFM is primarily supportive. Adjunctive therapies such as intravenous immunoglobulin, corticosteroids, plasmapheresis, and fluoxetine have not been found to improve long-term outcomes. Further research is urgently needed to characterize and optimize management of this emerging, yet poorly understood, condition.

Acute Transverse and Flaccid Myelitis in Children.

Abstract: The etiologies of myelitis in children are broad, and our understanding of inflammatory myelopathies in the pediatric population continues to evolve. Acute flaccid myelitis (AFM), increasingly linked to enterovirus infections, has risen in incidence over recent years. As with other infectious myelopathies, AFM can be challenging to distinguish from inflammatory causes of acute transverse myelitis (ATM) at initial presentation. This review outlines an approach to the treatment of children presenting with myelopathy of suspected inflammatory etiology, with attention to how management may differ in the specific case of acute flaccid myelitis. Although high-quality evidence is limited, intravenous corticosteroids, intravenous immunoglobulin, and plasma exchange have important roles in the acute management of ATM. Spinal cord injury in AFM, though similar to ATM in clinical presentation, is largely mediated by direct infection as opposed to a primary inflammatory process, and treatment with corticosteroids may worsen outcomes. Awareness of the distinguishing clinical features of AFM and the underlying inflammatory conditions that commonly manifest with ATM is essential to judicious selection of appropriate acute (and potentially chronic) therapies in children presenting with myelitis.

Magnetic resonance imaging in enterovirus-71, myelin oligodendrocyte glycoprotein antibody, aquaporin-4 antibody, and multiple sclerosis-associated myelitis in children.

Abstract: Aim We used magnetic resonance imaging (MRI) to compare the neuroimaging of children with their first episode of clinical enterovirus 71-associated transverse myelitis (EV71-TM), myelin oligodendrocyte glycoprotein antibody positive transverse myelitis (MOG-TM), aquaporin-4 antibody positive transverse myelitis (AQP4-TM), transverse myelitis in multiple sclerosis (MS-TM), and unclassified transverse myelitis (UNC-TM). Method We performed a retrospective blinded radiological assessment and compared the neuroimaging of 52 children (32 females, 20 males; mean age 9y 8mo, SD 5y 5mo, range 5mo-17y) presenting with their first episode of myelitis caused by EV71-TM (n=11), MOG-TM (n=10), AQP4-TM (n=9), MS-TM (n=13), and UNC-TM (n=9). Results In the EV71-TM group, lesions were distributed throughout the cord and enhancement of nerve roots (ventral and dorsal) was common. The MOG-TM group had lesions distributed throughout the cord and most commonly longitudinally extensive transverse myelitis and lesions involving the grey matter alone on axial scans. The AQP4-TM group had lesions distributed in the cervicothoracic spine, cavitation, and contrast enhancing lesions. All patients with AQP4-TM had an abnormal brain MRI scan. The MS-TM group characteristically had multiple short segment lesions of the cord involving the cervicothoracic spine. The UNC-TM group did not have distinctive spinal MRI findings but had a relative paucity of lesions on their brain MRI scans. Interpretation There are neuroimaging findings that are helpful in differentiating between myelitis associated with EV71, MOG, AQP4, and multiple sclerosis in children. These features may be useful early in the presentation of transverse myelitis while awaiting infectious/immunological testing, and/or further demyelinating events. What this paper adds Magnetic resonance imaging can help identify aetiologies for children presenting with a first episode of myelitis. Entervirus-71-associated myelitis lesions are distributed throughout the cord and enhancement of nerve roots is common. Lesions distributed throughout the cord are commonly seen in myelin oligodendrocyte-associated myelitis. Aquaporin-4-associated myelitis lesions are distributed in the cervicothoracic spine, cavitation and contrast enhancing lesions are common. Short segment lesions in the cervicothoracic spine are commonly seen in multiple sclerosis-associated myelitis.

Increased detection of enterovirus A71 infections, Germany, 2019.

Abstract: We report on the increased circulation of enterovirus A71 in Germany in 2019. Strains were mainly identified in hospitalised patients with suspected aseptic meningitis/encephalitis. Molecular analysis showed co-circulation of EV-A71 sub-genogroups C1 and C4, a signal for physicians and public health authorities to include/intensify EV diagnostic in patients showing signs of aseptic meningitis, encephalitis or acute flaccid paralysis/myelitis.

Spinal cord syndromes in patients with systemic lupus erythematosus: differentiating lupus myelitis, neuromyelitis optica, and multiple sclerosis.

Abstract: ObjectiveNon-infectious myelitis in systemic lupus erythematosus (SLE) may be due to SLE myelitis, comorbid multiple sclerosis (MS), or neuromyelitis optica (NMO). We compared characteristics of th...

Acute Flaccid Myelitis Associated With Enterovirus D68: A Review.

Abstract: Acute flaccid myelitis is a disease that affects the anterior horn cells of the spinal cord, leading to rapid onset of flaccid paralysis. Recent biennial epidemics, beginning in the summer of 2014, have been associated with enterovirus D68, although the underlying pathophysiology is unknown. Patients present with asymmetric flaccid weakness of the extremities, with cranial neuropathy and without encephalopathy, and often have residual disability. Here we review the current literature on this disabling disease and discuss treatment modalities and ongoing research.

Clinical, neuroimaging and therapeutic response in AQP4-positive NMO patients from India.

Abstract: Background Neuromyelitis Optica (NMO) is an autoimmune astrocytopathic disorder due to AQP4 antibodies. Objectives To analyse clinical, neuroimaging features in NMO patients and assess the efficacy of various therapeutics. Methods AQP4+ve NMO patients were diagnosed based on consensus diagnostic criteria. Results 101 AQP4+ve NMO patients were seen with female (90) predominance. Adult population (71.3%) formed the larger group followed by pediatric (19.8%) and late-onset (8.9%). Myelopathy (36.2%) was most commonly seen followed by optic neuritis (19.1%), brainstem (17.1%), opticomyelopathy (16.1%), area postrema involvement (10.5%) and encephalopathy (1%). Encephalopathy and brainstem/cerebellar involvement were most common in pediatric population while opticomyelopathy was more common in late-onset patients. Hyperintensities of lower medulla was seen in 67.3% subjects and 49.5% had involvement of obex. Differential T2 hyperintensity of the long segment myelitis was found in 30.7%. Plasmapheresis was given in 71 subjects followed by maintenance therapy. Most of them showed significant improvement with EDSS score of 1 in 30.7%. Conclusions Clinical manifestations in AQP4+ve NMO patients may vary depending on the age at onset of illness. MRI features affecting cervicomedullary junction, obex, differential T2 hyperintensities of the spinal cord may form a useful diagnostic clue. Plasmapheresis is helpful in achieving remission along with immunomodulation.

Radiation myelitis after pembrolizumab administration, with favorable clinical evolution and safe rechallenge: a case report and review of the literature

Abstract: Neurologic complications as myelitis are very rare but extremely deleterious adverse effects of both immunotherapy and radiotherapy. Many recent studies have focused on the possible synergy of these two treatment modalities due to their potential to enhance each other’s immunomodulatory actions, with promising results and a safe tolerance profile. We report here the case of a 68-year-old man with metastatic non-small-cell lung cancer (NSCLC) who developed myelitis after T12-L2 vertebral radiotherapy, with motor deficit and sphincter dysfunction, while on treatment with pembrolizumab (an immune checkpoint inhibitor). The spinal abnormalities detected by magnetic resonance imaging (MRI), suggestive of myelitis, faithfully matched the area previously irradiated with 30 Gy in 10 fractions, six and a half months earlier. After immunotherapy discontinuation and steroid treatment, the patient rapidly and completely recovered. On progression, pembrolizumab was rechallenged and, after 8 cycles, the patient is on response and there are no signs of myelitis relapse. The confinement within the radiation field and the latency of appearance are suggestive of delayed radiation myelopathy. Nevertheless, the relatively low dose of radiation received and the full recovery after pembrolizumab discontinuation and steroid therapy plead for the contribution of both radiotherapy and immunotherapy in the causality of this complication, as an enhanced inflammatory reaction on a focal post-radiation chronic inflammatory state. In the three previously described cases of myelopathy occurring after radiotherapy and immunotherapy, a complete recovery had not been obtained and the immunotherapy was not rechallenged. The occurrence of a radiation recall phenomenon, in this case, can not be excluded, and radiation recall myelitis has already been described with chemotherapy and targeted therapy. Safe rechallenges with the incriminated drug, even immunotherapy, have been reported after radiation recall, but we describe it for the first time after myelitis.

A case of neuromyelitis optica spectrum disorder following seasonal influenza vaccination.

Abstract: There have been reports of central nervous systemic inflammatory disease associated with vaccination. We describe a female patient who developed longitudinally extensive transverse myelitis following seasonal influenza vaccination. A 38-year-old woman had severe neck and back pain with urinary retention. She received influenza vaccine 3 days before symptom onset. Examination revealed mild quadriparesis with diffuse hyperreflexia. Magnetic resonance imaging (MRI) of the spine showed a T2 hyperintense lesion with gadolinium enhancement in the spinal cord extending from the cervicomedullary junction to the level of T10. Brain MRI revealed no specific finding for demyelinating lesions. Cerebrospinal fluid had a white blood cell count of 60/L (mononuclear cells 95%) with a protein concentration of 78.2 mg/dL and the blood serum was positive for anti-aquaporin-4 antibodies. She was treated with high-dose methylprednisolone for 5 days followed by tapering of prednisolone. Symptoms improved significantly after treatment. We report a case of neuromyelitis optica spectrum disorder following seasonal influenza vaccination. Neuromyelitis optica spectrum disorder may have been triggered by the recent influenza vaccination, although a pathogenic link has not been established.

Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study.

Abstract: Neuromyelitis optica spectrum disorders lack imaging biomarkers associated with disease course and supporting prognosis. This complex and heterogeneous set of disorders affects many regions of the central nervous system, including the spinal cord and visual pathway. Here, we use graph theory-based multimodal network analysis to investigate hypothesis-free mixed networks and associations between clinical disease with neuroimaging markers in 40 aquaporin-4-immunoglobulin G antibody seropositive patients (age = 48.16 ± 14.3 years, female:male = 36:4) and 31 healthy controls (age = 45.92 ± 13.3 years, female:male = 24:7). Magnetic resonance imaging measures included total brain and deep grey matter volumes, cortical thickness and spinal cord atrophy. Optical coherence tomography measures of the retina and clinical measures comprised of clinical attack types and expanded disability status scale were also utilized. For multimodal network analysis, all measures were introduced as nodes and tested for directed connectivity from clinical attack types and disease duration to systematic imaging and clinical disability measures. Analysis of variance, with group interactions, gave weights and significance for each nodal association (hyperedges). Connectivity matrices from 80% and 95% F-distribution networks were analyzed and revealed the number of combined attack types and disease duration as the most connected nodes, directly affecting changes in several regions of the central nervous system. Subsequent multivariable regression models, including interaction effects with clinical parameters, identified associations between decreased nucleus accumbens (β = -0.85, P = 0.021) and caudate nucleus (β = -0.61, P = 0.011) volumes with higher combined attack type count and longer disease duration, respectively. We also confirmed previously reported associations between spinal cord atrophy with increased number of clinical myelitis attacks. Age was the most important factor associated with normalized brain volume, pallidum volume, cortical thickness and the expanded disability status scale score. The identified imaging biomarker candidates warrant further investigation in larger-scale studies. Graph theory-based multimodal networks allow for connectivity and interaction analysis, where this method may be applied in other complex heterogeneous disease investigations with different outcome measures.

Motoric Recovery After Transplantation of Bone Marrow Derived Mesenchymal Stem Cells in Chronic Spinal Cord Injury: A Case Report

Abstract: BACKGROUND For the past 20 years, numerous of clinical trials focusing on the use of mesenchymal stem cells (MSC) in spinal cord injury (SCI) treatment has been conducted. However, controversies over whether stem cells are the main factor in a patient's recovery still persisted in sub-acute SCI. This study aimed to evaluate the motoric recovery in a chronic SCI patient treated with bone marrow derived MSC (BM-MSC) transplantation. CASE REPORT We present a case report of patient with a 12-year-long-chronic SCI that was treated by BM-MSC) transplantation using a serial administration protocol. The protocol consisted of direct parenchymal injection to the affected lesion and multiple (5 times) intravenous stem cell injection as the adjuncts. There was no complication or serious adverse effects encountered during the procedure and follow up. At the final follow up of 5 years, the patient neurological status improved from American Spinal Injury Association (ASIA) A status to ASIA C status, which signifies improvement in his ambulatory status. Magnetic resonance imaging and electrophysiology examination also showed changes that indicated recovery of the neurologic function. CONCLUSIONS Based on the limited adverse reaction and outcome, our case report may serve as an additional alternative protocol in stem cell administration to improve the outcome of chronic spinal cord injury patients.

Neuromyelitis optica spectrum disorders (NMO-SD) in a Sub-Saharan Africa country: A preliminary study of sixteen Senegalese cases.

Abstract: Background Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system. In Sub-Saharan Africa, publications are rare and deal with isolated cases. Our goal was to analyze the characteristics of NMO spectrum disorders in a Senegalese cohort compiled in Dakar. Patients and method This was a retrospective descriptive study conducted at the Neurology Department of Fann Teaching Hospital. We included all patients with NMO-SD according to the 2014 diagnostic criteria. Results Sixteen patients were enrolled, 4 men and 12 women with an average age of 30 years. Ten patients (62.5%) presented an acute myelopathy associated with retrobulbar optic neuritis and 5 (31.25%) had isolated spinal cord injury. Spinal MRI showed abnormal cervical (6 patients), dorsal (4 patients), bulbar-cervical (3 patients) or cervico-dorsal (2 patients) signal extended (≥3 vertebral segments) of the spinal cord. Visual evoked potentials (VEP) showed demyelinating optic nerve involvement in 8 patients. Ten patients were positive to AQP-4 IgG. Systemic corticosteroid therapy was the rule in all patients, associated with azathioprine in 10 of them. The clinical course at 3 months was predominantly favourable (10 patients). Conclusion This cohort is the first one compiled in Dakar. African multicentric epidemiological studies are needed.

Viral Sequences Detection by High-Throughput Sequencing in Cerebrospinal Fluid of Individuals with and without Central Nervous System Disease.

Abstract: Meningitis, encephalitis, and myelitis are various forms of acute central nervous system (CNS) inflammation, which can coexist and lead to serious sequelae. Known aetiologies include infections and immune-mediated processes. Despite advances in clinical microbiology over the past decades, the cause of acute CNS inflammation remains unknown in approximately 50% of cases. High-throughput sequencing was performed to search for viral sequences in cerebrospinal fluid (CSF) samples collected from 26 patients considered to have acute CNS inflammation of unknown origin, and 10 patients with defined causes of CNS diseases. In order to better grasp the clinical significance of viral sequence data obtained in CSF, 30 patients without CNS disease who had a lumbar puncture performed during elective spinal anaesthesia were also analysed. One case of human astrovirus (HAstV)-MLB2-related meningitis and disseminated infection was identified. No other viral sequences that can easily be linked to CNS inflammation were detected. Viral sequences obtained in all patient groups are discussed. While some of them reflect harmless viral infections, others result from reagent or sample contamination, as well as index hopping. Altogether, this study highlights the potential of high-throughput sequencing in identifying previously unknown viral neuropathogens, as well as the interpretation issues related to its application in clinical microbiology.

Virus-triggered spinal cord demyelination is followed by a peripheral neuropathy resembling features of Guillain-Barré Syndrome

Abstract: Theiler’s murine encephalomyelitis virus (TMEV)-induces a demyelinating disease in the spinal cord (SC) of susceptible but not in resistant (B6) mouse strains. The aim of the present study was to induce SC demyelination and a peripheral neuropathy in resistant mice by switching the infection site from cerebrum to SC. B6 mice were intraspinally inoculated with TMEV. Infected mice showed clinical signs starting at 7 days post infection (dpi). Histopathology revealed a mononuclear myelitis, centred on the injection site at 3 dpi with subsequent antero- and retrograde spread, accompanied by demyelination and axonal damage within the SC. Virus protein was detected in the SC at all time points. SC inflammation decreased until the end of the investigation period (28 dpi). Concurrent with the amelioration of SC inflammation, the emergence of a peripheral neuropathy, characterized by axonal damage, demyelination and macrophage infiltration, contributing to persistent clinical sings, was observed. Intraspinal TMEV infection of resistant mice induced inflammation, demyelination and delayed viral clearance in the spinal cord and more interestingly, subsequent, virus-triggered inflammation and degeneration within the PN associated with dramatic and progressive clinical signs. The lesions observed in the PN resemble important features of Guillain-Barre syndrome, especially of acute motor/motor-sensory axonal forms.

Pure spinal multiple sclerosis: A possible novel entity within the multiple sclerosis disease spectrum.

Abstract: We identified five female patients retrospectively with relapsing short-segment partial myelitis whose clinical and paraclinical features were suggestive of cord involvement of multiple sclerosis (MS)-type albeit not rigidly fulfilling the 2017 McDonald criteria. Notably, these patients had not developed any typical MS-like brain lesions despite repeated neuroimaging assessments over years. Comprehensive work-up for differential diagnoses of MS and other causes of transverse myelitis particularly neuromyelitis optica spectrum disorders had been consistently negative on longitudinal follow-up. Thus, we postulate a possible entity of pure spinal MS which may represent a novel forme fruste within the MS disease spectrum.

Clinical Approach to Pediatric Transverse Myelitis, Neuromyelitis Optica Spectrum Disorder and Acute Flaccid Myelitis

Abstract: Pediatric transverse myelitis (TM) is an acquired, immune-mediated disorder that leads to injury of the spinal cord and often manifests as weakness, numbness, bowel dysfunction, and/or bladder dysfunction. Multiple etiologies for myelitis can result in a similar clinical presentation, including idiopathic transverse myelitis (TM), multiple sclerosis (MS), neuromyeltis optica spectrum disorder (NMOSD) associated with anti-aquaporin 4 antibodies, MOG antibody-associated disease, and acute flaccid myelitis (AFM). Diagnosis relies on clinical recognition of the syndrome and confirming inflammation through imaging and/or laboratory studies. Acute treatment is targeted at decreasing immune-mediated injury, and chronic preventative therapy may be indicated if TM is determined to be a manifestation of a relapsing disorder (i.e., NMOSD). Timely recognition and treatment of acute transverse myelitis is essential, as it can be associated with significant morbidity and long-term disability.