Gait Characteristics in Youth With Transverse Myelitis.

BACKGROUND: Transverse myelitis (TM) in childhood is a rare disorder characterized by the presence of spinal cord inflammation. Gait difficulty in children with TM is common; however, there is a paucity of literature regarding quantitative assessment of gait in children and adolescents with TM. OBJECTIVES: To characterize gait patterns in a cohort of ambulatory children with TM and age-matched, typically developing peers in order to better understand the functional mobility of patients diagnosed with childhood TM. METHODS: This was a retrospective study of 26 ambulatory pediatric patients with a confirmed diagnosis of TM who had undergone three-dimensional, instrumented gait analysis (3D-IGA) at 3 years of age or older. A group of 38 typically developing children served as a control group. RESULTS: Gait in children with TM was characterized by moderate kinematic deviations as measured by the Gait Deviation Index (GDI) and a crouched gait pattern (p < .001), increased anterior pelvic tilt (p < .001), decreased motion at the knees (p < .001), and a wider base of support (foot progression angle, p < .001). The TM group had a slower walking speed (p < .001), shorter strides (p < .001), and an increased stance phase compared to controls. CONCLUSION: Our study results showed moderate kinematic deviations quantified by the GDI. Overall, the gait pattern in the TM population tested had greater hip and knee flexion with wider foot progression angle. Identification of gait characteristics in children with TM is the first step in predicting changes in gait pattern as they mature over time, which may ultimately allow for targeted intervention to maintain their ambulatory function.

Acute Transverse Myelitis (ATM):Clinical Review of 43 Patients With COVID-19-Associated ATM and 3 Post-Vaccination ATM Serious Adverse Events With the ChAdOx1 nCoV-19 Vaccine (AZD1222).

Introduction: Although acute transverse myelitis (ATM) is a rare neurological condition (1.34-4.6 cases per million/year) COVID-19-associated ATM cases have occurred during the pandemic. Case-finding methods: We report a patient from Panama with SARS-CoV-2 infection complicated by ATM and present a comprehensive clinical review of 43 patients with COVID-19-associated ATM from 21 countries published from March 2020 to January 2021. In addition, 3 cases of ATM were reported as serious adverse events during the clinical trials of the COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results: All patients had typical features of ATM with acute onset of paralysis, sensory level and sphincter deficits due to spinal cord lesions demonstrated by imaging. There were 23 males (53%) and 20 females (47%) ranging from ages 21- to 73- years-old (mean age, 49 years), with two peaks at 29 and 58 years, excluding 3 pediatric cases. The main clinical manifestations were quadriplegia (58%) and paraplegia (42%). MRI reports were available in 40 patients; localized ATM lesions affected ≤3 cord segments (12 cases, 30%) at cervical (5 cases) and thoracic cord levels (7 cases); 28 cases (70%) had longitudinally-extensive ATM (LEATM) involving ≥4 spinal cord segments (cervicothoracic in 18 cases and thoracolumbar-sacral in 10 patients). Acute disseminated encephalomyelitis (ADEM) occurred in 8 patients, mainly women (67%) ranging from 27- to 64-years-old. Three ATM patients also had blindness from myeloneuritis optica (MNO) and two more also had acute motor axonal neuropathy (AMAN). Conclusions: We found ATM to be an unexpectedly frequent neurological complication of COVID-19. Most cases (68%) had a latency of 10 days to 6 weeks that may indicate post-infectious neurological complications mediated by the host's response to the virus. In 32% a brief latency (15 hours to 5 days) suggested a direct neurotropic effect of SARS-CoV-2. The occurrence of 3 reported ATM adverse effects among 11,636 participants in the AZD1222 vaccine trials is extremely high considering a worldwide incidence of 0.5/million COVID-19-associated ATM cases found in this report. The pathogenesis of ATM remains unknown, but it is conceivable that SARS-CoV-2 antigens -perhaps also present in the AZD1222 COVID-19 vaccine or its chimpanzee adenovirus adjuvant- may induce immune mechanisms leading to the myelitis.

Prognostic factors for relapse and outcome in pediatric acute transverse myelitis.

OBJECTIVE: It may be difficult for clinicians to estimate the prognosis of pediatric acute transverse myelitis (ATM). The aim of this study was to define prognostic factors for relapsing disease and poor outcome in pediatric ATM. METHODS: This prospective cohort study included 49 children, 18 boys and 31 girls (median age 13.1 years, IQR 6.5-16.2) with a first episode of ATM. Factors associated with relapsing disease and poor outcome (Expanded Disability Status Scale (EDSS) ≥ 4) were assessed during a median follow-up of 37 months (IQR 18-75). RESULTS: In total, 14 patients (29%) experienced ≥ 1 relapse(s) and nine patients (18%) had a poor outcome. Factors at onset associated with relapsing disease included higher age (16.1 vs. 11.6 years, p = 0.002), longer time to maximum severity of symptoms (5.5 vs. 3 days, p = 0.01), lower maximum EDSS score (4.0 vs. 6.5, p = 0.003), short lesion on spinal MRI (64 vs. 21%, p = 0.006), abnormalities on brain MRI (93 vs. 44%, p = 0.002) and presence of oligoclonal bands in cerebrospinal fluid (67 vs. 14%, p = 0.004). The only factor associated with poor outcome was presence of a spinal cord lesion on MRI without cervical involvement (56 vs. 14%, p = 0.02). CONCLUSION: Pediatric ATM patients presenting with clinical, radiological and laboratory features associated with multiple sclerosis (MS) are at risk for relapsing disease. In absence of these known MS risk factors at onset of disease these patients are at low risk for relapses. Only a minority of pediatric ATM patients in this cohort have a poor outcome.

Neuromyelitis optica spectrum disorder (NMOSD) presenting as acute transverse myelitis with positive aquaporin 4 antibodies.

An 80-year-old, previously healthy patient presents with acute transverse myelitis with sensory level at T8. The MRI scan of the spinal cord showed longitudinal extensive transverse myelitis, and she tested positive for aquaporin 4 antibodies in serum. She received treatment with intravenous and oral steroids, with no improvement and then underwent plasma exchange. She was then started on azathioprine for prevention of relapses, while continuing physiotherapy and occupational therapy. Eventually, she was transferred to a specialised spinal cord centre for long-term rehabilitation.

Longitudinally extensive transverse myelitis following acute COVID-19 infection.

Corona Virus Disease 2019 (COVID-19) is a new illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the increasing number of confirmed cases and the accumulating clinical data, a broad spectrum of neurological complications has been reported in the literature, including encephalopathy, stroke, Guillain-Barré syndrome, meningo-encephalitis, acute necrotizing hemorrhagic encephalopathy, and inflammatory central nervous system syndromes. Here, we describe the case of a 38-year-old woman presenting with longitudinally extensive transverse myelitis, revealed by bilateral lower limb weakness, decreased sensation below the Th4 level and urinary retention, and occuring 15 days after she had been diagnosed with COVID-19.

Tubercular longitudinally extensive transverse myelitis with lower motor neuron paralysis.

Transverse myelitis typically extends two or less spinal segments, whereas longitudinal extensive transverse myelitis (LETM) extends three or more spinal segments in length and may occasionally span all the segments of the spinal cord. We present a case of spinal tuberculosis presenting with LETM with true lower motor neuron-type flaccid paraplegia.

Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic.

BACKGROUND: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations. METHODS: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes. CONCLUSION: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.

Les impacts neurologiques et neuropsychiatriques d'une infection à la COVID-19. CONTEXTE: Bien qu'il s'agisse principalement d'une maladie des voies respiratoires, la maladie infectieuse à coronavirus apparue en 2019 (COVID-19) s'est avérée avoir un lien de causalité avec une pléthore d'impacts d'ordre neurologique, neuropsychiatrique et psychologique. Cette étude entend donc analyser ces impacts tout en discutant l'évolution des recommandations thérapeutiques se rapportant à cette maladie. MÉTHODES: Les bases de données PubMed et Google Scholar ont été interrogées entre les 1er janvier et 30 mai 2020. Les termes clés suivants ont été utilisés : « COVID-19 ¼, « SRAS ­ CoV-2 ¼, « Pandémie ¼, « Neuro ­ COVID ¼, « AVC ­ COVID ¼, « Épilepsie ­ COVID ¼, « COVID ­ encéphalopathie ¼, « SRAS ­ CoV-2 ­ encéphalite ¼, « SRAS ­ CoV-2 ­ rhabdomyolyse ¼, « COVID ­ maladie démyélinisante ¼, « Manifestations neurologiques ¼, « Manifestations psychosociales ¼, « Recommandations thérapeutiques ¼, « COVID-19 et changement thérapeutiques ¼, « Psychiatrie ¼, « Marginalisés ¼, « Télémédecine ¼, « Santé mentale ¼, « Quarantaine ¼, « Infodémique ¼ et « Médias sociaux ¼. De plus, quelques articles de journaux relatifs à la pandémie de COVID-19 et à ses impacts psychosociaux ont également été ajoutés en fonction du contexte. RÉSULTATS: Il appert que les manifestations neurologiques et neuropsychiatriques des infections à la COVID-19 sont nombreuses. Les caractéristiques cliniques d'une implication des systèmes nerveux central et périphérique sautent désormais aux yeux. Ces caractéristiques ont fait l'objet d'une brève analyse systématique à l'aide de publications scientifiques. En outre, la plupart des impacts d'ordre psychologique de cette pandémie se sont révélés moins apparents que les changements réglementaires, socioéconomiques et psychosociaux. CONCLUSION: Les manifestations neurologiques et neuropsychiatriques de cette maladie ne font que commencer à être élucidées. Cela exige donc une capacité accrue de vigilance en vue d'un diagnostic rapide, et ce, afin de prévenir des complications additionnelles et une mortalité accrue.

A clinico-neurophysiological study of urogenital dysfunction in MOG-antibody transverse myelitis.

OBJECTIVE: To assess the clinical, urodynamic, and neurophysiologic features of patients with persisting bladder, bowel, and sexual dysfunction after transverse myelitis in myelin oligodendrocyte glycoprotein antibody (MOG-Ab) disease. METHODS: Patients with a history of MOG-Ab disease-related transverse myelitis seen prospectively in a tertiary center uro-neurology service between 2017 and 2019 were included. They received cross-sectional clinical assessment; completed standardized questionnaires on bladder, bowel, and sexual symptoms; and underwent urodynamic and pelvic neurophysiologic investigations. RESULTS: Twelve patients (9 male) were included with a total of 17 episodes of transverse myelitis. Mean age at first attack was 26 (SD 9) years, and median follow-up duration was 50 (interquartile range 32-87) months. Acute urinary retention requiring bladder catheterization occurred in 14 episodes and was the first symptom in 10 episodes. Patients with lesions affecting the conus medullaris required catheterization for significantly longer durations than those without a conus lesion (median difference 15.5 days, p = 0.007). At follow-up, all patients had recovered full ambulatory function, but persisting bladder and bowel dysfunction moderately or severely affected quality of life in 55% and 36%, respectively, and 82% had sexual dysfunction. Pelvic neurophysiology demonstrated abnormal residual conus function in 6 patients. Urodynamic findings predominantly showed detrusor overactivity and/or detrusor-sphincter dyssynergia, indicative of a supraconal pattern of lower urinary tract dysfunction. CONCLUSIONS: Persisting urogenital and bowel dysfunction is common despite motor recovery. Although a proportion of patients had neurophysiologic evidence of residual conus abnormalities at follow-up, predominant urodyamic findings suggest that ongoing lower urinary tract dysfunction results from supraconal injury.

Aquaporin-4 neuromyelitis optica spectrum disorder in a 2-year-old girl: Diagnostic and treatment considerations.

We describe a case of an unusually early and severe manifestation of Aquaporin-4 (AQP-4) positive Neuromyelitis Optica Spectrum Disorder (NMOSD) in a two-year-old girl. We discuss learning points from her clinical presentation and highlight differences between pediatric and adult presentations of the disease. We argue that AQP-4 NMOSD should always be considered in the differential diagnosis for any child presenting with an acute neuroimmunological process given the morbidity associated with the condition and the importance of early diagnosis and treatment.

Prognostic indicators of improvement with therapeutic plasma exchange in pediatric demyelination.

OBJECTIVES: To determine the safety and clinical benefit of therapeutic plasma exchange (TPE) as rescue therapy in children with acute inflammatory demyelinating CNS syndromes and to identify baseline prognostic indicators of treatment improvement. METHODS: This single-center retrospective pediatric cohort included all consecutive patients admitted to our hospital over the period from 2003 to 2017 because of a steroid-refractory acute CNS event presumed to be inflammatory who required TPE. Functional status assessment to identify improvement included the following performance category scales: visual outcome, bladder control, gait, and Expanded Disability Status Scale (EDSS). These assessments were performed before and after TPE in every patient. RESULTS: Sixty-five children requiring TPE to treat 78 CNS attacks were included for analysis. Median age at TPE was 10.5 years (1.9-18 years); 45% were girls. Seropositivity (aquaporin-4 water channel-immunoglobulin G [IgG] or myelin oligodendrocyte glycoprotein-IgG) was found in 20 of 42 (48%) patients. Attack phenotypes leading to TPE were optic neuritis (ON) in 42%, longitudinally extensive transverse myelitis (LETM) in 31%, ON + LETM in 15%, and other combined syndromes in 11%. Overall, moderate to marked neurologic improvement was observed in 72% of children at the end of TPE and in 88.5% at 6 months of follow-up. Lower baseline scores on the EDSS, visual outcome, and gait scales were found to be independent prognostic indicators of treatment benefit. Sex, age at onset and at TPE, attack phenotype, disease duration, and time from attack onset to TPE initiation were not significantly associated with treatment outcome. Adverse events were observed in 31 of 524 (5.9%) procedures, being severe in 4. CONCLUSIONS: TPE was an effective rescue therapy associated with functional improvement. No therapeutic window for TPE initiation was identified in this pediatric cohort. Overall frequency of adverse events was low; however, serious events should be anticipated and avoided. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with acute inflammatory demyelinating CNS syndromes, TPE leads to functional improvement.

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

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 < .001) and multiple cord lesions (18 patients [39%] vs 7 patients [10%]; P < .001). Approximately 50% of patients with MOG-Ab disease had only short cord lesions when the TM occurred as a relapse. Median (range) recovery EDSS score was lower in patients with MOG-Ab disease than patients with AQP4-Ab disease (1.8 [1.0-8.0] vs 3.0 [1.0-8.0]). Persistent bladder dysfunction associated with an increased prevalence of conus lesions occurred more frequently in patients with MOG-Ab disease than in patients with AQP4-Ab disease (27 patients [59%] vs 33 patients [48%]). Long-term catheter requirement was roughly equal between groups (9 patients [20%] vs 16 patients [23%]). Relapses after TM occurred in 17 patients with MOG-Ab disease (37%) and 36 patients with AQP4-Ab disease (52%). Concomitant brainstem lesions in patients with MOG-Ab disease were associated with a higher mean (SD) EDSS score at recovery (3.5 [2.3] vs 1.4 [0.9]; P < .001). In patients with AQP4-Ab disease, those younger than 50 years were more likely to relapse (27 of 36 patients aged <50 years [75%] vs 9 of 33 patients aged ≥50 years [27%]; P < .001) and those 50 years and older were more likely to reach an EDSS score of 6 (19 of 33 patients aged ≥50 years [58%] vs 11 of 36 patients aged <50 years [31%]; P = .03). 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.

GRP 78 antibodies are associated with clinical phenotype in neuromyelitis optica.

BACKGROUND: We previously reported the association between blood-brain barrier (BBB) dysfunction and glucose-regulated protein 78 (GRP 78) autoantibodies in neuromyelitis optica (NMO). OBJECTIVE: We clarify whether the BBB-endothelial cell activation induced by immunoglobulin G (IgG) is associated with the clinical phenotype, disease activity, and markers of BBB disruption. METHODS: We purified serum IgG from 24 serum samples from patients with NMO spectrum disorder (NMOSD), who were positive for anti-AQP4 antibodies (longitudinally extensive transverse myelitis [LETM], n = 14; optic neuritis [ON], n = 6; other phenotype, n = 4) and nine healthy controls. IgG was exposed to human brain microvascular endothelial cells (TY10) and the number of nuclear NF-κB p65-positive cells, as a marker of endothelial cell activation, was analyzed using a high-content imaging system. Change in BBB permeability was also measured. The presence of GRP78 autoantibodies was detected by Western blotting. RESULTS: In the LETM group, IgG significantly induced the nuclear translocation of NF-κB p65 in comparison to the ON and healthy control groups. A significant correlation was observed between the number of NF-κB nuclear-positive cells and clinical markers of BBB disruption, including Gd enhancement in spinal MRI and the cerebrospinal fluid/serum albumin ratio. This effect was significantly reduced at the remission phase in the individual NMOSD patients. Furthermore, GRP78 antibody positivity was associated with the LETM phenotype and disease severity in NMOSD patients. CONCLUSION: Endothelial cell activation was associated with the LETM phenotype, clinical markers of BBB disruption and disease activity. These observations may explain the phenotypic differences between the NMOSD subtypes, LETM, and isolated ON.

Acute extensive myelopathy after single heroin and cocaine exposure in a patient with toxicological evidence of long-term drug abstinence.

Heroin-related myelopathy is an uncommon but often devastating complication of heroin intake. It is usually reported in individuals exposed to intravenous heroin after a variable drug-free period, leading to acute and complete spinal cord injury with poor long-term outcome. We describe an original case of acute longitudinally extensive transverse myelopathy following single heroin and cocaine intravenous exposure after a long period of abstinence confirmed by toxicological hair and retrospective urine drug analysis. This case could provide new insights in the understanding of this rare neurological complication.

Longitudinal extensive transverse myelitis: a rare neurological complication of systemic lupus erythematosus.

We present a 47-year-old woman with recently diagnosed systemic lupus erythematosus who developed progressive numbness and tingling of her upper and lower extremities, followed by weakness and difficulty ambulating. She was diagnosed with longitudinal extensive transverse myelitis involving her entire cervical and thoracic spinal cord. Infectious workup was unrevealing. She failed to respond to pulse-dose intravenous steroids, but slowly improved with the addition of plasmapheresis and cyclophosphamide. Following maintenance treatment with mycophenolate mofetil and slow tapering of oral steroids, she has maintained complete remission with significant recovery of neurological function.

New onset transverse myelitis diagnostic accuracy and patient experiences.

IMPORTANCE: Patients afflicted with rare diseases often have a delay in diagnosis and treatment. Understanding the prevalence and impact of delayed diagnosis in transverse myelitis could trigger directed educational initiatives to increase clinician awareness and improve care. OBJECTIVE: To determine if symptoms at onset or care provider initially approached was associated with time to diagnosis, treatment or outcome in patients with transverse myelitis. DESIGN: This was an online patient and caregiver standardized survey to collect data about the initial medical experience. Patients were recruited through social media to complete a survey about initial symptoms, care provider approached for diagnosis, first events (hospital admission, testing, sent home, etc.), first diagnosis, time to treatment and outcomes. The data was collected by an independent, non-profit patient advocacy organization (The Transverse Myelitis Association) and provided to researchers for analysis. SETTING: This was an online survey of a prevalent cohort of individuals diagnosis with transverse myelitis. PARTICIPANTS: Patients with various autoimmune disorders responded to the survey. These included patients with multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis and idiopathic transverse myelitis. Only data about patients, greater than a year of age, with a diagnosis of transverse myelitis were included in the study.

The coexistence of recurrent cerebral tumefactive demyelinating lesions with longitudinally extensive transverse myelitis and demyelinating neuropathy.

Combined central and peripheral demyelination (CCPD) is a rare chronic inflammatory disorder of the nervous system. In this article, we report on a CCPD patient with a very unusual pattern of central demyelination, comprising recurrent cerebral tumefactive demyelinating lesions (three times, each one in a new area of the brain) and one episode of longitudinally extensive transverse myelitis. This patient could not be classified as having multiple sclerosis, or neuromyelitis optica spectrum disorder, or any other well-known inflammatory disorder of the central nervous system, associated with demyelinating neuropathy. A diagnosis of idiopathic inflammatory demyelinating disorder (IIDD) was made while waiting for more knowledge concerning the diseases currently characterized as IIDD.