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Abstract: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed or refractory hematologic malignancies, but it comes with unique toxicities, notably cytokine release syndrome and ICANS (immune effector cell-associated neurotoxicity syndrome). As experience with CAR T-cell therapy grows, distinct and infrequent neurologic complications are becoming increasingly evident. Recently, reports of acute myelopathy after the administration of CAR T-cell therapies have been accumulating. Despite the establishment of consensus guidelines for managing ICANS, there remains limited guidance on the appropriate investigations and treatments for this rare complication. In this manuscript, we delve into the clinical features, pathophysiology, and strategies for the optimal management of acute myelitis after CAR T-cell therapy and draw insights from reported cases in the literature., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Acute flaccid myelitis (AFM) is a childhood illness characterized by sudden-onset weakness impairing function. The primary goal was to compare the motor recovery patterns of patients with AFM who were discharged home or to inpatient rehabilitation. Secondary analyses focused on recovery of respiratory status, nutritional status, and neurogenic bowel and bladder in both cohorts., Methods: Eleven tertiary care centers in the United States performed a retrospective chart review of children with AFM between January 1, 2014, and October 1, 2019. Data included demographics, treatments, and outcomes on admission, discharge, and follow-up visits., Results: Medical records of 109 children met inclusion criteria; 67 children required inpatient rehabilitation, whereas 42 children were discharged directly home. The median age was 5 years (range 4 months to 17 years), and the median time observed was 417 days (interquartile range = 645 days). Distal upper extremities recovered better than the proximal upper extremities. At acute presentation, children who needed inpatient rehabilitation had significantly higher rates of respiratory support (P < 0.001), nutritional support (P < 0.001), and neurogenic bowel (P = 0.004) and bladder (P = 0.002). At follow-up, those who attended inpatient rehabilitation continued to have higher rates of respiratory support (28% vs 12%, P = 0.043); however, the nutritional status and bowel/bladder function were no longer statistically different., Conclusions: All children made improvements in strength. Proximal muscles remained weaker than distal muscles in the upper extremities. Children who qualified for inpatient rehabilitation had ongoing respiratory needs at follow-up; however, recovery of nutritional status and bowel/bladder were similar., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition., Study Design: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition., Results: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001)., Conclusions: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Acute flaccid myelitis (AFM) is a "polio-like" neurologic disorder of the spinal cord gray matter characterized by asymmetric, flaccid limb weakness of rapid onset following prodromal viral illness. It has affected the pediatric population of the United States since 2014, but there is a paucity of literature describing the post-acute comprehensive rehabilitation management that maximizes functional outcomes for patients. This case series attempts to mitigate this by describing the complete acute and post-acute care course of six children diagnosed with AFM in Western Pennsylvania. It is critical that pediatric rehabilitation medicine providers be knowledgeable about the complex medical and rehabilitation management for patients with AFM.

Background: Acute flaccid myelitis (AFM) is a devastating neurologic condition in children, manifesting as acute limb weakness and/or paralysis. Despite increased awareness of AFM following initiation of U.S. surveillance in 2014, no treatment consensus exists. The purpose of this systematic review was to summarize the most current knowledge regarding AFM epidemiology, cause, clinical features, diagnosis, and supportive and operative management, including nerve transfer., Methods: The authors systematically reviewed the literature based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using multiple databases to search the keywords ("acute flaccid myelitis"), ('acute flaccid myelitis'/exp OR 'acute flaccid myelitis'), and (Acute AND flaccid AND myelitis). Included articles reported on (1) AFM diagnosis and (2) patient-specific data regarding epidemiology, cause, clinical features, diagnostic features, or management of AFM., Results: Ninety-nine articles were included in this review. The precise cause and pathophysiologic mechanism of AFM remain undetermined, but AFM is strongly associated with nonpolio enterovirus infections. Clinical presentation typically comprises preceding viral prodrome, pleocytosis, spinal cord lesions on T2-weighted magnetic resonance imaging, and acute onset of flaccid weakness/paralysis with hyporeflexia in at least one extremity. Supportive care includes medical therapy and rehabilitation. Early studies of nerve transfer for AFM have shown favorable outcomes for patients with persistent weakness., Conclusions: Supportive care and physical therapy are the foundation of a multidisciplinary approach to managing AFM. For patients with persistent limb weakness, nerve transfer has shown promise for improving function in distal muscle groups. Surgeons must consider potential spontaneous recovery, patient selection, donor nerve availability, recipient nerve appropriateness, and procedure timing., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Tick-Borne Encephalitis (TBE) - Clinical and Therapeutical Aspects Abstract. Tick-borne encephalitis (TBE) is an acute inflammatory disease of the central nervous system transmitted by ticks and caused by the TBE virus, which is found in more and more parts of Europe and Asia. Only 2-30% of infections are symptomatic, and a biphasic course of fever is typical in the prodromal stage. Clinically-neurologically, 50% of cases develop meningitis, 40% meningoencephalitis, and 10% meningoencephalomyelitis. The latter is often associated with feared brainstem involvement. Encephalitis is characterized by impaired consciousness, fatigue, emotional lability, and neurocognitive deficits; myelitis is characterized by flaccid paralysis of the arms or legs. Simultaneous detection of TBEV-specific IgM and IgG antibodies in serum and a matching inflammatory CSF syndrome is required to confirm the diagnosis. Meningitis heals without sequelae; 80% of cases of encephalitis and only 20% of cases of myelitis recover completely. The overall lethality rate is 1%. Immunocompromised, elderly, and myelitic patients are at higher risk for severe disease progression and mortality. Because no specific antiviral therapy is available, active TBE vaccination remains the most important preventive measure for all persons 6 years of age and older residing in high-risk areas.

Acute flaccid myelitis (AFM) is a neuroinflammatory disease characterized by acute asymmetric weakness of the limbs associated with lesions of the gray matter of the spinal cord. It mainly affects children and has been increasingly identified since 2014., Objective: To describe a severe emerging neurological disease in Chile., Clinical Case: Three children (2 females), previously healthy were in cluded. The age at the onset was between 4 and 6 years. All presented an acute febrile illness associated with upper respiratory symptoms, rapid onset of proximal asymmetric limb weakness, spinal fluid pleocytosis, and enterovirus isolated from nasopharyngeal swab; two patients developed tetraparesis. The MRI of the spinal cord showed T2 hyperintensity of the grey matter. The three patients were admitted to the Pediatric Intensive Care Unit (PICU), and two required mechanical ventilation. No significant improvements were observed after the use of immunomodulatory therapy and plasma ex change. At 12 months of follow-up, one case was quadriplegic and ventilator-dependent; the second died of ventricular arrhythmia in the PICU, and the third one is under rehabilitation with partial recovery., Conclusions: We report the first cases of this severe emerging neurological disease in our country. In a child with predominantly proximal and asymmetric acute limb paralysis, pediatricians must have a high index of suspicion for AFM. Since it can progress rapidly and lead to respiratory failure, suspected AFM should be considered a medical emergency.

Abstract: Since 2014, biennial rises in acute flaccid myelitis (AFM) have brought attention to this rare but debilitating condition. Children with AFM typically present with acute onset, flaccid weakness accompanied by longitudinally extensive gray matter injury demonstrated on magnetic resonance imaging. A clearer understanding of the epidemiology and suspected pathogenesis of AFM may result in increased recognition. The purpose of this review article is to guide emergency physicians in recognizing key clinical features, initiating diagnostic evaluation and providing appropriate interventions for children with suspected AFM., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Infections of the spine and spinal cord are associated with a high risk of morbidity and mortality and, therefore, require prompt clinical recognition, efficient diagnostic evaluation, and interdisciplinary treatment. This article reviews the pathophysiology, epidemiology, clinical manifestations, diagnosis, and treatment of infections of the spine and spinal cord to help practicing clinicians recognize, evaluate, and manage patients with such infections., Recent Findings: Aging of the population, increasing use of immunosuppressive medications, and other factors have contributed to increasing rates of spinal infections. Although the most common agents responsible for spinal infections remain bacteria and viruses, fungal infections occur in individuals who are immunocompromised, and parasitic infections are common in endemic regions, but patterns are in evolution with migration and climate change. Recent outbreaks of acute flaccid myelitis in children have been associated with enteroviruses A71 and D68., Summary: Infections of the spine and spinal cord can be challenging to diagnose, requiring a thorough history and neurologic examination, laboratory studies of serum and CSF, neuroimaging (particularly MRI), and, in some instances, biopsy, to establish a diagnosis and treatment regimen. Interdisciplinary management including collaboration with experts in internal medicine, infectious disease, and neurosurgery is important to improve clinical outcomes., (Copyright © 2021 American Academy of Neurology.)

Acute flaccid myelitis (AFM) is an incompletely understood neurologic disorder occurring in epidemic fashion causing weakness ranging from mild paresis to devastating paralysis in children and some adults. This article reviews the case definition of AFM as well as its epidemiology and association with enteroviral infection. The clinical presentation, diagnostic investigation with particular attention to electrodiagnostics, acute management, and surgical options are described. Clinical outcomes and considerations for acute and long-term rehabilitation management are discussed extensively based on review of current literature, highlighting avenues for further study., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The study aimed to describe the cases of neurological disease related to the outbreak of enterovirus (EV) in three regions in Northern Spain during 2016., Materials and Methods: Multicenter retrospective observational study. Clinical, radiological, and microbiological data were analyzed from patients younger than 15 years with confirmed EV-associated neurological disease admitted to 10 hospitals of Asturias, Cantabria, and Castile and Leon between January 1 and December 31, 2016., Results: Fifty-five patients were included. Median age was 24 months (interquartile range = 18.5 months). Fifteen patients were classified as aseptic meningitis (27.3%). In total, 37 cases presented brainstem encephalitis (67.3%), 25 of them due to EV-A71 with excellent prognosis (84.6% asymptomatic 2 months following the onset). Three cases of acute flaccid myelitis (5.5%) by EV-D68 were reported and presented persistent paresis 2 months following the onset. Microbiological diagnosis by reverse transcriptase polymerase chain reaction was performed in all cases, finding EV in cerebrospinal fluid in meningitis, but not in brainstem encephalitis and acute flaccid myelitis, where EV was found in respiratory or rectal samples. Step therapy was administrated with intravenous immunoglobulin (IVIG; 32.7%), methylprednisolone (10%), and plasmapheresis (3.6%). Four patients received fluoxetine (7.3%). Twenty patients needed to be admitted to pediatric intensive care unit (36.4%)., Conclusion: Clinical, microbiological, and radiological diagnosis is essential in outbreaks of EV neurological disease, taking into account that it can be difficult to identify EV-A71 and EV-D68 in CSF, requiring throat or rectal samples. There is not specific treatment to these conditions and the efficacy and understanding of the mechanism of action of immune-modulatory treatment (IVIG, corticosteroids, and plasmapheresis) is limited., Competing Interests: None declared., (Thieme. All rights reserved.)

Acute flaccid myelitis is an emerging neurologic disease, first described in 2014 and predominantly affecting young children. Acute flaccid myelitis cases tend to spike every 2 years, in the late summer to fall, and the next peak is expected in 2020. The diagnosis of acute flaccid myelitis is often delayed, leading to suboptimal evaluation, including incomplete laboratory assessment. Acute and chronic morbidity are high, and a standardized, multidisciplinary approach to evaluation and treatment is essential to optimizing outcomes. In a review of acute flaccid myelitis patients treated in 2018 at our institution, we noted considerable variability in days to presentation, evaluation, and treatment. In response, the authors developed a protocol for the evaluation and management of pediatric patients suspected of having acute flaccid myelitis. The protocol was developed using local experience/case review, expert consensus, and the relevant literature. The protocol spans the spectrum of care, from initial evaluation in a primary care or emergency setting, to acute hospital management and evaluation and long-term inpatient and rehabilitation settings. The purpose of this report is both to share the findings from our 2018 case review and to disseminate our acute flaccid myelitis protocol. Our hope is that publication of our protocol will both inform the development of a standardized approach to acute flaccid myelitis and to encourage other centers to form a multidisciplinary acute flaccid myelitis team to provide expert care throughout the disease process, from presentation to recovery.

Background: Clinical characteristics and timing associated with nonsurgical recovery of upper extremity function in acute flaccid myelitis are unknown., Methods: A single-institution retrospective case series was analyzed to describe clinical features of acute flaccid myelitis diagnosed between October of 2013 and December of 2016. Patients were consecutively sampled children with a diagnosis of acute flaccid myelitis who were referred to a hand surgeon. Patient factors and initial severity of paralysis were compared with upper extremity muscle strength outcomes using the Medical Research Council scale every 3 months up to 18 months after onset., Results: Twenty-two patients with acute flaccid myelitis (aged 2 to 16 years) were studied. Proximal upper extremity musculature was more frequently and severely affected, with 56 percent of patients affected bilaterally. Functional recovery of all muscle groups (≥M3) in an individual limb was observed in 43 percent of upper extremities within 3 months. Additional complete limb recovery to greater than or equal to M3 after 3 months was rarely observed. Extraplexal paralysis, including spinal accessory (72 percent), glossopharyngeal/hypoglossal (28 percent), lower extremity (28 percent), facial (22 percent), and phrenic nerves (17 percent), was correlated with greater severity of upper extremity paralysis and decreased spontaneous recovery. There was no correlation between severity of paralysis or recovery and patient characteristics, including age, sex, comorbidities, prodromal symptoms, or time to paralysis., Conclusions: Spontaneous functional limb recovery, if present, occurred early, within 3 months of the onset of paralysis. The authors recommend that patients without signs of early recovery warrant consideration for early surgical intervention and referral to a hand surgeon or other specialist in peripheral nerve injury., Clinical Question/level of Evidence: Risk, III., (Copyright © 2020 by the American Society of Plastic Surgeons.)

The human amnion has been used for decades in wound healing, particularly burns. Amnion epithelial cells (AECs) have been the focus of extensive research based on their possible pluripotent differentiation ability. A novel, cultured cell population derived from AECs, termed human amnion-derived multipotent progenitor (AMP) cells, secrete numerous cytokines and growth factors that enhance tissue regeneration and reduce inflammation. This AMP cell secretome, termed ST266, is a unique biological solution that accumulates in eyes and optic nerves following intranasal delivery, resulting in selective suppression of optic neuritis in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, but not myelitis at the administered dose. We tested the hypothesis that systemic AMP cell administration could suppress both optic neuritis and myelitis in EAE. Intravenous and intraperitoneal administration of AMP cells significantly reduced ascending paralysis and attenuated visual dysfunction in EAE mice. AMP cell treatment increased retinal ganglion cell (RGC) survival and decreased optic nerve inflammation, with variable improvement in optic nerve demyelination and spinal cord inflammation and demyelination. Results show systemic AMP cell administration inhibits RGC loss and visual dysfunction similar to previously demonstrated effects of intranasally delivered ST266. Importantly, AMP cells also promote neuroprotective effects in EAE spinal cords, marked by reduced paralysis. Protective effects of systemically administered AMP cells suggest they may serve as a potential novel treatment for multiple sclerosis.

Background: Acute flaccid myelitis (AFM) is characterised by rapid onset of limb weakness with spinal cord grey-matter abnormalities on MRI scan. We aimed to assess whether detection of enterovirus in respiratory or other specimens can help predict prognosis in children with AFM., Methods: In this nationwide, longitudinal study, we evaluated the significance of detection of enterovirus in any sample in predicting outcomes in a cohort of Canadian children younger than 18 years presenting with AFM to tertiary paediatric hospitals in Canada in 2014 and 2018. All patients fulfilled the 2015 US Centers for Disease Control and Prevention case definition for definite AFM or probable AFM. Clinical data, laboratory findings, treatment, and neuroimaging results were collected (follow up period up to 5 years). We assessed neurological function and motor outcomes using Kurtzke's Expanded Disability Status Scale (EDSS) and a Weakest Limb Score., Findings: 58 children with AFM (median age 5·1 years, IQR 3·8-8·3) were identified across five of Canada's ten provinces and three territories. 25 (43%) children had enterovirus detected in at least one specimen: 16 (64%) with EV-D68, two (8%) with EV-A71, two (8%) with coxsackievirus, 10 (40%) with untyped enterovirus. Children who were enterovirus positive were more likely than those that were negative to have had quadriparesis (12 [48%] of 25 vs four [13%] of 30; p=0·028), bulbar weakness (11 [44%] of 25 vs two [7%] of 30; p=0·028), bowel or bladder dysfunction (14 [56%] of 25 vs seven [23%] of 30; p=0·040), cardiovascular instability (nine [36%] of 25 vs one [3%] of 30; p=0·028), and were more likely to require intensive care unit admission (13 [52%] of 25 vs 5 [17%] of 30; p=0·028). On MRI, most children who were enterovirus positive showed brainstem pontine lesions (14 [61%] of 23), while other MRI parameters did not correlate with enterovirus status. Median EDSS of enterovirus positive (EV+) and enterovirus negative (EV-) groups was significantly different at all timepoints: baseline (EDSS 8·5, IQR 4·1-9·5 vs EDSS 4·0, IQR 3·0-6·0; p=0·0067), 3 months (EDSS 4·0, IQR 3·0-7·4 vs EDSS 3·0, IQR 1·5-4·3; p=0·0067), 6 months (EDSS 3·5, IQR 3·0-7·0 vs EDSS 3·0, IQR 1·0-4·0; p=0·029), and 12 months (EDSS 3·0, IQR 3·0-6·9 vs EDSS 2·5 IQR 0·3-3·0; p=0·0067). Kaplan-Meier survival analysis of a subgroup of patients showed significantly poorer motor recovery among children who tested positive for enterovirus than for those who tested negative (p=0·037)., Interpretation: Detection of enterovirus in specimens from non-sterile sites at presentation correlated with more severe acute motor weakness, worse overall outcomes and poorer trajectory for motor recovery. These results have implications for rehabilitation planning as well as counselling of families of children with these disorders. The findings of this study support the need for early testing for enterovirus in non-CNS sites in all cases of AFM., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Acute flaccid myelitis, defined by acute flaccid limb weakness in the setting of grey matter lesions of the spinal cord, became increasingly recognised in 2014 following outbreaks in Colorado and California, temporally associated with an outbreak of enterovirus D68 respiratory disease. Since then, there have been biennial increases in late summer/early fall. A viral infectious aetiology, most likely enteroviral, is strongly suspected, but a definitive connection has yet to be established. Patients typically present with asymmetric weakness, maximal proximally, in the setting of a febrile illness. MRI demonstrates T2/FLAIR abnormalities in the central grey matter of the spinal cord, and cerebrospinal fluid typically shows a lymphocytic pleocytosis with variable elevation in protein. The weakness may be progressive over several days and involve respiratory muscles, making early recognition and close monitoring essential. Other complications in the acute period may include autonomic instability and bowel/bladder involvement. There is no clear recommended treatment at this time, although intravenous immunoglobulin, steroids and plasma exchange have been used. Intensive therapies and rehab services have shown benefit in maximising function, and surgical interventions may be considered in cases without optimal response to therapies. Close attention should also be paid to psychosocial factors. Prognosis is generally guarded, and additional factors that predict final outcome, including host factors and treatment effects, have yet to be elucidated. Multicentre collaborative efforts will be required to provide answers about this rare but serious disorder., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Acute flaccid myelitis (AFM) is a severe illness similar to paralytic poliomyelitis. It is unclear how frequently AFM occurred in U.S. children after poliovirus elimination. In 2014, an AFM cluster was identified in Colorado, prompting passive US surveillance that yielded 120 AFM cases of unconfirmed etiology. Subsequently, increased reports were received in 2016 and 2018. To help inform investigations on causality of the recent AFM outbreaks, our objective was to determine how frequently AFM had occurred before 2014, and if 2014 cases had different characteristics., Methods: We conducted a retrospective study covering 2005-2014 at 5 pediatric centers in 3 U.S. regions. Possible AFM cases aged ≤18 years were identified by searching discharge ICD-9 codes and spinal cord MRI reports (>37,000). Neuroradiologists assessed MR images, and medical charts were reviewed; possible cases were classified as AFM, not AFM, or indeterminate., Results: At 5 sites combined, 26 AFM cases were identified from 2005-2013 (average annual number, 3 [2.4 cases/100,000 pediatric hospitalizations]) and 18 from 2014 (12.6 cases/100,000 hospitalizations; Poisson exact p<0.0001). A cluster of 13 cases was identified in September-October 2014 (temporal scan p = 0.0001). No other temporal or seasonal trend was observed. Compared with cases from January 2005-July 2014 (n = 29), cases from August-December 2014 (n = 15) were younger (p = 0.002), more frequently had a preceding respiratory/febrile illness (p = 0.03), had only upper extremities involved (p = 0.008), and had upper extremity monoplegia (p = 0.03). The cases had higher WBC counts in cerebrospinal fluid (p = 0.013)., Conclusion: Our data support emergence of AFM in 2014 in the United States, and those cases demonstrated distinctive features compared with preceding sporadic cases., Competing Interests: R.M. reports financial interests with Siemens Healthineers (travel, meals, lodging), Philips Healthcare (travel, meals, lodging) and Guerbet, LLC (consulting fees and travel expenses). S.H. receives salary support from the CDC for activities related to AFM surveillance. A.K. was employed by IHRC, Inc., a contracting agency to CDC. IHRC provided support in the form of salary for A.K. but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of A.K. is articulated in the ‘author contributions’ section. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Acute flaccid myelitis (AFM) are reported to be associated with enterovirus D68 infection. Though an increasing number of AFM cases were reported with EV-D68 infection in the US, few such cases have been found in China., Case Presentation: A 6-year-old boy presented with acute flaccid myelitis (AFM) involving left arm after fever and respiratory symptoms for 6 days. Computed Tomography (CT) revealed inflammation in both lungs and magnetic resonance imaging (MRI) of the brain and spine showed swelling in the left frontal lobe and brain stem. The patient was diagnosed with meningomyelitis. EV-D68 was detected from pharyngeal samples 36 days after the onset of the disease., Conclusion: We report the first EV-D68 infection in case of AFM in mainland China. AFM surveillance systems is recommended to be established in China to guide diagnosis, case reporting, and specimen collection and testing for better understanding its etiologies.

Enterovirus D68 was first identified in 1962 and caused a worldwide outbreak starting from the North America in 2014. Enterovirus D68 has been in continuous circulation among many countries recently, including Taiwan. Reports also reveal high seroprevalence, which indicates that the disease burden of enterovirus D68 may be underestimated via viral culture or polymerase chain reaction results. Although most infected cases have mild respiratory illness, severe complications including acute flaccid myelitis and acute respiratory distress syndrome have also been reported. In the position of an emerging pathogen, enterovirus D68 poses a threat to public health and may cause devastating diseases. Diverse severity of neurological sequelae remains inevitable among acute flaccid myelitis patients, but no curable treatment is available currently. According to the management suggestions of the American Centers of Disease Control, uses of corticosteroids and plasmapheresis are either preferred or avoided and intravenous immunoglobulin also has no clear indication in the treatment for acute flaccid myelitis. In this review article, we provide information about the epidemiology, clinical recognition and treatment strategy of enterovirus D68. Better understanding of this disease is the foothold for advanced investigation and monitoring in the future., (Copyright © 2019. Published by Elsevier B.V.)

Background: We aimed to characterize the outcomes of 167 children affected by acute flaccid myelitis by leveraging the power of social media., Methods: Members of a closed social media (Facebook) group were invited to participate in an anonymous online survey. Descriptive statistics were applied to quantitative responses, and free-text responses were grouped into themes using a grounded theory approach., Results: Caregivers provided information about 167 affected children; 77% were at least 6 months since onset. Clinical features matched those of larger published case series (e.g., walking impairment in 76.7%, intravenous immunoglobulin treatment in 80.8%; 28.2% tested positive for Enterovirus D68; 17% children had asthma before acute flaccid myelitis onset). Mean duration of initial hospitalization was 49.1 (S.D., 74.0) days, and of initial inpatient rehabilitation was 42.3 (S.D., 67.6) days. Among challenges, parents frequently reported delays in diagnosis, including lack of neurological examination at initial medical evaluation for weakness. Other challenges included familial and professional impact of protracted hospitalizations, uncertainty about cause or prognosis of acute flaccid myelitis, and the dynamic nature of care needs in growing children. The social media group played a critical role not only for social support but also for dissemination of rehabilitation approaches and of networks of expert clinicians., Conclusions: Children with acute flaccid myelitis have persistent and dynamic deficits, but many continue to show ongoing functional improvements beyond the initial expected window of recovery. In an emerging disease paralyzing young children, social media can strengthen knowledge networks and focus on rehabilitation., (Copyright © 2019. Published by Elsevier Inc.)

Acute flaccid myelitis (AFM) is a rare condition associated with spinal cord gray matter abnormalities and frequent persistent motor deficits in the limbs. We present our experience with the diagnosis, management, and outcomes of affected children in 2014 and 2016, emphasizing features that should trigger early consideration of AFM. Early viral testing may increase the rate of detecting associated viruses., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Infectious pathogens can directly affect the spinal cord or trigger autoimmune reactions, which may result in permanent damage to cord structures. The most common aetiology comes from virus but depend on age, location of the patient and co-morbidities. Acute Flaccid paralysis and acute transverse myelitis are considered as emergencies. Differential diagnosis is mainly relapses of autoimmune diseases, which can mimic infectious myelopathies., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Acute flaccid myelitis is characterized by the combination of acute flaccid paralysis and a spinal cord lesion largely restricted to the gray matter on magnetic resonance imaging. The term acute flaccid myelitis was introduced in 2014 after the upsurge of pediatric cases in the USA with enterovirus D68 infection. Since then, an increasing number of cases have been reported worldwide. Whereas the terminology is new, the clinical syndrome has been recognized in the past in association with several other neurotropic viruses such as poliovirus.Conclusion: This review presents the current knowledge on acute flaccid myelitis with respect to the clinical presentation and its differential diagnosis with Guillain-Barré syndrome and acute transverse myelitis. We also discuss the association with enterovirus D68 and the presumed pathophysiological mechanism of this infection causing anterior horn cell damage. Sharing clinical knowledge and insights from basic research is needed to make progress in diagnosis, treatment, and prevention of this new polio-like disease. What is Known: • Acute flaccid myelitis (AFM) is a polio-like condition characterized by rapid progressive asymmetric weakness, together with specific findings on MRI • AFM has been related to different viral agents, but recent outbreaks are predominantly associated with enterovirus D68. What is New: • Improving knowledge on AFM must increase early recognition and adequate diagnostic procedures by clinicians. • The increasing incidence of AFM urges cooperation between pediatricians, neurologists, and microbiologists for the development of treatment and preventive options.

Spinal cord injury (SCI) is a disaster that can cause severe motor, sensory, and functional disorders. Implanting biomaterials have been regarded as hopeful strategies to restore neurological function. However, no optimized scaffold has been available. In this study, a novel 3D printing technology was used to fabricate the scaffold with designed structure. The composite biomaterials of collagen and chitosan were also adopted to balance both compatibility and strength. Female Sprague-Dawley rats were subjected to a T8 complete-transection SCI model. Scaffolds of C/C (collagen/chitosan scaffold with freeze-drying technology) or 3D-C/C (collagen/chitosan scaffold with 3D printing technology) were implanted into the lesion. Compared with SCI or C/C group, 3D-C/C implants significantly promoted locomotor function with the elevation in Basso-Beattie-Bresnahan (BBB) score and angle of inclined plane. Decreased latency and increased amplitude were observed both in motor-evoked potential and somatosensory-evoked potential in 3D-C/C group compared with SCI or C/C group, which further demonstrated the improvement of neurological recovery. Fiber tracking of diffusion tensor imaging (DTI) showed the most fibers traversing the lesion in 3D-C/C group. Meanwhile, we observed that the correlations between the locomotor (BBB score or angle of inclined plane) and the DTI parameters (fractional anisotropy values) were positive. Although C/C implants markedly enhanced biotin dextran amine (BDA)-positive neural profiles compared with SCI group, rats implanted with 3D-C/C scaffold displayed the largest degree of BDA profiles regeneration. Collectively, our 3D-C/C scaffolds demonstrated significant therapeutic effects on rat complete-transected spinal cord model, which provides a promising and innovative therapeutic approach for SCI. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1898-1908, 2019., (© 2019 Wiley Periodicals, Inc.)

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.

Study Design: Retrospective case series., Objectives: To describe the epidemiological, clinical, MRI and therapeutic features and the outcomes of patients with syphilitic myelitis in a third-level hospital in Marrakesh in southern Morocco., Setting: The Neurology Department, University Hospital Mohamed VI Marrakesh, Morocco., Methods: Twelve charts of persons with syphilitic myelitis over a period of 17 years were reviewed to determine demographics, presenting symptoms, clinical and radiological findings, biological features, treatment received and outcomes., Results: There were 120 reports of neurosyphilis. Twelve patients (10%) had syphilitic myelitis. Eleven patients (92%) were male with mean age of 44 at presentation. Tabes dorsalis was the most common clinical form. Cerebrospinal fluid analysis showed lymphocytic meningitis in nine patients (75%). Spine MRI was abnormal in four patients (33%). All patients were treated with 30 million units of aqueous penicillin G IV per day for 10 days, every 3 months. In follow-up, two patients (17%) with clinical syphilitic meningomyelitis improved significantly, eight patients (66%) with tabes dorsalis and subacute transverse myelitis showed partial improvement but clinical status was stationary for two patients (17%) with Erb paraplegia., Conclusions: All patients with myelopathy should undergo syphilitic serology because of nonspecific manifestations and curability of this disease., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© International Spinal Cord Society 2019.)

Objective We evaluated the clinical effects of a telephone call service for psychological symptoms such as anxiety, depression or apathy in subacute myelo-optico-neuropathy (SMON) patients living alone or with a single caregiver. Methods Up to 16 SMON patients (4 men, 12 women) and 32 control subjects were evaluated by the geriatric depression scale (GDS), apathy scale (AS) and state and trait anxiety inventory (STAI) forms X-I, including the P and A values for depression, apathy and state anxiety including disturbed peace of mind and enhanced anxiety, respectively, before (pre) and three months after (post) the telephone call service. Results The SMON patients, especially women, had significantly worse baseline scores in GDS (depression), AS (apathy) and STAI (state anxiety) than control subjects. The automated telephone call service significantly improved the high baseline STAI scores, including the P and A scores (disturbed peace of mind and enhanced anxiety), of SMON patients but not the GDS or AS scores. Conclusion SMON patients, especially women, living alone or with a single caregiver showed higher baseline depression, apathy and anxiety scores than the control subjects. The present automated telephone call service proved to be a useful care tool for improving the anxiety of SMON patients with high STAI P and A scores.

Since 2014, acute flaccid myelitis (AFM), a long-recognized condition associated with polioviruses, nonpolio enteroviruses, and various other viral and nonviral causes, has been reemerging globally in epidemic form. This unanticipated reemergence is ironic, given that polioviruses, once the major causes of AFM, are now at the very threshold of global eradication and cannot therefore explain any aspect of AFM reemergence. Instead, the new AFM epidemic has been temporally associated with reemergences of nonpolio enteroviruses such as EV-D68, until recently thought to be an obscure virus of extremely low endemicity. This perspective reviews the enigmatic epidemiologic, virologic, and diagnostic aspects of epidemic AFM reemergence; examines current options for clinical management; discusses future research needs; and suggests that the AFM epidemic offers important clues to mechanisms of viral disease emergence., (Copyright © 2019 Morens et al.)

Objective: To analyze whether myelin oligodendrocyte glycoprotein antibody (MOG-Ab) titres at onset of the disease were different according to the clinical phenotype at presentation, and to investigate whether the titres were associated with risk of further relapses or predicted clinical outcome in adult patients. Finally, we assessed an alternative method to the classical measurement of MOG-Ab levels by serial dilutions., Methods: This is a retrospective study including 79 MOG-Ab-positive adult patients, whose samples were obtained at first episode. MOG-Ab were tested by cell-based assay. HEK293 cells were transfected (tHEK293) with human-MOG plasmid. Non-tHEK293 cells were used as negative controls. Assessment of antibody titres was performed by serial dilution, and delta mean fluorescence intensity ratio signal (MOG-ratio ΔMFI) by flow cytometry. MOG-ratio ΔMFI was calculated as follows: (MFI tHEK293cells- MFI non-tHEK293cells)/MFI non-tHEK293cells. MOG-ratio ΔMFI was calculated from the first serum dilution at 1:320. The association between MOG-Ab titres and risk of relapse was analyzed by Cox regression. The association between MOG-Ab titres and visual or motor disability at last follow-up was performed by binary logistic regression. Poor visual outcome was defined when patients displayed some degree of visual disability (visual acuity [VA] < 20/20) and poor motor outcome when patients displayed some degree of motor disability (Disability Status Scale [DSS] > 1). We also investigated correlations between MOG-Ab titres and MOG-ratio ΔMFI., Results: MOG-Ab titres were higher in Caucasians than in those with other ethnicities, and in patients with a more severe VA (VA ≤ 20/100) or motor disability (DSS ≥ 3.0) at onset (p = 0.006, 0.034, and 0.058, respectively). MOG-Ab titres were not associated with risk of relapses or with the final clinical outcome. MOG-ratio ΔMFI correlated with MOG-Ab titres in the whole cohort (ρ = 0.90; p < 0.001), and when stratified by initial clinical phenotype., Conclusion: High MOG-Ab titres at onset are associated with a more severe presentation, but do not predict the future disease course. MOG-ratio ΔMFI is an alternative and straightforward method to determine MOG-Ab levels.

Enterovirus D68 (EV-D68) is an emerging infection associated with acute flaccid myelitis (AFM). Cases of AFM associated with EV-D68 infection have increased in recent years and the evidence for a causal link is growing. However, our understanding of the epidemiology, clinical features, prognosis, and neurological sequelae of EV-D68 requires ongoing surveillance and investigation. We report five cases of AFM in previously typically developing children (2-6y) from South East Scotland during September and October 2016 after infection with EV-D68 (all detected in the nasopharyngeal aspirates). All cases presented with significant neurological symptoms, which were severe in two cases requiring intensive care support because of respiratory paralysis. At 18-month follow-up, two cases remain ventilator-dependent with other cases requiring ongoing community rehabilitation. These cases represent one of the largest reported paediatric cluster of AFM associated with EV-D68 in Europe. The epidemiology and clinical information add to the knowledge base and the 18-month outcome will help clinicians to counsel families. WHAT THIS PAPER ADDS: Nasopharyngeal aspirate is more sensitive for viral isolation and isolated in all cases. Clinical outcome at 18 months after enterovirus D68 with acute flaccid myelitis provides information on extent of recovery and level of disability., (© 2018 Mac Keith Press.)

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.

Over the past two decades, West Nile virus has become the most common arbovirus in North America, leading to several outbreaks and infecting thousands of people. Mosquitos help transmit the virus in the majority of cases, but transmission occurs via blood transfusions, organ transplantation, and possibly pregnancy and breastfeeding. While most infected patients experience mild to no symptoms, thousands of West Nile virus-associated neuroinvasive cases have been reported in the United States, with over 700 cases occurring in children from 2003 to 2016. Neuroinvasive disease presents as meningitis, encephalitis, or acute flaccid paralysis, and carries a high likelihood of poor outcome, including severe neurological disability or death. To date, no pharmacologic treatment has proven effective. Therapeutic clinical trials have not been successfully completed due to the sporadic nature of viral outbreaks and resultant poor study enrollment. Although older age and chronic disease are risk factors for neuroinvasive West Nile virus disease in adults, the specific factors that influence the risk in pediatric populations have not been fully elucidated. This review summarizes the most recent literature regarding West Nile virus-associated neuroinvasive disease, especially as it pertains to the pediatric population. Moreover, the review describes the epidemiology, clinical, laboratory, and radiographic findings, and outlines the various therapies that have been trialed and potential future research directions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Infection of the central nervous system is often a life-threatening emergency. In many cases, the clinician faces an unknown pathogen and must rely upon clinical acumen and a thorough, systematic diagnostic investigation to establish a diagnosis and initiate appropriate treatment. Because patients typically present with a syndrome, such as temporal lobe encephalitis, rather than a known pathogen (e.g., herpes simplex virus 1 encephalitis), we describe diagnostic considerations in the context of their neuroanatomic tropisms and patterns of disease. This paradigm reflects the challenges clinicians face; however, tropisms are not absolute, patterns of disease are not specific, and this approach does not obviate the need for empirical treatment while a systematic diagnostic investigation is underway. Specific treatment is available for many infectious agents, including bacterial, fungal, and parasitic pathogens, as well as the herpesviruses. In cases with no specific treatment, clinicians must strive to establish the diagnosis (and thereby spare unneeded treatment), anticipate and recognize complications and pitfalls, and initiate appropriate supportive care, all of which are best achieved with a well-prepared multidisciplinary team., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

A 48-year-old man with rapid onset of fever elevation developed acute myelitis over a period of a week. MRI of the spinal cord revealed a longitudinal T 2 -hyperintense intraspinal lesion extending from C6 to Th8 level. Clinical symptoms and findings resolved with immunotherapy. In serological analysis, no antibodies related to various collagen diseases, anti-aquaporin-4 (AQP4) antibody and anti-myelin oligodendrocyte glycoprotein (MOG) antibody were detected. Anti-lactosylceramide (LacCer) antibodies were detected in the acute phase of serum and cerebrospinal fluid, with titers showing decrements in the recovery phase. The present case supports the notion that acute myelitis can occur as an anti-neutral glycolipid antibody-related disorder. Anti-neutral glycolipid antibodies should be examined in future pertinent cases of myelitis.

Competing Interests: Competing interests: None declared relating to this work.

Infectious diseases are an important cause of spinal cord dysfunction. Infectious myelopathies are of growing concern given increasing global travel and migration and expanding prevention and treatment with vaccinations, antibiotics, and antiretrovirals. Clinicians must recognize these pathologies because outcomes can dramatically improve with prompt diagnosis and management. We provide a complete review of the most frequent infectious agents that can affect the spinal cord. For each pathogen we describe epidemiology, pathophysiology, anatomic location, characteristic clinical syndromes, diagnostic approach, treatment, and prognosis. The review includes spinal imaging from selected cases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Rationale: We present the first case of enterovirus (EV) D68, lineage B3 infection, associated with acute flaccid myelitis (AFM) in Taiwan. AFM caused by EV D68 is relatively rare. This report highlights the importance of clinical recognition of the disease and discusses treatments that can benefit such patients., Patient Concerns: A 5-year-old boy experienced sudden onset of acute flaccid paralysis (AFP) involving left arm after fever and respiratory symptoms for 3 days., Diagnoses: Magnetic resonance imaging (MRI) of the spinal cord revealed signal changes over segments C1 to T5 on a T2-weighted image (T2WI), compatible with the diagnosis of AFM. The EV D68 strain, cultured from the throat of the patient was identified., Interventions: We administered intravenous immunoglobulin (IVIG, 1g/kg, twice), pulse steroid therapy (methylprednisolone, 30 mg/kg, twice) and oral prednisolone (1mg/kg/day). Rehabilitation was also arranged., Outcomes: The patient still had mild muscle atrophy over left arm after following-up for 1 year., Lessons: Early diagnosis and prompt management are essential for managing this kind of patient. IVIG, pulse therapy, and oral prednisolone may play crucial roles in controlling its clinical course.

Glial fibrillary acidic protein antibody-positive meningoencephalomyelitis is a newly described, possibly under-recognised, severe inflammatory condition of the nervous system. The clinical presentation is variable but most commonly is a combination of meningitis, encephalitis and myelitis; other manifestations may include seizures, psychiatric symptoms and tremor. There is a significant association with malignancies, often occult, and with other autoimmune conditions. Although the disease responds well to corticosteroids acutely, it typically relapses when these are tapered, and so patients need long-term immunosuppression. We report a young man presenting with subacute meningoencephalitis and subsequent myelitis, and discuss the typical presentation and management of this severe but treatable condition., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Rehabilitative training is one of the most successful therapies to promote motor recovery after spinal cord injury, especially when applied early after injury. Polytrauma and management of other medical complications in the acute post-injury setting often preclude or complicate early rehabilitation. Therefore, interventions that reopen a window of opportunity for effective motor training after chronic injury would have significant therapeutic value. Here, we tested whether this could be achieved in rats with chronic (8 weeks) dorsolateral quadrant sections of the cervical spinal cord (C4) by inducing mild neuroinflammation. We found that systemic injection of a low dose of lipopolysaccharide improved the efficacy of rehabilitative training on forelimb function, as assessed using a single pellet reaching and grasping task. This enhanced recovery was found to be dependent on the training intensity, where a high-intensity paradigm induced the biggest improvements. Importantly, in contrast to training alone, the combination of systemic lipopolysaccharide and high-intensity training restored original function (reparative plasticity) rather than enhancing new motor strategies (compensatory plasticity). Accordingly, electrophysiological and tract-tracing studies demonstrated a recovery in the cortical drive to the affected forelimb muscles and a restructuration of the corticospinal innervation of the cervical spinal cord. Thus, we propose that techniques that can elicit mild neuroinflammation may be used to enhance the efficacy of rehabilitative training after chronic spinal cord injury.

Background: Cardiovascular autonomic dysfunction is a relatively common secondary complication of tetraplegia. In addition to low baseline arterial blood pressure, tetraplegics can develop sudden-onset hypertensive episodes associated with a variety of symptoms and signs (so-called autonomic dysreflexia). Unfortunately, this potentially life-threatening medical entity is often overlooked and mismanaged. With this, a case of typical presentation of autonomic dysreflexia in an individual with acute severe cervical spinal cord impairment due to neuromyelitis optica (NMO) is reported and discussed., Case Report: A 60-year-old, Asian woman developed a rapidly progressive tetraplegia associated with neurogenic bladder and bowel, and cardiovascular autonomic dysfunction due to NMO. In addition to low baseline blood pressure and orthostatic hypotension, the patient developed episodes of autonomic dysreflexia during the acute stage following C2 motor complete tetraplegia. The episodes of autonomic dysreflexia resolved after fecal disimpaction. Her blood pressure stabilized after fecal disimpaction, even though occasional, milder episodes of autonomic dysreflexia occurred during bowel routines in the acute and subacute stages after tetraplegia. Her cardiovascular function normalized as she also regained motor and sensory function in the chronic stage after initial flare of NMO., Conclusions: This case report illustrates a clinically relevant, but still under-recognized cardiovascular autonomic complication of severe, cervical or high-thoracic spinal cord impairment due to NMO. In addition to low baseline blood pressure and orthostatic hypotension, the patient developed episodes of autonomic dysreflexia during the acute stage after tetraplegia. Autonomic dysreflexia requires early diagnosis and proper treatment in order to prevent severe complications or death. Greater awareness of this potentially life-threatening cardiovascular emergency of spinal cord impairment is needed among patients, caregivers, and healthcare professionals, including neurologists., (Copyright © 2018. Published by Elsevier B.V.)