Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications.

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.

Acute flaccid myelitis: cause, diagnosis, and management.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

Listening to Transgender and Gender Diverse Students on Christian College Campuses.

This study was an initial investigation of important areas of interest within the literature on transgender and gender diverse students, namely psychological health, well-being and campus climate for transgender and gender diverse students in young adulthood. What is unique is that data were obtained from Christian transgender and gender diverse students attending Christian college and universities. A sample of 31 undergraduate transgender students at nine Christian institutions in which staff were affiliated with the Association for Christians in Student Development completed an online survey. Participants reported high levels of religiosity, diversity in their attitudes about gender identity, negative perceptions of campus climate, lower levels of social support for gender identity than in general, moderate to high levels of psychological distress, and low to moderate levels of psychological well-being.

Comparative quantitative clinical, neuroimaging, and functional profiles in children with acute flaccid myelitis at acute and convalescent stages of disease.

AIM: To quantify characteristics in acute flaccid myelitis (AFM) at acute and convalescent stages. METHOD: This was a retrospective case series of children with AFM evaluated at a single institution in the USA (2014-2017). Acute inflammatory/ischemic myelopathies were excluded. Neurological assessments and segmental quantitative analysis of signal abnormalities on magnetic resonance imaging (MRI) of the brain and spinal cord were performed. RESULTS: Sixteen patients (11 males, five females) were evaluated. Median age at onset was 4 years (interquartile range [IQR] 3-6y). All had parainfectious acute-onset limb weakness, lower motor neuron examination, and spinal fluid pleocytosis. On acute spinal cord MRI, longitudinally extensive T2 hyperintensities were identified throughout the spinal cord mostly within grey matter; five out of 12 patients had dorsal brainstem T2 hyperintensities. At a median of 2 months follow-up (IQR 2-3mo), spinal cord MRI improved in seven out of nine patients although focal T2 hyperintensities persisted in cervical and lumbar grey matter. At a median follow-up of 4 months (IQR 2-6mo), Medical Research Council sum score rose from a median of 29 to 32; distal muscle groups improved more than proximal ones; four out of 16 patients were ventilator-dependent; and two out of 16 patients were quadriplegic. INTERPRETATION: While patients may show marked improvement on neuroimaging from acute to convalescent stages, the majority of children with AFM have limited motor recovery and continued disability. Clinicians should consider the timing of clinical and neuroimaging exams when assessing diagnosis and prognosis. WHAT THIS PAPER ADDS: During the 2014 to 2017 acute flaccid myelitis outbreak in the USA, clinical recovery was better in distal than proximal muscle groups. Lumbar spinal cord showed more residual abnormalities at convalescence.

4-Aminopyridine in pediatric traumatic spinal cord injury: A case report.

Context: Spinal cord injury (SCI) presents significant challenges due to its debilitating nature and potential complications. While few medications have shown efficacy in improving neurological recovery, 4-Aminopyridine (4-AP), a voltage-gated potassium channel blocker, has been used clinically off-label to improve neurologic function in adults with spinal cord-related paralysis. However, evidence regarding its safety and effectiveness in the pediatric population remains scarce, as it is approved for use in older patients.Findings: This manuscript reports the case of a pediatric patient who sustained a traumatic cervical SCI. Initial neurological assessment indicated a C1 motor complete SCI. Surgical intervention for bullet removal and spinal fusion was carried out, followed by comprehensive inpatient rehabilitation.Conclusion/clinical relevance: 4-AP was introduced three months post-injury and was well-tolerated without obvious adverse effects. Notably, he exhibited neurological and functional improvement after four months of 4-AP use, though his improvement followed the expected trajectory of recovery. To date, this case represents the first case of 4-AP administration in a pediatric SCI patient, and therefore these findings contribute valuable clinical insight. By documenting the clinical trajectory of this case, this manuscript suggests 4-AP may be safe for use in pediatric patients.

Nerve Transfer Surgery in Acute Flaccid Myelitis: Prognostic Factors, Long-Term Outcomes, Comparison With Natural History.

BACKGROUND: Nerve transfer surgery is sometimes offered to patients with acute flaccid myelitis (AFM). The objectives of this study were to evaluate surgical efficacy, assess which clinical and neurophysiological data are valuable for preoperative planning, and report long-term outcomes. METHODS: This is a single-center, retrospective case series of patients with AFM who received nerve transfer surgery. All patients had preoperative electromyography and nerve conduction studies (EMG/NCS). Matched control muscles that did not receive nerve transfer surgery were defined in the same cohort. RESULTS: Ten patients meeting inclusion criteria received a total of 23 nerve transfers (19 upper extremity, four lower extremity). The mean age at symptom onset was 3.8 years, surgery was 0.5 to 1.25 years after diagnosis, and mean follow-up was 2.3 years (range 1.3 to 4.5 years). Among muscles with preoperative strength Medical Research Council (MRC) grade 0, muscles receiving nerve transfers performed significantly better than those that did not (MRC grade 2.17 ± 0.42 vs 0 ± 0, respectively, P = 0.0001). Preoperative EMG/NCS predicted worse outcomes in recipient muscles with more abundant acute denervation potentials (P = 0.0098). Donor nerves found to be partially denervated performed equally well as unaffected nerves. Limited data suggested functional improvement accompanying strength recovery. CONCLUSIONS: Nerve transfer surgery is an effective strategy to restore strength for patients with AFM with persistent, severe motor deficits. Postoperative outcomes in patients with complete paralysis are better than the natural history of disease. This study demonstrates the utility of preoperative clinical and electrophysiological data in guiding patient selection for nerve transfer surgery.

Nudging policymakers on gendered impacts of policy.

Despite the proliferation of nudge research in the last few decades, very little published work aims to nudge the behavior of policymakers. Here we explore the impact of a well-established nudge on policymakers in the Northwest Territories of Canada. In a pre-registered randomized controlled trial, we emailed an invitation to policymakers (N = 263) to attend an online briefing on gendered impacts of policy. In the treatment condition (N = 133), the invitation contained personal stories of two women whose lives were disproportionally impacted by public policies more than men. In the control condition (N = 130), the invitation did not contain such stories. After the briefing, we sent all participants in both conditions a link to a public pledge that they could sign. The pledge was to lead and advocate for equity-oriented policymaking. Contrary to our prediction, there was a small backfiring effect where policymakers in the treatment condition (3.0%) were less likely to attend the briefing than the control condition (7.7%). However, two policymakers (1.5%) in the treatment condition signed the public pledge compared to one (0.8%) in the control condition. The current findings reveal the limits of using personal stories as a nudge to influence policymakers. We discuss insights gained from this experiment and follow-up debriefings with policymakers on how to improve future behavioral interventions designed to nudge policymakers.

Description of Bone Health Changes in a Cohort of Children With Acute Flaccid Myelitis (AFM).

OBJECTIVES: To qualitatively describe bone health changes in children with acute flaccid myelitis (AFM) and assess relationships with muscle mass and strength and functional performance. METHODS: Retrospective analysis of a cohort of 79 children with AFM seen consecutively in one specialized academic center between January 1, 2007, and December 31, 2019. RESULTS: Of the 79 participants who were aged 4 months to 21 years old, 41 (52%) had bone density measured by dual energy absorptiometry (DXA) and 32 of them (78%) were diagnosed with low bone mass (LBM). We recorded 25 fractures that occurred after onset of neurologic deficit in 14 of the children in the cohort (18%). Lean muscle mass correlated with bone mass and functional performance as assessed by Physical Abilities and Mobility Scale (PAMS) but not with muscle strength as assessed by manual muscle testing (MMT). Bone density in the lower limbs was associated with ambulatory status. CONCLUSION: Children with AFM have a high likelihood of muscle and bone loss and frequently sustain pathologic fractures. Bone health in children with AFM should be carefully monitored, and efforts should be made to preserve bone mass and maximize muscle mass.

Bilateral Dega and Varus Derotational Osteotomies for Painful Hip Subluxation in Acute Flaccid Myelitis: A Case Report.

Introduction: Acute flaccid myelitis (AFM) is a recently described diagnosis that primarily impacts the pediatric population. It is characterized by profound proximal muscle weakness with resultant orthopedic manifestations similar to well-known neuromuscular conditions. While the incidence of AFM has been rising, management outcomes are understudied. Here, we describe the first known case of hip reconstruction in AFM. Case Report: A 5-year-old female presented with painful bilateral hip subluxations 2 years after being diagnosed with AFM. Imaging confirmed substantial uncovering of the femoral heads, right greater than left, with reduction on abduction views. Given the extent of her hip pathology and symptoms, she underwent bilateral Dega and varus derotational osteotomies with adductor lengthening, achieving a 35° correction in femoral neck angle and 30° reduction in femoral anteversion bilaterally. At 2 years postoperatively, she was asymptomatic without recurrence of hip displacement. Conclusion: Reconstructive femoral osteotomies can be effective for achieving painless, reduced hips in patients with AFM. Thus, surgeons may reasonably extrapolate current concepts utilized for other low-tone neuromuscular conditions to inform approach to AFM.

Acute flaccid myelitis: long-term outcomes recorded in the CAPTURE study compared with paediatric transverse myelitis.

BACKGROUND: Since 2014, the USA has documented three outbreaks of acute flaccid myelitis (AFM). Unique features and treatment responses of this myelitis variant have not been prospectively studied. This study prospectively measured outcomes in paediatric myelitis patients relative to treatments. METHODS: This was a prospective, multicentre, non-randomised, observational cohort study. The study duration was 5 years and the length of follow-up was 1 year. This study collected data from children and families in North America. Patients were enrolled at academic centres with expertise in myelitis or online via a web portal. Paediatric patients diagnosed with myelitis were eligible for enrolment in the study within 6 months of onset of symptoms. Patients were characterised as transverse myelitis (TM) or the AFM variant based on clinical and radiographic findings. RESULTS: The cohort of 90 patients included patients with AFM and TM. Of the 51 patients with AFM there was evidence of two clinically relevant patterns. This included a grey matter restricted form of AFM and a cohort with concomitant white matter that could explain lower extremity motor deficits in patients with lesions restricted to the cervical spine. The improvement in deficits with the use of corticosteroids was similar to what was observed in the TM cohort (p=0.97). CONCLUSIONS: Clinicians should consider on a case by case basis the approach to therapy for AFM patients. Prospective controlled studies of long-term outcomes would be useful in this growing patient population.

Improvements in Function Following Inpatient Activity-Based Therapy for Children With Acute Flaccid Myelitis.

BACKGROUND: Acute flaccid myelitis (AFM) is an illness defined by rapid onset of flaccid paralysis in one or more limbs or bulbar muscles, with MRI findings of predominantly spinal cord gray matter abnormalities spanning one or more spinal segments following a viral illness. Individuals with AFM may require rehabilitation to promote recovery. Activity-based restorative therapy (ABRT) has previously been shown to result in positive outcomes in children with neurologic deficits related to AFM. OBJECTIVES: This study examined functional changes in a group of children with AFM who participated in ABRT in an inpatient setting. METHODS: Retrospective chart review of children with AFM admitted to a single inpatient rehabilitation unit from 2014 to 2018. Children were assessed using the Functional Independence Measure for Children (WeeFIM), Manual Muscle Testing (MMT), Spinal Cord Independence Measure (SCIM), and the Physical Abilities and Mobility Scale (PAMS) as part of routine clinical care; the Modified Rankin Scale for Neurologic Disability was completed retrospectively. RESULTS: Children showed significant improvements across all outcome measures, with effect sizes ranging from moderate to large. Significant change was also seen across all muscle groups on MMT, with effect sizes ranging from small to large. Consistent with previous reports, children demonstrated better function in distal than proximal muscle groups at both admission and discharge. CONCLUSION: Children with AFM who participated in ABRT increased muscle strength and made functional gains across all outcome measures. These results support the utility of rehabilitation in the long-term care of children with AFM and residual neurologic deficit.

Interdisciplinary, Intensive, Activity-Based Treatment for Intrauterine Spinal Cord Infarct: A Case Report.

Intrauterine spinal cord infarcts (IUSCI) with resulting tetraplegia are extremely rare, and there is minimal evidence describing outcomes in this population. This case describes the functional progress of a 3-year-old girl born with IUSCI who participated in activity-based therapies (ABT). Children have developing nervous systems and are particularly suited to benefit from ABT. Over the course of treatment, the child in this case has demonstrated improvements in developmental milestone achievement including fine and gross motor skills and social/cognitive development. Intense, interdisciplinary ABT should be considered for the treatment of children with IUSCI.

Acute flaccid myelitis: Rehabilitation challenges and outcomes in a pediatric cohort.

PURPOSE: To describe one institution's experience in the rehabilitation of children with acute flaccid myelitis (AFM). This study reviews the medical and rehabilitative course and functional outcomes of a cohort of children who underwent Activity Based Restorative Therapy (ABRT) at a single center. METHODS: Children with AFM presenting for rehabilitation between March 2005 and January 2017 were identified and a retrospective chart review was conducted. Changes in medical and functional status were assessed using multiple standardized instruments, as well as a chart review of medical progress. RESULTS: Thirty-one children with AFM treated at our institution in the study time period were identified. Of these, seventeen received inpatient treatment, and fourteen received solely outpatient interventions. Their medical and functional outcomes are described with use of standardized measures when available. CONCLUSIONS: Children with flaccid paralysis due to AFM undergoing structured, comprehensive rehabilitation interventions, even when these are initiated long after paralysis onset, can make significant neurologic and functional gains. Recovery of function and prevention of comorbidities are the main therapeutic targets for interventions in this population.

Comment: 2004's fastest organic and biomolecular chemistry!

In January 2004, the Royal Society of Chemistry launched Organic & Biomolecular Chemistry (OBC) - a journal promising to provide high quality research from all aspects of synthetic, physical and biomolecular organic chemistry. The journal was set to build upon the foundations laid down by its predecessor publications (J. Chem. Soc., Perkin Trans. 1 and J. Chem. Soc., Perkin Trans. 2) as well as complement the subject coverage already published in prestigious general chemistry journals such as Chemical Communications and Chemical Society Reviews. Nearly two years on, just how is the programme developing and what can the community expect to see from the Royal Society of Chemistry (RSC)?

Rehabilitation in transverse myelitis.

The consequences of neurologic injuries related to transverse myelitis (TM) are long-lasting and require rehabilitative interventions in about two-thirds of cases. Because numerous neural repair mechanisms are dependent on maintenance of an optimal amount of activity both above and below the injury level, rehabilitation and exercise are useful not only for compensatory functional purposes but also as tools in neural system restoration. The application of established neurophysiologic principles to post-TM rehabilitation has substantial impact on optimizing residual functional capabilities while facilitating the processes of central plasticity and reorganization of sensory and motor programming. The process of neurorehabilitation thereby serves both to treat the patient with TM and to help physicians interrogate and dissect the mechanisms involved in spinal cord injury, neuroprotection, and, ultimately, recovery. Post-TM rehabilitation is lifelong and should be integrated into daily living in a home setting as part of the global management of paralysis, a chronic condition with significant comorbidities.

Comment: 2004's fastest organic and biomolecular chemistry!

In January 2003, the Royal Society of Chemistry launched Organic & Biomolecular Chemistry (OBC)--a journal promising to provide high quality research from all aspects of synthetic, physical and biomolecular organic chemistry. The journal was set to build upon the foundations laid down by its predecessor publications (J. Chem. Soc., Perkin Trans. 1 and J. Chem. Soc., Perkin Trans. 2) as well as complement the subject coverage already published in prestigious general chemistry journals such as Chemical Communications and Chemical Society Reviews. Nearly two years on, just how is the programme developing and what can the community expect to see from the Royal Society of Chemistry (RSC)?

Comment: 2004's fastest organic and biomolecular chemistry!

In January 2003, the Royal Society of Chemistry launched Organic & Biomolecular Chemistry (OBC)--a journal promising to provide high quality research from all aspects of synthetic, physical and biomolecular organic chemistry. The journal was set to build upon the foundations laid down by its predecessor publications (J. Chem. Soc., Perkin Trans. 1 and J. Chem. Soc., Perkin Trans. 2) as well as complement the subject coverage already published in prestigious general chemistry journals such as Chemical Communications and Chemical Society Reviews. Nearly two years on, just how is the programme developing and what can the community expect to see from the Royal Society of Chemistry (RSC)?