Acute Flaccid Myelitis in Early Infancy: A Rare Presentation

1. Raymond Cai, MD* 2. Vikram Bhise, MD† 1. *Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 2. †Department Neurology and Pediatrics, Robert Wood Johnson University Hospital, New Brunswick, NJ I spent a week with medical students and family medicine residents in northeast Africa earlier this year. There, bright, clinically astute trainees at a major university use Pediatrics in Review as a core foundation of their pediatric curriculum. Wherever you are in the world this month, may these Index of Suspicion cases help you advance your knowledge and practice of pediatrics. Philip R. Fischer, MD Associate Editor, Index of Suspicion A 13-year-old girl presented to the emergency department with acute onset of lower extremity weakness. She first awoke with dizziness but soon developed severe back pain, bilateral lower extremity pain and numbness, slurred speech, and inability to move her lower extremities or ambulate. She reports having a 2-day history of headaches and back pain. Due to worsening of her symptoms, she went to an urgent care center the previous day. A rapid viral test showed she was influenza positive, and she took 2 doses of oseltamivir before admission. The patient had an upper respiratory tract infection approximately 2 to 3 weeks ago. In the emergency department, the patient is unable to void spontaneously despite being able to at home, and a urinary catheter is placed. On physical examination her vital signs are as follows: temperature, 98.6°F (37.0°C); heart rate, 77 beats/min; respiratory rate, 20 breaths/min; and blood pressure, 119/74 mm Hg. Her BMI was within the 75th to 85th percentile. Her lower extremities bilaterally had 1/5 strength, diminished sensation to pinprick and temperature, and 0/5 patellar reflexes. She also had a 0/5 right Achilles reflex but a 1/5 …

Pediatric weakness, pediatric neurologic disorders, acute flaccid myelitis, Gullian-Barré Syndrome, neuromuscular weakness.

Acute Flaccid Myelitis: A Clinical Overview for 2019

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. This study examined functional changes in a group of children with AFM who participated in ABRT in an inpatient setting. 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. 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. 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.

Identification of Enterovirus at Presentation Predicts Outcomes in Acute Flaccid Myelitis A Canadian Nationwide Study in Canada

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

Evolution of neuroimaging features in children with acute flaccid myelitis compared to other forms of childhood myelitis.

Background and purposeDifferentiation between acute flaccid myelitis (AFM) and Guillain–Barré syndrome (GBS) can be difficult, particularly in children. Our objective was to improve the diagnostic accuracy by giving recommendations based on a comparison of clinical features and diagnostic criteria in children with AFM or GBS.MethodsA cohort of 26 children with AFM associated with enterovirus D68 was compared to a cohort of 156 children with GBS. The specificity of the Brighton criteria, used for GBS diagnosis, was evaluated in the AFM cohort and the specificity of the Centers for Disease Control and Prevention (CDC) AFM diagnostic criteria in the GBS cohort.ResultsChildren with AFM compared to those with GBS had a shorter interval between onset of weakness and nadir (3 vs. 8 days, p < 0.001), more often had asymmetric limb weakness (58% vs. 0%, p < 0.001), and less frequently had sensory deficits (0% vs. 40%, p < 0.001). In AFM, cerebrospinal fluid leukocyte counts were higher, whereas protein concentrations were lower. Spinal cord lesions on magnetic resonance imaging were only found in AFM patients. No GBS case fulfilled CDC criteria for definite AFM. Of the AFM cases, 8% fulfilled the Brighton criteria for GBS, when omitting the criterion of excluding an alternate diagnosis.ConclusionsDespite the overlap in clinical presentation, we found distinctive early clinical and diagnostic characteristics for differentiating AFM from GBS in children. Diagnostic criteria for AFM and GBS usually perform well, but some AFM cases may fulfill clinical diagnostic criteria for GBS. This underlines the need to perform diagnostic tests early to exclude AFM in children suspected of atypical GBS.

Acute flaccid myelitis (AFM) is an acute flaccid paralysis syndrome with spinal motor neuron involvement of unknown etiology. We investigated the characteristics and prognostic factors of AFM clusters coincident with an enterovirus D68 (EV-D68) outbreak in Japan during autumn 2015. An AFM case series study was conducted following a nationwide survey from August to December 2015. Radiographic and neurophysiologic data were subjected to centralized review, and virology studies were conducted for available specimens. Fifty-nine AFM cases (58 definite, 1 probable) were identified, including 55 children and 4 adults (median age, 4.4 years). The AFM epidemic curve showed strong temporal correlation with EV-D68 detection from pathogen surveillance, but not with other pathogens. EV-D68 was detected in 9 patients: 5 in nasopharyngeal, 2 in stool, 1 in cerebrospinal fluid (adult case), and 1 in tracheal aspiration, nasopharyngeal, and serum samples (a pediatric case with preceding steroid usage). Cases exhibited heterogeneous paralysis patterns from 1- to 4-limb involvement, but all definite cases had longitudinal spinal gray matter lesions on magnetic resonance imaging (median, 20 spinal segments). Cerebrospinal fluid pleocytosis was observed in 50 of 59 cases (85%), and 8 of 29 (28%) were positive for antiganglioside antibodies, as frequently observed in Guillain-Barré syndrome. Fifty-two patients showed variable residual weakness at follow-up. Good prognostic factors included a pretreatment manual muscle strength test unit score >3, normal F-wave persistence, and EV-D68-negative status. EV-D68 may be one of the causative agents for AFM, while host susceptibility factors such as immune response could contribute to AFM development.

Introduction: Enterovirus-D68 (EV68) is associated with acute flaccid myelitis (AFM) in children. Since August 2014, 120 pediatric AFM cases have occurred in the United States, coinciding with a nationwide EV68 endemic. Like poliovirus, EV68 induces limb paralysis through inflammation and destruction of anterior horn cells of the cervical spine. Objectives: To date, no medical intervention has altered the course of EV68-induced AFM. Of 120 recently described AFM cases, only 2 children have recovered full limb function. We report nerve transfers in 7 limbs of 6 patients as a potential treatment of EV68-induced AFM. Methods: We performed nerve transfers in 6 pediatric patients from 2 centers with sustained neuropathy following EV68-induced AFM. Postoperative outcomes included muscle strength, graded on the British Medical Research Council (BMRC) scale. Results: In all, 3/6 patients were male, with a mean age of 6.9 ± 5.3 years. All patients reported a viral prodrome prior to neurologic symptom onset, with an average latency time of 3.25 ± 2.5 days. In addition, 3/6 patients had bilateral upper extremity involvement, of which 2 developed quadriparesis that has since resolved, 2/6 had unilateral involvement on the right side, and 1/6 had unilateral involvement on the left. The mean delay in presentation for evaluation was 6.7 ± 2.2 months. Preoperative electrodiagnostic testing in all patients revealed abnormal motor but normal sensory function. In addition, 4/6 patients had magnetic resonance imaging that demonstrated T2 hyperintensity in the gray matter of the cervical spine. Also, 5/6 limbs were treated with proximal nerve transfers. One patient with proximal upper extremity involvement on the right side and distal involvement on the left side underwent bilateral nerve transfers. Transfers performed for shoulder abduction included the following: spinal accessory nerve to suprascapular nerve, contralateral C7 to the upper trunk with an interposition sural nerve graft, thoracodorsal to axillary nerve, medial pectoral branch to axillary nerve, and radial fascicular to axillary nerve. Transfers performed for elbow flexion included intercostals (2-4) to the musculocutaneous nerve and median fascicular to brachialis branch of the musculocutaneous nerve. Finally, transfers for wrist and finger flexion included brachialis to anterior interosseous nerve and side to side flexor digitorum profundus (FDP) transfers in the wrist. The mean follow-up time was 7.7 ± 2.0 months. Early results in the 3 patients demonstrated promising signs of recovery with contraction and even active motion with gravity eliminated for shoulder abduction, external rotation, and elbow flexion. Three patients with longer clinical follow-up improved from 0 for all functions to 2 to 3 for shoulder abduction, 2 for external rotation, and 3 to 4 for elbow flexion. At 6 months postoperatively, the one patient treated with distal nerve transfers demonstrated active flexor pollicis longus (FPL) and FDP pinch. Conclusion: We present early outcomes of a promising reconstructive technique for this emerging and devastating viral endemic. Detailed physical examination and preoperative electrodiagnostic testing is essential to determine available donor nerves, as traditional donors may not be available, necessitating custom solutions. Our patients presented late in the course of their disease; early recognition and identification of EVD68 may improve the outcome of nerve reconstruction for treating EV-D68-induced nerve palsy.

Acute flaccid myelitis associated with enterovirus type D68 infection

Recognition and Management of Acute Flaccid Myelitis in Children

BackgroundReporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM.Case presentationA previously healthy 4-year-old boy presented with sudden weakness and limited mobility in his left arm. Two days earlier, he had an upper respiratory illness with mild fever. At admission, his physical examination showed that the child was febrile (38.5 °C) and alert but had a stiff neck and weakness in his left arm, which was hypotonic and areflexic. Cerebrospinal fluid (CSF) examination showed a mild increase in white blood cell count (80/mm3, 41% neutrophils) and a slightly elevated protein concentration (76 gm/dL). Bacterial culture and molecular biology tests for detecting viral infection in CSF were negative. The patient was then treated with intravenous ceftriaxone and acyclovir. Despite therapy, within 24 h, the muscle weakness extended to all four limbs, which exhibited greatly reduced mobility. Due to his worsening clinical prognosis, the child was transferred to our Pediatric Intensive Care Unit; at admission he was diagnosed with acute flaccid paralysis of all four limbs. Brain magnetic resonance imaging (MRI) was negative, except for a focal signal alteration in the dorsal portion of the medulla oblongata, also involving the pontine tegmentum, whereas spine MRI showed an extensive signal alteration of the cervical and dorsal spinal cord reported as myelitis. Signal alteration was mainly localized in the central grey matter, most likely in the anterior horns. Molecular biology tests performed on nasopharyngeal aspirate and on bronchoalveolar lavage fluid were negative for bacteria but positive for EV-D68 clade B3. Plasmapheresis was performed and corticosteroids and intravenous immunoglobulins were administered. After 4 weeks of treatment, the signs and symptoms of AFM were significantly reduced, although some weakness and tingling remained in the patient’s four limbs. MRI acquired after 3 weeks showed that the previously reported alterations were no longer present.ConclusionThis case suggests that EV-D68 is a neurotropic agent that can cause AFM and strains are circulating in Europe. EV-D68 disease surveillance is required to better understand EV-D68 pathology and to compare various strains that cause AFM.

Imaging of other encephalitis and of noncompressive acute transverse myelopathies

The association between enterovirus D68 and acute flaccid myelitis was first described in the United States in 2014. Since then, sporadic cases have been reported in Canada and Europe. This study describes a series of cases of acute flaccid myelitis at Hospital de Pediatría "Prof. Dr. Juan P. Garrahan," in Buenos Aires, Argentina, during 2016. Descriptive, retrospective study. All patients with acute flaccid myelitis and lesions in the spinal cord involving the gray matter, as observed in the magnetic resonance imaging (MRI) scan, hospitalized from 04/01/2016 to 07/01/2016, were included in the study. Samples of nasopharyngeal secretions, fecal swabs and cerebrospinal fluid were collected and processed to look for the causative agent. Ten patients were included. The median age was 4 years old (range from 3 months to 5 years old). Eight patients had a self-limiting febrile condition before the onset of neurological symptoms. Neurological findings were flaccid weakness in, at least, one limb, cervical paralysis (n= 2) and facial paralysis (n= 2). All patients had longitudinal lesions in the spinal cord, with gray matter involvement, mainly in the anterior horn. In all cases, a lumbar puncture (spinal tap) was performed. Pleocytosis was observed in 7 patients. In four children, enterovirus D68 was identified in nasopharyngeal secretions, and in one, it was detected in the cerebrospinal fluid. Neurological deficit persisted in all patients at the time of discharge. The first outbreak of acute flaccid myelitis associated to enterovirus D68 is reported in Argentina. Active epidemiological surveillance will help to determine the true incidence, epidemiology and etiology of this disease.