Central nervous system infection in a pediatric population in West Java.

Central nervous system (CNS) viral infections are critical causes of morbidity and mortality in children; however, comprehensive data on etiology is lacking in developing countries such as Indonesia. To study the etiology of CNS infections in a pediatric population, 50 children admitted to two hospitals in Bandung, West Java, during 2017-2018 were enrolled in a CNS infection study. Cerebrospinal fluid and serum specimens were tested using molecular, serological, and virus isolation platforms for a number of viral and bacteriological agents. Causal pathogens were identified in 10 out of 50 (20%) and included cytomegalovirus (n = 4), Streptococcus pneumoniae (n = 2), tuberculosis (n = 2), Salmonella serotype Typhi (n = 1) and dengue virus (n = 1). Our study highlights the importance of using a wide range of molecular and serological detection methods to identify CNS pathogens, as well as the challenges of establishing the etiology of CNS infections in pediatric populations of countries with limited laboratory capacity.

Rehabilitation Outcomes in Children With Acute Flaccid Myelitis From 2014 to 2019: A Multicenter Retrospective Review.

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.

Comparison of acute flaccid myelitis and transverse myelitis in children and evaluation of diagnostic criteria.

BACKGROUND AND PURPOSE: Acute flaccid myelitis (AFM) and transverse myelitis (TM) are serious conditions that may be difficult to differentiate, especially at onset of disease. In this study, we compared clinical features of pediatric AFM and TM and evaluated current diagnostic criteria, aiming to improve early and accurate diagnosis. METHODS: Two cohorts of children with enterovirus D68-associated AFM and clinically diagnosed TM were compared regarding presenting clinical features, additional investigations, and outcome. Current diagnostic criteria for AFM and TM were applied to evaluate their specificity. RESULTS: Children with AFM (n = 21) compared to those with TM (n = 36) were younger (median 3 vs. 10 years), more often had a prodromal illness (100% vs. 39%), predominant proximal weakness (69% vs. 17%), and hyporeflexia (100% vs. 44%), and less often had sensory deficits (0% vs. 81%), bowel and/or bladder dysfunction (12% vs. 69%), and hyperreflexia (0% vs. 44%). On magnetic resonance imaging, brainstem involvement was more common in AFM (74% vs. 21%), whereas supratentorial abnormalities were only seen in TM (0% vs. 40%). When omitting the criterion of a sensory level, 11 of 15 (73%) children with AFM fulfilled the diagnostic criteria for TM. Of children with TM, four of 33 (12%) fulfilled the diagnostic criteria for probable/definite AFM. CONCLUSIONS: Although there is considerable overlap between AFM and TM in children, we found important early differentiating clinical and diagnostic features. Meeting diagnostic criteria for AFM in children with TM and vice versa underlines the importance of thorough clinical examination and early and accurate diagnostic studies.

Acute Flaccid Myelitis in a Pediatric Patient With Coronavirus Disease 2019.

The etiology of acute flaccid myelitis (AFM) has yet to be determined. Viral link has been suggested, but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated AFM has not been reported in children. We describe a three-year-old boy, with AFM associated with coronavirus disease 2019 (COVID-19) infection. In the era of COVID-19 pandemic, patients with AFM should be tested for SARS-CoV-2.

Animal Models of Enterovirus D68 Infection and Disease.

Human enterovirus D68 (EV-D68) is a globally reemerging respiratory pathogen that is associated with the development of acute flaccid myelitis (AFM) in children. Currently, there are no approved vaccines or treatments for EV-D68 infection, and there is a paucity of data related to the virus and host-specific factors that predict disease severity and progression to the neurologic syndrome. EV-D68 infection of various animal models has served as an important platform for characterization and comparison of disease pathogenesis between historic and contemporary isolates. Still, there are significant gaps in our knowledge of EV-D68 pathogenesis that constrain the development and evaluation of targeted vaccines and antiviral therapies. Continued refinement and characterization of animal models that faithfully reproduce key elements of EV-D68 infection and disease is essential for ensuring public health preparedness for future EV-D68 outbreaks.

[Acute flaccid myelitis and enterovirus infection: a severe emerging disease]. / Mielitis flácida aguda e infección por enterovirus: una enfermedad grave emergente.

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.

Acute flaccid myelitis and Guillain-Barré syndrome in children: A comparative study with evaluation of diagnostic criteria.

BACKGROUND AND PURPOSE: Differentiation 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. METHODS: A 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. RESULTS: Children 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. CONCLUSIONS: Despite 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.

An Overview of Acute Flaccid Myelitis.

Acute Flaccid Myelitis is defined by the presence of Acute Flaccid Paralysis (AFP) and a spinal cord lesion on magnetic resonance imaging that is primarily limited to the grey matter. AFM is a difficult situation to deal with when you have a neurologic illness. According to the Centers for Disease Control and Prevention (CDC), a large number of cases were discovered in the United States in 2014, with 90% of cases occurring in children. Although the exact cause of AFM is unknown, mounting evidence suggests a link between AFM and enterovirus D68 (EV-D68). In 2014, an outbreak of AFM was discovered in the United States. The condition was initially linked to polioviruses; however, it was later found that the viruses were caused by non-polioviruses Enteroviruses D-68 (EV-D68). The number of cases has increased since 2014, and the disease has been declared pandemic in the United States. The sudden onset of muscle weakness, usually in an arm or leg, as well as pain throughout the body, the change in patient's facial expression (facial weakness), and shortness of breath, ingesting, and speaking are all common symptoms in patients suffering from neurologic disease. This article includes graphic and histogram representations of reported AFM incidents and criteria for causality, epidemiology, various diagnostic approaches, signs and symptoms, and various investigational guidelines. It also includes key statements about recent clinical findings related to AFM disease.

Does acute flaccid myelitis cause respiratory failure in children?

INTRODUCTION: Acute flaccid myelitis (AFM) is a rare disease that affects spinal cord gray matter, results in acute flaccid weakness of one or more limbs and predominantly involves the cervical spinal cord, which places patients at higher risk for respiratory failure. Our study aims to describe respiratory failure in pediatric AFM patients with emphasis on the need for assisted ventilation and respiratory nerve involvement from an acute and long-term perspective. MATERIALS AND METHODS: We reviewed the medical records of patients diagnosed with AFM seen in a multidisciplinary clinic for persistent limb weakness between 2016 and 2020. RESULTS: We studied 54 patients, 35% were female. The median age of patients at illness onset was 5 years (range 7 months-19 years). The median age of patients at the time of study was 8.5 years (range 2-20 years). Eleven patients (20%) required assisted ventilation for acute respiratory failure. Of those that experienced acute respiratory failure, 81% developed chronic respiratory failure. Fifty-six percent of patients with chronic respiratory failure were able to wean off assisted ventilation by 1 year. All patients that experienced unilateral diaphragm impairment with AFM onset experienced acute and chronic respiratory failure. DISCUSSION: Many patients with AFM may experience respiratory compromise and develop chronic respiratory failure. However, most of these patients can be weaned off ventilatory support by 1 year from illness onset. Most children with unilateral diaphragm impairment can sustain adequate ventilation without the need for long-term ventilatory support.

Three-Year Longitudinal Motor Function and Disability Level of Acute Flaccid Myelitis.

BACKGROUND: We summarize the long-term motor outcome and disability level in a cluster of pediatric patients with acute flaccid myelitis (AFM) associated with the enterovirus D68 outbreak in 2015. METHODS: This is a nationwide follow-up questionnaire analysis study. Clinical data including the motor function (manual muscle strength test) and other neurological symptoms were collected at the acute (nadir), recovery (six months), and chronic (three years) stages. We use the Barthel index, which measures 10 variables describing activity of daily living and mobility to assess the disability level. RESULTS: Clinical data of 33 patients with AFM (13 females, 20 males; median age = 4.1 years) were available. Among patients with tetraplegia or triplegia, paraplegia, and monoplegia at the acute stage, two of seven, four of thirteen, and two of thirteen exhibited complete recovery without paralysis; of those five of seven, eight of thirteen, and two of thirteen showed improvement with lesser limb involvement at the chronic stage, respectively. Nine patients (27%) demonstrated improvement at the recovery-to-chronic period. All six patients with positive isolation of enterovirus D68 from biological samples at the acute stage showed persistent motor deficits. Other neurological findings had better prognosis than motor weakness. Better Barthel index score at the chronic stage was observed (P < 0.001; median difference [95% confidence interval], 53 [40 to 63]), implying an improved disability level even in patients with persistent motor deficits. CONCLUSIONS: AFM has a high rate of persistent motor deficits showing one- to two-limb paralysis. Disability level of patients with AFM, however, generally improved at the three-year time point.

Characteristics of Upper Extremity Recovery in Acute Flaccid Myelitis: A Case Series.

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.

Peripheral Facial Nerve Palsy in Children With Enterovirus Infection.

Enteroviruses are one of the leading causes of central nervous system infections, but their causative role in peripheral facial nerve palsy is unresolved. We used data from a large national Enterovirus Surveillance Database to identify cases of facial nerve palsy, showing a rate of 3.8% of patients with facial nerve palsy to have enterovirus infection.

JC Polyomavirus, progressive multifocal leukoencephalopathy and immune reconstitution inflammatory syndrome: a review.

The human neurotropic virus JC Polyomavirus, a member of the Polyomaviridae family, is the opportunistic infectious agent causing progressive multifocal leukoencephalopathy, typically in immunocompromised individuals. The spectrum of underlying reasons for the systemic immunosuppression that permits JCV infection in the central nervous system has evolved over the past 2 decades, and therapeutic immunosuppression arousing JCV infection in the brain has become increasingly prominent as a trigger for PML. Effective immune restoration subsequent to human immunodeficiency virus-related suppression is now recognized as a cause for unexpected deterioration of symptoms in patients with PML, secondary to a rebound inflammatory phenomenon called immune reconstitution inflammatory syndrome, resulting in significantly increased morbidity and mortality in a disease already infamous for its lethality. This review addresses current knowledge regarding JC Polyomavirus, progressive multifocal leukoencephalopathy, progressive multifocal leukoencephalopathy-related immune reconstitution inflammatory syndrome, and the immunocompromised states that incite JC Polyomavirus central nervous system infection, and discusses prospects for the future management of these conditions.

Central Nervous System Virus Infection in African Children with Cerebral Malaria.

We aimed to identify the contribution of central nervous system (CNS) viral coinfection to illness in African children with retinopathy-negative or retinopathy-positive cerebral malaria (CM). We collected cerebrospinal fluid (CSF) from 272 children with retinopathy-negative or retinopathy-positive CM and selected CSF from 111 of these children (38 retinopathy positive, 71 retinopathy negative, 2 retinopathy unknown) for analysis by metagenomic next-generation sequencing. We found CSF viral coinfections in 7/38 (18.4%) retinopathy-positive children and in 18/71 (25.4%) retinopathy-negative children. Excluding HIV-1, human herpesviruses (HHV) represented 61% of viruses identified. Excluding HIV-1, CNS viral coinfection was equally likely in children who were retinopathy positive and retinopathy negative (P = 0.1431). Neither mortality nor neurological morbidity was associated with the presence of virus (odds ratio [OR] = 0.276, 95% CI: 0.056-1.363). Retinopathy-negative children with a higher temperature, lower white blood cell count, or being dehydrated were more likely to have viral coinfection. Level of consciousness at admission was not associated with CNS viral coinfection in retinopathy-negative children. Viral CNS coinfection is unlikely to contribute to coma in children with CM. The herpesviruses other than herpes simplex virus may represent incidental bystanders in CM, reactivating during acute malaria infection.

Revisión de la bibliografía. Coronavirus (COVID-19) y Sistema Nervioso Central. Un panorama para analizar en una situación de pandemia. Consideraciones sobre el neurotrofismo del Coronavirus / Literature review. Coronavirus (COVID-19) and Nervous System Central. A panorama to analyze in a pandemic situation. Considerations on coronavirus neurotrophy

En humanos, las infecciones virales del tracto respiratorio son una causa principal de morbilidad y mortalidad en todo el mundo. Varios agentes virales respiratorios reconocidos tienen una capacidad neuroinvasiva, ya que pueden propagarse desde el tracto respiratorio hasta el sistema nervioso central (SNC). Una vez allí, la infección de las células del SNC (neurotropismo) podría conducir a problemas de salud humana, como encefalitis y enfermedades neurológicas a largo plazo. Los coronavirus (HCoV) generalmente infectan el tracto respiratorio superior, donde se asocian principalmente con resfriados comunes. Sin embargo, en las poblaciones más vulnerables, como los recién nacidos, los bebés, los ancianos y las personas inmunocomprometidas, también pueden afectar el tracto respiratorio inferior y provocar neumonía, exacerbaciones del asma, síndrome de dificultad respiratoria o incluso síndrome respiratorio agudo severo (SRAS) . Se ha establecido claramente la afectación respiratoria del VHC desde la década de 1960. Además, durante casi tres décadas, la literatura científica también ha demostrado que los HCoV son neuroinvasivos y neurotrópicos y podrían inducir una activación excesiva del sistema inmune.

In humans, viral infections of the respiratory tract are a leading cause of morbidity and mortality worldwide. Several recognized respiratory viral agents have a neuroinvasive capacity since they can spread from the respiratory tract to the central nervous system (CNS). Once there, infection of CNS cells (neurotropism) could lead to human health problems, such as encephalitis and long-term neurological diseases. Coronaviruses (HCoV) usually infect the upper respiratory tract, where they are mainly associated with common colds. However, in more vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, can also affect the lower respiratory tract, leading to pneumonia, exacerbations of asthma, respiratory distress syndrome, or even severe acute respiratory syndrome (SARS). It has been clearly established the respiratory involvement of HCoV since the 1960s. In addition, for almost three decades now, the scientific literature has also demonstrated that HCoV are neuroinvasive and neurotropic and could induce an over activation of the immune system

Unmet Needs in the Evaluation, Treatment, and Recovery for 167 Children Affected by Acute Flaccid Myelitis Reported by Parents Through Social Media.

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.