Neuroinfectious Diseases in Children: Pathophysiology, Outcomes, and Global Challenges.

Pathogens with affinity for the central nervous system (CNS) in children are diverse in their mechanisms of infecting and attacking the brain. Infections can reach the CNS via hematogenous routes, transneurally thereby avoiding the blood-brain barrier, and across mucosal or skin surfaces. Once transmission occurs, pathogens can wreak havoc both by direct action on host cells and via an intricate interplay between the protective and pathologic actions of the host's immune system. Pathogen prevalence varies depending on region, and susceptibility differs based on epidemiologic factors such as age, immune status, and genetics. In addition, some infectious diseases are monophasic, whereas others may lie dormant for years, thereby causing a dynamic effect on outcomes. Outcomes in survivors are highly variable for each particular pathogen and depend on the vaccination and immune status of the patient as well as the speed by which the patient receives evidence-based treatments. Given pathogens cause communicable diseases that can cause morbidity and mortality on a population level when spread, the burden is often the greatest and the outcomes the worst in low-resource settings. Here we will focus on the most common infections with a propensity to affect a child's brain, the pathologic mechanisms by which they do so, and what is known about the developmental outcomes in children who are affected by these infections.

Characteristics of pediatric patients with multiple sclerosis and related disorders infected with SARS-CoV-2.

BACKGROUND: Pediatric patients with multiple sclerosis (POMS) and related disorders, clinically isolated syndrome (CIS), myelin oligodendrocyte glycoprotein antibody disorder (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), are commonly treated with immunosuppressants. Understanding the impact of SARS-CoV-2 infection in patients may inform treatment decisions. OBJECTIVE: Characterize SARS-CoV-2 infection prevalence and severity among a cohort of patients with POMS and related disorders, as well as the impact of disease-modifying therapies (DMTs). METHODS: POMS and related disorders patients enrolled in a large, prospective registry were screened for COVID-19 during standard-of-care neurology visits. If confirmed positive of having infection, further analysis was undertaken. RESULTS: Six hundred and sixty-nine patients were surveyed between March 2020 and August 2021. There were 73 confirmed COVID-19 infections. Eight of nine hospitalized patients (89%), and all patients admitted to the ICU were treated with B cell depleting therapy. The unadjusted odds ratio of hospitalization among those who tested positive of having had COVID-19 was 15.27 among those on B-cell-depleting therapy (p = 0.016). CONCLUSIONS: B-cell-depleting treatment was associated with a higher risk of COVID-19, higher rates of hospitalization, and ICU admission, suggesting this therapy carries a higher risk of severe infection in POMS and related disorders.

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.

Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis.

OBJECTIVE: To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM). METHODS: A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength. RESULTS: Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, p = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, p = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, p = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, p = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients (p = 0.015). CONCLUSION: Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.

Gynecologic and surgical complications in type IV Ehlers-Danlos syndrome.

BACKGROUND: Although type IV Ehlers-Danlos syndrome is a rare condition, it is critical that physicians be aware of this disease because it presents unique management challenges. CASE: We present a young woman who was admitted with a pelvic abscess after having a miscarriage and an appendiceal perforation. She had an exploratory laparotomy secondary to a persistent pelvic abscess and endured multiple postoperative complications. Based on her family history and physical characteristics, type IV Ehlers-Danlos syndrome was diagnosed. CONCLUSION: The decision to proceed with surgery should be weighed against tissue fragility in patients with type IV Ehlers-Danlos syndrome. A conservative, multidisciplinary team approach addresses whether to proceed with surgery and minimize postoperative complications if surgery is performed.

A comparison of cigarette smoking profiles in opioid-dependent pregnant patients receiving methadone or buprenorphine.

INTRODUCTION: Little is known about the relationship between cigarette smoking and agonist treatment in opioid-dependent pregnant patients. The objective of this study is to examine the extent to which cigarette smoking profiles differentially changed during the course of pregnancy in opioid-dependent patients receiving either double-blind methadone or buprenorphine. Patients were participants in the international, randomized controlled Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. METHODS: A sample of opioid-maintained pregnant patients (18-41 years old) with available smoking data who completed a multisite, double-blind, double-dummy, randomized controlled trial of methadone (n = 67) and buprenorphine (n = 57) between 2005 and 2008. Participants were compared on smoking variables based on opioid agonist treatment condition. RESULTS: Overall, 95% of the sample reported cigarette smoking at treatment entry. Participants in the two medication conditions were similar on pretreatment characteristics including smoking rates and daily cigarette amounts. Over the course of the pregnancy, no meaningful changes in cigarette smoking were observed for either medication condition. The fitted difference in change in adjusted cigarettes per day between the two conditions was small and nonsignificant (ß = -0.08, SE = 0.05, p = .132). CONCLUSIONS: Results support high rates of smoking with little change during pregnancy among opioid-dependent patients, regardless of the type of agonist medication received. These findings are consistent with evidence that suggests nicotine effects, and interactions may be similar for buprenorphine compared with methadone. The outcomes further highlight that aggressive efforts are needed to reduce/eliminate smoking in opioid-dependent pregnant women.

Adult attachment to transitional objects and borderline personality disorder.

Borderline personality disorder (BPD) is characterized by tumultuous, unstable personal relationships, difficulty being alone, and an inability to self-soothe. This may explain why patients with BPD tend to develop strong attachments to transitional objects such as stuffed animals. Research in hospital settings has linked the use of transitional objects to the presence of BPD. Using a nonclinical community sample (N = 80) we explored the link between attachments to transitional objects and various aspects of personality pathology, as well as to childhood trauma, and parental rearing styles. People who reported intense current attachments to transitional objects were significantly more likely to meet criteria for a BPD diagnosis than those who did not; they also reported more childhood trauma, rated their early caregivers as less supportive, and had more attachment problems as adults. Heavy emotional reliance on transitional objects in adulthood may be an indicator of underlying pathology, particularly BPD.