Pediatric Neurologic Complications Associated With Influenza A H1N1

doi:10.1016/j.pediatrneurol.2010.08.011

Pediatric Neurology

Volume 44, Issue 1, January 2011, Pages 47-51

https://doi.org/10.1016/j.pediatrneurol.2010.08.011 Get rights and content

Influenza is associated with a variety of neurologic complications. Although the epidemiologic and clinical characteristics of influenza A H1N1 were reviewed in depth, only brief descriptions of neurologic complications exist. We describe the neurologic complications of children hospitalized with influenza A H1N1 infection. We undertook a retrospective study of all hospitalized children with laboratory-confirmed influenza A H1N1 infection accompanied by neurologic complications during a 4-month winter period. Their demographics and clinical characteristics of neurologic presentations were reviewed. Fourteen of 74 children (19%) with laboratory-confirmed influenza A H1N1 infection presented with neurologic complications. Eleven (11/14, 79%) were previously healthy, and three exhibited chronic conditions. Ten (10/14, 71%) presented with seizures: six were febrile, and four were nonfebrile. Other complications included transverse myelitis, myositis, expressive aphasia, and syncope. Only the child with transverse myelitis required a course of rehabilitation. Neurologic complications associated with influenza A H1N1 in our patients were relatively mild. Seizures (febrile or nonfebrile) were the most common. However, the possibility of influenza A H1N1 infection should be borne in mind when diagnosing children with neurologic signs during the influenza A H1N1 season.

Introduction

Influenza is a major cause of various respiratory infections, and is also associated with a variety of neurologic complications, including seizures, Guillain-Barré syndrome, transverse myelitis, encephalopathy, and Reye syndrome [1], [2]. Seizures are the most frequently reported neurologic complication, and most of these in young children are thought to be febrile [3], [4]. Two recent retrospective studies demonstrated that 8.5% of laboratory-confirmed infections in children hospitalized with influenza involved influenza-related neurologic complications, and the most common neurologic complications were seizures and encephalopathy [2], [4].

The one predictable aspect of influenza is its unpredictability. Whereas attention has focused on the threat of an avian influenza H5N1 pandemic originating in Asia, a novel influenza virus of swine origin emerged in North America in 2009. It was an H1N1 virus unrelated to human seasonal influenza viruses, and it caused the first pandemic in the past four decades [5], [6]. The epidemiologic and clinical characteristics of influenza A H1N1 were analyzed in depth [7], [8], but neurologic complications associated with the virus were only briefly described in a few case reports and case series regarding children [9], [10] or adults [11], [12]. We are unaware of any published studies that characterized the epidemiology of neurologic complications caused by this infection. Therefore, we designed this study to identify such complications among hospitalized children with laboratory-confirmed influenza A H1N1 infection.

Section snippets

Materials and Methods

We conducted a retrospective cohort study of patients hospitalized with laboratory-confirmed influenza A H1N1 during the 4-month winter period from October 1, 2009, to January 31, 2010 at Dana Children’s Hospital, an academic, tertiary-care hospital at the Tel Aviv Sourasky Medical Center. To facilitate the appropriate cohorting of patients, cases were identified by using virology laboratory records (polymerase chain reaction findings from deep nasopharyngeal swab samples) and medical discharge

Results

Between October 1, 2009 and January 31, 2010, out of a total of 1312 pediatric admissions, 74 children were hospitalized with laboratory-confirmed influenza A H1N1 infection. Their mean age was 5.4 ± 4.4 years S.D. (range, 2 months to 16 years), and 42 (55%) were boys. Fourteen children (19%; 11 boys; mean age, 6.6 ± 5.1 years S.D.) exhibited associated neurologic complications (Table 1). None of these 14 had been previously immunized against influenza A H1N1, because this specific vaccination

Discussion

In his treatise, Smith Ely Jeliffe described a wide range of neurologic manifestations associated with influenza, ranging from minor signs such as increased fatigue to severe consequences such as coma and death [4], [13]. With the advent of serologic testing, confirmed cases of infection with influenza virus were associated with seizures (febrile and nonfebrile), altered mental status, Guillain-Barré syndrome, acute disseminated encephalomyelitis, transverse myelitis, and other neuropsychiatric

Conclusions

We report on 14 children with influenza A H1N1 and associated neurologic complications. The incidence of neurologic complications in our study was higher than in previously reported influenza-related cases. The neurologic presentations in our patients were, for the most part, relatively mild. Seizures (febrile or nonfebrile) comprised the most common neurologic complication. This finding is in line with previously reported influenza-related neurologic complications. Neurologic complications

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Cited by (45)

Influenza-associated neurologic complications in children from an H3N2 outbreak in Shenzhen, China during COVID-19 lockdown
2023, International Journal of Infectious Diseases
To identify the characteristics of influenza-associated neurologic complications (INCs) in children from a recent H3N2 outbreak in Shenzhen, China during COVID-19 lockdown.
A retrospective cohort study of INCs in children hospitalized with H3N2 infection was conducted.
From June 01, 2022 to July 01, 2022, 513 children with H3N2 infection were hospitalized and 97 developed INCs. Of the 18 patients with encephalopathy/encephalitis, 13 were previously healthy. Three developed acute necrotizing encephalopathy and two died. Of the 63 patients with febrile seizures, 55 (87%) had simple febrile seizures. Of the 14 patients with an exacerbation of seizure with underlying epilepsy, the seizure symptoms occurred mostly within 24 hours of disease onset (13/14). The comparison of the three groups (encephalopathy/encephalitis, febrile seizure and exacerbation of seizure with underlying epilepsy) reported no significant differences in sex, pre-existing neurologic diseases, vaccination rate, white blood cell count, C-reactive protein, procalcitonin, blood glucose, lactic acid, or duration of fever. The influenza vaccination rates were generally low (22% vs 32% vs 21%). Patients with encephalopathy/encephalitis had a higher rate of elevated alanine aminotransferase (28% vs 3% vs 0, P = 0.005).
H3N2-related neurologic complications in children mainly occur early in the disease course. Most patients were previously healthy and unvaccinated against influenza. Elevated alanine aminotransferase is more common in encephalopathy/encephalitis.
Influenza-Associated Neurologic Complications in Hospitalized Children
2021, Journal of Pediatrics
Citation Excerpt :
The influenza-associated neurologic complications observed in this study were heterogeneous. Although seizures and encephalopathy are well described in the literature,3,4,9,11-13 other complications of influenza that we observed, such as arterial ischemic stroke, ataxia, PRES, and cerebral edema, have been less frequently described. Any type of recent infection has been demonstrated to increase risk of arterial ischemic strokes in children by 6-fold,14 which may account for the one arterial ischemic stroke that we observed.
To define the incidence and characteristics of influenza-associated neurologic complications in a cohort of children hospitalized at a tertiary care pediatric hospital with laboratory-confirmed influenza and to identify associated clinical, epidemiologic, and virologic factors.
This was an historical cohort study of children aged 0.5-18.0 years old hospitalized between 2010 and 2017 with laboratory-confirmed influenza. Children with immune compromise or a positive test due to recent receipt of live virus vaccine or recently resolved illness were excluded. Influenza-associated neurologic complications were defined as new-onset neurologic signs/symptoms during acute influenza illness without another clear etiology.
At least 1 influenza-associated neurologic complication was identified in 10.8% (95% CI 9.1-12.6%, n = 131 of 1217) of hospitalizations with laboratory-confirmed influenza. Seizures (n = 97) and encephalopathy (n = 44) were the most commonly identified influenza-associated neurologic complications, although an additional 20 hospitalizations had other influenza-associated neurologic complications. Hospitalizations with influenza-associated neurologic complications were similar in age and influenza type (A/B) to those without. Children with a pre-existing neurologic diagnosis (n = 326) had a greater proportion of influenza-associated neurologic complications compared with those without (22.7% vs 6.4%, P < .001). Presence of a pre-existing neurologic diagnosis (aOR 4.6, P < .001), lack of seasonal influenza vaccination (aOR 1.6, P = .020), and age ≤5 years (aOR 1.6, P = .017) were independently associated with influenza-associated neurologic complications.
Influenza-associated neurologic complications are common in children hospitalized with influenza, particularly those with pre-existing neurologic diagnoses. A better understanding of the epidemiology and factors associated with influenza-associated neurologic complications will direct future investigation into potential neuropathologic mechanisms and mitigating strategies. Vaccination is recommended and may help prevent influenza-associated neurologic complications in children.
Prevalence, Risk Factors, and Outcomes of Influenza-Associated Neurologic Complications in Children
2021, Journal of Pediatrics
Citation Excerpt :
Factors associated with neurologic complications included Asian and other races, male sex, and chronic neurologic conditions. Much of the literature on influenza associated neurologic complications has involved a small number of cases (eg, 6 children,21 8 children,18 14 children,19 and 23 children20). In a study of 72 children hospitalized with influenza during the 2002-2004 influenza seasons, 10% had neurologic complications.7
To determine the frequency of neurologic complications associated with influenza in hospitalized children.
We performed a cross-sectional study of children (2 months through 17 years of age) with influenza discharged from 49 children's hospitals in the Pediatric Health Information System during the influenza seasons of 2015-2020. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. We assessed length of stay (LOS), intensive care unit (ICU) admission, ICU LOS, 30-day hospital readmissions, deaths, and hospital costs associated with these events. Patient-level risk factors associated with neurologic complications were identified using multivariable logistic regression.
Of 29 676 children hospitalized with influenza, 2246 (7.6%) had a concurrent diagnosis of a neurologic complication; the most frequent were febrile seizures (5.0%), encephalopathy (1.7%), and nonfebrile seizures (1.2%). Hospital LOS, ICU admission, ICU LOS, deaths, and hospital costs were greater in children with neurologic complications compared with those without complications. Risk factors associated with neurologic complications included male sex (aOR 1.1, 95% CI 1.02-1.21), Asian race/ethnicity (aOR 1.7, 95% CI 1.4-2.1) (compared with non-Hispanic White), and the presence of a chronic neurologic condition (aOR 3.7, 95% CI 3.1-4.2).
Neurologic complications are common in children hospitalized with influenza, especially among those with chronic neurologic conditions, and are associated with worse outcomes compared with children without neurologic complications. These findings emphasize the strategic importance of influenza immunization and treatment, especially in high-risk populations.
Vaccine coverage among children with epilepsy in two Canadian provinces: A Canadian immunization research network study
2021, Vaccine
Citation Excerpt :
Children with epilepsy, one of the most common chronic neurological disorders, are at increased risk of complications from vaccine-preventable infections. This includes an increased risk of complications during influenza infections, including hospitalization and death [1–4]. Around two-thirds of measles, mumps, rubella, and influenza infections in children with Dravet syndrome lead to neurological complications [5].
Children with epilepsy are at increased risk of complications from vaccine-preventable infections, yet information on vaccine coverage in these children is scarce. We aimed to compare vaccine coverage among children with epilepsy to children without epilepsy.
We conducted a retrospective cohort study including all 2005–2013 births in Manitoba and Ontario, Canada, creating two cohorts: 2-year-olds and 7-year-olds (followed to age 2 and 7 years). We split each cohort into epilepsy and non-epilepsy subcohorts. We assessed vaccination coverage based on provincial schedules and determined timeliness of MMR (measles, mumps, rubella) dose 1 (recommended at 12 months) and DTaP (diphtheria, tetanus, pertussis) dose 4 (recommended at 18 months). We used logistic regression to calculate adjusted odds ratios (aORs) of the association between epilepsy and vaccination, combining both provincial estimates using random effects meta-analysis.
We included 16,558 2-year-olds (Manitoba, 653; Ontario, 15,905) and 13,004 7-year-olds (Manitoba, 483; Ontario, 12,521) with epilepsy. At age 2 years, the aOR for up-to-date vaccination among children with versus without epilepsy was 0.9 (95% confidence interval 0.8–1.1); at age 7 years it was 1.0 (0.9–1.1). Infants diagnosed with epilepsy before age 6 months were less likely to be up-to-date at age 2 years (0.9; 0.8–0.9), although this difference disappeared by age 7 years. Vaccine timeliness was similar between children with and without epilepsy for MMR dose 1 and DTaP dose 4.
Overall, this study suggests that children with epilepsy are not significantly under-vaccinated compared to their peers without epilepsy. As children with epilepsy are at a higher risk of complications from vaccine-preventable diseases, vaccination in children with epilepsy should be optimized, especially early in life, as these children may not be able to rely on herd protection.
Neurological Complications of Respiratory Disease
2017, Seminars in Pediatric Neurology
Citation Excerpt :
Influenza-related neurological complications (INC) are less frequent, having been reported in 2%-12% of pediatric cases with laboratory confirmed influenza.16-18 Neurological complications have been reported more frequently with type A influenza infection, than type B.19,20 Several recent studies have shed more light on INC after the influenza A (H1N1) pandemic in 2009.21,22 Seizures, encephalopathy or encephalitis, Guillain-Barre syndrome (GBS), acute disseminated encephalomyelitis (ADEM), transverse myelitis, aseptic meningitis, myositis, and Reye syndrome have been reported.16-18,23
The respiratory and central nervous systems are intimately connected. Ventilatory control is strictly regulated by central mechanisms in a complex process that involves central and peripheral chemoreceptors, baroreceptors, the cardiovascular system, and specific areas of the brain responsible for autonomic control. Disorders of the lung and respiratory system can interfere with these mechanisms and temporarily or permanently disrupt this complex network resulting in mild to severe neurological sequelae. This article explores the wide variety of neurological problems resulting from respiratory dysfunction, with emphasis on its pathophysiology, clinical features, prognosis, and long-term outcome.
Diagnostic Imaging: Pediatrics
2017, Diagnostic Imaging: Pediatrics

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Original ArticlePediatric Neurologic Complications Associated With Influenza A H1N1

Introduction

Section snippets

Materials and Methods

Results

Discussion

Conclusions

J Pediatr

J Clin Virol

Lancet

Lancet Neurol

Influenza viruses

Influenza A infection is an important cause of febrile seizures

Pediatrics

Neurologic complications associated with influenza A in children during the 2003-2004 influenza season in Houston, Texas

Pediatrics

Emergence of a novel swine-origin Influenza A virus (S-OIV) H1N1 virus in humans

J Clin Virol

2009 Pandemic Influenza A (H1N1) Virus Hospitalizations Investigation Team. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009

N Engl J Med

Neurologic complications associated with novel influenza A (H1N1) virus infection in children—Dallas, Texas, May 2009

MMWR

Original Article
Pediatric Neurologic Complications Associated With Influenza A H1N1