Current Respiratory Medicine Reviews - Volume 21, Issue 1, 2025

The most significant viral contributors to acute respiratory tract infections in children are Respiratory Syncytial Viruses (RSV) and influenza virus, causing substantial seasonal respiratory infections annually. Furthermore, severe neurological complications, notably seizures and encephalopathy, can be attributed to these viruses. Children with chronic or pre-existing neurological conditions are particularly susceptible to increased morbidity and sequelae. An active area of research to date is focused on the potential mechanisms of viral neurological invasion, which could be relevant for future therapeutic strategies. Influenza virus is frequently an important cause of epidemic or pandemic disease causing high costs of hospitalization and primary care. Furthermore, different subtypes of influenza viruses can induce various influenza-associated neurological complications, varying from mild (i.e., headache) to severe (i.e., meningoencephalitis and acute necrotizing encephalopathy), both in adults and children. While affecting the respiratory tract, RSV can also give rise to neurological manifestations, potentially resulting in long-term neurological impairment. Neurological changes associated with RSV encompass seizures, lethargy, ataxia, febrile or epileptic states, central apnea, difficulties in feeding or swallowing, tone abnormalities, strabismus, abnormalities in cerebrospinal fluid, and encephalopathy. Patients infected with RSV can also develop neuromotor difficulties or present learning impairment. In conclusion, viral respiratory infections can result in significant extrapulmonary symptoms, potentially leading to enduring health consequences in affected children. Substantial research efforts are necessary to prevent or treat these infections, particularly within the most vulnerable populations.

Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder. Its incidence has dramatically risen during the last few decades. ASD is a multifactorial disorder. In addition to genetic factors, the environment plays a key role during critical periods of neurodevelopment. The prenatal environment, as well as perinatal and postnatal exposures to infection and inflammation, are increasingly identified as potential risk factors for autism and can influence development and increase neurodevelopmental disorders. Immune dysfunction and dysregulation are considered an important factor contributing to the pathogenesis of autism and may influence the course and severity of the disease. This study aims to analyze the data available in the scientific literature regarding the correlation between respiratory infections and autism.

Breathing is an automatic process generated by the central nervous system, crucial for the homeostasis of several body processes. This vital process is underpinned by an intricate network in which distinct functional and anatomical factors and structures play a role. Transcription factors (i.e., PHOX2B and Pbx proteins), as well as neuromodulators (i.e., serotonin, noradrenaline, GABA, and glycine), have been demonstrated as implicated in the regulation of breathing. Besides, the several intertwined excitatory and inhibitory brainstem neural circuits comprising the so-called central pattern generator (CPG) have recently demonstrated a potential role of cerebellar structures and circuits in coordinating the complex and coordinated respiratory act in eupnea. A disruption affecting one of these components, which may also occur on a genetic basis, may indeed result in complex and heterogeneous disorders, including neurodevelopmental ones (such as Rett and Prader-Willi syndrome), which may also present with neuropsychiatric and breathing manifestations and potentially lead to sudden infant death syndrome (SIDS). Herein, we discuss the main factors and systems involved in respiratory control and modulation, outlining some of the associated neurodevelopmental disorders (NDDs) deriving from an impairment in their expression/function. Further studies are needed to deepen our knowledge of the complexity underpinning “breathing” and the relation between respiratory implications and congenital and developmental disorders.

Rett Syndrome (RTT) is a rare and severe neurodevelopmental disorder affecting children in the early stages of infancy and associated with a MECP2 mutation in 95-97% of individuals with typical RTT. Nearly all of the patients show breathing abnormalities during their lifespan, both in wake and sleep and respiratory illness represents an important cause of morbidity and mortality in RTT. Pathogenic mechanisms underlying breath-holding and other breathing abnormalities in RTT are mainly related to dysautonomia and an alteration in respiratory control at different levels, including several regions of the central and peripheral nervous system. Pathogenic variants in the MECP2 gene have been implicated in the dysfunction of respiratory pathways, affecting chemosensitivity and the response to neurotransmitters. In addition, frequent comorbidities such as scoliosis, dysphagia, sleep disorders, and epilepsy can further impair the respiratory function in these patients.

COVID-19, previously considered a mere respiratory illness affecting predominantly the adult age, is today acknowledged as the cause of a wide spectrum of multisystemic signs and symptoms, ranging from mild to severe degrees, including neurological manifestations. Even if less frequently than adults, pediatric patients may also develop severe COVID-19 and present with peculiar clinical pictures, including multi-system inflammatory syndrome (MIS-C) and neuropsychiatric manifestations. Mounting evidence is available on the potential pathogenic mechanisms underpinning the nervous system involvement and on the Post-COVID19 sequelae. However, little is known about EEG changes that may come along with them, particularly in the pediatric age. Herein, we briefly overview the neuropsychiatric COVID-19-related features in pediatric patients and the reported potential EEG correlates. Further research may help unravel new insights and provide new biomarkers regarding diagnosis, prognosis, and treatment options for post- COVID-19 neuro-cognitive disorders.

Inborn Errors of Metabolism (IEMs) are a large heterogeneous group of monogenic disorders that affect specific metabolic pathways. Although the clinical picture is variable and shows a multisystemic impairment, most of these defects encompass neurologic symptoms and signs. The respiratory involvement may represent a late-onset feature of a complex multisystemic disease or the only manifestation of an underlying IEM. The severity of the respiratory disease can range from mild aspecific symptoms, such as tachypnea and respiratory distress in response to metabolic acidosis, to severe conditions, such as respiratory failure and restrictive disease. This review aims to offer an overview of the principal IEMs with neurologic and respiratory involvement, highlighting the significance of early recognition and multidisciplinary management for optimal patient care.