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Possible role of the rhinovirus in Lennox-Gastaut Syndrome exacerbation

Jonathan Quinonez

Introduction: Lennox-Gastaut syndrome (LGS) refers to a rare form of childhood-onset epilepsy characterized by cognitive dysfunction, generalized multiple type seizures, and slow spike-wave seen on an electroencephalogram (EEG). LGS presents between the ages of 3-5 and can persist into adulthood. LGS is associated with brain tumors and malformations, congenital infections, gene mutations and related disorders not limited to tuberous sclerosis. The management of LGS is limited due to treatment-resistant seizures. Respiratory viral infections are implicated in both protection from, and inception of, allergic airway disease. Severe lower respiratory tract viral infections are associated with recurrent wheeze, asthma and atopy. It is unclear if this association is causal and the underlying mechanisms governing this are unknown. Whilst respiratory viral infections are the major precipitants of acute exacerbations of wheezing illness, early life infections are also clearly associated with protection from allergic diseases. This article aims to review the current understanding of the complex relationship between lower respiratory tract viral infections and their impact upon development of atopy in the airway. Rhinoviruses are a major cause of asthma exacerbations in children and adults. With the use of sensitive RT-PCR methods, respiratory viruses are found in approximately 80% of wheezing episodes in children and in approximately one half of such episodes in adults. Rhinovirus is a member of the family Picornaviridae, and acute rhinovirus infections occur predominantly in the upper airway. This virus has also been identified in the lower airway, and it might cause acute wheezing through the production of proinflammatory mediators with a resulting neutrophilic inflammatory response. Precisely how this process leads to increases in airway hyperresponsiveness and airway obstruction is not fully established. The recent development of PCR for the diagnosis of respiratory viral infections has permitted studies revealing the importance of virus infections in acute exacerbations of asthma. Several studies implicate rhinovirus as the major virus type in mild and severe wheezing illness in children of all age groups, but particularly over 1 year of age. Rhinoviruses have been shown to replicate in the lower airway, suggesting that virus induced asthma exacerbations result from direct inoculation, spread of the virus from the upper to the lower airway. The importance of RS virus infection in bronchiolitis and wheezing in infants has been reaffirmed. Recent studies using PCR to detect C pneumoniae, suggests a high prevalence of chronic infection in asthmatic children, and that the immune response to this organism may play a pathological role in asthma. These studies now require confirmation with larger carefully controlled studies. However, risk factors for wheezing with colds include asthma and atopy, extremes in age, and perhaps having a deficient TH1 response to rhinovirus. With the use of in vitro models and experimental inoculation studies, significant advances have led to a better understanding of the mechanisms by which rhinovirus infections cause asthma exacerbations. Advances in our understanding of this interaction might provide knowledge that could ultimately lead to specific treatment modalities to prevent and/or treat this significant burden of asthma exacerbations. Children with asthma were studied during the Southern hemisphere winter and summer of 2001-2002. Human rhinovirus (hRV) was significantly associated (P=.0001) with asthma exacerbations in winter and spring/summer, but not in intervening asymptomatic periods. Although hRV was also found in children with upper respiratory tract infection (URTI) who underwent sampling at the same time, it was present in significantly higher numbers of children with symptomatic asthma (P