Cystic fibrosis (CF) clinical care guidelines exist for the care of infants up to age 2 years and for individuals ≥6 years of age. An important gap exists for preschool children between the ages of 2 and 5 years. This period marks a time of growth and development that is critical to achieve optimal nutritional status and maintain lung health. Given that disease often progresses in a clinically silent manner, objective and sensitive tools that detect and track early disease are important in this age group. Several challenges exist that may impede the delivery of care for these children, including adherence to therapies. A multidisciplinary committee was convened by the CF Foundation to develop comprehensive evidence-based and consensus recommendations for the care of preschool children, ages 2 to 5 years, with CF. This document includes recommendations in the following areas: routine surveillance for pulmonary disease, therapeutics, and nutritional and gastrointestinal care.

Clinical Practice Guidelines From the Cystic Fibrosis Foundation for Preschoolers With Cystic Fibrosis

Cystic fibrosis is a life-limiting, recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Increased survival outcomes and the multisystem nature of the disease, including the involvement of hepatobiliary and gastrointestinal tracts, now require the need for more extensive knowledge and expertise in cystic fibrosis among gastroenterologists. Manifestations are either a direct consequence of the primary defect in cystic fibrosis or a secondary complication of the disease or therapy. Adult patients with cystic fibrosis also have an increased risk of malignancy in the gastrointestinal and pancreatico-biliary tracts compared with the general population. Novel treatments that target the basic defects in the CFTR protein have emerged, but to date not much is known about their effects on the gastrointestinal and hepatobiliary systems. The introduction of such therapies has provided new opportunities for the application of intestinal endpoints in clinical trials and the understanding of underlying disease mechanisms that affect the gut in cystic fibrosis.

Cystic fibrosis from the gastroenterologist's perspective

Background— Epidemiological studies demonstrate that childhood infections, including varicella zoster virus, are associated with an increased risk of arterial ischemic stroke (AIS). Other herpesviruses have been linked to childhood AIS in case reports. We sought to determine whether herpesvirus infections, which are potentially treatable, increase the risk of childhood AIS.

Methods and Results— We enrolled 326 centrally confirmed cases of AIS and 115 stroke-free controls with trauma (29 days to 18 years of age) with acute blood samples (≤3 weeks after stroke/trauma); cases had convalescent samples (7–28 days later) when feasible. Samples were tested by commercial enzyme-linked immunosorbent assay kits for immunoglobulin M/immunoglobulin G antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, and varicella zoster virus. An algorithm developed a priori classified serological evidence of past and acute herpesvirus infection as dichotomous variables. The median (quartiles) age was 7.7 (3.1–14.3) years for cases and 10.7 (6.9–13.2) years for controls ( P =0.03). Serological evidence of past infection did not differ between cases and controls. However, serological evidence of acute herpesvirus infection doubled the odds of childhood AIS, even after adjusting for age, race, and socioeconomic status (odds ratio, 2.2; 95% confidence interval, 1.2–4.0; P =0.007). Among 187 cases with acute and convalescent blood samples, 85 (45%) showed evidence of acute herpesvirus infection; herpes simplex virus 1 was found most often. Most infections were asymptomatic.

Conclusions— Herpesviruses may act as a trigger for childhood AIS, even if the infection is subclinical. Antivirals like acyclovir might have a role in the prevention of recurrent stroke if further studies confirm a causal relationship.

# CLINICAL PERSPECTIVE {#article-title-48}

/pdf/herpesvirus-infections-and-childhood-arterial-ischemic-39my8uppe0.pdf

Herpesvirus Infections and Childhood Arterial Ischemic Stroke: Results of the VIPS Study.

Intracerebral hemorrhage and ischemic stroke are increasingly recognized complications of central nervous system (CNS) infection by herpes simplex virus (HSV). To analyze clinical, imaging, and laboratory findings and outcomes of cerebrovascular manifestations of HSV infection. Systematic literature review from January 2000 to July 2018. We identified 38 patients (median age 45 years, range 1–73) comprising 27 cases of intracerebral hemorrhage, 10 of ischemic stroke, and 1 with cerebral venous sinus thrombosis. Intracerebral hemorrhage was predominantly (89%) a complication of HSV encephalitis located in the temporal lobe. Hematoma was present on the first brain imaging in 32%, and hematoma evacuation was performed in 30% of these cases. Infarction was frequently multifocal, and at times preceded by hemorrhage (20%). Both a stroke-like presentation and presence of HSV encephalitis in a typical location were rare (25% and 10%, respectively). There was evidence of cerebral vasculitis in 63%, which was exclusively located in large-sized vessels. Overall mortality was 21% for hemorrhage and 0% for infarction. HSV-1 was a major cause of hemorrhagic complications, whereas HSV-2 was the most prevalent agent in the ischemic manifestations. We found a distinct pathogenesis, cause, and outcome for HSV-related cerebral hemorrhage and infarction. Vessel disruption within a temporal lobe lesion caused by HSV-1 is the presumed mechanism for hemorrhage, which may potentially have a fatal outcome. Brain ischemia is mostly related to multifocal cerebral large vessel vasculitis associated with HSV-2, where the outcome is more favorable.

/pdf/cerebrovascular-manifestations-of-herpes-simplex-virus-1v2ui3r9j7.pdf

Cerebrovascular manifestations of herpes simplex virus infection of the central nervous system: a systematic review

The role of infection in cerebrovascular disease is complex and remains incompletely understood. Over the last 5 years, investigators have made notable inroads in untangling this thorny topic. In this review, we examine these recent developments, concentrating on four aspects of the relationship between infection and stroke. We first discuss specific infectious agents as direct causes of stroke, focusing on recent work implicating herpesviruses and HIV in cerebral vasculopathy. We then discuss systemic infection of any type as a stroke trigger, focusing on the relationship of infection to timing of acute stroke, both in children and adults, as well as the role of vaccination in stroke prevention. We examine the evidence for chronic infection or “infectious burden” as a stroke risk factor. Finally, we discuss recent work on infection as a risk factor for increased morbidity after stroke, possible mechanisms mediating this effect, and the evidence for prophylactic antibiotics.

/pdf/infection-and-stroke-an-update-on-recent-progress-h9m5t5zhe7.pdf

Infection and Stroke: an Update on Recent Progress

https://www.cysticfibrosisjournal.com/article/S1569-1993(14)00030-7/pdf

Prediction of acute pancreatitis risk based on PIP score in children with cystic fibrosis.

Primary herpes virus infection and ischemic stroke in childhood: a new association?

Acute muscle pain and walking difficulty are symptoms compatible with both benign and severe degenerative diseases. As a consequence, in some cases invasive tests and hospitalizations are improperly scheduled. We report the case of a 7-year-old child suffering from acute calf pain and abnormal gait following flu-like symptoms. A review of the literature will be helpful to better define differential diagnosis in cases of muscle pain in children. Daily physical examination and urine dipstick are sufficient to confirm the diagnosis of benign acute childhood myositis (BACM) during the acute phase, to promptly detect severe complications and to rule out degenerative diseases. Children with BACM do not require hospitalization, medical interventions or long-term follow-up.

Simple diagnosis of benign acute childhood myositis: Lessons from a case report

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Prediction of acute pancreatitis risk based on PIP score in children with cystic fibrosis.

Primary herpes virus infection and ischemic stroke in childhood: a new association?

Simple diagnosis of benign acute childhood myositis: Lessons from a case report