The first case of hemorrhagic shock and encephalopathy syndrome with fulminant hypercytokinemia associated with pediatric COVID-19.

BACKGROUND: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead not only to respiratory symptoms but also to neurologic symptoms with various levels of severity. After the worldwide prevalence of Omicron variant, severe neurological manifestations of coronavirus disease 2019 (COVID-19) such as febrile seizure, demyelinating disease, and cerebrovascular disease, have been reported. However, reports of acute encephalopathy in patients with COVID-19 are quite limited. Especially in terms of cytokine storm-inducing hemorrhagic shock and encephalopathy syndrome (HSES), there is no case reported related to COVID-19. CASE PRESENTATION: We describe the case of an 8-year-old girl who presented with fatal HSES associated with pediatric SARS-CoV-2 infection. Status epilepticus occurs after the onset of fever and diarrhea and lasted for at least an hour. Unconsciousness was followed by circulatory failure and ultimately leading to death within 2 days after the fever onset. Analysis of forty-eight cytokines and chemokines measured in three consecutive serum samples revealed that interferon (IFN)-γ, interleukin (IL)-6, IL-10, IL-17A, tumor necrosis factor (TNF)-a, IL-8, Interferon gamma inducible protein (IP)-10, and Monocyte chemoattractant protein (MCP)-1, were increased within an hour after the onset of impaired consciousness. CONCLUSION: Here, we describe a case of fatal fulminant encephalopathy with rapid progression because of HSES associated with COVID-19. High levels of cytokines and chemokines observed in this case may be because of the SARS-CoV-2-associated cytokine storm. This study is the first COVID-19-associated case of HSES.

Neonatal onset of Niemann-Pick disease type C in a patient with cholesterol re-accumulation in the transplanted liver and inflammatory bowel disease.

BACKGROUND: Niemann-Pick disease type C (NPC) is an autosomal recessive inherited and neurodegenerative disorder. Approximately 10% of NPC patients have acute liver failure and sometimes need liver transplantation (LT), and 7% reportedly develop inflammatory bowel disease (IBD). We report the case of a girl with NPC who had a re- accumulation of cholesterol in the transplanted liver and NPC-related IBD. CASE REPORT: The patient underwent living donor liver transplantation (LDLT) due to severe acute liver failure caused by an unknown etiology inherited from her father. At 1 year and 6 months (1Y6M), she developed neurological delay, catalepsy, and vertical supranuclear gaze palsy. The foam cells were found in her skin, and fibroblast Filipin staining was positive; hence, she was diagnosed with NPC. It was identified that her father had NPC heterozygous pathogenic variant. At 2 years, she had anal fissure, skin tag and diarrhea. She was diagnosed with NPC-related IBD, using a gastrointestinal endoscopy. Three years after LT, liver biopsy revealed foam cells and numerous fatty droplets. At 8 years, broken hepatocytes and substantial fibrosis were observed. She died from circulation failure due to hypoalbuminemia at 8Y2M. CONCLUSIONS: In NPC, load of cholesterol metabolism is suggested to persist even after LT. LDLT from NPC heterozygous variant donor was insufficient to metabolize cholesterol overload. In NPC patients, the possibility of cholesterol re-accumulation should be considered when LT is performed. NPC-related IBD should be considered when NPC patients have anorectal lesions or diarrhea.

Survey on children with cerebral palsy in Tochigi Prefecture, Japan.

BACKGROUND: The incidence of cerebral palsy (CP) is influenced by perinatal medicine and regional medical systems. We investigated the recent incidence of CP and the current problems of children with CP in living at home under an advanced perinatal medical system in Tochigi Prefecture, Japan. METHODS: A clinical datasheet survey was performed among 13 hospitals and six rehabilitation facilities treating children with CP born in Tochigi Prefecture to estimate the incidence of CP among children born between 2009 and 2013. The severity of motor and intellectual impairment, presumed causal factors, complications, and provided medical interventions were investigated and compared between preterm and term-born children with CP. RESULTS: The incidence of CP was 1.6 per 1000 live births. Shorter gestation period and lower birthweight were associated with a higher incidence of CP. Fifty-one percent of children with CP were non-ambulatory and 55% had severe to profound intellectual impairment. Episodes of neonatal asphyxia and periventricular leukomalacia were the most frequent causal factors; both were significantly more frequent in preterm than in term-born children. Approximately 30% of children with CP had respiratory disorders, dysphagia, or epilepsy; 62% received medical interventions, including medication, mechanical ventilation, oxygen therapy, tube feeding, and intraoral/intranasal suction. CONCLUSION: We found the incidence of CP to be lower in comparison to previous Japanese studies. However, the motor and intellectual impairments were severe, and many children with CP and their families were burdened by daily medical care. Public support systems should be developed, as well as the perinatal medical system.