ABSTRACT
Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is an ongoing pandemic that has affected over 400 million people worldwide and caused nearly 6 million deaths. Hemorrhagic encephalitis is an uncommon but serious complication of COVID-19. The etiology of this disease is multifactorial, including secondary to severe hypoxemia, systemic inflammation, direct viral invasion, hypercoagulability, etc. The clinical spectrum of COVID-19-related hemorrhagic encephalitis is also varied, ranging from leukoencephalopathy with microhemorrhage, acute necrotizing hemorrhagic encephalitis (ANHE) involving the cortex, basal ganglia, rarely brain stem and cervical spine, hemorrhagic posterior reversible encephalopathy syndrome (PRES) to superimposed co-infection with other organisms. We report a case series of three young patients with different presentations of hemorrhagic encephalitis after COVID-19 infection and a review of the literature. One patient had self-limiting ANHE in the setting of mild COVID-19 systemic illness. The second patient had self-limiting leukoencephalopathy with microhemorrhages in the setting of severe systemic diseases and ARDS, and clinically improved with the resolution of systemic illness. Both patients were healthy and did not have any premorbid conditions. The third patient with poorly controlled diabetes and hypertension had severe systemic illness with neurological involvement including multiple ischemic strokes, basal meningitis, hemorrhagic encephalitis with pathological evidence of cerebral mucormycosis, and Epstein-Barr virus coinfection, and improved after antifungal therapy.
ABSTRACT
OBJECTIVE: To describe long-term outcomes of children with early-infantile Krabbe disease who underwent hematopoietic stem cell transplantation (HSCT) in the first 7 weeks of life. METHODS: In this prospective longitudinal study, evaluations performed at baseline and follow-up included brain imaging, neurodiagnostic tests, and neurobehavioral evaluations. RESULTS: Of the 18 patients in this study (11 girls, 7 boys; mean follow-up 9.5 years, range 4-15), 5 died (3 of peritransplant complications, 1 of a surgical complication unrelated to Krabbe disease, 1 of disease progression). One of the surviving patients has normal cognitive function and 10 continue to develop cognitive skills at a slightly slower rate than normal. All surviving patients continue to gain receptive language skills, with 7 falling within the normal range. Ten patients receive speech therapy, and 2 of these patients require augmentative communication devices. Gross motor development varies widely, but 3 patients can walk independently, and 7 walk with assistive devices. Spasticity ranges from mild to severe, and 12 patients wear orthotics. Fine motor skills are generally preserved. Brain myelination and atrophy stabilized in 8 patients, improved in 4 patients, and worsened in 1 patient. Nerve conduction velocities initially improved but continue to be abnormal in most patients. CONCLUSIONS: The surviving patients function at a much higher level than untreated children or symptomatic children who underwent HSCT. These results show that early HSCT changes the natural history of this disease by improving both lifespan and functional abilities. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for children with early-infantile Krabbe disease, early HSCT improves lifespan and functional abilities.
