MRI Patterns in Pediatric CNS Hemophagocytic Lymphohistiocytosis.

BACKGROUND AND PURPOSE: Neuroimaging has an important role in detecting CNS involvement in children with systemic or CNS isolated hemophagocytic lymphohistiocytosis. We characterized a cohort of pediatric patients with CNS hemophagocytic lymphohistiocytosis focusing on neuroradiologic features and assessed whether distinct MR imaging patterns and genotype correlations can be recognized. MATERIALS AND METHODS: We retrospectively enrolled consecutive pediatric patients diagnosed with hemophagocytic lymphohistiocytosis with CNS involvement treated at 2 pediatric neurology centers between 2010 and 2018. Clinical and MR imaging data were analyzed. RESULTS: Fifty-seven children (40 primary, 70%) with a median age of 36 months (interquartile range, 5.5-80.8 months) were included. One hundred twenty-three MR imaging studies were assessed, and 2 broad imaging patterns were identified. Pattern 1 (significant parenchymal disease, 32/57, 56%) was seen in older children (P = .004) with worse clinical profiles. It had 3 onset subpatterns: multifocal white matter lesions (21/32, 66%), brainstem predominant disease (5, 15%), and cerebellitis (6, 19%). All patients with the brainstem pattern failed to meet the radiologic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. An attenuated imaging phenotype (pattern 2) was seen in 25 patients (44%, 30 studies) and was associated with younger age. CONCLUSIONS: Distinct MR imaging patterns correlating with clinical phenotypes and possible genetic underpinnings were recognized in this cohort of pediatric CNS hemophagocytic lymphohistiocytosis. Disruptive mutations and missense mutations with absent protein expression correlate with a younger onset age. Children with brainstem and cerebellitis patterns and a negative etiologic work-up require directed assessment for CNS hemophagocytic lymphohistiocytosis.

Clinical and Radiologic Findings of Acute Necrotizing Encephalopathy in Young Adults.

Acute necrotizing encephalopathy after an acute febrile illness, although initially described exclusively in the pediatric age group, has been recently shown to have an adult onset as well. In this study, we describe 10 patients (16 years of age or older) with acute necrotizing encephalopathy. In our study, bilateral thalamic involvement with the trilaminar pattern of diffusion restriction on MR imaging was the predominant finding seen in all of the patients reviewed. Ancillary findings of cerebral white matter, brain stem, and cerebellum involvement with sparing of the basal ganglia were also noted. A poorer outcome was observed in patients with a higher degree of thalamic involvement. The cause of an underlying infection was identified in 4 patients (dengue in 3 and influenza in 1). Overall, a sizeable portion of young adults with acute necrotizing encephalopathy have shown a poorer outcome, with dengue being an important underlying trigger in an endemic region.

Brain Imaging in Cases with Positive Serology for Dengue with Neurologic Symptoms: A Clinicoradiologic Correlation.

BACKGROUND AND PURPOSE: Dengue is a common arboviral disease, which uncommonly involves the brain. There has been a recent surge in dengue cases and dengue-related deaths in tropical countries. The aim of this study was to describe brain imaging findings in patients with dengue infection having neurologic symptoms. MATERIALS AND METHODS: Thirty-five patients with positive serology for dengue with CNS symptoms undergoing imaging of the brain were included in the study. Clinical, laboratory, and imaging parameters were assessed and correlated to poor outcome. RESULTS: A Glasgow Coma Scale score of ≤12 at presentation, clinical classification of severe-type dengue, and the presence of acute renal failure were associated with poor outcome. Imaging parameters associated with poor outcome were involvement of the thalami and cerebellar peduncles and the presence of diffusion restriction and hemorrhagic foci in the brain parenchyma. CONCLUSIONS: Although not specific, dengue infection has imaging findings that can be used to narrow down the differential list and help in prognostication.

Chest radiographic manifestations of scrub typhus.

BACKGROUND AND RATIONALE: Respiratory system involvement in scrub typhus is seen in 20-72% of patients. In endemic areas, good understanding and familiarity with the various radiologic findings of scrub typhus are essential in identifying pulmonary complications. MATERIALS AND METHODS: Patients admitted to a tertiary care center with scrub typhus between October 2012 and September 2013 and had a chest X ray done were included in the analysis. Details and radiographic findings were noted and factors associated with abnormal X-rays were analyzed. RESULTS: The study cohort contained 398 patients. Common presenting complaints included fever (100%), generalized myalgia (83%), headache (65%), dyspnea (54%), cough (24.3%), and altered sensorium (14%). Almost half of the patients (49.4%) had normal chest radiographs. Common radiological pulmonary abnormalities included pleural effusion (14.6%), acute respiratory distress syndrome (14%), airspace opacity (10.5%), reticulonodular opacities (10.3%), peribronchial thickening (5.8%), and pulmonary edema (2%). Cardiomegaly was noted in 3.5% of patients. Breathlessness, presence of an eschar, platelet counts of <20,000 cells/cumm, and total serum bilirubin >2 mg/dL had the highest odds of having an abnormal chest radiograph. Patients with an abnormal chest X-ray had a higher requirement of noninvasive ventilation (odds ratio [OR]: 13.98; 95% confidence interval CI: 5.89-33.16), invasive ventilation (OR: 18.07; 95% CI: 6.42-50.88), inotropes (OR: 8.76; 95% CI: 4.35-17.62), higher involvement of other organ systems, longer duration of hospital stay (3.18 ± 3 vs. 7.27 ± 5.58 days; P< 0.001), and higher mortality (OR: 4.63; 95% CI: 1.54-13.85). CONCLUSION: Almost half of the patients with scrub typhus have abnormal chest radiographs. Chest radiography should be included as part of basic evaluation at presentation in patients with scrub typhus, especially in those with breathlessness, eschar, jaundice, and severe thrombocytopenia.

Regional variability in the time course of TGF-beta 1 expression, cellular proliferation and extracellular matrix expansion following arterial injury.

Transforming growth factor-beta 1 (TGF-beta 1) has been variably associated with the regulation of cellular proliferation and extracellular matrix expansion after arterial injury. We tested these associations in vivo in the rat carotid injury model. At 0, 3, 7, 14 and 28 days following arterial balloon injury, regional expression of TGF-beta 1 mRNA was assessed using in situ hybridization and the results compared to measures of cellular proliferation and extracellular matrix expansion. Both the TGF-beta 1 concentration measured in culture media of explanted carotid arteries and the quantitative in situ hybridization signal for TGF-beta 1 arterial media and neointima were maximal at 14 days after balloon injury. However, medial cellular proliferation was maximal at 3 days whereas neointimal proliferation was maximal at 14 days and significantly greater than medial proliferation. Neointimal cell density declined significantly between 7 and 14 days, indicating the expansion of extracellular matrix; however, medial cell density was unchanged between 3 and 28 days after balloon injury. Thus, differences in the regional arterial wall relationships between the time course of cellular proliferation, extracellular matrix expansion and the level of TGF-beta 1 expression demonstrate in vivo variability in the response to TGF-beta 1.