Swift Spontaneous Regression of a Pediatric Traumatic Acute Subdural Hematoma.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadWe report the case of a 4-year-old girl with acute subdural hematoma who presented to the emergency department after an unwitnessed fall of the balcony. The hematoma was hyperdense along the left convexity of 9 mm thickness with a consequent mass effect with obliteration of the adjacent sulci, left lateral ventricle compression and a midline shift of 7 mm. During her stay in the emergency department while waiting for transfer to the children intensive care unit elsewhere she slightly deteriorated neurologically. Repeat CT scan of the brain 4 h after initial presentation remarkably showed that the subdural hematoma had now largely disappeared, with a decrease in volume and density. Consequently, the mass effect diminished with a near normalization of the midline shift

Formation and immunomodulatory function of meningeal B cell aggregates in progressive CNS autoimmunity

Meningeal B lymphocyte aggregates have been described in autopsy material of patients with chronic multiple sclerosis. The presence of meningeal B cell aggregates has been correlated with worse disease. However, the functional role of these meningeal B cell aggregates is not understood. Here, we use a mouse model of multiple sclerosis, the spontaneous opticospinal encephalomyelitis model, which is built on the double transgenic expression of myelin oligodendrocyte glycoprotein-specific T-cell and B-cell receptors, to show that the formation of meningeal B cell aggregates is dependent on the expression of alpha 4 integrins by antigen-specific T cells. T cell-conditional genetic ablation of alpha 4 integrins in opticospinal encephalomyelitis mice impaired the formation of meningeal B cell aggregates, and surprisingly, led to a higher disease incidence as compared to opticospinal encephalomyelitis mice with alpha 4 integrin-sufficient T cells. B cell-conditional ablation of alpha 4 integrins in opticospinal encephalomyelitis mice resulted in the entire abrogation of the formation of meningeal B cell aggregates, and opticospinal encephalomyelitis mice with alpha 4 integrin-deficient B cells suffered from a higher disease burden than regular opticospinal encephalomyelitis mice. While anti-CD20 antibody-mediated systemic depletion of B cells in opticospinal encephalomyelitis mice after onset of disease failed to efficiently decrease meningeal B cell aggregates without significantly modulating disease progression, treatment with anti-CD19 chimeric antigen receptor-T cells eliminated meningeal B cell aggregates and exacerbated clinical disease in opticospinal encephalomyelitis mice. Since about 20% of B cells in organized meningeal B cell aggregates produced either IL-10 or IL-35, we propose that meningeal B cell aggregates might also have an immunoregulatory function as to the immunopathology in adjacent spinal cord white matter. The immunoregulatory function of meningeal B cell aggregates needs to be considered when designing highly efficient therapies directed against meningeal B cell aggregates for clinical application in multiple sclerosis

The glioblastoma multiforme tumor site promotes the commitment of tumor-infiltrating lymphocytes to the TH17 lineage in humans

Although glioblastoma multiforme (GBM) is not an invariably cold tumor, checkpoint inhibition has largely failed in GBM. In order to investigate T cell-intrinsic properties that contribute to the resistance of GBM to endogenous or therapeutically enhanced adaptive immune responses, we sorted CD4(+) and CD8(+) T cells from the peripheral blood, normal-appearing brain tissue, and tumor bed of nine treatment-naive patients with GBM. Bulk RNA sequencing of highly pure T cell populations from these different compartments was used to obtain deep transcriptomes of tumor-infiltrating T cells (TILs). While the transcriptome of CD8(+) TILs suggested that they were partly locked in a dysfunctional state, CD4(+) TILs showed a robust commitment to the type 17 T helper cell (T(H)17) lineage, which was corroborated by flow cytometry in four additional GBM cases. Therefore, our study illustrates that the brain tumor environment in GBM might instruct T(H)17 commitment of infiltrating T helper cells. Whether these properties of CD4(+) TILs facilitate a tumor-promoting milieu and thus could be a target for adjuvant anti-T(H)17 cell interventions needs to be further investigated

Information environment and equity risk premium volatility around the world

This paper examines whether and how differences in investors' information environments (measured by a country's information disclosure, accounting standards, and financial transparency) are related to cross-country differences in the market risk premium volatility. We use the vector-autoregressive and implied cost of capital methods to extract time variation in risk premiums for 41 developed and emerging markets worldwide. Consistent with theoretical predictions, countries with better information environments tend to experience a lower risk premium volatility, even after controlling for various country variables that are potentially associated with variation in risk premiums. Our analysis of two exogenous events, specifically the 1997 Asian financial crisis and 2008 global financial crisis, further corroborates our key finding that information environments play an important role in explaining market risk premium variability

The world price of home bias

Theoretical arguments suggest that as the degree of a country's home bias increases, the global risk sharing between domestic and foreign investors will reduce and thereby increase the country's cost of capital. Consistent with this prediction, we find international differences in the cost of capital to be strongly and positively related to varying degrees of home bias for 38 markets. This finding is robust to different cost of capital proxies, different control variables, alternative home-bias measures, international tradability of stocks, and alternative specifications. Therefore, the overall evidence implies that countries may enjoy a significantly lower cost of capital by reducing the extent of their home bias and hence, increasing global risk sharing.Mutual fund holdings Cost of capital Market segmentation Home bias

Development of spontaneous leg movements in infants with and without periventricular leukomalacia

The main question asked in the present study was whether support could be found for the notion that supraspinal influences on the generation of spontaneous kicking movements become increasingly apparent in the first half-year after birth. In comparing groups of infants with and without damage in tracts connected with the cortex surrounding the central sulcus, such support would consist of the finding that similar patterns of spontaneous kicking are observed early in development, whereas differences between groups should occur with increasing age. Using 3-D registrations, the spontaneous kicking movements of 19 infants with differing degrees of periventricular, lobar, and subcortical leukomalacia based on white matter (WM) abnormalities on ultrasound were compared to those of 10 healthy control infants at 6, 12, 18, and 26 weeks of corrected age. Magnetic resonance imaging recordings were used to identify the location and severity of the brain lesions. Infants with extensive lesions in the periventricular and lobar WM with or without diffuse lesions in the subcortical WM showed a decreased variability on some spatial and temporal parameters of kicks. More importantly, these infants showed a different developmental course for intralimb couplings when compared to the other infants; they were unable to dissociate tight intralimb couplings at 18 and 26 weeks. As all of these infants had substantial damage of the corticospinal tracts, these findings suggest that these tracts are involved in the regulation of intralimb joint dissociations between 4 and 6 months of age. However, caution is needed as areas outside those in which the corticospinal tracts are located could be damaged as well and most of the infants with moderate to severe lesions in the corticospinal tract had additional psychomotor problems. For interlimb couplings and most of the spatial and temporal parameters of kicks, no differences were found between groups. This strengthens the claim that inter- and intralimb couplings are organized in fundamentally different ways

Early MR features of hypoxic-ischemic brain injury in neonates with periventricular densities on sonograms

BACKGROUND AND PURPOSE: In the early 1980s, diagnosing periventricular leukomalacia (PVL) in neonates by using cranial sonography was possible for the first time. Our purpose was to investigate the possibility of diagnosing PVL in the acute stage by using MR imaging. We evaluated early MR features of hypoxic-ischemic brain injury in neonates with periventricular densities (flares) on cranial sonograms to determine the added value of MR imaging over sonography alone for early diagnosis of brain damage. METHODS: In a prospective study, infants who showed flares and/or cysts on sonograms underwent MR imaging during the (sub)acute stage. RESULTS: Fifty infants were classified according to the highest sonographic grade up to the day of MR imaging: 23 infants had sonographic grade 1 (flares < 1 week), 15 had sonographic grade 2 (flares ≥ 1 week), four had sonographic grade 3 (small localized cysts), and eight had sonographic grade 4 (extensive periventricular cysts); none had sonographic grade 5 (multicystic leukomalacia) on the day of MR imaging. Overall, the additional information provided by MR imaging (over sonography alone) consisted of the depiction of hemorrhagic lesions in 64% of the infants. Extent and severity of the hemorrhages varied from isolated punctate lesions to extensive hemorrhages throughout the white matter; the latter were followed by cystic degeneration at autopsy in two infants. In nine of the 12 infants with cystic PVL, MR images showed more numerous or more extensive cysts. In addition, in two infants, MR images showed cysts not present on sonograms. In 32% of the infants, MR imaging provided no additional information; in these children, all but one had flares on sonograms whereas MR images showed no abnormalities or a zone of mild periventricular signal change. CONCLUSION: MR imaging can depict the precise site and extent of hypoxic-ischemic brain injury at an earlier stage and allows a wider differentiation of lesions as compared with sonography alone. Hemorrhagic PVL is considered to be rare, but was present in 64% of our study population

Formation and immunomodulatory function of meningeal B-cell aggregates in progressive CNS autoimmunity

Meningeal B lymphocyte aggregates have been described in autopsy material of patients with chronic Multiple Sclerosis. The presence of meningeal B cell aggregates has been correlated with worse disease. However, the functional role of these meningeal B cell aggregates is not understood. Here, we use a mouse model of Multiple Sclerosis, the spontaneous opticospinal encephalomyelitis model, which is built on the double transgenic expression of myelin oligodendrocyte glycoprotein-specific T cell- and B cell-receptors, to show that the formation of meningeal B cell aggregates is dependent on the expression of α4 integrins by antigen-specific T cells. T cell-conditional genetic ablation of α4 integrins in opticospinal encephalomyelitis mice impaired the formation of meningeal B cell aggregates, and surprisingly, led to a higher disease incidence as compared to opticospinal encephalomyelitis mice with α4 integrin-sufficient T cells. B cell-conditional ablation of α4 integrins in opticospinal encephalomyelitis mice resulted in the entire abrogation of the formation of meningeal B cell aggregates, and opticospinal encephalomyelitis mice with α4 integrin-deficient B cells suffered from a higher disease burden than regular opticospinal encephalomyelitis mice. While anti-CD20 antibody-mediated systemic depletion of B cells in opticospinal encephalomyelitis mice after onset of disease failed to efficiently decrease meningeal B cell aggregates without significantly modulating disease progression, treatment with anti-CD19 chimeric antigen receptor-T cells eliminated meningeal B cell aggregates and exacerbated clinical disease in opticospinal encephalomyelitis mice. Since about 20 percent of B cells in organised meningeal B cell aggregates produced either IL-10 or IL-35, we propose that meningeal B cell aggregates might also have an immunoregulatory function as to the immunopathology in adjacent spinal cord white matter. The immunoregulatory function of meningeal B cell aggregates needs to be considered when designing highly efficient therapies directed against meningeal B cell aggregates for clinical application in Multiple Sclerosis

Long-term outcomes for females with early-onset dystrophinopathy

AIM: To study long-term disease course for females with early-onset dystrophinopathy, including common (female) symptoms, challenges in social participation, the need for care, and current healthcare management to support guideline development. METHOD: Twelve females with early-onset dystrophinopathy were followed for a median period of more than 17 years (range 1-36). RESULTS: One patient died owing to end-stage cardiac failure. Cardiac abnormalities were observed in three of the remaining 11 participants. Respiratory function was reduced in seven of 10 participants. Fatigue, myalgia, lower back pain, and arthralgia were reported in more than six of the participants. Functional status varied from exercise intolerance to wheelchair dependency. Most or all of the 10 participants reported restrictions in participation in work (n = 10), household duties (n = 10), sports (n = 9), and education (n = 8). Only a few participants received followed-up pulmonary (n = 2) or rehabilitation (n = 3) care. INTERPRETATION: Females with early-onset dystrophinopathy experience a wide range of impairments, comorbidities, limitations in activities, and restrictions in social participation. The whole spectrum should be acknowledged in the healthcare setting. Neuromuscular and cardiac follow-up are indispensable. Additional respiratory assessment and rehabilitation care are expected to improve health status and support daily activities and participation