CSF Surfactant Protein Changes in Preterm Infants After Intraventricular Hemorrhage.

Introduction: Surfactant proteins (SP) have been shown to be inherent proteins of the human CNS and are altered during acute and chronic disturbances of CSF circulation. Aim of the study was to examine the changes of surfactant protein concentrations in CSF of preterm babies suffering from intraventricular hemorrhage. Patients and Methods: Consecutive CSF samples of 21 preterm infants with intraventricular hemorrhages (IVH) and posthemorrhagic hydrocephalus (PHHC) were collected at primary intervention, after 5-10 days and at time of shunt insertion ~50 days after hemorrhage. Samples were analyzed for surfactant proteins A, B, C, and G by ELISA assays and the results were compared to 35 hydrocephalus patients (HC) without hemorrhage and 6 newborn control patients. Results and Discussion: Premature patients with IVH showed a significant elevation of surfactant proteins SP-A, C, and G compared to HC and control groups: mean values for the respective groups were SP-A 4.19 vs. 1.08 vs. 0.38 ng/ml. Mean SP-C 3.63 vs. 1.47 vs. 0.48 ng/ml. Mean SP-G 3.86 vs. 0.17 vs. 0.2 ng/ml. SP-A and G concentrations were slowly falling over time without reaching normal values. SP-C levels declined faster following neurosurgical interventions and reached levels comparable to those of hydrocephalus patients without hemorrhage. Conclusion: Intraventricular hemorrhages of premature infants cause posthemorrhagic CSF flow disturbance and are associated with highly significant elevations of surfactant proteins A, C, and G independent of total CSF protein concentrations.

Localization, Occurrence, and CSF Changes of SP-G, a New Surface Active Protein with Assumable Immunoregulatory Functions in the CNS.

Conventional surfactant proteins (A, B, C, and D) are important players of the innate immunity in the central nervous system and serve as effective regulators of cerebrospinal fluid rheology, probably being involved in clearance of detrimental metabolites like beta-amyloid and phospho-tau. Recently, a novel surfactant protein, SP-G, was described in kidneys and peripheral endocrine and exocrine glands. So far, its presence and possible functions in the central nervous system are unknown. Therefore, our study aimed to elucidate the presence of SP-G in the brain and its concentration in normal and pathologic samples of cerebrospinal fluid in order to gain first insight into its regulation and possible functions. A total of 121 samples of human cerebrospinal fluid (30 controls, 60 hydrocephalus patients, 7 central nervous system infections, and 24 brain hemorrhage patients) and 21 rat brains were included in our study. CSF samples were quantified using a commercially available ELISA system. Results were analyzed statistically using SPSS 22, performing Spearman Rho correlation and ANOVA with Dunnett's post hoc analysis. Rat brains were investigated via immunofluorescence to determine SP-G presence and colocalization with common markers like aquaporin-4, glial fibrillary acidic protein, platelet endothelial adhesion molecule 1, and neuronal nuclear antigen. SP-G occurs associated with brain vessels, comparable to other conventional SPs, and is present in a set of cortical neurons. SP-G is furthermore actively produced by ependymal and choroid plexus epithelium and secreted into the cerebrospinal fluid. Its concentrations are low in control subjects and patients suffering from aqueductal stenosis, higher in normal pressure hydrocephalus (p < 0.01), and highest in infections of the central nervous system and brain hemorrhage (p < 0.001). Interestingly, SP-G did correlate with total CSF protein in patients with CNS infections and hemorrhage, but not with cell count. Based on the changes in CSF levels of SP-G in hydrocephalus, brain hemorrhage, and CNS infections as well as its abundance at CSF flow-related anatomical structures closely associated with immunological barrier systems, importance for CSF rheology, brain waste clearance, and host defense is assumable. Thus, SP-G is a potential new CSF biomarker, possibly not only reflecting aspects of CNS innate immune responses, but also rheo-dynamically relevant changes of CSF composition, associated with CSF malabsorbtion. However, further studies are warranted to validate our findings and increase insight into the physiological importance of SP-G in the CNS.

Hydrocephalus in aqueductal stenosis--a retrospective outcome analysis and proposal of subtype classification.

UNLABELLED: Treatment of aqueductal stenosis (AQS) has undergone several paradigm shifts during the past decades. Currently, endoscopic ventriculostomy (ETV) is recommended as treatment of choice. Several authors have addressed the issue of variable ETV success rates depending on age and pathogenetic factors. However, success rates have usually been defined as "ETV non-failure." The aim of the study was a retrospective analysis of radiological and neurological treatment response after ETV or VP-shunting (VPS) in age-dependent subtypes of AQS. PATIENTS AND METHODS: Eighty patients (median age 12.0 years, range 0-79 years) have been treated for MRI-proven aqueductal stenosis. Neurological treatment success was defined by neurological improvement and, in childhood, head circumference. Radiological response was measured as Evan's index in follow-up MRI. Initial signs and symptoms, type of surgery, and complications were analyzed. RESULTS: Four types of AQS have been defined with distinct age ranges and symptomatology: congenital type I (n = 24), chronic progressive (tectal tumor-like) type II (n = 23), acute type III (n = 10), and adult chronic (normal-pressure hydrocephalus-like) type IV (n = 23). Retrospective analysis of neurological and radiological outcome suggested that congenital type I (<1 years of age) may be more successfully treated with VPS than with ETV (81 vs. 50 %). Treatment of chronic juvenile type II (age 2-15) by ETV 19 % compared to 57 % after VP-shunt, but similar neurological improvement (>80 %). There has been no influence of persistent ventriculomegaly in type II after ETV in contrast to VPS therapy for neurological outcome. Adult acute type III (age > 15 years) responded excellent to ETV. Chronic type IV (iNPH-like) patients (age > 21) responded neurologically in 70 % after ETV and VPS, but radiological response was low (5 %). CONCLUSION: AQS can be divided into four distinct age groups and types in regards of clinical course and symptomatology. Depending on the AQS type, ETV cannot be unequivocally recommended. Congenital type I AQS may have a better neurological outcome with VP-shunt whereas acute type III offers excellent ETV results. Chronic progressive type II still requires prospective investigation of long-term ETV outcome, especially when ventriculomegaly persists. Late chronic type IV seems to result in similar outcome after VP-shunt and ETV.