Optimal intraventricular hemorrhage volume cutoff for predicting poor outcome in patients with intracerebral hemorrhage.

BACKGROUND AND OBJECTIVES: The prognosis of patients with spontaneous intracerebral hemorrhage (ICH) is often influenced by hematoma volume, a well-established predictor of poor outcome. However, the optimal intraventricular hemorrhage (IVH) volume cutoff for predicting poor outcome remains unknown. METHODS: We analyzed 313 patients with spontaneous ICH not undergoing evacuation, including 7 cases with external ventricular drainage (EVD). These patients underwent a baseline CT scan, followed by a 24-hour CT scan for measurement of both hematoma and IVH volume. We defined hematoma growth as hematoma growth > 33 % or 6 mL at follow-up CT, and poor outcome as modified Rankin Scale score≥3 at three months. Cutoffs with optimal sensitivity and specificity for predicting poor outcome were identified using receiver operating curves. RESULTS: The receiver operating characteristic analysis identified 6 mL as the optimal cutoff for predicting poor outcome. IVH volume> 6 mL was observed in 53 (16.9 %) of 313 patients. Patients with IVH volume>6 mL were more likely to be older and had higher NIHSS score and lower GCS score than those without. IVH volume>6 mL (adjusted OR 2.43, 95 % CI 1.13-5.30; P = 0.026) was found to be an independent predictor of poor clinical outcome at three months in multivariable regression analysis. CONCLUSIONS: Optimal IVH volume cutoff represents a powerful tool for improving the prediction of poor outcome in patients with ICH, particularly in the absence of clot evacuation or common use of EVD. Small amounts of intraventricular blood are not independently associated with poor outcome in patients with intracerebral hemorrhage. The utilization of optimal IVH volume cutoffs may improve the clinical trial design by targeting ICH patients that will obtain maximal benefit from therapies.

Multicenter Validation of the max-ICH Score in Intracerebral Hemorrhage.

OBJECTIVE: Outcome prognostication unbiased by early care limitations (ECL) is essential for guiding treatment in patients presenting with intracerebral hemorrhage (ICH). The aim of this study was to determine whether the max-ICH (maximally treated ICH) Score provides improved and clinically useful prognostic estimation of functional long-term outcomes after ICH. METHODS: This multicenter validation study compared the prognostication of the max-ICH Score versus the ICH Score regarding diagnostic accuracy (discrimination and calibration) and clinical utility using decision curve analysis. We performed a joint investigation of individual participant data of consecutive spontaneous ICH patients (n = 4,677) from 2 retrospective German-wide studies (RETRACE I + II; anticoagulation-associated ICH only) conducted at 22 participating centers, one German prospective single-center study (UKER-ICH; nonanticoagulation-associated ICH only), and 1 US-based prospective longitudinal single-center study (MGH; both anticoagulation- and nonanticoagulation-associated ICH), treated between January 2006 and December 2015. RESULTS: Of 4,677 included ICH patients, 1,017 (21.7%) were affected by ECL (German cohort: 15.6% [440 of 2,377]; MGH: 31.0% [577 of 1,283]). Validation of long-term functional outcome prognostication by the max-ICH Score provided good and superior discrimination in patients without ECL compared with the ICH Score (area under the receiver operating curve [AUROC], German cohort: 0.81 [0.78-0.83] vs 0.74 [0.72-0.77], p < 0.01; MGH: 0.85 [0.81-0.89] vs 0.78 [0.74-0.82], p < 0.01), and for the entire cohort (AUROC, German cohort: 0.84 [0.82-0.86] vs 0.80 [0.77-0.82], p < 0.01; MGH: 0.83 [0.81-0.85] vs 0.77 [0.75-0.79], p < 0.01). Both scores showed no evidence of poor calibration. The clinical utility investigated by decision curve analysis showed, at high threshold probabilities (0.8, aiming to avoid false-positive poor outcome attribution), that the max-ICH Score provided a clinical net benefit compared with the ICH Score (14.1 vs 2.1 net predicted poor outcomes per 100 patients). INTERPRETATION: The max-ICH Score provides valid and improved prognostication of functional outcome after ICH. The associated clinical net benefit in minimizing false poor outcome attribution might potentially prevent unwarranted care limitations in patients with ICH. ANN NEUROL 2021;89:474-484.

Neonatal Cranial Ultrasound Findings among Infants Born Extremely Preterm: Associations with Neurodevelopmental Outcomes at 10 Years of Age.

OBJECTIVE: To examine the association between neonatal cranial ultrasound (CUS) abnormalities among infants born extremely preterm and neurodevelopmental outcomes at 10 years of age. STUDY DESIGN: In a multicenter birth cohort of infants born at <28 weeks of gestation, 889 of 1198 survivors were evaluated for neurologic, cognitive, and behavioral outcomes at 10 years of age. Sonographic markers of white matter damage (WMD) included echolucencies in the brain parenchyma and moderate to severe ventricular enlargement. Neonatal CUS findings were classified as intraventricular hemorrhage (IVH) without WMD, IVH with WMD, WMD without IVH, and neither IVH nor WMD. RESULTS: WMD without IVH was associated with an increased risk of cognitive impairment (OR 3.5, 95% CI 1.7, 7.4), cerebral palsy (OR 14.3, 95% CI 6.5, 31.5), and epilepsy (OR 6.9; 95% CI 2.9, 16.8). Similar associations were found for WMD accompanied by IVH. Isolated IVH was not significantly associated these outcomes. CONCLUSIONS: Among children born extremely preterm, CUS abnormalities, particularly those indicative of WMD, are predictive of neurodevelopmental impairments at 10 years of age. The strongest associations were found with cerebral palsy.

Long-Term Outcomes after Severe Traumatic Brain Injury in Older Adults. A Registry-based Cohort Study.

Rationale: Older adults (≥65 yr old) account for an increasing proportion of patients with severe traumatic brain injury (TBI), yet clinical trials and outcome studies contain relatively few of these patients.Objectives: To determine functional status 6 months after severe TBI in older adults, changes in this status over 2 years, and outcome covariates.Methods: This was a registry-based cohort study of older adults who were admitted to hospitals in Victoria, Australia, between 2007 and 2016 with severe TBI. Functional status was assessed with Glasgow Outcome Scale Extended (GOSE) 6, 12, and 24 months after injury. Cohort subgroups were defined by admission to an ICU. Features associated with functional outcome were assessed from the ICU subgroup.Measurements and Main Results: The study included 540 older adults who had been hospitalized with severe TBI over the 10-year period; 428 (79%) patients died in hospital, and 456 (84%) died 6 months after injury. There were 277 patients who had not been admitted to an ICU; at 6 months, 268 (97%) had died, 8 (3%) were dependent (GOSE 2-4), and 1 (0.4%) was functionally independent (GOSE 5-8). There were 263 patients who had been admitted to an ICU; at 6 months, 188 (73%) had died, 39 (15%) were dependent, and 32 (12%) were functionally independent. These proportions did not change over longer follow-up. The only clinical features associated with a lower rate of functional independence were Injury Severity Score ≥25 (adjusted odds ratio, 0.24 [95% confidence interval, 0.09-0.67]; P = 0.007) and older age groups (P = 0.017).Conclusions: Severe TBI in older adults is a condition with very high mortality, and few recover to functional independence.

Reactive microglia and astrocytes in neonatal intraventricular hemorrhage model are blocked by mesenchymal stem cells.

Severe intraventricular hemorrhage (IVH) in premature infants triggers reactive gliosis, causing acute neuronal death and glial scar formation. Transplantation of mesenchymal stem cells (MSCs) has often showed improved CNS recovery in an IVH model, but whether this response is related to reactive glial cells is still unclear. Herein, we suggest that MSCs impede the response of reactive microglia rather than astrocytes, thereby blocking neuronal damage. Astrocytes alone showed mild reactiveness under hemorrhagic conditions mimicked by thrombin treatment, and this was not blocked by MSC-conditioned medium (MSC-CM) in vitro. In contrast, thrombin-induced microglial activation and release of proinflammatory cytokines were inhibited by MSC-CM. Interestingly, astrocytes showed greater reactive response when co-cultured with microglia, and this was abolished in the presence of MSC-CM. Gene expression profiles in microglia revealed that transcript levels of genes for immune response and proinflammatory cytokines were altered by thrombin treatment. This result coincided with the robust phosphorylation of STAT1 and p38 MAPK, which might be responsible for the production and release of proinflammatory cytokines. Furthermore, application of MSC-CM diminished thrombin-mediated phosphorylation of STAT1 and p38 MAPK, supporting the acute anti-inflammatory role of MSCs under hemorrhagic conditions. In line with this, activation of microglia and consequent cytokine release were impaired in Stat1-null mice. However, reactive response in Stat1-deficient astrocytes was maintained. Taken together, our results demonstrate that MSCs mainly block the activation of microglia involving STAT1-mediated cytokine release and subsequent reduction of reactive astrocytes.

Influence of the Extent of Intraventricular Hemorrhage on Functional Outcome and Mortality in Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVE: Intraventricular hemorrhage (IVH) is a verified independent prognostic parameter in patients with intracerebral hemorrhage (ICH). However, the impact of the extent of IVH on clinical outcomes is unestablished. METHODS: We analyzed 1,112 consecutive primary ICH patients of the UKER-ICH cohort (NCT03183167) and hypothesized that there is no difference in outcome between patients without IVH and patients with minor IVH not leading to obstructive hydrocephalus. Propensity score matching and multivariable analyses were performed to account for imbalances in baseline characteristics. Primary outcome was defined as functional outcome 3 months after ICH -assessed using the modified Rankin Scale (mRS) dichotomized into favorable (mRS = 0-3) and unfavorable outcome (mRS = 4-6). Secondary outcomes included mortality at 3  months and a Graeb score-based threshold analysis for association of the extent of IVH with unfavorable clinical outcome. RESULTS: Among the 461 out of 1,112 (41.5%) ICH patients with IVH, 191 out of 461 (41.4%) showed IVH without obstructive hydrocephalus and no requirement of external ventricular drain (EVD) placement. After adjusting for baseline imbalances we found no difference in functional outcome at 3 months between patients without IVH (No-IVH) and patients with IVH not requiring EVD (IVH-w/o-EVD): mRS 0-3: No-IVH 64/161 (39.8%) vs. IVH-w/o-EVD 53/170 (31.2%); p = 0.103. However, there was a trend toward a higher mortality in IVH-w/o-EVD patients (mRS 6: No IVH 40/161 [24.8%] vs. IVH-w/o-EVD 57/170 [33.5%]; p = 0.083). Multivariable analysis revealed that a Graeb score >2 was independently associated with unfavorable outcome (mRS 4-6: OR 3.16 [1.54-6.48]; p = 0.002), and higher mortality (mRS 6: OR 2.57 [1.40-4.74]; p = 0.002) in IVH patients. CONCLUSIONS: Small amounts of intraventricular blood (Graeb score ≤2) not leading to obstructive hydrocephalus are not associated with unfavorable outcome or death after ICH. Thus, IVH per se should not be considered a binary variable in outcome prediction for ICH patients.

Intraventricular hemorrhage and posthemorrhagic hydrocephalus in preterm infants: diagnosis, classification, and treatment options.

PURPOSE: Intraventricular hemorrhage is the most important adverse neurologic event for preterm and very low weight birth infants in the neonatal period. This pathology can lead to various delays in motor, language, and cognition development. The aim of this article is to give an overview of the knowledge in diagnosis, classification, and treatment options of this pathology. METHOD: A systematic review has been made. RESULTS: The cranial ultrasound can be used to identify the hemorrhage and grade it according to the modified Papile grading system. There is no standardized protocol of intervention as there are controversial results on which of the temporizing neurosurgical procedures is best and about the appropriate parameters to consider a conversion to ventriculoperitoneal shunt. However, it has been established that the most important prognosis factor is the involvement and damage of the white matter. CONCLUSION: More evidence is required to create a standardized protocol that can ensure the best possible outcome for these patients.

Feasibility and Safety of Transnasal High Flow Air to Reduce Core Body Temperature in Febrile Neurocritical Care Patients: A Pilot Study.

BACKGROUND: Fever is an important determinant of prognosis following acute brain injury. Current non-pharmacologic techniques to reduce fever are limited and induce a shivering response. We investigated the safety and efficacy of a novel transnasal unidirectional high flow air device in reducing core body temperature in the neurocritical care unit (NCCU) setting. METHODS: This pilot study included seven consecutive patients in the NCCU who were febrile (> 37.5 °C) for > 24 h despite standard non-pharmacologic and first-line antipyretic agents. Medical grade high flow air was delivered transnasally using a standard continuous positive airway pressure machine with a positive pressure of 20 cmH2O for 2 h. Core esophageal and tympanic temperature were continuously monitored. RESULTS: Mean age was 40 ± 14 yo, and 72% (5/7 patients) were men. Five patients had intracerebral or intraventricular hemorrhage, one subject had transverse myelitis, and the remaining patient had anoxic brain injury due to a cardiac arrest. After 2 h of cooling, core temperature was significantly lower than the baseline pre-cooling temperature (37.3 ± 0.5 °C vs. 38.4 ± 0.6 °C; p < 0.002). Mean transnasal airflow rate was 57.5 ± 6.5 liters per minute. Five of the seven subjects were normothermic at the end of the 2-h period. One subject with severe hyperthermia (39.7 °C) and the other with multiple interruptions to therapy due to technical reasons did not cool. The core temperature within 30 min of cessation of airflow increased and was similar to the pre-cooling baseline temperature (38.3 ± 0.4 °C vs. 38.4 ± 0.6 °C, p = NS). Rate of core cooling was 0.6 ± 0.15 °C per hour at this flow rate. No shivering response was observed. No protocol-related adverse events occurred. CONCLUSIONS: High flow transnasal air in a unidirectional fashion lowers core body temperature in febrile patients in the NCCU setting. No adverse events were seen, and the process showed no signs of shivering or any other serious side effects during short-term exposure. This pilot study should inform further investigation.

Stem Cells for Extreme Prematurity.

Regenerative medicine is a bourgeoning field promising to repair damaged organs and thus has created high hopes in neonatology to curb some of the complications due to extreme preterm birth. Extensive laboratory investigations over the past 15 years have tried to harness the regenerative potential of a variety of (stem) cell-based therapies. Most preclinical studies have focused on experimental neonatal lung and brain injury. These promising results lead to the initiation of phase I clinical trials for chronic lung disease of prematurity and severe intraventricular hemorrhage, two of the most devastating complications of extreme preterm birth. Despite this relative rapid clinical translation, major gaps persist in our understanding of the biology of these putative repair cells and our ability to predict the quality and thus the efficacy of the cell product. This review will provide a brief overview of the various cell-based therapies that have been investigated in experimental neonatal lung injury and the remaining challenges in utilizing these new, disruptive therapies to their full extend to realize the promise of regenerative medicine in neonatology.

Isolated cervical anterior spinal artery aneurysm: case report.

Isolated cervical anterior spinal artery (CASA) aneurysms are extremely rare with most of them mostly associated with arteriovenous malformation. The underlying pathology is not known but some factors leading to the aneurysm are inflammatory, infection and connective tissue disorders. Trauma with formation of pseudoaneurysm has also been reported. We report a case which presented with fourth ventricle bleed and was managed successfully with conservative treatment.

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial.

BACKGROUND: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. METHODS: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. FINDINGS: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88-1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90-1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41-0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22-3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31-0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64-0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37-3·91], p=0·771) was similar. INTERPRETATION: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status. FUNDING: National Institute of Neurological Disorders and Stroke.

Behavioral Organization in Infants with Intraventricular Hemorrhage: Characteristics and Clinical Implications.

PURPOSE: This study examined the neurobehavioral functioning in preterm infants diagnosed with intraventricular hemorrhage (IVH) grades III and IV, using the Assessment of Preterm Infants' Behavior (APIB). DESIGN AND SAMPLE: The APIB was completed on nine infants with IVH III/IV at 36 and 40weeks postmenstrual age to determine the effects of IVH on the neurobehavioral functioning and maturation over time. The APIB neurobehavioral scores (i.e., physiologic, motor, state, attention/interaction, regulatory, and examiner facilitation subsystem scores) were examined in relation to the two different testing times and to infants without lesion. RESULTS: APIB scores at 36weeks suggested easily disorganized and poorly modulated behavioral regulation and low threshold of disorganization and stress. At 40 weeks, poor overall behavioral regulation persisted; only motor differences statistically improved between the two ages. Neurobehavior was significantly poor in all but state subsystems when tested at both ages in infants with a brain lesion.

Optimized Flat-Detector CT in Stroke Imaging: Ready for First-Line Use?

BACKGROUND: Using flat-detector CT (FD-CT) for stroke imaging has the advantage that both diagnostic imaging and endovascular therapy can be performed directly within the Angio Suite without any patient transfer and time delay. Thus, stroke management could be speeded up significantly, and patient outcome might be improved. But as precondition for using FD-CT as primary imaging modality, a reliable exclusion of intracranial hemorrhage (ICH) has to be possible. This study aimed to investigate whether optimized native FD-CT, using a newly implemented reconstruction algorithm, may reliably detect ICH in stroke patients. Additionally, the potential to identify ischemic changes was evaluated. METHODS: Cranial FD-CT scans were obtained in 102 patients presenting with acute ischemic stroke (n = 32), ICH (n = 45) or transient ischemic attack (n = 25). All scans were reconstructed with a newly implemented half-scan cone-beam algorithm. Two experienced neuroradiologists, unaware of clinical findings, evaluated independently the FD-CTs screening for hemorrhage or ischemic signs. The findings were correlated to CT, and rater and inter-rater agreement was assessed. RESULTS: FD-CT demonstrated high sensitivity (95-100%) and specificity (100%) in detecting intracerebral and intraventricular hemorrhage (IVH). Overall, interobserver agreement (κ = 0.92) was almost perfect and rater agreement to CT highly significant (r = 0.81). One infratentorial ICH and 10 or 11 of 22 subarachnoid hemorrhages (SAHs) were missed of whom 7 were perimesencephalic. The sensitivity for detecting acute ischemic signs was poor in blinded readings (0 or 25%, respectively). CONCLUSIONS: Optimized FD-CT, using a newly implemented reconstruction algorithm, turned out as a reliable tool for detecting supratentorial ICH and IVH. However, detection of infratentorial ICH and perimesencephalic SAH is limited. The potential of FD-CT in detecting ischemic changes is poor in blinded readings. Thus, plain FD-CT seems insufficient as a standalone modality in acute stroke, but within a multimodal imaging approach primarily using the FD technology, native FD-CT seems capable to exclude reliably supratentorial hemorrhage. Currently, FD-CT imaging seems not yet ready for wide adoption, replacing regular CT, and should be reserved for selected patients. Furthermore, prospective evaluations are necessary to validate this approach in the clinical setting.

Factors Associated with the Need for Intensive Care Unit Admission Following Supratentorial Intracerebral Hemorrhage: The Triage ICH Model.

BACKGROUND: Providing the correct level of care for patients with intracerebral hemorrhage (ICH) is crucial, but the level of care needed at initial presentation may not be clear. This study evaluated factors associated with admission to intensive care unit (ICU) level of care. METHODS: This is an observational study of all adult patients admitted to our institution with non-traumatic supratentorial ICH presenting within 72 h of symptom onset between 2009-2012 (derivation cohort) and 2005-2008 (validation cohort). Factors associated with neuroscience ICU admission were identified via logistic regression analysis, from which a triage model was derived, refined, and retrospectively validated. RESULTS: For the derivation cohort, 229 patients were included, of whom 70 patients (31 %) required ICU care. Predictors of neuroscience ICU admission were: younger age [odds ratio (OR) 0.94, 95 % CI 0.91-0.97; p = 0.0004], lower Full Outline of UnResponsiveness (FOUR) score (0.39, 0.28-0.54; p < 0.0001) or Glasgow Coma Scale (GCS) score (0.55, 0.45-0.67; p < 0.0001), and larger ICH volume (1.04, 1.03-1.06; p < 0.0001). The model was further refined with clinician input and the addition of intraventricular hemorrhage (IVH). GCS was chosen for the model rather than the FOUR score as it is more widely used. The proposed triage ICH model utilizes three variables: ICH volume ≥30 cc, GCS score <13, and IVH. The triage ICH model predicted the need for ICU admission with a sensitivity of 94.3 % in the derivation cohort [area under the curve (AUC) = 0.88; p < 0.001] and 97.8 % (AUC = 0.88) in the validation cohort. CONCLUSIONS: Presented are the derivation, refinement, and validation of the triage ICH model. This model requires prospective validation, but may be a useful tool to aid clinicians in determining the appropriate level of care at the time of initial presentation for a patient with a supratentorial ICH.

Primary Intraventricular Hemorrhage: Clinical Characteristics and Outcomes.

BACKGROUND: Primary intraventricular hemorrhage (IVH) in adults is a rare neurologic disorder. The typical course, etiology, complications, and outcomes have not been well established. MATERIALS AND METHODS: Consecutive patient records with a diagnosis of intracerebral hemorrhage admitted between May 2009 and June 2014 at a tertiary care center were retrospectively reviewed. Subjects were included in the study cohort if all neurologists and the radiology report agreed that the subject had an isolated IVH. Patients with intraparenchymal hemorrhage, subarachnoid hemorrhage, malignancy with hemorrhagic components, and hemorrhagic transformation of ischemic stroke were excluded. The electronic medical record, imaging report, and imaging studies were reviewed. FINDINGS: Of 1692 cases reviewed, 33 (1.9%) had primary IVH. The most common presenting symptoms included altered mental status (48.5%), headache, (39.4%), and nausea (24.2%). In 36.3%, hypertension was found to be a contributing factor; 27.2% were attributed solely to hypertension. Vascular abnormalities were the primary etiology in 21.3% of patients. When observing outcomes, 61.8% were discharged home or to rehab, whereas 20.5% died or were placed in hospice care. A higher Graeb score was associated with an increased likelihood of death or hospice (8 versus 5, P = .02) CONCLUSION: This study is one of few to describe the etiology, contributing factors, and outcomes of primary IVH. As in prior studies, hypertension was a contributing factor, and vascular lesions were less common than expected. More research is necessary to further define the course and characteristics of this rare type of intracerebral hemorrhage.

Intraventricular Hemorrhage in Premature Infants: A Historical Review.

Intraventricular hemorrhage (IVH) is common in premature newborns and poses a high risk for morbidity with lifelong disability. We searched the available literature for original and secondary literature regarding the epidemiology, pathogenesis, and treatment of IVH in order to trace changes in the management of this disease over time. We examined IVH pathogenesis and epidemiology and reviewed the history of medical and surgical treatment for intraventricular hemorrhage in preterm children. Initial medical management strategies aimed at correcting coagulopathy and eventually targeted mediators of perinatal instability including respiratory distress. Surgical management centered around cerebrospinal fluid diversion, initially through serial lumbar punctures, progressing to ventriculoperitoneal shunting, with more recent interventions addressing intraventricular clot burden. We provide a historical review of the evolution of treatment for IVH in newborns. While the management of IVH has grown significantly over time, IVH remains a common neurosurgical disease that continues to affect patient and caregiver quality of life and health care costs. Despite advances in treatment over more than a century, IVH remains a significant cause of morbidity and mortality in premature infants, and an understanding of past approaches may inform the development of new treatments.

Survival of Ventilated Extremely Premature Neonates With Severe Intraventricular Hemorrhage.

BACKGROUND: Severe intraventricular hemorrhage (IVH) is a leading mortality risk factor among extremely premature neonates. Because other life-threatening conditions also occur in this population, it is unclear whether severe IVH is independently associated with death. The existence and potential implications of regional variation in severe IVH-associated mortality are unknown. METHODS: We performed a retrospective cohort study of mechanically ventilated neonates born at 22 to 29 weeks' gestation who received care in 242 American NICUs between 2000 and 2014. After building groups composed of propensity score-matched and center-matched pairs, we used the Cox proportional hazards analysis to test our hypothesis that severe IVH would be associated with greater all-cause in-hospital mortality, defined as death before transfer or discharge. We also performed propensity score-matched subgroup analyses, comparing severe IVH-associated mortality among 4 geographic regions of the United States. RESULTS: In our analysis cohort, we identified 4679 patients with severe IVH. Among 2848 matched pairs, those with severe IVH were more likely to die compared with those without severe IVH (hazard ratio 2.79; 95% confidence interval 2.49-3.11). Among 1527 matched pairs still hospitalized at 30 days, severe IVH was associated with greater risk of death (hazard ratio 2.03; 95% confidence interval 1.47-2.80). Mortality associated with severe IVH varied substantially between geographic regions. CONCLUSIONS: The early diagnosis of severe IVH is independently associated with all-cause in-hospital mortality in extremely premature neonates. Regional variation in severe IVH-associated mortality suggests that shared decision-making between parents and neonatologists is strongly influenced by ultrasound-based IVH assessment and classification.

Mesenchymal stem cell therapy for intractable neonatal disorders.

Mesenchymal stem cell (MSC) transplantation has emerged as a new promising therapeutic strategy for the treatment of intractable and devastating neonatal disorders with complex multifactorial etiologies, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and hypoxic-ischemic encephalopathy (HIE). In response to inflammatory and noxious environments, MSCs secrete various paracrine factors that perform several reparative functions, including exerting anti-inflammatory, anti-oxidative, anti-apoptotic, and anti-fibrotic effects, to enhance the regeneration of damaged cells and tissues. In this review, we summarize recent advances in stem cell research focusing on the use of MSCs in the prevention and treatment of newborn BPD, IVH and HIE, with particular emphasis on preclinical and clinical data.