Acute effects of intracranial hypertension and ARDS on pulmonary and neuronal damage: a randomized experimental study in pigs

Abstract PURPOSE: To determine reciprocal and synergistic effects of acute intracranial hypertension and ARDS on neuronal and pulmonary damage and to define possible mechanisms. METHODS: Twenty-eight mechanically ventilated pigs were randomized to four groups of seven each: control; acute intracranial hypertension (AICH); acute respiratory distress syndrome (ARDS); acute respiratory distress syndrome in combination with acute intracranial hypertension (ARDS + AICH). AICH was induced with an intracranial balloon catheter and the inflation volume was adjusted to keep intracranial pressure (ICP) at 30-40 cmH2O. ARDS was induced by oleic acid infusion. Respiratory function, hemodynamics, extravascular lung water index (ELWI), lung and brain computed tomography (CT) scans, as well as inflammatory mediators, S100B, and neuronal serum enolase (NSE) were measured over a 4-h period. Lung and brain tissue were collected and examined at the end of the experiment. RESULTS: In both healthy and injured lungs, AICH caused increases in NSE and TNF-alpha plasma concentrations, extravascular lung water, and lung density in CT, the extent of poorly aerated (dystelectatic) and atelectatic lung regions, and an increase in the brain tissue water content. ARDS and AICH in combination induced damage in the hippocampus and decreased density in brain CT. CONCLUSIONS: AICH induces lung injury and also exacerbates pre-existing damage. Increased extravascular lung water is an early marker. ARDS has a detrimental effect on the brain and acts synergistically with intracranial hypertension to cause histological hippocampal damage

The Swedish Malignant Middle cerebral artery Infarction Study: Long-term results from a prospective study of hemicraniectomy combined with standardized neurointensive care

Hemicraniectomy in patients with malignant middle cerebral artery (mMCA) infarct may be life-saving. The long-term prognosis is unknown. Patients with mMCA infarct treated with hemicraniectomy between 1998 and 2002 at three hospitals were included. The criterion for surgical intervention was if the patients deteriorated from awake to being responding to painful stimuli only. All patients were followed for at least 1 year. Outcome was defined as alive/dead, walkers/non-walkers or modified Rankin Scale (mRS) score <= 2. Thirty patients were included (median age at stroke onset 49 years, range 17-67 years). Fourteen patients had mMCA infarct on the left side and 16 patients on the right side. Fourteen patients had pupil dilatation before surgery. Hemicraniectomy was performed at a median of 52 h (range 13-235 h) after stroke onset. Nine patients died within 1 month after surgery because of cerebral herniation (n = 6), myocardial infarction (n = 1) or intensive care complications (n = 2). No further deaths occurred during follow-up, which was at median 3.4 years after surgery. Status for the 21 survivors at the last follow-up was: mRS 2 or less (n = 6) and mRS 3-5 (n = 15). The oldest patient with mRS 2 or less was 53 years at stroke onset. Thirteen patients (43%) could walk without substantial aid. The long-term survival after mMCA infarction treated with hemicraniectomy seems to be favourable if the patient survives the acute phase. The outcome as measured with mRS may be better among younger patients

Disease Tracking Markers for Alzheimer's Disease at the Prodromal (MCI) Stage

Older persons with Mild Cognitive Impairment (MCI) feature neurobiological Alzheimer's Disease (AD) in 50% to 70% of the cases and develop dementia within the next 5 to 7 years. Current evidence suggests that biochemical, neuroimaging, electrophysiological, and neuropsychological markers can track the disease over time since the MCI stage (also called prodromal AD). The amount of evidence supporting their validity is of variable strength. We have reviewed the current literature and categorized evidence of validity into three classes: Class A, availability of multiple serial studies; Class B a single serial study or multiple cross sectional studies of patients with increasing disease severity from MCI to probable AD; and class C, multiple cross sectional studies of patients in the dementia stage, not including the MCI stage. Several Class A studies suggest that episodic memory and semantic fluency are the most reliable neuropsychological markers of progression. Hippocampal atrophy, ventricular volume and whole brain atrophy are structural MRI markers with class A evidence. Resting-state fMRI and connectivity, and diffusion MR markers in the medial temporal white matter (parahippocampus and posterior cingulum) and hippocampus are promising but require further validation. Change in amyloid load in MCI patients warrant further investigations, e.g. over longer period of time, to assess its value as marker of disease progression. Several spectral markers of resting state EEG rhythms that might reflect neurodegenerative processes in the prodromal stage of AD (EEG power density, functional coupling, spectral coherence, and synchronization) suffer from lack of appropriately designed studies. Although serial studies on late event-related potentials (ERPs) in healthy elders or MCI patients are inconclusive, others tracking disease progression and effects of cholinesterase inhibiting drugs in AD, and cross-sectional including MCI or predicting development of AD offer preliminary evidence of validity as a marker of disease progression from the MCI stage. CSF Markers, such as A beta(1-42), t-tau and p-tau are valuable markers which support the clinical diagnosis of Alzheimer's disease. However, these markers are not sensitive to disease progression and cannot be used to monitor the severity of Alzheimer's disease. For Isoprostane F2 some evidence exists that its increase correlates with the progression and the severity of AD. RI Jovicich, Jorge/D-2293-201

NSE and S100 after hypoxia in the newborn pig

Perinatal asphyxia is an important cause of neonatal morbidity and mortality. There is the potential to halt cerebral damage if neural rescue strategies are applied within a short period of time after an insult. It is therefore important to be able to accurately identify neonates who may benefit from neural rescue therapies. Recent studies in asphyxiated neonates have correlated S100B and NSE with outcome; however, interpretation of these studies were difficult, as the timing of the measurements were not consistent. We measured NSE and S100 in I-d-old piglets after a mild or severe hypoxic insult. Measurements were performed at 6-72 h after the insult and correlated with histologic outcome. There were no differences of the NSE or S100 concentrations between controls and the mild hypoxia group. After 24 h, there was a significant difference of NSE between the control/mild insult group and severe insult group. After 48 h, the S100 concentrations were significantly different between the control/ mild insult group and the severe insult group. Both proteins showed good correlation at these time points with outcome as measured by histology score at 72 h. In conclusion, NSE and S100B measured in the serum of piglets after hypoxia increased significantly and correlated with outcome. This increase occurs too late to be used within the first 24 h but might be helpful for the clinician in determining the timing of an insult