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Background: Hypotension is recognized as a potentially damaging secondary insult after traumatic brain injury. Systems to give clinical teams some early warning of likely hypotensive instability could be added to the range of existing techniques used in the management of this group of patients. By using the Edinburgh University Secondary Insult Grades (EUSIG) definitions for -hypotension (systolic arterial pressure <90 mmHg OR mean arterial -pressure <70 mmHg) we collected a group of ∼2,000 events by analyzing the Brain-IT database. We then constructed a Bayesian Artificial Neural Network (an advanced statistical modeling technique) that is able to provide some early warning when trained on this previously collected demographic and physiological data., Materials and Methods: Using EUSIG defined event data from the Brain-IT database, we identified a Bayesian artificial neural network (BANN) topology and constructed a series of datasets using a group of clinically guided input variables. This allowed us to train a BANN, which was then tested on an unseen set of patients from the Brain-IT database. The initial tests used a particularly harsh assessment criterion whereby a true positive prediction was only allowed if the BANN predicted an upcoming event to the exact minute. We have now developed the system to the point where it is about to be used in a two-stage Phase II clinical trial and we are also researching a more realistic assessment technique., Key Results: We have constructed a BANN that is able to provide early warning to the clinicians based on a model that uses information from the physiological inputs; systolic and mean arterial pressure and heart rate; and demographic variables age and gender. We use 15-min SubWindows starting at 15 and 30 min before an event and process mean, slope and standard deviations. Based on 10 simulation runs, our current sensitivity is 36.25% (SE 1.31) with a specificity of 90.82% (SE 0.85). Initial results from a Phase I clinical study shows a model sensitivity of 40.95% (SE 6%) and specificity of 86.46% (SE 3%) Although this figure is low it is considered clinically useful for this dangerous condition, provided the false positive rate can be kept sufficiently low as to be practical in an intensive care environment., Conclusion: We have shown that using advanced statistical modeling techniques can provide clinical teams with useful information that will assist clinical care.

Background: Hypotension is a recognized -secondary insult after traumatic brain injury (TBI). There are many definitions of hypotension, an often cited example being the Brain Trauma Foundation's current (2007) "Guidelines for the Management of Severe Traumatic Brain Injury," which defines hypotension as systolic pressure <90 mmHg. However, this same document declares "The importance of mean arterial pressure, as opposed to systolic pressure should also be stressed, …." Our work shows that when using the Edinburgh University Secondary Insult Grades (EUSIG) definitions, which require monitoring of both systolic and mean arterial pressures, that most hypotensive events are in fact triggered by a breach of the mean arterial level of 70 mmHg. We suggest that close monitoring of mean arterial pressure would enable clinical teams to avoid more potentially damaging hypotensive events., Materials and Methods: An analysis of 100 patients from the Brain-IT database was performed. Using the EUSIG definitions, 2,081 events can be obtained by analyzing the systolic and mean blood pressures on a minute by minute basis. A software program was written to identify and classify the trigger pattern for each event. A categorical analysis of these triggering patterns has been carried out., Key Results: Our analysis shows that most events are triggered by a drop in mean arterial pressure. In fact a large number of events (91%) occur where the mean arterial pressure is below the threshold limits whereas the systolic pressure does not cross the 90 mmHg limit at all., Conclusion: We suggest that more emphasis should be placed on closely monitoring mean arterial pressure as well as systolic pressure when trying to guard against hypotensive problems in traumatically brain injured patients. In future work we will study the underlying physiological mechanisms and attempt to further classify concomitant conditions that may be contributing to the onset of a hypotensive event.

Background: The BrainIT group works collaboratively on developing standards for collection and analyses of data from brain injured patients towards providing a more efficient infrastructure for assessing new health technology., Materials and Methods: Over a 2 year period, core dataset data (grouped by nine categories) were collected from 200 head-injured patients by local nursing staff. Data were uploaded by the BrainIT web and random samples of received data were selected automatically by computer for validation by data validation (DV) research nurse staff against gold standard sources held in the local centre. Validated data was compared with original data sent and percentage error rates calculated by data category., Findings: Comparisons, 19,461, were made in proportion to the size of the data received with the largest number checked in laboratory data (5,667) and the least in the surgery data (567). Error rates were generally less than or equal to 6%, the exception being the surgery data class where an unacceptably high error rate of 34% was found., Conclusions: The BrainIT core dataset (with the exception of the surgery classification) is feasible and accurate to collect. The surgery classification needs to be revised.

Background: The BrainIT project was conceived in 1997 and has grown into an international collaboration with the purpose of gathering high time resolution data from head injured patients utilising standardised methodologies., Materials and Methods: From 1998, 22 participating neuroscience centres collected three main types of information: demographic, physiological data and clinical treatment information. A data collection solution was provided for each centre dependent on their existing facilities and data were collected for the duration of monitoring as defined by the routine care in each centre. On completion of ICP monitoring all personal information was removed and then transferred to Glasgow via the internet where it was converted into a standard format and entered into a central database. Outcome was measured using the extended Glasgow Outcome Score using an interview questionnaire., Findings: Data has been obtained from a total of 349 patients (277 male and 72 female) The age of these patients ranged from 1 to 87 years (median 31); 145 had been involved in a traffic accident and 32 were pedestrians; 78 had suffered a fall; 24 were assaulted and the remaining 70 of other causes. A large amount of physiological data was collected (e.g. BP 2,531 days, ICP 2,212 days in total). This dataset has provided the opportunity to perform unique analysis and these include the statistical features of blood pressure, diurnal variations in ICP, optimal sampling rate determination and a comparison of summary measures of secondary insults., Conclusions: This challenging collaboration has brought together a large number of centres and developed a successful clinical research network focussed on improving the treatment of head injured patients. It has successfully collected a vast quantity of high quality data that provides a rich source for analysis and hypothesis testing.

Introduction: Intraventricular hemorrhage (IVH), either independent of or as an extension of intracranial bleed, is thought to carry a grave prognosis. Although the effect of IVH on outcome in patients with subarachnoid hemorrhage has been extensively reviewed in the literature, reports of spontaneous intracerebral hemorrhage (ICH) in similar situations have been infrequent. The association of hydrocephalus in such situations and its influence on outcome is also uncertain., Patients and Methods: As a sub-analysis of data obtained through the international Surgical Trial in Intracerebral Hemorrhage (STICH), the impact of IVH, with or without the presence of hydrocephalus, on outcome in patients with spontaneous ICH was analyzed. CT scans of randomized patients were examined for IVH and/or hydrocephalus. Other characteristics of hematoma were evaluated to see if they influenced outcome, as defined by the STICH protocol., Results: Favorable outcomes were more frequent when IVH was absent (31.4% vs. 15.1%; p < 0.00001). The presence of hydrocephalus lowered the likelihood of favorable outcome still further to 11.5% (p = 0.031). In patients with IVH, early surgical intervention had a more favorable outcome (17.8%) compared to initial conservative management (12.4%) (p = 0.141)., Conclusion: The presence of IVH and hydrocephalus are independent predictors of poor outcome in spontaneous ICH. Early surgery is of some benefit in those with IVH.

Introduction: Of all forms of stroke, spontaneous intracerebral haemorrhage (ICH) causes the highest morbidity and mortality. The Surgical Trial in Intracerebral Haemorrhage (STICH) found no difference in outcomes between patients randomized to surgical or conservative treatment., Patients and Methods: Of 530 patients randomized to initial conservative treatment, 140 crossed over to surgery. This study examines the variables associated with crossover., Results: Dominant features of the crossover group were: male, (p = 0.04), right-sided clot (p = 0.03), lobar clot (p = 0.003), clot volume (median 64 mL for crossovers vs. 38 mL for others, p < 0.00001), midline shift (median 6 mm for crossovers vs. 3 mm for others, p < 0.00001), superficial clot (median 1.3 mm for crossovers vs. 11.5 mm for others, p < 0.00001), and randomization within 12 hours of ictus (p < 0.0005). Thalamic location (p = 0.002) was under-represented. Intraventricular haemorrhage, hydrocephalus, and focal deficits were not associated with crossover. Craniotomy was the method of evacuation in 85% of crossover patients., Conclusions: Crossover to surgery was more likely when ICH had these features: Right side, lobar location, superficial, large volume, big shift, and early randomization. Crossovers formed a worse prognostic group compared to non-crossovers. Surgery did not affect trial results, which were analyzed by intention-to-treat.

Sixty-two patients with a spontaneous supratentorial haemorrhage had continuous Intracranial Pressure (ICP) and Cerebral Perfusion Pressure (CPP) monitoring. In addition to the recordings of physiological data their past medical history, presenting neurological state, Computed Tomograph (CT) findings, daily Glasgow Coma Score (GCS) and outcome were noted. The mean age was 57.6 years (sd 13.3). Onset of recording, after ictus was at a mean of 32.6 hours (sd 26.0). Average length of recording was 62.0 hours (sd 39.8). Thirty-one patients had evacuation of haematoma, 6 insertion of External Ventricular Drain (EVD). Preoperative measures of ICP were significantly related to delayed neurological deterioration, death within three days and Glasgow Outcome Scale (GOS) at neurosurgical discharge. No such relationships existed with preoperative measures of CPP and neither ICP nor CPP was related to outcome at 6 months. Post-operative measures of both ICP and CPP demonstrated a significant relationship with death within three days of ictus and GOS at neurosurgical discharge. Again no relationship existed with these parameters and outcome at six months. Surgical evacuation of haematoma acted to significantly reduce ICP and improve CPP. Given that these factors seem to be related to deterioration, death and early outcome, it would seem that surgery could play a role in reducing mortality and improving outcome following Intra cerebral Haemorrhage (ICH).

Cerebral ischaemia and reperfusion injury may be exacerbated by leukocyte recruitment and activation. Adhesion molecules play a pivotal role in leukocyte recruitment. We report a prospective study of the potential role of the selectin family of adhesion molecules (E-, P- and L-selectin) in delayed cerebral ischaemia (DID) following aneurysmal subarachnoid haemorrhage. In patients with good grade SAH, we have compared serum concentrations of E-, P- and L-selectin, between patients who do, and do not develop delayed cerebral ischaemia. There was no difference in E-selectin concentration between the two groups (44.0 ng/ml vs. 37.4 ng/ml). Serum P-selectin concentration was significantly higher in patients with DID compared to those patients without DID (149.5 ng/ml vs. 112.9 ng/ml, p = 0.039). Serum L-selectin concentrations were significantly lower in patients with DID (633.8 ng/ml vs 897.9 ng/ml, p = 0.013). We conclude that P- and L-selectin are involved in the pathogenesis of DID following aneurysmal subarachnoid haemorrhage. The results of this study do not elucidate the exact role of each selectin in DID.