Traumatic Cerebral Microbleeds in the Subacute Phase Are Practical and Early Predictors of Abnormality of the Normal-Appearing White Matter in the Chronic Phase.

BACKGROUND AND PURPOSE: In the chronic phase after traumatic brain injury, DTI findings reflect WM integrity. DTI interpretation in the subacute phase is less straightforward. Microbleed evaluation with SWI is straightforward in both phases. We evaluated whether the microbleed concentration in the subacute phase is associated with the integrity of normal-appearing WM in the chronic phase. MATERIALS AND METHODS: Sixty of 211 consecutive patients 18 years of age or older admitted to our emergency department ≤24 hours after moderate to severe traumatic brain injury matched the selection criteria. Standardized 3T SWI, DTI, and T1WI were obtained 3 and 26 weeks after traumatic brain injury in 31 patients and 24 healthy volunteers. At baseline, microbleed concentrations were calculated. At follow-up, mean diffusivity (MD) was calculated in the normal-appearing WM in reference to the healthy volunteers (MDz). Through linear regression, we evaluated the relation between microbleed concentration and MDz in predefined structures. RESULTS: In the cerebral hemispheres, MDz at follow-up was independently associated with the microbleed concentration at baseline (left: B = 38.4 [95% CI 7.5-69.3], P = .017; right: B = 26.3 [95% CI 5.7-47.0], P = .014). No such relation was demonstrated in the central brain. MDz in the corpus callosum was independently associated with the microbleed concentration in the structures connected by WM tracts running through the corpus callosum (B = 20.0 [95% CI 24.8-75.2], P < .000). MDz in the central brain was independently associated with the microbleed concentration in the cerebral hemispheres (B = 25.7 [95% CI 3.9-47.5], P = .023). CONCLUSIONS: SWI-assessed microbleeds in the subacute phase are associated with DTI-based WM integrity in the chronic phase. These associations are found both within regions and between functionally connected regions.

Correction to: Safety and efficacy of Cerebrolysin in acute brain injury and neurorecovery: CAPTAIN I-a randomized, placebo-controlled, double-blind, Asian-Pacific trial.

The above article was published online with incorrect abbreviations in Figures 2 and 3 last sentence of the legend. HDA should be corrected to HADS.

Safety and efficacy of Cerebrolysin in acute brain injury and neurorecovery: CAPTAIN I-a randomized, placebo-controlled, double-blind, Asian-Pacific trial.

OBJECTIVE: To evaluate the safety and efficacy of Cerebrolysin as an add-on therapy to local standard treatment protocol in patients after moderate-to-severe traumatic brain injury. METHODS: The patients received the study medication in addition to standard care (50 mL of Cerebrolysin or physiological saline solution daily for 10 days, followed by two additional treatment cycles with 10 mL daily for 10 days) in a prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-centre phase IIIb/IV trial. The primary endpoint was a multidimensional ensemble of 14 outcome scales pooled to be analyzed by means of the multivariate, correlation-sensitive Wei-Lachin procedure. RESULTS: In 46 enrolled TBI patients (Cerebrolysin 22, placebo 24), three single outcomes showed stand-alone statistically significant superiority of Cerebrolysin [Stroop Word/Dots Interference (p = 0.0415, Mann-Whitney(MW) = 0.6816, 95% CI 0.51-0.86); Color Trails Tests 1 and 2 (p = 0.0223/0.0170, MW = 0.72/0.73, 95% CI 0.53-0.90/0.54-0.91), both effect sizes lying above the benchmark for "large" superiority (MW > 0.71)]. While for the primary multivariate ensemble, statistical significance was just missed in the intention-to-treat population (pWei-Lachin < 0.1, MWcombined = 0.63, 95% CI 0.48-0.77, derived standardized mean difference (SMD) 0.45, 95% CI -0.07 to 1.04, derived OR 2.1, 95% CI 0.89-5.95), the per-protocol analysis showed a statistical significant superiority of Cerebrolysin (pWei-Lachin = 0.0240, MWcombined = 0.69, 95% CI 0.53 to 0.85, derived SMD 0.69, 95% CI 0.09 to 1.47, derived OR 3.2, 95% CI 1.16 to 12.8), with effect sizes of six single outcomes lying above the benchmark for "large" superiority. Safety aspects were comparable to placebo. CONCLUSION: Our trial suggests beneficial effects of Cerebrolysin on outcome after TBI. Results should be confirmed by a larger RCT with a comparable multidimensional approach.

Health-related quality of life after mild, moderate and severe traumatic brain injury: patterns and predictors of suboptimal functioning during the first year after injury.

BACKGROUND: The Glasgow Outcome Scale Extended (GOSE) is the established functional outcome scale to assess disability following traumatic brain injury (TBI), however does not capture the patient's subjective perspective. Health-related quality of life (HRQL) does capture the individual's perception of disability after TBI, and has therefore been recognized as an important outcome in TBI. In contrast to GOSE, HRQL enables comparison of health outcome across various disease states and with healthy individuals. We aimed to assess functional outcome, HRQL, recovery, and predictors of 6 and 12-month outcome in a comprehensive sample of patients with mild, moderate or severe TBI, and to examine the relationship between functional impairment (GOSE) and HRQL. METHODS: A prospective cohort study was conducted among a sample of 2066 adult TBI patients who attended the emergency department (ED). GOSE was determined through questionnaires or structured interviews. Questionnaires 6 and 12 months after ED treatment included socio-demographic information and HRQL measured with Short-Form Health Survey (SF-36; reflecting physical, mental and social functioning) and Perceived Quality of Life Scale (PQoL; measuring degree of satisfaction with functioning). RESULTS: 996 TBI survivors with mild, moderate or severe TBI completed the 6-month questionnaire. Functional outcome and HRQL after moderate or severe TBI was significantly lower than after mild TBI. Patients with moderate TBI showed greatest improvement. After one year, the mild TBI group reached outcomes comparable to population norms. TBI of all severities highly affected SF-36 domains physical and social functioning, and physical and emotional role functioning. GOSE scores were highly related to all SF-36 domains and PQoL scores. Female gender, older age, co-morbidity and high ISS were strongest independent predictors of decreased HRQL at 6 and 12 months after TBI. CONCLUSIONS: HRQL and recovery patterns differ for mild, moderate and severe TBI. This study indicates that GOSE, although clinically relevant, fails to capture the subjective perspective of TBI patients, which endorses the use of HRQL as valuable addition to established instruments in assessing disability following TBI. Influence of TBI severity on recovery, together with female gender, older age, co-morbidity and high ISS should be considered in long-term follow-up and intervention programs.

The vegetative state/unresponsive wakefulness syndrome: a systematic review of prevalence studies.

One of the worst outcomes of acquired brain injury is the vegetative state, recently renamed 'unresponsive wakefulness syndrome' (VS/UWS). A patient in VS/UWS shows reflexive behaviour such as spontaneous eye opening and breathing, but no signs of awareness of the self or the environment. We performed a systematic review of VS/UWS prevalence studies and assessed their reliability. Medline, Embase, the Cochrane Library, CINAHL and PsycINFO were searched in April 2013 for cross-sectional point or period prevalence studies explicitly stating the prevalence of VS/UWS due to acute causes within the general population. We additionally checked bibliographies and consulted experts in the field to obtain 'grey data' like government reports. Relevant publications underwent quality assessment and data-extraction. We retrieved 1032 papers out of which 14 met the inclusion criteria. Prevalence figures varied from 0.2 to 6.1 VS/UWS patients per 100 000 members of the population. However, the publications' methodological quality differed substantially, in particular with regards to inclusion criteria and diagnosis verification. The reliability of VS/UWS prevalence figures is poor. Methodological flaws in available prevalence studies, the fact that 5/14 of the studies predate the identification of the minimally conscious state (MCS) as a distinct entity in 2002, and insufficient verification of included cases may lead to both overestimation and underestimation of the actual number of patients in VS/UWS.

Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To characterize the cerebrospinal fluid (CSF) concentrations of glial fibrillary acidic protein, neuron specific enolase (NSE), S-100ß, tau and neurofilament heavy chain (NFH) within 24 h of an acute traumatic spinal cord injury (SCI), and to correlate these concentrations with the baseline severity of neurologic impairment as graded by the American Spinal Injury Association impairment scale (AIS). METHODS: A lumbar puncture was performed to obtain CSF from 16 acute traumatic SCI patients within 24 h post injury. Neurological examinations were performed within 24 h of injury and again at 6 or 12 months post injury. The correlations between the CSF concentrations and initial AIS were calculated by using Pearson correlation coefficients. In addition, an independent Student's t-test was used to test for differences in CSF concentrations between patients of different AIS grades. RESULTS: The CSF NSE concentrations were significantly correlated with the baseline neurologic impairment being either 'motor complete' (AIS A, B) or 'motor incomplete' (AIS C, D) (r=0.520, P<0.05). The mean S-100ß concentration in motor complete patients was significantly higher compared with motor incomplete patients; 377.2 µg l(-1) (s.d.±523 µg l(-1)) vs 57.1 µg l(-1) (s.d.±56 µg l(-1)) (P<0.05), respectively. Lastly, the mean NFH concentration in motor complete patients was significantly higher compared with motor incomplete patient, 11 813 ng l(-1) (s.d.±16 195 ng l(-1)) vs 1446.8 ng l(-1) (s.d.±1533 ng l(-1)), (P<0.05), respectively. CONCLUSION: In this study we identified differences in the structural CSF biomarkers NSE, S-100ß and NFH between motor complete and motor incomplete SCI patients. Our data showed no clear differences in any of the protein concentrations between the different AIS grades.

Physician-based emergency medical service deployment characteristics in severe traumatic brain injury: a Dutch multicenter study.

INTRODUCTION: Prehospital guidelines advise advanced life support in all patients with severe traumatic brain injury (TBI). In the Netherlands, it is recommended that prehospital advanced life support is particularly provided by a physician-based helicopter emergency medical service (P-HEMS) in addition to paramedic care (EMS). Previous studies have however shown that a substantial part of severe TBI patients is exclusively treated by an EMS team. In order to better understand this phenomenon, we evaluated P-HEMS deployment characteristics in severe TBI in a multicenter setting. METHODS: The database included patient demographics, prehospital and injury severity parameters and determinants of EMS or EMS/P-HEMS dispatch in 334 patients with severe TBI admitted to level 1 trauma centres in the Netherlands. RESULTS: P-HEMS was deployed in 62% of patients with severe TBI. Patients treated by the P-HEMS had a higher injury severity score (29 (20-38)) vs. (25 (16-30); P<0.001), more frequently required blood product transfusions (41% vs. 29%; P=0.03) and recurrently suffered from TBI with extracranial injuries (33% vs. 6%; P<0.001) than patients solely treated by an EMS. The prehospital endotracheal intubation rate was higher in the P-HEMS group in isolated TBI (93% vs. 19%; P<0.001) or TBI with extracranial injuries (96% vs. 43%; P<0.001) compared to the EMS group. In the EMS group, more patients were secondary referred to a level 1 trauma centre (32% vs. 4%; P<0.001 vs. P-HEMS). Despite higher injury severity levels in P-HEMS patients, 6-month mortality rates were similar among groups, irrespective of the presence of extracranial injuries in addition to TBI. Deployment of P-HEMS estimated 52% and 72% (P<0.001) in urban and rural regions, respectively, with comparable endotracheal intubation rates among regions. CONCLUSIONS: This study shows that a physician-based HEMS was more frequently deployed in patients with severe TBI in the presence of extracranial injuries, and in rural trauma regions. Treatment of severe TBI patients by a paramedic EMS only was associated with a higher incidence of secondary referrals to a level I trauma centre. Our data support adjustment of local prehospital guidelines for patients with severe TBI to the geographical context.

Effects of physician-based emergency medical service dispatch in severe traumatic brain injury on prehospital run time.

INTRODUCTION: Prehospital care by physician-based helicopter emergency medical services (P-HEMS) may prolong total prehospital run time. This has raised an issue of debate about the benefits of these services in traumatic brain injury (TBI). We therefore investigated the effects of P-HEMS dispatch on prehospital run time and outcome in severe TBI. METHODS: Prehospital run times of 497 patients with severe TBI who were solely treated by a paramedic EMS (n = 125) or an EMS/P-HEMS combination (n = 372) were retrospectively analyzed. Other study parameters included the injury severity score (ISS), Glasgow Coma Scale (GCS), prehospital endotracheal intubation and predicted and observed outcome rates. RESULTS: Patients who received P-HEMS care were younger and had higher ISS values than solely EMS-treated patients (10%; P = 0.04). The overall prehospital run time was 74 ± 54 min, with similar out-of-hospital times for EMS and P-HEMS treated patients. Prehospital endotracheal intubation was more frequently performed in the P-HEMS group (88%) than in the EMS group (35%; P<0.001). The prehospital run time for intubated patients was similar for P-HEMS (66 (51-80)min) and EMS-treated patients (59 (41-88 min). Unexpectedly, mortality probability scores and observed outcome scores were less favourable for EMS-treated patients when compared to patients treated by P-HEMS. CONCLUSION: P-HEMS dispatch does not increase prehospital run times in severe TBI, while it assures prehospital intubation of TBI patients by a well-trained physician. Our data however suggest that a subgroup of the most severely injured patients received prehospital care by an EMS, while international guidelines recommend advanced life support by a physician-based EMS in these cases.

Association between thyroid function, thyroid autoimmunity, and state and trait factors of depression.

OBJECTIVE: The aim of this study was to investigate whether thyroid function and thyroid peroxidase antibodies (TPOAb) are associated with depression, when using both state and trait parameters of depression. METHOD: In 1125 participants of the Nijmegen Biomedical Study, thyroid-stimulating hormone (TSH), free thyroxine (FT4), and TPOAb were measured twice. The Beck Depression Inventory (BDI), a self-reported lifetime diagnosis of depression, and the neuroticism scale of the Eysenck Personality Questionnaire Revised Short Scale (EPQ-RSS) were used to evaluate the presence of state and trait features of depression. RESULTS: We found no association between TSH and FT4 levels and BDI score, current depression, lifetime diagnosis of depression, and EPQ-RSS neuroticism score. Subjects with TPOAb had higher EPQ-RSS neuroticism scores in comparison with subjects without TPOAb, mean score 4.1 vs. 3.2 (regression coefficient 0.70; 95% CI 0.1-1.3; P-value 0.02 after adjustment for confounders). The prevalence of a lifetime diagnosis of depression was higher in subjects with positive TPOAb in comparison with participants without TPOAb: 24.2% vs. 16.7% (relative risk 1.4; 95% CI 1.0-2.1; P-value 0.04 after adjustment for confounders). CONCLUSION: Thyroid peroxidase antibodies are positively associated with trait markers of depression. The presence of TPOAb may be a vulnerability marker for depression.

Mild traumatic brain injury.

Traumatic Brain Injury (TBI) is among the most frequent neurological disorders. Of all TBIs 90% are considered mild with an annual incidence of 100­300/100.000. Intracranial complications of Mild Traumatic Brain Injury (MTBI) are infrequent (10%), requiring neurosurgical intervention in a minority of cases (1%), but potentially life-threatening (case fatality rate 0,1%). Hence, a true health management problem exists because of the need to exclude the small chance of a life threatening complication in large numbers of individual patients. The 2002 EFNS guidelines used a best evidence approach based on the literature until 2001 to guide initial management with respect to indications for CT, hospital admission, observation and follow up of MTBI patients. This updated EFNS guideline version for initial management inMTBI proposes a more selectively strategy for CT when major (dangerous mechanism, GCS<15, 2 points deterioration on the GCS, clinical signs of (basal) skull fracture, vomiting, anticoagulation therapy, post traumatic seizure) or minor (age, loss of consciousness, persistent anterograde amnesia, focal deficit, skull contusion, deterioration on the GCS) risk factors are present based on published decision rules with a high level of evidence. In addition clinical decision rules for CT now exist for children as well. Since 2001 recommendations, although with a lower level of evidence, have been published for clinical in hospital observation to prevent and treat other potential threads to the patient including behavioral disturbances (amnesia, confusion and agitation) and infection.

Potential risk factors for developing heterotopic ossification in patients with severe traumatic brain injury.

BACKGROUND: Heterotopic ossification (HO) is a frequent complication after traumatic brain injury (TBI). The current preliminary study is intended to provide additional data on the potential roles that brain injury severity, concomitant orthopaedic trauma, and specific intensive care complicating events may play in the prediction of HO in patients who have sustained severe TBI. METHODS: A prospective cohort study in patients with severe TBI. RESULTS: Ninety-seven of the 176 patients were eligible for follow-up; 13 patients (13%) developed 19 clinically relevant HOs at 1 or more sites. Univariate analysis indicated that patients with HO remained in coma longer (P < .001) and were ventilated during a longer period (P = .002). Autonomic dysregulation (relative risk = 6.11, 95% confidence interval: 2.53-14.76) and surgically treated extremity fractures (relative risk = 5.02, 95% confidence interval: 1.68-15.04) also showed significant associations with the development of HO. CONCLUSION: Prolonged coma duration and mechanical ventilation, coexistent surgically treated bone fractures and clinical signs of autonomic dysregulation should be given further consideration as potential risk factors for developing clinically relevant HO. Larger-scale studies are needed to develop a valid risk profile that takes into account the interrelationships between variables.

GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study.

BACKGROUND: Biomarker levels in blood after traumatic brain injury (TBI) may offer diagnostic and prognostic tools in addition to clinical indices. This study aims to validate glial fibrillary acidic protein (GFAP) and S100B concentrations in blood as outcome predictors of TBI using cutoff levels of 1.5 µg/L for GFAP and 1.13 µg/L for S100B from a previous study. METHODS: In 79 patients with TBI (Glasgow Coma Scale score [GCS] ≤12), serum, taken at hospital admission, was analyzed for GFAP and S100B. Data collected included injury mechanism, age, gender, mass lesion on CT, GCS, pupillary reactions, Injury Severity Score (ISS), presence of hypoxia, and hypotension. Outcome was assessed, using the Glasgow Outcome Scale Extended (dichotomized in death vs alive and unfavorable vs favorable), 6 months post injury. RESULTS: In patients who died compared to alive patients, median serum levels were increased: GFAP 33.4-fold and S100B 2.1-fold. In unfavorable compared to favorable outcome, GFAP was increased 19.8-fold and S100B 2.1-fold. Univariate logistic regression analysis revealed that mass lesion, GFAP, absent pupils, age, and ISS, but not GCS, hypotension, or hypoxia, predicted death and unfavorable outcome. Multivariable analysis showed that models containing mass lesion, pupils, GFAP, and S100B were the strongest in predicting death and unfavorable outcome. S100B was the strongest single predictor of unfavorable outcome with 100% discrimination. CONCLUSION: This study confirms that GFAP and S100B levels in serum are adjuncts to the assessment of brain damage after TBI and may enhance prognostication when combined with clinical variables.

Dysautonomia after severe traumatic brain injury.

BACKGROUND: Dysautonomia after traumatic brain injury (TBI) is characterized by episodes of increased heart rate, respiratory rate, temperature, blood pressure, muscle tone, decorticate or decerebrate posturing, and profuse sweating. This study addresses the incidence of dysautonomia after severe TBI, the clinical variables that are associated with dysautonomia, and the functional outcome of patients with dysautonomia. METHODS: A historic cohort study in patients with severe TBI [Glasgow Coma Scale (GCS) < or = 8 on admission]. RESULTS: Seventy-six of 119 patients survived and were eligible for follow-up. The incidence of dysautonomia was 11.8%. Episodes of dysautonomia were prevalent during a mean period of 20.1 days (range 3-68) and were often initiated by discomfort. Patients with dysautonomia showed significant longer periods of coma (24.78 vs. 7.99 days) and mechanical ventilation (22.67 vs. 7.21 days). Dysautonomia was associated with diffuse axonal injury (DAI) [relative risk (RR) 20.83, CI 4.92-83.33] and the development of spasticity (RR 16.94, CI 3.96-71.42). Patients with dysautonomia experienced more secondary complications. They tended to have poorer outcome. CONCLUSIONS: Dysautonomia occurs in approximately 10% of patients surviving severe TBI and is associated with DAI and the development of spasticity at follow-up. The initiation of dysautonomia by discomfort supports the Excitatory: Inhibitory Ratio model as pathophysiological mechanism.

Biomarkers in spinal cord injury.

STUDY DESIGN: Literature review. OBJECTIVES: In traumatic spinal cord injury (SCI), much effort has been put into the evaluation of SCI severity and the prediction of recovery potential. An accurate prediction of the initial damage of the spinal cord that differentiates between the severities of SCI however, may help physicians in choosing a particular neuroprotective treatment in the acute phase. Neurochemical biomarkers may possibly fulfil these requirements. The aim of this review was to describe (1) the current status of neurochemical biomarkers in SCI; (2) their potential diagnostic role in SCI. METHODS: MEDLINE was searched from 1966 to 2008 to identify publications concerning biomarkers in traumatic SCI. RESULTS: The biomarkers S-100beta, neuron-specific enolase, neurofilament light chain, and Glial fibrillary acidic protein are significantly increased in cases of (experimental) spinal cord injury. Furthermore, increased serum concentrations of S-100beta have been correlated with an unfavourable functional outcome. Although biomarkers in SCI show promising results, considerations and shortcomings, such as polytrauma, haemolysis, extracerebral sources, and poor resuscitation, must be studied in greater detail before biomarkers can be utilised in the clinical care of SCI. CONCLUSIONS: Quantitative standards for determining the extent of SCI during the acute phase must be developed and validated. Even though increased concentrations of neurochemical biomarkers have been identified in patients with SCI, these do not yet provide a sensitive prognostic tool. Considering the limited availability of sensitive prognostic tools, neurochemical biomarkers of SCI should be evaluated and validated in future clinical trials.

Outcome after complicated minor head injury.

BACKGROUND AND PURPOSE: Functional outcome in patients with minor head injury with neurocranial traumatic findings on CT is largely unknown. We hypothesized that certain CT findings may be predictive of poor functional outcome. MATERIALS AND METHODS: All patients from the CT in Head Injury Patients (CHIP) study with neurocranial traumatic CT findings were included. The CHIP study is a prospective, multicenter study of consecutive patients, > or =16 years of age, presenting within 24 hours of blunt head injury, with a Glasgow Coma Scale (GCS) score of 13-14 or a GCS score of 15 and a risk factor. Primary outcome was functional outcome according to the Glasgow Outcome Scale (GOS). Other outcome measures were the modified Rankin Scale (mRS), the Barthel Index (BI), and number and severity of postconcussive symptoms. The association between CT findings and outcome was assessed by using univariable and multivariable regression analysis. RESULTS: GOS was assessed in 237/312 patients (76%) at an average of 15 months after injury. There was full recovery in 150 patients (63%), moderate disability in 70 (30%), severe disability in 7 (3.0%), and death in 10 (4.2%). Outcome according to the mRS and BI was also favorable in most patients, but 82% of patients had postconcussive symptoms. Evidence of parenchymal damage was the only independent predictor of poor functional outcome (odds ratio = 1.89, P = .022). CONCLUSION: Patients with neurocranial complications after minor head injury generally make a good functional recovery, but postconcussive symptoms may persist. Evidence of parenchymal damage on CT was predictive of poor functional outcome.

Early prediction of favourable recovery 6 months after mild traumatic brain injury.

BACKGROUND: Predicting outcome after mild traumatic brain injury (MTBI) is notoriously difficult. Although it is recognised that milder head injuries do not necessarily mean better outcomes, less is known about the factors that do enable early identification of patients who are likely to recover well. OBJECTIVE: To develop and internally validate two prediction rules for identifying patients who have the highest chance for good 6 month recovery. METHODS: A prospective cohort study was conducted among patients with MTBI admitted to the emergency department. Apart from MTBI severity indices, a range of pre-, peri- and early post-injury variables were considered as potential predictors, including emotional and physical functioning. Logistic regression modelling was used to predict the absence of postconcussional symptoms (PCS) and full return to work (RTW). RESULTS: At follow-up, 64% of the 201 participating patients reported full recovery. Based on our prediction rules, patients without premorbid physical problems, low levels of PCS and post-traumatic stress early after injury had a 90% chance of remaining free of PCS. Patients with over 11 years of education, without nausea or vomiting on admission, with no additional extracranial injuries and only low levels of pain early after injury had a 90% chance of full RTW. The discriminative ability of the prediction models was satisfactory, with an area under the curve >0.70 after correction for optimism. CONCLUSIONS: Early identification of patients with MTBI who are likely to have good 6 month recovery was feasible on the basis of relatively simple prognostic models. A score chart was derived from the models to facilitate clinical application.

A history of loss of consciousness or post-traumatic amnesia in minor head injury: "conditio sine qua non" or one of the risk factors?

OBJECTIVE: A history of loss of consciousness (LOC) or post-traumatic amnesia (PTA) is commonly considered a prerequisite for minor head injury (MHI), although neurocranial complications also occur when LOC/PTA are absent, particularly in the presence of other risk factors. The purpose of this study was to evaluate whether known risk factors for complications after MHI in the absence of LOC/PTA have the same predictive value as when LOC/PTA are present. METHODS: A prospective multicentre study was performed in four university hospitals between February 2002 and August 2004 of consecutive blunt head injury patients (> or = 16 years) presenting with a normal level of consciousness and a risk factor. Outcome measures were any neurocranial traumatic CT finding and neurosurgical intervention. Common odds ratios (OR) were estimated for each of the risk factors and tested for homogeneity. RESULTS: 2462 patients were included: 1708 with and 754 without LOC/PTA. Neurocranial traumatic findings on CT were present in 7.5% and were more common when LOC/PTA was present (8.7%). Neurosurgical intervention was required in 0.4%, irrespective of the presence of LOC/PTA. ORs were comparable across the two subgroups (p>0.05), except for clinical evidence of a skull fracture, with high ORs both when LOC/PTA was present (OR = 37, 95% CI 17 to 80) or absent (OR = 6.9, 95% CI 1.8 to 27). LOC and PTA had significant ORs of 1.9 (95% CI 1.0 to 2.7) and 1.7 (95% CI 1.3 to 2.3), respectively. CONCLUSION: Known risk factors have comparable ORs in MHI patients with or without LOC or PTA. MHI patients without LOC or PTA need to be explicitly considered in clinical guidelines.

Increased GFAP and S100beta but not NSE serum levels after subarachnoid haemorrhage are associated with clinical severity.

Assessment of initial disease severity after subarachnoid haemorrhage (SAH) remains difficult. The objective of the study is to identify biochemical markers of brain damage in peripheral blood after SAH. Hospital admission S100beta, glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) serum levels were analysed in 67 patients with SAH. Disease severity was determined by using the World Federation of Neurological Surgeons (WFNS) scale and the Fisher CT (computerized tomography) grading scale. Mean astroglial serum concentrations taken at hospital admission were increased (S100beta 2.8-fold and GFAP 1.8-fold) compared with the upper limit of normal laboratory reference values (P95). The mean NSE concentration was within normal limits. S100beta (P < 0.001) and GFAP (P =0.011) but not NSE levels were higher in patients who were in coma at the time of hospital admission compared with patients who were not. Similarly S100beta and GFAP but not NSE serum levels increased with higher WFNS scores, raised intracranial pressure and higher CT Fisher grade scores. Concerning the location of the aneurysm, S100beta and GFAP serum levels were within normal limits after a perimesencephalic type of haemorrhage and significantly increased after aneurysmal type SAH. Increased glial (S100beta and GFAP) but not neuronal (NSE) protein serum concentrations are found after SAH, associated to the clinical severity of the initial injury.

Prediction of poor outcome within the first 3 days of postanoxic coma.

OBJECTIVE: To determine the optimal timing of somatosensory evoked potential (SSEP) recordings and the additional value of clinical and biochemical variables for the prediction of poor outcome in patients who remain comatose after cardiopulmonary resuscitation (CPR). METHODS: A prospective cohort study was conducted in 32 intensive care units including adult patients still unconscious 24 hours after CPR. Clinical, neurophysiologic, and biochemical variables were recorded 24, 48, and 72 hours after CPR and related to death or persisting unconsciousness after 1 month. RESULTS: Of 407 included patients, 356 (87%) had a poor outcome. In 301 of 305 patients unconscious at 72 hours, at least one SSEP was recorded, and in 136 (45%), at least one recording showed bilateral absence of N20. All these patients had a poor outcome (95% CI of false positive rate 0 to 3%), irrespective of the timing of SSEP. In the same 305 patients, neuron-specific enolase (NSE) was determined at least once in 231, and all 138 (60%) with a value >33 microg/L at any time had a poor outcome (95% CI of false positive rate 0 to 3%). The test results of SSEP and NSE overlapped only partially. The performance of all clinical tests was inferior to SSEP and NSE testing, with lower prevalences of abnormal test results and wider 95% CI of false positive rates. CONCLUSION: Poor outcome in postanoxic coma can be reliably predicted with somatosensory evoked potentials and neuron-specific enolase as early as 24 hours after cardiopulmonary resuscitation in a substantial number of patients.