Juha Öhman

EBIC-Guidelines for Management of Severe Head Injury in Adults

SummaryGuidelines for the management of severe head injury in adults as evolved by the European Brain Injury Consortium are presented and discussed. The importance of preventing and treating secondary insults is emphasized and the principles on which treatment is based are reviewed. Guidelines presented are of a pragmatic nature, based on consensus and expert opinion, covering the treatment from accident site to intensive care unit. Specific aspects pertaining to the conduct of clinical trials in head injury are highlighted. The adopted approach is further discussed in relation to other approaches to the development of guidelines, such as evidence based analysis.

Susceptibility loci for intracranial aneurysm in European and Japanese populations

Stroke is the worlds third leading cause of death. One cause of stroke, intracranial aneurysm, affects ∼2% of the population and accounts for 500,000 hemorrhagic strokes annually in mid-life (median age 50), most often resulting in death or severe neurological impairment. The pathogenesis of intracranial aneurysm is unknown, and because catastrophic hemorrhage is commonly the first sign of disease, early identification is essential. We carried out a multistage genome-wide association study (GWAS) of Finnish, Dutch and Japanese cohorts including over 2,100 intracranial aneurysm cases and 8,000 controls. Genome-wide genotyping of the European cohorts and replication studies in the Japanese cohort identified common SNPs on chromosomes 2q, 8q and 9p that show significant association with intracranial aneurysm with odds ratios 1.24–1.36. The loci on 2q and 8q are new, whereas the 9p locus was previously found to be associated with arterial diseases, including intracranial aneurysm. Associated SNPs on 8q likely act via SOX17, which is required for formation and maintenance of endothelial cells, suggesting a role in development and repair of the vasculature; CDKN2A at 9p may have a similar role. These findings have implications for the pathophysiology, diagnosis and therapy of intracranial aneurysm.

The European Brain Injury Consortium. Nemo solus satis sapit: nobody knows enough alone.

tUniversity Department of Neurosurgery, Institute of Neurological Sciences, Southern General Hospital, Glasgow, U.K., 2Berkel Enschot, The Netherlands, 3Department of Neurosurgery, Hopital Pellegrin, Bordeaux, France, 4Department of Anaesthetics, Leeds General Infirmary, Leeds, U.K., 5Department of Clinical Neurosciences, Southampton General Hospital, Southampton, U.K., 6Neurochirurgische Klinik, Universitfit K61n, K61n, Federal Republic of Germany, 7Centre Hospitalier Universitaire de Poitiers, Service de Neurochirurgie, Poitiers, France, 8Department of Neurosurgery, University Hospital Rotterdam, Rotterdam, The Netherlands, 9Medical Statistics Unit, University of Edinburgh Medical School, Edinburgh, U.K., 1~ of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland, l lDepartment of Neurosurgery, Akademiska Hospital, Uppsala, Sweden, ~2Azienda USL Cesena, Ospedal M. Bufalini, Cesena, Italy, 13Terapia Intensiva Nenrochirurgica, Serv. Anestesia e Rianimazione-Ospedale Policlinico, IRCCS, Milano, Italy, 14Department of Neurosurgery, University Medical School, Lublin, Poland, and 15Department of Neurosurgery, Virchow-Klinikum, Medizinische Fakultfit, Humboldt UniversitSt Berlin, Berlin, Federal Republic of Germany

Cranioplasty with adipose-derived stem cells and biomaterial: a novel method for cranial reconstruction.

BACKGROUND:There is no optimal method for reconstruction of large calvarial defects. Because of the limitations of autologous bone grafts and alloplastic materials, new methods for performing cranioplasties are needed. OBJECTIVE:To create autologous bone to repair cranial defects. METHODS:We performed a cranioplasty procedure with this new method in 4 patients who had large calvarial defects of different etiologies. We used autologous adipose-derived stem cells seeded in beta-tricalcium phosphate granules. For 2 patients, we used a bilaminate technique with resorbable mesh. RESULTS:During follow-up, there were no clinically relevant postoperative complications. The computed tomography scans revealed satisfactory outcome in ossification, and in the clinical examinations, the outcomes were good. The cranioplasty was measured in Hounsfield units from each computed tomography scan. The Hounsfield units increased gradually to equal the value of bone. CONCLUSION:The combination of scaffold material such as beta-tricalcium phosphate and autologous adipose-derived stem cells constitutes a promising model for reconstruction of human large cranial defects. The success of these clinical cases paves way for further studies and clinical applications to turn this method into a reliable treatment regimen.

Traumatic Subarachnoid Hemorrhage: Demographic and Clinical Study of 750 Patients from the European Brain Injury Consortium Survey of Head Injuries

OBJECTIVE Previous reports identified the presence of traumatic subarachnoid hemorrhage (tSAH) on admission computed tomographic (CT) scans as an independent prognostic factor in worsening outcomes. The mechanism underlying the link between tSAH and prognosis has not been clarified. The aim of this study was to investigate the association between CT evidence of tSAH and outcomes after moderate or severe head injuries. METHODS In a survey organized by the European Brain Injury Consortium, data on initial severity, treatment, and subsequent outcomes were prospectively collected for 1005 patients with moderate or severe head injuries who were admitted to one of the 67 European neurosurgical units during a 3-month period in 1995. The CT findings were classified according to the Traumatic Coma Data Bank classification system, and the presence or absence of tSAH was recorded separately in the initial CT scan forms. RESULTS Complete data on early clinical features, CT findings, and outcomes at 6 months were available for 750 patients, of whom 41% exhibited evidence of tSAH on admission CT scans. There was a strong, highly statistically significant association between the presence of tSAH and poor outcomes. In fact, 41% of patients without tSAH achieved the level of good recovery, whereas only 15% of patients with tSAH achieved this outcome. Patients with tSAH were significantly older (median age, 43 yr; standard deviation, 21.1 yr) than those without tSAH (median age, 32 yr; standard deviation, 19.5 yr), and there was a significant tendency for patients with tSAH to exhibit lower Glasgow Coma Scale scores at the time of admission. A logistic regression analysis of favorable/unfavorable outcomes demonstrated that there was still a very strong association between tSAH and outcomes after simultaneous adjustment for age, Glasgow Coma Scale Motor Scores, and admission CT findings (odds ratio, 2.49; 95% confidence interval, 1.74–3.55;P < 0.001). Comparison of the time courses for 164 patients with early (within 14 d after injury) deaths demonstrated very similar patterns, with an early peak and a subsequent decline; there was no evidence of a delayed increase in mortality rates for either group of patients (with or without tSAH). CONCLUSION These findings for an unselected series of patients confirm previous reports of the adverse prognostic significance of tSAH. The data support the view that death among patients with tSAH is related to the severity of the initial mechanical damage, rather than to the effects of delayed vasospasm and secondary ischemic brain damage.

Persistent symptoms in mild to moderate traumatic brain injury associated with executive dysfunction

In order to improve detection of subtle cognitive dysfunction and to shed light on the etiology of persistent symptoms after mild-to-moderate traumatic brain injury (TBI), we employed an experimental executive reaction time (RT) test, standardized neuropsychological tests, and diffusion tensor imaging (DTI). The Executive RT-Test, an Executive Composite Score from standardized neuropsychological tests, and DTI-indices in the midbrain differentiated between patients with persistent symptoms from those fully recovered after mild-to-moderate TBI. We suggest that persistent symptoms in mild-to-moderate TBI may reflect disrupted fronto-striatal network involved in executive functioning, and the Executive RT-Test provides an objective and novel method to detect it.

Prediction of psychosocial recovery after head injury with cognitive tests and neurobehavioral ratings

A series of 53 patients was studied using a battery of tests and a neurobehavioral rating scale on average 4 months after closed-head injury (CHI). Social outcome was assessed 1 year after injury by interviewing a family member. The results supported the hypothesis that tests of flexibility and programming rather than tests of cognitive skills predict psychosocial recovery after CHI. Spatial Learning with Self-Set Goals and Sorting were measures of flexibility and programming. Contrary to expectation, word fluency performance was unrelated to these measures, but was associated with conventional intelligence tests, which did not predict psychosocial recovery. Cognition/Energy deficit on the Neurobehavioral Rating Scale and increased age were useful predictors of poor psychosocial outcome, whereas computed tomography findings or the Glasgow Coma Score were weakly related to the outcome indices. Evidently, cognitive flexibility and mental programming are very important psychological prerequisites of social recovery after CHI.

Routine cerebral angiography after surgery for saccular aneurysms: is it worth it?

OBJECTIVE: The objective of this study was to determine whether an angiographically proven rate of saccular intracranial aneurysm occlusion after surgical clipping suggests that postoperative angiography should continue to be used routinely or should be supplanted by intraoperative angiography. These data also should establish a basis for comparing surgery with new endovascular methods of treatment. METHODS: During a 3.5-year period, a consecutive series of 622 patients (955 aneurysms, 808 of which were surgically clipped) who underwent postoperative angiography were studied retrospectively. This series comprised 493 ruptured and 315 unruptured aneurysms. RESULTS: Complete aneurysm closure was achieved in 88% of aneurysms, a neck remnant was discovered in 9%, and a fundus remnant was revealed in 3%. Of 493 ruptured aneurysms, 86% were completely occluded. Of 315 unruptured aneurysms, 91% were completely occluded. The results for clipping of complex aneurysms, i.e., posterior circulation or large to giant aneurysms, were significantly inferior to those for small and anterior circulation aneurysms. In one-third of the large and giant aneurysms, a part of the base was left intentionally because of calcifications or strong wall or to prevent occlusion of any branches. In the series, a significant 5% complication rate of major vessel occlusion was detected. CONCLUSION: Our retrospective analysis revealed that ruptured, posterior circulation, and large/giant aneurysms are more prone to incomplete clipping. Therefore, these aneurysms require postoperative if not intraoperative evaluation with angiography. Many clippings of anterior circulation aneurysms experience unexpected failures, which suggests that intraoperative angiography could be beneficial. This series, which has no selection bias, can be used as a basis to compare the results of other series reporting surgical or endovascular treatment.

Adipose Stem Cells Used to Reconstruct 13 Cases With Cranio-Maxillofacial Hard-Tissue Defects

Although isolated reports of hard‐tissue reconstruction in the cranio‐maxillofacial skeleton exist, multipatient case series are lacking. This study aimed to review the experience with 13 consecutive cases of cranio‐maxillofacial hard‐tissue defects at four anatomically different sites, namely frontal sinus (3 cases), cranial bone (5 cases), mandible (3 cases), and nasal septum (2 cases). Autologous adipose tissue was harvested from the anterior abdominal wall, and adipose‐derived stem cells were cultured, expanded, and then seeded onto resorbable scaffold materials for subsequent reimplantation into hard‐tissue defects. The defects were reconstructed with either bioactive glass or β‐tricalcium phosphate scaffolds seeded with adipose‐derived stem cells (ASCs), and in some cases with the addition of recombinant human bone morphogenetic protein‐2. Production and use of ASCs were done according to good manufacturing practice guidelines. Follow‐up time ranged from 12 to 52 months. Successful integration of the construct to the surrounding skeleton was noted in 10 of the 13 cases. Two cranial defect cases in which nonrigid resorbable containment meshes were used sustained bone resorption to the point that they required the procedure to be redone. One septal perforation case failed outright at 1 year because of the postsurgical resumption of the patients uncontrolled nasal picking habit.

Social outcome related to cognitive performance and computed tomographic findings after surgery for a ruptured intracranial aneurysm

A series of 83 patients was examined with a battery of cognitive tests, a clinical interview, and computed tomography 1 year after surgery for a ruptured intracranial aneurysm. Disability on the Glasgow Outcome Scale (33%), failure to return to work (25%), impaired social relations (25%), and subjective or clinical mental impairment (56%) were found to be related to each other and to poor performance on cognitive tests, especially to verbal impairments in patients with left lateral infarctions and to memory deficits and cognitive inflexibility in patients with frontal medial infarctions. Furthermore, cognitive deficits and poor outcome were associated with diffuse brain damage. Depression and anxiety were unrelated to test performances, but were frequently reported by patients with right lateral infarctions.