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Biomedical subjects

J Ohman

Publications and source records attributed to J Ohman.

At least 19 recordsLinked to original sources

Fast vigilance decrement in closed head injury patients as reflected by the mismatch negativity (MMN).

Event-related potentials (ERPs) were measured from 24 chronic closed head injury (CHI) patients and 18 age- and education-matched controls. The oddball paradigm was applied while subjects were watching a silent movie. The standard (p=0.8) sound of 75 ms duration had a basic frequency of 500 Hz with harmonic partials of 1000 Hz and 1500 Hz, whereas these frequencies for the pitch deviant were each 10% higher. The frequencies of the duration deviant matched with those of the standard but was 25 ms in duration. The MMN (mismatch negativity), generated by the brain's automatic auditory change-detector mechanism, was elicited by both deviants. No significant differences in the MMN latency or amplitude for either pitch or duration deviants were found between the groups. However, the MMN amplitude for the pitch deviant decreased in the patient group during the experiment considerably faster than in controls, suggesting a faster vigilance decrement in the patients.

Acoustic Stimulation↗

Intensive care management of head-injured patients in Europe: a survey from the European brain injury consortium.

OBJECTIVES: (a) to describe current practice in the monitoring and treatment of moderate and severe head injuries in Europe; (b) to report on intracranial pressure and cerebral perfusion pressure monitoring, occurrence of measured and reported intracranial hypertension, and complications related to this monitoring; (c) to investigate the relationship between the severity of injury, the frequency of monitoring and management, and outcome. METHODS: A three-page questionnaire comprising 60 items of information has been compiled by 67 centres in 12 European countries. Information was collected prospectively regarding all severe and moderate head injuries in adults (> 16 years) admitted to neurosurgery within 24 h of injury. A total of 1005 adult head injury cases were enrolled in the study from 1 February 1995 to 30 April 1995. The Glasgow Outcome Scale was administered at 6 months. RESULTS: Early surgery was performed in 346 cases (35%); arterial pressure was monitored invasively in 631 (68%), ICP in 346 (37%), and jugular bulb saturation in 173 (18%). Artificial ventilation was provided to 736 patients (78%). Intracranial hypertension was noted in 55% of patients in whom ICP was recorded, while it was suspected in only 12% of cases without ICP measurement. There were great differences in the use of ventilation and CPP monitoring among the centres. Mortality at 6 months was 31%. There was an association between an increased frequency of monitoring and intervention and an increased severity of injury; correspondingly, patients who more frequently underwent monitoring and ventilation had a less favourable outcome. CONCLUSIONS: In Europe there are great differences between centres in the frequency of CPP monitoring and ventilatory support applied to head-injured patients. ICP measurement disclosed a high rate of intracranial hypertension, which was not suspected in patients evaluated on a clinical basis alone. ICP monitoring was associated with a low rate of complications. Cases with severe neurological impairment, and with the worse outcome, were treated and monitored more intensively.

Adult↗

Repinotan (BAY x 3702): a 5HT1A agonist in traumatically brain injured patients.

Repinotan is a high-affinity, selective, full agonist of the 5HT1A-receptor subtype with neuroprotective properties. This paper presents the results of a randomized, double-blind, placebo-controlled study examining the safety and tolerability of three different doses of repinotan in patients with severe traumatic brain injury. Sixty patients were enrolled to receive repinotan (0.5, 1.25, or 2.50 mg/day) or placebo, by continuous i.v. infusion for 7 days. Repinotan treatment had no apparent adverse effects on intracranial pressure, hemodynamic parameters or laboratory parameters. No seizures occurred during treatment, and the incidence and severity of adverse events was as expected for this indication. No serious adverse events were considered related to drug treatment, with the possible exception of one case of inappropriate ADH secretion. No further safety concerns were raised during the 3 months following treatment. On a descriptive basis, the proportion of patients having good outcome or moderate disability (Glasgow Outcome Scale) was somewhat greater in repinotan-treated patients (60%) than in placebo (50%).

Adolescent↗

Association of apolipoprotein E polymorphism with outcome after aneurysmal subarachnoid hemorrhage: a preliminary study.

BACKGROUND AND PURPOSE: Variation in the outcome after aneurysmal subarachnoid hemorrhage (SAH) is not fully explained by known prognostic factors. APOE genotype is the most important genetic determinant of susceptibility to Alzheimer's disease, and it is also shown to be associated with the outcome after traumatic brain injury. We studied the association of apolipoprotein E polymorphism with the outcome after aneurysmal SAH. METHODS: A total of 160 consecutive patients were admitted after SAH to a neurosurgical unit. The clinical assessment after the SAH was performed with the Hunt and Hess grading scale. The severity of the bleeding as visualized on CT was assessed by Fisher's grading system. Outcome was assessed with the Glasgow Outcome SCALE: APOE genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: 126 patients had aneurysmatic SAH, and detailed information on outcome and APOE genotype was available for 108 patients (86%). Sixteen (40%) of 40 patients with APOE epsilon4 had an unfavorable outcome compared with 13 (19%) of 68 without the APOE epsilon4 allele (OR 2.8, 95% CI 1.18 to 6.77). Association was more significant after adjustment for age, rebleeding, clinical status on admission, and CT scan findings (OR 7.1, 95% CI 1.9 to 26.3; P=0.0035). CONCLUSIONS: Our findings show a significant genetic association of APOE polymorphism with outcome after spontaneous aneurysmal SAH. Genetic factors thus seem to explain a part of individual differences in the recovery of SAH.

Apolipoproteins E↗

Increased distractibility in closed head injury as revealed by event-related potentials.

The present study demonstrates that event-related potentials (ERPs) may be used to reveal increased distractibility as a physiologically measurable condition after chronic closed head injury (CHI). ERPs were recorded from 17 chronic CHI subjects and from 17 healthy age-matched controls. Auditory stimuli consisted of variants of vowel /o/ (standards) occasionally replaced by an /e/ vowel (deviant). Subjects were instructed to ignore auditory stimuli while watching a silent movie. In the constant-standard condition, the vowel /o/ served as the standard and vowel /e/ as the deviant. In the roving-standard condition, four variants of the vowel /o/ were randomly used as standards in the same stimulus block. None of the stimuli were prototypes in the subjects' mother tongues. Deviant stimuli elicited significant MMNs in both groups in both conditions, which were significantly smaller in the roving-standard than in the constant-standard condition. CHI victims showed significantly larger P3a amplitudes than controls in both conditions, apparently reflecting their enhanced involuntary sifting of attention and thus their increased distractibility.

Acoustic Stimulation↗

The value of the "worst" computed tomographic scan in clinical studies of moderate and severe head injury. European Brain Injury Consortium.

OBJECTIVE: Computed tomographic (CT) scanning can reveal the pattern and severity of structural brain damage after head injury. With the proliferation of CT scanners in general hospitals, and with improvements in patient transport, the interval from injury to the first CT scan is decreasing. The potential result is an "admission" scan missing an evolving and potentially operable lesion. Furthermore, the literature is confusing regarding the timing and coding of CT findings. We sought to establish the frequency of deterioration in CT appearance from an admission scan to subsequent scans and the prognostic significance of such deterioration. METHODS: In a survey organized by the European Brain Injury Consortium, data on initial severity, management, and subsequent outcome were gathered prospectively for 1005 patients with moderate or severe head injury admitted to one of 67 European neurosurgical units during a 3-month period in 1995. The findings of the initial and the final ("worst") CT scan were classified according to the Traumatic Coma Data Bank system and were related to outcome as assessed using the Glasgow Outcome Scale 6 months after injury. RESULTS: Data on an initial and a final CT scan were available for 897 patients; of these, 724 patients were assessed using the Glasgow Outcome Scale at 6 months. The initial CT findings were classified as a diffuse injury for 53% of the cohort, with 16% of these diffuse injuries demonstrating deterioration on a subsequent scan. In 56 (74%) of 76 deteriorations, the change was from a diffuse injury to a mass lesion. When the initial CT scan demonstrated a diffuse injury without swelling or shift, evolution to a mass lesion was associated with a statistically significant increase in the risk of an unfavorable outcome (62% versus 38%). When the initial scan demonstrated evidence of swelling or shift, there was a nonsignificant trend in the opposite direction, although the numbers were limited. CONCLUSION: When an admission CT scan demonstrates evidence of a diffuse injury, follow-up scans should be performed, because approximately one in six such patients will demonstrate significant CT evolution. In studies comparing series of head-injured patients, correspondence of timing of CT scans is necessary for valid comparison.

Brain Injuries↗

Basal brain injury in aneurysm surgery.

OBJECTIVE: The goal of this study was to determine the frequency of lesions in the basal frontotemporal area that were related to surgical damage to the brain tissue. METHODS: A prospective series of 101 patients with ruptured intracranial aneurysms were examined with high-field magnetic resonance imaging, 2 to 6 years (mean, 3.3 yr) after early surgery. RESULTS: Lesions in the basal frontotemporal region, on the side of the pterional approach, were observed for 36 patients. These lesions were not visible in computed tomographic scans obtained pre- or postoperatively or 3 months after subarachnoid hemorrhage. Patients with ruptured aneurysms in the anterior communicating artery exhibited fewer of these lesions than did patients with aneurysms in the internal carotid artery or middle cerebral artery; this difference was not statistically significant. The age of the patient, the duration and depth of hypotension, the amount of blood or ventricular enlargement in pre- and postoperative computed tomographic scans, and the incidence and severity of angiographic vasospasm in pre- and postoperative angiograms did not predict the existence of these lesions. The clinical conditions of the patients, as assessed using the Glasgow Outcome Scale, at 3 months after surgery and at the time of magnetic resonance imaging did not predict the existence of these lesions. Nine of the 10 patients who underwent surgical treatment of unruptured aneurysms on the contralateral side exhibited no signs of tissue damage. CONCLUSION: Surgical treatment of ruptured intracranial aneurysms seems to cause damage in the basal frontotemporal region in one-third of patients. The significance of these lesions remains unclear.

Adult↗

Intubation and survival in severe paediatric blunt head injury.

The majority of severe childhood injuries are due to head injuries. We studied the impact of emergency intubation in a cohort of children suffering severe blunt head trauma. A 10-year retrospective case note analysis was performed on 176 children (age < 16 years) with severe blunt head trauma (abbreviated injury scale > or =4) in Southern Finland, who required intensive care in a level 1 trauma centre, or who died despite initiation of life supporting measures at the scene. Children in whom emergency intubation was performed either at the scene, or in the emergency room (ER) were analysed. Of the 59 children who fulfilled the study criteria, 20 had an isolated head injury. Most injuries (56/59) were caused by road traffic accidents. Field-intubation was performed in 24 children, and emergency intubation in the ERs of regional hospitals or the level 1 trauma centre, in 13 and 22 children respectively. Mortality was 54.2% (32/59), and was highest in children intubated in regional hospital ERs or in the field. Children intubated at the scene or in the ER of regional hospitals, had significantly worse AIS (head/neck), injury severity score (ISS), and Glasgow coma (GCS) scores than those children intubated in the ER of the level 1 trauma centre. Survival was better in field-intubated children compared with those intubated in regional hospital ERs, despite similar trauma scores (p = 0.05). It is concluded that although children with severe (AIS > or =4) head injury who require emergency intubation have a high overall mortality, field-intubation may improve survival, compared with 'scoop and run' with BLS airway management and deferred emergency intubation.

Abbreviated Injury Scale↗

Challenges in translating the efficacy of neuroprotective agents in experimental models into knowledge of clinical benefits in head injured patients.

Many agents have been shown to reduce brain damage in experimental models of brain injury; this is proving difficult to translate into improved outcome of patients for reasons that are reviewed in this article. It is possible that, even if fundamental mechanisms are similar, injury processes modelled experimentally may be proportionately less important in human cases, and there also may have been insufficient attention to ensuring that dosage regimens for patients are therapeutically appropriate both in terms of concentration and time window. The distribution of outcomes after head injury means that, in unselected populations, a proportional improvement to the extent usually sought may be difficult to achieve. Future studies may need to consider more extensive work in "targeted populations" (selected by type and severity of damage) as a preliminary step before proceeding to definitive studies of efficacy, in which expectations of effect need to be lower and correspondingly large numbers of patients studied. Recant experience in the evaluation of glutamate NMDA antagonists is reviewed.

Clinical Trials as Topic↗

The European Brain Injury Consortium survey of head injuries.

To provide a picture of contemporary practice, a survey was carried out of severely and moderately head injured patients admitted to 67 'neuro' centres in 12 European countries. 1,005 adult head injuries were recruited over a three month period. Sixty items of information on demography, clinical features, investigations, management and early complications were captured on a simple, two-page questionnaire and, information on outcome at six months on a third page. The median age of the subjects was 38 years, 74% were male and 51% injured in road traffic accidents; 57% of patients were transferred to the 'neuro' centre from another hospital. Assessment of clinical responsiveness was limited by the use of sedation and intubation and information from four early time points (pre-hospital, arrival at the Accident and Emergency department, post-resuscitation, and arrival at the 'neuro' unit) was combined to stratify the subjects as severe (58%), moderate (17%) or intermediate (19%). In 48% of patients classified the CT scan showed features of a 'mass lesion' and in 40% showed a subarachnoid haemorrhage. Fifty-five centres provided the data on outcome for 94% of the cases recruited in these centres six months after injury. 31% died, 3% were vegetative, 16% severely disabled, 20% moderately disabled and 31% had made a good recovery. Comparison of the data from different parts of Europe showed differences in the frequency of secondary transfer, cause of injury, occurrence of major extracranial injury, CT scan findings, intracranial operation, clinical severity of injury and utilisation of the components of intensive care and the occurrence of a favourable outcome, although the latter difference was not statistically significant when variations in the initial severity of injury were taken into account. The findings in the present survey are compared with newly analysed information for three previous large series: the International Data Bank involving the UK, the Netherlands and the USA, the North American Traumatic Coma Data Bank, and data from four centres in the UK. The comparisons showed substantial similarities and also differences that may reflect variations in policy for admission of the head injury to 'neuro' units, and evolution in methods of assessment, investigation and management. The effects of these differences on outcome requires further, rigorous prospective study.

Adolescent↗

Cost-effectiveness analysis of nimodipine treatment after aneurysmal subarachnoid hemorrhage and surgery.

OBJECTIVE: To assess the cost-effectiveness ratio of nimodipine administration after aneurysmal subarachnoid hemorrhage (SAH) and surgery. METHODS: One hundred twenty-seven patients of both sexes who had a ruptured aneurysm (verified using angiography), who presented with Hunt and Hess Grades I to III on admission, who underwent an operation within the first week after SAH, and who had participated in a randomized prospective clinical trial of nimodipine medication were enrolled in the study. The efficiency (cost-effectiveness) of nimodipine treatment was evaluated by incremental cost-effectiveness analysis. The cost-effectiveness ratio was evaluated for two groups: patients treated with nimodipine and patients given placebo. The cost was estimated as direct hospitalization costs, and the patient outcome was measured as life years gained. RESULTS: The incremental cost-effectiveness ratio for nimodipine treatment was $223 per life year gained on the basis of 1996 monetary values and contemporary management of SAH. Patients in the nimodipine group had an average of 3.46 years longer life expectancy (incremental effectiveness) than those in the placebo group. There was a significant difference in 3-month follow-up mortality and a slight difference in sickness pensions during the 10 years after SAH. Nimodipine treatment was associated with a significant decrease in mortality. There were no statistically significant differences between the treatment groups in the length of hospital stay. There were no statistically significant differences between the treatment groups in sickness pensions. CONCLUSION: Nimodipine is cost-effective. Therefore, its use in the management of patients with SAH seems economically justified because it increases patient life years at very low incremental cost.

Adolescent↗

QT dispersion after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) causes a stress response with increased concentrations of plasma catecholamines and serious cardiac arrhythmias. Increased QT dispersion has been shown to predispose to cardiac arrhythmias. In SAH patients, QT dispersion has not been studied previously. QT dispersion was analyzed in 26 patients with SAH and in 16 patients (control group) scheduled for ligation of a nonruptured cerebral aneurysm. In 15 patients with SAH, the plasma concentrations of catecholamines were analyzed, and an 18-hour continuous electrocardiogram (ECG) recording was obtained. In the other 11 patients, electrocardiography was repeated daily for up to 9 days for analysis of QT dispersion. The median (25th and 75th percentiles) QT dispersion in all SAH patients was 78 milliseconds (50 and 109 milliseconds, respectively), and in control patients, it was 25 milliseconds (15 and 33 milliseconds, respectively) (P < .001). There was a positive correlation with QT dispersion and the plasma concentration of DHPG, a metabolite of norepinephrine (P < .05). All patients had episodes of cardiac arrhythmia during the 18-hour recording period. In conclusion, increased QT dispersion is a common finding after SAH and may be a result of high plasma concentrations of catecholamines in these patients.

Adrenergic Agonists↗

Extracranial contribution to cerebral oximetry in brain dead patients: a report of six cases.

The near infrared spectroscopy offers a noninvasive method to monitor regional brain oxygenation. The problem with the technique appears to be possible extacranial contribution to the measurements. As a part of another study, we monitored regional saturation (rSO2) in six brain dead patients either during the test for spontaneous respiration or in those not eligible for organ donation, after discontinuation of mechanical ventilation. Relatively normal rSO2 values were obtained after brain death, and the values decreased concomitantly with the hemoglobin saturation of oxygen (SpO2) after the discontinuation of mechanical ventilation. A corresponding decrease in SpO2 and rSO2 suggests extracranial contribution to the measured rSO2. The diagnosis of brain death cannot be made based on this technology; furthermore the presence of extracranial contribution may limit its potential value even in other applications.

Adult↗

Severe and fatal childhood trauma.

We wanted to study epidemiology and the outcome of severe childhood trauma. A retrospective study was carried out of 347 severely injured children under 16 years of age, who required intensive care or died during a 10-year period in southern Finland. Of the severely injured children, 65.4 per cent were male. Blunt injuries were the most common (83.0 per cent) followed by penetrating injuries (4.9 per cent), burns (4.6 per cent) and others (7.5 per cent). Of the patients with blunt or penetrating trauma, 85.6 per cent had head injury alone, or combined with other injuries. The majority of all injuries (58.2 per cent) and deaths (59.3 per cent) in children were caused by road traffic accidents. Of this patient population, 64 died at the scene, 54 died in hospital and 229 survived. Most of the deceased trauma patients (77.1 per cent) died within the first 6 h following the incident and all the deaths occurred within 9 days. The annual incidence of severe trauma was 14.1 per 100,000 children, and the annual mortality was 4.8 per 100,000. All the trauma deaths occurred immediately or within a few days of the accident. Late trauma deaths due to sepsis or multiple organ failure were not seen in children.

Accidents, Home↗

EBIC-guidelines for management of severe head injury in adults. European Brain Injury Consortium.

Guidelines 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.

Adult↗