[Sharp increase in the number of sick leave cases with the diagnoses Concussion, S06.0, and Postconcussion syndrome F07.2]. / Kraftig ökning av sjukskrivningar på grund av hjärnskakning.

Statistics from the Swedish Social Insurance Agency show a sharp increase in the number of sick leave cases with the diagnoses Concussion, S06.0, and Postconcussional syndrome, F07.2, between the years 2010 and 2022. The reason for the increase has not been established and needs further investigation. One possible reason is that the acute phase treatment recommendations of individuals with mild traumatic brain injury have changed during the relevant time period. Future guidelines must ensure that treatment and management recommendations are based on controlled studies of an adequate population and that treatment outcomes are continuously evaluated.

Evaluation of the effects of AZD3480 on cardiac repolarization: a thorough QT/QTc study using moxifloxacin as a positive control.

In order to evaluate their potential effects on cardiac repolarization, all new drugs must undergo clinical electrocardiographic evaluation in a thorough QT/QTc (TQT) study. AZD3480, a central nervous system-selective, neuronal nicotinic receptor (NNR) agonist, is predominantly metabolized by cytochrome P450 2D6 (CYP2D6). Employing an innovative design, this TQT study assessed the effects of supratherapeutic doses of AZD3480, relative to those of placebo, on cardiac repolarization in healthy male volunteers genotyped as either poor metabolizers (PMs) or extensive metabolizers (EMs) of CYP2D6 substrates. Supratherapeutic doses of AZD3480-resulting in ~10- and ~50-fold higher exposures (PMs and EMs, respectively) than achieved with a 20-mg dose-had no pharmacologic effect on cardiac repolarization relative to placebo. Likewise, no safety/tolerability concerns were observed after either supratherapeutic or 20-mg dosing to either population. No clinically relevant treatment-related changes or trends were observed in laboratory parameters, vital signs, or electrocardiogram (ECG). This study demonstrated that AZD3480 does not prolong QT/QTc interval.

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

OBJECTIVES: Hemicraniectomy in patients with malignant middle cerebral artery (mMCA) infarct may be life-saving. The long-term prognosis is unknown. METHODS: 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

Penetration of fusidic acid and rifampicin into cerebrospinal fluid in low-grade inflammatory meningitis caused by Staphylococcus epidermidis.

Cerebrospinal fluid (CSF) concentration-time curves of rifampicin and fusidic acid were studied in a patient with post-operative meningitis caused by Staphylococcus epidermidis. The patient was treated with this combination of antimicrobial agents because of a severe hypersensitivity reaction to vancomycin. Peak CSF concentrations of rifampicin exceeded the MIC by > 60-fold, while those of fusidic acid just reached the MIC. CSF concentrations of fusidic acid were relatively stable within the range reported for patients with uninflamed meninges, but serum levels were surprisingly low. An increase in the metabolism of fusidic acid induced by rifampicin cannot be excluded.

Amphetamines for improving recovery after stroke.

BACKGROUND: Experimental animal research shows that treatment with amphetamines improves recovery after focal cerebral ischaemia. If the effect were similar in humans, amphetamine treatment could have a major impact on recovery from stroke. OBJECTIVES: The objective of this review was to assess the effects of amphetamine treatment in patients with stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched November 2002). In addition, we searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4 2002), MEDLINE (1966-September 2002), EMBASE (1980-November 2002), and Science Citation Index (1992-December 2002). The reference lists of all relevant articles and reviews were checked, and we contacted researchers in the field to identify further published and unpublished studies. SELECTION CRITERIA: Randomized unconfounded trials comparing amphetamine with placebo. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Seven studies involving 172 patients were included. The quality of the trials varied but was generally high. Based on two trials (85 patients) there was no evidence that amphetamine treatment reduced death or dependence (Peto's odds ratio, [Peto OR] 1.54; 95% Confidence Interval [CI] 0.64 to 3.73). In these two trials, there were imbalances at baseline, with more serious strokes allocated to amphetamine. This imbalance may account for the trend for more deaths at the end of follow-up among amphetamine allocated patients (Peto OR 3.33; 95% CI 0.99 to 11.24). Based on 4 studies (95 patients) there was evidence of a better relative change in motor function according to the Fugl-Meyer motor scale (Weighted Mean Difference, [WMD] -8.17 points; 95% CI -13.58 to -2.76) and based on 1 study (21 patients) there was evidence of a better change in language function as assessed by the Porch Index of Communicative Ability score (WMD -7.51 points; 95% CI -14.42 to -0.60) in amphetamine allocated patients. REVIEWER'S CONCLUSIONS: At present, too few patients have been studied to draw any definite conclusions about the effects of amphetamine treatment on recovery from stroke. The suggested benefits on motor and language function, and the non-significant trend towards increased risk of death, could be related to imbalances in prognostic variables or other bias in studies. Further research in this area is therefore justified.

Early cerebral hyperglycolysis after subarachnoid haemorrhage correlates with favourable outcome.

BACKGROUND: Intracerebral microdialysis (MD) was applied in patients with severe subarachnoid haemorrhage treated in a neurosurgical intensive care unit in order to explore their cerebral energy metabolism. METHOD: Brain MD fluid levels of glucose, lactate and pyruvate were measured for 3 to 12 days in 20 patients and 2,635 hourly samples were analysed. The MD data were related to computerized tomography and clinical outcome, assessed by the Glasgow Outcome Scale. FINDINGS: The study showed that most patients who made a good recovery had a specific curve pattern when plotting the studied metabolites over time, characterised by a distinct decrease in MD-glucose and a parallel increase in both MD-lactate and pyruvate. Patients who had an unfavourable outcome lacked this distinct curve pattern and exhibited more irregular changes, including increased levels of both MD-glucose and lactate and low MD-pyruvate levels. INTERPRETATION: This exploratory study suggests that accumulation of interstitial lactate and pyruvate, together with decreasing levels of glucose is a favourable prognostic pattern presumably reflecting increased glucose metabolism. Such hyperglycolysis may be elicited in patients with recovery potential to cope with an extreme metabolic demand set in motion by a brain insult to restore brain cell homeostasis and integrity.

Duplex scan findings in patients with spontaneous cervical artery dissections.

AIM: to report duplex scan findings in patients with spontaneous internal carotid artery (ICA) or vertebral artery (VA) dissection. MATERIAL AND METHODS: the records of 24 patients (13 males and 11 females, median age 48 years [range 25-68 years]) with spontaneous extracranial ICA dissection (n=20) or VA dissection (n=4), identified between January 1995 and December 1999, were retrospectively analysed. RESULTS: four different abnormal flow patterns were observed in patients with ICA dissection: (a) absence of flow (15%), (b) staccato flow (50%), (c) reduced flow velocity (25%) and, (d) stenotic flow (10%). B-mode ultrasound showed a homogenous echolucent lesion in eight patients and a double lumen in two. Staccato flow along the entire ICA was observed in only four patients without verified dissection during the study period. In the four patients with VA dissection, duplex scanning demonstrated staccato flow in three and reversed low-amplitude pulsatile flow in one. CONCLUSION: duplex scanning is an important noninvasive diagnostic modality in patients with cervical artery dissection. Staccato flow along the extracranial ICA strongly indicates the presence of spontaneous ICA dissection.

Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study.

BACKGROUND AND PURPOSE: Patients treated with oral anticoagulants (ACs) have an increased risk of intracerebral hemorrhage (ICH), which is more often fatal than spontaneous ICH. Options to reverse the AC effect include intravenous administration of vitamin K, plasma, and coagulation factor concentrate. However, the optimal management of AC-related ICH has not been determined in any randomized trial. In this study, the present management of AC-related ICH was surveyed, and determinants of survival were assessed. METHODS: We retrospectively reviewed the medical records of all AC-related ICHs at 10 Swedish hospitals during a 4-year period, 1993 to 1996. Survival status after the ICH was determined from the Swedish National population register. RESULTS: We identified 151 patients with AC-related ICH. Death rates were 53.6% at 30 days, 63.6% at 6 months, and 77.5% at follow-up (mean 3.5 years). The case fatality ratio at 30 days was 96% among patients unconscious on admission (n=27), 80% among patients who became unconscious before active treatment was started (n=15), 55% among patients in whom no special action was taken except withdrawal of AC treatment (n=42), and 28% among patients given active anti-coumarin treatment while they were still conscious (n=64). The case fatality ratio at 30 days was 11% in the group treated with plasma (n=18), 30% in the group treated with vitamin K (n=23), and 39% in the group treated with coagulation factor concentrate (n=23). Within the first 24 to 48 hours after admission, 47% of the patients deteriorated. Choice of therapy to reverse the AC effect differed substantially between the hospitals (P<0.0001), as did the time interval from symptom onset to start of treatment. Multiple logistic regression analysis showed only 2 factors (intraventricular extension of bleeding and ICH volume) that were independently related to case fatality at both 30 days and 6 months. The results were similar when the analysis was restricted to patients who were conscious on admission. CONCLUSIONS: In AC-related ICH, a progressive neurological deterioration during the first 24 to 48 hours after admission is frequent, and the mortality is high. Choice of therapy to reverse the AC effect differed considerably between the hospitals. There was no evidence that any treatment strategy was superior to the others. A randomized controlled trial is needed to determine the best choice of treatment.

The importance of Doppler angle of insonation on differentiation between 50-69% and 70-99% carotid artery stenosis.

AIM: to investigate the importance of Doppler angle differentiating between 50-69% and >/=70% internal carotid artery (ICA) stenosis. MATERIAL AND METHODS: fifty-one patients with a previous diagnosis of 50-69% ICA stenosis (n =53) were re-evaluated by duplex scanning. Spectral Doppler velocity waveforms were obtained from common carotid (CCA), ICA and external (ECA) carotid arteries with the same Doppler angle of insonation as used at the initial duplex scanning, followed by repeated measurements with a fixed 60 degrees angle of insonation. RESULTS: the peak systolic velocity (PSV) in the ICA was 181+/-55 cm/s (mean+/-SD) at the second duplex scanning when the same angle of insonation (mean 46 degrees +/-9) was used as during the initial investigation. When the examination was done with a 60 degrees angle of insonation, PSV ICA was 261+/-96 cm/s (mean+/-SD). In fifteen arteries the estimated degree of ICA stenosis changed from 50-69% to 70-99% due to the application of a fixed Doppler angle of insonation at 60 degrees. CONCLUSION: the Doppler angle of insonation has a significant effect on spectral Doppler velocity measurements. It is crucial that duplex criteria are standardised with a fixed angle of insonation and that this angle is consistently used during velocity estimations.

Improved survival after aneurysmal subarachnoid hemorrhage: review of case management during a 12-year period.

OBJECT: Based on the concept that unfavorable clinical outcome after aneurysmal subarachnoid hemorrhage (SAH), to a large extent, is a consequence of all ischemic insults sustained by the brain during the acute phase of the disease, management of patients with SAH changed at the authors' institution in the mid-1980s. The new management principles affected referral guidelines, diagnostic and monitoring methods, and pharmacological and surgical treatment in a neurointensive care setting. The impact of such changes on the outcome of aneurysmal SAH over a longer period of time has not previously been studied in detail. This was the present undertaking. METHODS: The authors analyzed all patients with SAH admitted to the neurosurgery department between 1981 and 1992. This period was divided in two parts, Period A (1981-1986) and Period B (1987-1992), and different aspects of management and outcome were recorded for each period. In total, 1206 patients with SAH (mean age 52 years, 59% females) were admitted; an aneurysm presumably causing the SAH was found in 874 (72%). The 30-day mortality rate decreased from 29% during the first 2 years (1981-1982) to 9% during the last 2 years (1991-1992) (Period A 22%; Period B 10%; p<0.0001) and the 6-month mortality rate decreased from 34 to 15% (Period A 26%; Period B 16%; p<0.001). At follow-up review conducted 2 to 9 years (mean 5.2 years) after SAH occurred, patients were evaluated according to the Glasgow Outcome Scale. Subarachnoid hemorrhage-related poor outcome (vegetative or dead) was reduced (Period A 30%; Period B 18%; p<0.001). There was an increase both in patients with favorable outcome (good recovery and moderate disability) (Period A 61 %; Period B 66%) and in those with severe disability (Period A 9%; Period B 16%; p<0.01). CONCLUSIONS: This study provides evidence that the prognosis for patients with aneurysmal SAH has improved during the last decades. The most striking results were a gradual reduction in mortality rates and improved clinical outcomes in patients with Hunt and Hess Grade I or II SAH and in those with intraventricular hemorrhage. The changes in mortality rates and the clinical outcomes of patients with Hunt and Hess Grades III to V SAH were less conspicuous, although reduced incidences of mortality were seen in some subgroups; however, few survivors subsequently appeared to attain a favorable outcome.

Influence of clinical factors, CT findings and early management on outcome in supratentorial intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Treatment of supratentorial intracerebral hemorrhage (SICH) is still controversial and new adequately sized randomized controlled trials (RCTs) of surgical evacuation are greatly needed. Our aim was to identify and quantify the most important clinical and CT factors related to prognosis in patients with SICH, to estimate the treatment effect in various subpopulations of surgically treated patients and to make assumptions on target population and sample size in future trials. METHODS: Uni- and multivariate analysis of retrospectively collected data on clinical and CT factors on admission and early management in 203 patients with SICH, mortality at discharge, 30 days, 6 and 12 months and clinical outcome according to the modified Rankin Scale (mRS) at 6 months and follow-up at a mean of 3.1 years after admission. RESULTS: Level of consciousness according to the Glasgow Coma Scale (GCS) and age were the single two factors best related to mortality at 6 and 12 months. GCS and age, in association with hematoma volume and location, arterial hypertension and to some extent use of steroids, were also related to clinical outcome according to the mRS at 6 months and 3.1 years. Surgical evacuation seemed to have a positive effect on clinical outcome in only a small subgroup of the patients. CONCLUSIONS: Our data support a future RCT of surgical evacuation versus conservative treatment in SICH restricted to patients younger than 60-65 years with a GCS on admission in the range of 6-11 and a hematoma not mainly located in the thalamus with a volume in the range of 30-100 ml causing a midline shift of less than 10 mm. Randomization should be balanced within groups of patients with lobar and basal ganglion hematomas, arterial hypertension and intraventricular hemorrhage, and the use of steroids should be discouraged.

[Thrombolysis changes the care of stroke]. / Trombolys förändrar vården vid slaganfall.

Thrombolysis using tissue plasminogen activator (tPA) is not the leading strategy in the development of pharmacological treatments for acute ischaemic stroke. The prospect of tPA becoming routine treatment in ischaemic stroke raises several issues the magnitude of the treatment load, the requisite neurological and neuroradiological diagnostic qualifications, identification of local reperfusion effects in the brain, and the pre-hospital and hospital management of acute stroke patients. The results of large randomised trials of intravenous tPA treatment are reviewed in the article, and the current state of our knowledge about interventional thrombolysis is reported. Recruitment for the second European intravenous tPA trail, ECASS II, has recently been completed, and the study findings will be available during the latter half of 1988. In the USA, tPA is already recommended treatment for acute ischaemic stroke within three hours after the onset of symptoms. In Europe, the formulation of guidelines awaits the results of ECASS II.

Spontaneous internal carotid artery dissection. Review.

Spontaneous ICA dissection is an increasingly recognized cause of stroke especially in young adults. The most frequently reported site of involvement is the cervical part of the internal carotid artery (ICA). Although several primary arteriopathies have been related to the development of spontaneous ICA dissection the cause is not clear in most cases. The clinical picture varies from mild cerebral and/or cranial nerve dysfunction to a completed stroke. Angiography has been considered as gold standard in establishing diagnosis. Recently, duplex scanning has emerged as a powerful noninvasive diagnostic tool only in the initial assessment but in the serial follow-up of patients. Early diagnosis is essential as these lesions require anticoagulant treatment. Immediate heparinization is instituted after diagnosis, followed by oral anti-coagulation for at least six months. Surgical treatment is warranted in only few cases. Complete resolutions of the dissection is seen in at least 50% of cases. The risk of recurrent stroke remains low in patients discharged alive after spontaneous ICA dissection.

Intracranial pressure changes following middle cerebral artery occlusion in rats.

Prolonged recording of intracranial pressure (ICP) was performed on rats subjected to middle cerebral artery (MCA) occlusion. ICP was repeatedly recorded before and after occlusion of the vessel via a narrow catheter placed in the cisterna magna. MCA occlusion was followed by an increase in ICP, and a pressure peak occurred after 12-24 h in all animals. Subsequently, essentially two patterns of ICP changes were observed. These seemed to be related to the severity of neurological deficits and extension of the infarct area. In the most severely affected animals, raised ICP was noted throughout the 1st week after MCA occlusion; in rats with reversible neurological deficits, ICP returned to normal values after the first peak at 12-24 h. The present investigation shows that prolonged ICP recording is feasible in MCA-occluded rats. The MCA occlusion model in rats is well characterized. Thus, ICP registration can be used in conjunction with other methods for evaluating treatment against increased ICP.