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  • 1.
    Andersson, Nina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Grip, Helena
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brändström, Helge
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Air transport of patients with intracranial air: computer model of pressure effects2003In: Aviation, Space and Environmental Medicine, ISSN 0095-6562, E-ISSN 1943-4448, Vol. 74, no 2, p. 138-144Article in journal (Refereed)
  • 2.
    Arnell, Kai
    et al.
    Department of Paediatric Surgery, University Hospital, Uppsala.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Evaluation of Strata NSC and Codman Hakim adjustable cerebrospinal fluid shunts and their corresponding antisiphon devices: laboratory investigation2009In: Journal of Neurosurgery: Pediatrics, ISSN 1933-0707, E-ISSN 1933-0715, Vol. 3, no 3, p. 166-172Article in journal (Refereed)
    Abstract [en]

    OBJECT: The authors investigated and compared the in vitro characteristics of 2 CSF shunts, the Strata NSC and the Codman Hakim, and their corresponding antisiphon devices (ASDs).

    METHODS: Six new CSF shunts and the corresponding ASDs for each model were tested in an automated, computerized experimental setup based on pressure regulation. Opening pressure accuracy, resistance, sensitivity to abdominal pressure, antisiphon effect, and the influence of different ASD positions were determined.

    RESULTS: In general the shunts performed according to the manufacturers' specifications. However, at the lowest setting, the opening pressure of the Strata NSC was close to 0, and in the Codman Hakim shunt, it was higher than specified. The resistance in the Codman Hakim shunt (5.4 mm Hg/ml/min) was much higher than that in the Strata NSC (3.6 mm Hg/ml/min). Abdominal pressure affected opening pressure in both valves. Positioning the Strata ASD above or below the ventricular catheter tip resulted in higher and lower opening pressures, respectively, than when it was placed in line with the catheter. The positioning of the Codman Hakim ASD did not influence the opening pressure.

    CONCLUSIONS: Both CSF shunts work properly, but at the lowest setting the opening pressure of the Strata NSC was near 0 and in the Codman Hakim it was twice the manufacturer's specifications. The resistance in the Strata NSC was below the normal physiological range, and in the Codman Hakim device it was in the lower range of normal. The ASD did not change the shunt characteristics in the lying position and therefore might not do so in children. If this is the case, then a shunt system with an integrated ASD could be implanted at the first shunt insertion, thus avoiding a second operation and the possibility of infection.

  • 3.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Transcranial Doppler pulsatility index: not an accurate method to assess intracranial pressure.2010In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 66, no 6, p. 1050-1057Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Transcranial Doppler sonography (TCD) assessment of intracranial blood flow velocity has been suggested to accurately determine intracranial pressure (ICP). OBJECTIVE: We attempted to validate this method in patients with communicating cerebrospinal fluid systems using predetermined pressure levels. METHODS: Ten patients underwent a lumbar infusion test, applying 4 to 5 preset ICP levels. On each level, the pulsatility index (PI) in the middle cerebral artery was determined by measuring the blood flow velocity using TCD. ICP was simultaneously measured with an intraparenchymal sensor. ICP and PI were compared using correlation analysis. For further understanding of the ICP-PI relationship, a mathematical model of the intracranial dynamics was simulated using a computer. RESULTS: The ICP-PI regression equation was based on data from 8 patients. For 2 patients, no audible Doppler signal was obtained. The equation was ICP = 23*PI + 14 (R = 0.22, P < .01, N = 35). The 95% confidence interval for a mean ICP of 20 mm Hg was -3.8 to 43.8 mm Hg. Individually, the regression coefficients varied from 42 to 90 and the offsets from -32 to +3. The mathematical simulations suggest that variations in vessel compliance, autoregulation, and arterial pressure have a serious effect on the ICP-PI relationship. CONCLUSIONS: The in vivo results show that PI is not a reliable predictor of ICP. Mathematical simulations indicate that this is caused by variations in physiological parameters.

  • 4.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ambarki, Khalid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Intracranial Pressure and Pulsatility Index:  2011In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 69, no 4, p. E1033-E1034Article in journal (Refereed)
  • 5.
    Behrens, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lenfeldt, Niklas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Are intracranial pressure wave amplitudes measurable through lumbar puncture?2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 127, no 4, p. 233-241Article in journal (Refereed)
    Abstract [en]

     Objective The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings. Methods In ten patients with normal pressure hydrocephalus, simultaneous recordings of the intracranial pressure (ICP; intraparenchymal) and lumbar pressure (LP; cerebrospinal fluid pressure) were performed. During registration, pressure was altered between resting pressure and 45mmHg using an infusion test. Data were analyzed regarding pulsations (i.e., amplitudes). Also, the pressure sensors were compared in a bench test. Results The correlation between intracranial and lumbar amplitudes was 0.98. At resting pressure, and moderately elevated ICP, intracranial pulse amplitudes exceeded that of lumbar space with about 0.9mmHg. At the highest ICP, the difference changed to 0.2mmHg. The bench test showed that the agreement of sensor readings was good at resting pressure, but reduced at higher amplitudes. Conclusions Compared to intracranial registrations, amplitudes measured through lumbar puncture were slightly attenuated. The bench test showed that differences were not attributable to dissimilarities of the sensor systems. A lumbar pressure amplitude measurement is an alternative to ICP recording, but the thresholds for what should be interpreted as elevated amplitudes need to be adjusted.

  • 6.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up2007In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 21, no 5, p. 504-509Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) of the nucleus ventralis intermedius thalami (Vim) in the treatment of essential tremor (ET) is well documented concerning the acute effects. Reports of the long-term effects are, however, few and the aim of the present study was to analyse the long-term efficacy of this treatment. Nineteen patients operated with unilateral Vim-DBS were evaluated with the Essential Tremor Rating Scale (ETRS) before surgery, and after a mean time of 1 and 7 years after surgery. The ETRS score for tremor of the contralateral hand was reduced from 6.8 at baseline to 1.2 and 2.7, respectively, on stimulation at follow-up. For hand function (item 11 – 14) the score was reduced from 12.7 to 4.1 and 8.2, respectively. Vim-DBS is an efficient treatment for ET, also after many years of treatment. There is, however, a decreasing effect over time, most noticeable concerning tremor of action.

    Read More: http://informahealthcare.com/doi/abs/10.1080/02688690701552278

  • 7.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Jabre, Mazen
    Bejjani, Boulos-Paul
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Electromagnetic environmental influences on implanted deep brain stimulators2006In: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 9, no 4, p. 262-269Article in journal (Refereed)
    Abstract [en]

    Objective.  The objective of this study was to report our observations on the external electromagnetic field influences on deep brain stimulation (DBS) in our patient population and how these influences affected our patients’ lives and other healthcare-related conditions.

    Materials and Methods.  We have retrospectively analyzed data concerning the effects of external electromagnetic fields on 172 of our patients implanted with DBS.

    Results.  Identifiable electromagnetic sources turned the implantable pulse generator (IPG) off in 20 patients. In two patients, these episodes necessitated replacement of the Itrel II IPG (Medtronic Inc., Minneapolis, MN, USA) with the magnetically shielded Kinetra IPG (Medtronic Inc.). Six patients received cardiac pacemakers, leading, in two patients, to interference between the systems. Our experience concerning magnetic resonance imaging, electrocardiogram (ECG), heart defibrillation, electro-cautery, and other sources of electromagnetic interference also is described.

    Conclusions.  External electromagnetic interference may, in rare cases, constitute a severe threat to the well-being of the patient implanted with a DBS system. Also, malfunction of a DBS system may constitute a medical emergency. Nevertheless, in spite of these external electromagnetic influences, we consider DBS to be a safe method, provided safety protocols are followed, and provided that provider awareness about potential hazards is present.

  • 8.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan
    UCL Insitute of Neurology, Queen Square, London, Uk.
    Fytagoridis, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor2011In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 17, no 8, p. 617-620Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures. Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11-14 (hand tremor and hand function) were selected for analysis of tremor outcome. The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.

  • 9.
    Bobinski, Lukas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Complications following cranioplasty using autologous bone or polymethylmethacrylate-Retrospective experience from a single center2013In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 115, no 9, p. 1788-1791Article in journal (Refereed)
    Abstract [en]

    Objective: A decompressive hemicraniectomy is a potentially life-saving intervention following head trauma. Once performed patients are obliged to undergo a second procedure with cranioplasty. Two of the most commonly used materials are autologous bone and polymethylmethacrylate (PMMA). We have now evaluated complications following a cranioplasty using these materials. Materials and methods: During a 7-year period (2002-2008) 49 patients were operated with a decompressive craniectomy following head trauma. Patients received a cranioplasty consisting of autologous bone (30 patients, 61.2%) or PMMA (19 patients, 38.8%) and were followed at least 24 months. Patient data were collected retrospectively. Results: Twenty patients (20/49, 40.8%) experienced a complication that prompted a re-operation. There was a significantly higher rate of complications leading to a re-operation (53.3% vs. 21.1%, p = 0.03) and a shorter survival time of the cranioplasty (mean 48.1 +/- 7.8 vs. 79.5 +/- 9.0 months, p = 0.035) in patients with autologous bone compared to PMMA. Bone resorption and the presence of postoperative hematomas were significantly more common in patients with autologous bone. The material used for cranioplasty was the only variable that significantly correlated to the rate of complications. Conclusions: In our series we had a high percentage of patients needing re-operation due to complications following a cranioplasty. Though generally considered a straightforward procedure, complications and associated morbidity in patients undergoing cranioplasty should not be underestimated. 

  • 10.
    Bobinski, Lukas
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Dynamics of brain tissue changes induced by traumatic brain injury assessed with the Marshall, Morris-Marshall, and the Rotterdam classifications and its impact on outcome in a prostacyclin placebo-controlled study2012In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 154, no 6, p. 1069-1079Article in journal (Refereed)
    Abstract [en]

    The present study evaluates the types and dynamics of intracranial pathological changes in patients with severe traumatic brain injury (sTBI) who participated in a prospective, randomized, double-blinded study of add-on treatment with prostacyclin. Further, the changes of brain CT scan and their correlation to Glasgow Coma Scale score (GCS), maximal intracranial pressure (ICPmax), minimal cerebral perfusion pressure (CPPmin), and Glasgow Outcome Score (GOS) at 3, 6, and 12 months were studied. Forty-eight subjects with severe traumatic brain injury were treated according to an ICP-targeted therapy protocol based on the Lund concept with the addition of prostacyclin or placebo. The first available CT scans (CTi) and follow-up scans nearest to 24 h (CT24) were evaluated using the Marshall, Rotterdam, and Morris-Marshall classifications. There was a significant correlation of the initial Marshall, Rotterdam, Morris-Marshall classifications and GOS at 3 and 12 months. The CT24 Marshall classification did not significantly correlate to GOS while the Rotterdam and the Morris-Marshall classification did. The CTi Rotterdam classification predicted outcome evaluated as GOS at 3 and 12 months. Prostacyclin treatment did not influence the dynamic of tissue changes. The Rotterdam classification seems to be appropriate for describing the evolution of the injuries on the CT scans and contributes in predicting of outcome in patients treated with an ICP-targeted therapy. The Morris-Marshall classification can also be used for prognostication of outcome but it describes only the impact of traumatic subarachnoid hemorrhage (tSAH).

  • 11.
    Brorsson, Camilla
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Rodling-Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Severe traumatic brain injury: consequences of early adverse events2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 8, p. 944-951Article in journal (Refereed)
    Abstract [en]

    Background: Several factors associated with an unfavourable outcome after severe traumatic brain injury (TBI) have been described: prolonged pre-hospital time, secondary referral to a level 1 trauma centre, the occurrence of secondary insults such as hypoxia, hypotension or low end-tidal carbon dioxide (ETCO(2)). To determine whether adverse events were linked to outcome, patients with severe TBI were studied before arrival at a level 1 trauma centre.

    Methods: Prospective, observational study design. Patients with severe TBI (n = 48), admitted to Umea University Hospital between January 2002 to December 2005 were included. All medical records from the site of the accident to arrival at the level 1 trauma centre were collected and evaluated.

    Results: A pre-hospital time of >60 min, secondary referral to a level 1 trauma centre, documented hypoxia (oxygen saturation <95%), hypotension (systolic blood pressure <90 mmHg), hyperventilation (ETCO(2) <4.5 kPa) or tachycardia (heart rate >100 beats/min) at any time before arrival at a level 1 trauma centre were not significantly related to an unfavourable outcome (Glasgow Outcome Scale 1-3).

    Conclusion: Early adverse events before arrival at a level 1 trauma centre were without significance for outcome after severe TBI in the trauma system studied.

  • 12.
    Dahlqvist, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hägg, Erik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Testicular enlargement in a patient with a FSH-secreting pituitary adenoma2010In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 37, no 2, p. 289-293Article in journal (Refereed)
    Abstract [en]

    Clinically non-functional pituitary adenomas are often derived from gonadotropin producing cells. However, gonadotropinomas causing elevated serum levels of follicle-stimulating hormone (FSH) and clinical signs of FSH hypersecretion are very rarely described. Our patient, a 56-year-old man, was referred to our clinic with signs of hypogonadism. Magnetic resonance imaging (MRI) and biochemical examinations showed a large pituitary adenoma and excessive levels of serum FSH. Clinical examination and ultrasound measurement revealed bilaterally enlarged testes. After pituitary surgery, serum FSH levels normalized and there was a decrease in testicular volume. This case suggests that supraphysiological levels of FSH from a gonadotropinoma can cause a clinically observable effect, i.e. testicular enlargement. This is in line with experimental studies showing biological effect of FSH from pituitary adenomas and previous occasional reports of ovarian hyperstimulation and testicular enlargement in patients with FSH-secreting gonadotropinomas.

  • 13.
    Eklund, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Williams, Michael A
    Luciano, Mark G
    Dombrowski, Stephen M
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Hydrodynamics of the CertasTM programmable valve for the treatment of hydrocephalus2012In: Fluids and barriers of the CNS, ISSN 2045-8118, Vol. 9, no 1, p. 12-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The new CertasTM shunt for the treatment of hydrocephalus has seven standard pressure settings that according to the manufacturer range from 36 to 238 mmH2O, and an additional "Virtual Off" setting with an opening pressure >400 mmH2O. Information on actual pressure response and reliability of shunt performance is important in clinical application, especially the "Virtual Off" setting as a non-surgical replacement for shunt ligation. The objective of this study was to evaluate the in-vitro hydrodynamic performance of the CertasTM shunt.

    METHODS: Six new CertasTM shunts with proximal and distal catheters were tested with an automated, computerized test system that raised the pressure from zero to a maximum pressure and back to zero at each valve setting. Opening pressure and flow resistance were determined.

    RESULTS: For settings 1-7 the measured opening pressure range was 26 to 247 mmH2O, and the mean change in opening pressure for a one-step adjustment was between 33 and 38 mmH2O. For setting 8 ("Virtual Off") the measured mean opening pressure was 494 +/- 34 mmH2O (range 451 to 556 mmH2O). The mean outflow resistance was 7.0 mmHg/ml/min (outflow conductance 17.9 ul/s/kPa).

    CONCLUSIONS: The six shunts had similar characteristics and closely matched the manufacturer's specifications for opening pressure at settings 1-7. The opening pressure for the "Virtual Off" setting was nearly 500 mmH2O, which is 100 mmH2O higher than the manufacturer's specification of ">400" and should be functionally off for most patients with communicating hydrocephalus. Clinical studies are needed to evaluate if the CSF dynamic profile persists after implantation in patients.

  • 14. Grände, P-O
    et al.
    Koskinen, L-O
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Reinstrup, P
    Romner, B
    Conventional treatments for severe head injury: are they effective, ineffective, or even harmful?2007In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 51, no 10, p. 1294-1296Article in journal (Other academic)
  • 15.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life2008In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 118, no 6, p. 387-394Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To report long-term effects of thalamic deep brain stimulation (DBS) on activities of daily living (ADL) and health-related quality of life (HRQoL) in patients with essential tremor (ET).

    MATERIALS AND METHODS: Nineteen consecutive patients were evaluated at baseline, at a mean of 1 year, then at a mean of 7 years after DBS using Tremor Rating Scale, Mini Mental Test, ADL Taxonomy, Nottingham Health Profile, Life Satisfaction Checklist, Visual Analogue Scale and interview.

    RESULTS: There was a decrease of DBS efficacy on tremor between 1 and 7 years post-operatively. The marked improvement in ADL at 1 year was no longer sustained at long-term, except for the ability to eat. Social life remained improved.

    CONCLUSION: Although there is a decrease of DBS effect on tremor at 7 years, and even though further ageing and co-morbidities may impact on the well-being of patients, there is still relevant benefit of DBS on few aspects of ADL and HRQoL in patients with ET.

  • 16.
    Koskinen, L. O.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Olivecrona, M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rodling-Wahlstrom, M.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Prostacyclin treatment normalises the MCA flow velocity in nimodipine-resistant cerebral vasospasm after aneurysmal subarachnoid haemorrhage: a pilot study2009In: Acta Neurochir (Wien), Vol. 151, no 6, p. 595-9; discussion 599Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cerebral vasospasm triggered by subarachnoid haemorrhage is one of the major causes of post-haemorrhage morbidity and mortality. Several treatment modalities have been proposed, and none of them are fully effective. METHODS: In this study we treated five patients with prostacyclin suffering vasospasm after a ruptured aneurysm not responding to high i.v. doses of nimodipine. All patients were severely ill, unconscious and in need of intensive care. FINDINGS: A low dose of prostacyclin i.v. infusion for 72 h reversed the vasospasm as measured by transcranial Doppler technique. The mean MCA blood flow velocity decreased from 199 +/- 31 cm/s to 92 +/- 6 cm/s within 72 h after the start of the prostacyclin infusion. CONCLUSIONS: We suggest that low-dose prostacyclin treatment, an old treatment strategy, can be a treatment option in patients with vasospasm not responding to ordinary measures.

  • 17.
    Koskinen, Lars-Owe D
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sympathicotomy affects cutaneous blood flow, temperature, and sympathicus-mediated reflexes2008In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 118, no 6, p. 402-406Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the sympathetically mediated effects of transthoracic endoscopic sympathicotomy (TES) in the treatment of severe primary palmar hyperhidrosis.

    MATERIALS AND METHODS: The effects of TES, on sympathetic ganglia at the thoracic level of 2-3, finger blood flow, temperature, and on heat and cold provocation were investigated. Middle cerebral artery (MCA) blood flow velocities were studied by transcranial Doppler.

    RESULTS: The finger blood flow increased by about 700% after TES and finger temperature by 7.0 +/- 0.5 degrees C. Several autonomic reflexes were dramatically affected. A finger pulp-shrinking test showed a major decrease after surgery. MCA mean blood flow velocities were not affected by TES.

    CONCLUSIONS: Besides the high success rate of good clinical effect of TES on palmar hyperhidrosis, major effects on local blood flow and temperature are elicited by TES. Complex autonomic reflexes are also affected. The patient should be completely informed before surgery of the side effects elicited by TES.

  • 18.
    Koskinen, Lars-Owe D.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sjöberg, Rickard L.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Predicting improvement after surgery for palmar hyperhidrosis2012In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 126, no 5, p. 324-328Article in journal (Refereed)
    Abstract [en]

    Objectives Endoscopic transthoracic sympathectomy (ETS) is a surgical procedure used to improve Quality of Life (QoL) in patients with treatment resistant palmar hyperhidrosis (PHH). The aim of this study was to test the hypothesis that low preoperative scores on The Everyday Life Questionnaire (EDLQ) would predict QoL improvement after surgery. Materials and methods Pre- and post-operative QoL scores from a series of 30 consecutive patients who underwent ETS at our institution were analyzed. Results Preoperative QoL scores was a significant predictor of post-operative improvement across all dimensions covered by the questionnaire. Conclusion Preoperative low QoL can be used as a guide in selecting patients with most improved QoL after ETS.

  • 19.
    Koskinen, Lars-Owe D.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Grayson, David
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The complications and the position of the Codman MicroSensor (TM) ICP device: an analysis of 549 patients and 650 Sensors2013In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 155, no 11, p. 2141-2148Article in journal (Refereed)
    Abstract [en]

    Complications of and insertion depth of the Codman MicroSensor ICP monitoring device (CMS) is not well studied. To study complications and the insertion depth of the CMS in a clinical setting. We identified all patients who had their intracranial pressure (ICP) monitored using a CMS device between 2002 and 2010. The medical records and post implantation computed tomography (CT) scans were analyzed for occurrence of infection, hemorrhage and insertion depth. In all, 549 patients were monitored using 650 CMS. Mean monitoring time was 7.0 +/- 4.9 days. The mean implantation depth was 21.3 +/- 11.1 mm (0-88 mm). In 27 of the patients, a haematoma was identified; 26 of these were less than 1 ml, and one was 8 ml. No clinically significant bleeding was found. There was no statistically significant increase in the number of hemorrhages in presumed coagulopathic patients. The infection rate was 0.6 % and the calculated infection rate per 1,000 catheter days was 0.8. The risk for hemorrhagic and infectious complications when using the CMS for ICP monitoring is low. The depth of insertion varies considerably and should be taken into account if patients are treated with head elevation, since the pressure is measured at the tip of the sensor. To meet the need for ICP monitoring, an intraparenchymal ICP monitoring device should be preferred to the use of an external ventricular drainage (EVD).

  • 20.
    Koskinen, Lars-Owe D
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Intracranial pressure monitoring using the Codman MicroSensor2010In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 67, no 1, p. 221-Article in journal (Other academic)
  • 21.
    Koskinen, Lars-Owe D.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Runnerstam, Magnus
    Koch, Mona
    FOI, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
    Karlsson, Britt M.
    FOI, Swedish Defence Research Agency, SE-901 82 Umeå, Sweden.
    Cerebral microvascular effects of nimodipine in combination with soman2012In: Environmental Toxicology and Pharmacology, ISSN 1382-6689, E-ISSN 1872-7077, Vol. 34, no 3, p. 905-910Article in journal (Refereed)
    Abstract [en]

    Nimodipine, a calcium antagonist, has been shown to increase the detoxification of soman. In this study the cerebral microcirculatory effects of nimodipine and the acetylcholinesterase inhibitor soman was studied. Anaesthetised rats were administered nimodipine, 10 mg kg(-1) or vehicle intra-peritoneally, and 1 h later exposed to 45 mu g kg(-1) soman intravenously. The regional blood flows were measured using the microsphere method. Nimodipine and soman markedly increased the cerebral blood flow (CBF) and reduced the vascular resistance. Total CBF increased by 146% after nimodipine and by 105% after soman administration. Combined administration of nimodipine and soman caused additional but not fully additive effects on CBF and vascular resistance, indicating possible different mechanisms of the two agents. A part of the nimodipine induced increased detoxification after AChE-inhibition may be associated with this cerebral vasodilation. (C) 2012 Elsevier B.V. All rights reserved.

  • 22.
    Koskinen, Lars-Owe
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, Magnus
    Department of Anaesthesia and Intensive Care, University of Örebro, Sweden.
    Grande, P. O.
    Department of Clinical Science in Lund, Anaesthesia and Intensive Care, Lund University, Sweden.
    Severe traumatic brain injury management and clinical outcome using the Lund concept2014In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 283, p. 245-255Article, review/survey (Refereed)
    Abstract [en]

    This review covers the main principles of the Lund concept for treatment of severe traumatic brain injury. This is followed by a description of results of clinical studies in which this therapy or a modified version of the therapy has been used. Unlike other guidelines, which are based on meta-analytical approaches, important components of the Lund concept are based on physiological mechanisms for regulation of brain volume and brain perfusion and to reduce transcapillary plasma leakage and the need for plasma volume expanders. There have been nine non-randomized and two randomized outcome studies with the Lund concept or modified versions of the concept. The non-randomized studies indicated that the Lund concept is beneficial for outcome. The two randomized studies were small but showed better outcome in the groups of patients treated according to the modified principles of the Lund concept than in the groups given a more conventional treatment. This article is part of a Special Issue entitled: Brain compensation. For good?. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  • 23.
    Lehtipalo, Stefan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars Ove
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Kolmodin, Jane
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Continuous interscalene brachial plexus block for postoperative analgesia following shoulder surgery1999In: Acta Anaesthesiol Scand, Vol. 43, no 3, p. 258-64Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Severe postoperative pain is a well-known problem following shoulder surgery. This study evaluates the clinical efficacy of continuous interscalene brachial plexus block, patient-controlled analgesia, and morphine (i.v. and i.m.) for postoperative analgesia in this setting. METHODS: Thirty patients, scheduled for acromioplasty during general anesthesia, were randomly allocated to one of three different postoperative pain management groups. Group MO received morphine (5 mg i.m. and 2 mg i.v.) when visual analogue pain score (VAS) > 3, group PL received a continuous interscalene brachial plexus block with bupivacaine (1.25 mg kg-1 + 0.25 mg kg-1 h-1) and group PCA received patient-controlled analgesia with morphine (bolus 1 mg). Postoperative pain relief was assessed (24 h) by VAS, circulatory and respiratory stress parameters (heart rate, systemic arterial pressure and respiratory rate) and stress metabolites (glucose, lactate, glycerol by abdominal subcutaneous microdialysis). RESULTS: Pain relief in the PL group was effective (VAS < 3) and significantly more potent than in groups MO and PCA, except at 16 and 20 h. Lactate was significantly increased in the PL group, glucose was significantly increased in all groups, while glycerol showed a variable pattern. There were no significant stress metabolite differences among groups. VAS showed no statistical correlation with microdialysate, respiratory or circulatory data. CONCLUSION: Successful continuous interscalene brachial plexus block provides very good pain relief following shoulder surgery and is superior to the other methods studied. However, we were unable to demonstrate a correlation between VAS pain scores and stress indicators in metabolic, circulatory and respiratory parameters.

  • 24.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nilsson, Leif
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Cortisol levels are influenced by sedation in the acute phase after subarachnoid haemorrhage2013In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 4, p. 452-460Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Subarachnoid haemorrhage (SAH) is a life-threatening condition that may be aggravated by acute pituitary damage and cortisol insufficiency. Robust diagnostic criteria for critical illness-related corticosteroid insufficiency (CIRCI) are lacking. The aim of this study was to assess the frequency of CIRCI in the acute phase (0-240 h) after SAH and to evaluate associations between cortisol levels and clinical parameters (sedation, circulatory failure, gender, age, severity of disease, treatment). CIRCI was defined as a single morning serum cortisol (mSC) < 200 nmol/L. The lower limit for calculated free cortisol (cFC) was set at < 22 nmol/L, and for saliva cortisol at < 7.7 nmol/L.

    METHODS: Fifty patients were included. Serum/saliva cortisol and corticosteroid-binding globulin were obtained every second morning. A logistic regression model was used for multivariate analysis comparing cortisol levels with clinical parameters.

    RESULTS: Of the patients, 21/50 (42%) had an mSC < 200 nmol/L and 30/50 (60%) had a cFC < 22 nmol/L. In patients with continuous intravenous sedation, the odds ratio for a mSC to be < 200 nmol/L was 18 times higher (95% confidence interval 4.2-85.0, P < 0.001), and the odds ratio for a cFC to be < 22 nmol/L was 2.4 times higher (95% confidence interval 1.2-4.7, P < 0.05) compared with patients with no continuous intravenous sedation.

    CONCLUSIONS: Continuous intravenous sedation was significantly associated with cortisol values under defined limits (mSC < 200, cFC < 22 nmol/L). The possibility that sedating drugs per se may influence cortisol levels should be taken into consideration before CIRCI is diagnosed.

  • 25.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Borota, Ljubisa
    Department of Radiology, Oncology and Radiation Science, Uppsala University, Sweden .
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    ADMA levels and arginine/ADMA ratios reflect severity of disease and extent of inflammation after subarachnoid hemorraghe2014In: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 21, no 1, p. 91-101Article in journal (Refereed)
    Abstract [en]

    Background: Subarachnoid hemorrhage (SAH) is characterized by an inflammatory response that might induce endothelial dysfunction. The aim of this study was to evaluate if ADMA and arginine/ADMA ratios after SAH (indicators of endothelial dysfunction) are related to clinical parameters, inflammatory response, and outcome.

    Methods: Prospective observational study. ADMA, arginine, C-reactive protein (CRP), and cytokines were obtained 0–240 h (h) after SAH. Definition of severe clinical condition was Hunt&Hess (H&H) 3–5 and less severe clinical condition H&H 1–2. Impaired cerebral circulation was assessed by clinical examination, transcranial doppler, CT-scan, and angiography. Glasgow outcome scale (GOS) evaluated the outcome.

    Results: Compared to admission, 0–48 h after SAH, the following was observed 49–240 h after SAH; (a) ADMA was significantly increased at 97–240 h (highest 217–240 h), (b) CRP was significantly increased at 49–240 h (highest 73–96 h), (c) interleukin-6 (IL-6) was significantly lower at 97–240 h (highest 49–96 h), p < 0.05. ADMA, CRP, and IL-6 were significantly lower and peak arginine/ADMA ratio was significantly higher in patients with H&H 1–2 compared to patients with H&H 3–5, p < 0.05. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with (55 %) or without (45 %) signs of impaired cerebral circulation. The peak ADMA or the nadir arginine/ADMA ratio did not differ significantly between patients with GOS 1–3 and patients with GOS 4–5.

    Conclusions: ADMA increased significantly after SAH, and the increase in ADMA started after the pro-inflammatory markers (CRP and IL-6) had peaked. This might indicate that endothelial dysfunction, with ADMA as a marker, is induced by a systemic inflammation.

  • 26.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Edvardsson, Ludwig
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology. Göteborgs universitet.
    Long term survivors of subarachnoid haemorrhage have an increased risk of death due to cerebrovascular causesManuscript (preprint) (Other academic)
  • 27.
    Lindgren, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Edvardsson, L.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Naredi, S,
    Anestesiologi, Sahlgrenska Akademin, Göteborg.
    Long-term subarachnoid haemorrhage survivors still die due to cerebrovascular causes2015In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 132, no 6, p. 410-416Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Subarachnoid haemorrhage (SAH) is associated with sympathetic nervous activation and inflammation. SAH could therefore theoretically be a risk factor for development of cardiovascular disease. The aim of this study was to investigate whether long-term (>/=1 year) SAH survivors had an increased risk of death due to cardiovascular causes. MATERIAL & METHODS: SAH patients >/=18 years treated at Umea University Hospital between 1986 and 2006 were eligible for inclusion. Deceased patients were identified in the Swedish population register. Death certificates from long-term SAH survivors and causes of death in the general population were obtained from the National Board of Health and Welfare, Sweden. The prevalence of comorbidities at the time of SAH was compared with the distribution of cardiovascular risk factors in the northern Sweden MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) health survey. Analyses were stratified for age and sex. RESULTS: In the SAH patients, the median year of SAH was 1992 and the median year of death was 2001. The MONICA survey in 1994 and the distribution of deaths in the general population in 2001 were used for comparison. Long-term SAH survivors had, compared to the general population, a significantly increased risk for death due to cerebrovascular disease (P < 0.0001), but not for death due to cardiovascular disease. Hypertension was more common in SAH patients compared to survey participants (P < 0.01). CONCLUSION: Cerebrovascular causes of death were significantly more common in long-term survivors after SAH compared to the general population.

  • 28.
    Lindvall, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Ericsson, Mats
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Gothefors, Leif
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Reducing intracranial pressure may increase survival among patients with bacterial meningitis2004In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 38, no 3, p. 384-390Article in journal (Refereed)
    Abstract [en]

    We reported findings concerning continuous intracranial pressure (ICP) and cerebral perfusion pressure (CPP) measurements and mortality in patients with severe bacterial meningitis treated on the basis of an ICP-targeted approach. Eighteen patients with severe bacterial meningitis were admitted for neurointensive care at Umeå University Hospital (Umeå, Sweden). In 15 patients, ICP was measured continuously through an ICP measuring device. During care, all patients but one developed intracranial hypertension with an ICP of ⩾15 mm Hg (14 [93%] of 15 patients). Ten (67%) of 15 patients survived and were discharged, and 5 patients (33%) died. Mean ICP was significantly higher and CPP was markedly decreased in nonsurvivors, compared with survivors. Among the survivors, ICP was gradually reduced. Treatment of patients with severe bacterial meningitis should include neurointensive care and continuous ICP measurement. Increased ICP may be reduced by using the ICP-targeted therapy that closely resembles the “Lund concept.”

  • 29.
    Lindvall, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Anticoagulants and antiplatelet agents and the risk of development and recurrence of chronic subdural haematomas2009In: Journal of clinical neuroscience, ISSN 0967-5868, E-ISSN 1532-2653, Vol. 16, no 10, p. 1287-1290Article in journal (Refereed)
    Abstract [en]

    Seventy-one patients from northern Sweden were diagnosed with chronic subdural haematomas (CSDH) and treated at the Department of Neurosurgery at Umeå University Hospital over 12 months. Fifty-four patients with CSDH had a history of head trauma (trauma group), while 17 patients had no previous head trauma (non-trauma group). In the non-trauma group 71% of patients were treated with anticoagulants or antiplatelet aggregation agents (AAA) compared to 18% in the trauma group. Considering only AAA, 59% of the non-trauma patients were treated with these drugs versus 17% of patients in the trauma group. The recurrence rate for all patients was 17%. These findings confirm that the use of anticoagulants and AAA is over-represented in patients with non-traumatic CSDH. In our study, recurrence was not associated with previous use of anticoagulants or AAA.

  • 30.
    Lindvall, Peter
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Runnerstam, Magnus
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    The Fisher grading correlated to outcome in patients with subarachnoid haemorrhage2009In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 23, no 2, p. 188-192Article in journal (Refereed)
    Abstract [en]

    Cerebral vasospasm is the major cause of delayed ischemia in patients with subarachnoid haemorrhage (SAH). The Fisher grading scale has been used to predict patients in risk of developing vasospasm. Improved radiological techniques and treatment may have changed the relevance of the Fisher scale. We have now evaluated the Fisher scale, Hunt and Hess and age in relation to outcome in patients with SAH. Eighty- three patients were admitted with SAH during two years, and 84 aneurysms were treated in 78 patients. The Glasgow outcome score (GOS) within 3 months were as follows; GOS 1 (19%), GOS 2 (2%), GOS 3 (11%), GOS 4 (9%), GOS 5 (59%). There was a significant correlation between both the Fisher grading scale, Hunt and Hess scale and outcome. Age was not correlated to the Fisher grading scale or the Hunt and Hess scale. Age was also not correlated to outcome in our patients. Despite the correlation to outcome both Hunt and Hess and the Fisher grading scale had a limited predictive value of outcome due to a low specificity and/or sensitivity.

  • 31.
    Lundkvist, Bo
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Birgander, Richard
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Cerebrospinal fluid dynamics and long-term survival of the Strata(®) valve in idiopathic normal pressure hydrocephalus.2011In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 124, no 2, p. 115-121Article in journal (Refereed)
    Abstract [en]

    Objective -  Cerebrospinal fluid (CSF) dynamics and long-term shunt survival of the Strata(®) CSF shunt were evaluated in patients with idiopathic normal pressure hydrocephalus (INPH). Subjects and methods -  Seventy-two patients with INPH received a Strata(®) valve. A CSF infusion test, neuroimaging and video recording of gait were performed at baseline and at 6 months (n = 68) after surgery. Long-term shunt survivals were obtained from patient records. Results -  The shunt survival at 1 year was 94% and at 3 years 92.5%. Forty-nine patients (72%) had an improved gait. Two patients were improved despite non-functioning shunts, indicating a possible placebo response. Nineteen patients were not improved at the 6-month follow-up. The shunt tests revealed a functioning shunt in 12; thus, unnecessary shunt revisions could be avoided. Seventeen patients showed a siphoning effect. Shunt revisions were made in six patients. Eight hygromas/subdural hematomas were found. Conclusions -  The long-term survival of the Strata(®) valves was good, and a concern of complications is not a reason to exclude elderly with INPH from shunt surgery. Studies are needed to evaluate pros and cons of the anti-siphon device. Using a CSF shunt test, unnecessary shunt revisions may be avoided.

  • 32.
    Malm, J.
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Bergenheim, A. T.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Enblad, P.
    Department of Neuroscience/Neurosurgery, University Hospital, Uppsala, Sweden.
    Hårdemark, H.-G.
    Department of Neuroscience/Neurosurgery, University Hospital, Uppsala, Sweden.
    Koskinen, L-O D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Nordström, C.-H.
    Department of Clinical Sciences, Lund, University Hospital, Lund, Sweden.
    Norrving, B.
    Department of Clinical Sciences, Lund, University Hospital, Lund, Sweden.
    Uhlin, J.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Lindgren, A.
    Department of Clinical Sciences, Lund, University Hospital, Lund, Sweden.
    The Swedish Malignant Middle cerebral artery Infarction Study: long-term results from a prospective study of hemicraniectomy combined with standardized neurointensive care2006In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 113, no 1, p. 25-30Article in journal (Refereed)
    Abstract [en]

    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 ≤2.

    Results: Thirty patients were included (median age at stroke onset 49 years, range 17–67 years). Fourteen patients had mMCA infarct on the left side and 16 patients on the right side. Fourteen patients had pupil dilatation before surgery. Hemicraniectomy was performed at a median of 52 h (range 13–235 h) after stroke onset. Nine patients died within 1 month after surgery because of cerebral herniation (n = 6), myocardial infarction (n = 1) or intensive care complications (n = 2). No further deaths occurred during follow-up, which was at median 3.4 years after surgery. Status for the 21 survivors at the last follow-up was: mRS 2 or less (n = 6) and mRS 3–5 (n = 15). The oldest patient with mRS 2 or less was 53 years at stroke onset. Thirteen patients (43%) could walk without substantial aid.

    Conclusion:  The long-term survival after mMCA infarction treated with hemicraniectomy seems to be favourable if the patient survives the acute phase. The outcome as measured with mRS may be better among younger patients.

  • 33.
    Naredi, S.
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Koskinen, L. O.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Grände, P. O.
    Nordström, C. H.
    Nellgård, B.
    Rydenhag, B.
    Vegfors, M.
    Treatment of traumatic head injury--U.S./European guidelines or the Lund concept2003In: Crit Care Med, Vol. 31, no 11, p. 2713-4Article in journal (Refereed)
  • 34.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The IMPACT prognosis calculator used in patients with severe traumatic brain injury treated with an ICP-targeted therapy2012In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 154, no 9, p. 1567-1573Article in journal (Refereed)
    Abstract [en]

    The prognosis of severe traumatic brain injury (sTBI) is important. The International Mission on Prognosis in Traumatic Brain Injury (IMPACT) study group has developed a prediction calculator for the outcome of patients with sTBI, and this has been made available on the World Wide Web. We have studied the use of the IMPACT calculator on sTBI patients treated with an ICP-targeted therapy based on the Lund concept. The individual clinical data of patients in a prospective sTBI protocol-driven trial of the treatment of sTBI using the Lund concept were entered into the prognosis calculator, and the individual prognosis for each patient was calculated and compared with the actual outcome at 6 months. The use of the IMPACT calculator led to an overestimation of mortality and of an unfavourable outcome. Compared with the IMPACT database, the absolute risk reduction (ARR) for mortality was 13.6 %. There is a statistically significant probability for the prediction of mortality and unfavourable outcome. A ROC curve analysis shows an area under the curve (AUC) in the Core model for mortality of 0.744 and of unfavourable outcome of 0.731, in the Extended model of 0.751 and 0.721 respectively, and in the Lab model of 0.779 and 0.810 respectively. The IMPACT prognosis calculator should be used with caution for the prediction of outcome for an individual patient with sTBI treated with an ICP-targeted therapy based on the Lund concept. We conclude that we have to initiate treatment in all patients with blunt sTBI and an initial ICP > 10 mmHg. It seems that the outcome in sTBI patients treated in this fashion is better than would have been expected from the IMPACT prognosis.

  • 35.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rodling Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Effective ICP reduction by decompressive craniectomy in patients with severe traumatic brain injury treated by an ICP-targeted therapy2007In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 24, no 6, p. 927-935Article in journal (Refereed)
    Abstract [en]

    Severe traumatic brain injury (TBI) is one of the major causes of death in younger age groups. In Umea, Sweden, an intracranial pressure (ICP) targeted therapy protocol, the Lund concept, has been used in treatment of severe TBI since 1994. Decompressive craniectomy is used as a protocol-guided treatment step. The primary aim of the investigation was to study the effect of craniectomy on ICP changes over time in patients with severe TBI treated by an ICP-targeted protocol. In this retrospective study, all patients treated for severe TBI during 1998-2001 who fulfilled the following inclusion criteria were studied: GCS <or= 8 at intubation and sedation, first recorded cerebral perfusion pressure (CPP) of >10 mm Hg, arrival within 24 h of trauma, and need of intensive care for >72 h. Craniectomy was performed when the ICP could not be controlled by evacuation of hematomas, sedation, ventriculostomy, or low-dose pentothal infusion. Ninety-three patients met the inclusion criteria. Mean age was 37.6 years. Twenty-one patients underwent craniectomy as a treatment step. We found a significant reduction of the ICP directly after craniectomy, from 36.4 mm Hg (range, 18-80 mm Hg) to 12.6 mm Hg (range, 2-51 mm Hg). During the following 72 h, we observed an increase in ICP during the first 8-12 h after craniectomy, reaching approximately 20 mm Hg, and later levelling out at approximately 25 mm Hg. The reduction of ICP was statistically significant during the 72 h. The outcome as measured by Glasgow Outcome Scale (GOS) did not significantly differ between the craniectomized group (DC) and the non-craniectomized group (NDC). The outcome was favorable (GOS 5-4) in 71% in the craniectomized group, and in 61% in the non-craniectomized group. Craniectomy is a useful tool in achieving a significant reduction of ICP overtime in TBI patients with progressive intracranial hypertension refractory to medical therapy. The procedure seems to have a satisfactory effect on the outcome, as demonstrated by a high rate of favorable outcome and low mortality in the craniectomized group, which did not significantly differ compared with the non-craniectomized group.

  • 36.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rodling Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Prostacyclin treatment in severe traumatic brain injury: a microdialysis and outcome study2009In: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 26, no 8, p. 1251-1262Article in journal (Refereed)
    Abstract [en]

    Prostacyclin (PGI2) is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation. In trauma the balance between PGI2 and thromboxane A2 (TXA2) is shifted towards TXA2. External provided PGI2 would, from a theoretical and experimental point of view, improve the microcirculation in injured brain tissue. This study is a prospective consecutive double blinded randomised study on the effect of PGI2 versus placebo in severe traumatic brain injury (sTBI). All patients with sTBI were eligible. Inclusion criteria: verified sTBI, Glasgow Coma Score (GCS) at intubation and sedation ≤8, age 15 - 70 years, a first recorded cerebral perfusion pressure (CPP) of ≥ 10mmHg, and arrival within 24h of trauma. All subjects received an intra-cranial pressure (ICP) measuring device, bilateral intracerebral microdialysis catheters, and a microdialysis catheter in the abdominal subcutaneous adipose tissue. Subjects were treated according to an ICP targeted therapy based on the Lund concept. 48 patients, mean age of 35.5 years, and a median GCS 6 (3-8) were included. We found no significant effect of epoprostenol on either the lactate pyruvate ratio (L/P) at 24 hours or the brain glucose levels. There was no significant difference in clinical outcome between the two groups. The median Glasgow Outcome Score (GOS) at 3 months was 4, and mortality was 12.5%. The favourable outcome (GOS 4-5) was 52%. The initial L/P did not prognosticate for outcome. Thus our results indicate that there is no effect of PGI2 at a dose of 0.5 ng/kg/min on brain L/P, brain glucose levels or outcome at 3 months. The treatment seemed to yield a high number of favourable outcome and low mortality

  • 37.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rodling-Wahlstrom, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Prostacyclin treatment and clinical outcome in severe traumatic brain injury patients managed with an ICP-targeted therapy: A prospective study2012In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 26, no 1, p. 67-75Article in journal (Refereed)
    Abstract [en]

    Objective: To prospectively assess clinical outcome in patients with severe traumatic brain injury (sTBI) managed according to an ICP-targeted programme as well as additional treatment with prostacyclin.

    Materials and methods: Inclusion criteria were GCS <= 8, age 15-70 years, first recorded cerebral perfusion pressure (CPP)>10mmHg. Exclusion criteria were pregnancy, breastfeeding or penetrating brain injury. The patients were treated using the same ICP-guided protocol, with one group randomized to receive prostacyclin in a low dose (0.5 ng kg(-1) min(-1)). The clinical outcome was prospectively assessed at 3, 6, 12, 18 and 24 months using structured interviews.

    Results: Forty-eight patients were included, mean age 35.5 years, median GCS 6 (3-8), 69% were multi-traumatized. Mortality at 3 months was 12.5%. Median Glasgow Outcome Scale (GOS) at all follow-up points was 4. Favourable outcome (GOS 4-5) at 3 months was 52%, at 24 months 64%. Favourable outcome increased over time. There was a statistically significant association between GOS, GCS at admission and age. Higher ICP(max) was associated with worse outcome.

    Conclusion: With this treatment protocol, a low number of deaths and a high number of favourable outcomes in sTBI were observed. Prostacyclin in this low dose does not seem to improve the outcome. ICP(max) is a positive predictor of worse outcome. Higher GCS at admission and lower age are correlated to better outcome.

  • 38.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Rodling-Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy2009In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, no 11, p. 1241-1247Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To prospectively study S-100B and neuron specific enolase (NSE) levels in subjects treated for severe head injury (sTBI), and investigate the prognostic value of these biomarkers. METHODS: Subjects included in a prospective double blind randomised study for sTBI. Inclusion criteria: Glasgow Coma Score (GCS) 10 mm Hg and arrival <24 h after trauma. Subjects were treated with an intracranial pressure (ICP) targeted therapy. Blood samples for S-100B and NSE were drawn immediately after arrival and every 12 h for 5 days. Outcome was evaluated as Glasgow Outcome Scale (GOS) by independent staff at 3 and 12 months. RESULTS: 48 subjects, mean age 35.5 years, and median GCS 6 were included. The first blood sample was drawn at 15.6 (1.4) h after injury. Initial concentration of S-100B was 1.04 (0.21) microg/l and for NSE 18.94 (2.32) microg/l. The biomarkers were significantly higher in subjects with GCS 3 and in those who died compared with those with GCS 4-8 and GOS 2-5, respectively. Receiver operated characteristic curve analyses of the initial S-100B and NSE levels to GOS dichotomised as unfavourable (GOS 1-3) and favourable (GOS 4-5) showed a weak correlation: AUC 0.585 and 0.555, respectively. Using the dichotomisation dead (GOS 1)/alive (GOS 2-5), the AUC values were 0.687 and 0.734, respectively. Furthermore, a correlation was found between the biomarkers themselves and the biomarkers and ICP. CONCLUSION: At 3 and 12 months after trauma, no differences in prognostic values between the markers were apparent nor was there any clinical significant value of the markers as predictors of clinical outcome.

  • 39.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience.
    Rodling-Wahsltröm, Marie
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    S-100B and NSE are poor outcome predictors in severe traumatic brain injury treated by an ICP targeted therapyManuscript (Other academic)
  • 40.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Wildemyr, Zandra
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    The apolipoprotein E epsilon4 allele and outcome in severe traumatic brain injury treated by an intracranial pressure-targeted therapy2010In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 112, no 5, p. 1113-1119Article in journal (Refereed)
    Abstract [en]

    The presence of epsilon4 is not associated with long-term clinical outcome in patients with severe TBI treated with an ICP targeted therapy, based on the Lund concept.

  • 41.
    Olivecrona, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Zetterlund, Bo
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Rodling-Wahlström, Marie
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Absence of electroencephalographic seizure activity in patients treated for head injury with an ICP targeted therapy2009In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 110, no 2, p. 300-305Article in journal (Refereed)
    Abstract [en]

    OBJECT: The authors prospectively studied the occurrence of clinical and nonclinical electroencephalographically verified seizures during treatment with an intracranial pressure (ICP)-targeted protocol in patients with traumatic brain injury (TBI). METHODS: All patients treated for TBI at the Department of Neurosurgery, University Hospital Umea, Sweden, were eligible for the study. The inclusion was consecutive and based on the availability of the electroencephalographic (EEG) monitoring equipment. Patients were included irrespective of pupil size, pupil reaction, or level of consciousness as long as their first measured cerebral perfusion pressure was > 10 mm Hg. The patients were treated in a protocol-guided manner with an ICP-targeted treatment based on the Lund concept. The patients were continuously sedated with midazolam, fentanyl, propofol, or thiopental, or combinations thereof. Five-lead continuous EEG monitoring was performed with the electrodes at F3, F4, P3, P4, and a midline reference. Sensitivity was set at 100 muV per cm and filter settings 0.5-70 Hz. Amplitude-integrated EEG recording and relative band power trends were displayed. The trends were analyzed offline by trained clinical neurophysiologists. RESULTS: Forty-seven patients (mean age 40 years) were studied. Their median Glasgow Coma Scale score at the time of sedation and intubation was 6 (range 3-15). In 8.5% of the patients clinical seizures were observed before sedation and intubation. Continuous EEG monitoring was performed for a total of 7334 hours. During this time neither EEG nor clinical seizures were observed. CONCLUSIONS: Our protocol-guided ICP targeted treatment seems to protect patients with severe TBI from clinical and subclinical seizures and thus reduces the risk of secondary brain injury.

  • 42.
    Olivecrona, Zandra
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bobinski, Lucas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The association of ICP, CPP, CT findings and the levels of S-100B and NSE in severe traumatic head injury. Prognostic value of the biomarkers.Manuscript (preprint) (Other academic)
    Abstract [en]

    The first hypothesis was that biochemical markers of brain injury might be influenced by the intracranial pressure (ICP) and cerebral perfusion pressure (CPP) after severe traumatic brain injury (sTBI), in patients treated by an ICP targeted therapy. A second hypothesis was that there is a relationship between the biomarker levels and a systematic classification of the CT-scan of the brain. We also hypothesized that clinical outcome can be related to biomarker levels and that mortality may be predicted by the biomarkers. In this prospective consecutive study patients with sTBI were included. Inclusion criteria were Glasgow Coma Scale (GCS) score ≤ 8, age between 15 and 70 years, an initial cerebral perfusion pressure >10 mm Hg. Blood samples for neuron specific enolase (NSE) and S-100B were collected twice daily during five consecutive days. The initial (CTinit) and follow-up CT-scans (CT24h) were classified according to the Marshall, Rotterdam and Morris-Marshall classifications. Outcome was evaluated with extended Glasgow outcome scale (GOSE) at 3 months. There was a clear correlation of the maximal ICP (ICPmax) and minimal CPP (CPPmin) with the S-100B and NSE levels. A complex relation between biomarkers and the CT classifications were observed. Generally, the Marshall scores were correlated to the biomarker levels at 72 hrs and the Rotterdam scores correlated to the total (bulk) release. The Morris-Marshall scores correlated to all S-100B values, but not to any of the NSE values. A ROC curve analysis showed that the biomarkers had a moderate predictive value of mortality. S-100B bulk release and NSE at 72 hrs had the highest power in this prediction. A combination of the CT classification according to Morris-Marshall and the bulk release of S-100B further improved the prediction of clinical outcome.

  • 43.
    Olivecrona, Zandra
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bobinski, Lukas
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Association of ICP, CPP, CT findings and S-100B and NSE in severe traumatic head injury. Prognostic value of the biomarkers2015In: Brain Injury, ISSN 0269-9052, E-ISSN 1362-301X, Vol. 29, no 4, p. 446-454Article in journal (Refereed)
    Abstract [en]

    Objective: The association was studied of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) on S-100B and neuron-specific enolase (NSE) in severe traumatic brain injury (sTBI). The relationship was explored between biomarkers, ICP, CPP, CT-scan classifications and the clinical outcome.

    Materials and methods: Data were collected prospectively and consecutively in 48 patients with Glasgow Coma Scale score ≤ 8, age 15–70 years. NSE and S-100B were analysed during 5 consecutive days. The initial and follow-up CT-scans were classified according to the Marshall, Rotterdam and Morris-Marshall classifications. Outcome was evaluated with extended Glasgow outcome scale at 3 months.

    Results: Maximal ICP and minimal CPP correlated with S-100B and NSE levels. Complex relations between biomarkers and CT classifications were observed. S-100B bulk release (AUC = 0.8333, p = 0.0009), and NSE at 72 hours (AUC = 0.8476, p = 0.0045) had the highest prediction power of mortality. Combining Morris-Marshall score and S-100B bulk release improved the prediction of clinical outcome (AUC = 0.8929, p = 0.0008).

    Conclusion: Biomarker levels are associated with ICP and CPP and reflect different aspects of brain injury as evaluated by CT-scan. The biomarkers might predict mortality. There are several pitfalls influencing the interpretation of biomarker data in respect to ICP, CPP, CT-findings and clinical outcome.

  • 44.
    Olivecrona, Zandra
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Dahlqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Acute neuro-endocrine profile and prediction of outcome after severe brain injury2013In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 21, no 33Article in journal (Refereed)
    Abstract [en]

    Object: The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome.

    Methods: Prospective study, including consecutive patients, 15-70 years, with sTBI, Glasgow Coma Scale (GCS) score <= 8, initial cerebral perfusion pressure > 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08-10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17-19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E.

    Results: Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. < 276 nmol/L (= 10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3 and TSH at day 4 in patients with a poor outcome at 3 months. 5) A higher Marshall CT score was associated with higher day 1 LH/FSH-and lower day 4 TSH levels 6) In general no significant correlation between GCS, ICP or CPP and hormone levels were detected. Only ICPmax and LH day 1 in men was significantly correlated.

    Conclusion: Profound dynamic changes in hormone levels are found in the acute phase of sTBI. This is consistent with previous findings in different groups of critically ill patients, most of which are likely to be attributed to physiological adaptation to acute illness. Low cortisol levels were a common finding, and not associated with unfavorable outcome. A retained ability to a dynamic hormonal response, i.e. fast and strong suppression of the pituitary-gonadal axis (day 1) and ability to restore activity in the pituitary-thyroid axis (day 4) was associated with less severe injury according to CT-findings and favorable outcome.

  • 45.
    Olivecrona, Zandra
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    The release of S-100B and NSE in severe traumatic head injury is associated with APOE epsilon 42012In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 154, no 4, p. 675-680Article in journal (Refereed)
    Abstract [en]

    In this article we tested the hypothesis that the level of two biochemical markers of brain injury may be associated with the apolipoprotein E (APOE) epsilon 4 allele. In this prospective consecutive study patients with sTBI were included (n = 48). Inclusion criteria were Glasgow Coma Scale (GCS) score a parts per thousand currency signaEuro parts per thousand 8 at the time of intubation and sedation, patient age between 15 and 70 years, an initial cerebral perfusion pressure > 10 mmHg, and arrival to our level-one trauma university hospital within 24 h after trauma. Blood samples for neuron-specific enolase (NSE) and S-100B were collected as soon as possibly after arrival, and then twice daily (12-h intervals) for 5 consecutive days. Venous blood was used for APOE genotype determination. Clinical outcome at 3 months after injury was assessed with the Extended Glasgow Outcome Scale (GOSE). Significantly higher levels of the maximal S-100B (S-100B(max)) and area under the curve (S-100B(AUC)) were found in subjects with the APOE epsilon 4 allele compared to those with non-epsilon 4. A similar tendency was observed for NSEmax and NSEAUC, though not statistically significant. Our data indicate that there might be a gene-induced susceptibility to severe traumatic brain injury and that patients with the APOE epsilon 4 allele may be more predisposed to brain cellular damage measured as S-100B and NSE. Thus, it seems to be of importance to consider the APOE genotype in interpreting the levels of the biomarkers.

  • 46.
    Qvarlander, Sara
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Lundkvist, Bo
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus2013In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, no 7, p. 735-741Article in journal (Refereed)
    Abstract [en]

    Background: It is suggested that disturbed CSF dynamics are involved in the pathophysiology of idiopathic normal pressure hydrocephalus (INPH). The pulsatility curve describes the relationship between intracranial pressure (ICP) and the amplitude of cardiac related ICP pulsations. The position of baseline ICP on the curve provides information about the physiological state of the CSF dynamic system. The objective of the study was to investigate if shunt surgery modifies the pulsatility curve and the baseline position on the curve, and how this relates to gait improvement in INPH.

    Methods: 51 INPH patients were investigated with lumbar CSF dynamic investigations preoperatively and 5 months after shunt surgery. During the investigation, ICP was measured at baseline, and then a CSF sample was removed, resulting in pressure reduction. After this, ICP was regulated with an automated infusion protocol, with a maximum increase of 24 mm Hg above baseline. The pulsatility curve was thus determined in a wide range of ICP values. Gait improvement was defined as a gait speed increase >= 0.1 m/s.

    Results: The pulsatility curve was unaltered by shunting. Baseline ICP and amplitude were reduced (-3.0 +/- 2.9 mm Hg; -1.1 +/- 1.5 mm Hg; p < 0.05, n = 51). Amplitude reduction was larger for gait improvers (-1.2 +/- 1.6 mm Hg, n = 42) than non-improvers (-0.2 +/- 0.5 mm Hg, n = 9) (p < 0.05) although mean ICP reduction did not differ.

    Conclusions: The pulsatility curve was not modified by shunt surgery, while the baseline position was shifted along the curve. Observed differences between gait improvers and non-improvers support cardiac related ICP pulsations as a component of INPH pathophysiology.

  • 47.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bengtsson, Anders
    The Sahlgrenska Academy, University of Gothenburg.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Effects of prostacyclin on the early inflammatory response in patients with traumatic brain injury: a randomised clinical study2014In: SpringerPlus, E-ISSN 2193-1801, Vol. 3, article id 98Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE AND DESIGN: A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI).

    SUBJECTS: 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23).

    TREATMENT: Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours.

    METHODS: Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI.

    RESULTS: A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly lower in the epoprostenol group compared to the placebo group (p = 0.04). ADMA was significantly increased within 49-72 h and remained elevated, but there was no effect of epoprostenol on ADMA levels. No significant differences between the epoprostenol and placebo groups were detected for IL-8 or sICAM-1.

    CONCLUSIONS: Administration of the prostacyclin analogue epoprostenol significantly decreased CRP and, to some extent, IL-6 levels in patients with severe TBI compared to placebo. These findings indicate an interesting option for treatment of TBI and warrants future larger studies.

    TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01363583.

  • 48.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Ahlm, Clas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Infectious Diseases.
    Bengtsson, Anders
    Anestesi och intensivvård, Sahlgrenska Universitetssjukhuset, Göteborg.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Prostacyclin modulates the systemic inflammatory response in traumatic brain injury: a randomised clinical studyIn: Article in journal (Other academic)
    Abstract [en]

    Purpose:

    Systemic inflammatory response is common in patients with severe traumatic brain injury (TBI), and may contribute to a less favourable outcome. The aim was to evaluate the effect of prostacyclin on systemic inflammation.

    Methods:

    This study is part of a prospective, randomised, clinical trial on the effect of prosta­cyclin (epoprostenol, Flolan®) in patients with severe TBI. Epoprostenol/placebo was given during 72 hours and then de-escalated. Interleukin-6, interleukin-8, soluble intracellular adhesion molecules-1 (sICAM-1) and C-reactive protein (CRP) were sampled daily.

    Results:

    46 patients were included and randomised to 23 of each group (epopros­tenol/placebo). Interleukin-6 was statistically lower within 96 hours (p = 0.04), and CRP within 96 and 120 hours (p = 0.04 and p = 0.008 respectively) after trauma in the epoprostenol group compared to the placebo group. No significant differences were detected between the groups in the levels of interleukin-8 and sICAM-1 or in outcome.

    Conclusions:

    Administration of the prostacyclin analogue epoprostenol, compared to placebo significantly decreased interleukin-6 and CRP levels in patients with severe TBI. The beneficial effect of this decrease is further to investigate.

  • 49.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Anesthesiology and Intensive Care.
    Subarachnoid haemorrhage induces a long-lasting increase of asymmetric dimethylarginine, ADMA, in serumArticle in journal (Other academic)
    Abstract [en]

    Background and Purpose: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), inhibiting nitric oxide (NO) production and thus induces vasoconstriction and endothelial dysfunction. ADMA might therefore be involved in the cerebral vasospasm and cardiovascular complications observed after subarachnoid haemorrhage (SAH). The aim of this study was to evaluate whether ADMA was increased in subjects during the acute phase (first week) and non-acute phase (three months later) after SAH.

    Methods: Prospective clinical study of 20 subjects with SAH. ADMA in serum (ADMA/s) at admission was compared to sex and age matched controls. ADMA/s and ADMA in cerebrospinal fluid (ADMA/csf, from subjects with ventriculostomy) were determined by HPLC-based separation and detection.

    Results: There was no significant difference in ADMA/s the day after SAH (day 2) between SAH subjects and controls (0.22±0.10 vs. 0.25±0.12 µmol/L). ADMA/s increased by 68% during the first week after SAH (day 2; 0.22±0.10 vs. day 7; 0.37±0.34 µmol/L, p<0.05) and remained elevated at a three-month follow-up (0.36±0.10 µmol/L). ADMA/csf was significantly lower than ADMA/s throughout the study period.

    Conclusion; ADMA/s in SAH subjects increased significantly during the first week after SAH and remained elevated at a three-month follow-up. This might indicate that reduction of the available NO is involved in long-term effects after SAH.

  • 50.
    Rodling Wahlström, Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naredi, Silvana
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Hultin, Magnus
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Subarachnoid haemorrhage induces an inflammatory response followed by a delayed persisting increase in asymmetric dimethylarginine2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 6, p. 484-489Article in journal (Refereed)
    Abstract [en]

    Object: Subarachnoid haemorrhage (SAH) is associated with an inflammatory systemic response and cardiovascular complications. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and might contribute to cerebral vasoconstriction and cardiovascular complications after SAH. ADMA is also involved in inflammation and induces endo­thelial dysfunction.

    The aim of this study was to evaluate whether and how CRP (marker for systemic inflammation) and ADMA increased in patients during the acute phase (first week) after SAH. The ADMA level was also assessed in the patients in a non-acute phase (three months), and in healthy controls.

    Methods: Prospective study of 20 patients with aneurysmal SAH. ADMA and CRP were followed daily during the first week after SAH and a follow up sample for ADMA was obtained three months later. A single blood sample for ADMA was collected from age and sex matched healthy controls (n=40, 2 for each case).

    Results: CRP increased significantly from day 2; 16  (Confidence interval (CI) 10-23) mg/L to day 4; 84 (CI 47-120) mg/L, (p<0.01). ADMA increased significantly from day 2; 0.22 (CI 0.17-0.27) µmol/L, to day 7; 0.37 (CI 0.21-0.54) µmol/L, p<0.01. ADMA remained elevated at a three-month follow-up 0.36 (CI 0.31-0.42) µmol/L.

    ADMA in the first sample from the patients (day 1-3); 0.25 (CI 0.19-0.30) µmol/L, was not different from ADMA in matched healthy controls; 0.25 (CI 0.20-0.31), p>0.05.

    Conclusion: After SAH, CRP and ADMA in serum increased significantly during the first week and ADMA remained elevated three months later.

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