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  • 251.
    Popova, Svetlana N
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Dimberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Edqvist, Per-Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Ekman, Simon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ponten, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Sooman, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Subtyping of gliomas of various WHO grades by the application of immunohistochemistry2014Inngår i: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 64, nr 3, s. 365-379Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims

    In 2010, four subtypes (classical, proneural, mesenchymal, and neural) of glioblastoma multiforme (GBM) were defined by molecular genetic analyses. The objective of this study was to assess whether gliomas, independently of the type and grade, could be subdivided into protein-based subtypes.

    Methods and results

    A tissue microarray (TMA) approach was applied to incorporate tissue samples of low-grade and high-grade gliomas into five TMAs. High expression levels of epidermal growth factor receptor (EGFR), CD44, c-MER proto-oncogene tyrosine kinase (MERTK), platelet-derived growth factor receptor α, p53, oligodendrocyte transcription factor 2 (OLIG2) and isocitrate dehydrogenase 1 with the R132H mutation were assessed using immunohistochemistry (IHC). Glioma could be subdivided into four subtypes by IHC. The majority of the low-grade gliomas were of the proneural subtype, i.e. high p53 expression (63% of grade II). The classical subtype, with high EGFR and low p53 expression, was most common in GBMs (39%), followed by the proneural (29%) and mesenchymal (with high CD44 and MERTK expression) (29%) subtypes, a frequency that is in line with previously published data based on molecular genetics.

    Conclusions

    Assessment of the expression of the five proteins EGFR, CD44, MERTK, p53 and OLIG2 is sufficient for subtyping gliomas, and can be recommended for implementation in clinical practice for both low-grade and high-grade gliomas.

  • 252.
    Purins, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Brain Tissue Oxygenation in Traumatic Brain Injury: Experimental and Clinical Studies2013Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Traumatic brain injury (TBI) is a major cause of death and disability. TBI is frequently followed by cerebral ischemia which is a great contributor to secondary brain damage. The main causes of cerebral ischemia are pathophysiological changes in cerebral blood flow and metabolism. Treatment of TBI patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted treatment protocols. However, ICP and CPP alone do not provide information of the oxygen availability in the brain. Monitoring of brain tissue oxygenation (BtipO2) may give additional and valuable information about the risk for development of ischemia in TBI patients.

    The aims of this thesis were to study BtipO2 monitoring devices in-vitro regarding accuracy and stability, to detect threshold level of cerebral ischemia in-vivo and finally to examine the cerebral oxygen levels and cerebral metabolism in TBI patients.

    The BtipO2 probes performed with high accuracy and stability at different clinically relevant oxygen concentrations.

    A pig TBI model was developed by step-wise intracranial volume/pressure increase. Volume increase resulted in a gradual increased ICP, decreased CPP, intracranial compliance and BtipO2, respectively. Brain death (BD) was confirmed by negative CPP and negligible amount of previously injected microspheres in the brain tissue. The model simulated the clinical development of BD in humans with a classical pressure-volume response and systemic cardiovascular reactions. The model should be suitable for studies of brain injury mechanisms.

    From the same in-vivo model it was also possible to detect the threshold level of cerebral ischemia in the pig, where BtipO2 below 10 mmHg and CPP below 30 mmHg was associated with an impaired cerebral metabolism (microdialysis lactate to pyruvate ratio >30).

    BtipO2 together with cerebral microdialysis were studied in 23 severe TBI patients. We observed different patterns of changes in BtipO2 and cerebral microdialysis biomarkers in focal and diffuse TBI.  Increased cerebral microdialysis levels of glutamate, glycerol or the lactate/pyruvate ratio were observed at BtipO2 < 5 mmHg, indicating increased vulnerability of the brain at this critical level of tissue oxygenation in TBI patients.

    Delarbeid
    1. Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors
    Åpne denne publikasjonen i ny fane eller vindu >>Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors
    2010 (engelsk)Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, nr 4, s. 681-688Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    OBJECT: Periods of brain tissue ischemia are common after severe head injury, and their occurrence and duration are negatively correlated with outcome. Accurate and reliable measurement of brain tissue oxygenation (B(ti) pO(2)) may be a key to improve patient outcome after severe head injury. Knowledge of stability and accuracy of the B(ti) pO(2) systems is crucial. We have therefore conducted a bench test study of new Neurovent-PTO(R) (NV) and Licox(R) (LX) oxygen tension catheters to evaluate the sensor accuracy, response time to different oxygen tensions, response to temperature changes and long-term stability. METHODS: For all experiments five new fluorescent NV sensors and five new electrochemical LX sensors were used. The catheter probes were placed into a container filled with a buffer solution. The solution was equilibrated with five high precision calibration gases. The accuracy of the probes was recorded after an equilibration period of 20 min in O(2) concentrations of 5, 10, 20, 30 and 40 mmHg at 37.0 +/- 0.2 degrees C. The probe response to an increase in temperature from 37.0 degrees C to 38.5 degrees C to 40.0 degrees C in two different gases with O(2) concentrations of 10 and 20 mmHg were analysed. We also recorded the time for reaching 90% of a new oxygen concentration level when switching from one concentration to another. Finally, to test if there was a time-dependant drift in pO(2) recordings, all sensors were left in 10 mmHg O(2) solution for 10 days, and recordings were taken every 24 h. RESULTS: In all gas concentrations, NV and LX sensors measured pO(2) with high accuracy and stability in vitro (mean differences from calculated values were for NV 0.76-1.6 mmHg and for LX -0.46-0.26 mmHg). Both sensors showed a shorter response time to pO(2) increase (for NV 56 +/- 22 s and for LX 78 +/- 21 s) compared to pO(2) decrease (for NV 131 +/- 42 s and for LX 215 +/- 63 s). NV pO(2) values were more stable for changes in temperature, while LX sensors showed larger standard deviations with increasing temperature (the difference from the calculated values in 19.7 mmHg O(2) at 40 degrees C were for NV probes between 0.5 and 1.7 mmHg and LX between -2.3 and 1.9 mmHg). Both sensors gave stable results with low standard deviations during long-term (10 days) use, but with a slight elevation of measured pO(2) levels by time. CONCLUSIONS: Both NV and LX were accurate in detecting different oxygen tensions, and they did not deviate over longer recording times. However, LX needed a significantly longer time to detect changes in pO(2) levels compared to NV. Furthermore, LX probes showed an increased standard deviation with higher temperatures.

    Emneord
    Licox, Neurovent-PTO, Brain tissue oxygenation, Accuracy, Neurointensive care, Traumatic brain injury
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-110760 (URN)10.1007/s00701-009-0532-x (DOI)000275945600017 ()19826757 (PubMedID)
    Tilgjengelig fra: 2009-11-24 Laget: 2009-11-24 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    2. Standardized experimental brain death model for studies of intracranial dynamics, organ preservation, and organ transplantation in the pig
    Åpne denne publikasjonen i ny fane eller vindu >>Standardized experimental brain death model for studies of intracranial dynamics, organ preservation, and organ transplantation in the pig
    Vise andre…
    2011 (engelsk)Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 39, nr 3, s. 512-517Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    OBJECTIVES:: Brain death impairs organ function and outcome after transplantation. There is a need for a brain death model to allow studies of organ viability and preservation. For neurointensive care research, it is also of interest to have a relevant brain death model for studies of intracranial dynamics and evaluation of cerebral monitoring devices. Therefore, the objective was to develop a standardized clinically relevant brain death model. METHODS:: Six pigs of both sexes (10-12 wks old; mean weight, 24.5 ± 1.4 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure, intracranial compliance, cerebral perfusion pressure, and brain tissue oxygenation (BtiPo2) were recorded during stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 mins). Brain death criteria were decided to be reached when cerebral perfusion pressure was <0 mm Hg for 60 mins and at least 10 mL saline was inflated epidurally. BtiPo2 and arterial injections of microspheres were used for confirmation of brain death. RESULTS:: A gradual volume-dependent elevation of intracranial pressure was observed. After 10 mL of balloon infusion, mean intracranial pressure was 89.8 ± 9.7 (sd) mm Hg. Intracranial compliance decreased from 0.137 ± 0.069 mL/mm Hg to 0.007 ± 0.001 mL/mm Hg. The mean arterial pressure decreased and the heart rate increased when the intracranial volume was increased to between 5 and 6 mL. All animals showed cerebral perfusion pressure ≤0 after 7 to 10 mL of infusion. In all animals, the criteria for brain death with negative cerebral perfusion pressure and BtiPo2 ∼0 mm Hg were achieved. Only a negligible amount of microspheres were found in the cerebrum, confirming brain death. The kidneys showed small foci of acute tubular necrosis. CONCLUSIONS:: The standardized brain death model designed in pigs simulates the clinical development of brain death in humans with a classic pressure-volume response and systemic cardiovascular reactions. Brain death was convincingly confirmed.

    Emneord
    brain death, experimental animal model, intracranial pressure, cerebral perfusion pressure, brain tissue oxygenation, organ preservation
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-143532 (URN)10.1097/CCM.0b013e318206b824 (DOI)000287480000013 ()21187748 (PubMedID)
    Tilgjengelig fra: 2011-01-21 Laget: 2011-01-21 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    3. Brain Tissue Oxygenation and Cerebral Perfusion Pressure Thresholds of Ischemia in a Standardized Pig Brain Death Model
    Åpne denne publikasjonen i ny fane eller vindu >>Brain Tissue Oxygenation and Cerebral Perfusion Pressure Thresholds of Ischemia in a Standardized Pig Brain Death Model
    2012 (engelsk)Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 16, nr 3, s. 462-469Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND:

    Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. Monitoring brain tissue oxygenation (B(ti)pO(2)) is of considerable clinical interest, but the exact threshold level of ischemia has been difficult to establish due to the complexity of the clinical situation. The objective of this study was to use the Neurovent-PTO (NV) probe, and to define critical cerebral oxygenation- and CPP threshold levels of cerebral ischemia in a standardized brain death model caused by increasing the ICP in pig. Ischemia was defined by a severe increase of cerebral microdialysis (MD) lactate/pyruvate ratio (L/P ratio > 30).

    METHODS:

    B(ti)pO(2), L/P ratio, Glucose, Glutamate, Glycerol and CPP were recorded using NV and MD probes during gradual increase of ICP by inflation of an epidural balloon catheter with saline until brain death was achieved.

    RESULTS:

    Baseline level of B(ti)pO(2) was 22.9 ± 6.2 mmHg, the L/P ratio 17.7 ± 6.1 and CPP 73 ± 17 mmHg. B(ti)pO(2) and CPP decreased when intracranial volume was added. The L/P ratio increased above its ischemic levels, (>30) when CPP decreased below 30 mmHg and B(ti)pO(2) to <10 mmHg.

    CONCLUSIONS:

    A severe increase of ICP leading to CPP below 30 mmHg and B(ti)pO(2) below 10 mmHg is associated with an increase of the L/P ratio, thus seems to be critical thresholds for cerebral ischemia under these conditions.

    Emneord
    Brain tissue oxygenation, Cerebral perfusion pressure, Microdialysis, Threshold levels, Traumatic brain injury
    HSV kategori
    Forskningsprogram
    Neurokirurgi; Neurovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-170951 (URN)10.1007/s12028-012-9675-3 (DOI)000304619000019 ()
    Tilgjengelig fra: 2012-03-16 Laget: 2012-03-14 Sist oppdatert: 2018-01-12bibliografisk kontrollert
    4. Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury
    Åpne denne publikasjonen i ny fane eller vindu >>Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury
    Vise andre…
    2014 (engelsk)Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, artikkel-id 64Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Introduction: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. There are reasons to believe that knowledge of brain tissue oxygenation (BtipO2) would add information with the potential of improving patient outcome. The aim of this study was to examine BtipO2 and cerebral metabolism using the Neurovent-PTO probe and cerebral microdialysis (MD) in TBI patients.

    Methods: Twenty-three severe TBI patients with monitoring of physiological parameters, ICP, CPP, BtipO2, and MD for biomarkers of energy metabolism (glucose, lactate, and pyruvate) and cellular distress (glutamate, glycerol) were included. Patients were grouped according to injury type (focal/diffuse) and placement of the Neurovent-PTO probe and MD catheter (injured/non-injured hemisphere).

    Results: We observed different patterns in BtipO2 and MD biomarkers in diffuse and focal injury where placement of the probe also influenced the results (ipsilateral/contralateral). In all groups, despite fairly normal levels of ICP and CPP, increased MD levels of glutamate, glycerol, or the L/P ratio were observed at BtipO2 <5 mmHg, indicating increased vulnerability of the brain at this level.

    Conclusion: Monitoring of BtipO2 adds important information in addition to traditional ICP and CPP surveillance. Because of the different metabolic responses to very low BtipO2 in the individual patient groups we submit that brain tissue oximetry is a complementary tool rather than an alternative to MD monitoring.

    Emneord
    brain tissue oxygenation, cerebral metabolism, traumatic brain injury, cerebral ischemia, Neurovent-PTO
    HSV kategori
    Forskningsprogram
    Neurokirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-194684 (URN)10.3389/fneur.2014.00064 (DOI)000209629300064 ()24817863 (PubMedID)
    Forskningsfinansiär
    Swedish Research CouncilThe Swedish Brain Foundation
    Tilgjengelig fra: 2013-02-18 Laget: 2013-02-18 Sist oppdatert: 2017-12-06bibliografisk kontrollert
  • 253.
    Purins, Karlis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Sandhagen, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk fysiologi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Brain tissue oxygen monitoring: a study of in vitro accuracy and stability of Neurovent-PTO and Licox sensors2010Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, nr 4, s. 681-688Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECT: Periods of brain tissue ischemia are common after severe head injury, and their occurrence and duration are negatively correlated with outcome. Accurate and reliable measurement of brain tissue oxygenation (B(ti) pO(2)) may be a key to improve patient outcome after severe head injury. Knowledge of stability and accuracy of the B(ti) pO(2) systems is crucial. We have therefore conducted a bench test study of new Neurovent-PTO(R) (NV) and Licox(R) (LX) oxygen tension catheters to evaluate the sensor accuracy, response time to different oxygen tensions, response to temperature changes and long-term stability. METHODS: For all experiments five new fluorescent NV sensors and five new electrochemical LX sensors were used. The catheter probes were placed into a container filled with a buffer solution. The solution was equilibrated with five high precision calibration gases. The accuracy of the probes was recorded after an equilibration period of 20 min in O(2) concentrations of 5, 10, 20, 30 and 40 mmHg at 37.0 +/- 0.2 degrees C. The probe response to an increase in temperature from 37.0 degrees C to 38.5 degrees C to 40.0 degrees C in two different gases with O(2) concentrations of 10 and 20 mmHg were analysed. We also recorded the time for reaching 90% of a new oxygen concentration level when switching from one concentration to another. Finally, to test if there was a time-dependant drift in pO(2) recordings, all sensors were left in 10 mmHg O(2) solution for 10 days, and recordings were taken every 24 h. RESULTS: In all gas concentrations, NV and LX sensors measured pO(2) with high accuracy and stability in vitro (mean differences from calculated values were for NV 0.76-1.6 mmHg and for LX -0.46-0.26 mmHg). Both sensors showed a shorter response time to pO(2) increase (for NV 56 +/- 22 s and for LX 78 +/- 21 s) compared to pO(2) decrease (for NV 131 +/- 42 s and for LX 215 +/- 63 s). NV pO(2) values were more stable for changes in temperature, while LX sensors showed larger standard deviations with increasing temperature (the difference from the calculated values in 19.7 mmHg O(2) at 40 degrees C were for NV probes between 0.5 and 1.7 mmHg and LX between -2.3 and 1.9 mmHg). Both sensors gave stable results with low standard deviations during long-term (10 days) use, but with a slight elevation of measured pO(2) levels by time. CONCLUSIONS: Both NV and LX were accurate in detecting different oxygen tensions, and they did not deviate over longer recording times. However, LX needed a significantly longer time to detect changes in pO(2) levels compared to NV. Furthermore, LX probes showed an increased standard deviation with higher temperatures.

  • 254.
    Purins, Karlis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Brain Tissue Oxygenation and Cerebral Perfusion Pressure Thresholds of Ischemia in a Standardized Pig Brain Death Model2012Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 16, nr 3, s. 462-469Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. Monitoring brain tissue oxygenation (B(ti)pO(2)) is of considerable clinical interest, but the exact threshold level of ischemia has been difficult to establish due to the complexity of the clinical situation. The objective of this study was to use the Neurovent-PTO (NV) probe, and to define critical cerebral oxygenation- and CPP threshold levels of cerebral ischemia in a standardized brain death model caused by increasing the ICP in pig. Ischemia was defined by a severe increase of cerebral microdialysis (MD) lactate/pyruvate ratio (L/P ratio > 30).

    METHODS:

    B(ti)pO(2), L/P ratio, Glucose, Glutamate, Glycerol and CPP were recorded using NV and MD probes during gradual increase of ICP by inflation of an epidural balloon catheter with saline until brain death was achieved.

    RESULTS:

    Baseline level of B(ti)pO(2) was 22.9 ± 6.2 mmHg, the L/P ratio 17.7 ± 6.1 and CPP 73 ± 17 mmHg. B(ti)pO(2) and CPP decreased when intracranial volume was added. The L/P ratio increased above its ischemic levels, (>30) when CPP decreased below 30 mmHg and B(ti)pO(2) to <10 mmHg.

    CONCLUSIONS:

    A severe increase of ICP leading to CPP below 30 mmHg and B(ti)pO(2) below 10 mmHg is associated with an increase of the L/P ratio, thus seems to be critical thresholds for cerebral ischemia under these conditions.

  • 255.
    Purins, Karlis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Timothy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Brain tissue oxygenation and cerebral metabolic patterns in focal and diffuse traumatic brain injury2014Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, artikkel-id 64Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Neurointensive care of traumatic brain injury (TBI) patients is currently based on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targeted protocols. There are reasons to believe that knowledge of brain tissue oxygenation (BtipO2) would add information with the potential of improving patient outcome. The aim of this study was to examine BtipO2 and cerebral metabolism using the Neurovent-PTO probe and cerebral microdialysis (MD) in TBI patients.

    Methods: Twenty-three severe TBI patients with monitoring of physiological parameters, ICP, CPP, BtipO2, and MD for biomarkers of energy metabolism (glucose, lactate, and pyruvate) and cellular distress (glutamate, glycerol) were included. Patients were grouped according to injury type (focal/diffuse) and placement of the Neurovent-PTO probe and MD catheter (injured/non-injured hemisphere).

    Results: We observed different patterns in BtipO2 and MD biomarkers in diffuse and focal injury where placement of the probe also influenced the results (ipsilateral/contralateral). In all groups, despite fairly normal levels of ICP and CPP, increased MD levels of glutamate, glycerol, or the L/P ratio were observed at BtipO2 <5 mmHg, indicating increased vulnerability of the brain at this level.

    Conclusion: Monitoring of BtipO2 adds important information in addition to traditional ICP and CPP surveillance. Because of the different metabolic responses to very low BtipO2 in the individual patient groups we submit that brain tissue oximetry is a complementary tool rather than an alternative to MD monitoring.

  • 256.
    Purins, Karlis
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Sedigh, Amir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Molnar, Christian
    Jansson, Leif
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Lorant, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Tufveson, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Wennberg, Lars
    Wiklund, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Standardized experimental brain death model for studies of intracranial dynamics, organ preservation, and organ transplantation in the pig2011Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 39, nr 3, s. 512-517Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:: Brain death impairs organ function and outcome after transplantation. There is a need for a brain death model to allow studies of organ viability and preservation. For neurointensive care research, it is also of interest to have a relevant brain death model for studies of intracranial dynamics and evaluation of cerebral monitoring devices. Therefore, the objective was to develop a standardized clinically relevant brain death model. METHODS:: Six pigs of both sexes (10-12 wks old; mean weight, 24.5 ± 1.4 kg) were included. Mean arterial blood pressure, heart rate, intracranial pressure, intracranial compliance, cerebral perfusion pressure, and brain tissue oxygenation (BtiPo2) were recorded during stepwise elevation of intracranial pressure by inflation of an epidural balloon catheter with saline (1 mL/20 mins). Brain death criteria were decided to be reached when cerebral perfusion pressure was <0 mm Hg for 60 mins and at least 10 mL saline was inflated epidurally. BtiPo2 and arterial injections of microspheres were used for confirmation of brain death. RESULTS:: A gradual volume-dependent elevation of intracranial pressure was observed. After 10 mL of balloon infusion, mean intracranial pressure was 89.8 ± 9.7 (sd) mm Hg. Intracranial compliance decreased from 0.137 ± 0.069 mL/mm Hg to 0.007 ± 0.001 mL/mm Hg. The mean arterial pressure decreased and the heart rate increased when the intracranial volume was increased to between 5 and 6 mL. All animals showed cerebral perfusion pressure ≤0 after 7 to 10 mL of infusion. In all animals, the criteria for brain death with negative cerebral perfusion pressure and BtiPo2 ∼0 mm Hg were achieved. Only a negligible amount of microspheres were found in the cerebrum, confirming brain death. The kidneys showed small foci of acute tubular necrosis. CONCLUSIONS:: The standardized brain death model designed in pigs simulates the clinical development of brain death in humans with a classic pressure-volume response and systemic cardiovascular reactions. Brain death was convincingly confirmed.

  • 257.
    Rask-Andersen, Helge
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Nyberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kinnefors, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Ekvall, Lars
    Elektrisk stimulering av hjärnstammen: Behandling av döva med förstörd hörselnerv1996Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 93, nr 40, s. 3461-3464Artikkel i tidsskrift (Annet vitenskapelig)
  • 258.
    Ren, Zhi-Ping
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Olofsson, Tommie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Qu, Mingqi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Soussi, Thierry
    Kalimo, Hannu
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Nistér, Monica
    Molecular genetic analysis of p53 intratumoral heterogeneity in human astrocytic brain tumors2007Inngår i: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 66, nr 10, s. 944-954Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We investigated genetic heterogeneity of astrocytic gliomas using p53 gene mutations as a marker. Different parts of morphologically heterogeneous astrocytic gliomas were micro-dissected, and direct DNA sequencing of p53 gene exons 5 through 8 was performed. Thirty-five glioma samples and tumor-adjacent normal-appearing brain tissue from I I patients were analyzed. Sixteen different p53 gene mutations were found in 7 patients. We found that some tumors were devoid of p53 gene mutations, whereas other tumors carried I or often several (up to 3) different mutations. The mutations were present in grade II, III, and IV astrocytic glioma areas. Both severe functionally dead mutants and mutants with remaining transcriptional activity could be observed in the same tumor. We observed that morphologically different parts of a glioma could carry different or similar mutations in the p53 gene and could be either associated or not associated with the locus of heterozygosity at the mutant site. Coexistence of p53 gene mutations and the locus of heterozygosity was common, at least in astrocytomas grade III and in glioblastomas, and also occurred in astrocytoma grade 11 areas. These results support the notion that intratumoral heterogeneity in brain tumors originates from different molecular defects. Our results are of importance for a further understanding of the molecular mechanisms behind failure to treat glioma patients.

  • 259.
    Ribom, Dan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Eriksson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Hartman, Magdalena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Engler, Henry
    Uppsala University Positron Emission Tomography Center, University Hospital, Uppsala, Sweden.
    Nilsson, Anna
    Uppsala University Positron Emission Tomography Center, University Hospital, Uppsala, Sweden.
    Långstrom, Bengt
    Uppsala University Positron Emission Tomography Center, University Hospital, Uppsala, Sweden.
    Bolander, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Bergstrom, Mats
    Uppsala University Positron Emission Tomography Center, University Hospital, Uppsala, Sweden.
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Positron emission tomography 11C-methionine and survival in patients with low-grade gliomas2001Inngår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 92, nr 6, s. 1541-1549Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND

    Considerable numbers of patients with low-grade gliomas experience an early malignant course and may benefit from aggressive treatment. These patients are difficult to identify using established prognostic factors. A retrospective study was performed to determine whether the 11C-methionine uptake in tumor is a survival factor in adult patients with supratentorial gliomas classified as World Health Organization Grade 2.

    METHODS

    The authors identified 89 patients with histologically confirmed low-grade gliomas in whom an 11C-methionine positron emission tomography (PET) scan had been performed as part of the diagnostic tumor investigation from 1983 to 1998. Clinical data were collected, and the PET scans were re-evaluated according to a fixed protocol. The 11C-methionine uptake in the tumor and relevant clinical parameters were entered into univariate and multivariate survival analyses.

    RESULTS

    At the end of the study, 49 patients (55.1%) had died. The median overall survival was 5.7 years. Low methionine uptake was significantly favorable in the multivariate survival analysis (P = 0.04) along with oligodendroglioma (P = 0.003). In the histologic subgroups, 11C-methionine uptake was an important survival factor among patients with astrocytomas (P = 0.05) and oligodendrogliomas (P = 0.03). Tumor resection was a favorable prognostic factor in patients with high methionine uptake (P = 0.01) but not in patients with low uptake.

    CONCLUSIONS

    Baseline 11C-methionine PET is a prognostic indicator in patients with low-grade gliomas. The results imply that PET is a valuable tool in the clinical management of these patients and may assist in the selection of patients for therapy.

  • 260.
    Ribom, Dan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Smits, Anja
    Hartman, Magdalena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Persson, Lennart
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    On the issue of early and aggressive treatment in grade 2 gliomas2003Inngår i: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 129, nr 3, s. 154-160Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose

    To study the effects of surgery and timing of radiotherapy on patient survival in grade 2 gliomas.

    Methods

    One hundred and eighty-nine patients with diffuse astrocytomas, oligoastrocytomas, and oligodendrogliomas, World Health Organization grade 2, treated between 1982 and 2000 were identified. The impact of treatment given and clinical parameters were studied in univariate- and multivariate survival analyses.

    Results

    Median survival for the whole patient sample was 6.4 years and the 5-year survival rate was 60%. Macroscopic total resection was beneficial in the univariate analysis (P=0.03) but not when adjusting for confounders. Early subtotal resection did not prolong survival. Early radiotherapy was associated with a shorter survival time compared to delayed or no irradiation (P=0.004). However, this difference was mainly due to an unequal distribution of prognostic factors and was not significant in the multivariate analysis. The most important predictors for long survival time were young age (P<0.001), oligodendroglioma histology (P<0.001), and small tumour size (P=0.02).

    Conclusions

    Early conventional treatment with surgery and radiotherapy had no positive effect on patient survival. This opens up the possibility of trying and evaluating other first-line treatment regimens in this disease.

  • 261.
    Robinson, Yohan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Sheta, Reda
    Salci, Konstantin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Willander, Johan
    Blood Loss in Surgery for Aggressive Vertebral Haemangioma with and without Embolisation2015Inngår i: Asian spine journal, ISSN 1976-1902, Vol. 9, nr 3, s. 483-491Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite their benign nature some symptomatic aggressive vertebral haemangiomas (AVH) require surgery to decompress spinal cord and/or stabilise pathological fractures. Preoperative embolisation may reduce the considerable blood loss during surgical decompression. This systematic review investigated whether preoperative embolisation reduced surgical blood loss during treatment of symptomatic AVH. PubMed Medline, Web of Science, and Ovid Medline were searched for case reports and clinical studies on surgical AVH treatment. Included were cases from all publications on surgical treatment of AVH where the amount of surgical blood loss and the use of preoperative embolisation were documented. 51 cases with surgically treated AVH were retrieved from the included studies. Blood loss in the embolised treatment group (980±683 mL) was lower than the non-embolised control group (1,629±946 mL). This systematic review found that embolisation prior to AVH resection reduced surgical blood loss (level of evidence, very low) and can be recommended (strong recommendation).

  • 262.
    Rodriguez-Lorenzo, Andres
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Rydevik Mani, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Plastikkirurgi.
    Thor, Andreas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Käkkirurgi.
    Gudjonsson, Olafur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Olerud, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ekberg, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Fibula osteo-adipofascial flap for reconstruction of a cervical spine and posterior pharyngeal wall defect2014Inngår i: Microsurgery, ISSN 0738-1085, E-ISSN 1098-2752, Vol. 34, nr 4, s. 314-318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    When reconstructing combined defects of the cervical spine and the posterior pharyngeal wall the goals are bone stability along with continuity of the aerodigestive tract. We present a case of a patient with a cervical spine defect, including C1 to C3, associated with a posterior pharyngeal wall defect after excision of a chordoma and postoperative radiotherapy. The situation was successfully solved with a free fibula osteo-adipofascial flap. The reconstruction with a fibula osteo-adipofascial flap provided several benefits in comparison with a fibula osteo-cutaneous flap in our case, including an easier insetting of the soft tissue component at the pharyngeal level and less bulkiness of the flap allowing our patient to resume normal deglutition.

  • 263.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Borota, Ljubisa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Kothimbakam, Raj
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Outcome from spontaneous subarachnoid haemorrhage: results from 2007-2011 and comparison with our previous series2014Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 119, nr 1, s. 38-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives

    The management of patients with spontaneous subarachnoid haemorrhage (SAH) has changed, in part due to interventions now being extended to patients who are older and in a worse clinical condition. This study evaluates the effects of these changes on a complete 5-year patient material.

    Methods

    Demographic data and results from 615 patients with SAH admitted from 2007 to 2011 were put together. Aneurysms were found in 448 patients (72.8%). They were compared with the aneurysm group (n = 676) from a previously published series from our centre (2001-2006). Linear regression was used to determine variables predicting functional outcome in the whole aneurysm group (2001-2011).

    Results

    Patients in the more recent aneurysm group were older, and they were in a worse clinical condition on admission. Regarding younger patients admitted in World Federation of Neurosurgical Societies SAH grading (WFNS) 3, there were fewer with a good outcome. In the whole aneurysm group 2001-2011, outcome was best predicted by age, clinical condition at admission, and the size of the bleeding, and not by treatment mode or localization of aneurysm.

    Conclusion

    It seems important for the outcome that aneurysms are treated early. The clinical course after that depends largely on the condition of the patient on admission rather than on aneurysm treatment method. This, together with the fact that older patients and those in worse condition are now being admitted, increases demands on neurointensive care. Further improvement in patient outcome depends on better understanding of acute brain injury mechanisms and improved neurointensive care as well as rehabilitation measures.

  • 264.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Gál, Gyula
    Norbäck, Ola
    Ryttlefors, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Cesarini, Kristina Giuliana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Bolander, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Tovi, Metin
    Persson, Lennart
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Patients with spontaneous subarachnoid haemorrhage: presentation of a 10-year hospital series2009Inngår i: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 23, nr 5, s. 499-506Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this study we present the population-based patient material with spontaneous SAH, treated in our Neurosurgical unit during the 10 years (1997-2006) after the introduction of endovascular treatment of aneurysms (EVT) in our hospital. All patients that had a spontaneous SAH and a potential to survive were admitted. The present study comprises 1471 patients. 72 % had one or more aneurysms. AVM or other vascular pathological findings where found in 2%. Angiography was judged as normal in 21% and was not performed in 5%. 664 of the patients with aneurysms were treated by endovascular means, 333 were operated and 31 were treated with both methods. Thirty-five received no treatment. The main difference in admission parameters between the coiled and clipped aneurysms was the location of the aneurysm, with posterior circulation aneurysm exclusively being coiled and MCA aneurysms mainly clipped. The highest 6-month mortality for aneurysms presented in the untreated group (71.4%), and the lowest (3.2%) in the group treated with both clip and coil. Six-month mortality was 3.5% for the patients with a normal angiography. Of these, no one with Fisher grade 1 and 2/120 patients with Fisher 2 died. The mortality was high (89%) for those patients where angiography was not performed. The present patient group was compared to an earlier published a 12-year patient series from our clinic. The patients with aneurysmal SAH in the present series were older and had a lower 6-month mortality in our material compared to the published data from our clinic from 1981-1992. More patients were admitted in a good clinical condition in the present series, but there was also a higher proportion of patients from the worst clinical groups. The percentage of aneurysms treated had increased from 80% to 97% after EVT was introduced.

  • 265.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lundström, E
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Outcome After Spontaneous Subarachnoid Hemorrhage Measured With the EQ-5D2011Inngår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 42, nr 11, s. 3284-3286Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: The EQ-5D measures quality of life based on self-reported health status in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In this study, the EQ-5D was evaluated as an outcome measure for patients with subarachnoid hemorrhage.

    METHODS: The EQ-5D was completed in 710 patients 9 months after subarachnoid hemorrhage. Relevant demographic and clinical factors were evaluated as predictors of the 5 outcome dimensions in a series of linear regression models.

    RESULTS: Worse health status in mobility, self-care, and usual activities was predicted by increasing age and by a more severe disease as indicated by the presence of an aneurysm, worse clinical condition at admission, or more blood on the CT scan. Younger age and female gender predicted worse health status regarding anxiety/depression. '

    CONCLUSIONS: The evaluation of the EQ-5D reveals age-related differences in the nature of the challenges faced by these patients.

  • 266.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lundström, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Health-related quality of life at median 12 months after aneurysmal subarachnoid hemorrhage, measured with EuroQoL-5D2013Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 155, nr 4, s. 587-593Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    A measurement of quality of life (QoL) should cover the important aspects of daily life and be easy to perform. Ease of performance is especially important for patients with spontaneous subarachnoid haemorrhage (SAH), since fatigue and cognitive disabilities are known sequeles. EuroQoL (EQ-5D) is a preference-based instrument measuring QoL, based on self-reported health status in five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort and Anxiety/Depression. In the present study EuroQoL was used in patients with aneurysmal SAH (aSAH) in comparison with a Swedish reference population. We also determined the extent to which demographic characteristics and clinical parameters predicted outcome.

    METHODS:

    Seven hundred fifty-five patients with aSAH were studied after a median 12 months. The proportion of patients in the best QoL category for each dimension was compared with the corresponding proportion in an age matched reference population. Disease severity was measured using the World Federation of Neurosurgical Societies' SAH grading system and the Fisher scale. The extent to which demographic and clinical factors predicted outcome was evaluated using linear regression.

    RESULTS:

    Aneurysmal SAH patients generally had a worse QoL compared with the reference population, in all five dimensions of EQ-5D. In the patient population, disease severity predicted worse outcome in all five dimensions. Female gender and surgery as treatment method (in the case of anterior aneurysms) predicted worse outcome in Usual Activities and Anxiety/Depression.

    CONCLUSION:

    The nature of the sequeles after SAH depends on severity of disease, gender and treatment method. These factors should be more emphasised in planning rehabilitation.

  • 267.
    Ronne-Engström, Elisabeth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Popek, Edith
    Symptomatic colloid cysts in the third ventricle of monozygotic twins2015Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, nr 1, s. 59-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this case report we describe colloid cysts in the third ventricles of monozygotic twin sisters. They were 26 years old when their condition was discovered. One woman was admitted to us on an emergency basis, with signs of high intracranial pressure such as unconsciousness and extension posturing. Her sister was also brought to the hospital since she had a history of attacks of headache. They were both operated with removal of the colloid cysts, and the clinical courses are described in the case report. In reviewing the literature another 30 familial cases were found. Of these were two pairs of monozygotic and one pair of dizygotic twins.

  • 268.
    Roodakker, Kenney Roy
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Alhuseinalkhudhur, Ali
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Al-Jaff, Mohammed
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Georganaki, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Berntsson, Shala G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Danfors, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Strand, Robin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Avdelningen för visuell information och interaktion. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Bildanalys och människa-datorinteraktion.
    Edqvist, Per-Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Dimberg, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Vaskulärbiologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Region-by-region analysis of PET, MRI, and histology in en bloc-resected oligodendrogliomas reveals intra-tumoral heterogeneity2019Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 46, nr 3, s. 569-579Artikkel i tidsskrift (Fagfellevurdert)
  • 269.
    Rostami, Elham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Glucose and the injured brain-monitored in the neurointensive care unit2014Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, artikkel-id 91Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Brain has a continuous demand for energy that is met by oxidative metabolism of oxygen and glucose. This demand is compromised in the injured brain and if the inadequate supply persists it will lead to permanent tissue damage. Zero values of cerebral glucose have been associated with infarction and poor neurological outcome. Furthermore, hyperglycemia is common in patients with neurological insults and associated with poor outcome. Intensive insulin therapy (IIT) to control blood glucose has been suggested and used in neurointensive care with conflicting results. This review covers the studies reporting on monitoring of cerebral glucose with microdialysis in patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and ischemic stroke. Studies investigating IIT are also discussed. Available data suggest that low cerebral glucose in patients with TBI and SAH provides valuable information on development of secondary ischemia and has been correlated with worse outcome. There is also indication that the location of the catheter is important for correlation between plasma and brain glucose. In conclusion considering catheter location, monitoring of brain glucose in the neurointensive care not only provides information on imminent secondary ischemia it also reveals the effect of peripheral treatment on the injured brain.

  • 270.
    Rostami, Elham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Engquist, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Imaging of cerebral blood flow in patients with severe traumatic brain injury in the neurointensive care2014Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, artikkel-id 114Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ischemia is a common and deleterious secondary injury following traumatic brain injury (TBI). A great challenge for the treatment of TBI patients in the neurointensive care unit (NICU) is to detect early signs of ischemia in order to prevent further advancement and deterioration of the brain tissue. Today, several imaging techniques are available to monitor cerebral blood flow (CBF) in the injured brain such as positron emission tomography (PET), single-photon emission computed tomography, xenon computed tomography (Xenon-CT), perfusion-weighted magnetic resonance imaging (MRI), and CT perfusion scan. An ideal imaging technique would enable continuous non-invasive measurement of blood flow and metabolism across the whole brain. Unfortunately, no current imaging method meets all these criteria. These techniques offer snapshots of the CBF. MRI may also provide some information about the metabolic state of the brain. PET provides images with high resolution and quantitative measurements of CBF and metabolism; however, it is a complex and costly method limited to few TBI centers. All of these methods except mobile Xenon-CT require transfer of TBI patients to the radiological department. Mobile Xenon-CT emerges as a feasible technique to monitor CBF in the NICU, with lower risk of adverse effects. Promising results have been demonstrated with Xenon-CT in predicting outcome in TBI patients. This review covers available imaging methods used to monitor CBF in patients with severe TBI.

  • 271.
    Rostami, Elham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Engquist, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Howells, Timothy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Johnson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Early low cerebral blood flow and high cerebral lactate: prediction of delayed cerebral ischemia in subarachnoid hemorrhage2018Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 128, nr 6, s. 1762-1770Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE Delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH) is one of the major contributors to poor outcome. It is crucial to be able to detect early signs of DCI to prevent its occurrence. The objective of this study was to determine if low cerebral blood flow (CBF) measurements and pathological microdialysis parameters measured at the bedside can be observed early in patients with SAH who later developed DCI. METHODS The authors included 30 patients with severe SAH. The CBF measurements were performed at Day 0-3 after disease onset, using bedside xenon-CT. Interstitial glucose, lactate, pyruvate, glycerol, and glutamate were measured using microdialysis. RESULTS Nine of 30 patients developed DCI. Patients with DCI showed significantly lower global and regional CBF, and lactate was significantly increased in these patients. A high lactate/pyruvate ratio was also detected in patients with DCI. CONCLUSIONS Early low CBF measurements and a high lactate and lactate/pyruvate ratio may be early warning signs of the risk of developing DCI. The clinical value of these findings needs to be confirmed in larger studies.

  • 272.
    Rostami, Elham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Engquist, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Howells, Timothy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    The Correlation between Cerebral Blood Flow Measured by Bedside Xenon-CT and Brain Chemistry Monitored by Microdialysis in the Acute Phase following Subarachnoid Hemorrhage2017Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 8, artikkel-id 369Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cerebral microdialysis (MD) may be used in patients suffering from subarachnoid hemorrhage (SAH) to detect focal cerebral ischemia. The cerebral MD catheter is usually placed in the right frontal lobe and monitors the area surrounding the catheter. This generates the concern that a fall in cerebral blood flow (CBF) and ischemic events distant to the catheter may not be detected. We aimed to investigate if there is a difference in the association between the MD parameters and CBF measured around the MD catheter compared to global cortical CBF and to CBF in the vascular territories following SAH in the early acute phase. MD catheter was placed in the right frontal lobe of 30 SAH patients, and interstitial glucose, lactate, pyruvate, glycerol, and lactate/pyruvate ratio were measured hourly. CBF measurements were performed during day 0-3 after SAH. Global cortical CBF correlated strongly with CBF around the microdialysis catheter (CBF-MD) (r = 0.911, p ≤ 0.001). This was also the case for the anterior, middle, and posterior vascular territories in the right hemisphere. A significant negative correlation was seen between lactate and CBF-MD (r = -0.468, p = 0.009). The same relationship was observed between lactate and CBF in anterior vascular territory but not in the middle and posterior vascular territories. In conclusion, global CBF 0-3 days after severe SAH correlated strongly with CBF-MD. High lactate level was associated with low global CBF and low regional CBF in the right anterior vascular territory, when the MD catheter was placed in the right frontal lobe.

  • 273.
    Rostami, Elham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Engquist, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Johnson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Timothy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Monitoring of Cerebral Blood Flow and Metabolism Bedside in Patients with Subarachnoid Hemorrhage - A Xenon-CT and Microdialysis Study2014Inngår i: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, artikkel-id 89Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cerebral ischemia is the leading cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). Although 70% of the patients show angiographic vasospasm only 30% develop symptomatic vasospasm defined as delayed cerebral ischemia (DCI). Early detection and management of reversible ischemia is of critical importance in patients with SAH. Using a bedside Xenon enhanced computerized tomography (Xenon-CT) scanner makes it possible to measure quantitative regional Cerebral blood flow (CBF) bedside in the neurointensive care setting and intracerebral microdialysis (MD) is a method that offers the possibility to monitor the metabolic state of the brain continuously. Here, we present results from nine SAH patients with both MD monitoring and bedside Xenon-CT measurements. CBF measurements were performed within the first 72 h following bleeding. Six out of nine patients developed DCI at a later stage. Five out of six patients who developed DCI had initial global CBF below 26 ml/100 g/min whereas one had 53 ml/100 g/min. The three patients who did not develop clinical vasospasm all had initial global CBF above 27 ml/100 g/min. High lactate/pyruvate (L/P) ratio was associated with lower CBF values in the area surrounding the catheter. Five out of nine patients had L/P ratio ≥25 and four of these patients had CBF ≤ 22 ml/100 g/min. These preliminary results suggest that patients with initially low global CBF on Xenon-CT may be more likely to develop DCI. Initially low global CBF was accompanied with metabolic disturbances determined by the MD. Most importantly, pathological findings on the Xenon-CT and MD could be observed before any clinical signs of DCI. Combining bedside Xenon-CT and MD was found to be useful and feasible. Further studies are needed to evaluate if DCI can be detected before any other signs of DCI to prevent progress to infarction.

  • 274.
    Rostami, Elham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Gyorgy, Andrea
    Davidsson, Johan
    Walker, John
    Wingo, Daniel
    Angeria, Maria
    Bellander, Bo-Michael
    Agoston, Denes
    Risling, Mårten
    Time-Dependent Changes in Serum Level of Protein Biomarkers after Focal Traumatic Brain Injury2015Inngår i: International Journal of Neurorehabilitation, ISSN 2376-0281, Vol. 2, nr 168Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Serum biomarkers could indicate the pathological changes during the secondary injury process after traumatic brain injury (TBI). Furthermore, they could reflect specific pathological processes following different types of TBI. Here we analyzed time-dependent changes of select protein biomarkers in serum samples collected from a rodent model of penetrating type of injury (pen-TBI). The model is a controlled penetration of a 2 mm thick needle-shaped object, which is accelerated into the brain tissue with a bullet from an air gun. The results obtained in the current study were compared to previously reported results of levels of serum biomarker following a rotational acceleration injury that mimics mild TBI. A total of 24 animals were used, grouped in normal controls, sham-operated and injured animals. The rats were sacrificed at day 1, day 3 and day 14 post-injury and serum samples were analyzed for Tau, neurofilament heavy chain (NF-H), myelin basic protein (MBP), N-cadherin and S100B. We found that all markers but MBP showing a bi-phasic response to injury. Their serum levels significantly increased at day 1, dropped at 3 and increased again at day 14 post-injury. This was in contrast to rotational TBI model where the peak of biomarkers was found at day 3. Our study suggests that pen-TBI results in both acute axonal and neuronal damages as well as delayed changes likely part of the ongoing secondary injury process. These findings illustrate the dynamics of the injury process in pen-TBI and underline the importance of monitoring changes in serum biomarker levels for more accurate assessment of injury severity and outcome. In addition, comparison to rotational TBI model revealed distinctive temporal pattern of serum biomarker expression dependent on the type of injury.

  • 275.
    Rostami, Elham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Krueger, Frank
    Plantman, Stefan
    Davidsson, Johan
    Agoston, Denes
    Grafman, Jordan
    Risling, Mårten
    Alteration in BDNF and its receptors, full-length and truncated TrkB and p75NTR following penetrating traumatic brain injury2014Inngår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1542, s. 195-205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The evidence that BDNF is involved in neuroprotection, neuronal repair and recovery after traumatic brain injury (TBI) is substantial. We have previously shown that the polymorphism of the human BDNF gene predicts cognitive recovery and outcome following penetrating TBI. The distribution of expression of BDNF and its receptors after penetrating TBI has not been investigated. In this study we examined the expression of these genes in a rat model of penetrating TBI. The injury is produced by a controlled penetration of a 2 mm thick needle-shaped object, which is accelerated with a pellet from an air gun. We used in situ hybridization and investigated the mRNA expression of BDNF and its receptors: the full-length and the truncated TrkB and p75NTR, from 1 day to 8 weeks following penetrating TBI. In addition, the protein level of BDNF in frontal cortex and hippocampus was measured by reverse phase protein microarray (RPPM). The mRNA expression of BDNF and its receptors decreased in the hippocampus in the border zone ipsilateral to the injury while there was an increase in mRNA expression at the contralateral side. The increase in BDNF mRNA expression in the hippocampus was sustained for 2 weeks following injury, with the highest expression noted in the CA3 cell layer. Furthermore, the protein analysis by RPPM showed increased levels of BDNF in the frontal cortex and the hippocampus up to 2 weeks after TBI. At 8 weeks following injury there was an intense labeling of the truncated TrkB receptor and the p75NTR in the area surrounding the cavity. Our study is the first report on the expression of BDNF and its receptors following penetrating TBI and suggests that their expression is altered long after the acute phase of injury. Further studies are needed to investigate if the late expressions of these receptors are beneficial or deleterious. In either case it indicates the possibility to influence the recovery after brain injury during the chronic phase and the development of treatments that may improve the outcome of TBI patients.

  • 276.
    Rostami, Elham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nyström, Petra Witt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi. Skandionkliniken, Uppsala, Sweden.
    Libard, Sylwia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Wikström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Casar Borota, Olivera
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Gudjonsson, Olafur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Recurrent papillary craniopharyngioma with BRAFV600E mutation treated with neoadjuvant-targeted therapy.2017Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 159, nr 11, s. 2217-2221Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Craniopharyngiomas are histologically benign but locally aggressive tumors in the sellar region that may cause devastating neurological and endocrine deficits. They tend to recur following surgery with high morbidity; hence, postoperative radiotherapy is recommended following sub-total resection. BRAFV600E mutation is the principal oncogenic driver in the papillary variant of craniopharyngiomas. Recently, a dramatic tumor reduction has been reported in a patient with BRAFV600E mutated, multiply recurrent papillary craniopharyngioma using a combination therapy of BRAF inhibitor dabrafenib and MEK inhibitor trametinib. Here, we report on near-radical reduction of a growing residual BRAFV600E craniopharyngioma using the same neoadjuvant therapy.

  • 277.
    Rostami, Elham
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Rocksen, David
    Ekberg, Neda R.
    Goiny, Michel
    Ungerstedt, Urban
    Brain metabolism and oxygenation in healthy pigs receiving hypoventilation and hyperoxia2013Inngår i: Respiratory Physiology & Neurobiology, ISSN 1569-9048, E-ISSN 1878-1519, Vol. 189, nr 3, s. 537-542Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Modulation in ventilatory settings is one of the approaches and interventions used to treat and prevent secondary brain damage after traumatic brain injury (TBI). Here we investigate the effect of hyperoxia in combination with hypoventilation on brain oxygenation, metabolism and intracranial pressure. Twelve pigs were divided into three groups; groupl-100% hyperoxia (n=4), group 2-100% hyperoxia and 20% decrease in minute volume (MV) (n=4) and group 3-100% hyperoxia and 50% decrease in MV (n=4). Neither of the ventilator settings affected the lactate/pyruvate ratio significantly. However, there was a significant decrease of brain lactate (2.6+/-1.7 to 1.8+/-1.6 mM) and a rapid and marked increase in brain oxygenation (7.9+/-0.7 to 61.3+/-17.6 mmHg) in group 3. Intracranial pressure (ICP) was not significantly affected in this group, however, the ICP increased significantly in group 2 with 100% hyperoxia plus 20% reduction in minute volume. We conclude that hyperoxia in combination with 50% decrease in MV showed pronounced increase in partial brain oxygen tension (pbrO(2)) and decrease in brain lactate. The ventilatory modification, used in this study should be considered for further investigation as a possible therapeutic intervention for TBI patients.

  • 278.
    Roy, Ananya
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Libard, Sylwia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Weishaupt, Holger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Gustavsson, Ida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Uhrbom, Lene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Johansson, Fredrik K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Ponten, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Tchougounova, Elena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi.
    Mast Cell Infiltration in Human Brain Metastases Modulates the Microenvironment and Contributes to the Metastatic Potential2017Inngår i: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 7, artikkel-id 115Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Metastatic brain tumors continue to be a clinical problem, despite new therapeutic advances in cancer treatment. Brain metastases (BMs) are among the most common mass lesions in the brain that are resistant to chemotherapies, have a very poor prognosis, and currently lack any efficient diagnostic tests. Predictions estimate that about 40% of lung and breast cancer patients will develop BM. Despite this, very little is known about the immunological and genetic aberrations that drive tumorigenesis in BM. In this study, we demonstrate the infiltration of mast cells (MCs) in a large cohort of human BM samples with different tissues of origin for primary cancer. We applied patient-derived BM cell models to the study of BM cell-MC interactions. BM cells when cocultured with MCs demonstrate enhanced growth and self-renewal capacity. Gene set enrichment analyses indicate increased expression of signal transduction and transmembrane proteins related genes in the cocultured BM cells. MCs exert their effect by release of mediators such as IL-8, IL-10, matrix metalloprotease 2, and vascular endothelial growth factor, thereby permitting metastasis. In conclusion, we provide evidence for a role of MCs in BM. Our findings indicate MCs' capability of modulating gene expression in BM cells and suggest that MCs can serve as a new target for drug development against metastases in the brain.

  • 279.
    Ryttlefors, Mats
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Danfors, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Latini, Francesco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Montelius, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk strålningsvetenskap.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Experimentell och klinisk onkologi.
    Gudjonsson, Olafur
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Long-term evaluation of the effect of hypofractionated high-energy proton treatment of benign meningiomas by means of (11)C-L-methionine positron emission tomography2016Inngår i: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 43, nr 8, s. 1432-1443Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: To determine if (11)C-L-methionine PET is a useful tool in the evaluation of the long-term effect of proton beam treatment in patients with meningioma remnant.

    METHODS: Included in the study were 19 patients (4 men, 15 women) with intracranial meningioma remnants who received hypofractionated high-energy proton beam treatment. Patients were examined with (11)C-L-methionine PET and MRI prior to treatment and after 6 months, and 1, 2, 3, 5, 7 and 10 years. Temporal changes in methionine uptake ratio, meningioma volume, meningioma regrowth and clinical symptoms throughout the follow-up period were evaluated.

    RESULTS: In 17 patients the tumour volume was unchanged throughout the follow-up. The methionine uptake ratio on PET decreased over the years in most patients. In two patients the tumour remnant showed progression on MRI. In these patients, prior to the volume increase on MRI, the methionine uptake ratio increased. One patient experienced transient clinical symptoms and showed radiological evidence of a radiation-induced reaction close to the irradiated field.

    CONCLUSION: Proton beam treatment is a safe and effective treatment for achieving long-term growth arrest in meningioma remnants. Follow-up with (11)C-L-methionine PET may be a valuable adjunct to, but not a replacement for, standard radiological follow-up.

  • 280.
    Ryttlefors, Mats
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kerr, Richard S.C.
    Nuffield Dept Surgery, Radcliff, University of Oxford, UK.
    Molyneux, Andrew J.
    Neurovasc Res Unit, Radcliff, University of Oxford, UK.
    International Subarachnoid Aneurysm Trial of neurosurgical clipping versus endovascular coiling: Subgroup analysis of 278 elderly patients2008Inngår i: Stroke, Vol. 39, nr 10, s. 2720-2726Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: It is often thought that elderly patients in particular would benefit from endovascular aneurysm treatment. The aim of this analysis was therefore to compare the efficacy and safety of endovascular coiling (EVT) with neurosurgical clipping (NST) in the subgroup of elderly SAH patients in the International Subarachnoid Aneurysm Trial (ISAT). METHODS: In the ISAT cohort 278 SAH patients, 65 years or older, were enrolled. The patients were randomly allocated EVT (n=138) or NST (n=140). The primary outcome was the proportion of patients with a modified Rankin scale score of 0 to 2 (independent survival) at 1 year after the SAH. The rates of procedural complications and adverse events were also recorded. RESULTS: 83 of 138 (60.1%) patients allocated EVT were independent compared to 78 of 140 (56.1%) allocated NST (N.S.). 36 of 50 (72.0%) patients with internal carotid and posterior communicating artery aneurysms allocated EVT were independent compared to 26 of 50 (52.0%) allocated NST (P<0.05). 10 of 22 (45.5%) patients with middle cerebral artery aneurysms allocated EVT were independent compared to 13 of 15 (86.7%) allocated NST (P<0.05). The epilepsy frequency was 0.7% in the EVT group compared to 12.9% in the NST group (P<0.001). CONCLUSIONS: In good grade elderly SAH patients with small anterior circulation aneurysms, EVT should probably be the favored treatment for ruptured internal carotid and posterior communicating artery aneurysms, whereas elderly patients with ruptured middle cerebral artery aneurysms appear to benefit from NST. EVT resulted in a lower epilepsy frequency than NST.

  • 281.
    Ryttlefors, Mats
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Persson, Lennart
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ilodigwe, Don
    Macdonald, R. Loch
    Patient age and vasospasm after subarachnoid hemorrhage2010Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 67, nr 4, s. 911-917Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Subarachnoid hemorrhage (SAH) from a ruptured intracranial aneurysm is a devastating disease with high mortality and morbidity. The incidence of SAH increases with advancing age. OBJECTIVE: To determine whether age is an independent predictor of angiographic vasospasm, delayed ischemic neurological deficits (DINDs), or abnormal transcranial Doppler (TCD) measurements in patients with aneurysmal subarachnoid hemorrhage. METHODS: Data from CONSCIOUS-1 (Clazosentan to Overcome Neurological Ischemia and Infarct Occurring After Subarachnoid Hemorrhage study), a dose-finding study of clazosentan, were used. Data on angiographic vasospasm, DINDs, and TCD abnormalities were prospectively recorded as well as baseline characteristics and treatment data. Patient age was considered in 3 ways: as a continuous variable, dichotomized at age 65 years, and categorized by decade. Age was investigated as the main variable, whereas other possible confounding variables were adjusted for in the multiple logistic regression modeling with each of 3 dichotomized vasospasm outcome measures, presence or absence of angiographic vasospasm, DINDs, and TCD abnormalities as the dependent variable. RESULTS: The proportions of patients with angiographic vasospasm, DINDs, and TCD abnormalities were 45%, 19%, and 81%, respectively. Age, whether considered as a continuous, dichotomous, or a categorical variable, was not significantly associated with angiographic vasospasm, DINDs, or abnormal TCD measurements. CONCLUSION: Age does not seem to be a significant predictor for cerebral vasospasm after subarachnoid hemorrhage.

  • 282.
    Ryttlefors, Mats
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Tim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Neurointensive care is justified in elderly patients with severe subarachnoid hemorrhage--an outcome and secondary insults study2010Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 152, nr 2, s. 241-249Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: The aim was to study the outcome and the occurrence of secondary brain insults in elderly patients with severe subarachnoid hemorrhage (SAH) in comparison to younger patients. METHODS: Ninety-nine patients with severe SAH requiring a ventriculostomy and management at the neurointensive care unit with at least 120 h of multimodality monitoring data during the first 240 h following SAH were included. Data were continuously recorded for intracranial pressure (ICP), cerebral perfusion pressure, blood pressure, oxygen saturation, and temperature. Secondary insult levels were defined and quantified as percent of good monitoring time at insult level. Outcome according to the Glasgow Outcome Scale was evaluated at 6 months after the SAH. Age-dependent differences in occurrence of secondary insults and clinical characteristics were analyzed with multiple regression analysis. RESULTS: Good recovery or moderate disability was achieved in 24.1% of the elderly and in 42.9% of the younger patients. The frequency of severe disability was 41.4% in the elderly and 37.1% in the younger patients. The occurrence of ICP insults was lower and the occurrence of hypertensive, hypotensive, and hypoxemic insults were higher in the elderly patients. CONCLUSIONS: An independent outcome was achieved in a substantial proportion of the elderly with severe SAH, and the proportion of severe disability was not greater than among the younger patients, which justifies neurointensive care also in elderly patients. The occurrence of secondary insults was age dependent. Future studies of multimodality monitoring may provide age-specific secondary insult levels necessary for a tailored neurointensive care specific for elderly patients with severe SAH.

  • 283.
    Ryttlefors, Mats
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Latini, Francesco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Basma, Jaafar
    Krisht, Ali F
    Intraoperative Intratumoral Embolization of a Complex Recurrent Hemangiopericytoma: Technical Report and Review of the Literature2016Inngår i: Central European Neurosurgery, ISSN 2193-6315, E-ISSN 2193-6323, Vol. 77, nr 4, s. 361-366Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Objective Recurrent brain tumors represent a challenge for neurosurgeons because of the extensive blood loss and the time needed for surgical resection. Only a few hemostatic agents are useful to prevent the bleeding and thus facilitate the surgical resection. Fibrin sealant can be used to achieve sealing, tissue adherence, or hemostasis when other means of hemostasis are inadequate or inappropriate. We report the feasibility and positive effects of direct intratumoral injection of fibrin sealant during resection of a recurrent hemangiopericytoma. Material and Methods The intraoperative intratumoral injection of fibrin sealant changed the tumor properties of a recurrent hemangiopericytoma of the tentorium with infra- and supratentorial extension. From a loose friable briskly bleeding tumor, this complex lesion became a nonbleeding well-demarcated soft-firm tumor that could easily be dissected off the pial surface and totally resected without extensive bleeding. Results There are several benefits of intratumoral injection of fibrin sealant in hemangiopericytomas: (1) the extensive bleeding is diminished and blood loss minimized; (2) the restriction of the surgical view by the venous oozing is diminished, making the microsurgical dissection of the tumor capsule off the pial surface easier and safer; (3) the loose consistency of the tumor becomes firmer and facilitates the manipulation of the tumor and leads to a safer resection; and (4) a shorter operating time is needed. Conclusion The use of intratumoral fibrin glue injection is a safe and useful technique that could be used for hemostasis of highly vascularized tumors to facilitate a safer resection and to reduce blood loss.

  • 284.
    Salci, Konstantin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Goiny, Michel
    Contant, Charles F.
    Piper, Ian
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Metabolic effects of a late hypotensive insult combined with reduced intracranial compliance following traumatic brain injury in the rat2010Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 115, nr 4, s. 221-231Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction. Traumatic brain injury makes the brain vulnerable to secondary insults. Post-traumatic alterations in intracranial dynamics, such as reduced intracranial compliance (IC), are thought to further potentiate the effects of secondary insults. Reduced IC combined with intracranial volume insults leads to metabolic disturbances in a rat model. The aim of the present study was to discern whether a post-traumatic hypotensive insult in combination with reduced IC caused more pronounced secondary metabolic disturbances in the injured rat brain. Materials and methods. Rats were randomly assigned to four groups (n = 8/group): 1) trauma with hypotension; 2) trauma and reduced IC with hypotension; 3) sham injury with hypotension; and 4) sham injury and reduced IC with hypotension. A weight drop model of cortical contusion trauma was used. IC was reduced by gluing rubber film layers on the inside of bilateral bone flaps before replacement. Microdialysis probes were placed in the perimeter of the trauma zone. Hypotension was induced 2 h after trauma. Extracellular (EC) levels of lactate, pyruvate, hypoxanthine, and glycerol were analyzed. Results. The trauma resulted in a significant increase in EC dialysate levels of lactate, lactate/pyruvate ratio, hypoxanthine, and glycerol. A slight secondary increase in lactate was noted for all groups but group 2 during hypotension, otherwise no late effects were seen. There were no effects of reduced IC. Discussion. In conclusion, reduced IC did not increase the metabolic disturbances caused by the post-traumatic hypotensive insult. The results suggest that a mild to moderate hypotensive insult after initial post-traumatic resuscitation may be tolerated better than an early insult before resuscitation.

  • 285.
    Salci, Konstantin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Goiny, Michel
    Piper, Ian
    Contant, Charles
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Low intracranial compliance increases the impact of intracranial volume insults to the traumatized brain: A microdialysis study in a traumatic brain injury rodent model2006Inngår i: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 59, nr 2, s. 367-373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: The vulnerability of the brain is Considered to be increased after trauma. The present study was undertaken to determine whether intracranial volume insults in the posttraumatic period led to increased metabolic disturbances if intracranial compliance was decreased.

    METHODS: A weight drop technique with a brain compression of 1.5 mm was used for injury. Intracranial compensatory volume was decreased 60 mu l by placing rubber film between the dura mater and the bone. Intracranial volume insults were induced using the Bolus injection technique. Microdialysis was used to measure interstitial lactate, pyruvate, hypoxanthine, and glycerol. Fifty-two-rats Were allocated to trauma and sham groups with 0 to 3 layers of rubber film with and without intracranial volume insults.

    RESULTS: In the groups with reduced intracranial volume exposed to intracranial volume insults, the time course of metabolic markers showed higher increases and slower recovery rates than for the other groups. Reduced intracranial volume or intracranial volume insults alone did not cause any changes compared with controls.

    CONCLUSION: These results support the hypothesis that decreased intracranial compliance increases the vulnerability of the brain for secondary volume insults even with intracranial pressure at low levels between the insults. This finding has important clinical implications in that it stresses the need to identify patients with low intracranial compliance so that their treatment can be optimized.

  • 286.
    Samuelsson, Carolina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Microdialysis patterns in subarachnoid hemorrhage patients with focus on ischemic events and brain interstitial glutamine levels2009Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, nr 5, s. 437-446Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: This observational microdialysis (MD) study of 33 subarachnoid hemorrhage patients explores brain interstitial levels of glutamine, glutamate, lactate and pyruvate, and their relationship to clinical status and clinical course at the neurointensive care unit. METHODS: The focus was on ischemic events, defined by clinical criteria or by radiology, and the significance of brain interstitial glutamine levels and lactate/pyruvate (L/P) ratio. RESULTS: Eleven out of 12 periods with an ischemic MD pattern, defined as lactate/pyruvate (L/P) ratios exceeding 40, were either related to delayed ischemic neurological deficits (DIND) or CT-verified infarcts, confirming that L/P above 40 is a specific ischemic and pathological MD measure. Poor admittance WFNS grade (WFNS 4-5) patients had lower glutamine at the onset of monitoring than what good admittance WFNS grade (WFNS 1-3) patients had (P < 0.05). Interstitial glutamine increased over time in most patients. A "glutamine surge" was defined as a period where the interstitial glutamine concentration increased at least 150 microM over 12 h. Fifteen patients had a DIND and associated MD patterns were glutamine surges (n = 12) and/or L/P>40 (n = 6). Seven patients received vasospasm treatment; in five of these the only DIND-associated MD pattern was a glutamine surge. Seventy percent of the glutamine surges occurred during ongoing propofol sedation, and there was no association between extubations and glutamine surges. There was no difference in mean glutamine levels during the monitoring period between patients with favorable 6-month outcome and patients with poor 6-month outcome. CONCLUSION: We suggest that an increasing interstitial glutamine trend is a dynamic sign of augmented astrocytic metabolism with accelerated glutamate uptake and glutamine synthesis. This pattern is presumably present in metabolically challenged, but yet not overt ischemic tissue.

  • 287.
    Samuelsson, Carolina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Zetterling, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hesselager, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ryttlefors, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kumlien, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Salci, Konstantin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Cerebral glutamine and glutamate levels in relation to compromised energy metabolism: a microdialysis study in subarachnoid hemorrhage patients2007Inngår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 27, nr 7, s. 1309-1317Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within the astrocytes Glt is converted to glutamine (Gln), which is released and reconverted to Glt in neurons. The Glt–Gln cycle is energy demanding and impaired energy metabolism has been suggested to cause low interstitial Gln/Glt ratios. Using microdialysis (MD) measurements from visually noninjured cortex in 33 neurointensive care patients with subarachnoid hemorrhage, we have determined how interstitial Glt and Gln, as a reflection of the Glt–Gln cycle turnover, relate to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r=-0.66), but this correlation was not stronger than the correlation between L/P and Glt (r=0.68) or the correlation between lactate and Glt (r=0.65). A novel observation was a linear relationship between interstitial pyruvate and Gln (r=0.52). There were 13 periods (404 h) of 'energy crisis', defined by L/P ratios above 40. All were associated with high interstitial Glt levels. Periods with L/P ratios above 40 and low pyruvate levels were associated with decreased interstitial Gln levels, suggesting ischemia and failing astrocytic Gln synthesis. Periods with L/P ratios above 40 and normal or high pyruvate levels were associated with increased interstitial Gln levels, which may represent an astrocytic hyperglycolytic response to high interstitial Glt levels. The results imply that moderately elevated L/P ratios cannot always be interpreted as failing energy metabolism and that interstitial pyruvate levels may discriminate whether or not there is sufficient astrocytic capacity for Glt–Gln cycling in the brain.

  • 288.
    Samuelsson, Carolina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Timothy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kumlien, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Relationship between intracranial hemodynamics and microdialysis markers of energy metabolism and glutamate-glutamine turnover in patients with subarachnoid hemorrhage2009Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 111, nr 5, s. 910-915Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECT: The aim of this study was to explore the relationship between hemodynamics (intracranial and systemic) and brain tissue energy metabolism, and between hemodynamics and glutamate (Glt)-glutamine (Gln) cycle activity. METHODS: Brain interstitial levels of lactate, pyruvate, Glt, and Gln were prospectively monitored in the neurointensive care unit for more than 3600 hours using intracerebral microdialysis in 33 patients with subarachnoid hemorrhage (SAH). Intracranial pressure (ICP), mean arterial blood pressure, and cerebral perfusion pressure (CPP) were recorded using a digitalized system. RESULTS: Interstitial Gln and pyruvate correlated with CPP (r = 0.25 and 0.24, respectively). Intracranial pressure negatively correlated with Gln (r = -0.29) and the Gln/Glt ratio (r = -0.40). Levels of Gln and pyruvate and the Gln/Glt ratio were higher and levels of Glt and lactate and the lactate/pyruvate ratio were lower during periods of decreased ICP (<or= 10 mm Hg) as compared with values in periods of elevated ICP (> 10 mm Hg). In 3 patients, a poor clinical condition was attributed to high ICP levels (range 15-25 mm Hg). When CSF drainage was increased and the ICP was lowered to 10 mm Hg, there was an instantaneous sharp increase in interstitial Glt and pyruvate in these 3 patients. CONCLUSIONS: Increasing interstitial Gln and pyruvate levels appear to be favorable signs associated with improved CPP and low ICP. The authors suggest that this pattern indicates an energy metabolic situation allowing augmented astrocytic energy metabolism with accelerated Glt uptake and Gln synthesis. Moreover, their data raised the question of whether patients with SAH and moderately elevated ICP (15-20 mm Hg) would benefit from CSF drainage at lower pressure levels than what is usually indicated in current clinical protocols.

  • 289.
    Samuelsson, Carolina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Howells, Timothy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kumlien, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Response2009Inngår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 111, nr 5, s. 908-909Artikkel i tidsskrift (Fagfellevurdert)
  • 290.
    Shahim, Pashtun
    et al.
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
    Tegner, Yelverton
    Lulea Univ Technol, Dept Hlth Sci, Div Med Sci, Lulea, Sweden..
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hoeglund, Kina
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
    Portelius, Erik
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden..
    Brody, David L.
    Washington Univ, Sch Med, St Louis, MO 63130 USA..
    Blennow, Kaj
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden..
    Zetterberg, Henrik
    Gothenburg Univ, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41124 Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden.;UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London, England..
    Astroglial activation and altered amyloid metabolism in human repetitive concussion2017Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, nr 15, s. 1400-1407Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To determine whether postconcussion syndrome (PCS) due to repetitive concussive traumatic brain injury (rcTBI) is associated with CSF biomarker evidence of astroglial activation, amyloid deposition, and blood-brain barrier (BBB) impairment. Methods: A total of 47 participants (28 professional athletes with PCS and 19 controls) were assessed with lumbar puncture (median 1.5 years, range 0.25-12 years after last concussion), standard MRI of the brain, and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). The main outcome measures were CSF concentrations of astroglial activation markers (glial fibrillary acidic protein [GFAP] and YKL-40), markers reflecting amyloid precursor protein metabolism (A beta 38, A beta 40, A beta 42, sAPPa, and sAPPb), and BBB function (CSF: serum albumin ratio). Results: Nine of the 28 athletes returned to play within a year, while 19 had persistent PCS.1 year. Athletes with PCS.1 year had higher RPQ scores and number of concussions than athletes with PCS,1 year. Median concentrations of GFAP and YKL-40 were higher in athletes with PCS.1 year compared with controls, although with an overlap between the groups. YKL-40 correlated with RPQ score and the lifetime number of concussions. Athletes with rcTBI had lower concentrations of A beta 40 and A beta 42 than controls. The CSF: serum albumin ratio was unaltered. Conclusions: This study suggests that PCS may be associated with biomarker evidence of astroglial activation and b-amyloid (A beta) dysmetabolism in the brain. There was no clear evidence of Ab deposition as A beta 40 and A beta 42 were reduced in parallel. The CSF: serum albumin ratio was unaltered, suggesting that the BBB is largely intact in PCS.

  • 291.
    Shanks, J.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bloch, K. Markenroth
    Lund Univ, Bioimaging Ctr, Lund, Sweden.
    Laurell, K.
    Umea Univ, Dept Pharmacol & Clin Neurosci, Umea, Sweden.
    Cesarini, Kristina G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Fahlström, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Larsson, Elna-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Virhammar, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Aqueductal CSF Stroke Volume Is Increased in Patients with Idiopathic Normal Pressure Hydrocephalus and Decreases after Shunt Surgery2019Inngår i: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959X, Vol. 40, nr 3, s. 453-459Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE: Increased CSF stroke volume through the cerebral aqueduct has been proposed as a possible indicator of positive surgical outcome in patients with idiopathic normal pressure hydrocephalus; however, consensus is lacking. In this prospective study, we aimed to compare CSF flow parameters in patients with idiopathic normal pressure hydrocephalus with those in healthy controls and change after shunt surgery and to investigate whether any parameter could predict surgical outcome. MATERIALS AND METHODS: Twenty-one patients with idiopathic normal pressure hydrocephalus and 21 age- and sex-matched healthy controls were prospectively included and examined clinically and with MR imaging of the brain. Eighteen patients were treated with shunt implantation and were re-examined clinically and with MR imaging the day before the operation and 3 months postoperatively. All MR imaging scans included a phase-contrast sequence. RESULTS: The median aqueductal CSF stroke volume was significantly larger in patients compared with healthy controls (103.5 mu L; interquartile range, 69.8-142.8 mu L) compared with 62.5 mu L (interquartile range, 58.3-73.8 mu L; P < .01) and was significantly reduced 3 months after shunt surgery from 94.8 mu L (interquartile range, 81-241 mu L) to 88 mu L (interquartile range, 51.8-173.3 mu L; P < .05). Net flow in the caudocranial direction (retrograde) was present in 11/21 patients and in 10/21 controls. Peak flow and net flow did not differ between patients and controls. There were no correlations between any CSF flow parameters and surgical outcomes. CONCLUSIONS: Aqueductal CSF stroke volume was increased in patients with idiopathic normal pressure hydrocephalus and decreased after shunt surgery, whereas retrograde aqueductal net flow did not seem to be specific for patients with idiopathic normal pressure hydrocephalus. On the basis of the results, the usefulness of CSF flow parameters to predict outcome after shunt surgery seem to be limited.

  • 292.
    Shariatgorji, Mohammadreza
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Nilsson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Bonta, Maximilian
    TU Wien, Inst Chem Technol & Analyt, Vienna, Austria..
    Gan, Jinrui
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Fudan Univ, Dept Chem, Inst Biomed Sci, Shanghai, Peoples R China.;Fudan Univ, State Key Lab Mol Engn Polymers, Shanghai, Peoples R China..
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Clausen, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kallback, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Lodén, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Limbeck, Andreas
    TU Wien, Inst Chem Technol & Analyt, Vienna, Austria..
    Andrén, Per E.
    Direct imaging of elemental distributions in tissue sections by laser ablation mass spectrometry2016Inngår i: Methods, ISSN 1046-2023, E-ISSN 1095-9130, Vol. 104, s. 86-92Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We present a strategy for imaging of elements in biological tissues using laser ablation (LA) mass spectrometry (MS), which was compared to laser ablation inductively coupled plasma (LA-ICP) MS. Both methods were adopted for quantitative imaging of elements in mouse kidney, as well as traumatic brain injury model tissue sections. MS imaging (MSI) employing LA provides quantitative data by comparing signal abundances of sodium from tissues to those obtained by imaging quantitation calibration standards of the target element applied to adjacent control tissue sections. LA-ICP MSI provided quantitative data for several essential elements in both brain and kidney tissue sections using a dried-droplet approach. Both methods were used to image a rat model of traumatic brain injury, revealing accumulations of sodium and calcium in the impact area and its peripheral regions. LA MSI is shown to be a viable option for quantitative imaging of specific elements in biological tissue sections.

  • 293. Shaw, M
    et al.
    Piper, I
    Chambers, I
    Citerio, G
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Gregson, B
    Howells, Timothy
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Kiening, K
    Mattern, J
    Nilsson, Pelle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Ragauskas, A
    Sahuquillo, J
    Yau, YH
    The brain monitoring with information technology (BrainIT) collaborative network: data validation results2009Inngår i: Acta Neurochirurgica Supplements, Springer Vienna , 2009, Vol. 102, s. 217-221Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Background The BrainIT group works collaboratively on developing standards for collection and analyses of data from brain injured patients towards providing a more efficient infrastructure for assessing new health technology. Materials and methods Over a 2 year period, core dataset data (grouped by nine categories) were collected from 200 head-injured patients by local nursing staff. Data were uploaded by the BrainIT web and random samples of received data were selected automatically by computer for validation by data validation (DV) research nurse staff against gold standard sources held in the local centre. Validated data was compared with original data sent and percentage error rates calculated by data category. Findings Comparisons, 19,461, were made in proportion to the size of the data received with the largest number checked in laboratory data (5,667) and the least in the surgery data (567). Error rates were generally less than or equal to 6%, the exception being the surgery data class where an unacceptably high error rate of 34% was found. Conclusions The BrainIT core dataset (with the exception of the surgery classification) is feasible and accurate to collect. The surgery classification needs to be revised.

  • 294. Siegbahn, Malin
    et al.
    Lundin, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Olsson, Gun-Britt
    Stillesjö, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Kinnefors, Anders
    Rask-Andersen, Helge
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Nyberg, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Auditory Brainstem Implants (ABIs): 20 Years of Clinical Experience in Uppsala, Sweden2014Inngår i: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 134, nr 10, s. 1052-1061Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CONCLUSIONS:

    Even though sound perception may be limited after treatment with an auditory brainstem implant (ABI), it provides benefits and should be selectively offered to patients. Importantly the patients must be motivated, given reasonable expectations of outcome and offered long-term rehabilitation with a considerable 'learn to listen' period with the implant device.

    OBJECTIVES:

    To describe the clinical experiences and results of 24 ABI surgeries performed in Uppsala University Hospital between 1993 and 2013.

    METHODS:

    Most patients (n = 20) suffered from neurofibromatosis type 2 (NF2); a few patients (n = 4) were paediatric non-NF2 patients. The files were searched for information on the presurgery size of the vestibular schwannoma, whether the patient had undergone gamma knife treatment, the surgical approach, the side effects of the surgery and of the use of the implant, the electrode activation pattern and implant use, and categories of auditory performance (CAP) score.

    RESULTS:

    Our results show that many patients greatly benefited from an ABI, and most of the patients used their implants even though the hearing improvements usually consisted of awareness of surrounding sounds and improved lip-reading. No severe side effects were observed from implant stimulation.

  • 295.
    Skoglund, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    The neurological wake-up test increases stress hormone levels in patients with severe traumatic brain injury2012Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 40, nr 1, s. 216-222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: The "neurological wake-up test" is needed to evaluate the level of consciousness in patients with severe traumatic brain injury. However, the neurological wake-up test requires interruption of continuous sedation and may induce a stress response and its use in neurocritical care is controversial. We hypothesized that the neurological wake-up test induces an additional biochemical stress response in patients with severe traumatic brain injury.

    Patients: Twenty-four patients who received continuous propofol sedation and mechanical ventilation after moderate to severe traumatic brain injury (Glasgow Coma Scale score <= 8; patient age 18-71 yrs old) were analyzed. Exclusion criteria were age <18 yrs old, ongoing pentobarbital infusion, or markedly increased intracranial pressure on interruption of continuous sedation.

    Design: Single-center prospective study. During postinjury days 1-8, 65 neurological wake-up tests were evaluated. Adrenocorticotrophic hormone, epinephrine, and norepinephrine levels in plasma and cortisol levels in saliva were analyzed at baseline (during continuous intravenous propofol sedation) and during neurological wake-up test. Data are presented using medians and 25th and 75th percentiles.

    Setting: The study was performed in a university hospital neurocritical care unit.

    Interventions: None.

    Measurements and Main Results: At baseline, adrenocorticotrophic hormone and cortisol levels were 10.6 (6.0-19.4) ng/L and 16.0 (10.7-31.8) nmol/L, respectively. Immediately after the neurological wake-up test, adrenocorticotrophic hormone levels increased to 20.5 (11.1-48.4) ng/L (p < .05) and cortisol levels in saliva increased to 24.0 (12.3-42.5) nmol/L (p < .05). The plasma epinephrine and norepinephrine levels increased from a baseline of 0.3 (0.3-0.6) and 1.6 (0.9-2.3) nmol/L, respectively, to 0.75 (0.3-1.4) and 2.8 (1.28-3.58) nmol/L, respectively (both p < .05).

    Conclusions: The neurological wake-up test induces a biochemical stress response in patients with severe traumatic brain injury. The clinical importance of this stress response remains to be established but should be considered when deciding the frequency and use of the neurological wake-up test during neurocritical care.

  • 296.
    Skoglund, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Wake-up test and stress hormone levels in patients with brain injury: A focus on mechanisms involved: Reply2012Inngår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 40, nr 6, s. 2002-2003Artikkel i tidsskrift (Fagfellevurdert)
  • 297.
    Skoglund, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Effects of the neurological wake-up test on intracranial pressure and cerebral perfusion pressure in brain-injured patients2009Inngår i: Neurocritical care, ISSN 1541-6933, Vol. 11, nr 2, s. 135-142Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To evaluate the effects of the neurological "wake-up test" (NWT), defined as interruption of continuous propofol sedation and evaluation of the patient's level of consciousness, on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with severe subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). METHODS: A total of 127 NWT procedures in 21 severely brain-injured adult patients with either TBI (n = 12) or SAH (n = 9) were evaluated. ICP and CPP levels prior to, during and after the NWT procedure were recorded. RESULTS: During the NWT, ICP increased from 13.4 +/- 6 mmHg at baseline to 22.7 +/- 12 (P < 0.05) and the CPP increased from 75.6 +/- 11 to 79.1 +/- 21 mmHg (P < 0.05) in TBI patients. Eight patients showed a reduced CPP during the NWT due to increased ICP. In SAH patients, ICP increased from 10.6 +/- 5 to 16.8 +/- 8 mmHg (P < 0.05) and the CPP increased from 76.9 +/- 13 to 84.6 +/- 15 mmHg (P < 0.05). CONCLUSION: When continuous propofol sedation was interrupted and NWT was performed in severely brain-injured patients, the mean ICP and CPP levels were modestly increased. A subset of patients showed more pronounced changes. To date, the role of the NWT in the neurointensive care of TBI and SAH patients is unclear. Although the NWT is safe in the majority of patients and may provide useful clinical information about the patient's level of consciousness, alternate monitoring methods are suggested in patients showing marked ICP and/or CPP changes during NWT.

  • 298. Skoglund, Karin
    et al.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Monitoring and Sedation Differences in the Management of Severe Head Injury and Subarachnoid Hemorrhage Among Neurocritical Care Centers2013Inngår i: Journal of Neuroscience Nursing, ISSN 0888-0395, E-ISSN 1945-2810, Vol. 45, nr 6, s. 360-368Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The emergence of specialized neurocritical care (NCC) centers has been associated with an improved survival of patients with severe traumatic brain injury or subarachnoid hemorrhage. However, there are no established guidelines on sedation strategy or the frequency of evaluating the level of consciousness using the neurological wake-up test (NWT) in sedated NCC patients. Objectives: The aim was to compare the (1) monitoring techniques, (2) sedation principles, and (3) the use of the NWT in patients with severe traumatic brain injury or subarachnoid hemorrhage in 16 NCC centers. Method: A systematic survey of all 16 centers providing NCC in Scandinavia was performed using a questionnaire regarding the routine primary choice of sedative and analgesic compounds, monitoring techniques, and the frequency of the NWT, sent to the director of each center during 1999, 2004, and 2009. Results: The response rate was 100%. Except for one center in 1999, all included centers routinely used monitoring of intracranial and cerebral perfusion pressure. In contrast, newer monitoring techniques such as microdialysis, jugular bulb oximetry, and brain tissue oxygenation were infrequently used throughout the survey period. Approximately half of the NCC centers used propofol infusion as the primary sedative, whereas the remaining centers used midazolam infusion, and there was a marked variation in the choice of analgesia in each evaluated year. The NWT was never used in 50% of centers and six times daily in one center from 1999 to 2009. Most differences among the NCC centers remained unchanged over the evaluated 10-year period. Discussion: Although Scandinavian countries have similar healthcare systems, there were marked differences among the participating NCC centers in the choice of monitoring tools and sedatives and the routine use of the NWT. These differences likely reflect different clinical management traditions and a lack of evidence-based guidelines in routine NCC.

  • 299.
    Skoglund, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Hillered, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Purins, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Tsitsopoulos, Parmenion P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Flygt, Johanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Engquist, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lewen, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Marklund, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    The Neurological Wake-up Test Does not Alter Cerebral Energy Metabolism and Oxygenation in Patients with Severe Traumatic Brain Injury2014Inngår i: Neurocritical Care, ISSN 1541-6933, E-ISSN 1556-0961, Vol. 20, nr 3, s. 413-426Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The neurological wake-up test (NWT) is used to monitor the level of consciousness in patients with traumatic brain injury (TBI). However, it requires interruption of sedation and may elicit a stress response. We evaluated the effects of the NWT using cerebral microdialysis (MD), brain tissue oxygenation (PbtiO2), jugular venous oxygen saturation (SjvO(2)), and/or arterial-venous difference (AVD) for glucose, lactate, and oxygen in patients with severe TBI. Seventeen intubated TBI patients (age 16-74 years) were sedated using continuous propofol infusion. All patients received intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring in addition to MD, PbtiO2 and/or SjvO(2). Up to 10 days post-injury, ICP, CPP, PbtiO2 (51 NWTs), MD (49 NWTs), and/or SjvO(2) (18 NWTs) levels during propofol sedation (baseline) and NWT were compared. MD was evaluated at a flow rate of 1.0 mu L/min (28 NWTs) or the routine 0.3 mu L/min rate (21 NWTs). The NWT increased ICP and CPP levels (p < 0.05). Compared to baseline, interstitial levels of glucose, lactate, pyruvate, glutamate, glycerol, and the lactate/pyruvate ratio were unaltered by the NWT. Pathological SjvO(2) (< 50 % or > 71 %; n = 2 NWTs) and PbtiO2 (< 10 mmHg; n = 3 NWTs) values were rare at baseline and did not change following NWT. Finally, the NWT did not alter the AVD of glucose, lactate, or oxygen. The NWT-induced stress response resulted in increased ICP and CPP levels although it did not negatively alter focal neurochemistry or cerebral oxygenation in TBI patients.

  • 300.
    Sköld, Mattias
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi. Karolinska Inst, S-10401 Stockholm, Sweden.
    Gunther, M.
    Karolinska Inst, S-10401 Stockholm, Sweden.
    Ventral root avulsion and replantation - description of different gene expression patterns in acute and delayed replantation2016Inngår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042, Vol. 33, nr 3, s. A12-A13Artikkel i tidsskrift (Annet vitenskapelig)
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