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  • 51. Oeckl, Patrick
    et al.
    Weydt, Patrick
    Steinacker, Petra
    Anderl-Straub, Sarah
    Nordin, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Volk, Alexander E.
    Diehl-Schmid, Janine
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Neurology, Ulm University hospital, Ulm, Germany.
    Kornhuber, Johannes
    Danek, Adrian
    Fassbender, Klaus
    Fliessbach, Klaus
    Jahn, Holger
    Lauer, Martin
    Mueller, Kathrin
    Knehr, Antje
    Prudlo, Johannes
    Schneider, Anja
    Thal, Dietmar R.
    Yilmazer-Hanke, Deniz
    Weishaupt, Jochen H.
    Ludolph, Albert C.
    Otto, Markus
    Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase2019Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 90, nr 1, s. 4-10Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers.

    Methods: The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA.

    Results: CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (-80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05).

    Conclusion: Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome.

  • 52.
    Olivecrona, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Rodling-Wahlström, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Naredi, Silvana
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Koskinen, Lars-Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    S-100B and neuron specific enolase are poor outcome predictors in severe traumatic brain injury treated by an intracranial pressure targeted therapy2009Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, nr 11, s. 1241-1247Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

    Fulltekst (pdf)
    FULLTEXT01
  • 53. Orth, Michael
    et al.
    Handley, O J
    Schwenke, C
    Dunnett, S
    Wild, E J
    Tabrizi, S J
    Landwehrmeyer, G B
    Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY.2011Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 82, nr 12, s. 1409-12Artikkel i tidsskrift (Fagfellevurdert)
  • 54. Oshima, Toshinori
    et al.
    Kawahara, Satomi
    Ueda, Mitsuharu
    Kawakami, Yushi
    Tanaka, Rina
    Okazaki, Takahiro
    Misumi, Yohei
    Obayashi, Konen
    Yamashita, Taro
    Ohya, Yuki
    Ihse, Elisabet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
    Shinriki, Satoru
    Tasaki, Masayoshi
    Jono, Hirofumi
    Asonuma, Katsuhiro
    Inomata, Yukihiro
    Westermark, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Ando, Yukio
    Changes in pathological and biochemical findings of systemic tissue sites in familial amyloid polyneuropathy more than 10 years after liver transplantation2014Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, nr 7, s. 740-746Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective To elucidate the long-term effects of liver transplantation (LT) on familial amyloid polyneuropathy (FAP). Methods We investigated clinicopathological and biochemical characteristics of systemic tissues in four autopsied cases of FAP patients surviving more than 10 years after LT and seven autopsied cases without LT. For analysing the truncated form of transthyretin (TTR) in amyloid, we also employed specimens from additional 18 FAP patients. Results Several tissue sites such as the heart, tongue and spinal cord had moderate-to-severe amyloid deposits but other tissues showed no or mild amyloid deposition. Those findings seemed similar to those observed in senile systemic amyloidosis (SSA), a sporadic amyloidosis caused by wild-type (WT) TTR. Also, amyloid deposits in systemic tissue sites except for the spinal cord in patients after LT derived mostly from WT TTR secreted from the normal liver grafts. In addition, in non-transplantation patients, proportions of WT TTR seemed to be relatively high in those tissue sites in which patients after LT had severe amyloid deposition, which suggests that WT TTR tends to form amyloid in those tissue sites. Finally, although the truncation of TTR in amyloid deposits did not depend on undergoing LT, we elucidated the truncation of TTR occurred predominantly in patients from non-endemic areas of Japan, where FAP amyloidogenic TTR V30M patients are late onset and low penetrance, compared with patients from an endemic area of Japan. Conclusions FAP may shift to systemic WT TTR amyloid formation after LT, which seems to be similar to the process in SSA. The truncation of TTR in amyloid deposits may depend on some genetic or environmental factors other than undergoing LT.

  • 55.
    Pietz, K
    et al.
    Tyskland.
    Hagell, Peter
    Lund University Hospital.
    Odin, P
    Lund University Hospital.
    Subcutaneous apomorphine in late stage Parkinson's disease: a long term follow up1998Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 65, nr 5, s. 709-716Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Despite the recent introduction of new peroral drugs as well as neurosurgical methods for Parkinson's disease, treatment of late stage parkinsonian patients remains difficult and many patients become severely handicapped because of fluctuations in their motor status. Injections and infusions of apomorphine has been suggested as an alternative in the treatment of these patients, but the number of studies describing the effects of such a treatment over longer time periods is still limited. The objective was to investigate the therapeutic response and range of side effects during long term treatment with apomorphine in advanced Parkinson's disease.

    METHODS: Forty nine patients (30 men, 19 women; age range 42-80 years) with Parkinson's disease were treated for 3 to 66 months with intermittent subcutaneous injections or continuous infusions of apomorphine.

    RESULTS: Most of the patients experienced a long term symptomatic improvement. The time spent in "off" was significantly reduced from 50 to 29.5% with injections and from 50 to 25% with infusions of apomorphine. The quality of the remaining "off" periods was improved with infusion treatment, but was relatively unaffected by apomorphine injections. The overall frequency and intensity of dyskinesias did not change. The therapeutic effects of apomorphine were stable over time. The most common side effect was local inflammation at the subcutaneous infusion site, whereas the most severe were psychiatric side effects occurring in 44% of the infusion and 12% of the injection treated patients.

    CONCLUSION: Subcutaneous apomorphine is a highly effective treatment which can substantially improve the symptomatology in patients with advanced stage Parkinson's disease over a prolonged period of time.

  • 56.
    Pinto, Susana
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. Instituto de Fisiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
    Gromicho, Marta
    Swash, Michael
    deCarvalho, Mamede
    Cervical muscle weakness is a marker of respiratory dysfunction in amyotrophic lateral sclerosis2020Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 91, nr 3, s. 323-324Artikkel i tidsskrift (Fagfellevurdert)
  • 57. Press, R.
    et al.
    Askmark, H.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Andersen, O.
    Axelson, H. W.
    Stroemberg, U.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Isaksson, C.
    Johansson, J-EJ.
    Haegglund, H.
    Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP2014Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, nr 6, s. 618-624Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. Method Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. Results The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. Conclusions Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.

  • 58. Press, R
    et al.
    Askmark, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Svenningsson, A
    Andersen, O
    Axelson, Hans W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Strömberg, U
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Wahlin, A
    Isaksson, C
    Johansson, J-E J
    Hägglund, H
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Hematologi.
    Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP2014Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, nr 6, s. 618-624Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months.

    METHOD: Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients.

    RESULTS: The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis.

    CONCLUSIONS: Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.

  • 59. Pyykkö, O. T.
    et al.
    Helisalmi, S.
    Koivisto, A. M.
    Mölsä, J. A. A.
    Rummukainen, J.
    Nerg, O.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Savolainen, S.
    Soininen, H.
    Jääskeläinen, J. E.
    Rinne, J.
    Leinonen, V.
    Hiltunen, M.
    APOE4 predicts amyloid-β in cortical brain biopsy but not idiopathic normal pressure hydrocephalus2012Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, nr 11, s. 1119-1124Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate the association of apolipoprotein E (APOE) genotype, especially the APOE4 allele, to (1) idiopathic normal pressure hydrocephalus (iNPH) and (2) amyloid-β (Aβ) plaques in cortical brain biopsies of presumed NPH patients with and without a final clinical diagnosis of Alzheimer's disease (AD). Methods: 202 patients with presumed NPH were evaluated by intraventricular pressure monitoring and frontal cortical biopsy immunostained against Aβ (134 semiquantified by Aβ plaques/mm 2). The 202 patients and 687 cognitively healthy individuals were genotyped for APOE. The final clinical diagnoses in a median follow-up of 3.9 years were: 113 iNPH (94 shunt responsive, 16 shunt non-responsive, three not shunted); 36 AD (12 mixed iNPH + AD); 53 others. Results: The APOE genotypes distributed similarly in the 94 shunt responsive and 16 non-responsive iNPH patients and healthy controls. In multivariate analysis, the APOE4 allele correlated independently with Aβ plaques in the cortical biopsies (OR 8.7, 95% CI 3.6 to 20, p&lt;0.001). The APOE4 allele in presumed NPH predicted later AD as follows: sensitivity 61%; specificity 77%; positive predictive value 37%; negative predictive value 90%. Conclusion: In presumed NPH patients, APOE4 associates independently with the presence of Aβ plaques in the frontal cortical biopsy. APOE4 is not a risk factor for iNPH and does not predict the response to shunt. Our data further support the view that the iNPH syndrome is a distinct dementing disease.

  • 60.
    Qvarlander, Sara
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Lundkvist, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus2013Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, nr 7, s. 735-741Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

    Fulltekst (pdf)
    fulltext
  • 61.
    Reimer, J.
    et al.
    University Hospital, Lund.
    Grabowski, M.
    University Hospital, Lund.
    Lindvall, O.
    University Hospital, Lund.
    Hagell, Peter
    Lund University.
    Use and interpretation of on/off diaries in Parkinson's disease2004Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 75, nr 3, s. 396-400Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To explore the use and interpretation of self reported on/off diary data for assessment of daily motor fluctuations in Parkinson's disease.

    METHODS: 26 consecutive non-demented patients with fluctuating Parkinson's disease received standardised training on how to fill out the four category CAPSIT-PD on/off diary, followed by four hours of clinical observation and four weeks of daytime on/off diaries every 30 minutes at home.

    RESULTS: Overall patient-clinician agreement in diary entries was good (kappa = 0.62; weighted kappa = 0.84). Agreement for individual diary categories was good for "off" and "on with dyskinesias" (kappa = > or =0.72), but moderate for "partial off" and "on" (kappa = 0.49). The overall validity of patient kept diaries was supported by expected symptom severity variability across diary categories, as assessed in the clinic. One day's home diary data failed to predict outcomes from the full four weeks for all diary categories, and data from three days failed to yield good prediction (predefined as R(2) = > or =approximately 0.7) for the time spent in "off" and "partial off". Data from one week yielded good prediction (R(2) = > or =0.74) in all instances except "partial off", which could not be well predicted even when two weeks' home diary data were considered (R(2) = 0.52).

    CONCLUSIONS: The data provide support for the overall accuracy and validity of the four category CAPSIT-PD on/off diary, but suggest that a three category diary format may improve accuracy and validity. Interpretation of diary data beyond the assessed time frame should be made with caution unless diaries have been kept for sufficiently long periods.

  • 62.
    Ribom, D
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Andrae, J
    Frielingsdorf, M
    Hartman, M
    Nistér, M
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Prognostic value of platelet derived growth factor alpha receptor expression in grade 2 astrocytomas and oligoastrocytomas2002Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 72, nr 6, s. 782-787Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    To determine whether the expression of platelet derived growth factor alpha receptor (PDGFRalpha) in low grade astrocytomas and oligoastrocytomas is associated with survival.

    METHODS:

    Formalin fixed and paraffin embedded tumour samples of 40 consecutive patients with supratentorial diffuse astrocytomas and oligoastrocytomas of WHO grade 2, resected between 1986 and 1993, were used for immunohistochemical staining. The fraction of tumour cells expressing PDGFRalpha protein was quantified and entered into univariate and multivariate survival analyses. Changes in PDGFalpha expression over time were analysed in seven patients in whom reoperations had been performed.

    RESULTS:

    Patients with a relatively high fraction of PDGFRalpha expressing cells had a more favourable outcome in both univariate (p = 0.04) and multivariate analyses (p = 0.02). Expression of PDGFRalpha was greater in oligoastrocytomas than in astrocytomas (p = 0.05). In four reoperated patients with histologically confirmed malignant transformation, there was a marked decrease in the number of cells expressing the receptor.

    CONCLUSIONS:

    There is an association between high PDGFRalpha expression and long survival time in patients with grade 2 astrocytomas and oligoastrocytomas. The findings suggest that expression of the receptor may be a useful prognostic marker in such patients.

  • 63. Rydenhag, Bertil
    et al.
    Flink, Roland
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Malmgren, Kristina
    Surgical outcomes in patients with epileptogenic tumours and cavernomas in Sweden: good seizure control but late referrals.2013Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 84, nr 1, s. 49-53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Seizure outcome after epilepsy surgery is to an important extent related to underlying aetiology. In this study of patients who underwent epilepsy surgery with a lesional aetiology in Sweden 1990-2004, the aim was to investigate seizure outcome and prognostic factors. METHODS: All patients operated on during the time period with a histopathological diagnosis of an epileptogenic tumour (ganglioglioma (GGL), dysembryoblastic neuroepithelial tumour (DNET) and low grade astrocytoma (AST)) or a cavernous haemangioma (CAH) were identified in the population based Swedish National Epilepsy Surgery Register. Univariate and multivariate analyses were performed to determine the independent contribution of the following variables to seizure outcome: age at surgery; epilepsy duration; preoperative seizure frequency; localisation of the resection; and histopathology. RESULTS: Of the 156 identified patients who had a 2 year follow-up (103 adults and 53 children), 71% had temporal, 16% frontal and 13% parietal and occipital lobe resections. Mean presurgical epilepsy duration was 13 years in adults and 5 years in children. Main histopathological diagnosis was GGL or DNET in 67, CAH in 42 and AST in 47 patients. 77% of patients had sustained seizure freedom (with or without aura) 2 years after surgery. In the multivariate analysis, only diagnosis other than AST was independently associated with becoming seizure free. CONCLUSION: In this population based series, 120/156 patients (77%) with epileptogenic tumours and cavernomas were seizure free 2 years after surgery. Many had a very long epilepsy history. Seizure outcome can be improved if epilepsy surgery is considered earlier in patients with epileptogenic lesions.

  • 64. Schmidt, Hartmut
    et al.
    Adams, David
    Coelho, Teresa
    Conceicao, Isabel
    Waddington-Cruz, Marcia
    Buades, Juan
    Campistol, Josep
    Pouget, Jean
    Gollob, Jared
    Suhr, Ole
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Patisiran ph 2 open-label extension study in Familial Amyloidotic Polyneuropathy2016Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 87, nr 12Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background: Familial Amyloid Polyneuropathy (FAP) is a progressive disease caused by deposition of transthyretin (TTR). Patisiran is an investigational, small interfering RNA (siRNA) inhibiting TTR. This abstract highlights patisiran's long-term safety. Methods: Phase 2 OLE study to evaluate patisiran's safety. Patisiran's effect on serum TTR levels, impact on neuropathy impairment scores and QOL were assessed. Results: 27 patients with FAP enrolled; median age 64 years. Patisiran was generally well tolerated out to 23-months. Five patients experienced SAEs (unrelated) including one discontinuation (gastroesophageal cancer); patient subsequently died. Flushing (25.9%) and infusion-related reactions (18.5%) were mild in severity; no discontinuations resulted. Approximately 80% sustained mean serum TTR lowering resulted with a mean nadir of up to 93% between doses. Among the 20 evaluable patients, neuropathy impairment scores were stable through 18-months; mean change in mNIS+7 and NIS of 1.7 and 4.2 points, respectively. This compares favorably to 17–26 point mNIS+7/NIS increase estimated at 18-months from prior FAP studies. Stabilization of QOL measures and improvement of distal thigh sweat gland nerve fiber density observed. Conclusion: Data demonstrates that 18-months of patisiran administration was generally well tolerated, resulted in sustained mean serum TTR lowering, supporting the hypothesis that TTR knockdown potentially halts neuropathy progression.

  • 65. Sjögren, M
    et al.
    Davidsson, P
    Tullberg, M
    Minthon, L
    Wallin, A
    Wikkelso, C
    Granérus, Ann-Kathrine
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Geriatrik. Östergötlands Läns Landsting, MC - Medicincentrum, Geriatrik-LAH.
    Vanderstichele, H
    Vanmechelen, E
    Blennow, K
    Both total and phosphorylated tau are increased in Alzheimer's disease2001Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 70, nr 5, s. 624-630Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background - Pathological tau protein concentrations in CSF are found in both Alzheimer's disease (AD) and frontotemporal dementia (FTD), but studies on brain tissue have suggested that the tau pathology in AD differs from that in FTD and that the difference may be related to the degree of phosphorylation. As CSF tau protein is increased after stroke, tau may also be implicated in the pathophysiology of vascular dementia, of which subcortical arteriosclerotic encephalopathy (SAE) is a putative subtype. Objectives - To investigate the nature of tau protein in CSF and the involvement of total CSF tau and phosphorylated CSF tau (phosphotau) in various types of dementia. Methods - Using ELISAs for total tau and tau phosphorylated at Thr181 (phosphotau), the CSF concentrations of total tau and phosphotau were determined in patients with probable and possible AD (n=41 and 19, respectively), FTD (n=18), SAE (n=17), and Parkinson's disease (PD, n= 15) and in age matched controls (n=17). All the antibodies stained the lower molecular weight bands, whereas only the antibodies that recognise phosphorylated tau stained the higher molecular bands. Results - Both CSF tau and CSF phosphotau were increased in probable AD compared with FTD (p<0.001), SAE (p<0.001), PD (p<0.001), and controls (p<0.001). CSF phosphotau was increased in possible AD compared with FTD (p<0.001) and SAE (p<0.001). CSF tau and CSF phosphotau were positively correlated in all the groups. Molecular weight forms of tau ranging from 25 kDa to 80 kDa were found in the CSF Conclusion - Both phosphorylated and unphosphorylated tau isoforms were present in the CSF, and tau protein appeared in both truncated and full length forms. The results suggest that the CSF concentrations of tau and phosphotau are increased in about two thirds of patients with probable AD and in half of those with possible AD but are normal in FTD, SAE, and PD compared with normal aging. Values in the normal range do not exclude AD.

  • 66. Steinacker, Petra
    et al.
    Feneberg, Emily
    Weishaupt, Jochen
    Brettschneider, Johannes
    Tumani, Hayrettin
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    von Arnim, Christine A. F.
    Boehm, Sarah
    Kassubek, Jan
    Kubisch, Christian
    Lule, Dorothee
    Mueller, Hans-Peter
    Muche, Rainer
    Pinkhardt, Elmar
    Oeckl, Patrick
    Rosenbohm, Angela
    Anderl-Straub, Sarah
    Volk, Alexander E.
    Weydt, Patrick
    Ludolph, Albert C.
    Otto, Markus
    Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients2016Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 87, nr 1, s. 12-20Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Biomarkers for the diagnosis of motoneuron diseases (MND) are urgently needed to improve the diagnostic pathway, patient stratification and monitoring. The aim of this study was to validate candidate markers for MND in cerebrospinal fluid (CSF) and specify cut-offs based on large patient cohorts by especially considering patients who were seen under the initial differential diagnosis (MND mimics). Methods In a prospective study, we investigated CSF of 455 patients for neurofilament light chain (NfL), phosphorylated heavy chain (pNfH), tau protein (Tau) and phospho-tau protein (pTau). Analysed cohorts included patients with apparently sporadic and familial amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) (MND, n=253), MND mimics (n=85) and neurological control groups. Cut-off values were specified, and diagnostic performance and correlation with progression were analysed. Results Nfs were significantly higher in the MND group compared to the control groups, whereas Tau and pTau did not differ. At a cut-off level of 2200 pg/mL for NfL, a 77% diagnostic sensitivity (CI 71% to 82%), 85% specificity (CI 79% to 90%) and 87% positive predictive value (PPV) (CI 81% to 91%) were achieved. For pNfH, we calculated 83% sensitivity (CI 78% to 88%), 77% specificity (CI 71% to 83%) and 82% PPV (CI 77% to 86%) at 560 pg/mL. There were no significant differences between sporadic and genetic ALS or PLS. Nf levels were elevated at early disease stage, and correlated moderately with MND progression and duration. Conclusions Neurofilaments in CSF have a high relevance for the differential diagnosis of MNDs and should be included in the diagnostic work-up of patients. Their value as prognostic markers should be investigated further.

  • 67. Stephensen, H
    et al.
    Andersson, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Tisell, M
    Wikkelsö, C
    Objective B wave analysis in 55 patients with non-communicating and communicating hydrocephalus2005Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 76, s. 965-970Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: B waves, slow and rhythmic oscillations in intracranial pressure (ICP), are claimed to be one of the best predictors of outcome after surgery for normal pressure hydrocephalus (NPH).

    Object: To determine the relation between the percentage of B waves and outcome in patients with hydrocephalus, and also the diurnal variation of B waves.

    Methods: ICP and patient behaviour were recorded overnight (17 to 26 hours) in 29 patients with non-communicating hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the percentage of total monitoring time (% B waves) using a computer algorithm, and correlated with postoperative outcome, defined as changes in 12 standardised symptoms and signs.

    Results: There was no linear correlation between improvement after surgery in the 55 patients and total % B waves, but a correlation was found between improvement and % B waves during sleep (r = 0.39, p = 0.04). The percentage of B waves was the same during sleep and wakefulness, and patients with NPH had the same proportion of B waves as the non-communicating patients.

    Conclusions: B waves are commonly observed in patients with both communicating and non-communicating hydrocephalus, but are only weakly related to the degree of postsurgical improvement.

  • 68. Synofzik, Matthis
    et al.
    Fernández-Santiago, Rubén
    Maetzler, Walter
    Schöls, Ludger
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    The human G93A SOD1 phenotype closely resembles sporadic amyotrophic lateral sclerosis2010Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 81, nr 7, s. 764-767Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Transgenic mouse models of human SOD1 mutations have opened up an area of intense investigation into the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS). However, the human phenotype of the G93A SOD1 mutation-the most commonly studied mutation in rodent models-has remained essentially unknown. This complicates the interpretation and transfer of results from animal models. Here clinical, electrophysiological and genealogical data are presented from a large German pedigree with a G93A mutation in the SOD1 gene. This pedigree shows a highly homogenous phenotype which closely resembles the typical phenotype of sporadic ALS, thus implicating comparable disease pathology of G93A SOD1 ALS and sporadic ALS.

  • 69.
    Terent, Andreas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Asplund, Kjell
    Farahmand, Bahman
    Henriksson, Karin
    Norrving, Bo
    Stegmayr, Birgitta
    Wester, Per-Olov
    Hulter-Åsberg, Kerstin
    Åsberg, Signild
    Stroke unit care revisited - who benefits the most?: A cohort study of 105 043 patients in Riks-Stroke, the Swedish Stroke Register2009Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, nr 8, s. 881-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Treatment at stroke units is superior to treatment at other types of wards. The objective of the present study is to determine the effect size of stroke unit care in subgroups of stroke patients. This information might be useful in a formal priority setting. METHODS: All acute strokes reported to the Swedish Stroke Register the year 2001 through 2005, were followed up until January 31, 2007. The subgroups were age (18-64, 65-74, 75-84, 85 years and above), sex (male, female), stroke subtype (intracerebral haemorrhage, cerebral infarction and unspecified stroke), and level of consciousness (conscious, reduced, unconscious). Cox proportional hazards and logistic regression analyses was used to estimate the risk for death, institutional living or dependency. RESULTS: 105 043 patients wee registered at 86 hospitals in a population of 9 million inhabitants.79 689 patients (76%) were treated in stroke units and 25 354 patients (24%) in other types of wards. Stroke unit care was associated with better long-term survival in all subgroups. The best effect of stroke unit care was seen among the following subgroups: age 18-64 years (hazard ratio (HR) for death 0.53; 0.49 to 0.58), intracerebral haemorrhage (HR 0.61; 0.58 to 0.65) and unconsciousness (HR 0.70; 0.66 to 0.75). Stroke unit care was also associated with reduced risk for death or institutional living after 3 months. CONCLUSIONS: Stroke unit care was associated with better outcome in all subgroups, but younger patients, patients with intracerebral haemorrhage and patients who were unconscious had the best effect.

  • 70. Terént, A
    et al.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Farahmand, B
    Henriksson, K M
    Norrving, B
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wester, P-O
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Asberg, K H
    Asberg, S
    Stroke unit care revisited: who benefits the most? A cohort study of 105,043 patients in Riks-Stroke, the Swedish Stroke Register.2009Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, nr 8, s. 881-887Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Treatment at stroke units is superior to treatment at other types of wards. The objective of the present study is to determine the effect size of stroke unit care in subgroups of patients with stroke. This information might be useful in a formal priority setting. METHODS: All acute strokes reported to the Swedish Stroke Register from 2001 through 2005 were followed until January 2007. The subgroups were age (18-64, 65-74, 75-84, 85+ years and above), sex (male, female), stroke subtype (intracerebral haemorrhage, cerebral infarction and unspecified stroke) and level of consciousness (conscious, reduced, unconscious). Cox proportional hazards and logistic regression analyses were used to estimate the risk for death, institutional living or dependency. RESULTS: 105,043 patients were registered at 86 hospitals. 79,689 patients (76%) were treated in stroke units and 25,354 patients (24%) in other types of wards. Stroke unit care was associated with better long-term survival in all subgroups. The best relative effect was seen among the following subgroups: age 18-64 years (hazard ratio (HR) for death 0.53; 0.49 to 0.58), intracerebral haemorrhage (HR 0.61; 0.58 to 0.65) and unconsciousness (HR 0.70; 0.66 to 0.75). Stroke unit care was also associated with reduced risk for death or institutional living after 3 months. CONCLUSIONS: Stroke unit care was associated with better long-term survival in all subgroups, but younger patients, patients with intracerebral haemorrhage and patients who were unconscious had the best relative effect and may be given the highest priority to this form of care.

  • 71. van Es, Michael A
    et al.
    Dahlberg, Caroline
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Veldink, Jan Herman
    van den Berg, Leonard H
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Large-scale SOD1 mutation screening provides evidence for genetic heterogeneity in amyotrophic lateral sclerosis.2010Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 81, nr 5, s. 562-566Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To estimate the frequency of SOD1 mutations in a large referral cohort of familial amyotrophic lateral sclerosis (FALS) and sporadic amyotrophic lateral sclerosis (SALS) patients from The Netherlands and to compare this frequency with that of other developed countries. METHODS: A total of 451 sporadic and 55 FALS patients were screened for SOD1 mutations. The authors performed PCR amplification of all five coding exons of SOD1 followed by direct DNA sequencing using forward and reverse primers. RESULTS: One novel mutation (p.I99V) and a homozygous p.D90A mutation were identified in SALS patients. In a pedigree with Mendelian dominant FALS, one patient was found to be heterozygous for the p.D90A mutation. SOD1 mutation frequency was found to be significantly lower in The Netherlands compared with other countries with p=0.0004 for FALS (21.9% vs 2.5%) and p=0.005 for SALS (2.5% vs 0.44%). CONCLUSIONS: The authors demonstrate that SOD1 mutations are rare in The Netherlands in familial and SALS. This observation suggests that the genetic background of amyotrophic lateral sclerosis differs between different populations, countries and regions. This may have consequences for the interpretation of association studies and explain why replication of association studies has proven difficult in amyotrophic lateral sclerosis.

  • 72. Weber, M
    et al.
    Neuwirth, C
    Thierbach, J
    Schweikert, K
    Czaplinski, A
    Petersen, J
    Jung, HH
    Birve, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Marklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersen, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    ALS patients with SOD1 mutations in Switzerland show very diverse phenotypes and extremely long survival2012Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, nr 3, s. 351-353Artikkel i tidsskrift (Fagfellevurdert)
  • 73.
    Ågren Wilsson, A
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Roslin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, LO
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Bergenheim, AT
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Malm, J
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Intracerebral microdialysis and CSF hydrodynamics in idiopathic adult hydrocephalus syndrome2003Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 74, nr 2, s. 217-221Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: In idiopathic adult hydrocephalus syndrome (IAHS), a pathophysiological model of "chronic ischaemia" caused by an arteriosclerotic process in association with a CSF hydrodynamic disturbance has been proposed. OBJECTIVE: To investigate whether CSF hydrodynamic manipulation has an impact on biochemical markers related to ischaemia, brain tissue oxygen tension (PtiO(2)), and intracranial pressure. METHODS: A microdialysis catheter, a PtiO(2) probe, and an intracerebral pressure catheter were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. A subcutaneous microdialysis probe was used as reference. Intracranial pressure and intracerebral PtiO(2) were recorded continuously. Samples were collected for analysis between 2 and 4 pm on day 1 (baseline) and at the same time on day 2, two to four hours after a lumbar CSF hydrodynamic manipulation. The concentrations of glucose, lactate, pyruvate, and glutamate on day 1 and 2 were compared. RESULTS: After CSF drainage, there was a significant rise in the intracerebral concentration of lactate and pyruvate. The lactate to pyruvate ratio was increased and remained unchanged after drainage. There was a trend towards a lowering of glucose and glutamate. Mean intracerebral PtiO(2) was higher on day 2 than on day 1 in six of eight patients. CONCLUSIONS: There is increased glucose metabolism after CSF drainage, as expected in a situation of postischaemic recovery. These new invasive techniques are promising tools in the future study of the pathophysiological processes in IAHS.

  • 74.
    Ågren-Wilsson, Aina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, L-O D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Brain energy metabolism and intracranial pressure in idiopathic adult hydrocephalus syndrome2005Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 76, nr 8, s. 1088-1093Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance. OBJECTIVE: To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter. METHODS: A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate. RESULTS: When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p < 0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage. CONCLUSIONS: Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.

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