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  • 201.
    Gu, Weigang
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Norrlands universitetssjukhus, Umeå.
    Jonasson, Per
    Avdelningen för diagnostisk radiologi, Norrlands universitetssjukhus, Umeå.
    Trombektomi gav gott resultat vid basilaris­trombos: Förlängt tidsfönster för ingreppet föreslås2014Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 27-28, s. 1188-1190Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Basilaristrombos är ett akut och livshotande tillstånd. Intravenös trombolys är förstahandsbehandling, men ibland kan det vara en fördel att kombinera eller ersätta behandlingen med trombektomi. 

    Lyckade behandlingsresultat med trombektomi finns beskrivna ända upp till 12–24 timmar efter insjuknandet. 

    I fallbeskrivningarna diskuteras basilaristrombos hos två patienter som insjuknat med oklar medvetandesänkning. 

    DT-angiografi gav diagnosen, och trombektomi kunde utföras 10 respektive 13 timmar efter insjuknandet. Långtidsresultatet var gott. 

    Slutsatsen är att DT alltid ska kompletteras med DT-angiografi vid utredning av en akut medvetandepåverkad patient. 

    Trombektomi bör övervägas om basilaristrombos påvisas.

  • 202.
    Gustafsson, Helena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Aasly, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stråhle, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Nordstrom, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Low muscle strength in late adolescence and Parkinson disease later in life2015Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 84, nr 18, s. 1862-1869Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective:To evaluate maximal isometric muscle force at 18 years of age in relation to Parkinson disease (PD) later in life.Methods:The cohort consisted of 1,317,713 men who had their muscle strength measured during conscription (1969-1996). Associations between participants' muscle strength at conscription and PD diagnoses, also in their parents, were examined using multivariate statistical models.Results:After adjustment for confounders, the lowest compared to the highest fifth of handgrip strength (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.06-1.79), elbow flexion strength (HR 1.34, 95% CI 1.02-1.76), but not knee extension strength (HR 1.24, 95% CI 0.94-1.62) was associated with an increased risk of PD during follow-up. Furthermore, men whose parents were diagnosed with PD had reduced handgrip (fathers: mean difference [MD] -5.7 N [95% CI -7.3 to -4.0]; mothers: MD -5.0 N [95% CI -7.0 to -2.9]) and elbow flexion (fathers: MD -4.3 N [95% CI -5.7 to -2.9]; mothers: MD -3.9 N [95% CI -5.7 to -2.2]) strength, but not knee extension strength (fathers: MD -1.1 N [95% CI -2.9 to 0.8]; mothers: MD -0.7 N [95% CI -3.1 to 1.6]), than those with no such familial history.Conclusions:Maximal upper extremity voluntary muscle force was reduced in late adolescence in men diagnosed with PD 30 years later. The findings suggest the presence of subclinical motor deficits 3 decades before the clinical onset of PD.

  • 203. Hagglund, H.
    et al.
    Askmark, H.
    Stromberg, U.
    Axelsson, H.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Isaksson, C.
    Wahlin, A.
    Andersen, O.
    Johansson, J.
    Press, R.
    Autologous haematopoietic stem cell transplantation: a viable treatment option for chronic inflammatory demyelinating polyneuropathy2013Inngår i: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 48, s. S336-S336Artikkel i tidsskrift (Annet vitenskapelig)
  • 204.
    Hamberg, Katarina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    The decision-making process leading to deep brain stimulation in men and women with parkinson's disease: an interview study2014Inngår i: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 14, s. 89-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced parkinson's disease (PD). Research shows that women are under-represented among patients undergoing DBS surgery. This may be due to gender-biased selection of patients, but patients' wishes and attitudes may also contribute. This study investigated the decision making process to undergo DBS from the patient's perspective, and explored any gender patterns in the participants' decision-making. Methods: All patients operated on with DBS for PD at the University Hospital of Northern Sweden between January 2002 and April 2010 were invited to an interview study. In this way 39 patients were recruited, 31 men and eight women. Three additional women, operated elsewhere, were recruited to acheive a more gender-balanced sample. In a mixed-method analysis, the interviews were analysed according to the constant comparison technique in grounded theory and descriptive statistics was used to present demographics and compare categories. Results: Three different approaches to DBS were identified among the patients. `Taking own initiative', included 48% of the patients and implied that the patients' own initiatives and arguments had been crucial for having surgery. `Agreeing when offered', and accepting DBS when suggested by doctors embraced 43%. The third approach, `Hesitating and waiting' included < 10% of the patients. Most of the men were either `taking own initiative' or `agreeing when offered'. The 11 women were evenly distributed in all three approaches. Among the interviewed, more women than men expressed strong fear of complications and more women consulted friends and relatives prior to deciding about DBS. Half of the patients had held a leadership position at work or in another organisation, and among patients `taking own initiative' the proportion with leadership experiences was 80%. At time for surgery ten men but no woman were professionally active. Conclusion: This study suggests that many patients with advanced PD have to argue and struggle with their clinicians in order to be referred to a DBS-team. The study further suggests that patients' wishes, behaviour and position in society may all contribute to the skewed gender distribution among patients treated with DBS.

  • 205. Hamel, Wolfgang
    et al.
    Koeppen, Johannes A.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. nit of Functional Neurosurgery, UCL Institute of Neurology, London, UK.
    Krack, Paul
    Moll, Christian K. E.
    The Pioneering and Unknown Stereotactic Approach of Roeder and Orthner from Gottingen. Part I. Surgical Technique for Tailoring Individualized Stereotactic Lesions2016Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, nr 4, s. 240-253Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    During the 1950s through the 1970s, Hans Orthner and Fritz Roeder, two German neurologists from Gottingen, developed a sophisticated technique to perform functional stereotactic surgery with outstanding accuracy. They introduced direct air ventriculography performed in the same surgical session as the ablative stereotactic procedure. For individualized surgical targeting, Orthner prepared a stereo tactic atlas (>60 brains) with an ingenious brain-slicing device, the Gottinger macrotome. Brains were grouped based on similarity of six different head and ventricle measurements. A brain cluster representing the best match for a patient was selected for stereotactic targeting. Stereotactic lesions were tailored in an individual manner and shaped by stringing together multiple small coagulations following in-traoperative test stimulation. This was achieved from a single probe trajectory by using well-engineered string electrodes with calibrated curving and involved laborious calculations. Only high-frequency thermocoagulation was regarded as appropriate for lesioning. With this meticulous technique, the most advanced stereotactic procedures were performed, including bilateral pallidotomy that ultimately could be restricted to the ansa lenticularis and ventromedial hypothalamotomy, the most delicate stereotactic operation performed to date. Outside Gottingen, this technique has only been used by Prof. Dieter Muller in Hamburg, Germany. This elaborate stereotactic approach is widely unknown and deserves to be discussed in a historical context. 

  • 206. Hamel, Wolfgang
    et al.
    Koeppen, Johannes A.
    Mueller, Dieter
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, UCL Institute of Neurology, London, UK.
    Moll, Christian K. E.
    Krack, Paul
    The Pioneering and Unknown Stereotactic Approach of Roeder and Orthner from Gottingen. Part II: Long-Term Outcome and Postmortem Analysis of Bilateral Pallidotomy in the Pre-Levodopa Era2018Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 96, nr 6, s. 353-363Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Before the advent of levodopa, pallidotomy was initially the most effective treatment for Parkinson disease, but it was soon superseded by thalamotomy. It is widely unknown that, similar to Leksell, 2 neurologists from Gottingen, Orthner and Roeder, perpetuated pallidotomy against the mainstream of their time. Postmortem studies demonstrated that true posterior and ventral pallidoansotomy sparing the overwhelming mass of the pallidum was accomplished. This was due to a unique and individually tailored stereotactic technique even allowing bilateral staged pallidotomies. In 1962, the long-term effects (3-year follow-up on average) of the first 18 out of 36 patients with staged bilateral pallidotomies were reported in great detail. Meticulous descriptions of each case indicate long-term improvements in parkinsonian rigidity and associated pain, as well as posture, gait, and akinesia (e.g., improved repetitive movements and arm swinging). Alleviation of tremor was found to require larger lesions than needed for suppression of rigidity. No improvement in speech, drooling, or seborrhea was observed. By 1962, the team had operated 13 patients with postencephalitic oculogyric crises with remarkable results (mean follow-up: 5 years). They also described alleviation of nonparkinsonian hyperkinetic disorders (e.g., hemiballism and chorea) with pallidotomy. The reported rates for surgical mortality and other complications had been remarkably low, even if compared to those reported after the revival of pallidotomy by Laitinen in the post-levodopa era. This applies also to bilateral pallidotomy performed with a positive risk-benefit ratio that has remained unparalleled to date. The intricate history of pallidotomy for movement disorders is incomplete without an appreciation of the achievements of the Gottingen group.

  • 207. Hansson, Oskar
    et al.
    Janelidze, Shorena
    Hall, Sara
    Magdalinou, Nadia
    Lees, Andrew J.
    Andreasson, Ulf
    Norgren, Niklas
    Linder, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Constantinescu, Radu
    Zetterberg, Henrik
    Blennow, Kaj
    Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder2017Inngår i: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, nr 10, s. 930-937Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders. Methods: The study included 3 independent prospective cohorts: the Lund (n 5 278) and London (n 5 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n 5 109) of patients with PD, PSP, MSA, or CBS with disease duration <= 3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated. Results: We found strong correlations between blood and CSF concentrations of NfL (p >= 0.73-0.84, p <= 0.001). Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p, 0.001). Furthermore, in the Lund cohort, blood NfL could accurately distinguish PD from APD (area under the curve [AUC] 0.91) with similar results in both the London cohort (AUC 0.85) and the early disease cohort (AUC 0.81). Conclusions: Quantification of blood NfL concentration can be used to distinguish PD from APD. Blood-based NfL might consequently be included in the diagnostic workup of patients with parkinsonian symptoms in both primary care and specialized clinics.

  • 208.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Koskinen, Lars-Owe D
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life2008Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 118, nr 6, s. 387-394Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

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

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

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

  • 209.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Activities of daily living and quality of life in persons with newly diagnosed Parkinson's disease according to subtype of disease, and in comparison to healthy controls.2011Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 123, nr 1, s. 20-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE:

    To describe activity of daily living (ADL) and quality of life (QoL) at first visit to a neurological centre, in patients subsequently diagnosed with Parkinson's disease (PD), according to subtype of disease and compared to healthy controls.

    MATERIALS AND METHODS:

    99 patients and 31 controls were included. Patients were classified into three groups according to predominant symptoms: 50 Postural instability-gait difficulties (PIGD), 37 tremor dominant, 12 indeterminate. Evaluations included ADL-taxonomy, SF-36, and the Parkinson disease questionnaire (PDQ-39).

    RESULTS:

    Patients experienced early on limitations in ADL and QoL compared to controls. Patients with PIGD subtype had already at first visit a worse status, clinically and in ADL and QoL, than patients with tremor dominant type.

    CONCLUSIONS:

    Already at first visit to a neurological centre, patients who will eventually receive the diagnosis of PD exhibited restrictions in ADL and QoL. Patients with axial symptoms were affected most.

  • 210.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hamberg, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Perceptions of living with a device-based treatment: an account of patients treated with deep brain stimulation for Parkinson’s disease2014Inngår i: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 17, nr 3, s. 272-278Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives Deep brain stimulation (DBS) is an established treatment for Parkinson's disease. Little is known about patients' own perceptions of living with the implanted hardware. We aimed to explore patients' own perceptions of living with an implanted device. Materials and Methods Semistructured interviews with open-ended questions were conducted with 42 patients (11 women) who had been on DBS for a mean of three years. The questions focused on patients' experiences of living with and managing the DBS device. The interviews were transcribed verbatim and analyzed according to the difference and similarity technique in grounded theory. Results From the patients' narratives concerning living with and managing the DBS device, the following four categories emerged: 1) The device—not a big issue: although the hardware was felt inside the body and also visible from outside, the device as such was not a big issue. 2) Necessary carefulness: Patients expressed the need to be careful when performing certain daily activities in order not to dislocate or harm the device. 3) Continuous need for professional support: Most patients relied solely on professionals for fine-tuning the stimulation rather than using their handheld controller, even if this entailed numerous visits to a remote hospital. 4) Balancing symptom relief and side-effects: Patients expressed difficulties in finding the optimal match between decrease of symptoms and stimulation-induced side-effects. Conclusions The in-depth interviews of patients on chronic DBS about their perceptions of living with an implanted device provided useful insights that would be difficult to capture by quantitative evaluations.

  • 211.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL Institute of Neurology, Queen Square, London, UK.
    Limousin, P.
    Zrinzo, L.
    Tripoliti, E.
    Aviles-Olmos, I.
    Jahanshahi, M.
    Hamberg, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Foltynie, T.
    Gender differences in quality of life following subthalamic stimulation for Parkinson's disease2013Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 128, nr 4, s. 281-285Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives - Surveys of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD) have shown that this procedure is roughly twice more common in men than in women. Here, we investigate possible differences between women and men undergoing STN DBS, with respect to health-related quality of life.

    Materials and methods - Forty-nine consecutive patients (18 women) received STN DBS. The impact of PD and its surgical treatment was compared between women and men, before and at mean of 19 +/- 11months after surgery, using the Unified Parkinson Disease Rating Scale (UPDRS) and the Parkinson's Disease Questionnaire-39 (PDQ-39).

    Results - Duration of disease at surgery and off-medication scores of the motor part of the UPDRS were similar in women and men. At baseline, women had lower doses of dopaminergic medication than men, experienced more disability due to dyskinesias, had more sensory symptoms and perceived more difficulties in mobility. Following DBS, both men and women showed equal and significant (P<0.001) improvement in off-medication scores on the UPDRS III. On the PDQ-39, women expressed improvement in ADL to a greater extent than men. Moreover, women but not men showed a positive effect on mobility, stigma and cognition as well as on the summary score of PDQ-39.

    Conclusions - Although STN DBS results in equal degree of motor improvement between women and men, health-related quality of life seems to improve to a greater extent in women.

  • 212.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Limousin, Patricia
    Hamberg, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    "DBS means everything - for some time": Patients' Perspectives on Daily Life with Deep Brain Stimulation for Parkinson's Disease2016Inngår i: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 6, nr 2, s. 335-347Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease. However, patients' own perceptions of the impact of DBS on their daily living is not fully explored. 

    Objective: We aimed to collect and analyse patients' narratives about their everyday experiences of being on chronic DBS. 

    Methods: Semi-structured interviews with open-ended questions were conducted with 42 patients (11 women) who had been on DBS for a mean of three years. The questions were related to patients' ordinary daily life and eventual changes, both negative and positive, brought about by DBS. The interviews were transcribed verbatim and analysed according to the difference and similarity technique in grounded theory. 

    Results: From the patients' narratives the core category `DBS means everything - for some time' was established, and supported by the following categories: 1) Relief from invasive tremor. 2) A rescue from cramps and pain. 3) Easier movement swings and more predictable living space. 4) Hard, but compared to previous suffering, bearable adverse events. 5) Parkinson's disease is progressing despite DBS. 

    Conclusions: The analysis of the participants' narratives shed light on patients' unique perceptions and perspectives of the impact of DBS on their everyday lives. Patients with advanced PD highly appreciated the positive impact of DBS on their daily life even if this impact is limited in time. For the majority, the relief from the severe parkinsonian symptoms, especially tremor and painful cramps, outweighed the side effects of DBS. The study provided information not readily captured by pre-formulated questionnaires and scales.

  • 213.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lindberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Impact of thalamic deep brain stimulation on disability and health-related quality of life in patients with essential tremor2002Inngår i: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 72, nr 1, s. 47-52Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: To evaluate the impact of thalamic deep brain stimulation (DBS) on disability and health-related quality of life in patients with essential tremor.

    METHODS: Twenty seven consecutive patients were evaluated prospectively, before surgery and at a mean of 12 months (range 6-26) after thalamic DBS. Assessment tools included the Fahn-Tolosa-Marìn tremor rating scale (TRS), activities of daily living (ADL) taxonomy, Nottingham health profile (NHP) and the visual analogue scale (VAS) for measuring impact of disease on life. Additional information on the side effects of, and expectations from surgery was obtained by interview.

    RESULTS: Thalamic DBS improved the ability of the patients in eating, drinking, writing, home maintenance, hobbies, and participation in society. Activities of daily life requiring bimanual skills were less improved. The emotional condition of the patients was positively affected and the negative impact of the disease on life as a whole, and on social life was decreased. Seventy per cent of the patients considered that the surgical treatment met their expectations.

    CONCLUSIONS: After thalamic DBS, health-related quality of life including disability in ADL and social life were improved in patients with essential tremor.

  • 214.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Lindberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Bergenheim, A Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Does the ADL part of the unified Parkinson's disease rating scale measure ADL? An evaluation in patients after pallidotomy and thalamic deep brain stimulation.2003Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 18, nr 4, s. 373-381Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We evaluated the impact of pallidotomy and thalamic deep brain stimulation (DBS) on disability of patients with advanced Parkinson's disease and investigated whether the activities of daily living (ADL) section of the Unified Parkinson's Disease Rating Scale (UPDRS) measures disability in everyday life. Nineteen patients who had pallidotomy and 14 patients who had thalamic DBS were followed for a mean of 11 months. Evaluation tools included the UPDRS as well as a generic ADL scale, called ADL taxonomy. The 13 items belonging to the ADL part of the UPDRS were classified into two categories according to whether the items described a disability or impairment. The total scores of the UPDRS Part II (ADL) were ameliorated in both the pallidotomy and the thalamic DBS groups. When analysing separately the scores from the two categories of the ADL part of the UPDRS, i.e., disability and impairment, only patients who underwent pallidotomy showed improvement in disability-related items. These findings were confirmed when evaluating the patients with the ADL taxonomy. The ADL part of the UPDRS contains a mixture of impairment- and disability-related items. This mixture may confound results when evaluating the impact of surgery on ADL.

  • 215.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Arbetsterapi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nakajama, Takeshi
    UCL Institute of Neurology, Queen Square, London, UK; Department of Neurosurgery, Tokyo Women’s Medical University, Tokyo, Japan.
    Limousin, Patricia
    UCL Institute of Neurology, Queen Square, London, UK.
    Foltynie, Tom
    UCL Institute of Neurology, Queen Square, London, UK.
    Zrinzo, Ludvic
    UCL Institute of Neurology, Queen Square, London, UK.
    Jahanshahi, Marjan
    UCL Institute of Neurology, Queen Square, London, UK.
    Hamberg, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Gender distribution of patients with Parkinson's disease treated with subthalamic deep brain stimulation: a review of the 2000-2009 literature2011Inngår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 17, nr 3, s. 146-149Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Purpose: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been the mainstream surgical procedure for advanced Parkinson’s disease (PD) during the last decade. Reports from a few individual centres have hinted that women who receive STN DBS are under-represented. We aimed to evaluate the gender distribution of patients with PD who had received STN DBS during the last ten years, and to discuss the findings in relation to studies on gender prevalence of PD.

    Methods: A search of the PubMed database of clinical papers in English language related to STN DBS between 2000 and 2009 was conducted. Care was taken to minimize redundancies in reporting of published patients. The proportion of men and women were expressed in total and according to pre-defined geographic regions.

    Results: One hundred and thirty five papers were eligible for review. The gender of the patients was specified in 119 papers on a total of 3880 patients, of which 63% were men. According to geographic origin of publications, the percentage of men with STN DBS was 68% in North America, 62% in Europe, 69% in Australia and 50% in Asia.

    Conclusions: The proportion of male patients who undergo STN DBS seems to exceed the reported male/female ratio of patients with PD.

  • 216.
    Hariz, Gun-Marie
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Rehncrona, Stig
    Blomstedt, Patric
    Limousin, Patricia
    Hamberg, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL Institute of Neurology, Queen Square, London, UK.
    Women pioneers in basal ganglia surgery2014Inngår i: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 20, nr 2, s. 137-141Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Background: Stereotactic functional neurosurgery on basal ganglia has a long history and the pioneers are mostly men. We aimed at finding out if there were women who have contributed pioneering work in this field. Methods: The literature was searched to identify women who have been first to publish innovative papers related to human basal ganglia surgery. Results: Six women fulfilling our criteria were found: Marion Smith, a British neuropathologist, made unique observations on stereotactic lesions of basal ganglia and thalamus on autopsied brains, and the lesions' relation to the reported clinical outcome. Natalia Bechtereva, a Russian neurophysiologist, pioneered the technique of therapeutic chronic deep brain stimulation to treat various brain disorders, including Parkinson's disease (PD). Denise Albe-Fessard, a French neurophysiologist, pioneered the technique of microelectrode recording (MER) in stereotactic functional neurosurgery. Gunvor Kullberg, a Swedish neurosurgeon, contributed in early CT imaging as well as early functional imaging of stereotactic lesions in PD and psychiatric patients. Hilda Molina, a Cuban neurosurgeon, established the Centro Internacional de Restauracion Neurologica (CIREN) and pioneered there MER-guided transplant surgery in PD patients. Veerle Vandewalle, a Belgian neurosurgeon, pioneered in 1999 deep brain stimulation (DBS) for Tourette Syndrome. Conclusion: Although men constitute the great majority of neurosurgeons, neurologists and other neuro-specialists who have made groundbreaking contributions in basal ganglia surgery, there are women who have made equally important and unique contributions to the field. The principal two techniques used today in functional stereotactic neurosurgery, MER and DBS, have once upon a time been pioneered by women. (C) 2013 Elsevier Ltd. All rights reserved.

  • 217.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, UCL Institute of Neurology, London, UK.
    Early surgery for Parkinson's disease?: Maybe, but not just yet2013Inngår i: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 12, nr 10, s. 938-939Artikkel i tidsskrift (Annet vitenskapelig)
  • 218.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Simon Sainsbury Chair of Functional Neurosurgery, Unit of Functional Neurosurgery, UCL-Institute of Neurology, Queen Square, London, UK.
    My 25 Stimulating Years with DBS in Parkinson's Disease2017Inngår i: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, s. S35-S43Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The year 2017 marks the 30th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid, Pollak et al. in 1987, initially targeting the motor thalamus to treat tremor, and subsequently targeting the subthalamic nucleus (STN) for treatment of symptoms of advanced Parkinson's disease (PD). STN DBS is undoubtedly "the most important discovery since levodopa", as stated by David Marsden in 1994. In 2014, The Lasker-DeBakey Clinical Medical Research Award to "honor two scientists who developed deep brain stimulation of the subthalamic nucleus", was bestowed upon Benabid and DeLong. STN DBS remains today the main surgical procedure for PD, due to its effectiveness in ameliorating PD symptoms and because it is the only surgical procedure for PD that allows a radical decrease in medication. Future improvements of DBS include the possibility to deliver a "closed-loop", "on demand" stimulation, as highly preliminary studies suggest that it may improve both axial and appendicular symptoms and reduce side effects such as dysarthria. Even though DBS of the subthalamic nucleus is the main surgical procedure used today for patients with PD, all patients are not suitable for STN DBS; as a functional neurosurgeon performing since more than 25 years various surgical procedures the aim of which is not to save life but to improve the patient's quality of life, I consider that the surgery should be tailored to the patient's individual symptoms and needs, and that its safety is paramount.

  • 219.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Once STN DBS, Always STN DBS?-Clinical, Ethical, and Financial Reflections on Deep Brain Stimulation for Parkinson's Disease2016Inngår i: MOVEMENT DISORDERS CLINICAL PRACTICE, ISSN 2330-1619, Vol. 3, nr 3, s. 285-287Artikkel i tidsskrift (Fagfellevurdert)
  • 220.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Simon Sainsbury Chair of Functional Neurosurgery,Unit of Functional Neurosurgery,UCL — Institute of Neurology,Queen Square, London, UK.
    Stereotactic Ablative Surgery Does Not Just Mean "Adding Another Lesion"2017Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, nr 7, s. 1112-1113Artikkel i tidsskrift (Fagfellevurdert)
  • 221.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Striking similarities between pallidotomy and STN DBS at very long-term follow-up2012Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 27, nr 6, s. 806-806Artikkel i tidsskrift (Fagfellevurdert)
  • 222.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Twenty-five years of deep brain stimulation: Celebrations and apprehensions2012Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 27, nr 7, s. 930-933Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The year 2012 marks the 25th anniversary of the birth of modern deep brain stimulation (DBS), which was introduced by Benabid et al in 1987, initially to treat tremor with DBS of the ventral intermediate nucleus of the thalamus. The subsequent extension of DBS to the subthalamic nucleus (STN), demonstrating its efficacy on virtually all symptoms of advanced Parkinson's disease (PD), sparked an era of intense clinical and research activities, eventually transcending PD and movement disorders to encompass mood and mind. Investigations of the role of DBS in a variety of neurological, psychiatric, cognitive, and behavioral conditions is ongoing. Serendipitous discoveries and advances in functional imaging are providing new brain targets for an increasing number of pathologies. Toward the end of this quarter of a century of DBS, there have been some indications that the field may be at risk of gliding down a slippery slope, reminiscent of the excesses of the old-era DBS. Although there are many reasons this year to celebrate the achievements of 25 years of modern DBS, there are also reasons to fear the opening of a new Pandora's box.

  • 223.
    Hariz, Marwan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Zrinzo, Ludvic
    Future of Brain Stimulation: New Targets, New Indications, New Technology2013Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 28, nr 13, s. 1784-1792Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    In the last quarter of a century, DBS has become an established neurosurgical treatment for Parkinson's disease (PD), dystonia, and tremors. Improved understanding of brain circuitries and their involvement in various neurological and psychiatric illnesses, coupled with the safety of DBS and its exquisite role as a tool for ethical study of the human brain, have unlocked new opportunities for this technology, both for future therapies and in research. Serendipitous discoveries and advances in structural and functional imaging are providing abundant new brain targets for an ever-increasing number of pathologies, leading to investigations of DBS in diverse neurological, psychiatric, behavioral, and cognitive conditions. Trials and proof of concept studies of DBS are underway in pain, epilepsy, tinnitus, OCD, depression, and Gilles de la Tourette syndrome, as well as in eating disorders, addiction, cognitive decline, consciousness, and autonomic states. In parallel, ongoing technological development will provide pulse generators with longer battery longevity, segmental electrode designs allowing a current steering, and the possibility to deliver on-demand stimulation based on closed-loop concepts. The future of brain stimulation is certainly promising, especially for movement disordersthat will remain the main indication for DBS for the foreseeable futureand probably for some psychiatric disorders. However, brain stimulation as a technique may be at risk of gliding down a slippery slope: Some reports indicate a disturbing trend with suggestions that future DBS may be proposed for enhancement of memory in healthy people, or as a tool for treatment of antisocial behavior and for improving morality. (c) 2013 International Parkinson and Movement Disorder Society

  • 224.
    Hariz, Marwan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Therapeutic stimulation versus ablation2013Inngår i: Brain Stimulation, Volume 116: Handbook of Clinical Neurology / [ed] Aminoff, Boller, Swaab, Toronto: Elsevier, 2013, 116, s. 63-71Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    The renaissance of functional stereotactic neurosurgery was pioneered in the mid 1980s by Laitinen’s introduction of Leksell’s posteroventral pallidotomy for Parkinson´s disease (PD). This ablative procedure experienced a worldwide spread in the 1990s, owing to its excellent effect on dyskinesias and other symptoms of post-l-dopa PD. Modern deep brain stimulation (DBS), pioneered by Benabid and Pollak in 1987 for the treatment of tremor, first became popular when it was applied to the subthalamic nucleus (STN) in the mid 1990s, where it demonstrated a striking effect on all cardinal symptoms of advanced PD, and permitted reduced dosages of medication. DBS, as a nondestructive, adaptable, and reversible procedure that is proving safe in bilateral surgery on basal ganglia, has great appeal to clinicians and patients alike, despite the fact that it is expensive, laborious, and relies on very strict patient selection criteria, especially for STN DBS. Psychiatric surgery has experienced the same phenomenon, with DBS supplanting completely stereotactic ablative procedures. This chapter discusses the pros and cons of ablation versus stimulation and investigates the reasons why DBS has overshadowed proven efficient ablative procedures such as pallidotomy for PD, and capsulotomy and cingulotomy for obsessive–compulsive disorder and depression. 

  • 225.
    Hariz, Marwan I
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hirabayashi, Hidehiro
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Is there a relationship between size and site of the stereotactic lesion and symptomatic results of pallidotomy and thalamotomy?1997Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 69, nr 1-4, s. 28-45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Forty-six patients who had 50 stereotactic procedures (36 pallidotomies and 14 thalamotomies) were assessed clinically with regard to akinesia, tremor, dyskinesias and dystonias, and underwent a stereotactic imaging study 6 months after surgery. The surgical results were rated as excellent, good/fair or no change, respectively, for each symptom, and were correlated to the volume and location of the stereotactic lesion. The effect of pallidotomy on akinesia was moderate and correlated with a larger lesion volume. The positive effect of pallidotomy on dyskinesias, dystonia and tremor was more pronounced and unrelated to the size of the lesion. The effect of thalamotomy on tremor was also unrelated to the lesion volume. The location of the pallidal lesions correlated only with the effect on akinesia: the more posterior the lesion in the pallidum, the better the effect on this symptom. For thalamotomy, there was no relationship between lesion location and effect on tremor. It is concluded that improvement in akinesia following pallidotomy is more difficult to obtain than improvement of the other parkinsonian symptoms, and this improvement requires a larger lesion which is located very posterior in the ventral pallidum.

  • 226.
    Hariz, Marwan I
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Krack, Paul
    Melvill, Roger
    Jorgensen, Jan V
    Hamel, Wolfgang
    Hirabayashi, Hidehiro
    Department of Neurosurgery, Nara, Japan.
    Lenders, Mathieu
    Wesslen, Nils
    Tengvar, Magnus
    Yousry, Tarek A
    A quick and universal method for stereotactic visualization of the subthalamic nucleus before and after implantation of deep brain stimulation electrodes2003Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 80, nr 1-4, s. 96-101Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    For deep brain stimulation (DBS) of the subthalamic nucleus (STN), it would be an advantage if the STN could be visualized with fast acquisition of MR images, allowing direct and individual targeting. We present a protocol for T2-weighted, nonvolumetric fast-acquisition MRI, implemented at 8 centers in 6 countries. Acquisition time varied between 3 min 5 s and 7 min 48 s according to the center, and imaging often provided visualization of the STN on axial and coronal scans. Postoperatively, the same imaging protocol permitted visualization of the target area and DBS electrodes with minimum artifacts. This imaging technique may contribute to a decrease in the number of electrode passes at surgery.

  • 227.
    Hariz, Marwan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. UCL-Institute of Neurology, London, United Kingdom.
    Obeso, Jose A.
    What would Dr. James Parkinson think today?: I. The role of functional neurosurgery for Parkinson's disease2017Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, nr 1, s. 2-4Artikkel i tidsskrift (Fagfellevurdert)
  • 228.
    Hariz, Marwan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, University College London-Institute of Neurology, Queen Square, London, UK.
    Tabrizi, Sarah
    Patients with Huntington's disease pioneered human stereotactic neurosurgery 70 years ago2017Inngår i: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 140, s. 2516-2519Artikkel i tidsskrift (Annet vitenskapelig)
  • 229.
    Heldestad Lilliesköld, Victoria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Method-of-limits: Cold and warm perception thresholds at proximal and distal body regions2018Inngår i: Clinical neurophysiology practice, ISSN 2467-981X, Vol. 3, s. 134-140Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Thermal quantitative sensory testing with the 'Method-of-Limits' is an established rationale for detection of small nerve fiber dysfunction, but adequate reference values are crucial for such evaluations, regardless of the underlying cause. This study assessed reference data for cold- (CPT) and warm- (WPT) perception thresholds at both proximal and distal sites in eight body regions of the lower and upper extremities, all determined within the same test session for each subject.

    Methods: Seventy-five healthy subjects (aged 16-72 years) were tested according to the method-of-limit for CPT and WPT at the dorsum of the foot, the medial and lateral lower leg, the ventral thigh, the thenar eminence, the radial and ulnar part of the lower arm, and the anterior deltoid part of the upper arm.

    Results: Overall, thermal perception thresholds (TPT) varied with test location, but were higher in the lower than in the upper part of the body, also WPT were generally higher than CPT. TPT at the dorsum foot highly correlated with age, while inconsistent correlations were noted between TPT and age or height at other tested locations.

    Conclusion: This study describes for the first time reference values at eight defined body regions, at both proximal and distal sites.

    Significance: The report enables refined evaluations of general small nerve fiber function, as assessed by quantitative thermal sensory testing with the Method-of-Limits.

  • 230.
    Heldestad, Victoria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hörnsten, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Obayashi, Konen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR2011Inngår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 18, nr 4, s. 183-190Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with transthyretin amyloidosis (ATTR) polyneuropathy, a hereditary fatal disease, often report defects in both thermal perception and autonomic nervous system function as their first clinical symptoms. While elevated thermal perception thresholds (TPT) for cold and warmth only recently have been shown as an early marker of small nerve fiber dysfunction in these patients, heart rate variability (HRV) has frequently been used to quantify autonomic neuropathy. The main purpose with this report was to elucidate a possible relationship between estimates of HRV and TPT in a selected group of early and late-onset Swedish Val30Met ATTR patients. The results show significantly more pronounced elevation of TPT in early compared to late-onset patients. Significant correlations between HRV and TPT were found among late-onset cases, indicating a possible relationship between loss of thin nerve fibers in somatic and autonomic nerves, while generally no such relationships were found among early-onset cases. This observation emphasizes the importance of testing both HRV and TPT to ensure optimal early detection of neuropathic changes in an as wide as possible range of small nerve fibers in suspected ATTR patients. This is of particular importance as the phenotype of the ATTR disease varies between groups with different age of onset.

  • 231. Higelin, Julia
    et al.
    Catanese, Alberto
    Semelink-Sedlacek, Lena Luisa
    Oeztuerk, Sertap
    Lutz, Anne-Kathrin
    Bausinger, Julia
    Barbi, Gotthold
    Speit, Güenter
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Ludolph, Albert C.
    Demestre, Maria
    Boeckers, Tobias M.
    NEK1 loss-of-function mutation induces DNA damage accumulation in ALS patient-derived motoneurons2018Inngår i: Stem Cell Research, ISSN 1873-5061, E-ISSN 1876-7753, Vol. 30, s. 150-162Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mutations in genes coding for proteins involved in DNA damage response (DDR) and repair, such as C9orf72 and FUS (Fused in Sarcoma), are associated with neurodegenerative diseases and lead to amyotrophic lateral sclerosis (ALS). Heterozygous loss-of-function mutations in NEK1 (NIMA-related kinase 1) have also been recently found to cause ALS. NEK1 codes for a multifunctional protein, crucially involved in mitotic checkpoint control and DDR. To resolve pathological alterations associated with NEK1 mutation, we compared hiPSC-derived motoneurons carrying a NEK1 mutation with mutant C9orf72 and wild type neurons at basal level and after DNA damage induction. Motoneurons carrying a C9orf72 mutation exhibited cell specific signs of increased DNA damage. This phenotype was even more severe in NEK1c.2434A>T neurons that showed significantly increased DNA damage at basal level and impaired DDR after induction of DNA damage in an maturation-dependent manner. Our results provide first mechanistic insight in pathophysiological alterations induced by NEK1 mutations and point to a converging pathomechanism of different gene mutations causative for ALS. Therefore, our study contributes to the development of novel therapeutic strategies to reduce DNA damage accumulation in neurodegenerative diseases and ALS.

  • 232.
    Hirabayashi, Hidehiro
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stereotactic imaging in functional neurosurgery2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: The birth of stereotactic functional neurosurgery in 1947 was to a great extent dependent on the development of ventriculography. The last decades have witnessed a renaissance of functional stereotactic neurosurgery in the treatment of patients with movement disorders. Initially, these procedures were largely based on the same imaging technique that had been used since the birth of this technique, and that is still used in some centers. The introduction of new imaging modalities such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) provided new potentials, but also new challenges for accurate identification and visualisation of the targets in the basal ganglia and the thalamus with an urge to thoroughly evaluate and optimize the stereotactic targeting technique, as well as evaluate accurately in stereotactic space the location and extent of stereotactic Radiofrequency (RF) lesions and the position of deep brain stimulation (DBS) electrodes.

    Aims: To study the differences between CT and MRI regarding indirect atlas coordinates in thalamic and pallidal procedures and to evaluate and validate visualisation of the pallidum and the subthalamic nucleus in view of direct targeting irrespective of atlas-derived coordinates. Furthermore, to evaluate the contribution of RF parameters on the size of stereotactic lesions, as well as the impact of size and location on clinical outcome.

    Method: The coordinates in relation to the landmarks of the 3rd ventricle of the targets in the pallidum and ventrolateral thalamus were compared between CT and MRI in 34 patients. In another 48 patients direct visualization  of the pallidum was evaluated and compared to indirect atlas based targeting. The possibility and versatility of visualizing the Subthalamic Nucleus (STN) on short acquisition MRI were evaluated in a multicentre study, and the use of alternative landmarks in identification of the STN was demonstrated in another study. In 46 patients CT and MRI were compared regarding the volume of the visible RF lesions. The volume was analysed with regard to coagulation parameters, and the location and size of the lesions were further evaluated concerning the clinical outcome.

    Results:Minor deviations were seen between MRI and  CT coordinates of brain targets. The rostro-caudal direction of these deviations were such that they would be easily accounted for during surgery, why MRI can obviate the need for CT in these procedures. MRI using a proton density sequence provided detailed images of the pallidal structures, which demonstrated considerable inter-individual variations in relation to the landmarks of the 3rd ventricle. By using a direct visualization of the target, each patient will act as his or her own atlas, avoiding the uncertainties of atlas-based targeting. The STN could be visualized on various brands of MRI machines in 8 centers in 6 countries with good discrimination and with a short acquisition time, allowing direct visual targeting. The same scanning technique could be used for postoperative localization of the implanted electrodes. In cases where the lateral and inferior borders of the STN cannot be easily distinguished on MRI the Sukeroku sign and the dent internal-capsule-sign signs might be useful. The volume of a stereotactic RF lesion could be as accurately assessed by CT as by MRI. The lesion´s size was most strongly influenced by the temperature used for coagulation. The lesions´ volumes were however rather scattered and difficult to predict in the individual patient based solely on the coagulation parameters. For thalamotomy, the results on tremor was not related to the lesion´s volume. For pallidotomy, larger and more posterior-ventral lesions had better effect on akinesia while effects on tremor and dyskinesias were not related to size or location of the lesions.

    Conclusions: The minor deviations of MRI from CT coordinates can be accounted for during surgery, why MRI can obviate the need of CT in these procedures. Direct visualized targeting on MRI of the pallidum is superior to atlas based targeting. The targets in the pallidum and the STN, as well as the location of the electrodes, can be well visualized with short acquisition MRI. When borders of the STN are poorly defined on MRI the Sukeroku sign and the dent internal-capsule-sign signs proved to be useful. The volumes of RF lesions can be accurately assessed by both stereotactic thin slice CT and MRI. The size of these lesions is most strongly influenced by the temperature of coagulation, but difficult to predict in the individual patient based on the coagulation parameters.

    Within certain limits, there were no clear relationships between lesions´ volume and location and clinical effects of thalamotomies and pallidotomies.

  • 233.
    Hirabayashi, Hidehiro
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Fagerlund, M
    Comparison between stereotactic CT and MRI coordinates of pallidal and thalamic targets using the Laitinen noninvasive stereoadapter1998Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 71, nr 3, s. 117-130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The coordinates of one and the same target were compared between stereotactic CT and MRI studies, using the original Laitinen noninvasive Stereoadapter, and a slightly modified stereoadapter in 34 patients scheduled for pallidotomy or thalamotomy. The differences between CT and MRI coordinates were significant for the anteroposterior y (p < 0.001) and the vertical z (p < 0.01) coordinates. When the targets were analyzed separately for the coordinates in the right and left hemispheres, only those of the left-sided targets were significantly different between CT and MRI measurements. In patients where a vertex support was added to the Stereoadapter, there were no differences between CT and MRI target coordinates, regardless of the side of the target. However, in all patient groups, the three-dimensional vectorial difference between CT and MRI coordinates showed that the MRI-defined targets lay anterior and dorsal, that is, rostral, to the CT-defined targets, with a 95% confidence interval of the differences ranging from 1.8 to 2.4 mm. This rostral shift in target coordinates on MRI versus CT happens to coincide with the usual approach of the probe towards the target during surgery. It is concluded that the differences in target coordinates in our study are due partly to MRI distortion and partly to repositioning error of the Stereoadapter on the head. The relatively low magnitude of these differences does not preclude the use of the Stereoadapter for MRI-guided functional stereotactic surgery, provided careful impedance monitoring and macrostimulation of the target area prior to lesioning.

  • 234.
    Hirabayashi, Hidehiro
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wårdell, K
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Impact of parameters of radiofrequency coagulation on volume of stereotactic lesion in pallidotomy and thalamotomy2012Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 90, nr 5, s. 307-315Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: One of the many reasons why lesional surgery for movement disorders has been more or less abandoned may have been the difficulty in predicting the shape and size of the stereotactic radiofrequency (RF) lesion. Objectives: To analyse the contribution of various RF coagulation parameters towards the volume of pallidotomies and thalamotomies. Methods: The relationship between temperature of coagulation, length of coagulated area and duration of coagulation on the one hand, and lesion volume on the other was retrospectively evaluated. Lesion diameters were measured on stereotactic thin-slice CT and MRI scans, and volumes of lesions were calculated concerning 36 pallidotomies and 14 thalamotomies in 46 patients who were operated using the same RF generator and same RF electrode. Results: The coagulation temperature, length of coagulated area and duration of coagulation were all correlated to the lesion volume. However, for a given length of coagulated area, the lesion's size was most strongly influenced by the temperature. Despite this clear correlation, and the relatively homogenous coagulation parameters, the lesions' volumes were markedly scattered. Conclusions: The volume of the stereotactic RF lesions could be correlated with the coagulation parameters, especially the temperature, at a group level, but could not be predicted in individual patients based solely on the RF coagulation parameters.

  • 235.
    Hirabayashi, Hidehiro
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Tengvar, Magnus
    Hariz, Marwan I
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Stereotactic imaging of the pallidal target2002Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 17, nr suppl 3, s. S130-S134Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In 48 consecutive patients, we applied a new stereotactic imaging technique to individually visualize the pallidal target before surgery. A turbo spin-echo proton density sequence (acquisition time, 6 minutes 5 seconds) was used for 2-mm-thick contiguous axial scanning. Pallidocapsular border, medial putaminal border, and optic tract were visualized bilaterally in all patients. Boundaries of globus pallidus internus, globus pallidus externus, and lamina medullaris interna were clearly visualised in 71% of the patients. The anatomic target point was chosen in the middle of the visualized posteroventral pallidum, irrespective of the position of this point in relation to commissures. The lateralities of pallidocapsular border, lamina medullaris interna, and medial boundary of putamen were measured bilaterally in each patient, and the width of the posteroventral pallidum was assessed. The laterality of structures (measured from a point 2 mm anterior to midcommissural point and at a level 2-4 mm below anterior commissure-posterior commissure line) showed a wide range. The position of the pallidocapsular border varied by up to almost 1 cm between the most medial and the most lateral one. There were also variations in the position of the pallidal structures between left and right hemispheres in the same patients. The posteroventral pallidum was slightly more wide on the left than the right side. Given the significant inter- and intra-individual variabilities of the position of pallidal structures, it may be hazardous to rely solely on the atlas and the commissures for targeting. A magnetic resonance imaging sequence that enables visualization in each individual patient of the target area and its surroundings may contribute to less electrode passes during intraoperative physiological exploration and to more exact location of the lesion or chronic electrode in the posteroventral pallidum.

  • 236.
    Holmlund, Henny
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Frontal white matter lesions in Parkinson patients correlate with clinical phenotype and cognition.A diffusion tensor imaging study.2014Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
  • 237.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Eklund, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Sundström, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Malm, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Venous collapse regulates intracranial pressure in upright body positions2018Inngår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 314, nr 3, s. R377-R385Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent interest in intracranial pressure (ICP) in the upright posture has revealed that the mechanisms regulating postural changes in ICP are not fully understood. We have suggested an explanatory model where the postural changes in ICP depend on well-established hydrostatic effects in the venous system and where these effects are interrupted by collapse of the internal jugular veins (IJVs) in more upright positions. The aim of this study was to investigate this relationship by simultaneous invasive measurements of ICP, venous pressure and IJV collapse in healthy volunteers. ICP (monitored via the lumbar route), central venous pressure (PICC-line) and IJV cross-sectional area (ultrasound) were measured in 11 healthy volunteers (47±10 years) in seven positions, from supine to sitting (0°-69°). Venous pressure and anatomical distances were used to predict ICP in accordance with the explanatory model, and IJV area was used to assess IJV collapse. The hypothesis was tested by comparing measured ICP to predicted ICP. Our model accurately described the general behavior of the observed postural ICP changes (mean difference: -0.03±2.7 mmHg). No difference was found between predicted and measured ICP for any tilt-angle (p-values: 0.65 - 0.94). The results support the hypothesis that postural ICP changes are governed by hydrostatic effects in the venous system and IJV collapse. This improved understanding of the postural ICP regulation may have important implications for the development of better treatments for neurological and neurosurgical conditions affecting ICP.

  • 238.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    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, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Human jugular vein collapse in the upright posture: implications for postural intracranial pressure regulation2017Inngår i: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 14, artikkel-id 17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Intracranial pressure (ICP) is directly related to cranial dural venous pressure (P-dural). In the upright posture, P-dural is affected by the collapse of the internal jugular veins (IJVs) but this regulation of the venous pressure has not been fully understood. A potential biomechanical description of this regulation involves a transmission of surrounding atmospheric pressure to the internal venous pressure of the collapsed IJVs. This can be accomplished if hydrostatic effects are cancelled by the viscous losses in these collapsed veins, resulting in specific IJV cross-sectional areas that can be predicted from flow velocity and vessel inclination. Methods: We evaluated this potential mechanism in vivo by comparing predicted area to measured IJV area in healthy subjects. Seventeen healthy volunteers (age 45 +/- 9 years) were examined using ultrasound to assess IJV area and flow velocity. Ultrasound measurements were performed in supine and sitting positions. Results: IJV area was 94.5 mm(2) in supine and decreased to 6.5 +/- 5.1 mm(2) in sitting position, which agreed with the predicted IJV area of 8.7 +/- 5.2 mm(2) (equivalence limit +/- 5 mm(2), one-sided t tests, p = 0.03, 33 IJVs). Conclusions: The agreement between predicted and measured IJV area in sitting supports the occurrence of a hydrostatic-viscous pressure balance in the IJVs, which would result in a constant pressure segment in these collapsed veins, corresponding to a zero transmural pressure. This balance could thus serve as the mechanism by which collapse of the IJVs regulates P-dural and consequently ICP in the upright posture.

  • 239.
    Holmlund, Petter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Johansson, E.
    Umeå universitet.
    Qvarlander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ambarki, Khalid
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    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, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Jugular vein collapse in upright and its relation to intracranial pressure regulation2017Inngår i: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 37, s. 297-297Artikkel i tidsskrift (Fagfellevurdert)
  • 240. Holmén, Carolina
    et al.
    Piehl, Fredrik
    Hillert, Jan
    Fogdell-Hahn, Anna
    Lundkvist, Malin
    Karlberg, Elin
    Nilsson, Petra
    Dahle, Charlotte
    Feltelius, Nils
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Lycke, Jan
    Olsson, Tomas
    A Swedish national post-marketing surveillance study of natalizumab treatment in multiple sclerosis2011Inngår i: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 17, nr 6, s. 708-719Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: A post marketing surveillance study was conducted to evaluate safety and efficacy of natalizumab in Swedish multiple sclerosis (MS) patients since its introduction in August 2006 until March 2010.

    METHODS: Patients were registered in the web-based Swedish MS-registry at 40 locations and evaluated every 6 months. Adverse events and clinical outcomes were recorded.

    RESULTS: One thousand one hundred and fifty-two patients were included (71.4% female) and 149 patients stopped treatment; the main reason was planned pregnancy. Anti-natalizumab antibodies were found in 4.5% (52 patients) of which 1.6% displayed persistent antibodies. Serious adverse events were rare, but included three cases with progressive multifocal leukoencephalopathy (PML). There were seven fatal cases, probably unrelated to the natalizumab treatment. For relapsing-remitting MS patients (n=901), mean Expanded Disability Status Scale (EDSS, -10.7%), Multiple Sclerosis Severity Scale (MSSS, -20.4%), Multiple Sclerosis Impact Scale (MSIS-29, physical -9.9%, psychological -13.3%) and Symbol Digit Modalities Test (SDMT, +10.7%) all showed significant improvements during 24 months of treatment with natalizumab. The Swedish web-based MS quality registry proved to function as a platform for post-marketing MS drug surveillance, providing long-term data regarding drug effects and adverse events beyond clinical trials.

    CONCLUSIONS: Our results indicate that natalizumab is generally well tolerated and has sustained efficacy for patients with active MS, though the risk of PML is still an important concern.

  • 241.
    Horvath, Istvan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Iashchishyn, Igor A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Department of General Chemistry, Sumy State University, Ukraine.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Morozova-Roche, Ludmilla A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Immunochemical Detection of alpha-Synuclein Autoantibodies in Parkinson's Disease: Correlation between Plasma and Cerebrospinal Fluid Levels2017Inngår i: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 8, nr 6, s. 1170-1176Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Autoantibodies to Parkinson's disease (PD) amyloidogenic protein, a-synuclein, were recognized as a prospective biomarker for early disease diagnostics, yet there is inconsistency in previous reports, potentially related to PD status. Therefore, plasma and cerebrospinal fluid (CSF) of the cross-sectional cohort of 60 individuals, including recently diagnosed PD patients with mild and moderate PD and age-matched controls, were examined by enzyme-linked immunosorbent assay (ELISA). Nonparametric statistics was used for data analysis. We found significantly elevated levels of a-synuclein autoantibodies in both plasma and CSF in mild PD compared to controls, followed by some decrease in moderate PD. Receiver operating characteristic and effect size analyses confirmed the diagnostic power of a-synuclein antibodies in both plasma and CSF. For the first time, we showed the correlation between plasma and CSF a-synuclein antibody levels for mild, moderate, and combined PD groups. This indicates the potentiality of a-synuclein antibodies as PD biomarker and the increased diagnostic power of their simultaneous analysis in plasma and CSF.

  • 242.
    Horvath, Istvan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Jia, Xueen
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Johansson, Per
    Wang, Chao
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Moskalenko, Roman
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Department of Pathology, Sumy State University, Sumy 40000, Ukraine.
    Steinau, Andreas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Forsgren, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Wågberg, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Svensson, Johan
    Zetterberg, Henrik
    Morozova-Roche, Ludmilla A
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Pro-inflammatory S100A9 Protein as a Robust Biomarker Differentiating Early Stages of Cognitive Impairment in Alzheimer's Disease2016Inngår i: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 7, nr 1, s. 34-39Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pro-inflammatory protein S100A9 was established as a biomarker of dementia progression and compared with others such as Aβ1-42 and tau-proteins. CSF samples from 104 stringently diagnosed individuals divided into five subgroups were analyzed, including nondemented controls, stable mild cognitive impairment (SMCI), mild cognitive impairment due to Alzheimer's disease (MCI-AD), Alzheimer's disease (AD), and vascular dementia (VaD) patients. ELISA, dot-blotting, and electrochemical impedance spectroscopy were used as research methods. The S100A9 and Aβ1-42 levels correlated with each other: their CSF content decreased already at the SMCI stage and declined further under MCI-AD, AD, and VaD conditions. Immunohistochemical analysis also revealed involvement of both Aβ1-42 and S100A9 in the amyloid-neuroinflammatory cascade already during SMCI. Tau proteins were not yet altered in SMCI; however their contents increased during MCI-AD and AD, diagnosing later dementia stages. Thus, four biomarkers together, reflecting different underlying pathological causes, can accurately differentiate dementia progression and also distinguish AD from VaD.

  • 243.
    Hosseinzadeh, Ava
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Rofougaran, Reza
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Vodnala, Munender
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Kötemann, A
    Hofer, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Urban, Constantin F.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Adenosine is a drugable negative regulator of neutrophil activity during Candida albicans infectionManuskript (preprint) (Annet vitenskapelig)
  • 244. Huijben, Jilske A.
    et al.
    Wiegers, Eveline J. A.
    de Keizer, Nicolette F.
    Maas, Andrew I. R.
    Menon, David
    Ercole, Ari
    Citerio, Giuseppe
    Lecky, Fiona
    Wilson, Lindsay
    Cnossen, Maryse C.
    Polinder, Suzanne
    Steyerberg, Ewout W.
    van der Jagt, Mathieu
    Lingsma, Hester F.
    Aries, Marcel
    Badenes, Rafael
    Beishuizen, Albertus
    Bilotta, Federico
    Chieregato, Arturo
    Cingolani, Emiliano
    Cnossen, Maryse
    Coburn, Mark
    Coles, Jonathan P.
    Delargy, Mark
    Depreitere, Bart
    Flaatten, Hans
    Golyk, Volodymyr
    Grauwmeijer, Erik
    Haitsma, Iain
    Helbok, Raimund
    Hoedemaekers, Cornelia
    Jacobs, Bram
    Jellema, Korne
    Koskinen, Lars-Owe D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Maegele, Marc
    Martin Delgado, Maria Cruz
    Moller, Kirsten
    Moreno, Rui
    Nelson, David
    Oldenbeuving, Annemarie W.
    Payen, Jean-Francois
    Pejakovic, Jasmina
    Ribbbers, Gerard M.
    Rossaint, Rolf
    Schoonman, Guus Geurt
    Steiner, Luzius A.
    Stocchetti, Nino
    Silvio, Fabio
    Takala, Riikka
    Tenovuo, Olli
    Valeinis, Eglis
    van den Bergh, Walter M.
    van Essen, Thomas
    van Leeuwen, Nikki
    Verhofstad, Michael H. J.
    Vos, Pieter E.
    Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury2019Inngår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 23, artikkel-id 95Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators.

    Methods: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool.

    Results. The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N=24, 48%) and neurosurgeons (N=7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N=49, 98%) and indicated routine measurement in registries (N=41, 82%), benchmarking (N=42, 84%), and quality improvement programs (N=41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N=48, 98%).

    Conclusions: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future.

  • 245. Hultin, Emilie
    et al.
    Arroyo Mühr, Laila Sara
    Bzhalava, Zurab
    Hortlund, Maria
    Lagheden, Camilla
    Sundström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Dillner, Joakim
    Viremia preceding multiple sclerosis: Two nested case-control studies2018Inngår i: Virology, ISSN 0042-6822, E-ISSN 1096-0341, Vol. 520, s. 21-29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Infections have been suggested to be involved in Multiple Sclerosis (MS). We used metagenomic sequencing to detect both known and yet unknown microorganisms in 2 nested case control studies of MS. Two different cohorts were followed for MS using registry linkages. Serum samples taken before diagnosis as well as samples from matched control subjects were selected.

    In cohort1 with 75 cases and 75 controls, most viral reads were Anelloviridae-related and >95% detected among the cases. Among samples taken up to 2 years before MS diagnosis, Anellovirus species TTMV1, TTMV6 and TTV27 were significantly more common among cases. In cohort2, 93 cases and 93 controls were tested under the pre-specified hypothesis that the same association would be found. Although most viral reads were again related to Anelloviridae, no significant case-control differences were seen. We conclude that the Anelloviridae-MS association may be due to multiple hypothesis testing, but other explanations are possible.

  • 246. Hung, Noelyn
    et al.
    Chen, Yu-Jen
    Taha, Ahmad
    Olivecrona, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Boet, Ronald
    Wiles, Anna
    Warr, Tracy
    Shaw, Alisha
    Eiholzer, Ramona
    Baguley, Bruce C.
    Eccles, Michael R.
    Braithwaite, Antony W.
    MacFarlane, Martin
    Royds, Janice A.
    Slatter, Tania
    Increased paired box transcription factor 8 has a survival function in Glioma2014Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, s. 159-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:

    The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis.

    Methods:

    PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression.

    Results:

    Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death.

    Conclusions:

    PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas.

  • 247. Huotarinen, Antti
    et al.
    Kivisaari, Riku
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, University College London – Institute of Neurology, London, United Kingdom.
    Laitinen's Subgenual Cingulotomy: Anatomical Location and Case Report2018Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 96, nr 5, s. 342-346Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The widespread use of deep brain stimulation (DBS) for movement disorders has renewed the interest in DBS for psychiatric disorders. Lauri Laitinen was a pioneer of stereotactic psychosurgery in the 1950s to 1970s, especially by introducing the subgenual cingulotomy. Our aim here was to verify the anatomical target used by Laitinen, to report on a patient who underwent this procedure, and to review the literature. Materials and Methods: The records of Helsinki University Hospital were searched for psychosurgical cases performed between 1970 and 1974. Alive consenting patients were interviewed and underwent a brain MRI. Results: We found 1 patient alive who underwent subgenual cingulotomy in 1971 for obsessive thoughts, anxiety, and compulsions, diagnosed at that time as "schizophrenia psychoneurotica." MRI showed bilateral subgenual cingulotomy lesions (254 and 160 mm(3), respectively). The coordinates of the center of the lesions in relation to the midcommissural point for the right and left, respectively, were: 7.1 and 7.9 mm lateral; 0.2 mm inferior and 1.4 mm superior, and 33.0 and 33.9 anterior, confirming correct subgenual targeting. The patient reported retrospective satisfactory results. Conclusions: The lesion in this patient was found to be in the expected location, which gives some verification of the correct placement of Laitinen's subgenus cingulotomy target.

  • 248. Hyam, Jonathan A
    et al.
    Akram, Harith
    Foltynie, Thomas
    Limousin, Patricia
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, Queen Square, London, United Kingdom.
    Zrinzo, Ludvic
    What You See Is What You Get: Lead Location Within Deep Brain Structures Is Accurately Depicted by Stereotactic Magnetic Resonance Imaging2015Inngår i: Operative Neurosurgery, ISSN 2332-4252, Vol. 11, nr 3, s. 412-419Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Magnetic resonance imaging (MRI)-verified deep brain stimulation relies on the correct interpretation of stereotactic imaging documenting lead location in relation to visible anatomic target. However, it has been suggested that local signal distortion from the lead itself renders its depiction on MRI unreliable. OBJECTIVE: To compare lead location on stereotactic MRI with subsequent location of its brain track after removal. METHODS: Patients underwent deep brain stimulation with the use of MRI-guided and MRI-verified Leksell frame approach. Infection or suboptimal efficacy required lead removal and subsequent reimplantation by using the same technique. Postimplantation stereotactic MR images were analyzed. Lateral (x) and anteroposterior (y) distances from midcommissural point to center of the lead hypointensity were recorded at the anterior commissure-posterior commissure plane (pallidal electrode) or z = 24 (subthalamic electrode). Stereotactic MRI before the second procedure, x and y distances from the center of the visible lead track hypointensity to midcommissural point were independently recorded. Vectorial distance from center of the lead hypointensity to the center of its track was calculated. RESULTS: Sixteen electrode tracks were studied in 10 patients. Mean differences between lead artifact location and lead track location were: x coordinate 0.4 mm +/- 0.2; y coordinate 0.6 mm +/- 0.3. Mean vectorial distance was 0.7 mm +/- 0.2. CONCLUSION: Stereotactic distance between lead location and subsequent brain track location on MRI was small. The mean discrepancy was approximately half the deep brain stimulation lead width. This suggests that lead hypointensity seen on postimplantation MRI is indeed an accurate representation of its real location within deep brain structures.

  • 249.
    Hägglund, Patricia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Sandström, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Karlsson, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Voice Tremor in Patients With Essential Tremor: Effects of Deep Brain Stimulation of Caudal Zona Incerta2016Inngår i: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 30, nr 2, s. 228-233Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives. The present study aimed at evaluating the effect of deep brain stimulation (DBS) of the caudal zona incerta (cZi) on voice tremor in patients with essential tremor (ET). Study Design. This is a prospective nonrandomized design with consecutive patients.

    Methods. Twenty-six patients operated with cZi DBS were evaluated under two conditions: without stimulation (Stim OFF) and with stimulation (Stim ON). Voice tremor was assessed on the basis of recordings of sustained vowel productions using a four-point rating scale in a blinded and randomized procedure. Averaged values of multiple assessments for each stimulus were used in statistical testing. The group of patients with voice tremor in Stim OFF was analyzed separately from the group of patients without voice tremor.

    Results. Voice tremor was significantly reduced on stimulation compared with off for the subgroup with initial voice tremor. Voice tremor prevalence was found to be 50% (13 patients). Individual differences in voice tremor outcome were noticeable. Six of the patients with voice tremor at baseline improved substantially by cZi DBS treatment.

    Conclusions. On the group level, voice tremor in patients with ET was found to reduce when stimulating the cZi. Bilateral stimulation was indicated to be more effective in reducing voice tremor than unilateral stimulation. However, individual voice tremor outcomes suggest that not all patients benefit from cZi DBS. Severity of voice tremor at baseline may not be a good predictor of voice tremor outcome after cZi DBS. Patients should be informed before surgery regarding individual differences in response to DBS treatment.

  • 250.
    Häggman-Henrikson, Birgitta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Lampa, Ewa
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Altered thermal sensitivity in facial skin in chronic whiplash-associated disorders2013Inngår i: International Journal of Oral Science, ISSN 1674-2818, Vol. 5, nr 3, s. 150-154Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is a close functional relationship between the jaw and neck regions and it has been suggested that trigeminal sensory impairment can follow whiplash injury. Inclusion of manageable routines for valid assessment of the facial sensory capacity is thus needed for comprehensive evaluations of patients exposed to such trauma. The present study investigated facial thermal thresholds in patients with chronic whiplash-associated disorders (WADs) with both a qualitative method and quantitative sensory testing (QST). Ten women with pain and dysfunction following a whiplash injury were compared to 10 healthy age-matched women. Thermal detection thresholds were assessed by qualitative chair-side testing and by QST according to the method-of-limits. Seven test sites in the facial skin (overlying each trigeminal branch bilaterally, and the midpoint of the chin) were examined. The detection warm and cold thresholds were defined as the mean values of 10 individual thresholds. For the WAD patients, the qualitative assessment demonstrated both reduced and increased sensitivity compared to the healthy, whereas QST systematically showed significantly higher detection thresholds (i.e., decreased sensitivity) for both cold and warm stimuli. For the individuals who were assessed as having increased sensitivity in the qualitative assessment, the QST displayed either normal or higher thresholds, i.e., decreased sensitivity. The results suggest that QST is more sensitive for detecting thermal sensory disturbances in the face than a qualitative method. The impaired thermal sensitivity among the patients corroborates the notion of altered thermal detection capacity induced by WAD-related pain.

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