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  • 301.
    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.

  • 302.
    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.

  • 303.
    Hariz, Marwan
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Battery obsolescence, industry profit and deep brain stimulation2019Inngår i: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 161, nr 10, s. 2047-2048Artikkel i tidsskrift (Annet vitenskapelig)
  • 304.
    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)
  • 305.
    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.

  • 306.
    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)
  • 307.
    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.

  • 308.
    Hariz, Marwan
    et al.
    Institute of Neurology Queen Square, London, United Kingdom.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Limousin, Patricia
    The myth of microelectrode recording in ensuring a precise location of the DBS electrode within the sensorimotor part of the subthalamic nucleus2004Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 19, nr 7, s. 863-864Artikkel i tidsskrift (Annet vitenskapelig)
  • 309.
    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

  • 310.
    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. 

  • 311.
    Hariz, Marwan I
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Blomstedt, Patric
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Zrinzo, Ludvic
    Deep brain stimulation between 1947 and 1987: the untold story2010Inngår i: Neurosurgical focus, ISSN 1092-0684, Vol. 29, nr 2, s. E1-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Deep brain stimulation (DBS) is the most rapidly expanding field in neurosurgery. Movement disorders are well-established indications for DBS, and a number of other neurological and psychiatric indications are currently being investigated. Numerous contemporary opinions, reviews, and viewpoints on DBS fail to provide a comprehensive account of how this method came into being. Misconceptions in the narrative history of DBS conveyed by the wealth of literature published over the last 2 decades can be summarized as follows: Deep brain stimulation was invented in 1987. The utility of high-frequency stimulation was also discovered in 1987. Lesional surgery preceded DBS. Deep brain stimulation was first used in the treatment of movement disorders and was subsequently used in the treatment of psychiatric and behavioral disorders. Reports of nonmotor effects of subthalamic nucleus DBS prompted its use in psychiatric illness. Early surgical interventions for psychiatric illness failed to adopt a multidisciplinary approach; neurosurgeons often worked "in isolation" from other medical specialists. The involvement of neuro-ethicists and multidisciplinary teams are novel standards introduced in the modern practice of DBS for mental illness that are essential in avoiding the unethical behavior of bygone eras. In this paper, the authors examined each of these messages in the light of literature published since 1947 and formed the following conclusions. Chronic stimulation of subcortical structures was first used in the early 1950s, very soon after the introduction of human stereotaxy. Studies and debate on the stimulation frequency most likely to achieve desirable results and avoid side effects date back to the early days of DBS; several authors advocated the use of "high" frequency, although the exact frequency was not always specified. Ablative surgery and electrical stimulation developed in parallel, practically since the introduction of human stereotactic surgery. The first applications of both ablative surgery and chronic subcortical stimulation were in psychiatry, not in movement disorders. The renaissance of DBS in surgical treatment of psychiatric illness in 1999 had little to do with nonmotor effects of subthalamic nucleus DBS but involved high-frequency stimulation of the very same brain targets previously used in ablative surgery. Pioneers in functional neurosurgery mostly worked in multidisciplinary groups, including when treating psychiatric illness; those "acting in isolation" were not neurosurgeons. Ethical concerns have indeed been addressed in the past, by neurosurgeons and others. Some of the questionable behavior in surgery for psychiatric illness, including the bygone era of DBS, was at the hands of nonneurosurgeons. These practices have been deemed as "dubious and precarious by yesterday's standards."

  • 312.
    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.

  • 313. Hariz, Marwan I
    et al.
    Johansson, Folke
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Shamsgovara, Parvis
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Johansson, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Fagerlund, Markku
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Bilateral subthalamic nucleus stimulation in a parkinsonian patient with preoperative deficits in speech and cognition: persistent improvement in mobility but increased dependency2000Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 15, nr 1, s. 136-139Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report a patient with advanced Parkinson's disease, including severe and frequent off periods with freezing of gait, moderate dysphonia, and some cognitive impairment, who underwent bilateral subthalamic nucleus (STN) stimulation. The patient was followed for 1 year after surgery, showing persistent good mobility without off periods and without freezing, which reverted completely when stopping the stimulation. There was deterioration of cognition as well as increased aphonia and drooling, all of which remained when the stimulation was turned off. The striking improvement in motor symptoms following STN stimulation was not paralleled by improvement in disability, probably as a result of a cognitive decline, suggesting a diagnosis of Parkinson's disease with dementia. We conclude that chronic STN stimulation is efficient in alleviating akinetic motor symptoms including gait freezing; this surgery should be offered before patients start to exhibit speech or cognitive disturbances.

  • 314.
    Hariz, Marwan I
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Krack, P
    Alesch, F
    Augustinsson, L-E
    Bosch, A
    Ekberg, R
    Johansson, F
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Johnels, B
    Meyerson, B A
    N'Guyen, J-P
    Pinter, M
    Pollak, P
    von Raison, F
    Rehncrona, S
    Speelman, J D
    Sydow, O
    Benabid, A-L
    Multicentre European study of thalamic stimulation for parkinsonian tremor: a 6 year follow-up2008Inngår i: Journal of neurology, neurosurgery and psychiatry, ISSN 1468-330X, Vol. 79, nr 6, s. 694-699Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery.

    METHODS: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation.

    RESULTS: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group.

    CONCLUSION: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.

  • 315.
    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.

  • 316.
    Hariz, Marwan I
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Shamsgovara, P
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi.
    Johansson, F
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurologi.
    Hariz, Gun-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Neurokirurgi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Fodstad, H
    Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor1999Inngår i: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 72, nr 2-4, s. 208-218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fifty-eight patients, 36 with essential tremor (ET) and 22 with Parkinson's disease (PD), received deep brain stimulation (DBS) in the thalamic ventral intermediate (Vim) nucleus. The mean follow-up was 17 months for ET and 21 months for PD patients. Stimulation parameters were adjusted as needed, at various intervals after surgery. Results were assessed using routine clinical evaluation and established outcome scales. All patients needed incremental increase in stimulation parameters at various intervals during the first 6-12 months after surgery. The mean voltage 1 week postoperatively was 1. 45 V in PD patients, and 1.37 V in ET patients. Twelve months later, the figures were 2.14 V in PD and 2.25 V in ET patients. At 1 year, the Essential Tremor Rating Scale (ETRS) improved from 54 to 28 (p < 0.0001). The motor part of the Unified Parkinson's Disease Rating Scale (UPDRS) improved from 37 to 26 (p < 0.01). Tremor items of the UPDRS improved more markedly (p < 0.0001). One week postoperatively 90% of PD, and 89% of ET patients were tremor free. One year later, 70% of PD and 60% of ET patients remained mostly tremor free. Upon switching off stimulation, there was a clear tendency for tremor rebound (p = 0.07) in the PD group, requiring continuous 24-hour stimulation in some patients. Permanent non-adjustable ataxia was induced by stimulation in 2 PD patients.

  • 317.
    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)
  • 318.
    Hart, Andrew McKay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Blond-McIndoe Laboratories, Royal Free and University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London, UK.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Blond-McIndoe Laboratories, Royal Free and University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London, UK.
    Primary sensory neurons and satellite cells after peripheral axotomy in the adult rat: timecourse of cell death & elimination2002Inngår i: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 142, nr 3, s. 308-318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The timecourse of cell death in adult dorsal root ganglia after peripheral axotomy has not been fully characterised. It is not clear whether neuronal death begins within I week of axotomy or continues beyond 2 months after axotomy. Similarly, neither the timecourse of satellite cell death in the adult, nor the effect of nerve repair has been described. L4 and L5 dorsal root ganglia were harvested at 1-14 days, 1-6 months after sciatic nerve division in the adult rat, in accordance with the Animals (Scientific Procedures) Act 1986. In separate groups the nerve was repaired either immediately or following a 1-week delay, and the ganglia were harvested 2 weeks after the initial transection. Microwave permeabilisation and triple staining enabled combined TUNEL staining, morphological examination and neuron counting by the stereological optical dissector technique. TUNEL-positive neurons, exhibiting a range of morphologies, were seen at all timepoints (peak 25 cells/group 2 weeks after axotomy) in axotomised ganglia only. TUNEL-positive satellite cell numbers peaked 2 months after axotomy and were more numerous in axotomised than control ganglia. L4 control ganglia contained 13,983 (SD 568) neurons and L5, 16,285 (SD 1,313). Neuron loss was greater in L5 than L4 axotomised ganglia, began at I week (15%, P=0.045) post-axotomy, reached 35% at 2 months (P<0.001) and was not significantly greater at 4 months or 6 months. Volume of axotomised ganglia fell to 19% of control by 6 months (P<0.001). In animals that underwent nerve repair, both the number of TUNEL-positive neurons and neuron loss were reduced. Immediate repair was more protective than repair after a 1-week delay. Thus TUNEL positivity precedes actual neuron loss, reflecting the time taken to complete cell death and elimination. Neuronal death begins within I day of peripheral axotomy, the majority occurs within the first 2 months, and limited death is still occurring at 6 months. Neuronal death is modulated by peripheral nerve repair and by its timing after axotomy. Secondary satellite cell death also occurs, peaking 2 months after axotomy. These results provide a logical framework for future research into neuronal and satellite cell death within the dorsal root ganglia and provide further insight into the process of axotomy induced neuronal death.

  • 319.
    Hart, Andrew McKay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Blond–McIndoe Centre, Royal Free and University College Medical School, London, UK.
    Exogenous leukaemia inhibitory factor enhances nerve regeneration after late secondary repair using a bioartificial nerve conduit2003Inngår i: British Journal of Plastic Surgery, ISSN 0007-1226, E-ISSN 1465-3087, Vol. 56, nr 5, s. 444-450Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The clinical outcome of peripheral nerve injuries remains disappointing, even in the ideal situation of a primary repair performed with optimal microsurgical techniques. Primary repair is appropriate for only about 85% of injuries, and outcome is worse following secondarynerverepair, partly owing to the reduced regenerative potential of chronically axotomised neurons. Leukaemiainhibitoryfactor (LIF) is a gp-130 neurocytokine that is thought to act as an ‘injury factor’, triggering the early-injury phenotype within neurons and potentially boosting their regenerative potential aftersecondarynerverepair. At 2–4 months after sciatic nerve axotomy in the rat, 1 cm gaps were repaired using either nerve isografts or poly-3-hydroxybutyrate conduits containing a calcium alginate and fibronectin hydrogel.

    Regeneration was determined by quantitative immunohistochemistry 6 weeks afterrepair, and the effect of incorporating recombinant LIF (100 ng/ml) into the conduits was assessed. LIF increased the regeneration distance in repairs performed after both 2 months (69%, P=0.019) and 4 months (123%, P=0.021), and was statistically comparable to nerve graft. The total area of axonal immunostaining increased by 21% (P>0.05) and 63% (P>0.05), respectively. Percentage immunostaining area was not increased in the 2 months group, but increased by 93% in the repairs performed 4 months after axotomy. Exogenous LIF, therefore, has a potential role in promoting peripheral nerveregenerationaftersecondaryrepair, and can be effectively delivered within poly-3-hydroxybutyrate bioartificialconduits used for nerverepair.

  • 320.
    Hart, Andrew McKay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi. Blond-McIndoe Centre, Royal Free and University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl-L-carnitine treatment2002Inngår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 334, nr 3, s. 181-185Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Peripheral nerve trauma remains a major cause of morbidity, largely due to the death of similar to40% of innervating sensory neurons, and to slow regeneration after repair. Acetyl-L-carnitine (ALCAR) is a physiological peptide that virtually eliminates sensory neuronal death, and may improve regeneration after primary nerve repair. This study determines the effect of ALCAR upon regeneration after secondary nerve repair, thereby isolating its effect upon neuronal regenerative capacity. Two months after unilateral sciatic nerve division 1 cm nerve graft repairs were performed (n = 5), and treatment with 50 mg/kg/day ALCAR was commenced for 6 weeks until harvest. Regeneration area and distance were determined by quantitative immunohistochemistry. ALCAR treatment significant increased immunostaining for both nerve fibres (total area 264% increase, P < 0.001; percentage area 229% increase, P < 0.001), and Schwann cells (total area 264% increase, P < 0.05; percentage area 86% increase, P < 0.05), when compared to no treatment. Regeneration into the distal stump was greatly enhanced (total area 2242% increase, P = 0.008; percentage area 3034% increase, P = 0.008). ALCAR significantly enhances the regenerative capacity of neurons that survive peripheral nerve trauma, in addition to its known neuroprotective effects.

  • 321.
    Hart, Andrew McKay
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Blond-McIndoe Centre, Royal Free & University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Youle, Mike
    Royal Free Centre for HIV Medicine, Royal Free Hospital, London, UK.
    Terenghi, Giorgio
    Blond-McIndoe Centre, Royal Free & University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London, NW3 2PF, UK.
    Systemic acetyl-L-carnitine eliminates sensory neuronal loss after peripheral axotomy: a new clinical approach in the management of peripheral nerve trauma2002Inngår i: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 145, nr 2, s. 182-189Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several hundred thousand peripheral nerve injuries occur each year in Europe alone. Largely due to the death of around 40% of primary sensory neurons, sensory outcome remains disappointingly poor despite considerable advances in surgical technique; yet no clinical therapies currently exist to prevent this neuronal death. Acetyl-L-carnitine (ALCAR) is a physiological peptide with roles in mitochondrial bioenergetic function, which may also increase binding of nerve growth factor by sensory neurons. Following unilateral sciatic nerve transection, adult rats received either one of two doses of ALCAR or sham, or no treatment. Either 2 weeks or 2 months later, L4 and L5 dorsal root ganglia were harvested bilaterally, in accordance with the Animal (Scientific Procedures) Act 1986. Neuronal death was quantified with a combination of TUNEL [TdT (terminal deoxyribonucleotidyl transferase) uptake nick end labelling] and neuron counts obtained using the optical disector technique. Sham treatment had no effect upon neuronal death. ALCAR treatment caused a large reduction in the number of TUNEL-positive neurons 2 weeks after axotomy (sham treatment 33/group; low-dose ALCAR 6/group, P=0.132; high-dose ALCAR 3/group, P<0.05), and almost eliminated neuron loss (sham treatment 21%; low-dose ALCAR 0%, P=0.007; high-dose ALCAR 2%, P<0.013). Two months after axotomy the neuroprotective effect of high-dose ALCAR treatment was preserved for both TUNEL counts (no treatment five/group; high-dose ALCAR one/group) and neuron loss (no treatment 35%; high-dose ALCAR -4%, P<0.001). These results provide further evidence for the role of mitochondrial bioenergetic dysfunction in post-traumatic sensory neuronal death, and also suggest that acetyl-L-carnitine may be the first agent suitable for clinical use in the prevention of neuronal death after peripheral nerve trauma.

  • 322.
    Hart, Andrew
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Terenghi, Giorgio
    Wiberg, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Tissue Engineering for Peripheral Nerve Regeneration2011Inngår i: Tissue Engineering: From Lab to Clinic / [ed] Norbert Pallua, Christoph V. Suscheck, Berlin: Springer Berlin/Heidelberg, 2011, s. 245-262Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    The outcome of peripheral nerve repair has changed very little over the past 50 years, and clinical outcomes remain generally poor. Surgical technique has evolved to a high level of technical microsurgical proficiency, but this approach remains unable to adequately address the neurobiological barriers to the optimization of nerve regeneration. Reconstruction of complex segmental injuries, as in the brachial plexus, additionally requires a considerable length of interpositional nerve autograft, which may be unobtainable without considerable donor morbidity.

    Research has therefore turned to the modulation of the repair-site environment to optimise nerve regeneration across neurorraphies, and to the creation of nerve conduits to reduce the need for nerve autograft. Tissue engineering has involved the use of growth factors to modulate neuronal and glial cell behaviour, and the creation of macro, micro and nanoscale constructs from a variety of materials in order to replace the connective tissue functions of nerve autograft. Implantation of cultured Schwann and stem cells is an area of particular development given the necessity of viable support cells to facilitate neuronal growth. These approaches are reviewed in the light of current published work.

    The future of peripheral nerve repair lies in the modulation of neuronal and glial cell responses to nerve injury, and during regeneration, while taking account of the clinical requirements and practical limitations. The peripheral nervous system also provides a simpler model for nerve regeneration than the central nervous system, but with translational potential.

  • 323.
    Haukenes, Inger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Norwegian Inst Publ Hlth, Div Mental Hlth, Dept Publ Mental Hlth, Bergen, Norway.
    Hensing, G.
    Stålnacke, Britt-Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Hammarström, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Socialmedicin. Norwegian Inst Publ Hlth, Div Mental Hlth, Dept Publ Mental Hlth, Bergen, Norway.
    Does pain severity guide selection to multimodal pain rehabilitation across gender?2015Inngår i: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 19, nr 6, s. 826-833Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Studies have addressed the effect of multimodal pain rehabilitation (MMR), whereas criteria for selection are sparse. This study examines whether higher scores on musculoskeletal pain measures are associated with selection to MMR, and whether this differs across gender.

    Method A clinical population of 262 male and 589 female patients was recruited consecutively during 3 years, 2007-2010. The patients were referred from primary care to a pain rehabilitation clinic in Northern Sweden for assessment and selection to MMR. Register-based data on self-reported pain were linked to patients' records where outcome (MMR or not) was stated. We modelled odds ratios for selection to MMR by higher scores on validated pain measures (pain severity, interference with daily life, pain sites and localized pain vs. varying pain location). Covariates were age, educational level and multiple pain measures. Anxiety and depression (Hospital, Anxiety and Depression Scale) and working status were used in sensitivity tests.

    Results Higher scores of self-reported pain were not associated with selection to MMR in multivariate models. Among women, higher scores on pain severity, pain sites and varying pain location (localized pain=reference) were negatively associated with selection to MMR. After adjustment for multiple pain measures, the negative odds ratio for varying location persisted (OR=0.59, 95% CI=0.39-0.89).

    Conclusion Higher scores on self-reported pain did not guide selection to MMR and a negative trend was found among women. Studies of referral patterns and decision processes may contribute to a better understanding of the clinical practice that decides selection to MMR.

  • 324.
    Heldestad, Victoria
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurofysiologi.
    Nordh, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurofysiologi.
    Quantified sensory abnormalities in early genetically verified transthyretin amyloid polyneuropathy2007Inngår i: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 35, nr 2, s. 189-195Artikkel i tidsskrift (Fagfellevurdert)
  • 325. Hellgren, Charlotte
    et al.
    Akerud, Helena
    Skalkidou, Alkistis
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Sundstrom-Poromaa, Inger
    Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy2014Inngår i: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 69, nr 3, s. 147-153Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) is a neurosteroid which has an inhibitory function through interaction with the GABA(A) receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy covary with concurrent self-rated symptoms of depression and anxiety. Methods: Ninety-six women in pregnancy weeks 37-40 rated symptoms of depression and anxiety with the Montgomery-Asberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory. Their serum allopregnanolone was analyzed by Celite chromatography and radioinnmunoassay. Results: Ten women had elevated depression scores (MADRS-S >= 13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the normal range (39.0 +/- 17.9 vs. 54.6 +/- 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson's correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. Conclusion: High allopregnanolone serum concentrations may protect against depressed mood during pregnancy. (C) 2014 S. Karger AG, Basel

  • 326. Henriksson, Karin M.
    et al.
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Asberg, Signild
    Statin Therapy is Associated with Decreased Risk of First Intracerebral Hemorrhage and Reduced 30-Day Fatality: Results of a Nationwide Observational Study Including 7,696 Cases and 14,670 Controls2013Inngår i: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 22, s. 399-400Artikkel i tidsskrift (Annet vitenskapelig)
  • 327.
    Henriksson, Roger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Asklund, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Poulsen, Hans Skovgaard
    Radiumhemmet, Karolinska Hospital, Stockholm, Sweden; Department of Oncology, Finsencenter, University Hospital, 9 Blegdamsvej, 2100 Copenhagen, Denmark.
    Impact of therapy on quality of life, neurocognitive function and their correlates in glioblastoma multiforme: a review2011Inngår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 104, nr 3, s. 639-646Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    The maintenance of quality of life (QoL) in patients with high-grade glioma is an important endpoint during treatment, particularly in those with glioblastoma multiforme (GBM) given its dismal prognosis despite limited advances in standard therapy. It has proven difficult to identify new therapies that extend survival in patients with recurrent GBM, so one of the primary aims of new therapies is to reduce morbidity, restore or preserve neurologic functions, and the capacity to perform daily activities. Apart from temozolomide, cytotoxic chemotherapeutic agents do not appear to significantly impact response or survival, but produce toxicity that is likely to negatively impact QoL. New biological agents, such as bevacizumab, can induce a clinically meaningful proportion of durable responses among patients with recurrent GBM with an acceptable safety profile. Emerging evidence suggests that bevacizumab produces an improvement or preservation of neurocognitive function in GBM patients, suggestive of QoL improvement, in most poor-prognosis patients who would otherwise be expected to show a sudden and rapid deterioration in QoL.

  • 328.
    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.

  • 329.
    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.

  • 330.
    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.

  • 331.
    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.

  • 332. Hohsfield, Lindsay A.
    et al.
    Daschil, Nina
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Strömberg, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Humpel, Christian
    Vascular pathology of 20-month-old hypercholesterolemia mice in comparison to triple-transgenic and APPSwDI Alzheimer's disease mouse models2014Inngår i: Molecular and cellular neuroscience, ISSN 1044-7431, Vol. 63, s. 83-95Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several studies have shown that elevated plasma cholesterol levels (i.e. hypercholesterolemia) serve as a risk factor for late-onset Alzheimer's disease (AD). However, it remains unclear how hypercholesterolemia may contribute to the onset and progression of AD pathology. In order to determine the role of hypercholesterolemia at various stages of AD, we evaluated the effects of high cholesterol diet (5% cholesterol) in wild-type (WT; C57BL6) and triple-transgenic AD (3xTg-AD: Psen1, APPSwe, tauB301L) mice at 7, 14, and 20 months. The transgenic APP-Swedish/Dutch/Iowa AD mouse model (APPSwDI) was used as a control since these animals are more pathologically-accelerated and are known to exhibit extensive plaque deposition and cerebral amyloid angiopathy. Here, we describe the effects of high cholesterol diet on: (1) cognitive function and stress, (2) AD-associated pathologies, (3) neuroinflammation, (4) blood-brain barrier disruption and ventricle size, and (5) vascular dysfunction. Our data show that high dietary cholesterol increases weight, slightly impairs cognitive function, promotes glial cell activation and complement-related pathways, enhances the infiltration of blood-derived proteins and alters vascular integrity, however, it does not induce AD-related pathologies. While normal-fed 3xTg-AD mice display a typical AD-like pathology in addition to severe cognitive impairment and neuroinflammation at 20 months of age, vascular alterations are less pronounced. No microbleedings were seen by MRI, however, the ventricle size was enlarged. Triple-transgenic AD mice, on the other hand, fed a high cholesterol diet do not survive past 14 months of age. Our data indicates that cholesterol does not markedly potentiate AD-related pathology, nor does it cause significant impairments in cognition. However, it appears that high cholesterol diet markedly increases stress-related plasma corticosterone levels as well as some vessel pathologies. Together, our findings represent the first demonstration of prolonged high cholesterol diet and the examination of its effects at various stages of cerebrovascular- and AD-related disease.

  • 333.
    Holm, Linus
    et al.
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Ullén, Fredrik
    Karolinska institutet, Institutionen för kvinnor och barns hälsa, Stockholm Brain Institute.
    Madison, Guy
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Intelligence and temporal accuracy of behaviour: unique and shared associations with reaction time and motor timing2011Inngår i: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 214, nr 2, s. 175-183Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Intelligence is associated with accuracy in a wide range of timing tasks. One source of such associations is likely to be individual differences in top-down control, e.g. sustained attention, that influence performance in both temporal tasks and other cognitively controlled behaviors. In addition, we have studied relations between intelligence and a simple rhythmic motor task, isochronous serial interval production (ISIP), and found a substantial component of that relation, which is independent of fluctuations in top-down control. The main purpose of the present study was to investigate whether such bottom-up mechanisms are involved also in the relation between intelligence and reaction time (RT) tasks. We thus investigated if common variance between the ISIP and RT tasks underlies their respective associations with intelligence. 112 participants performed a simple RT task, a choice RT task and the ISIP task. Intelligence was assessed with the Raven SPM Plus. The analysed timing variables included mean and variability in the RT tasks and two variance components in the ISIP task. As predicted, RT and ISIP variables were associated with intelligence. The timing variables were positively intercorrelated and a principal component analysis revealed a substantial first principal component that was strongly related to all timing variables, and positively correlated with intelligence. Furthermore, a commonality analysis demonstrated that the relations between intelligence and the timing variables involved a commonality between the timing variables as well as unique contributions from choice RT and ISIP. We discuss possible implications of these findings, and argue that they support our main hypothesis, i.e. that relations between intelligence and RT tasks have a bottom-up component.

  • 334.
    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.

  • 335.
    Holmlund, Thorbjörn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Franklin, Karl A.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Levring Jäghagen, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Lindqvist, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Larsson, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Sahlin, C.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Berggren, Diana
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Tonsillectomy in adults with obstructive sleep apnea2016Inngår i: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, s. 161-161Artikkel i tidsskrift (Annet vitenskapelig)
  • 336. Holmqvist, Marie
    et al.
    Simard, Julia F.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Arkema, Elizabeth V.
    Stroke in systemic lupus erythematosus: a meta-analysis of population-based cohort studies2015Inngår i: RMD Open, E-ISSN 2056-5933, Vol. 1, nr 1, artikkel-id UNSP e000168Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Previous studies of stroke in systemic lupus erythematosus (SLE) have had limited statistical power, combined stroke subtypes into composite outcomes, and lacked a reference population estimate. Therefore, we conducted a systematic review and meta-analysis of cohort studies to summarise the stroke subtype-specific risk in patients with SLE compared to the general population. A systematic search of MEDLINE and EMBASE was performed for cohort studies examining the risk of stroke in SLE and including a general population comparator. Random effects models were used to pool the risk ratio (RR) for stroke. Subgroup analyses were carried out to investigate potential sources of heterogeneity. 10 studies were included which reported RRs for overall stroke (n=5), ischaemic stroke (n=6), intracerebral haemorrhage (n=3) and subarachnoid haemorrhage (n=3). The pooled RR for overall stroke was 2.53 (95% CI 1.96 to 3.26), ischaemic stroke 2.10 (95% CI 1.68 to 2.62), intracerebral haemorrhage 2.72 (95% CI 2.15 to 3.44) and subarachnoid haemorrhage 3.85 (95% CI 3.20 to 4.64). Significant heterogeneity among studies for ischaemic stroke was detected (p=0.002). Relative risk of stroke was highest among individuals younger than 50 years of age. Individuals with SLE have a twofold higher risk of ischaemic stroke, a threefold higher risk of intracerebral haemorrhage, and an almost fourfold higher risk of subarachnoid haemorrhage compared to the general population. Future studies should focus on whether comorbidity and disease flares are related to stroke, when individuals are at the highest risk, and how the targeting of specific groups of patients with SLE may reduce this risk.

  • 337. 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.

  • 338. Holsti, Liisa
    et al.
    Grunau, Ruth E
    Whifield, Michael F
    Oberlander, Tim F
    Lindh, Viveca
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Behavioral responses to pain are heightened after clustered care in preterm infants born between 30 and 32 weeks gestational age2006Inngår i: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 22, nr 9, s. 757-764Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To compare biobehavioral pain responses of preterm infants born at differing gestational ages (GAs) when pain was preceded by a rest period or by a series of routine nursing interventions.

    METHODS: In a randomized, within subjects, cross-over design, facial (Neonatal Facial Coding System), sleep/wake state and heart rate (HR) responses of 43 preterm infants [mean birth weight: 1303 g (range 590 g to 2345 g); mean GA at birth: 30 weeks (range 25 to 32)] were examined across 3 phases of blood collection (Baseline, Lance, and Recovery) under 2 conditions: pain after a 30-minute rest period versus pain after a series of routine nursing interventions (clustered care). Infant behavioral responses were coded from continuous bedside videotapes. HR was analyzed using custom physiologic signal processing software.

    RESULTS: Infants born at earlier GA (<30 wk) had equally intense facial responses during the Lance phase regardless of condition. However, later born infants (> or =30 wk GA) showed heightened facial responses indicative of sensitized responses during blood collection when it was preceded by clustered care (P=0.05). Moreover, later born infants had significantly lower facial (P=0.05) and HR (P=0.04) reactivity during Recovery when blood collection followed clustered care.

    DISCUSSION: Earlier born preterm infants showed heightened states of arousal and poor ability to modulate HR during Recovery when an invasive procedure was preceded by routine tactile nursing procedures. Alternatively, later born infants exhibited sensitized responses when clustered care preceded blood collection. Our findings support the importance of cue based individualized approaches to care.

  • 339. Holtz, Anders
    et al.
    Levi, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Spinal cord injury2010Bok (Annet vitenskapelig)
  • 340.
    Horvath, Istvan
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Iashchishyn, Igor
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. Department of General Chemistry, Sumy State University, Sumy 40007, Ukraine.
    Moskalenko, Roman A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik. 3 Department of Pathology, Sumy State University, Sumy 40007, Ukraine.
    Wang, Chao
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Warmlander, Sebastian K. T. S.
    Wallin, Cecilia
    Graslund, Astrid
    Kovacs, Gabor G.
    Morozova-Roche, Ludmilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Co-aggregation of pro-inflammatory S100A9 with alpha-synuclein in Parkinson's disease: ex vivo and in vitro studies2018Inngår i: Journal of Neuroinflammation, ISSN 1742-2094, E-ISSN 1742-2094, Vol. 15, artikkel-id 172Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Chronic neuroinflammation is a hallmark of Parkinson's disease (PD) pathophysiology, associated with increased levels of pro-inflammatory factors in PD brain tissues. The pro-inflammatory mediator and highly amyloidogenic protein S100A9 is involved in the amyloid-neuroinflammatory cascade in Alzheimer's disease. This is the first report on the co-aggregation of alpha-synuclein (alpha-syn) and S100A9 both in vitro and ex vivo in PD brain.

    Methods: Single and sequential immunohistochemistry, immunofluorescence, scanning electron and atomic force (AFM) microscopies were used to analyze the ex vivo PD brain tissues for S100A9 and alpha-syn location and aggregation. In vitro studies revealing S100A9 and alpha-syn interaction and co-aggregation were conducted by NMR, circular dichroism, Thioflavin-T fluorescence, AFM, and surface plasmon resonance methods.

    Results: Co-localized and co-aggregated S100A9 and alpha-syn were found in 20% Lewy bodies and 77% neuronal cells in the substantia nigra; both proteins were also observed in Lewy bodies in PD frontal lobe (Braak stages 4-6). Lewy bodies were characterized by ca. 10-23 mu m outer diameter, with S100A9 and alpha-syn being co-localized in the same lamellar structures. S100A9 was also detected in neurons and blood vessels of the aged patients without PD, but in much lesser extent. In vitro S100A9 and alpha-syn were shown to interact with each other via the alpha-syn C-terminus with an apparent dissociation constant of ca. 5 mu M. Their co-aggregation occurred significantly faster and led to formation of larger amyloid aggregates than the self-assembly of individual proteins. S100A9 amyloid oligomers were more toxic than those of alpha-syn, while co-aggregation of both proteins mitigated the cytotoxicity of S100A9 oligomers.

    Conclusions: We suggest that sustained neuroinflammation promoting the spread of amyloidogenic S100A9 in the brain tissues may trigger the amyloid cascade involving alpha-syn and S100A9 and leading to PD, similar to the effect of S100A9 and A beta co-aggregation in Alzheimer's disease. The finding of S100A9 involvement in PD may open a new avenue for therapeutic interventions targeting S100A9 and preventing its amyloid self-assembly in affected brain tissues.

  • 341.
    Hu, Xiao-Lei
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Bergström, Sven-Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Brink, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rönnbäck, Annica
    Karolinska Institute, Dept NVS, KI-Alzheimer Disease Research Center, KASPAC, Novum, SE-141 57 Huddinge, Sweden.
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Enriched environment increases spinophilin mRNA expression and spinophilin immunoreactive dendritic spines in hippocampus and cortex2010Inngår i: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 476, nr 2, s. 79-83Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Housing rodents in an enriched environment (EE) induces structural and functional plasticity in the adult brain, including increased dendritic sprouting and number of dendritic spines. However, the molecular mechanisms behind EE-induced brain plasticity remain largely unknown. Circadian rhythm plays an important role in memory processing but the neurobiological mechanisms of how circadian rhythm affects memory and brain plasticity remain controversial. In the current study, we studied the expression of spinophilin, a protein highly enriched in dendritic spines and involved in spine morphology and synaptic plasticity, to examine the effects of EE and circadian rhythm in rats housed in EE for different periods of time. Spinophilin mRNA expression was studied by in situ hybridization and the density of spinophilin immunoreactive puncta was quantified after immunohistochemical staining. Compared to rats living in a deprived environment (DE), we found a transient increase in the density of spinophilin immunoreactive puncta in hippocampus and cortex after 1 week of EE housing and persistent elevations of spinophilin mRNA expression during 1-4 weeks of environmental enrichment. Increased spinophilin expression was found during the light phase of the diurnal cycle, but not the dark phase. Thus, enriched housing altered the diurnal variation in spinophilin mRNA expression, suggesting that circadian modulation is likely to be important for experience dependent plasticity. The current results suggest a possible role for spinophilin in neuronal plasticity induced by environmental enrichment, but further studies are needed to establish a cause-effect relation.

  • 342.
    Hu, Xiaolei
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering.
    Heyn, Patricia C.
    Schwartz, Jaclyn
    Roberts, Pamela
    What is mild stroke?2017Inngår i: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 98, nr 11, s. 2347-2349Artikkel, forskningsoversikt (Fagfellevurdert)
  • 343.
    Hu, Xiaolei
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Heyn, Patricia C.
    Schwartz, Jaclyn
    Roberts, Pamela
    What Is Mild Stroke?2017Inngår i: Archives of Physical Medicine and Rehabilitation, ISSN 0003-9993, E-ISSN 1532-821X, Vol. 98, nr 11, s. 2347-2349Artikkel i tidsskrift (Fagfellevurdert)
  • 344.
    Hu, Xiao-Lei
    et al.
    Neurorehab, Neuro-Huvud-Hals Centrum / Norrlands Universitetssjukhus.
    Stibrant Sunnerhagen, Katharina
    Stroke, rehabilitering2018Annet (Fagfellevurdert)
  • 345.
    Hu, Xiao-Lei
    et al.
    Neurorehab, Neuro-Huvud-Hals Centrum / Norrlands Universitetssjukhus.
    Stibrant Sunnerhagen, Katharina
    Stroke, rehabilitering2018Annet (Fagfellevurdert)
  • 346.
    Hu, Xiao-Lei
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin. Neurocentrum, NUS.
    Wester, Per
    Stibrant Sunnerhagen, Katharina
    Rehabilitering efter stroke - Socialstyrelsens strokeriktlinjer medför nya utmaningar2018Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, nr 51-52, artikkel-id FDIXArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Stroke rehabilitation has often been based on tradition instead of evidence-based methods in the clinical practice. The recently updated Swedish national stroke guidelines have emphasized the amount of evidence-based stroke rehabilitation that is expected to be implemented in clinical practice. The most important recommendations in regarding stroke rehabilitation are the early support discharge, a structured follow-up at the subacute stage for identifying unmet rehabilitation needs and high intensity task-specific training from early to chronic phases.  Meanwhile, we have to use the resource in a most cost-effective ways, such as a newly developed Rehab-Compass, group education for patients and caregivers ("stroke school") and sufficient number of employees of different occupational groups including rehab-assistants, to provide stroke survivors more evidence-based rehabilitation. These inputs will not only improve quality of stroke care but also save the medical and community resource in the near future.

  • 347. 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.

  • 348.
    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.

  • 349.
    Håglin, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Bäckman, L
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    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.
    Domellöf, Magdalena
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Early Recognition of Cognitive Ability and Nutritional Markers for Dementia in Parkinson’s Disease2018Inngår i: Journal of Aging Research & Clinical Practice, ISSN 2258-8094, Vol. 7, s. 156-162Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cognitive decline and dementia are common non-motor problems in Parkinson’s disease (PD). The underlying aetiology is multifaceted and both chronic and reversible causes for cognitive decline are likely to be present. Malnutrition is frequent in the Parkinson population, both early and late in the disease, and nutritional deficiencies could play a role in some cognitive deficits. Objectives: The objective is to study the association between nutritional status with focus on iron intake and homeostasis, mild cognitive impairment (MCI), and PD dementia (PDD). Setting and Participants: This study included 73 out of 145 patients with PD participating in a population-based study in northern Sweden. Measurements: Registration of nutritional status by laboratory analyses of blood plasma and neuropsychological assessments at time of diagnosis were performed. MCI and PDD were assessed yearly up to ten years after diagnosis. Mini Nutritional Assessments (Full-MNA score) and plasma variables detecting iron homeostasis were compared between patients with MCI and patients with normal cognition (NC). Motor severity was measured using the Unified Parkinson´s disease rating scale III, (UPDRS III) and Hoehn and Yahr (H&Y) staging scale. Cox proportional Hazard model were performed to see if any variables that differed between MCI and NC could predict PDD at follow-up. Results: Patients with MCI at time of diagnosis had lower levels of plasma iron (P-Fe) and albumin (P-Albumin) as well as a lower score on Full-MNA score. Dietary intake of iron was higher in patients with MCI than in patients with NC (p = 0.012). In logistic regression models adjusted for age, sex, and UPDRS III, lower levels of P-Fe (p = 0.025) and P-Albumin (p = 0.011) and higher dietary iron intake (p = 0.019) were associated with MCI at baseline. A Cox regression model with dementia as endpoint revealed that lower levels of P-Fe increase the risk of dementia at follow-up with adjustments for age, sex, UPDRS III, and MCI at baseline (HR 95% CI = 0.87 (0.78-0.98), p = 0.021). Conclusions: Low P-Fe was associated with cognitive disturbance at baseline and predicted dementia up to ten years after diagnosis in patients with PD. Low P-Albumin and malnutrition assessed with Full-MNA score were associated with MCI at baseline but did not predict dementia at follow-up.

  • 350.
    Hörnsten, Carl
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Lövheim, Hugo
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    The association between stroke, depression, and 5-year mortality among very old people2013Inngår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 44, nr 9, s. 2587-2589Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Purpose: Depression after stroke has been associated with increased mortality, but little is known about this association among very old people.

    Methods: A population-based study among people ≥85 years of age was conducted in northern Sweden and Finland, comprising cross-sectional assessments and subsequent survival data. The 452 individuals who had completed the Geriatric Depression Scale-15 assessment were selected. Depression was defined as a score of ≥5 on the geriatric depression scale.

    Results: Of those with a history of stroke, 38 of 88 (43.2%) people were depressed, and 11 of the 38 (28.9%) were treated with antidepressants, compared with 91 of 364 (25.0%) depressed (P=0.001) and 17 of 91 (18.7%) treated with antidepressants among those without stroke. Having a history of stroke and ongoing depression was associated with increased 5-year mortality compared with having only stroke (hazard ratio, 1.90; confidence interval, 1.15–3.13), having only depression (hazard ratio, 1.59; confidence interval, 1.03–2.45), and compared with having neither stroke nor depression (hazard ratio, 2.50; confidence interval, 1.69–3.69). Having only stroke without depression did not increase mortality compared with having neither stroke nor depression.

    Conclusions: A history of stroke was associated with increased mortality among very old people but only among those who were also depressed. Depression seemed to be underdiagnosed and undertreated.

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