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  • 301. Gunnarsson, Martin
    et al.
    Malmestrom, Clas
    Rosengren, Lars
    Lycke, Jan
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The Neurofilament Light Chain is Not Stable in Vitro Reply2011In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 69, no 6, p. 1066-1067Article in journal (Refereed)
  • 302. Gunnarsson, Martin
    et al.
    Malmeström, Clas
    Axelsson, Markus
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Dahle, Charlotte
    Vrethem, Magnus
    Olsson, Tomas
    Piehl, Fredrik
    Norgren, Niklas
    Rosengren, Lars
    Svenningsson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Lycke, Jan
    Axonal damage in relapsing multiple sclerosis is markedly reduced by natalizumab2011In: Annals of Neurology, ISSN 0364-5134, E-ISSN 1531-8249, Vol. 69, no 1, p. 83-89Article in journal (Refereed)
    Abstract [en]

    Our data demonstrate that natalizumab treatment reduces the accumulation of nerve injury in relapsing forms of MS. It is anticipated that highly effective anti-inflammatory treatment can reduce axonal loss, thereby preventing development of permanent neurological disability.

  • 303.
    Gustafsson, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Aasly, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stråhle, Stefan
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Nordström, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Nordstrom, Peter
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine.
    Low muscle strength in late adolescence and Parkinson disease later in life2015In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 84, no 18, p. 1862-1869Article in journal (Refereed)
    Abstract [en]

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

  • 304. Gustavsson, Anders
    et al.
    Svensson, Mikael
    Jacobi, Frank
    Allgulander, Christer
    Alonso, Jordi
    Beghi, Ettore
    Dodel, Richard
    Ekman, Mattias
    Faravelli, Carlo
    Fratiglioni, Laura
    Gannon, Brenda
    Jones, David Hilton
    Jennum, Poul
    Jordanova, Albena
    Jönsson, Linus
    Karampampa, Korinna
    Knapp, Martin
    Kobelt, Gisela
    Kurth, Tobias
    Lieb, Roselind
    Linde, Mattias
    Ljungcrantz, Christina
    Maercker, Andreas
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Moscarelli, Massimo
    Musayev, Amir
    Norwood, Fiona
    Preisig, Martin
    Pugliatti, Maura
    Rehm, Juergen
    Salvador-Carulla, Luis
    Schlehofer, Brigitte
    Simon, Roland
    Steinhausen, Hans-Christoph
    Stovner, Lars Jacob
    Vallat, Jean-Michel
    Van den Bergh, Peter
    van Os, Jim
    Vos, Pieter
    Xu, Weili
    Wittchen, Hans-Ulrich
    Jönsson, Bengt
    Olesen, Jes
    Cost of disorders of the brain in Europe 20102011In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 21, no 10, p. 718-779Article in journal (Refereed)
    Abstract [en]

    Background: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, ofan increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.

    Aims: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.

    Methods: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders),dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis,neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27 + Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.

    Results: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.

    Discussion: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.

    Recommendations: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.

  • 305.
    Haage, David
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Laboratory of Ionic Channels of Cell Membranes, Institute of Cytology, Russian Academy of Sciences, Russia.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Allopregnanolone modulates spontaneous GABA release via presynaptic Cl- permeability in rat preoptic nerve terminals2002In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 958, no 2, p. 405-413Article in journal (Refereed)
    Abstract [en]

    The endogenous neurosteroid 3alpha-hydroxy-5alpha-pregnane-20-one (allopregnanolone) affects presynaptic nerve terminals and thereby increases the frequency of spontaneous GABA release. The present study aimed at clarifying the mechanisms underlying this presynaptic neurosteroid action, by recording the frequency of spontaneous GABA-mediated inhibitory postsynaptic currents (sIPSCs) in neurons from the medial preoptic nucleus (MPN) of rat. Acutely dissociated neurons with functional adhering nerve terminals were studied by perforated-patch recording under voltage-clamp conditions. It was shown that the sIPSC frequency increased with the external K(+) concentration ([K(+)](o)). Further, the effect of allopregnanolone on the sIPSC frequency was strongly dependent on [K(+)](o). In a [K(+)](o) of 5 mM, 2.0 microM allopregnanolone caused a clear increase in sIPSC frequency. However, the effect declined rapidly with increased [K(+)](o) and at high [K(+)](o) allopregnanolone reduced the sIPSC frequency. The effect of allopregnanolone was also strongly dependent on the external Cl(-) concentration ([Cl(-)](o)). In a reduced [Cl(-)](o) (40 mM, but with a standard [K(+)](o) of 5 mM), the effect on sIPSC frequency was larger than that in the standard [Cl(-)](o) of 146 mM. The dependence of the effect of allopregnanolone on [K(+)](o) and on estimated presynaptic membrane potential was also altered by the reduction in [Cl(-)](o). As in standard [Cl(-)](o), the effect in low [Cl(-)](o) declined when [K(+)](o) was raised, but reversed at a higher [K(+)](o). The GABA(A) receptor agonist muscimol also potentiated the sIPSC frequency. Altogether, the results suggest that allopregnanolone exerts its presynaptic effect by increasing the presynaptic Cl(-) permeability, most likely via GABA(A) receptors.

  • 306.
    Hadrevi, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Barbe, M. F.
    Ortenblad, N.
    Frandsen, U.
    Boyle, E.
    Lazar, S.
    Sjogaard, G.
    Sogaard, K.
    Calcium Fluxes in Work-Related Muscle Disorder: Implications from a Rat Model2019In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, Vol. 2019, article id 5040818Article in journal (Refereed)
    Abstract [en]

    Introduction: Ca2+ regulatory excitation-contraction coupling properties are key topics of interest in the development of work-related muscle myalgia and may constitute an underlying cause of muscle pain and loss of force generating capacity.

    Method: A well-established rat model of high repetition high force (HRHF) work was used to investigate if such exposure leads to an increase in cytosolic Ca2+ concentration ([Ca2+]i) and changes in sarcoplasmic reticulum (SR) vesicle Ca2+ uptake and release rates.

    Result: Six weeks exposure of rats to HRHF increased indicators of fatigue, pain behaviors, and [Ca2+]i, the latter implied by around 50–100% increases in pCam, as well as in the Ca2+ handling proteins RyR1 and Casq1 accompanied by an ∼10% increased SR Ca2+ uptake rate in extensor and flexor muscles compared to those of control rats. This demonstrated a work-related altered myocellular Ca2+ regulation, SR Ca2+ handling, and SR protein expression.

    Discussion: These disturbances may mirror intracellular changes in early stages of human work-related myalgic muscle. Increased uptake of Ca2+ into the SR may reflect an early adaptation to avoid a sustained detrimental increase in [Ca2+]i similar to the previous findings of deteriorated Ca2+ regulation and impaired function in fatigued human muscle.

  • 307. Hallberg, S.
    et al.
    Boremalm, Malin
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Evertsson, B.
    Lillvall, E.
    Johansson, F.
    Lycke, J.
    Piehl, F.
    Salzer, Jonatan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Svenningsson, A.
    Risk of hypogammaglobulinemia in long-term treatment with rituximab in multiple sclerosis2019In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 25, p. 20-20Article in journal (Other academic)
  • 308.
    Hamberg, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The decision-making process leading to deep brain stimulation in men and women with parkinson's disease: an interview study2014In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 14, p. 89-Article in journal (Refereed)
    Abstract [en]

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

  • 309. Hamel, Wolfgang
    et al.
    Koeppen, Johannes A.
    Mueller, Dieter
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, UCL Institute of Neurology, London, UK.
    Moll, Christian K. E.
    Krack, Paul
    The Pioneering and Unknown Stereotactic Approach of Roeder and Orthner from Gottingen. Part II: Long-Term Outcome and Postmortem Analysis of Bilateral Pallidotomy in the Pre-Levodopa Era2018In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 96, no 6, p. 353-363Article, review/survey (Refereed)
    Abstract [en]

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

  • 310.
    Hansson, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Normative Video Head Impulse Test Data in Subjects with and without vascular risk factors2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 311. Hansson, Oskar
    et al.
    Janelidze, Shorena
    Hall, Sara
    Magdalinou, Nadia
    Lees, Andrew J.
    Andreasson, Ulf
    Norgren, Niklas
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Constantinescu, Radu
    Zetterberg, Henrik
    Blennow, Kaj
    Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 88, no 10, p. 930-937Article in journal (Refereed)
    Abstract [en]

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

  • 312.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hamberg, Katarina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Perceptions of living with a device-based treatment: an account of patients treated with deep brain stimulation for Parkinson’s disease2014In: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, Vol. 17, no 3, p. 272-278Article in journal (Refereed)
    Abstract [en]

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

  • 313.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. UCL Institute of Neurology, Queen Square, London, UK.
    Limousin, P.
    Zrinzo, L.
    Tripoliti, E.
    Aviles-Olmos, I.
    Jahanshahi, M.
    Hamberg, Katarina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Foltynie, T.
    Gender differences in quality of life following subthalamic stimulation for Parkinson's disease2013In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 128, no 4, p. 281-285Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 314.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Limousin, Patricia
    UCL Institute of Neurology, Sobell Department of Motor Neuroscience and Movement Disorders, Unit of Functional Neurosurgery, London, United Kingdom.
    Tisch, Stephen
    Department of Neurology, St. Vincent’s Hospital, Darlinghurst, NSW, Australia.
    Jahanshahi, Marjan
    UCL Institute of Neurology, Sobell Department of Motor Neuroscience and Movement Disorders, Unit of Functional Neurosurgery, London, United Kingdom.
    Fjellman-Wiklund, Anncristine
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Patients' perceptions of life shift after deep brain stimulation for primary dystonia: a qualitative study2011In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 26, no 11, p. 2101-2106Article in journal (Refereed)
    Abstract [en]

    Studies of deep brain stimulation for dystonia have shown significant motor improvement. However, patients' perceptions of surgery and its effects have been less studied. We aimed to explore perceptions of changes in life in patients with primary dystonia after deep brain stimulation. Thirteen patients underwent thematic interviews 8-60 months after pallidal deep brain stimulation. Interviews were transcribed verbatim and analyzed with grounded theory. Patients described a profound impact of dystonia on daily life. After surgery, physical changes with a more upright posture and fewer spasms translated into an easier, more satisfying life with greater confidence. Notwithstanding this positive outcome, the transition from a limited life before surgery to opportunities for a better life exhibited obstacles: The "new life" after deep brain stimulation was stressful, including concern about being dependent on the stimulator as well as having to deal with interfering side effects from deep brain stimulation. The whole coping process meant that patients had to quickly shift focus from struggling to adapt to a slowly progressive disorder to adjustment to a life with possibilities, but also with new challenges. In this demanding transition process, patients wished to be offered better professional guidance and support. Even though deep brain stimulation provides people with primary dystonia with a potential for better mobility and more confidence, patients experienced new challenges and expressed the need for support and counseling after surgery. Grounded theory is a useful method to highlight patients' own experience and contributes to a deeper understanding of the impact of deep brain stimulation on patients with dystonia.

  • 315.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindberg, Margareta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Impact of thalamic deep brain stimulation on disability and health-related quality of life in patients with essential tremor2002In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 72, no 1, p. 47-52Article in journal (Refereed)
    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.

  • 316.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindberg, Margareta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    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.2003In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 18, no 4, p. 373-381Article in journal (Refereed)
    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.

  • 317.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Battery obsolescence, industry profit and deep brain stimulation2019In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 161, no 10, p. 2047-2048Article in journal (Other academic)
  • 318.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, UCL Institute of Neurology, London, UK.
    Early surgery for Parkinson's disease?: Maybe, but not just yet2013In: Lancet Neurology, ISSN 1474-4422, E-ISSN 1474-4465, Vol. 12, no 10, p. 938-939Article in journal (Other academic)
  • 319.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. 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 Disease2017In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, p. S35-S43Article, review/survey (Refereed)
    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.

  • 320.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Striking similarities between pallidotomy and STN DBS at very long-term follow-up2012In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 27, no 6, p. 806-806Article in journal (Refereed)
  • 321.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Twenty-five years of deep brain stimulation: Celebrations and apprehensions2012In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 27, no 7, p. 930-933Article in journal (Other academic)
    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.

  • 322.
    Hariz, Marwan
    et al.
    Institute of Neurology Queen Square, London, United Kingdom.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Limousin, Patricia
    The myth of microelectrode recording in ensuring a precise location of the DBS electrode within the sensorimotor part of the subthalamic nucleus2004In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 19, no 7, p. 863-864Article in journal (Other academic)
  • 323.
    Hariz, Marwan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Zrinzo, Ludvic
    Future of Brain Stimulation: New Targets, New Indications, New Technology2013In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 28, no 13, p. 1784-1792Article, review/survey (Refereed)
    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

  • 324.
    Hariz, Marwan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Therapeutic stimulation versus ablation2013In: Brain Stimulation, Volume 116: Handbook of Clinical Neurology / [ed] Aminoff, Boller, Swaab, Toronto: Elsevier, 2013, 116, p. 63-71Chapter in book (Refereed)
    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. 

  • 325.
    Hariz, Marwan I
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Zrinzo, Ludvic
    Deep brain stimulation between 1947 and 1987: the untold story2010In: Neurosurgical focus, ISSN 1092-0684, Vol. 29, no 2, p. E1-Article in journal (Refereed)
    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."

  • 326.
    Hariz, Marwan I
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hirabayashi, Hidehiro
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Is there a relationship between size and site of the stereotactic lesion and symptomatic results of pallidotomy and thalamotomy?1997In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 69, no 1-4, p. 28-45Article in journal (Refereed)
    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.

  • 327. Hariz, Marwan I
    et al.
    Johansson, Folke
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Shamsgovara, Parvis
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Johansson, Eva
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Fagerlund, Markku
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Bilateral subthalamic nucleus stimulation in a parkinsonian patient with preoperative deficits in speech and cognition: persistent improvement in mobility but increased dependency2000In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 15, no 1, p. 136-139Article in journal (Refereed)
    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.

  • 328.
    Hariz, Marwan I
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Krack, P
    Alesch, F
    Augustinsson, L-E
    Bosch, A
    Ekberg, R
    Johansson, F
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    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-up2008In: Journal of neurology, neurosurgery and psychiatry, ISSN 1468-330X, Vol. 79, no 6, p. 694-699Article in journal (Refereed)
    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.

  • 329.
    Hariz, Marwan I
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    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 electrodes2003In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 80, no 1-4, p. 96-101Article in journal (Refereed)
    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.

  • 330.
    Hariz, Marwan I
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Shamsgovara, P
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Johansson, F
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Fodstad, H
    Tolerance and tremor rebound following long-term chronic thalamic stimulation for Parkinsonian and essential tremor1999In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 72, no 2-4, p. 208-218Article in journal (Refereed)
    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.

  • 331.
    Hariz, Marwan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. 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 ago2017In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 140, p. 2516-2519Article in journal (Other academic)
  • 332.
    Hart, Andrew McKay
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. 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 University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    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 & elimination2002In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 142, no 3, p. 308-318Article in journal (Refereed)
    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.

  • 333.
    Hart, Andrew McKay
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    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 conduit2003In: British Journal of Plastic Surgery, ISSN 0007-1226, E-ISSN 1465-3087, Vol. 56, no 5, p. 444-450Article in journal (Refereed)
    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.

  • 334.
    Hart, Andrew McKay
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery. 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 University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Terenghi, Giorgio
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl-L-carnitine treatment2002In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 334, no 3, p. 181-185Article in journal (Refereed)
    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.

  • 335.
    Hart, Andrew McKay
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. 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 University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    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 trauma2002In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 145, no 2, p. 182-189Article in journal (Refereed)
    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.

  • 336.
    Hart, Andrew
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Terenghi, Giorgio
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Tissue Engineering for Peripheral Nerve Regeneration2011In: Tissue Engineering: From Lab to Clinic / [ed] Norbert Pallua, Christoph V. Suscheck, Berlin: Springer Berlin/Heidelberg, 2011, p. 245-262Chapter in book (Other academic)
    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.

  • 337.
    Haukenes, Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Norwegian Inst Publ Hlth, Div Mental Hlth, Dept Publ Mental Hlth, Bergen, Norway.
    Hensing, G.
    Stålnacke, Britt-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine.
    Hammarström, Anne
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Social medicine. Norwegian Inst Publ Hlth, Div Mental Hlth, Dept Publ Mental Hlth, Bergen, Norway.
    Does pain severity guide selection to multimodal pain rehabilitation across gender?2015In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 19, no 6, p. 826-833Article in journal (Refereed)
    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.

  • 338.
    Heldestad, Victoria
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Quantified sensory abnormalities in early genetically verified transthyretin amyloid polyneuropathy2007In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 35, no 2, p. 189-195Article in journal (Refereed)
  • 339. Hellgren, Charlotte
    et al.
    Akerud, Helena
    Skalkidou, Alkistis
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sundstrom-Poromaa, Inger
    Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy2014In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 69, no 3, p. 147-153Article in journal (Refereed)
    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

  • 340. Henriksson, Karin M.
    et al.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    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 Controls2013In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 22, p. 399-400Article in journal (Other academic)
  • 341.
    Henriksson, Roger
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Asklund, Thomas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    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 review2011In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 104, no 3, p. 639-646Article, review/survey (Refereed)
    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.

  • 342.
    Hirabayashi, Hidehiro
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stereotactic imaging in functional neurosurgery2012Doctoral thesis, comprehensive summary (Other academic)
    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.

  • 343.
    Hirabayashi, Hidehiro
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Fagerlund, M
    Comparison between stereotactic CT and MRI coordinates of pallidal and thalamic targets using the Laitinen noninvasive stereoadapter1998In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 71, no 3, p. 117-130Article in journal (Refereed)
    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.

  • 344.
    Hirabayashi, Hidehiro
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wårdell, K
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Impact of parameters of radiofrequency coagulation on volume of stereotactic lesion in pallidotomy and thalamotomy2012In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 90, no 5, p. 307-315Article in journal (Refereed)
    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.

  • 345.
    Hirabayashi, Hidehiro
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Tengvar, Magnus
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stereotactic imaging of the pallidal target2002In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 17, no suppl 3, p. S130-S134Article in journal (Refereed)
    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.

  • 346. Hohsfield, Lindsay A.
    et al.
    Daschil, Nina
    Orädd, Greger
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Strömberg, Ingrid
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Humpel, Christian
    Vascular pathology of 20-month-old hypercholesterolemia mice in comparison to triple-transgenic and APPSwDI Alzheimer's disease mouse models2014In: Molecular and cellular neuroscience, ISSN 1044-7431, Vol. 63, p. 83-95Article in journal (Refereed)
    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.

  • 347.
    Holm, Linus
    et al.
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Ullén, Fredrik
    Karolinska institutet, Institutionen för kvinnor och barns hälsa, Stockholm Brain Institute.
    Madison, Guy
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Intelligence and temporal accuracy of behaviour: unique and shared associations with reaction time and motor timing2011In: Experimental Brain Research, ISSN 0014-4819, E-ISSN 1432-1106, Vol. 214, no 2, p. 175-183Article in journal (Refereed)
    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.

  • 348.
    Holmlund, Petter
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Koskinen, Lars-Owe D.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Johansson, Elias
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sundström, Nina
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Qvarlander, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Venous collapse regulates intracranial pressure in upright body positions2018In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 314, no 3, p. R377-R385Article in journal (Refereed)
    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.

  • 349.
    Holmlund, Thorbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindqvist, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Larsson, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sahlin, C.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Tonsillectomy in adults with obstructive sleep apnea2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, p. 161-161Article in journal (Other academic)
  • 350. Holmqvist, Marie
    et al.
    Simard, Julia F.
    Asplund, Kjell
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Arkema, Elizabeth V.
    Stroke in systemic lupus erythematosus: a meta-analysis of population-based cohort studies2015In: RMD Open, E-ISSN 2056-5933, Vol. 1, no 1, article id UNSP e000168Article, review/survey (Refereed)
    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.

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