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  • 1. Abosch, Aviva
    et al.
    Timmermann, Lars
    Bartley, Sylvia
    Rietkerk, Hans Guido
    Whiting, Donald
    Connolly, Patrick J.
    Lanctin, David
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    An International Survey of Deep Brain Stimulation Procedural Steps2013In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 91, no 1, p. 1-11Article, review/survey (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) surgery is standard of care for the treatment of certain movement disorders.

    Objective: We sought to characterize the spectrum of steps performed in DBS surgery, at centers around the world where this surgery is performed.

    Methods: We identified the main steps in DBS surgery workflow and grouped these 19 steps into 3 phases (preoperative, operative, and postoperative). A survey tool, informed by a pilot survey, was administered internationally by trained study personnel at high- and low-volume DBS centers. Procedural components, duration, and surgeon motivational factors were assessed. Cluster analysis was used to identify procedural and behavioral clusters.

    Results: One hundred eighty-five procedure workflow surveys (143 DBS centers) and 65 online surveys of surgeon motivational drivers were completed (45% response rate). Significant heterogeneity in technique, operative time, and surgeon motivational drivers was reported across centers.

    Conclusions: We provide a description of the procedural steps involved in DBS surgery and the duration of these steps, based on an international survey. These data will enable individual surgeons and centers to examine their own experience relative to colleagues at other centers and in other countries. Such information could also be useful in comparing efficiencies and identifying workflow obstacles between different hospital environments.

  • 2. Akram, Harith
    et al.
    Dayal, Viswas
    Mahlknecht, Philipp
    Georgiev, Dejan
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Jahanshahi, Marjan
    Ashburner, John
    Behrens, Tim
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK.
    Zrinzo, Ludvic
    Connectivity derived thalamic segmentation in deep brain stimulation for tremor2018In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 18, p. 130-142Article in journal (Refereed)
    Abstract [en]

    The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

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  • 3. Akram, Harith
    et al.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Zrinzo, Ludvic
    Connectivity derived thalamic segmentation: Separating myth from reality2019In: NeuroImage: Clinical, E-ISSN 2213-1582, Vol. 22, article id 101758Article in journal (Refereed)
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  • 4. Akram, Harith
    et al.
    Limousin, Patricia
    Hyam, Jonathan
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London.
    Zrinzo, Ludvic
    Aim for the Suprasternal Notch: Technical Note to Avoid Bowstringing after Deep Brain Stimulation2015In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 93, no 4, p. 227-230Article in journal (Refereed)
    Abstract [en]

    Background: Bowstringing may occur when excessive fibrosis develops around extension cables in the neck after deep brain stimulation (DBS) surgery. Though the occurrence of this phenomenon is rare, we have noted that it tends to cause maximal discomfort when the cables cross superficially over the convexity of the clavicle. We hypothesise that bowstringing may be avoided by directing the extension cables towards the suprasternal notch. Methods: When connecting DBS leads to an infraclavicular pectoral implantable pulse generator (IPG), tunnelling is directed towards the suprasternal I notch, before being directed laterally towards the IPG pocket. In previously operated patients with established fibrosis, the fibrous tunnel is opened and excised as far cranially as possible, allowing medial rerouting of cables. Using this approach, we reviewed our series of patients who underwent DBS surgery over 10 years. Results: In 429 patients, 7 patients (2%) with cables tunnelled over the convexity of the clavicle complaining of bowstringing underwent cable exploration and rerouting. This eliminated bowstringing and provided better cosmetic results. When the cable trajectory was initially directed towards the suprasternal notch, no bowstringing was observed. Conclusion:The tunnelling trajectory appears to influence postoperative incidence of fibrosis associated with DBS cables. Modifying the surgical technique may reduce the incidence of this troublesome adverse event. (C) 2015 S.Karger AG, Basel

  • 5. Akram, Harith
    et al.
    Miller, Sarah
    Lagrata, Susie
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ashburner, John
    Behrens, Tim
    Matharu, Manjit
    Zrinzo, Ludvic
    Optimal deep brain stimulation site and target connectivity for chronic cluster headache2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, no 20, p. 2083-2091Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the mechanism of action of deep brain stimulation for refractory chronic cluster headache and the optimal target within the ventral tegmental area. Methods: Seven patients with refractory chronic cluster headache underwent high spatial and angular resolution diffusion MRI preoperatively. MRI-guided and MRI-verified electrode implantation was performed unilaterally in 5 patients and bilaterally in 2. Volumes of tissue activation were generated around active lead contacts with a finite-element model. Twelve months after surgery, voxel-based morphometry was used to identify voxels associated with higher reduction in headache load. Probabilistic tractography was used to identify the brain connectivity of the activation volumes in responders, defined as patients with a reduction of >= 30% in headache load. Results: There was no surgical morbidity. Average follow-up was 34 +/- 14 months. Patients showed reductions of 76 +/- 33% in headache load, 46 +/- 41% in attack severity, 58 +/- 41% in headache frequency, and 51 +/- 46% in attack duration at the last follow-up. Six patients responded to treatment. Greatest reduction in headache load was associated with activation in an area cantered at 6 mm lateral, 2 mm posterior, and 1 mm inferior to the midcommissural point of the third ventricle. Average responders' activation volume lay on the trigeminohypothalamic tract, connecting the trigeminal system and other brainstem nuclei associated with nociception and pain modulation with the hypothalamus, and the prefrontal and mesial temporal areas. Conclusions: We identify the optimal stimulation site and structural connectivity of the deep brain stimulation target for cluster headache, explicating possible mechanisms of action and disease pathophysiology.

  • 6. Akram, Harith
    et al.
    Sotiropoulos, Stamatios N.
    Jbabdi, Saad
    Georgiev, Dejan
    Mahlknecht, Philipp
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
    Ashburner, John
    Behrens, Tim
    Zrinzo, Ludvic
    Subthalamic deep brain stimulation sweet spots and hyperdirect cortical connectivity in Parkinson's disease2017In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 158, p. 332-345Article in journal (Refereed)
    Abstract [en]

    Objectives: Firstly, to identify subthalamic region stimulation clusters that predict maximum improvement in rigidity, bradykinesia and tremor, or emergence of side-effects; and secondly, to map-out the cortical fingerprint, mediated by the hyperdirect pathways which predict maximum efficacy.

    Methods: High angular resolution diffusion imaging in twenty patients with advanced Parkinson's disease was acquired prior to bilateral subthalamic nucleus deep brain stimulation. All contacts were screened one-year from surgery for efficacy and side-effects at different amplitudes. Voxel-based statistical analysis of volumes of tissue activated models was used to identify significant treatment clusters. Probabilistic tractography was employed to identify cortical connectivity patterns associated with treatment efficacy.

    Results: All patients responded well to treatment (46% mean improvement off medication UPDRS-III [p < 0.0001]) without significant adverse events. Cluster corresponding to maximum improvement in tremor was in the posterior, superior and lateral portion of the nucleus. Clusters corresponding to improvement in bradykinesia and rigidity were nearer the superior border in a further medial and posterior location. The rigidity cluster extended beyond the superior border to the area of the zona incerta and Forel-H-2 field. When the clusters where averaged, the coordinates of the area with maximum overall efficacy was X = -10(-9.5), Y = -3(-1) and Z = -7(-3) in MNI(AC-PC) space. Cortical connectivity to primary motor area was predictive of higher improvement in tremor; whilst that to supplementary motor area was predictive of improvement in bradykinesia and rigidity; and connectivity to prefrontal cortex was predictive of improvement in rigidity.

    Interpretation: These findings support the presence of overlapping stimulation sites within the subthalamic nucleus and its superior border, with different cortical connectivity patterns, associated with maximum improvement in tremor, rigidity and bradykinesia.

  • 7. Akram, Harith
    et al.
    Wu, Chengyuan
    Hyam, Jonathan
    Foltynie, Thomas
    Limousin, Patricia
    De Vita, Enrico
    Yousry, Tarek
    Jahanshahi, Marjan
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, Queen Square, London, UK.
    Behrens, Timothy
    Ashburner, John
    Zrinzo, Ludvic
    L-Dopa Responsiveness Is Associated With Distinctive Connectivity Patterns in Advanced Parkinson's Disease2017In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, no 6, p. 874-883Article in journal (Refereed)
    Abstract [en]

    Background: Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. Methods: To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to L-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3x3x2.5mm(3) voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an L-dopa challenge. False discovery rate-corrected P was set at < 0.05 for a 2-tailed t test. Results: A greater improvement in UPDRS-III scores following L-dopa administration was characterized by higher resting-state functional connectivity between the prefrontal cortex and the striatum (P=0.001) and lower resting-state functional connectivity between the pallidum (P=0.001), subthalamic nucleus (P=0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas). Conclusions: Our findings show characteristic basal ganglia resting-state functional connectivity patterns associated with different degrees of L-dopa responsiveness in patients with advanced Parkinson's disease. L-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response.

  • 8. Antonsson, Johan
    et al.
    Eriksson, Ola
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Richter, Johan
    Zsigmond, Peter
    Wårdell, Karin
    Diffuse reflectance spectroscopy measurements for tissue-type discrimination during deep brain stimulation.2008In: Journal of neural engineering, ISSN 1741-2560, Vol. 5, no 2, p. 185-190Article in journal (Refereed)
    Abstract [en]

    Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.

  • 9. Aziz, Tipu Z.
    et al.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. UCL Institute of Neurology, Unit of Functional Neurosurgery, London, England.
    To sleep or not to sleep during deep brain stimulation surgery for Parkinson disease?2017In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 89, no 19, p. 1938-1939Article in journal (Other academic)
  • 10.
    Bergenheim, Tommy A
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Larsson, Eva
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. UCL Institute of Neurology, London, UK.
    Selective peripheral denervation for cervical dystonia: long-term follow-up2015In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, no 12, p. 1307-1313Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: 61 procedures with selective peripheral denervation for cervical dystonia were retrospectively analysed concerning surgical results, pain, quality of life (QoL) and recurrences.

    METHODS: The patients were assessed with the Tsui torticollis scale, Visual Analogue Scale (VAS) for pain and Fugl-Meyer scale for QoL. Evaluations were performed preoperatively, early postoperatively, at 6 months, then at a mean of 42 (13-165) months. All patients underwent electromyogram at baseline, which was repeated in cases who presented with recurrence of symptoms after surgery.

    RESULTS: Six months of follow-up was available for 55 (90%) of the procedures and late follow-up for 34 (56%). The mean score of the Tsui scale was 10 preoperatively. It improved to 4.5 (p<0.001) at 6 months, and 5.3 (p<0.001) at late follow-up. VAS for pain improved from 6.5 preoperatively to 4.2 (p<0.001) at 6 months and 4 (p<0.01) at late follow-up. The Fugl-Meyer score for QoL improved from 43.3 to 46.6 (p<0.05) at 6 months, and to 51.1 (p<0.05) at late follow-up. Major reinnervation and/or change in the dystonic pattern occurred following 29% of the procedures, and led in 26% of patients to reoperation with either additional denervation or pallidal stimulation.

    CONCLUSIONS: Selective peripheral denervation remains a surgical option in the treatment of cervical dystonia when conservative measures fail. Although the majority of patients experience a significant relief of symptoms, there is a substantial risk of reinnervation and/or change in the pattern of the cervical dystonia.

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  • 11.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Fytagoridis, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    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.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Unilateral caudal Zona incerta deep brain stimulation for Parkinsonian tremor2012In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 18, no 10, p. 1062-1066Article in journal (Other academic)
    Abstract [en]

    Background: The subthalamic nucleus is currently the target of choice in deep brain stimulation (DBS) for Parkinson's disease (PD), while thalamic DBS is used in some cases of tremor-dominant PD. Recently, a number of studies have presented promising results from DBS in the posterior subthalamic area, including the caudal zona incerta (cZi). The aim of the current study was to evaluate cZi DBS in tremor-dominant Parkinson's disease.

    Methods: 14 patients with predominately unilateral tremor-dominant PD and insufficient relief from pharmacologic therapy were included and evaluated according to the motor part of the Unified Parkinson Disease Rating Scale (UPDRS). The mean age was 65 ± 6.1 years and the disease duration 7 ± 5.7 years. Thirteen patients were operated on with unilateral cZi DBS and 1 patient with a bilateral staged procedure. Five patients had non-L-dopa responsive symptoms. The patients were evaluated on/off medication before surgery and on/off medication and stimulation after a minimum of 12 months after surgery.

    Results: At the follow-up after a mean of 18.1 months stimulation in the off-medication state improved the contralateral UPDRS III score by 47.7%. Contralateral tremor, rigidity, and bradykinesia were improved by 82.2%, 34.3%, and 26.7%, respectively. Stimulation alone abolished tremor at rest in 10 (66.7%) and action tremor in 8 (53.3%) of the patients.

    Conclusion: Unilateral cZi DBS seems to be safe and effective for patients with severe Parkinsoniantremor. The effects on rigidity and bradykinesia were, however, not as profound as in previous reports of DBS in this area.

  • 12.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Pallidotomy versus pallidal stimulation2006In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 12, no 5, p. 296-301Article in journal (Refereed)
    Abstract [en]

    Both posteroventral pallidotomy and pallidal deep brain stimulation (DBS) have a documented effect on Parkinsonian symptoms. DBS is more costly and more laborious than pallidotomy. The aim of this study was to analyse the respective long-term effect of each surgical procedure on contralateral symptoms in the same patients. Five consecutive patients, two women and three men, who at first surgery had a mean age of 64 years and a mean duration of disease of 18 years, received a pallidotomy contralateral to the more symptomatic side of the body. At a mean of 14 months later, the same patients received a pallidal DBS on the side contralateral to the pallidotomy. All patients had on–off phenomena and dyskinesias. There were three left-sided and two right-sided pallidotomies, and, subsequently, two left-sided and three right-sided pallidal DBS. The latest evaluation was performed 37 months (range 22–60) after the pallidotomy and 22 months (range 12–33) after the pallidal DBS. Mean UPDRS motor score pre-operatively was 49 and at last follow-up 33 (32.7% improvement, p<0.05). Appendicular items 20–26 contralateral to pallidotomy remained improved more significantly than contralateral to DBS. Dyskinesia scores were also improved more markedly contralateral to the pallidotomy. Two patients exhibited moderate dysarthria and one patient severe dysphonia following DBS. Symptoms contralateral to the chronologically older pallidotomy, especially dyskinesias, rigidity and tremor, were still more improved than symptoms contralateral to the more recent pallidal DBS, despite numerous post-operative patient visits to optimise stimulation parameters.

  • 13.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Koskinen, Lars-Owe D
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up2007In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 21, no 5, p. 504-509Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) of the nucleus ventralis intermedius thalami (Vim) in the treatment of essential tremor (ET) is well documented concerning the acute effects. Reports of the long-term effects are, however, few and the aim of the present study was to analyse the long-term efficacy of this treatment. Nineteen patients operated with unilateral Vim-DBS were evaluated with the Essential Tremor Rating Scale (ETRS) before surgery, and after a mean time of 1 and 7 years after surgery. The ETRS score for tremor of the contralateral hand was reduced from 6.8 at baseline to 1.2 and 2.7, respectively, on stimulation at follow-up. For hand function (item 11 – 14) the score was reduced from 12.7 to 4.1 and 8.2, respectively. Vim-DBS is an efficient treatment for ET, also after many years of treatment. There is, however, a decreasing effect over time, most noticeable concerning tremor of action.

    Read More: http://informahealthcare.com/doi/abs/10.1080/02688690701552278

  • 14.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, UCL Institute of Neurology, Queen Square, London, UK.
    Closed loop stimulation for tremor was invented in 19802019In: Brain Stimulation, ISSN 1935-861X, E-ISSN 1876-4754, Vol. 12, no 4, p. 1072-1073Article in journal (Refereed)
  • 15.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, University College of London, Institute of Neurology, London, UK.
    The paper that wrote itself – A ghost story2018In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 33, no 9, p. 1509-1510Article in journal (Refereed)
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  • 16.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Are complications less common in deep brain stimulation than in ablative procedures for movement disorders?2006In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 84, no 2-3, p. 72-81Article in journal (Refereed)
    Abstract [en]

    The side effects and complications of deep brain stimulation (DBS) and ablative lesions for tremor and Parkinson’s disease were recorded in 256 procedures (129 DBS and 127 lesions). Perioperative complications (seizures, haemorrhage, confusion) were rare and did not differ between the two groups. The rate of hardware-related complications was 17.8%. In ventral intermediate (Vim) thalamotomies, the rate of side effects was 74.5%, in unilateral Vim-DBS 47.3%, while in 7 bilateral Vim-DBS 13 side effects occurred. Most of the side effects of Vim-DBS were reversible upon switching off, or altering, stimulation parameters. In unilateral pallidotomy, the frequency of side effects was 21.9%, while in bilateral staged pallidotomies it was 33.3%. Eight side effects occurred in 11 procedures with pallidal DBS. In 22 subthalamic nucleus DBS procedures, 23 side effects occurred, of which 8 were psychiatric or cognitive. Unilateral ablative surgery may not harbour more postoperative complications or side effects than DBS. Some of the side effects following lesioning are transient and most but not all DBS side effects are reversible. In the Vim DBS is safer than lesioning, while in the pallidum, unilateral lesions are well tolerated.

    Copyright © 2006 S. Karger AG, Basel

  • 17.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Deep brain stimulation for movement disorders before DBS for movement disorders2010In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 16, no 7, p. 429-433Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) is an established surgical treatment for Parkinson's disease (PD), essential tremor and dystonia. It is generally acknowledged that the development of DBS as we know it today started with the publication of Benabid, Pollak et al in 1987 on thalamic DBS for tremor. This technique gained momentum in the mid-Nineties after that Pollak and Benabid introduced the subthalamic nucleus as a target in advanced PD. This paper reviews the gestational pre-natal era of deep brain stimulation, before 1987. The origin of DBS can be traced back to the practice of intra-operative electrical stimulation, used for target exploration prior to lesioning, during the early years of stereotactic functional neurosurgery. During the 60s, Sem-Jacobsen and others implanted externalised electrodes which were used for intermittent stimulation and evaluation during weeks or months, prior to subsequent ablation of thalamic and other basal ganglia targets. In the early 70s Bechtereva treated PD patients using "therapeutic electrical stimulation" through electrodes implanted for up to 1.5 years. In the late 70s and early 80s the term Deep Brain Stimulation was coined and few groups attempted treatment of Parkinson's disease, non-Parkinsonian tremor and dystonia with high-frequency stimulation using chronically implanted DBS systems. Cumbersome, un-sophisticated DBS hardware, together with the general decline of all surgery for PD following the introduction of levodopa, may have contributed to the lack of popularity of old-times DBS. It is to the credit of the Grenoble Group to have reinvented, modernised and expanded modern DBS in surgical treatment of movement disorders.

  • 18.
    Blomstedt, Patric
    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, Neurosurgery.
    Silberstein, P
    Lees, A
    Limousin, P
    Yelnik, J
    Agid, Y
    Acute severe depression induced by intraoperative stimulation of the Substatia Nigra: a case-report2008In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 14, no 3, p. 253-256Article in journal (Other academic)
    Abstract [en]

    We present a 62 years old man with Parkinson's disease (PD) who underwent bilateral stimulation in the subthalamic nucleus (STN). During the intraoperative evaluation, stimulation through the lowest contact in the right STN area, induced an acute depressive state, during which the patient was crying and expressing that he did not want to live. The patient returned to his normal state of mood within seconds after the cessation of stimulation. Repeated blinded stimulations resulted in the same response. Immediate postoperative magnetic resonance imaging (MRI) revealed that the lowest contact of the right electrode was located in the substantia nigra.

  • 19.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Tisch, Stephen
    Holmberg, Monica
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Bergenheim, Tommy A
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    A family with a hereditary form of torsion dystonia from northern Sweden treated with bilateral pallidal deep brain stimulation2009In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 24, no 16, p. 2415-2419Article in journal (Refereed)
    Abstract [en]

    To evaluate pallidal DBS in a non-DYT1 form of hereditary dystonia. We present the results of pallidal DBS in a family with non-DYT1 dystonia where DYT5 to 17 was excluded. The dystonia is following an autosomal dominant pattern. Ten members had definite dystonia and five had dystonia with minor symptoms. Four patients received bilateral pallidal DBS. Mean age was 47 years. The patients were evaluated before surgery, and "on" stimulation after a mean of 2.5 years (range 1-3) using the Burke-Fahn-Marsden scale (BFM). Mean BFM score decreased by 79 % on stimulation, from 42.5 +/- 24 to 9 +/- 6.5 at the last evaluation. Cervical involvement improved by 89%. The 2 patients with oromandibular dystonia and blepharospasm demonstrated a reduction of 95% regarding these symptoms. The present study confirms the effectiveness of pallidal DBS in a new family with hereditary primary segmental and generalized dystonia.

  • 20.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Lindvall, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Olivecrona, Magnus
    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.
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Reoperation after failed deep brain stimulation for essential tremor2012In: World Neurosurgery, ISSN 1878-8750, Vol. 78, no 5, p. 554.e1-554.e5Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the effects of reoperation with deep brain stimulation (DBS) in the caudal zona incerta (cZi) in patients with failed DBS in the ventral intermediate (Vim) nucleus of the thalamus for essential tremor. METHODS: The results of reoperation with cZi DBS in five patients with failed Vim DBS were retrospectively analyzed. RESULTS: Two patients had early failure of Vim DBS, and three after several years of good effect. The mean deviation from the atlas Vim target point was 1.4 mm. Before the reoperation Vim DBS improved hand function and tremor in the treated hand at 25 %, whereas cZi DBS achieved an improvement of 57%. Although cZi was more efficient than Vim DBS, also in the patients with late failure of Vim DBS, they still exhibited a considerable residual tremor on cZi DBS. CONCLUSIONS: The effect on tremor was, in this small sample population, improved by implanting an electrode in the cZi. The effect was modest in those patients suffering a deterioration years after the initial operation.

  • 21.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Olivecrona, Magnus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sailer, Alexandra
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Dittmar and the history of stereotaxy: or rats, rabbits, and references2007In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 60, no 1, p. 198-201Article in journal (Other academic)
    Abstract [en]

    The renaissance of stereotactic functional neurosurgery has resulted in increased interest in its origins. Twenty articles concerning this field trace the history back to a paper published in 1873 by Dittmar: “Über die Lage des sogenannten Gefaesszentrums in der Medulla oblongata” [On the location of the so-called vasomotor center in the medulla oblongata]. Few facts are presented. But, taken together, the impression given by the secondary sources is that Dittmar, in 1873, presented a guiding device for localization of intracranial structures for the positioning of electrodes/blades in the medulla oblongata in rats. Of the publications that cite Dittmar's original article as their only quoted source, half did not specify the inserted object and the animal of the experiment. The remaining articles reported either that the introduced object was an electrode or that the experiments were performed on rats. Dittmar's original article, however, did not report use of his apparatus for insertion of electrodes, nor did he use rats. All experiments were performed by making incisions in the medulla oblongata in rabbits. Dittmar's apparatus was constructed to allow more precision when performing incisions in the medulla oblongata than could be obtained performing incisions freehand. The incision point was chosen and the blade introduced with direct visual guidance. This has been described as “spatial localization of intracranial structures,” “a special targeting instrument,” or simply, “a guiding device.” In our opinion, it can most properly be classified as a supportive arm.

  • 22.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan
    UCL Insitute of Neurology, Queen Square, London, Uk.
    Fytagoridis, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor2011In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 17, no 8, p. 617-620Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures. Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11-14 (hand tremor and hand function) were selected for analysis of tremor outcome. The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.

  • 23.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sandvik, Ulrika
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Fredricks, Anna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Deep brain stimulation of the subthalamic nucleus versus the zona incerta in the treatment of essential tremor2011In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 153, no 12, p. 2329-2335Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) is an effective treatment for essential tremor (ET). Currently the ventrolateral thalamus is the target of choice, but the posterior subthalamic area (PSA), including the caudal zona incerta (cZi), has demonstrated promising results, and the subthalamic nucleus (STN) has been suggested as a third alternative. The objective of the current study was to evaluate the effect of STN DBS in ET and to compare this to cZi DBS.

    Methods: Four patients with ET were implanted with two ipsilateral electrodes, one in the STN and one in the cZi. All contacts were evaluated concerning the acute effect on tremor, and the effect of chronic DBS in either target was analyzed.

    Results: STN and cZi both proved to be potent targets for DBS in ET. DBS in the cZi was more efficient, since the same degree of tremor reduction could here be achieved at lower energy consumption. Three patients became tremor-free in the treated hand with either STN or cZi DBS, while the fourth had a minor residual tremor after stimulation in either target.

    Conclusion: In this limited material, STN DBS was demonstrated to be an efficient treatment for ET, even though cZi DBS was more efficient. The STN may be an alternative target in the treatment of ET, pending further investigations to decide on the relative merits of the different targets.

  • 24.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Sjöberg, Richard
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hansson, Maja
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bodlund, Owe
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Deep brain stimulation in the treatment of depression2011In: Acta Psychiatrica Scandinavica, ISSN 0001-690X, E-ISSN 1600-0447, Vol. 123, no 1, p. 4-11Article in journal (Refereed)
    Abstract [en]

    Objective:  To present the technique of deep brain stimulation (DBS) and to evaluate the studies conducted on DBS in the treatment of therapy-refractory major depressive disorder (MDD).

    Method:  A review of the literature on DBS in the treatment of MDD was conducted.

    Results:  The results of DBS in MDD have been presented in 2 case reports and 3 studies of 47 patients operated upon in 5 different target areas. Positive effects have been presented in all studies and side effects have been minor. DBS in the nucleus accumbens resulted in a mean reduction of Hamilton depression rating scale (HDRS) of 36% after 1 year and 30% of the 10 patients achieved remission. DBS in the internal capsule/ventral striatum resulted in a reduction of 44% after 1 year, and at the last evaluation after in mean 2 years, 40% of the 15 patients were in remission. The 20 patients with subcallosal cingulated gyrus DBS had a reduction of HDRS of 52% after 1 year, and 35% were within 1 point from remission or in remission.

    Conclusion:  DBS is a promising treatment for therapy-refractory MDD. The published experience is, however, limited, and the method is at present an experimental therapy.

  • 25.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sjöberg, Rickard L
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hansson, Maja
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. University Hospital of Umeå.
    Bodlund, Owe
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry. University Hospital of Umeå.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Deep brain stimulation in the treatment of obsessive-compulsive disorder2013In: World Neurosurgery, ISSN 1878-8750, E-ISSN 1878-8769, Vol. 80, no 6, p. e245-e253Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Deep brain stimulation (DBS) has emerged as a treatment for severe cases of therapy-refractory obsessive-compulsive disorder (OCD), and promising results have been reported. The literature might, however, be somewhat unclear, considering the different targets used, and due to repeated inclusion of individual patients in multiple publications. The aim of this report was to review the literature on DBS for OCD.

    METHODS: The modern literature concerning studies conducted on DBS in the treatment of OCD was reviewed.

    RESULTS: The results of DBS in OCD have been presented in 25 reports with 130 patients, of which, however, only 90 contained individual patients. Five of these reports included at least 5 individual patients not presented elsewhere. Sixty-eight of these patients underwent implantation in the region of the internal capsule/ventral striatum, including the nucleus accumbens. The target in this region has varied between groups and over time, but the latest results from bilateral procedures in this area have shown a 50% reduction of OCD scores, depression, and anxiety. The subthalamic nucleus has been suggested as an alternative target. Although beneficial effects have been demonstrated, the efficacy of this procedure cannot be decided, because only results after 3 months of active stimulation have been presented so far.

    CONCLUSIONS: DBS is a promising treatment for therapy-refractory OCD, but the published experience is limited and the method is at present an experimental therapy.

  • 26.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenmark Persson, Rasmus
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    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.
    Linder, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Fredricks, Anna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Häggström, Björn
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Philipson, Johanna
    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.
    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.
    Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation2018In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 89, no 7, p. 710-716Article in journal (Refereed)
    Abstract [en]

    Background: Several open-label studies have shown good effect of deep brain stimulation (DBS) in the caudal zona incerta (cZi) on tremor, including parkinsonian tremor, and in some cases also a benefit on akinesia and axial symptoms. The aim of this study was to evaluate objectively the effect of cZi DBS in patients with Parkinson's disease (PD).

    Method: 25 patients with PD were randomised to either cZi DBS or best medical treatment. The primary outcomes were differences between the groups in the motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS-III) rated single-blindly at 6 months and differences in the Parkinson's Disease Questionnaire 39 items (PDQ-39). 19 patients, 10 in the medical arm and 9 in the DBS arm, fulfilled the study.

    Results: The DBS group had 41% better UPDRS-III scores off-medication on-stimulation compared with baseline, whereas the scores of the non-surgical patients off-medication were unchanged. In the on-medication condition, there were no differences between the groups, neither at baseline nor at 6 months. Subitems of the UPDRS-III showed a robust effect of cZi DBS on tremor. The PDQ-39 domains 'stigma' and 'ADL' improved only in the DBS group. The PDQ-39 summary index improved in both groups.

    Conclusion: This is the first randomised blinded evaluation of cZi DBS showing its efficacy on PD symptoms. The most striking effect was on tremor; however, the doses of dopaminergic medications could not be decreased. cZi DBS in PD may be an addition to existing established targets, enabling tailoring the surgery to the needs of the individual patient.

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  • 27.
    Blomstedt, Yulia
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Stenmark Persson, Rasmus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Awad, Amar
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Philipson, Johanna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. UCL Institute of Neurology, Queen Square, London, United Kingdom.
    Fytagoridis, Anders
    Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    10 years follow-up of deep brain stimulation in the caudal zona incerta/posterior subthalamic area for essential tremor2023In: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 10, no 5, p. 783-793Article in journal (Refereed)
    Abstract [en]

    Background: Long-term data on the effects of deep brain stimulation (DBS) for essential tremor (ET) is scarce, especially regarding DBS in the caudal Zona incerta (cZi) and the posterior subthalamic area (PSA). Objectives: The aim of this prospective study was to evaluate the effect of cZi/PSA DBS in ET at 10 years after surgery.

    Methods: Thirty-four patients were included. All patients received cZi/PSA DBS (5 bilateral/29 unilateral) and were evaluated at regular intervals using the essential tremor rating scale (ETRS).

    Results: One year after surgery, there was a 66.4% improvement of total ETRS and 70.7% improvement of tremor (items 1–9) compared with the preoperative baseline. Ten years after surgery, 14 patients had died and 3 were lost to follow-up. In the remaining 17 patients, a significant improvement was maintained (50.8% for total ETRS and 55.8% for tremor items). On the treated side the scores of hand function (items 11–14) had improved by 82.6% at 1 year after surgery, and by 66.1% after 10 years. Since off-stimulation scores did not differ between year 1 and 10, this 20% deterioration of on-DBS scores was interpreted as a habituation. There was no significant increase in stimulation parameters beyond the first year.

    Conclusions: This 10 year follow up study, found cZi/PSA DBS for ET to be a safe procedure with a mostly retained effect on tremor, compared to 1 year after surgery, and in the absence of increase in stimulation parameters. The modest deterioration of effect of DBS on tremor was interpreted as habituation.

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  • 28. Capelle, Hans-Holger
    et al.
    Blahak, Christian
    Schrader, Christoph
    Baezner, Hansjoerg
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Krauss, Joachim K.
    Bilateral deep brain stimulation for cervical dystonia in patients with previous peripheral surgery2012In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 27, no 2, p. 301-304Article in journal (Refereed)
    Abstract [en]

    Background: There are no data available concerning whether patients with cervical dystonia who have recurrent or new symptoms after peripheral denervation surgery benefit similarly from pallidal deep brain stimulation compared with patients who receive primarily pallidal stimulation. Methods: Data on 7 cervical dystonia patients with recurrent or progressive dystonia after peripheral denervation who underwent pallidal stimulation were prospectively collected. Deep brain stimulation was performed in Mannheim/ Hannover, Germany, or in Umea, Sweden. To the subgroup from Mannheim/Hannover, a second group of patients without previous peripheral surgery was matched. Assessments included the Toronto Western Spasmodic Torticollis Rating Scale and the Burke-FahnMarsden dystonia rating scale, as well as the Tsui scale in the Swedish patients. Results: The 4 patients from Mannheim/Hannover experienced sustained improvement from pallidal stimulation by a mean of 57.5% according to the Toronto Western Spasmodic Torticollis Rating Scale (P <.05) and by a mean of 69.5% according to the Burke-FahnMarsden dystonia rating scale (P <.05) at long-term follow-up of 40.5 months. The patients from Umea had a mean Tsui score of 7 prior to surgery and a mean score of 3 at the mean follow-up of 8 months (62.5%). In the matched group the Toronto Western Spasmodic Torticollis Rating Scale improved by 58.8% and the Burke-Fahn-Marsden dystonia rating scale by 67% (P <.05) at long-term follow-up (mean, 41.5 months). Conclusions: Patients who had prior peripheral surgery for cervical dystonia experience improvement from subsequent pallidal stimulation that is comparable to that of de novo patients. (C) 2011 Movement Disorder Society

  • 29. Cappon, Davide
    et al.
    Beigi, Mazda
    Kefalopoulou, Zinovia
    Zrinzo, Ludvic
    Candelario, Joseph
    Milabo, Catherine
    Akram, Harith
    Dayal, Viswas
    Hyam, Jonathan
    Kass-Iliyya, Lewis
    Silverdale, Monty
    Evans, Julian
    Limousin, Patricia
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK.
    Joyce, Eileen
    Foltynie, Thomas
    Jahanshahi, Marjan
    Globus pallidal deep brain stimulation for Tourette syndrome: Effects on cognitive function2019In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 69, p. 14-18Article in journal (Refereed)
    Abstract [en]

    Introduction: In a double-blind randomized crossover trial, we previously established that bilateral deep brain stimulation of the anteromedial globus pallidus internus (GPiam-DBS) is effective in significantly reducing tic severity in patients with refractory Tourette syndrome (TS). Here, we report the effects of bilateral GPiam-DBS on cognitive function in 11 of the 13 patients who had participated in our double-blind cross-over trial of GPi-DBS.

    Methods: Patients were assessed at baseline (4 weeks prior to surgery) and at the end of each of the three-month blinded periods, with stimulation either ON or OFF. The patients were evaluated on tests of memory (California Verbal Learning Test-II (CVLT-II); Corsi blocks; Short Recognition Memory for Faces), executive function (D-KEFS Stroop color-word interference, verbal fluency, Trail-making test, Hayling Sentence Completion test), and attention (Paced Auditory Serial Addition Test, Numbers and Letters Test).

    Results: GPiam-DBS did not produce any significant change in global cognition. Relative to pre-operative baseline assessment verbal episodic memory on the CVLT-II and set-shifting on the Trail-making Test were improved with DBS OFF. Performance on the cognitive tests were not different with DBS ON versus DBS OFF. GPiam-DBS did not alter aspects of cognition that are impaired in TS such as inhibition on the Stroop interference task or the Hayling Sentence Completion test.

    Conclusions: This study extends previous findings providing data showing that GPiam-DBS does not adversely affect cognitive domains such as memory, executive function, verbal fluency, attention, psychomotor speed, and information processing. These results indicate that GPiam-DBS does not produce any cognitive deficits in TS.

  • 30.
    Cappon, Davide
    et al.
    Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom; Hinda and Arthur Marcus Institute for Aging Research, Hebrew Senior Life, MA, Boston, United States; Deanna and Sidney Wolk Center for Memory Health, Hebrew Senior Life, MA, Boston, United States; Department of Neurology, Harvard Medical School, MA, Boston, United States.
    Gratwicke, James
    Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
    Zrinzo, Ludvic
    Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
    Akram, Harith
    Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
    Hyam, Jonathan
    Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
    Limousin, Patricia
    Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
    Foltynie, Thomas
    Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
    Jahanshahi, Marjan
    Unit of Functional Neurosurgery, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, United Kingdom.
    Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson's Disease Dementia: A 36 Months Follow Up Study2022In: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 9, no 6, p. 765-774Article in journal (Refereed)
    Abstract [en]

    Background: Degeneration of the nucleus basalis of Meynert (NBM) and cortical cholinergic dysfunction are hallmarks of Parkinson's disease dementia (PDD). There is no effective therapy for PDD. Deep brain stimulation of the NBM (NBM-DBS) has been trialed as a potential treatment.

    Objective: Our primary aim was to evaluate the sustained tolerability of NBM-DBS in PDD, and its impact on global cognition, behavioral symptoms, quality of life and caregiver burden and distress. Second, we aimed to determine whether baseline measures of arousal, alertness, and attention were predictive of the three year response to NBM-DBS in PDD patients.

    Methods: Five of the six PDD patients who completed the baseline assessment participated in a 3 year follow up assessment. We assessed the participants after three years of NBM-DBS on the Mini Mental State Examination, Dementia Rating Scale-2, Blessed Dementia Rating Scale, Neuropsychiatric Inventory, and the SF36.

    Results: The five patients showed varying trajectories of cognitive decline, with two showing a slower progression over the three-year follow-up period. A slower progression of decline on global cognition was associated with higher baseline accuracy on the Posner covert orienting of attention test, and less daytime sleepiness.

    Conclusions: Whether slower progression of cognitive decline in two patients was in any way related to individual variability in responsiveness to NBM-DBS requires confirmation in a larger series including an unoperated PDD control group. Higher accuracy in covertly orienting attention and better sleep quality at baseline were associated with better cognitive outcomes at 36 months assessment. These results require validation in future studies with larger samples.

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  • 31. Cif, Laura
    et al.
    Hariz, Marwan
    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.
    Seventy Years of Pallidotomy for Movement Disorders2017In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 32, no 7, p. 972-982Article in journal (Other academic)
    Abstract [en]

    The year 2017 marks the 70th anniversary of the birth of human stereotactic neurosurgery. The first procedure was a pallidotomy for Huntington's disease. However, it was for Parkinson's disease that pallidotomy was soon adopted worldwide. Pallidotomy was abandoned in the late 1950s in favor of thalamotomy because of the latter's more striking effect on tremor. The advent of levodopa put a halt to all surgery for PD. In the mid-1980s, Laitinen reintroduced the posteroventral pallidotomy of Leksell, and this procedure spread worldwide thanks to its efficacy on most parkinsonian symptoms including levodopa-induced dyskinesias and thanks to basic scientific work confirming the role of the globus pallidus internus in the pathophysiology of PD. With the advent of deep brain stimulation of the subthalamic nucleus, pallidotomy was again abandoned, and even DBS of the GPi has been overshadowed by STN DBS. The GPi reemerged in the late 1990s as a major stereotactic target for DBS in dystonia and, recently, in Tourette syndrome. Lately, lesioning of the GPI is being proposed to treat refractory status dystonicus or to treat DBS withdrawal syndrome in PD patients. Hence, the pallidum as a stereotactic target for either lesioning or DBS has been the phoenix of functional stereotactic neurosurgery, constantly abandoned and then rising again from its ashes. This review is a tribute to the pallidum on its 70th anniversary as a surgical target for movement disorders, analyzing its ebbs and flows and highlighting its merits, its versatility, and its resilience.

  • 32. Cif, Laura
    et al.
    Ruge, Diane
    Gonzalez, Victoria
    Limousin, Patricia
    Vasques, Xavier
    Hariz, Marwan I.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Rothwell, John
    Coubes, Philippe
    The Influence of Deep Brain Stimulation Intensity and Duration on Symptoms Evolution in an OFF Stimulation Dystonia Study2013In: Brain stimulation, ISSN 1935-861X, Vol. 6, no 4, p. 500-505Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is an established therapy for primary generalized dystonia. However, the evolution of dystonia symptoms after DBS discontinuation after years of therapy has only rarely been reported. We therefore longitudinally studied the main physiological measurements known to be impaired in dystonia, with DBS ON and then again after termination of DBS, after at least five years of continuous DBS. Objective: We studied whether dystonia evolution after DBS discontinuation in patients benefiting from long-term GPi DBS is different from that observed in earlier stages of the therapy. Methods: In eleven DYT1 patients treated with bilateral GPi DBS for at least 5 years, dystonia was assessed ON-DBS, immediately after switch-off (OFF-DBS1) and 48 h after DBS termination (OFF-DBS2). We studied the influence of DBS intensity on dystonia when DBS was discontinued. Results: On average a significant difference in symptoms was measured only between ON-DBS and OFF-DBS1 conditions. Importantly, none of the patients returned to their preoperative dystonia severity, even 48 h after discontinuation. The amount of clinical deterioration in the OFF conditions positively correlated with higher stimulation current in the chronic ON-DBS condition. Conclusions: The duration of DBS application influences symptom evolution after DBS termination. DBS intensity seems to have a prominent role on evolution of dystonic symptoms when DBS is discontinued. In conclusion, DBS induces changing modulation of the motor network with less worsening of symptoms after long term stimulation, when DBS is stopped.

  • 33. Dayal, Viswas
    et al.
    Grover, Timothy
    Tripoliti, Elina
    Milabo, Catherine
    Salazar, Maricel
    Candelario-McKeown, Joseph
    Athauda, Dilan
    Zrinzo, Ludvic
    Akram, Harith
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Limousin, Patricia
    Foltynie, Thomas
    Short Versus Conventional Pulse-Width Deep Brain Stimulation in Parkinson's Disease: A Randomized Crossover Comparison2020In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 35, no 1, p. 101-108Article in journal (Refereed)
    Abstract [en]

    Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for selected Parkinson's disease patients with motor fluctuations, but can adversely affect speech and axial symptoms. The use of short pulse width (PW) has been shown to expand the therapeutic window acutely, but its utility in reducing side effects in chronic STN-DBS patients has not been evaluated. Objective To compare the effect of short PW settings using 30-mu s with conventional 60-mu s settings on stimulation-induced dysarthria in Parkinson's disease patients with previously implanted STN-DBS systems.

    Methods: In this single-center, double-blind, randomized crossover trial, we assigned 16 Parkinson's disease patients who had been on STN-DBS for a mean of 6.5 years and exhibited moderate dysarthria to 30-mu s or 60-mu s settings for 4 weeks followed by the alternative PW setting for a further 4 weeks. The primary outcome was difference in dysarthric speech measured by the Sentence Intelligibility Test between study baseline and the 2 PW conditions. Secondary outcomes included motor, nonmotor, and quality of life measures.

    Results: There was no difference in the Sentence Intelligibility Test scores between baseline and the 2 treatment conditions (P = 0.25). There were also no differences noted in motor, nonmotor, or quality of life scores. The 30-mu s settings were well tolerated, and adverse event rates were similar to those at conventional PW settings. Post hoc analysis indicated that patients with dysarthria and a shorter duration of DBS may be improved by short PW stimulation.

    Conclusions: Short PW settings using 30 mu s did not alter dysarthric speech in chronic STN-DBS patients. A future study should evaluate whether patients with shorter duration of DBS may be helped by short PW settings.

  • 34.
    Dayal, Viswas
    et al.
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Rajabian, Ali
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Jahanshahi, Marjan
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Aviles-Olmos, Iciar
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Cowie, Dorothy
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Peters, Amy
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Day, Brian
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Hyam, Jonathan
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Akram, Harith
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Limousin, Patricia
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Zrinzo, Ludvic
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Foltynie, Thomas
    Department of Clinical and Movement Neurosciences, University College London Institute of Neurology, and the National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
    Pedunculopontine nucleus deep brain stimulation for parkinsonian disorders: a case series2021In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 99, no 4, p. 287-294Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in parkinsonian disorders, with equivocal results so far.

    Objectives: To summarize the clinical outcomes of PPN-DBS-treated patients at our centre and elicit any patterns that may guide future research.

    Materials and Methods: Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for 6 PPN-DBS-treated patients, 3 with Parkinson's disease (PD), and 3 with progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first 3 patients and bilaterally in the latter 3, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20-30 Hz and optimized in an iterative manner.

    Results: Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PD patient with habituation to the initial benefit reproduced substantial improvements in freezing of gait (FOG) 3 years post-operatively. Among the PSP patients, 1 with a parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit.

    Conclusions: PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation; the response in PSP patients may depend on the disease subtype; and diurnal cycling of stimulation to overcome habituation merits further investigation.

  • 35. Foltynie, T
    et al.
    Zrinzo, L
    Martinez-Torres, I
    Tripoliti, E
    Petersen, E
    Holl, E
    Aviles-Olmos, I
    Jahanshahi, M
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Limousin, P
    MRI-guided STN DBS in Parkinson's disease without microelectrode recording: efficacy and safety2011In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 82, no 4, p. 358-363Article in journal (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinson's disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6)&emsp14;mm. There were no haemorrhagic complications. At a median follow-up period of 12&emsp14;months, there was a mean improvement in the off-medication motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinson's disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.

  • 36. Foltynie, Thomas
    et al.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Surgical management of Parkinson's disease2010In: Expert review of neurotherapeutics, ISSN 1744-8360, Vol. 10, no 6, p. 903-914Article in journal (Refereed)
    Abstract [en]

    There has been a renaissance in the surgical treatment of Parkinson's disease (PD) over the last 15-20 years as a result of the long-term complications of L-DOPA use. The current cornerstone of surgical treatment for PD is high-frequency deep-brain stimulation (DBS) of the subthalamic nucleus (STN) using implantable electrodes and an implantable pulse generator/battery. Among well-selected patients, that is, patients with idiopathic PD, L-DOPA-responsive symptoms and no significant psychiatric comorbidities or cognitive decline, STN DBS can provide improvements in motor symptoms and quality of life, with low risks of adverse effects. In this article, we briefly describe the evolution of surgical treatments for PD, and the rationale for current DBS procedures. We also provide details of our practice, including patient selection, surgical technique and postoperative stimulation programming and medication adjustment. Current and possible future alternatives to DBS of the STN are also discussed.

  • 37.
    Georgiev, Dejan
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy. Department of Neurology, University Clinical Centre Ljubljana, Ljubljana, Slovenia; Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, UK.
    Hamberg, Katarina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College London, London, UK.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hariz, Gun-Marie
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Gender differences in Parkinson's disease: a clinical perspective2017In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 6, p. 570-584Article in journal (Refereed)
    Abstract [en]

    Available data indicate that there are gender differences in many features of Parkinson's disease (PD). Precise identification of the gender differences is important to tailor treatment, predict outcomes, and meet other individual and social needs in women and men with PD. The aim of this study was to review the available clinical data on gender differences in PD. Original articles and meta-analyses published between 1990 and 2016 systematically exploring gender differences in PD were reviewed. There is slight male preponderance in incidence and prevalence of PD. PD starts earlier in men. Women tend to be more prone to develop tremor-dominant PD but are less rigid than men. Motor improvement after deep brain stimulation is equal in both sexes, but women tend to show better improvement in activities of daily living. Furthermore, women with PD show better results on tests for general cognitive abilities, outperform men in verbal cognitive tasks, show more pain symptoms, and score higher on depression scales. It seems, however, that the differences in cognition, mood, and pain perception are not disease specific as similar gender differences can be found in healthy subjects and in other neurological conditions. Despite PD being the most frequently studied movement disorder, studies investigating gender differences in PD are still scarce with most of the studies being cross-sectional. Good-quality, prospective, longitudinal studies analyzing gender differences in PD and comparing them to matched healthy controls are needed in order to properly address the issues of gender differences in PD.

  • 38. Gratwicke, James
    et al.
    Oswal, Ashwini
    Akram, Harith
    Jahanshahi, Marjan
    Hariz, Marwan
    Department of Clinical and Movement Neurosciences, UCL Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
    Zrinzo, Ludvic
    Foltynie, Tom
    Litvak, Vladimir
    Resting state activity and connectivity of the nucleus basalis of Meynert and globus pallidus in Lewy body dementia and Parkinson's disease dementia2020In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 221, article id 117184Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are two related diseases which can be difficult to distinguish. There is no objective biomarker which can reliably differentiate between them. The synergistic combination of electrophysiological and neuroimaging approaches is a powerful method for interrogation of functional brain networks in vivo. We recorded bilateral local field potentials (LFPs) from the nucleus basalis of Meynert (NBM) and the internal globus pallidus (GPi) with simultaneous cortical magnetoencephalography (MEG) in six PDD and five DLB patients undergoing surgery for deep brain stimulation (DBS) to look for differences in underlying resting-state network pathophysiology. In both patient groups we observed spectral peaks in the theta (2-8 Hz) band in both the NBM and the GPi. Furthermore, both the NBM and the GPi exhibited similar spatial and spectral patterns of coupling with the cortex in the two disease states. Specifically, we report two distinct coherent networks between the NBM/GPi and cortical regions: (1) a theta band (2-8 Hz) network linking the NBM/GPi to temporal cortical regions, and (2) a beta band (13-22 Hz) network coupling the NBM/GPi to sensorimotor areas. We also found differences between the two disease groups: oscillatory power in the low beta (13-22Hz) band was significantly higher in the globus pallidus in PDD patients compared to DLB, and coherence in the high beta (22-35Hz) band between the globus pallidus and lateral sensorimotor cortex was significantly higher in DLB patients compared to PDD. Overall, our findings reveal coherent networks of the NBM/GPi region that are common to both DLB and PDD. Although the neurophysiological differences between the two conditions in this study are confounded by systematic differences in DBS lead trajectories and motor symptom severity, they lend support to the hypothesis that DLB and PDD, though closely related, are distinguishable from a neurophysiological perspective.

  • 39. Hamel, Wolfgang
    et al.
    Koeppen, Johannes A.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. nit of Functional Neurosurgery, UCL Institute of Neurology, London, UK.
    Krack, Paul
    Moll, Christian K. E.
    The Pioneering and Unknown Stereotactic Approach of Roeder and Orthner from Gottingen. Part I. Surgical Technique for Tailoring Individualized Stereotactic Lesions2016In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, no 4, p. 240-253Article in journal (Refereed)
    Abstract [en]

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

  • 40. 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.

  • 41.
    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.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Lindberg, Margareta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Assessment of ability/disability in patients treated with chronic thalamic stimulation for tremor.1998In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 13, no 1, p. 78-83Article in journal (Refereed)
    Abstract [en]

    Chronic thalamic stimulation (CTS) has a documented good effect on tremor in patients with Parkinson's disease (PD) and essential tremor (ET). This study evaluates whether the alleviation of impairment, i.e., tremor, translates into improvement of the patient's ability in performing instrumental activities of daily living (IADL). Thirteen patients were assessed with an occupational therapy tool called Assessment of Motor and Process Skills (AMPS). This observation-based scale rates the patient's motor and process skills needed to perform a given task. The evaluations were done at a mean of 13 months after surgery in the patient's home, and included assessments of IADL with the CTS activated and switched off, respectively. The results showed that most patients improved to variable degrees in their IADL ability when the thalamic stimulation was on. The improvement was more marked in patients operated on for tremor of their dominant hand. The improvement concerned mainly the skill items related to the patients' abilities of coordination, calibration, endurance, and accommodation during IADL task performance. The authors concluded that for some patients with tremor, CTS can improve independence in domestic activities of daily living.

  • 42.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Fredricks, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Stenmark Persson, Rasmus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences. UCL Institute of Neurology, Queen Square, London, UK.
    Forsgren, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Blinded Versus Unblinded Evaluations of Motor Scores in Patients with Parkinson's Disease Randomized to Deep Brain Stimulation or Best Medical Therapy2021In: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 8, no 2, p. 285-287Article in journal (Refereed)
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  • 43.
    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.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Gender distribution in surgery for Parkinson's disease.2000In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 6, no 3, p. 155-157Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease (PD) affects both women and men. The surgical treatment of this disease has experienced a worldwide increase since the mid-eighties. In order to document eventual differences in gender distribution of patients undergoing various stereotactic surgical procedures for PD, we reviewed scientific papers published during the last 14years.A literature search provided 145 clinical papers, published between January 1985 and February 1999, and dealing with pallidotomy, thalamotomy and deep brain stimulation procedures. These papers were scrutinised with respect to redundancies or other overlap of reported patients. The resulting numbers of patients were compiled according to gender, to surgical procedure, and to geographic area of origin of the publishing centers.In one third of the reviewed publications the gender of the patients was not specified. In the remaining papers, the overall sex distribution of patients who underwent surgery was 35% females and 65% males. These proportions between sexes were relatively consistent regardless of surgical procedure, and regardless of geographic origin of the publications.Male preponderance in patients undergoing surgery for PD cannot be explained by a corresponding difference in gender-prevalence of the disease. The criteria of selection, and patterns of referral, of patients for surgery, as well as the respective attitude of female and male patients toward surgery, may account for the uneven gender distribution in surgical PD patients.

  • 44.
    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.

  • 45.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Lindberg, Margareta
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Hariz, Marwan I
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Bergenheim, A Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Gender differences in disability and health-related quality of life in patients with Parkinson's disease treated with stereotactic surgery2003In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 108, no 1, p. 28-37Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    To investigate eventual differences between women and men with Parkinson's disease (PD) before and after surgery, with respect to clinical status, disability and health-related quality of life (HRQoL).

    MATERIAL AND METHODS:

    Twenty-four men and 14 women with PD received a total of 46 surgical procedures (pallidotomy, thalamotomy and deep brain stimulation of the thalamus, pallidum or subthalamic nucleus). The impact of PD on disability and other aspects of HRQoL was analysed separately in men and women before and at a mean of 11 months after surgery, using the following assessment tools: The Unified Parkinson's Disease Rating Scale (UPDRS), the ADL Taxonomy, the Nottingham Health Profile, the Life Satisfaction Questionnaire and a Visual Analogue Scale.

    RESULTS:

    At surgery, women had a significantly longer duration of disease than men (mean: 15 vs. 10 years, P < 0.01). They had a higher stage on the Hoehn and Yahr scale and worse scores on UPDRS parts II (ADL) and IV (complications), as well as on the Schwab and England scale and on the ADL Taxonomy. Following surgery, both men and women showed improvement, but women experienced greater benefit than men in ADL, in emotions, and in social life.

    CONCLUSIONS:

    Perhaps women with PD should be offered surgery more often and earlier in the course of their disease.

  • 46.
    Hariz, Gun-Marie
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation.
    Rehncrona, Stig
    Blomstedt, Patric
    Limousin, Patricia
    Hamberg, Katarina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. UCL Institute of Neurology, Queen Square, London, UK.
    Women pioneers in basal ganglia surgery2014In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 20, no 2, p. 137-141Article, review/survey (Refereed)
    Abstract [en]

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

  • 47.
    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)
  • 48.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. UCL Institute of Neurology, Department of Clinical Neuroscience, London, United Kingdom.
    DBS in psychiatry and the pendulum of history2015In: Neurosurgical treatments for psychiatric disorders / [ed] Bomin Sun; Antonio De Salles, Springer, 2015, p. 47-51Chapter in book (Refereed)
    Abstract [en]

    Recent published statements on Deep brain stimulationdeep brain stimulation (DBS) by psychiatrists and ethicists claim that DBS was developed first for movement disorders and is now applied in psychiatry; that it was the behavioural and psychiatric side-effects of DBS in subthalamic nucleus (STN) in Parkinsonian patients that prompted investigation of DBS in psychiatry; and that neurosurgeons should not act alone in this field, but should be within multidisciplinary teams in order not to repeat abuses of the past. The present author conducted a review of old literature since the birth of human stereotactic neurosurgery in 1947 and established the following: (1) The first applications of DBS in the early 1950s were in the field of psychiatry, and promoted mainly by neurologists and psychiatrists without involvement of neurosurgeons. (2) Some of these old psychiatric applications of DBS were found to be dubious and precarious even by yesterday’s ethical standards. (3) Modern DBS for psychiatric illness started in 1999 on the initiative of neurosurgeons who had involved from the beginning psychiatrists, and it had nothing to do with non-motor side-effects of STN DBS. (4) A recent consensus meeting on psychiatric DBS insisted in its guidelines on multidisciplinarity and included 30 panelists none of whom a neurosurgeon.

  • 49.
    Hariz, Marwan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience. Unit of Functional Neurosurgery, UCL Institute of Neurology, Queen Square, London, United Kingdom.
    Deep brain stimulation: new techniques2014In: Parkinsonism & Related Disorders, ISSN 1353-8020, E-ISSN 1873-5126, Vol. 20, no Suppl.1, p. S192-S196Article in journal (Refereed)
    Abstract [en]

    The technology of the hardware used in deep brain stimulation (DBS), and the mode of delivering the stimulation have not significantly evolved since the start of the modern era of DBS 25 years ago.However, new technology is now being developed along several avenues. New features of the implantable pulse generator (IPG) allow fractionation of the electric current into variable proportions between different contacts of the multi-polar lead. Another design consists in leads that allow selective current steering from directionally placed electrode contacts that would deliver the stimulation in a specific direction or even create a directional shaped electric field that would conform to the anatomy of the brain target aimed at, avoiding adjacent structures, and thus avoiding side effects.Closed loop adaptive stimulation technologies are being developed, allowing a tracking of the pathological local field potential of the brain target, and delivering automatically the stimulation to suppress the pathological activity as soon as it is detected and for as long as needed. This feature may contribute to a DBS therapy "on demand", instead of continuously.Finally, advances in imaging technology are providing "new" brain targets, and increasingly allowing DBS to be performed accurately while avoiding the risks of microelectrode recording. 

  • 50.
    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)
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