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  • 1. Agren, Richard
    et al.
    Bartek, Jiri, Jr.
    Johansson, Anders
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Fytagoridis, Anders
    Pulse Width and Implantable Pulse Generator Longevity in Pallidal Deep Brain Stimulation for Dystonia: A Population-Based Comparative Effectiveness Study2020In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 98, no 5, p. 331-336Article in journal (Refereed)
    Abstract [en]

    Introduction: A wide range of pulse widths (PWs) has been used in globus pallidus internus (GPi) deep brain stimulation (DBS) for dystonia. However, no specific PW has demonstrated clinical superiority, and the paradigm may differ among DBS centers.

    Objective: To investigate how different paradigms of PWs in GPi DBS for dystonia affect implantable pulse generator (IPG) longevities and energy consumption.

    Methods: Thirty-nine patients with dystonia treated with bilateral GPi DBS at 2 Swedish DBS centers from 2005 to 2015 were included. Different PW paradigms were used at the 2 centers, 60–90 µs (short PWs) and 450 µs (long PW), respectively. The frequency of IPG replacements, pulse effective voltage (PEV), IPG model, pre-/postoperative imaging, and clinical outcome based on the clinical global impression (CGI) scale were collected from the medical charts and compared between the 2 groups.

    Results: The average IPG longevity was extended for the short PWs (1,129 ± 50 days) compared to the long PW (925 ± 32 days; χ2 = 12.31, p = 0.0005, log-rank test). IPG longevity correlated inversely with PEV (Pearson’s r = –0.667, p < 0.0001). IPG longevities did not differ between Kinetra® and Activa® PC in the short (p = 0.319) or long PW group (p = 0.858). Electrode distances to the central sensorimotor region of the GPi did not differ between the short or long PW groups (p = 0.595). Pre- and postoperative CGI did not differ between groups.

    Conclusions: Short PWs were associated with decreased energy consumption and increased IPG longevity. These effects were not dependent on the IPG model or the anatomic location of the electrodes. PWs did not correlate with symptom severities or clinical outcomes. The results suggest that the use of short PWs might be more energy efficient and could therefore be preferred initially when programming patients with GPi DBS for dystonia.

  • 2. Androulidakis, Alexandros G
    et al.
    Kühn, Andrea A
    Chen, Chiung Chu
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Kempf, Florian
    Kupsch, Andreas
    Schneider, Gerd-Helge
    Doyle, Louise
    Dowsey-Limousin, Patricia
    Hariz, Marwan I
    Brown, Peter
    Dopaminergic therapy promotes lateralized motor activity in the subthalamic area in Parkinson's disease2007In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 130, no Pt 2, p. 457-468Article in journal (Other academic)
  • 3. 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.

  • 4.
    Asplund, Pär
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Bergenheim, A. Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Percutaneous Balloon Compression vs Percutaneous Retrogasserian Glycerol Rhizotomy for the Primary Treatment of Trigeminal Neuralgia2016In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 78, no 3, p. 421-428Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Despite >30 years of clinical use, the literature is still sparse when it comes to comparisons between percutaneous balloon compression (PBC) and percutaneous retrogasserian glycerol rhizolysis (PRGR) as treatments for trigeminal neuralgia.

    OBJECTIVE: To perform a retrospective cohort comparison between PBC and PRGR with regard to therapeutic effect, side effects, and complications.

    METHODS: Medical records and follow-up data from 124 primary PRGRs performed from 1986 to 2000 and 82 primary PBCs performed from 2000 to 2013 were reviewed. All patients had undergone clinical sensory testing and assessment of sensory thresholds. Analyses were performed to compare duration of pain relief, frequency of sensory disturbances, and side effects.

    RESULTS: Median duration of pain relief was 21 months after PRGR and 20 months after PBC. Both methods carried a high risk of hypesthesia/hypalgesia (P < .001) that was partly reversed with time. Decreased corneal sensibility was common after PRGR (P < .001) but not after PBC. Dysesthesia was more common after PRGR (23%) compared after PBC (4%; P < .001). Other side effects were noted but uncommon.

    CONCLUSION: PBC and PRGR are both effective as primary surgical treatment of trigeminal neuralgia. Both carry a risk of postoperative hypesthesia, but in this series, the side effect profile favored PBC. Furthermore, PBC is technically less challenging, whereas PRGR requires fewer resources. Between these 2 techniques, we propose PBC as the primary surgical technique for percutaneous treatment of trigeminal neuralgia on the basis of its lower incidence of dysesthesia, corneal hypesthesia, and technical failures.

    ABBREVIATIONS: MS, multiple sclerosisPBC, percutaneous balloon compressionPRGR, percutaneous retrogasserian glycerol rhizotomyTN, trigeminal neuralgiaThis is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work, provided it is properly cited. The work cannot be changed in any way or used commercially.

  • 5.
    Awad, Amar
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Deep brain stimulation in the caudal zona incerta modulates the sensorimotor cerebello-cerebral circuit in essential tremor2020In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 209, article id 116511Article in journal (Refereed)
    Abstract [en]

    Essential tremor is effectively treated with deep brain stimulation (DBS), but the neural mechanisms underlying the treatment effect are poorly understood. Essential tremor is driven by a dysfunctional cerebello-thalamo-cerebral circuit resulting in pathological tremor oscillations. DBS is hypothesised to interfere with these oscillations at the stimulated target level, but it is unknown whether the stimulation modulates the activity of the cerebello-thalamo-cerebral circuit during different task states (with and without tremor) in awake essential tremor patients. To address this issue, we used functional MRI in 16 essential tremor patients chronically implanted with DBS in the caudal zona incerta. During scanning, the patients performed unilateral tremor-inducing postural holding and pointing tasks as well as rest, with contralateral stimulation turned On and Off.

    We show that DBS exerts both task-dependent as well as task-independent modulation of the sensorimotor cerebello-cerebral regions (p ​≤ ​0.05, FWE cluster-corrected for multiple comparisons). Task-dependent modulation (DBS ​× ​task interaction) resulted in two patterns of stimulation effects. Firstly, activity decreases (blood oxygen level-dependent signal) during tremor-inducing postural holding in the primary sensorimotor cortex and cerebellar lobule VIII, and activity increases in the supplementary motor area and cerebellar lobule V during rest (p ​≤ ​0.05, post hoc two-tailed t-test). These effects represent differences at the effector level and may reflect DBS-induced tremor reduction since the primary sensorimotor cortex, cerebellum and supplementary motor area exhibit less motor task-activity as compared to the resting condition during On stimulation. Secondly, task-independent modulation (main effect of DBS) was observed as activity increase in the lateral premotor cortex during all motor tasks, and also during rest (p ​≤ ​0.05, post hoc two-tailed t-test). This task-independent effect may mediate the therapeutic effects of DBS through the facilitation of the premotor control over the sensorimotor circuit, making it less susceptible to tremor entrainment.

    Our findings support the notion that DBS in essential tremor is modulating the sensorimotor cerebello-cerebral circuit, distant to the stimulated target, and illustrate the complexity of stimulation mechanisms by demonstrating task-dependent as well as task-independent actions in cerebello-cerebral regions.

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  • 6.
    Awad, Amar
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Westling, Göran
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Functional imaging of Essential Tremor treated with Deep Brain Stimulation In the caudal Zona incerta2017Conference paper (Refereed)
  • 7.
    Awad, Amar
    et al.
    Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Grill, Filip
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Deep brain stimulation does not modulate fMRI resting- state functional connectivity in essential tremorManuscript (preprint) (Other academic)
  • 8.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Analysis of deep brain stimulation and ablative lesions in surgical treatment of movement disorders: with emphasis on safety aspects2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background The last decade has witnessed a renaissance of functional stereotactic neurosurgery in the treatment of patients with movement disorders, especially advanced Parkinson’s disease (PD), essential tremor (ET) and dystonia. Ablative lesions such as thalamotomy and pallidotomy have been gradually replaced by the technique of chronic deep brain stimulation (DBS) applied to targets in the basal ganglia and thalamus, and assumed to be more lenient to the brain than stereotactic radiofrequency lesions. Since the aim of functional neurosurgery is to alleviate symptoms of these chronic, progressive, non-fatal diseases, and to improve life quality of the patients, it is imperative that the surgical procedures remain safe and do not result in complications mitigating any anticipated positive effect of the surgery on the symptoms of the disease.

    Aim The aim of this thesis is to evaluate, compare and analyse the safety of various surgical procedures used to treat patients with movement disorders, and to document side effects and complications both peri operatively and in a long term follow-up. Further to compare the effects of pallidotomy and pallidal DBS, and to evaluate the longterm efficacy of Vim-DBS.

    Method 256 consecutive surgical procedures, 129 DBS and 127 stereotactic lesions, were reviewed with respect to complications in 197 treated patients. In a series of 119 patients operated on with DBS during a 10 year period, the occurrence of hardware related complications (infection, breakage, erosion etc) was documented and analysed. Additionally, the interference of external magnetic field with the stimulation was documented. In one patient operated on with subthalamic nucleus DBS, a highly unusual and unexpected psychiatric side effect was carefully analysed. In 5 patients operated on with both methods (lesion and DBS) on each hemisphere, respectively, the effect and side effects of each method were compared. The long term effect and side effects of thalamic DBS was analysed in a series of patients with ET followed for 7 years.

    Results There were no deaths and few severe neurological complications in this material. Unilateral ablative lesions in the pallidum were well tolerated by patients with advanced PD, while for tremor, thalamic DBS was much safer than thalamotomy, even if its effect on certain aspects of tremor could show some decrease of efficacy over time. Some of the side effects of lesioning are transient while most but not all side effects of DBS are reversible. Hardware-related complications were not uncommon especially in the early “learning curve” period, and the DBS technique, being a life-long therapy, will necessitate a life long follow up of patients. Provided safety protocols are followed and provided patient’s and carer’s education and awareness, external electromagnetic interference should not constitute a risk for patients with DBS. PD patients undergoing STN DBS should be carefully selected to avoid psychiatric or cognitive side effects, due to this brain target´s proximity to, and involvment in, non-motor associative and limbic circuitry.

    Conclusions In terms of mortality and morbidity, modern stereotactic neurosurgery for movement disorders, both ablation and DBS, is a safe procedure even in advanced stages of disease. Symptoms of PD, ET and dystonia can be alleviated mainly with DBS and even unilaterally with pallidal lesions, at the expense of, in most cases, minor side-effects.

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  • 9.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cataract surgery in ancient Egypt2014In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 40, no 3, p. 485-489Article, review/survey (Refereed)
    Abstract [en]

    Ophthalmology was one of the most important specialties in Egyptian medicine, and more specialists are known in this field than in any other. This specialization seems, however, to have been of a purely noninvasive nature. Even though it has been claimed that cataract surgery was performed in pharaonic Egypt, careful analysis of the sources does not support the claim. No example of cataract surgery or of any other invasive ophthalmologic procedure can be found in the original sources.

  • 10.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Cerebral Impaludation - An Ignoble Procedure between Two Nobel Prizes: Frontal Lobe Lesions before the Introduction of Leucotomy2020In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 98, no 3, p. 150-159Article in journal (Refereed)
    Abstract [en]

    During the 20th century, only two persons have been awarded the Nobel Prize for psychiatric discoveries, Julius Wagner-Jauregg in 1927 for the introduction of malaria inoculation in dementia paralytica and Egas Moniz in 1949 for prefrontal leucotomy. According to traditional narrative, Moniz was inspired by a presentation by Carlyle Jacobsen on prefrontal lesions in chimpanzees at a congress in London in 1935. A few months later, he performed the first operations with the help of a young neurosurgeon. These leucotomies were done using injections of a small amount of alcohol into each frontal lobe through a single burr hole on each side of the skull, and the findings from the first 20 patients were published soon after that in 1936. It has, however, been difficult to reconstruct the path leading Moniz to frontal leucotomy, due to his unwillingness to acknowledge contributions from others. Maurice Ducoste, psychiatrist at Villejuif in Paris, France, started his work with psychiatric patients in the early 1920s with mechanical lesions in schizophrenia and continued with injections into the frontal lobes. Later, he focused on general paresis of the insane in neurosyphilis. Here, he introduced injections of malaria-infested blood into the frontal lobes - cerebral impaludation. Injections were used also in schizophrenia, mania, melancholia, and other psychiatric conditions. These injections were up to 5 mL in volume and could be repeated up to 12 times in an individual patient, which must have created significant lesions. Ducoste performed his procedure in hundreds of psychiatric patients before Moniz attempted leucotomy, and his work was presented in several publications before that by Moniz. Moniz basically used the same entry point, target depth, and technique in his first leucotomies. The major difference was that Moniz used alcohol with the clear intent of producing a lesion. Further, Moniz must have been aware of the work of Ducoste, since they presented papers, one after the other, at a meeting of the French Academy of Medicine in 1932. Even so, Moniz never acknowledged any contribution by Ducoste. In my opinion, it would be appropriate to acknowledge the contribution of Maurice Ducoste to the introduction of lobotomy.

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  • 11.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Dental surgery in ancient Egypt2013In: Journal of the history of dentistry, ISSN 1089-6287, Vol. 61, no 3, p. 129-142Article in journal (Refereed)
    Abstract [en]

    Many different surgical procedures have over the years been attributed to the ancient Egyptians. This is also true regarding the field of dental surgery. The existence of dentists in ancient Egypt is documented and several recipes exist concerning dental conditions. However, no indications of dental surgery are found in the medical papyri or in the visual arts. Regarding the osteological material/mummies, the possible indications of dental surgery are few and weak. There is not a single example of a clear tooth extraction, nor of a filling or of an artificial tooth. The suggested examples of evacuation of apical abscesses can be more readily explained as outflow sinuses. Regarding the suggested bridges, these are constituted of one find likely dating to the Old Kingdom, and one possibly, but perhaps more likely, dating to the Ptolemaic era. Both seem to be too weak to have served any possible practical purpose in a living patient, and the most likely explanation would be to consider them as a restoration performed during the mummification process. Thus, while a form of dentistry did certainly exist in ancient Egypt, there is today no evidence of dental surgery.

  • 12.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hyperhidrosis caused by deep brain stimulation in the posterior subthalamic area2017In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 380, p. 277-279Article in journal (Refereed)
  • 13.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Imhotep and the discovery of cerebrospinal fluid2014In: Anatomy Research International, ISSN 2090-2743, E-ISSN 2090-2751, Vol. 2014, article id 256105Article in journal (Refereed)
    Abstract [en]

    Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned.

  • 14.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Orthopedic surgery in ancient Egypt2014In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 85, no 6, p. 670-676Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Ancient Egypt might be considered the cradle of medicine. The modern literature is, however, sometimes rather too enthusiastic regarding the procedures that are attributed an Egyptian origin. I briefly present and analyze the claims regarding orthopedic surgery in Egypt, what was actually done by the Egyptians, and what may have been incorrectly ascribed to them.

    METHODS: I reviewed the original sources and also the modern literature regarding surgery in ancient Egypt, concentrating especially on orthopedic surgery.

    RESULTS: As is well known, both literary sources and the archaeological/osteological material bear witness to treatment of various fractures. The Egyptian painting, often claimed to depict the reduction of a dislocated shoulder according to Kocher's method, is, however, open to interpretation. Therapeutic amputations are never depicted or mentioned in the literary sources, while the specimens suggested to demonstrate such amputations are not convincing.

    INTERPRETATION: The ancient Egyptians certainly treated fractures of various kinds, and with varying degrees of success. Concerning the reductions of dislocated joints and therapeutic amputations, there is no clear evidence for the existence of such procedures. It would, however, be surprising if dislocations were not treated, even though they have not left traces in the surviving sources. Concerning amputations, the general level of Egyptian surgery makes it unlikely that limb amputations were done, even if they may possibly have been performed under extraordinary circumstances.

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  • 15.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Tracheostomy in ancient Egypt2014In: Journal of Laryngology and Otology, ISSN 0022-2151, E-ISSN 1748-5460, Vol. 128, no 8, p. 665-668Article, review/survey (Refereed)
    Abstract [en]

    It has often been reported that the ancient Egyptians performed tracheostomies. An analysis of this claim demonstrates it to be founded on only two depictions from the Protodynastic period (thirty-first century BC). These depictions are difficult to reconcile with tracheostomy from an anatomical point of view and can more easily be explained as human sacrifices. Considering that Egyptian surgery included only minor procedures even at its zenith during later dynastic periods, it is difficult to imagine that they would have developed such an advanced procedure at such an early date.

  • 16.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Transnasal surgery2012In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 117, no 2, p. 381-382Article in journal (Refereed)
  • 17.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    When the head is too big for the frame2014In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 92, no 4, p. 264-264Article in journal (Refereed)
  • 18.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Bjartmarz, Hjalmar
    Intracerebral infections as a complication of deep brain stimulation2012In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 90, no 2, p. 92-96Article in journal (Refereed)
    Abstract [en]

    Background: Intracerebral infections after deep brain stimulation (DBS) are rare. The published material is limited to 2 case reports. A review of 20 publications of 3,818 patients focusing on complications of DBS did not reveal one single case. For that reason, we decided to present our own experience of 4 patients with this complication.

    Objectives: To analyze and present our material regarding intracerebral infections after DBS.

    Methods: Four patients with intracerebral infection after DBS were retrospectively analyzed. Results: The 4 patients exhibited signs of intracerebral infection 2-14 days after DBS for Parkinson's disease. CT and MRI verified signs of possible cerebral involvement. In 3 patients, positive cultures were obtained from the extracted electrodes. All patients recovered completely following treatment with antibiotics and removal of the implanted hardware. Two of the patients were later re-implanted.

    Conclusions: Intracerebral infection is a rare complication of DBS. It does, however, occur occasionally and should be taken into consideration when evaluating the risks of DBS.

    Copyright (c) 2012 S. Karger AG, Basel

  • 19.
    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.

  • 20.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Fytagoridis, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Tisch, S
    Deep brain stimulation of the posterior subthalamic area in the treatment of tremor2009In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 151, no 1, p. 31-36Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several studies have described lesional therapy in the posterior subthalamic area (PSA) in the treatment of various movement disorders. Recently, some publications have illustrated the effect of deep brain stimulation (DBS) in this area in patients with Parkinson's disease, essential tremor, MS-tremor, and other forms of tremor. Even though the clinical series is small, the reported benefits prompted us to explore DBS in this area in the treatment of tremor.

    METHOD: Five patients with tremor were operated using unilateral DBS of the PSA. Two patients had dystonic tremor, one primary writing tremor, one cerebellar tremor and the other neuropathic tremor. All patients were assessed before and 1 year after surgery using items 5 and 6 (tremor of the upper extremity), 11-14 (hand function), and when appropriate item 10 (handwriting) from the essential tremor rating scale.

    FINDINGS: The mean improvement on stimulation after 1 year was 87%. A pronounced and sustained microlesional effect was seen in several of the patients, and while the mean improvement off stimulation was 56% the reduction in the three patients with the most pronounced effect was 89%. The two patients with dystonic tremor did also become free of the dystonic symptoms and pain in the treated arm. No severe complication occurred.

    CONCLUSIONS: DBS of the PSA in this small group of patients had an excellent effect on the different forms of tremor, except for the neuropathic tremor where the effect was moderate. These preliminary results suggest PSA to be an effective target for the treatment of various forms of tremor. Further studies concerning indications, safety and efficacy of DBS in the posterior subthalamic area are required.

  • 21.
    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.

  • 22.
    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

  • 23.
    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)
  • 24.
    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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  • 25.
    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

  • 26.
    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.

  • 27.
    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.

  • 28.
    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.

  • 29.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Jabre, Mazen
    Bejjani, Boulos-Paul
    Koskinen, Lars-Owe
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Electromagnetic environmental influences on implanted deep brain stimulators2006In: Neuromodulation, ISSN 1094-7159, E-ISSN 1525-1403, Vol. 9, no 4, p. 262-269Article in journal (Refereed)
    Abstract [en]

    Objective.  The objective of this study was to report our observations on the external electromagnetic field influences on deep brain stimulation (DBS) in our patient population and how these influences affected our patients’ lives and other healthcare-related conditions.

    Materials and Methods.  We have retrospectively analyzed data concerning the effects of external electromagnetic fields on 172 of our patients implanted with DBS.

    Results.  Identifiable electromagnetic sources turned the implantable pulse generator (IPG) off in 20 patients. In two patients, these episodes necessitated replacement of the Itrel II IPG (Medtronic Inc., Minneapolis, MN, USA) with the magnetically shielded Kinetra IPG (Medtronic Inc.). Six patients received cardiac pacemakers, leading, in two patients, to interference between the systems. Our experience concerning magnetic resonance imaging, electrocardiogram (ECG), heart defibrillation, electro-cautery, and other sources of electromagnetic interference also is described.

    Conclusions.  External electromagnetic interference may, in rare cases, constitute a severe threat to the well-being of the patient implanted with a DBS system. Also, malfunction of a DBS system may constitute a medical emergency. Nevertheless, in spite of these external electromagnetic influences, we consider DBS to be a safe method, provided safety protocols are followed, and provided that provider awareness about potential hazards is present.

  • 30.
    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.

  • 31.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Naesström, Matilda
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Bodlund, Owe
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Deep brain stimulation in the bed nucleus of the stria terminalis and medial forebrain bundle in a patient with major depressive disorder and anorexia nervosa2017In: Clinical Case Reports, E-ISSN 2050-0904, Vol. 5, no 5, p. 679-684Article in journal (Refereed)
    Abstract [en]

    Key Clinical Message Deep brain stimulation (DBS) may be considered in severe cases of therapy-refractory major depressive disorder (MDD). However, DBS for MDD is still an experimental therapy. Therefore, it should only be administered in clinical studies driven by multidisciplinary teams, including surgeons with substantial experience of DBS in the treatment of other conditions.

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  • 32.
    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.

  • 33.
    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.
    Fytagoridis, Anders
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Tisch, Stephen
    Department of Neurology, St Vincent's Hospital, University of New South Wales, Sydney, Australia.
    The posterior subthalamic area in the treatment of movement disorders: past, present, and future2009In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 64, no 6, p. 1029-1038Article in journal (Refereed)
    Abstract [en]

    The introduction of thalamotomy in 1954 led naturally to exploration of the underlying subthalamic area, with the development of such procedures as campotomy and subthalamotomy in the posterior subthalamic area. The most popular of these procedures was the subthalamotomy, which was performed in thousands of patients for various movement disorders. Today, in the deep brain stimulation (DBS) era, subthalamic nucleus DBS is the treatment of choice for Parkinson's disease, whereas thalamic and pallidal DBS are mainly used for nonparkinsonian tremor and dystonia, respectively. The interest in DBS in the posterior subthalamic area has been quite limited, however, with a total of 95 patients presented in 14 articles. During recent years, interest has increased, and promising results have been published concerning both Parkinson's disease and nonparkinsonian tremor. We reviewed the literature to investigate the development of surgery in the posterior subthalamic area from the lesional era to the present.

  • 34.
    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.

  • 35.
    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.

  • 36.
    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.
    Tisch, Stephen
    Deep brain stimulation in the posterior subthalamic area in the treatment of essential tremor2010In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 25, no 10, p. 1350-1356Article in journal (Refereed)
    Abstract [en]

    To evaluate the posterior subthalamic area (PSA) as a target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). The ventral intermediate nucleus of the thalamus is the traditional target for DBS in the treatment of ET. Recent studies have presented beneficial effects of DBS in the PSA in the treatment of tremor. Twenty-one patients with ET were included in this study. All patients were evaluated before and 1 year after surgery, on and off stimulation, using the essential tremor rating scale (ETRS). A marked microlesional effect was noticed in 83%, in some cases obviating the need for electrical stimulation for many months. The total ETRS was reduced from 46.2 at baseline to 18.7 (60%). Item 5/6 (tremor of the upper extremity) was improved from 6.2 to 0.3 (95%), and items 11 to 14 (hand function) from 9.7 to 1.3 (87%) concerning the contralateral hand. Activities of daily living were improved by 66%. No severe complication occurred. Eight patients presented a postoperative mild dysphasia that regressed within days to weeks. DBS in the PSA resulted in a marked reduction of tremor.

  • 37.
    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.

  • 38.
    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.
    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, 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.

  • 39.
    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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  • 40.
    Blomstedt, Patric
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Taira, Takaomi
    Hariz, Marwan
    Rescue pallidotomy for dystonia through implanted deep brain stimulation electrode2016In: Surgical Neurology International, ISSN 2152-7806, E-ISSN 2152-7806, Vol. 7, p. S815-S817Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Some patients with deep brain stimulation (DBS), where removal of implants is indicated due to hardware related infections, are not candidates for later re-implantation. In these patients a rescue lesion through the DBS electrode has been suggested as an option. In this case report we present a patient where a pallidotomy was performed using the DBS electrode.

    CASE DESCRIPTION: An elderly woman with bilateral Gpi DBS suffered an infection around the left burr hole involving the DBS electrode. A unilateral lesion was performed through the DBS electrode before it was removed. No side effects were encountered. Burke-Fahn-Marsden (BFM) dystonia movement scale score was 39 before DBS. With DBS before lesioning BFM score was 2.5 points. The replacement of the left sided stimulation with a pallidotomy resulted in only a minor deterioration of the score to 5 points.

    CONCLUSIONS: In the case presented here a small pallidotomy performed with the DBS electrode provided a satisfactory effect on the patient's dystonic symptoms. Thus, rescue lesions through the DBS electrodes, although off-label, might be considered in patients with Gpi DBS for dystonia when indicated.

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  • 41.
    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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  • 42.
    Fytagoridis, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Complications and side effects of deep brain stimulation in the posterior subthalamic area.2010In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 88, no 2, p. 88-93Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The posterior subthalamic area (PSA), including the zona incerta and prelemniscal radiation (Raprl), has recently been presented in number of publications as a promising target for deep brain stimulation (DBS) in the treatment of various movement disorders. In order to evaluate the safety of the procedure, we analyzed our initial 40 patients for complications and side effects. METHODS: 40 patients treated with PSA DBS for Parkinson's disease, essential tremor and other forms of tremor were included. RESULTS: The most severe complication was 1 transient mild hemiparesis and 1 infection. Minor complications and side effects were relatively frequent, including mild transient dysphasia in 22.5% of the patients. CONCLUSIONS: Few serious complications were encountered, and we consider the PSA to be a safe target for DBS.

  • 43.
    Fytagoridis, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Neurosurgery, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm. Asia-Pacific Centre for Neuromodulation, Queensland Brain Institute, University of Queensland.
    Heard, Tomas
    Samuelsson, Jennifer
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Neurosurgery, Sahlgrenska University Hospital, Göteborg.
    Zsigmond, Peter
    Jiltsova, Elena
    Skyrman, Simon
    Skoglund, Thomas
    Coyne, Terry
    Silburn, Peter
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Surgical Replacement of Implantable Pulse Generator in Deep Brain Stimulation: Adverse Events and Risk Factors in a Multicenter Cohort2016In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, no 4, p. 235-239Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) is a growing treatment modality, and most DBS systems require replacement of the implantable pulse generator (IPG) every few years. The literature regarding the potential impact of adverse events of IPG replacement on the longevity of DBS treatments is rather scarce. Objective: To investigate the incidence of adverse events, including postoperative infections, associated with IPG replacements in a multicenter cohort. Methods: The medical records of 808 patients from one Australian and five Swedish DBS centers with a total of 1,293 IPG replacements were audited. A logistic regression model was used to ascertain the influence of possible predictors on the incidence of adverse events. Results: The overall incidence of major infections was 2.3% per procedure, 3.7% per patient and 1.7% per replaced IPG. For 28 of 30 patients this resulted in partial or complete DBS system removal. There was an increased risk of infection for males (OR 3.6, p = 0.026), and the risk of infection increased with the number of prior IPG replacements (OR 1.6, p < 0.005). Conclusions: The risk of postoperative infection with DBS IPG replacement increases with the number of previous procedures. There is a need to reduce the frequency of IPG replacements. 

  • 44.
    Fytagoridis, Anders
    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.
    Åström, Mattias
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor2012In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, no 3, p. 258-262Article in journal (Refereed)
    Abstract [en]

    Purpose The ventral intermediate nucleus of thalamus is the standard target for deep brain stimulation (DBS) in essential tremor (ET). However, favourable data have recently highlighted the caudal zona incerta (cZi) as an alternative target. Reports concerning the long-term results are however lacking, and we have therefore evaluated the long-term effects in our patients with ET and cZi DBS.

    Methods 18 patients were evaluated using the Essential Tremor Rating Scale (ETRS) before and on-/off-stimulation at 1 and 3-5 years after surgery (mean 48.5±10.6 months). Two patients were operated on bilaterally but all electrodes were evaluated separately. The stimulation parameters were recorded and the stimulation strength calculated.

    Results A baseline total ETRS mean score of 46.0 decreased to 21.9 (52.4%) at the final evaluation. On the treated side, tremor of the upper extremity (item 5 or 6) improved from 6.1 to 0.5 (91.8%) and hand function (items 11-14) improved from 9.3 to 2.0 (78.0%). Activities of daily living improved by 65.8%. There was no increase in stimulation strength over time.

    Conclusion cZi DBS is a safe and effective treatment for the long term suppression of ET.

  • 45.
    Fytagoridis, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Sjöberg, Richard
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Åström, Mattias
    Fredricks, Anna
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Effects of deep brain stimulation in the caudal Zona incerta on verbal fluency2013In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 91, no 1, p. 24-29Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) of the caudal zona incerta (cZi) is a relatively unexplored and promising treatment in patients with severe essential tremor (ET). Preliminary data further indicate that the ability to produce language may be slightly affected by the treatment.

    Objective: To evaluate the effects on verbal fluency following cZi DBS in patients with ET.

    Method: Seventeen consecutive patients who had undergone DBS of the cZi for ET were tested regarding verbal fluency before surgery, 3 days after surgery and after 1 year. Ten patients were also evaluated by comparing performance on versus off stimulation after 1 year.

    Results: The total verbal fluency score decreased slightly, but significantly, from 22.7 (SD = 10.9) before surgery to 18.1 (SD = 7.5) 3 days after surgery (p = 0.036). After 1 year the score was nonsignificantly decreased to 20.1 (SD = 9.7, p = 0.2678). There was no detectable difference between stimulation on and off after 1 year.

    Conclusion: There was a tendency of an immediate and mostly transient postoperative decline in verbal fluency following cZi DBS for ET. In some of the patients this reduction was, however, more pronounced and also sustained over time.

  • 46.
    Fytagoridis, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery. Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
    Åström, M.
    Wårdell, K.
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurosurgery.
    Stimulation-induced side effects in the posterior subthalamic area: distribution, characteristics and visualization2013In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 115, no 1, p. 65-71Article in journal (Refereed)
    Abstract [en]

    Objective: The posterior subthalamic area (PSA) is an emerging but relatively unexplored target for DBS treatment of tremor. The aim of the study was to explore the area further by evaluating the spatial distribution and the characteristics of stimulation-induced side effects in this area.

    Methods: Twenty-eight patients with essential tremor (ET) implanted with 33 DBS electrodes were evaluated concerning stimulation-induced side effects by testing each contact separately one year after surgery. The location of the side effects were plotted on axial slides of the Morel Stereotactic Atlas and a 3-dimensional model of the area for visualization was created.

    Results: Visualization of the contacts eliciting stimulation-induced side effects demonstrated that identical responses can be elicited from various points in the PSA and its vicinity. The majority of contacts inducing muscular affection and cerebellar symptoms, including dysarthria, could not be attributed to an effect on the internal capsule. Paresthesias, affecting various body parts were elicited throughout the area without a clear somatotopic pattern.

    Conclusion: Stimulation-induced side effects in the PSA and its vicinity were difficult to attribute to certain anatomical areas as the same response was induced from various locations. Therefore, this study could not provide a meaningful somatotopic map with regard to stimulation-induced side effects in the PSA.

  • 47.
    Fytagoridis, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience. Department of Clinical Neuroscience, Neurosurgery, Karolinska Institutet, Stockholm.
    Åström, Mattias
    Samuelsson, Jennifer
    Blomstedt, Patric
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Deep Brain Stimulation of the Caudal Zona Incerta: Tremor Control in Relation to the Location of Stimulation Fields2016In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, no 6, p. 363-370Article in journal (Refereed)
    Abstract [en]

    Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.

  • 48.
    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.
    Blomstedt, Patric
    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.
    Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life2008In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 118, no 6, p. 387-394Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 49.
    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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  • 50.
    Hariz, Marwan
    et al.
    Department of Clinical Neuroscience, University Hospital of Umeå, Umeå, Sweden; 2UCL-Queen Square Institute of Neurology, London, UK.
    Blomstedt, Patric
    Department of Clinical Neuroscience, University Hospital of Umeå, Umeå, Sweden.
    Deep brain stimulation for Parkinson's disease2022In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 292, no 5, p. 764-778Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease (PD) is a progressive neurodegenerative illness with both motor and nonmotor symptoms. Deep brain stimulation (DBS) is an established safe neurosurgical symptomatic therapy for eligible patients with advanced disease in whom medical treatment fails to provide adequate symptom control and good quality of life, or in whom dopaminergic medications induce severe side effects such as dyskinesias. DBS can be tailored to the patient's symptoms and targeted to various nodes along the basal ganglia-thalamus circuitry, which mediates the various symptoms of the illness; DBS in the thalamus is most efficient for tremors, and DBS in the pallidum most efficient for rigidity and dyskinesias, whereas DBS in the subthalamic nucleus (STN) can treat both tremors, akinesia, rigidity and dyskinesias, and allows for decrease in doses of medications even in patients with advanced stages of the disease, which makes it the preferred target for DBS. However, DBS in the STN assumes that the patient is not too old, with no cognitive decline or relevant depression, and does not exhibit severe and medically resistant axial symptoms such as balance and gait disturbances, and falls. Dysarthria is the most common side effect of DBS, regardless of the brain target. DBS has a long-lasting effect on appendicular symptoms, but with progression of disease, nondopaminergic axial features become less responsive to DBS. DBS for PD is highly specialised; to enable adequate selection and follow-up of patients, DBS requires dedicated multidisciplinary teams of movement disorder neurologists, functional neurosurgeons, specialised DBS nurses and neuropsychologists.

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