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3. Deep brain stimulation for obsessive–compulsive disorder: a crisis of access

Author

Visser-Vandewalle, Veerle, Andrade, Pablo, Mosley, Philip E., Greenberg, Benjamin D., Schuurman, Rick, McLaughlin, Nicole C., Voon, Valerie, Krack, Paul, Foote, Kelly D., Mayberg, Helen S., Figee, Martijn, Kopell, Brian H., Polosan, Mircea, Joyce, Eileen M., Chabardes, Stephan, Matthews, Keith, Baldermann, Juan C., Tyagi, Himanshu, Holtzheimer, Paul E., Bervoets, Chris, Hamani, Clement, Karachi, Carine, Denys, Damiaan, Zrinzo, Ludvic, Blomstedt, Patric, Naesström, Matilda, Abosch, Aviva, Rasmussen, Steven, Coenen, Volker A., Schlaepfer, Thomas E., Dougherty, Darin D., Domenech, Philippe, Silburn, Peter, Giordano, James, Lozano, Andres M., Sheth, Sameer A., Coyne, Terry, Kuhn, Jens, Mallet, Luc, Nuttin, Bart, Hariz, Marwan, and Okun, Michael S.

Published
2022
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6. Deep brain stimulation does not modulate resting-state functional connectivity in essential tremor

Author

Awad, Amar, Grill, Filip, Blomstedt, Patric, Nyberg, Lars, Eriksson, Johan, Awad, Amar, Grill, Filip, Blomstedt, Patric, Nyberg, Lars, and Eriksson, Johan

Abstract

While the effectiveness of deep brain stimulation in alleviating essential tremor is well-established, the underlying mechanisms of the treatment are unclear. Essential tremor, as characterized by tremor during action, is proposed to be driven by a dysfunction in the cerebello-thalamo-cerebral circuit that is evident not only during motor actions but also during rest. Stimulation effects on resting-state functional connectivity were investigated by functional MRI in 16 essential tremor patients with fully implanted deep brain stimulation in the caudal zona incerta during On-and-Off therapeutic stimulation, in a counterbalanced design. Functional connectivity was calculated between different constellations of sensorimotor as well as non-sensorimotor regions (as derived from seed-based and data-driven approaches), and compared between On and Off stimulation. We found that deep brain stimulation did not modulate resting-state functional connectivity. The lack of modulation by deep brain stimulation during resting-state, in combination with previously demonstrated effects on the cerebello-thalamo-cerebral circuit during motor tasks, suggests an action-dependent modulation of the stimulation in essential tremor.

Published
2024
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7. Deep Brain Stimulation with Double Targeting of the VIM and PSA for the Treatment of Rare Tremor Syndromes.

Author

Yilmaz, Atilla, Eray, Halit Anıl, Cakir, Murtaza, Ceylan, Mustafa, and Blomstedt, Patric

Abstract

Introduction: In tremor syndromes, pharmacological therapy is the primary treatment, but deep brain stimulation (DBS) is used when it is insufficient. We explore the use of DBS, focusing on the globus pallidus internus for dystonia and the ventral intermediate nucleus (VIM) for tremor conditions. We introduce the posterior subthalamic area (PSA) as a potential target, suggesting its efficacy in tremor reduction, particularly in rare tremor syndromes. We aim to evaluate the efficacy and safety of double targeting the VIM and PSA in rare tremor conditions, highlighting the limited existing data on this. Methods: Between 2019 and 2023, 22 patients with rare tremor syndromes were treated with bilateral DBS of the VIM and PSA. This case series consisted of 7 isolated head tremor, 1 hepatic encephalopathic tremor due to Abernethy syndrome, 2 voice tremor, 4 dystonic tremor, and 8 Holmes tremor (2 multiple sclerosis, 2 cerebellar insult, and 4 posttraumatic) patients. Patients' preoperative and 12-month postoperative tremor scores were compared, and the optimum VIM and PSA stimulation areas were investigated. Results: There was a significant reduction in the mean TRS score from 3.70 (±0.57) to 0.45 (±0.68) after 12 months of surgery. Specific outcomes for different indications were observed: for head tremor, 6 of 7 patients showed a reduction in TRS scores to 0 points; the vocal tremor patients demonstrated improvement; this change was not statistically significant, which is likely to be due to the low number of patients in this subgroup; the dystonic tremor patients showed either complete tremor abolition or a reduction in TRS scores; the Holmes tremor patients showed an 80% reduction in TRS scores; and the hepatic encephalopathy tremor and Abernethy syndrome patients showed a 75% improvement in TRS scores. The stimulation parameters converged on the VIM and dorsal PSA. Complications included the need for electrode repositioning, infections requiring electrode removal and re-implantation, dysarthria, and stimulation-induced ataxia, which was resolved by adjusting the stimulation parameters. Discussion: The literature on DBS for rare tremors is limited. Double targeting of the VIM and PSA appears to produce promising improvements on the outcomes reported in the existing literature on VIM-only DBS. The proximity of the VIM and PSA allows for flexible electrode placement, contributing to the potential success of the dual-target approach. We also discuss the theoretical advantages of targeting the PSA based on the distribution of tremor circuits, emphasizing the need for further research and electrophysiological studies. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Thirty years of global deep brain stimulation : 'plus ça change, plus c'est la même chose'?

Author

Hariz, Marwan, Cif, Laura, Blomstedt, Patric, Hariz, Marwan, Cif, Laura, and Blomstedt, Patric

Abstract

Background: The advent of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease 30 years ago has ushered a global breakthrough of DBS as a universal method for therapy and research in wide areas of neurology and psychiatry. The literature of the last three decades has described numerous concepts and practices of DBS, often branded as novelties or discoveries. However, reading the contemporary publications often elicits a sense of déjà vu in relation to several methods, attributes, and practices of DBS. Here, we review various applications and techniques of the modern-era DBS and compare them with practices of the past. Summary: Compared with modern literature, publications of the old-era functional stereotactic neurosurgery, including old-era DBS, show that from the very beginning multidisciplinarity and teamwork were often prevalent and insisted upon, ethical concerns were recognized, brain circuitries and rational for brain targets were discussed, surgical indications were similar, closed-loop stimulation was attempted, evaluations of surgical results were debated, and controversies were common. Thus, it appears that virtually everything done today in the field of DBS bears resemblance to old-Time practices, or has been done before, albeit with partly other tools and techniques. Movement disorders remain the main indications for modern DBS as was the case for lesional surgery and old-era DBS. The novelties today consist of the STN as the dominant target for DBS, the tremendous advances in computerized brain imaging, the sophistication and versatility of implantable DBS hardware, and the large potential for research. Key Messages: Many aspects of contemporary DBS bear strong resemblance to practices of the past. The dominant clinical indications remain movement disorders with virtually the same brain targets as in the past, with one exception: The STN. Other novel brain targets-that are so far subject to DBS trials-are the pedunculop

Published
2023
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15. Long-term follow-up of unilateral deep brain stimulation targeting the caudal zona incerta in 13 patients with parkinsonian tremor

Author

Stenmark Persson, Rasmus, Fytagoridis, Anders, Ryzhkov, Maxim, Hariz, Marwan, Blomstedt, Patric, Stenmark Persson, Rasmus, Fytagoridis, Anders, Ryzhkov, Maxim, Hariz, Marwan, and Blomstedt, Patric

Abstract

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease (PD) and other movement disorders. The ventral intermediate nucleus of the thalamus (Vim) is considered as the target of choice for tremor disorders, including tremor-dominant PD not suitable for DBS in the subthalamic nucleus (STN). In the last decade, several studies have shown promising results on tremor from DBS in the posterior subthalamic area (PSA), including the caudal zona incerta (cZi) located postero-medial to the STN. The aim of this study was to evaluate the long-term effect of unilateral cZi/PSA-DBS in patients with tremor-dominant Parkinson’s disease. Methods: Thirteen patients with PD with medically refractory tremor were included. The patients were evaluated using the motor part of the Unified Parkinson Disease Rating Scale (UPDRS) off/on medication before surgery and off/on medication and stimulation 1-2 years (short-term) after surgery and at a minimum of 3 years after surgery (long-term). Results: At short-term follow-up DBS improved contralateral tremor by 88% in the off-medication state. This improvement persisted after a mean of 62 months. Contralateral bradykinesia was improved by 40% at short-term and 20% at long-term follow-up and the total UPDRS-III by 33% at short-term and by 22% at long-term follow-up with stimulation alone. Conclusions: Unilateral cZi/PSA-DBS seems to remain an effective treatment for patients with severe Parkinsonian tremor several years after surgery. There was also a modest improvement on bradykinesia.

Published
2023
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16. How Sample Size Impacts Probabilistic Stimulation Maps in Deep Brain Stimulation

Author

Nordin, Teresa, Blomstedt, Patric, Hemm-Ode, Simone, Wårdell, Karin, Nordin, Teresa, Blomstedt, Patric, Hemm-Ode, Simone, and Wårdell, Karin

Abstract

Probabilistic stimulation maps of deep brain stimulation (DBS) effect based on voxel-wise statistics (p-maps) have increased in literature over the last decade. These p-maps require correction for Type-1 errors due to multiple testing based on the same data. Some analyses do not reach overall significance, and this study aims to evaluate the impact of sample size on p-map computation. A dataset of 61 essential tremor patients treated with DBS was used for the investigation. Each patient contributed with four stimulation settings, one for each contact. From the dataset, 5 to 61 patients were randomly sampled with replacement for computation of p-maps and extraction of high- and low-improvement volumes. For each sample size, the process was iterated 20 times with new samples generating in total 1140 maps. The overall p-value corrected for multiple comparisons, significance volumes, and dice coefficients (DC) of the volumes within each sample size were evaluated. With less than 30 patients (120 simulations) in the sample, the variation in overall significance was larger and the median significance volumes increased with sample size. Above 120 simulations, the trends stabilize but present some variations in cluster location, with a highest median DC of 0.73 for n = 57. The variation in location was mainly related to the region between the high- and low-improvement clusters. In conclusion, p-maps created with small sample sizes should be evaluated with caution, and above 120 simulations in single-center studies are probably required for stable results., Funding Agencies|Swedish Foundation for Strategic Research [SSF BD15-0032]; Swedish Research Council [VR 2016-03564]

Published
2023
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17. 10 years follow-up of deep brain stimulation in the caudal zona incerta/posterior subthalamic area for essential tremor

Author

Blomstedt, Yulia, Stenmark Persson, Rasmus, Awad, Amar, Hariz, Gun-Marie, Philipson, Johanna, Hariz, Marwan, Fytagoridis, Anders, Blomstedt, Patric, Blomstedt, Yulia, Stenmark Persson, Rasmus, Awad, Amar, Hariz, Gun-Marie, Philipson, Johanna, Hariz, Marwan, Fytagoridis, Anders, and Blomstedt, Patric

Abstract

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.

Published
2023
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18. Anthropology of Deep Brain Stimulation; the 30th Anniversary of STN DBS in 2023

Author

Hariz, Marwan, Blomstedt, Yulia, Blomstedt, Patric, Hariz, Gun-Marie, Hariz, Marwan, Blomstedt, Yulia, Blomstedt, Patric, and Hariz, Gun-Marie

Abstract

Background: The year 2023 marks the 30th anniversary of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson’s disease (PD). This procedure prompted a universal interest in DBS for various brain disorders and resulted in a unique expansion of clinical and scientific collaboration between many disciplines, with impact on many aspects of society. Objective: To study the anthropology of DBS, that is, its ethno-geographic origins, its evolution, its impact on clinicians and scientists, and its influence on society at large. Material and Methods: The authors scrutinized the geo-ethnic origins of the pioneers of modern DBS, and they evaluated, based on the literature and on a long-term praxis, the development of DBS and its impact on clinicians, on healthcare, and on society. Results: Scientists and clinicians from various geo-ethnic origins pioneered modern DBS, leading to worldwide spread of this procedure and to the establishment of large multidisciplinary teams in many centers. Neurologists became actively involved in surgery and took on new laborious tasks of programming ever more complicated DBS systems. Publications sky-rocketed and the global spread of DBS impacted positively on several aspects of society, including healthcare, awareness of neurological diseases, interdisciplinary relations, conferences, patient organizations, unemployment, industry, etc. Conclusions: STN DBS has boosted the field of deep brain electrotherapy for many neurological and psychiatric illnesses, and DBS has generated a global benefit on many aspects of society, well beyond its clinical benefits on symptoms of diseases. With the ever-increasing indications for DBS, more positive global impact is expected.

Published
2023
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19. Advances in technical aspects of deep brain stimulation surgery

Author

Schulder, Michael, Mishra, Akash, Mammis, Antonios, Horn, Andres, Boutet, Alexandre, Blomstedt, Patric, Chabardes, Stephan, Flouty, Oliver, Lozano, Andres M., Neimat, Joseph S., Ponce, Francisco, Starr, Philip A., Krauss, Joachim K., Hariz, Marwan, Chang, Jin Woo, Schulder, Michael, Mishra, Akash, Mammis, Antonios, Horn, Andres, Boutet, Alexandre, Blomstedt, Patric, Chabardes, Stephan, Flouty, Oliver, Lozano, Andres M., Neimat, Joseph S., Ponce, Francisco, Starr, Philip A., Krauss, Joachim K., Hariz, Marwan, and Chang, Jin Woo

Abstract

Background: Deep brain stimulation has become an established technology for the treatment of patients with a wide variety of conditions, including movement disorders, psychiatric disorders, epilepsy, and pain. Surgery for implantation of DBS devices has enhanced our understanding of human physiology, which in turn has led to advances in DBS technology. Our group has previously published on these advances, proposed future developments, and examined evolving indications for DBS. Summary: The crucial roles of structural MR imaging pre-, intra-, and post-DBS procedure in target visualization and confirmation of targeting are described, with discussion of new MR sequences and higher field strength MRI enabling direct visualization of brain targets. The incorporation of functional and connectivity imaging in procedural workup and their contribution to anatomical modelling is reviewed. Various tools for targeting and implanting electrodes, including frame-based, frameless, and robot-assisted, are surveyed, and their pros and cons are described. Updates on brain atlases and various software used for planning target coordinates and trajectories are presented. The pros and cons of asleep versus awake surgery are discussed. The role and value of microelectrode recording and local field potentials are described, as well as the role of intraoperative stimulation. Technical aspects of novel electrode designs and implantable pulse generators are presented and compared.

Published
2023
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20. Funktionell neurokirurgi möjlig hjälp vid svåra neurogena tillstånd

Author

Fytagoridis, Anders, Carstam, Louise, Jalakas, Mattis, Jiltsova, Elena, Zsigmond, Peter, Blomstedt, Patric, Fytagoridis, Anders, Carstam, Louise, Jalakas, Mattis, Jiltsova, Elena, Zsigmond, Peter, and Blomstedt, Patric

Abstract

Funktionell neurokirurgi är ett samlingsnamn för en bred arsenal av neurokirurgiska metoder för att lindra besvär vid olika neurogena tillstånd. Syftet är genomgående att förbättra livskvalitet, och verksamheterna präglas av ett uttalat multidisciplinärt och tvärprofessionellt samarbete. Detta underlättar en god patientselektion, vilket är helt avgörande för att uppnå ett lyckat resultat. Med rätt urval och uppföljning erbjuder dessa ingrepp säker och effektiv lindring eller till och med bot för notoriskt svårbehandlade och ofta starkt funktionsnedsättande tillstånd.

Published
2023

23. Advances in Technical Aspects of Deep Brain Stimulation Surgery

Author

Schulder, Michael, primary, Mishra, Akash, additional, Mammis, Antonios, additional, Horn, Andres, additional, Boutet, Alexandre, additional, Blomstedt, Patric, additional, Chabardes, Stephan, additional, Flouty, Oliver, additional, Lozano, Andres M., additional, Neimat, Joseph S., additional, Ponce, Francisco, additional, Starr, Philip A., additional, Krauss, Joachim K., additional, Hariz, Marwan, additional, and Chang, Jin Woo, additional

Published
2023
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24. Advances in Technical Aspects of DBS Surgery

Author

Schulder, Michael, Mishra, Akash, Mammis, Antonios, Horn, Andres, Boutet, Alexandre, Blomstedt, Patric, Chabardes, Stephan, Flouty, Oliver, Lozano, Andres M., Neimat, Joseph S., Ponce, Francisco, Starr, Philip A., Krauss, Joachim K., Hariz, Marwan, and Chang, Jin Woo

Subjects
Article
Abstract

BACKGROUND: Deep brain stimulation has become an established technology for the treatment of patients with a wide variety of conditions, including movement disorders, psychiatric disorders, epilepsy, and pain. Surgery for implantation of DBS devices has enhanced our understanding of human physiology, which in turn has led to advances in DBS technology. Our group has previously published on these advances, proposed future developments, and examined evolving indications for DBS. SUMMARY: The crucial roles of structural MR imaging pre-, intra-, and post-DBS procedure in target visualization and confirmation of targeting are described, with discussion of new MR sequences and higher-field strength MRI enabling direct visualization of brain targets. The incorporation of functional and connectivity imaging in procedural workup and their contribution to anatomical modelling is reviewed. Various tools for targeting and implanting electrodes, including frame-based, frameless, and robot-assisted, are surveyed, and their pros and cons are described. Updates on brain atlases and various software used for planning target coordinates and trajectories are presented. The pros and cons of asleep versus awake surgery are discussed. The role and value of microelectrode recording and local field potentials are described, as well as the role of intraoperative stimulation. Technical aspects of novel electrode designs and implantable pulse generators are presented and compared. KEY MESSAGES: DBS as a therapeutic procedure is rapidly expanding, and the techniques of DBS system implantation have been greatly improved by developments in stereotactic technology, surgical techniques, and imaging. Innovations in DBS technology and surgery promise to make DBS surgery more accurate and effective, with potentially improved outcomes for a wider spectrum of patients, provided that technological advancements do not become so complicated and cumbersome that their dissemination and widespread use are hindered. Additional multidisciplinary work is needed, aiming at making these technological advances more user-friendly, which should result in further patient benefits.

Published
2023

29. Ipsilateral Effects of Unilateral Deep Brain Stimulation for Essential Tremor

Author

Österlund, Erik, Blomstedt, Patric, Fytagoridis, Anders, Österlund, Erik, Blomstedt, Patric, and Fytagoridis, Anders

Abstract

BACKGROUND: Essential tremor (ET) is the most common adult movement disorder. For the relatively large group of patients who do not respond adequately to pharmacological therapy, deep brain stimulation (DBS) is a well-established treatment option. Most ET patients will have bilateral symptoms, and many of them receive bilateral DBS. Unilateral DBS is however still the most common procedure, and some papers suggest an ipsilateral effect in these patients. OBJECTIVES: The aim of this study was to analyze if there is an ipsilateral effect of DBS for ET. METHOD: We retrospectively analyzed our patient cohort with DBS surgery from 1996 to 2017, selecting patients with ET that underwent surgery with unilateral DBS without previous DBS or lesional surgery. A total number of 68 patients (39 males, 29 females) were identified. The patients were evaluated twice: first, at a mean time of 12 months after surgery defined as short-term follow-up and then again at a mean time of 49 months after surgery defined as long-term follow-up, using the clinical rating scale for tremor (CRST). RESULTS: The total CRST score was reduced from mean 49.5 points at baseline before surgery to 20.2 (p < 0.001) at short-term and 28.3 (p < 0.001) at long-term follow-up. Contralateral tremor was reduced from mean 6.1 to 0.4 (p < 0.001) and 1.2 (p < 0.001), respectively. Contralateral hand function was reduced from 11.5 to 2.6 (p < 0.001) and 4.6 (p < 0.001), respectively. Ipsilateral hand function scored 9 at baseline, 8.3 at 1 year, and then again 9.4 at long-term follow-up. Ipsilateral tremor scored 4.0 at baseline, 3.7 at 1 year, and 4.3 at long-term follow-up. Neither ipsilateral hand function nor ipsilateral tremor showed significant difference. CONCLUSIONS: There was no difference in severity of ipsilateral tremor, neither at 1 year nor in the long term. We believe ipsilateral effects of DBS for ET merits limited consideration regarding decision-making or patient counseling bef

Published
2022
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30. Judith Balkányi-Lepintre (1912–1982) : first woman neurosurgeon, first woman war neurosurgeon, and first woman pediatric neurosurgeon in France

Author

Hariz, Marwan, Eröss, Loránd, Hariz, Gun-Marie, Eröss, Botond, Cif, Laura, Blomstedt, Patric, Agid, Yves, Hariz, Marwan, Eröss, Loránd, Hariz, Gun-Marie, Eröss, Botond, Cif, Laura, Blomstedt, Patric, and Agid, Yves

Abstract

Recently, a series of historical reports portrayed the first women neurosurgeons in various countries. One such woman, a pioneer on many levels, remained unrecognized: Judith Balkányi-Lepintre. She was the first woman neurosurgeon in France, the first woman war neurosurgeon for the French Army, and the first woman pediatric neurosurgeon in France. Born in 1912 to a Hungarian Jewish family, she graduated with honors from medical school in Budapest in 1935, then moved to Paris where she started neurosurgical training in 1937 at L’Hôpital de la Pitié under the mentorship of Clovis Vincent, the founder of French neurosurgery. Shortly after marrying a French colleague in 1940, she had to escape the Geheime Staatspolizei (Gestapo) in Paris and ended up in Algeria, where she joined the French Army of De Gaulle. As a neurosurgeon, she participated in the campaigns of Italy and France between 1943 and 1945. After the war, she returned to work at La Pitié Hospital. In 1947, she defended her doctoral thesis, “Treatment of cranio-cerebral wounds by projectiles and their early complications.” Soon thereafter, she joined Europe’s first dedicated children’s hospital, Hôpital Necker-Enfants Malades in Paris, and contributed to the establishment of pediatric neurosurgery in France. She remained clinically and academically active at Necker until her death in 1982 but was never promoted.

Published
2022
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32. Probabilistic maps for deep brain stimulation – Impact of methodological differences

Author

Nordin, Teresa, Vogel, Dorian, Österlund, Erik, Johansson, Johannes, Blomstedt, Patric, Fytagoridis, Anders, Hemm, Simone, Wårdell, Karin, Nordin, Teresa, Vogel, Dorian, Österlund, Erik, Johansson, Johannes, Blomstedt, Patric, Fytagoridis, Anders, Hemm, Simone, and Wårdell, Karin

Abstract

Background: Group analysis of patients with deep brain stimulation (DBS) has the potential to help understand and optimize the treatment of patients with movement disorders. Probabilistic stimulation maps (PSM) are commonly used to analyze the correlation between tissue stimulation and symptomatic effect but are applied with different methodological variations. Objective: To compute a group-specific MRI template and PSMs for investigating the impact of PSM model parameters. Methods: Improvement and occurrence of dizziness in 68 essential tremor patients implanted in caudal zona incerta were analyzed. The input data includes the best parameters for each electrode contact (screening), and the clinically used settings. Patient-specific electric field simulations (n = 488) were computed for all DBS settings. The electric fields were transformed to a group-specific MRI template for analysis and visualization. The different comparisons were based on PSMs representing occurrence (N-map), mean improvement (M-map), weighted mean improvement (wM-map), and voxel-wise t-statistics (p-map). These maps were used to investigate the impact from input data (clinical/screening settings), clustering methods, sampling resolution, and weighting function. Results: Screening or clinical settings showed the largest impacts on the PSMs. The average differences of wM-maps were 12.4 and 18.2% points for the left and right sides respectively. Extracting clusters based on wM-map or p-map showed notable variation in volumes, while positioning was similar. The impact on the PSMs was small from weighting functions, except for a clear shift in the positioning of the wM-map clusters. Conclusion: The distribution of the input data and the clustering method are most important to consider when creating PSMs for studying the relationship between anatomy and DBS outcome.

Published
2022
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33. Serendipity and Observations in Functional Neurosurgery : From James Parkinson's Stroke to Hamani's & Lozano's Flashbacks

Author

Hariz, Marwan, Lees, Andrew J., Blomstedt, Yulia, Blomstedt, Patric, Hariz, Marwan, Lees, Andrew J., Blomstedt, Yulia, and Blomstedt, Patric

Abstract

Background: Serendipity and observations have a noble tradition in medicine, including neurology, and are responsible for many medical treatments (carbamazepine for tic douloureux, amantadine for Parkinson's disease, gabapentin for restless legs...). We aimed at examining the contribution of serendipity and observations to functional neurosurgery. Scholarly publications relevant to the history of functional neurosurgery for movement and psychiatric disorders were reviewed, starting from the pre-stereotactic era. The documents were scrutinized with respect to indications for surgery, surgical methods, and brain targets, in view of determining whether serendipitous discoveries and other observations contributed to various functional neurosurgical procedures. Summary: James Parkinson's observation that tremors disappeared in the arm of a person with shaking palsy after a hemiparetic stroke encouraged neurosurgeons in the first half of the 20th century to perform ablative procedures on central motor pathways. Following a lobotomy performed by Browder that extended too far medially in a psychiatric patient with coexisting Parkinson's disease (PD), it was noted that the Parkinsonian signs improved. This encouraged Russel Meyers to carry out open surgery on the caudate nucleus and basal ganglia in PD. Cooper introduced ligation of the anterior choroidal artery as a treatment for PD following a surgical accident during a pedunculotomy. Cooper later started to perform stereotactic surgery on the ventrolateral thalamus following the pathological finding that an intended pallidal lesion had in fact targeted the thalamus. Leksell discovered the ideal location of a pallidal lesion being in the posteroventral area empirically, long before the advent of the basal ganglia model of PD. Modern Deep Brain Stimulation (DBS) that started in the thalamus for tremor was the result of an observation by Benabid that intraoperative high-frequency stimulation during a thalamotomy reduced trem

Published
2022
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34. Deep brain stimulation in the ALIC-BNST region targeting the bed nucleus of stria terminalis in patients with obsessive–compulsive disorder: effects on cognition after 12 months

Author

Philipson, Johanna, Naesström, Matilda, Johansson, Johannes D., Hariz, Marwan, Blomstedt, Patric, Jahanshahi, Marjan, Philipson, Johanna, Naesström, Matilda, Johansson, Johannes D., Hariz, Marwan, Blomstedt, Patric, and Jahanshahi, Marjan

Abstract

Purpose: The aim of this study was to evaluate cognitive effects 12 months after Deep Brain Stimulation (DBS) of the Bed Nucleus of Stria Terminalis (BNST) in patients with refractory Obsessive–Compulsive Disorder (OCD). Methods: Eight patients (5 female; mean ± SD age 36 ± 15) with OCD were included. A neuropsychological test battery covering verbal and spatial episodic memory, executive function, and attention was administered preoperatively and 12 months after surgery. Medical records were used as a source for descriptive data to probe for any changes not covered by standardized checklists and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the primary outcome measure. Results: At 12 months, seven patients showed response to DBS: three were full responders (i.e., Y-BOCS ≥ 35% improvement), and four were partial responders (Y-BOCS 25–34% improvement). Relative to baseline, there was a slight decline on visuo-spatial learning (p = 0.027), and improved performance on the Color-Word Interference inhibition/switching subtest (p = 0.041), suggesting improvement in cognitive flexibility. Conclusions: DBS in the BNST for treatment refractory OCD generates very few adverse cognitive effects and improves cognitive flexibility after 12 months of stimulation. The improvement in Y-BOCS and the absence of major cognitive side effects support the BNST as a potential target for DBS in severe OCD.

Published
2022
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35. Deep brain stimulation for Parkinson's disease

Author

Hariz, Marwan, Blomstedt, Patric, Hariz, Marwan, and Blomstedt, Patric

Abstract

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.

Published
2022
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Aarabi, Bizhan, Abbott, Rick, Abd-El-Barr, Muhammad M., Abel, Taylor J., Abou-Al-Shaar, Hussam, Acar, Feridun, Achey, Rebecca L., Ackerman, Laurie L., Adappa, Nithin D., Adelson, P. David, Agarwal, Nitin, Aguirre-Padilla, David H., Ahluwalia, Manmeet S., Ahmad, Shahjehan, Ahmed, A. 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Richard, Wintermark, Max, Wipplinger, Christoph, Witiw, Christopher D., Wolfla, Christopher E., Wolinsky, Jean-Paul, Wong, Eric T., Worrell, Gregory A., Wrensch, Margaret R., Wright, Christina H., Wu, Jau-Ching, Wu, Jenny, Wu, Kyle C., Wu, Pang Hung, Xu, David S., Xu, Linda Wei, Xu, Yifan, Xu, Zhen, Xu, Zhiyuan, Yaeger, Kurt A., Yahanda, Alexander T., Yan, Rachel E., Yan, Yuanqing, Yang, George L., Yasuno, Katsuhito, Yen, Chun-Po, Yokota, Kazuya, Yolcu, Yagiz Ugur, Young, Timothy P., Yu, Jennifer S., Yue, John K., Yuh, Esther L., Zabramski, Joseph M., Zacest, Andrew, Zacko, J. Christopher, Zada, Gabriel, Zafonte, Ross D., Zager, Eric L., Zakare-Fagbamila, Rasheedat T., Zakeri, Amanda, Zanotti, Bruno, Zawar, Ifrah, Zeineddine, Hussein A., Zellner, Elizabeth G., Zhan, Shikun, Zhang, Chencheng, Zhang, Michael, Zhang, Yingying, Zibly, Zion, Zigler, Jack E., Zipfel, Gregory J., Zipser, Carl Moritz, Zrinzo, Ludvic, and Zumofen, Daniel W.

Published
2023
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41. Awake versus asleep deep brain stimulation targeting the caudal zona incerta for essential tremor.

Author

Stenmark Persson R, Blomstedt Y, Fytagoridis A, Hariz M, and Blomstedt P

Abstract

To compare awake and asleep deep brain stimulation (DBS) surgery for Essential Tremor (ET), we conducted this retrospective cohort study of patients consecutively operated with DBS targeting the caudal Zona incerta (cZi). 37 underwent surgery awake and 55 asleep. Tremor before surgery and on/off stimulation one year after surgery were evaluated using the Essential Tremor Rating Scale (ETRS). Procedural time, electrode localization, stimulation parameters and adverse events were noted and compared. ETRS scores were similar at baseline between the groups except for contralateral arm tremor, which was slightly worse in the awake group. Total ETRS, contralateral arm tremor and activities of daily living scores showed no significant difference between the groups on-stimulation at one-year follow-up. Compared to the awake group, the asleep group had shorter procedural time and lower stimulation parameters. There were no intracranial haemorrhages nor surgery site-infections. Both groups showed a good improvement of tremor at one-year follow-up. Image-guided DBS surgery targeting the cZi enables safe and efficient asleep surgery for ET., Competing Interests: Competing interests: The authors disclose following unrelated financial engagements: YB is a shareholder in Mithridaticum AB. MH has received fees and travel expenses from Boston Scientific for speaking at meetings. PB is consultant for Abbott and Boston Scientific and a shareholder in Mithridaticum AB. RSP and AF declare no conflict of interest., (© 2024. The Author(s).)

Published
2024
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42. Deep brain stimulation does not modulate resting-state functional connectivity in essential tremor.

Author

Awad A, Grill F, Blomstedt P, Nyberg L, and Eriksson J

Abstract

While the effectiveness of deep brain stimulation in alleviating essential tremor is well-established, the underlying mechanisms of the treatment are unclear. Essential tremor, as characterized by tremor during action, is proposed to be driven by a dysfunction in the cerebello-thalamo-cerebral circuit that is evident not only during motor actions but also during rest. Stimulation effects on resting-state functional connectivity were investigated by functional MRI in 16 essential tremor patients with fully implanted deep brain stimulation in the caudal zona incerta during On-and-Off therapeutic stimulation, in a counterbalanced design. Functional connectivity was calculated between different constellations of sensorimotor as well as non-sensorimotor regions (as derived from seed-based and data-driven approaches), and compared between On and Off stimulation. We found that deep brain stimulation did not modulate resting-state functional connectivity. The lack of modulation by deep brain stimulation during resting-state, in combination with previously demonstrated effects on the cerebello-thalamo-cerebral circuit during motor tasks, suggests an action-dependent modulation of the stimulation in essential tremor., Competing Interests: F.G., L.N., and J.E. report no conflicts of interest. A.A. is a consultant for Elekta. P.B. is a consultant for Abbott and Boston Scientific and a shareholder in Mithridaticum AB., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2024
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44. Serendipity and Observations in Functional Neurosurgery: From James Parkinson's Stroke to Hamani's & Lozano's Flashbacks.

Author

Hariz M, Lees AJ, Blomstedt Y, and Blomstedt P

Subjects
Deep Brain Stimulation, History, 20th Century, Humans, Parkinson Disease surgery, Psychosurgery, Stroke surgery, Tremor surgery, Neurosurgery history, Observation
Abstract

Background: Serendipity and observations have a noble tradition in medicine, including neurology, and are responsible for many medical treatments (carbamazepine for tic douloureux, amantadine for Parkinson's disease, gabapentin for restless legs…). We aimed at examining the contribution of serendipity and observations to functional neurosurgery. Scholarly publications relevant to the history of functional neurosurgery for movement and psychiatric disorders were reviewed, starting from the pre-stereotactic era. The documents were scrutinized with respect to indications for surgery, surgical methods, and brain targets, in view of determining whether serendipitous discoveries and other observations contributed to various functional neurosurgical procedures., Summary: James Parkinson's observation that tremors disappeared in the arm of a person with shaking palsy after a hemiparetic stroke encouraged neurosurgeons in the first half of the 20th century to perform ablative procedures on central motor pathways. Following a lobotomy performed by Browder that extended too far medially in a psychiatric patient with coexisting Parkinson's disease (PD), it was noted that the Parkinsonian signs improved. This encouraged Russel Meyers to carry out open surgery on the caudate nucleus and basal ganglia in PD. Cooper introduced ligation of the anterior choroidal artery as a treatment for PD following a surgical accident during a pedunculotomy. Cooper later started to perform stereotactic surgery on the ventrolateral thalamus following the pathological finding that an intended pallidal lesion had in fact targeted the thalamus. Leksell discovered the ideal location of a pallidal lesion being in the posteroventral area empirically, long before the advent of the basal ganglia model of PD. Modern Deep Brain Stimulation (DBS) that started in the thalamus for tremor was the result of an observation by Benabid that intraoperative high-frequency stimulation during a thalamotomy reduced tremor. Both the discoveries of the anterior limbic subthalamic nucleus as a DBS target for OCD and the medial forebrain bundle as a DBS target for depression occurred by chance. Hamani and Lozano observed memory flashbacks in a patient who was undergoing DBS for obesity, which led to the discovery of the fornix as a potential DBS target for Alzheimer's disease., Key Messages: In the history of functional neurosurgery, serendipity and observations have resulted in discoveries of several procedures, brain targets for lesioning or DBS as well as new clinical surgical indications. In this era of neuromodulation, this technology should be exquisite in allowing potential serendipitous discoveries, provided that clinicians remain both observant and prepared., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Published
2022
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