Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming

Artusi, Carlo Alberto; Farooqi, Ashar; Romagnolo, Alberto; Marsili, Luca; Balestrino, Roberta; Sokol, Leonard L.; Wang, Lily L.; Zibetti, Maurizio; Duker, Andrew P.; Mandybur, George T.; Lopiano, Leonardo; Merola, Aristide

doi:10.1007/s00415-018-8823-x

Cited by 34 publications

(48 citation statements)

References 93 publications

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“…(B) Spatial relationship between commonly used deep brain stimulation (DBS) targets for Holmes tremor (blue) and our lesion‐based Holmes tremor circuit (red; see also Fig A). Average clinical response rate (% good response) is shown according to Artusi et al Note that the globus pallidus interna (GPi) target was immediately adjacent to our Holmes tremor circuit, whereas subthalamic nucleus (STN) and ventral intermediate nucleus of thalamus (VIM) were not. VOP = ventral oralis posterior; ZI = zona incerta.…”

Section: Resultssupporting

confidence: 64%

“…Given these results, we tested whether DBS targets commonly used to treat Holmes tremor (GPi, STN, VIM) fell within the network connected to all 36 lesion locations. None of the current targets matched our network exactly (see Fig B); however, the GPi target was immediately adjacent to our network, potentially consistent with its higher rate of good clinical response reported for this target …”

Section: Resultsmentioning

confidence: 99%

“…Based on the published literature, the most commonly targeted regions for DBS in Holmes tremor include ventral intermediate nucleus of thalamus (VIM), globus pallidus interna (GPi), and subthalamic nucleus (STN) . Clinical response rates for these targets were taken directly from a recent systematic review, where good clinical response was defined as ≥80% improvement in the clinical scale used in the study: 10/31 for VIM, 11/14 for GPi, and 1/6 for STN . The probabilistic coordinates for each of the neuroanatomical treatment targets were taken from previously published work .…”

Section: Methodsmentioning

confidence: 99%

“…The tremor is usually slow, large in amplitude, and present at rest, with movement, and often with sustained posture . Holmes tremor is frequently debilitating given its large amplitude, lack of response to medications, and heterogeneous response to deep brain stimulation (DBS) …”

mentioning

confidence: 99%

“…One hypothesis to explain this heterogeneity is that lesions causing Holmes tremor map to one or more connected brain circuit(s) . However, which circuit has remained unclear, leading to uncertainty as to the most appropriate DBS target . The hypothesis that lesion locations causing Holmes tremor localize to one (or more) connected brain circuit(s) has never been formally tested.…”

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confidence: 99%

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Mapping holmes tremor circuit using the human brain connectome

Joutsa

Shih

Fox

2019

Annals of Neurology

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Objective Holmes tremor is a debilitating movement disorder with limited treatment options. Lesions causing Holmes tremor can occur in multiple different brain locations, leaving the neuroanatomical substrate unclear. Here, we test whether lesion locations that cause Holmes tremor map to a connected brain circuit and whether this circuit might serve as a useful therapeutic target. Methods Case reports of Holmes tremor caused by focal brain lesions were identified through a systematic literature search. Connectivity between each lesion location and the rest of the brain was computed using resting state functional connectivity magnetic resonance imaging data from 1,000 healthy volunteers. Commonalities across lesion locations were identified. This Holmes tremor circuit was then compared to neurosurgical treatment targets and clinical efficacy. Results We identified 36 lesions causing Holmes tremor, which were scattered across multiple different brain regions. However, all lesion locations were connected to a common brain circuit with nodes in the red nucleus, thalamus, globus pallidus, and cerebellum. In cases with effective neurosurgical treatment, the treatment target was connected with the lesion location, indicating that a second hit to the same circuit might be beneficial. Commonly used deep brain stimulation targets such as the ventral intermediate nucleus and subthalamic nucleus fell outside our Holmes tremor circuit, whereas the globus pallidus target was close, consistent with published clinical response rates for these targets. Interpretation Lesions causing Holmes tremor are part of a single connected brain circuit that may serve as an improved therapeutic target. ANN NEUROL 2019;86:812–820

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Section: Resultssupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mapping holmes tremor circuit using the human brain connectome

Joutsa

Shih

Fox

2019

Annals of Neurology

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Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions

Fasano

Helmich²

2019

Movement Disorders

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DBS of the ventral intermediate nucleus is an extremely effective treatment for essential tremor, although a waning benefit is observed after a variable time in a variable proportion of patients (ranging from 0% to 73%), a concept historically defined as “tolerance.” Tolerance is currently an established concept in the medical community, although there is debate on its real existence. In fact, very few publications have actually addressed the problem, thus making tolerance a typical example of science based on “eminence rather than evidence.” The underpinnings of the phenomena associated with the progressive loss of DBS benefit are not fully elucidated, although the interplay of different—not mutually exclusive—factors has been advocated. In this viewpoint, we gathered the evidence explaining the progressive loss of benefit observed after DBS. We grouped these factors in three categories: disease‐related factors (tremor etiology and progression); surgery‐related factors (electrode location, microlesional effect and placebo); and stimulation‐related factors (not optimized stimulation, stimulation‐induced side effects, habituation, and tremor rebound). We also propose possible pathophysiological explanations for the phenomenon and define a nomenclature of the associated features: early versus late DBS failure; tremor rebound versus habituation (to be preferred over tolerance). Finally, we provide a practical approach for preventing and treating this loss of DBS benefit, and we draft a possible roadmap for the research to come. © 2019 International Parkinson and Movement Disorder Society

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Deep Brain Stimulation in Movement Disorders: From Experimental Surgery to Evidence‐Based Therapy

Volkmann²,

et al. 2019

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Deep brain stimulation (DBS) of 3 different targets is the most important therapeutic innovation of the past 30 years for patients with fluctuating Parkinson's disease (PD), disabling dystonia, tremors, and refractory Gilles de la Tourette syndrome. When compared with medical treatment alone, controlled studies have shown better motor, nonmotor, and particularly quality‐of‐life outcomes with large effect sizes for advanced complicated PD that cannot be improved with medication, and also for PD patients with only early fluctuations. Class 1 studies have also shown superiority over medical treatment for generalized, segmental, and botulinum‐toxin refractory focal cervical dystonia. Long‐term efficacy is established for all indications with open studies. For tremors, open studies have shown that DBS is remarkably effective on PD and essential tremor, but efficacy on severe essential tremor and cerebellar tremors is limited by a tendency for tolerance/habituation, including concerns about long‐term efficacy. Open studies of disabling Gilles de la Tourette syndrome show an improvement in tics. New developments hold a promise for further improvement. New hardware with directional stimulation and new stimulation paradigms are further areas of research. The targets of DBS are refined with new imaging processing that will help to diversify the surgical targets. New indications are being explored. Closed‐loop DBS using brain or peripheral sensor signals have shown favorable clinical short‐term results. Long‐term data are lacking, and it is hoped that similar approaches for other movement or behavioral disorders may be developed. Exciting new developments carry the hope for a more pathophysiology‐based approach for DBS for various brain circuit disorders. © 2019 International Parkinson and Movement Disorder Society

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Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming

Cited by 34 publications

References 93 publications

Mapping holmes tremor circuit using the human brain connectome

Mapping holmes tremor circuit using the human brain connectome

Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions

Deep Brain Stimulation in Movement Disorders: From Experimental Surgery to Evidence‐Based Therapy

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