Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy

E H Middlebrooks; R A Popple; E Greco; L Okromelidze; H C Walker; D A Lakhani; A R Anderson; E M Thomas; H D Deshpande; B A McCullough; N P Stover; V W Sung; A P Nicholas; D G Standaert; T Yacoubian; M N Dean; J A Roper; S S Grewal; M T Holland; J N Bentley; B L Guthrie; M Bredel

doi:10.3174/ajnr.A7778

Connectomic Basis for Tremor Control in Stereotactic Radiosurgical Thalamotomy

AJNR Am J Neuroradiol. 2023 Feb;44(2):157-164. doi: 10.3174/ajnr.A7778. Epub 2023 Jan 26.

Authors

E H Middlebrooks^{1

2}, R A Popple³, E Greco⁴, L Okromelidze⁴, H C Walker⁵, D A Lakhani^{4

6}, A R Anderson³, E M Thomas^{3

7}, H D Deshpande⁸, B A McCullough⁵, N P Stover⁵, V W Sung⁵, A P Nicholas⁵, D G Standaert⁵, T Yacoubian⁵, M N Dean⁵, J A Roper⁹, S S Grewal², M T Holland¹⁰, J N Bentley¹⁰, B L Guthrie¹⁰, M Bredel³

Affiliations

¹ From the Departments of Radiology (E.H.M., E.G., L.O., D.A.L.) Middlebrooks.Erik@mayo.edu.
² Neurosurgery (E.H.M., S.S.G.), Mayo Clinic, Jacksonville, Florida.
³ Departments of Radiation Oncology (R.A.P., A.R.A., E.M.T., M.B.).
⁴ From the Departments of Radiology (E.H.M., E.G., L.O., D.A.L.).
⁵ Neurology (H.C.W., B.A.M., N.P.S., V.W.S., A.P.N., D.G.S., T.Y., M.N.D.).
⁶ Department of Radiology (D.A.L.), West Virginia University, Morgantown, West Virginia.
⁷ Department of Radiation Oncology (E.M.T.), Ohio State University, Columbus, Ohio.
⁸ Radiology (H.D.D.).
⁹ School of Kinesiology (J.A.R.), Auburn University, Auburn, Alabama.
¹⁰ Neurosurgery (M.T.H., J.N.B., B.L.G.), University of Alabama at Birmingham, Birmingham, Alabama.

Abstract

Background and purpose: Given the increased use of stereotactic radiosurgical thalamotomy and other ablative therapies for tremor, new biomarkers are needed to improve outcomes. Using resting-state fMRI and MR tractography, we hypothesized that a "connectome fingerprint" can predict tremor outcomes and potentially serve as a targeting biomarker for stereotactic radiosurgical thalamotomy.

Materials and methods: We evaluated 27 patients who underwent unilateral stereotactic radiosurgical thalamotomy for essential tremor or tremor-predominant Parkinson disease. Percentage postoperative improvement in the contralateral limb Fahn-Tolosa-Marin Clinical Tremor Rating Scale (TRS) was the primary end point. Connectome-style resting-state fMRI and MR tractography were performed before stereotactic radiosurgery. Using the final lesion volume as a seed, "connectivity fingerprints" representing ideal connectivity maps were generated as whole-brain R-maps using a voxelwise nonparametric Spearman correlation. A leave-one-out cross-validation was performed using the generated R-maps.

Results: The mean improvement in the contralateral tremor score was 55.1% (SD, 38.9%) at a mean follow-up of 10.0 (SD, 5.0) months. Structural connectivity correlated with contralateral TRS improvement (r = 0.52; P = .006) and explained 27.0% of the variance in outcome. Functional connectivity correlated with contralateral TRS improvement (r = 0.50; P = .008) and explained 25.0% of the variance in outcome. Nodes most correlated with tremor improvement corresponded to areas of known network dysfunction in tremor, including the cerebello-thalamo-cortical pathway and the primary and extrastriate visual cortices.

Conclusions: Stereotactic radiosurgical targets with a distinct connectivity profile predict improvement in tremor after treatment. Such connectomic fingerprints show promise for developing patient-specific biomarkers to guide therapy with stereotactic radiosurgical thalamotomy.

Trial registration: ClinicalTrials.gov NCT03305588.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Connectome*
Essential Tremor* / surgery
Humans
Magnetic Resonance Imaging
Radiosurgery*
Thalamus / diagnostic imaging
Thalamus / surgery
Treatment Outcome
Tremor / diagnostic imaging
Tremor / surgery

Associated data

ClinicalTrials.gov/NCT03305588