Longitudinal Change in Fine Motor Skills After Brain Radiotherapy and in Vivo Imaging Biomarkers Associated with Decline

Overview

Journal Neuro Oncol

Publisher Oxford University Press

Specialties Neurology
Oncology

Date 2021 Feb 5

PMID 33543265

Citations 6

Authors

Mia Salans

Michelle D Tibbs

Roshan Karunamuni

Anthony Yip

Minh-Phuong Huynh-Le

Anna Christina Macari

Anny Reyes

Kathryn Tringale

Carrie R McDonald

Jona A Hattangadi-Gluth

Affiliations

Soon will be listed here.

Abstract

Background: We explored fine motor skills (FMS) before and after brain radiotherapy (RT), analyzing associations between longitudinal FMS and imaging biomarkers of cortical and white matter (WM) integrity in motor regions of interest (ROIs).

Methods: On a prospective trial, 52 primary brain tumor patients receiving fractionated brain RT underwent volumetric brain MRI, diffusion tensor imaging, and FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS], Grooved Pegboard Dominant Hands [PDH], and Grooved Pegboard Nondominant Hands [PNDH]) at baseline and 3-, 6-, and 12-month post-RT. Motor ROIs autosegmented included: sensorimotor cortices and superficial WM, corticospinal tracts, cerebellar cortices and WM, and basal ganglia. Volume (cc) was measured in all ROIs at each timepoint. Diffusion biomarkers (FA [fractional anisotropy] and MD [mean diffusivity]) were additionally measured in WM ROIs. Linear mixed-effects models assessed biomarkers as predictors of FMS scores. P values were corrected for multiple comparisons.

Results: Higher RT dose was associated with right paracentral cortical thinning (β = -2.42 Gy/(month × mm), P = .03) and higher right precentral WM MD (β = 0.69 Gy/(month × µm2/ms), P = .04). Higher left (β = 38.7 points/(month × µm2/ms), P = .004) and right (β = 42.4 points/(month × µm2/ms), P = .01) cerebellar WM MD, left precentral cortical atrophy (β = -8.67 points/(month × mm), P = .02), and reduced right cerebral peduncle FA (β = -0.50 points/month, P = .01) were associated with worse DKEFS-MS performance. Left precentral cortex thinning was associated with worse PDH scores (β = -17.3 points/(month × mm), P = .02). Left (β = -0.87 points/(month × cm3), P = .001) and right (β = -0.64 points/(month × cm3), P = .02) cerebellar cortex, left pons (β = -19.8 points/(month × cm3), P = .02), and right pallidum (β = -10.8 points/(month × cm3), P = .02) atrophy and reduced right internal capsule FA (β = -1.02 points/month, P = .03) were associated with worse PNDH performance.

Conclusions: Biomarkers of microstructural injury in motor-associated brain regions were associated with worse FMS. Dose avoidance in these areas may preserve FMS.

Citing Articles

Cognitive phenotypes: Unraveling the heterogeneity in cognitive dysfunction among patients with primary brain tumors receiving radiotherapy.

Reyes A, Stasenko A, Hopper A, Kohli J, Helm J, Salans M Neuro Oncol. 2024; 27(2):466-478.

PMID: 39248576 PMC: 11812028. DOI: 10.1093/neuonc/noae183.

Brain Plasticity Profiling as a Key Support to Therapeutic Decision-Making in Low-Grade Glioma Oncological Strategies.

Ng S, Duffau H Cancers (Basel). 2023; 15(14).

PMID: 37509359 PMC: 10378506. DOI: 10.3390/cancers15143698.

Fine Motor Skill Decline After Brain Radiation Therapy-A Multivariate Normal Tissue Complication Probability Study of a Prospective Trial.

Connor M, Salans M, Karunamuni R, Unnikrishnan S, Huynh-Le M, Tibbs M Int J Radiat Oncol Biol Phys. 2023; 117(3):581-593.

PMID: 37150258 PMC: 10911396. DOI: 10.1016/j.ijrobp.2023.04.033.

Dose Reduction to Motor Structures in Adjuvant Fractionated Stereotactic Radiotherapy of Brain Metastases: nTMS-Derived DTI-Based Motor Fiber Tracking in Treatment Planning.

Diehl C, Rosenkranz E, Schwendner M, Misslbeck M, Sollmann N, Ille S Cancers (Basel). 2023; 15(1).

PMID: 36612277 PMC: 9818359. DOI: 10.3390/cancers15010282.

Neurocognitive considerations in the treatment of meningioma with radiation therapy: applications for quantitative neuroimaging and precision radiation medicine.

Hopper A, Salans M, Karunamuni R, Hattangadi-Gluth J J Neurooncol. 2022; 161(2):277-286.

PMID: 36572802 DOI: 10.1007/s11060-022-04175-5.

References

Nimsky C, Ganslandt O, Merhof D, Sorensen A, Fahlbusch R . Intraoperative visualization of the pyramidal tract by diffusion-tensor-imaging-based fiber tracking. Neuroimage. 2005; 30(4):1219-29. DOI: 10.1016/j.neuroimage.2005.11.001. View

Jovicich J, Czanner S, Greve D, Haley E, van der Kouwe A, Gollub R . Reliability in multi-site structural MRI studies: effects of gradient non-linearity correction on phantom and human data. Neuroimage. 2005; 30(2):436-43. DOI: 10.1016/j.neuroimage.2005.09.046. View

Schindler M, Forbes M, Robbins M, Riddle D . Aging-dependent changes in the radiation response of the adult rat brain. Int J Radiat Oncol Biol Phys. 2008; 70(3):826-34. PMC: 2268759. DOI: 10.1016/j.ijrobp.2007.10.054. View

Nazeri A, Chakravarty M, Rajji T, Felsky D, Rotenberg D, Mason M . Superficial white matter as a novel substrate of age-related cognitive decline. Neurobiol Aging. 2015; 36(6):2094-106. DOI: 10.1016/j.neurobiolaging.2015.02.022. View

Tibbs M, Huynh-Le M, Karunamuni R, Reyes A, Macari A, Tringale K . Microstructural Injury to Left-Sided Perisylvian White Matter Predicts Language Decline After Brain Radiation Therapy. Int J Radiat Oncol Biol Phys. 2020; 108(5):1218-1228. PMC: 7680351. DOI: 10.1016/j.ijrobp.2020.07.032. View

Chapman C, Zhu T, Nazem-Zadeh M, Tao Y, Buchtel H, Tsien C . Diffusion tensor imaging predicts cognitive function change following partial brain radiotherapy for low-grade and benign tumors. Radiother Oncol. 2016; 120(2):234-40. PMC: 5003665. DOI: 10.1016/j.radonc.2016.06.021. View

Connor M, Karunamuni R, McDonald C, White N, Pettersson N, Moiseenko V . Dose-dependent white matter damage after brain radiotherapy. Radiother Oncol. 2016; 121(2):209-216. PMC: 5136508. DOI: 10.1016/j.radonc.2016.10.003. View

Courchesne E, Townsend J, Akshoomoff N, Saitoh O, Lincoln A, James H . Impairment in shifting attention in autistic and cerebellar patients. Behav Neurosci. 1994; 108(5):848-65. DOI: 10.1037//0735-7044.108.5.848. View

Graybiel A . The basal ganglia. Curr Biol. 2000; 10(14):R509-11. DOI: 10.1016/s0960-9822(00)00593-5. View

10.

Alexander A, Lee J, Lazar M, Field A . Diffusion tensor imaging of the brain. Neurotherapeutics. 2007; 4(3):316-29. PMC: 2041910. DOI: 10.1016/j.nurt.2007.05.011. View

11.

Chang E, Wefel J, Hess K, Allen P, Lang F, Kornguth D . Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol. 2009; 10(11):1037-44. DOI: 10.1016/S1470-2045(09)70263-3. View

12.

Hagler Jr D, Ahmadi M, Kuperman J, Holland D, McDonald C, Halgren E . Automated white-matter tractography using a probabilistic diffusion tensor atlas: Application to temporal lobe epilepsy. Hum Brain Mapp. 2008; 30(5):1535-47. PMC: 2754725. DOI: 10.1002/hbm.20619. View

13.

Chapman C, Nagesh V, Sundgren P, Buchtel H, Chenevert T, Junck L . Diffusion tensor imaging of normal-appearing white matter as biomarker for radiation-induced late delayed cognitive decline. Int J Radiat Oncol Biol Phys. 2011; 82(5):2033-40. PMC: 3157581. DOI: 10.1016/j.ijrobp.2011.01.068. View

14.

Brown P, Jaeckle K, Ballman K, Farace E, Cerhan J, Anderson S . Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA. 2016; 316(4):401-409. PMC: 5313044. DOI: 10.1001/jama.2016.9839. View

15.

Lambrecht M, Eekers D, Alapetite C, Burnet N, Calugaru V, Coremans I . Radiation dose constraints for organs at risk in neuro-oncology; the European Particle Therapy Network consensus. Radiother Oncol. 2018; 128(1):26-36. DOI: 10.1016/j.radonc.2018.05.001. View

16.

Alahmadi A, Pardini M, Samson R, DAngelo E, Friston K, Toosy A . Differential involvement of cortical and cerebellar areas using dominant and nondominant hands: An FMRI study. Hum Brain Mapp. 2015; 36(12):5079-100. PMC: 4737094. DOI: 10.1002/hbm.22997. View

17.

Karunamuni R, Bartsch H, White N, Moiseenko V, Carmona R, Marshall D . Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma. Int J Radiat Oncol Biol Phys. 2016; 94(2):297-304. PMC: 4747044. DOI: 10.1016/j.ijrobp.2015.10.026. View

18.

Maruyama K, Kamada K, Ota T, Koga T, Itoh D, Ino K . Tolerance of pyramidal tract to gamma knife radiosurgery based on diffusion-tensor tractography. Int J Radiat Oncol Biol Phys. 2007; 70(5):1330-5. DOI: 10.1016/j.ijrobp.2007.08.010. View

19.

Seibert T, Karunamuni R, Kaifi S, Burkeen J, Connor M, Krishnan A . Cerebral Cortex Regions Selectively Vulnerable to Radiation Dose-Dependent Atrophy. Int J Radiat Oncol Biol Phys. 2017; 97(5):910-918. PMC: 5403140. DOI: 10.1016/j.ijrobp.2017.01.005. View

20.

Peterson R, Tabori U, Bouffet E, Laughlin S, Liu F, Scantlebury N . Predictors of neuropsychological late effects and white matter correlates in children treated for a brain tumor without radiation therapy. Pediatr Blood Cancer. 2019; 66(10):e27924. DOI: 10.1002/pbc.27924. View