Objective: To identify the neural substrates of limb ataxia caused by stroke lesions.

Background: Ataxia is a neurological sign defined by incoordination of voluntary movements. It is considered to originate from the cerebellum but can also occur without obvious cerebellar damage. Ataxia is a frequent symptom of stroke and studying stroke lesions offers a window to brain regions causally involved in ataxia. Here we studied a large sample of stroke patients with and without ataxia using both lesion mapping and lesion network mapping to identify the neural substrates of limb ataxia.

Method: Two hundred patients with new-onset stroke were prospectively enrolled into the study. The patients were examined 1) at the hospital ward, and 2) approximately 3 months later to assess acute and chronic ataxia, respectively. Brain lesions were delineated on the brain images obtained as a part of the clinical routine, and transformed to MNI space. Lesion locations and functional connectivity, computed using an external dataset of 1,000 healthy volunteers [1], were compared voxel-by-voxel across the whole brain between patients with and without ataxia, as described earlier [2].

Results: Thirty-five patients had new-onset acute limb ataxia at baseline and a total of seven patients had chronic ataxia at follow-up. There were no lesion locations significantly associated with ataxia. Nineteen (54%) of the lesions causing acute ataxia and four (57%) of the lesions causing chronic ataxia were located outside the cerebellum and cerebellar peduncles. Lesions causing limb ataxia were connected to a common network defined by connectivity to intermediate zone cerebellar structures, including the interposed and dentate nuclei. The results were similar when analyzing acute or chronic ataxia and including only lesions outside the cerebellum, and showed expected laterality in the cerebellum when analyzing left- and right-sided ataxia separately.

Conclusion: Brain lesions causing limb ataxia occur in heterogenous locations but are connected to a common network with a hub in the intermediate zone of the cerebellum. These findings can aid in clinical localization of lesions causing limb ataxia and identify the neural substrates of limb ataxia.

References: [1] Fox MD. Mapping Symptoms to Brain Networks with the Human Connectome. N Engl J Med. 2018 Dec 6;379(23):2237-2245. doi: 10.1056/NEJMra1706158.

[2] Joutsa J, Moussawi K, Siddiqi SH, Abdolahi A, Drew W, Cohen AL, Ross TJ, Deshpande HU, Wang HZ, Bruss J, Stein EA, Volkow ND, Grafman JH, van Wijngaarden E, Boes AD, Fox MD. Brain lesions disrupting addiction map to a common human brain circuit. Nat Med. 2022 Jun;28(6):1249-1255. doi: 10.1038/s41591-022-01834-y.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/network-localization-of-limb-ataxia/