Lesions causing limb ataxia in stroke not centrally located, form common network

Key takeaways:

• Areas of the brain in those with stroke were analyzed for lesion activity and functional connectivity.
• In 54% of those with acute limb ataxia resulting from stroke, lesions were found outside the cerebellum.

For individuals with stroke, lesions that cause ataxia of the limbs occur in different regions of the brain but are connected by a common network, according to new research published in Neurology.

“Generally, ataxia is strongly associated with lesions in the cerebellum or its direct connections, transversing through the cerebellar peduncles or through the spinocerebellar tracts,” Oliver Liesmaki, MD, MSc, of the department of clinical neurosciences at the University of Turku in Finland, and colleagues wrote.

As prior research has established that ataxia may also occur without damage to the cerebellum, Liesmaki and colleagues sought to investigate whether lesions in the brain due to stroke that result in limb ataxia can be identified as part of a common neural network.

Their prospective cohort study included 197 individuals (mean age, 67.2 years; 39% women) with new-onset stroke and visible lesions on CT or MRI who were admitted to Turku University Hospital (TUH) during the years 2020 and 2021. All participants were examined following stroke while still admitted to the hospital, then again at a 4-month follow up to determine the presence of limb ataxia.

The researchers analyzed the location of brain lesions from 133 individuals (23 with, 110 without limb ataxia). Any nonbrain tissue were removed from imaging sources via computerized software.

The researchers then compared, on a voxel-by-voxel basis, whole-brain lesion locations and their functional connectivity from all patients, utilizing data from 1,000 healthy volunteers from the Brain Genome Superstruct Project via voxel-based lesion-symptom mapping as well as lesion network mapping.

A separate independent confirmation dataset was compiled from an additional 96 individuals diagnosed with new-onset stroke from TUH and included in data analyses.

The findings were confirmed in an independent cohort of patients with stroke who had identical clinical assessments.

According to the results, at baseline, 35 individuals were diagnosed with new-onset acute limb ataxia and 162 were not. At the 4-month follow up, four additional patients had developed late-onset limb ataxia. A total of 118 individuals were not diagnosed with ataxia at any point (n = 40 with missing follow-up data).

Liesmaki and colleagues wrote that, in 54% of the patients with acute limb ataxia, lesions were found outside the cerebellum and cerebellar peduncles, with no discernible associations between specific lesion locations and ataxia occurrence.

However, the researchers reported that lesions causing acute limb ataxia were connected to a common network centered on the intermediate zone cerebellum and cerebellar peduncles (lesion connectivity in patients with acute limb ataxia vs. those without, pFWE < 0.05), with similar results found when comparing both patient groups when excluding lesions in the cerebellum and cerebellar peduncles (pFWE < 0.05).

These findings were replicated within the independent stroke dataset (OR = 2.27; 95% CI, 1.32–3.91) for limb ataxia.

“Our findings lend insight into the mechanisms of extracerebellar lesions causing limb ataxia, which may help in clinical localization of lesions causing limb ataxia and possibly also avoiding ataxia in neurosurgical treatments of brain disorders,” Liesmaki and colleagues wrote.