Localizing parkinsonism based on focal brain lesions

Bradykinesia, rigidity, and tremor frequently co-occur, a clinical syndrome known as parkinsonism. Because this syndrome is commonly seen in Parkinson's disease, symptoms are often attributed to cell loss in the substantia nigra. However, parkinsonism occurs in several other neurological disorders and often fails to correlate with nigrostriatal pathology, raising the question of which brain region(s) cause this syndrome. Here, we studied cases of new-onset parkinsonism following focal brain lesions. We identified 29 cases, only 31% of which hit the substantia nigra. Lesions were located in a variety of different cortical and subcortical locations. To determine whether these heterogeneous lesion locations were part of a common brain network, we leveraged the human brain connectome and a recently validated technique termed lesion network mapping. Lesion locations causing parkinsonism were functionally connected to a common network of regions including the midbrain, basal ganglia, cingulate cortex, and cerebellum. The most sensitive and specific connectivity was to the claustrum. This lesion connectivity pattern matched atrophy patterns seen in Parkinson's disease, progressive supranuclear palsy, and multiple system atrophy, suggesting a shared neuroanatomical substrate for parkinsonism. Lesion connectivity also predicted medication response and matched the pattern of effective deep brain stimulation, suggesting relevance as a treatment target. Our results, based on causal brain lesions, lend insight into the localization of parkinsonism, one of the most common syndromes in neurology. Because many patients with parkinsonism fail to respond to dopaminergic medication, these results may aid the development of alternative treatments.