Objective: To determine whether rare cases in which spontaneously occurring brain lesions improved tremor can be used to identify a therapeutic target.

Background: The search for brain locations to surgically induce therapeutic lesions or implant deep brain stimulation electrodes has been guided in large part by trial-and-error targeting. Spontaneously occurring brain lesions such as stroke can occasionally result in paradoxical functional benefit and might be used to inform target selection. For example, patients with essential tremor who subsequently have a stroke can see improvement in tremor and overall limb function. However, these lesions are rare and occur in multiple different brain locations, leaving the therapeutic target unclear. Further, functional benefit can come from the effect of the lesion on remote but connected brain regions. A new technique, lesion network mapping (Boes et al., 2015), uses a map of brain connectivity to link heterogenous lesion locations to a common network. Here, we test whether this method can be combined with lesions causing tremor relief to identify a therapeutic target.

Methods: Cases of individuals with essential tremor who experienced relief of tremor following stroke without severe motor paresis were identified using a PubMed literature search with the terms “tremor”, “essential tremor”, “stroke”, and “ischemic stroke”. Lesion network mapping proceeded in three steps: 1) lesion locations from published images were mapped to a standard brain, 2) the lesion volume was used as a seed region of interest in a resting state functional connectivity MRI analysis using data from 1,000 healthy individuals, and 3) the resulting network associated with each lesion volume was thresholded and overlaid across each other to identify common sites of network overlap.

Results: We found 11 cases where a brain lesion resulted in symptom relief in patients with essential tremor. The lesions were in heterogeneous brain locations but all were a part of a single, functionally connected network. Importantly, the peak node in this network occurred at the precise location in the ventral intermediate nucleus of thalamus that has proven an effective deep brain stimulation target for tremor relief.

Conclusions: These results suggest that lesion network mapping can identify the common substrate underlying spontaneously occurring therapeutic lesions, highlighting treatment targets. Future work is needed to extend this technique beyond tremor.

References: Boes AD, Prasad S, Liu H, Liu Q, Pascual-Leone A, Caviness VS, Jr, Fox MD. Network localization of neurological symptoms from focal brain lesions. Brain 2015; 138(Pt 10): 3061-75. *J.Joutsa and L.Shih contributed equally to this work.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identifying-therapeutic-targets-from-spontaneous-beneficial-brain-lesions/