Better Than Before: Mapping Beneficial Brain Injuries

A study of rare cases of improvement after stroke sheds light on potential therapeutic targets in the brain

BOSTON – Ischemic stroke occurs when narrowed or blocked arteries disrupt blood flow to the brain. The resulting damage can result in paralysis, memory loss and diminished cognitive function. In rare cases, however, the brain damage caused by stroke – also called a lesion – can lead to an improvement of pre-existing symptoms. 

In a first-of-its-kind study, neuroscientists led by Michael Fox, MD, PhD, at Beth Israel Deaconess Medical Center (BIDMC) used a novel technique to map brain injuries that alleviated symptoms of essential tremor – the benign, involuntary shaking of hands experienced by about ten percent of people 71 and older. Their findings, published in July in the Annals of Neurology, demonstrate how the brain lesion network mapping technique – pioneered by Fox at BIDMC – might be used to identify therapeutic targets in the brain.

“Previous lesion network mapping studies have been restricted to lesions that cause specific symptoms,” said Fox, Co-Director of the Deep Brain Stimulation Program at BIDMC and an  Associate Professor in Neurology at Harvard Medical School. “By investigating lesions that improve pre-existing symptoms, we show that our mapping technique could potentially identify therapeutic targets for treatment of movement disorders, depression, migraine and addiction.” 

Fox and colleagues identified 11 cases in the medical literature in which ischemic stroke caused relief of patients’ pre-existing essential tremor. Fox’s lesion network mapping method revealed that even though the lesions were in various locations in the brain, all 11 were connected to common nodes in the cerebellum and thalamus – already a proven deep brain stimulation target for improving tremor. 

The scientists note that this study is limited by its small sample size and lack of optimal control group. However, the results suggest that lesion network mapping can be used to systematically identify effective therapeutic targets for a range of conditions. 

“Until now, the search for locations to induce therapeutic lesions to improve tremor or any other brain disorder have been guided in large part by trial and error or serendipity,” said Juho Joutsa, MD, PhD, a research fellow at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital and BIDMC’s Berenson-Allen Center. “We hope the current paper will motivate further research moving forward.” 

In addition to Fox and Joutsa, co-authors include Ludy C. Shih, MD, and Martin M. Reich, MD, of Beth Israel Deaconess Medical Center; Andreas Horn, MD, of Charite Universitatsmedizin zu Berlin; and Ona Wu, PhD, and Natalia S. Rost, MD, of Massachusetts General Hospital. 

Dr. Joutsa was supported by the Academy of Finland (grant # 295580), the Finnish Medical Foundation and the Orion Research Foundation. Dr. Shih was supported by private donor support to the Department of Neurology. Dr. Horn was supported by DFG KFO247, Thiemann Foundation, Berlin Institute of Health, Stiftung Charité. Dr. Reich was supported by Interdisciplinary Center for Clinical Research (Grant Number Z-3/64) of the University Hospital Wuerzburg and German section of the international Federation of Clinical Neurophysiology. Dr. Fox was supported by the Dystonia Medical Research Foundation, Nancy Lurie Marks Foundation, Mather’s Foundation, and the NIH (K23NS083741, R01MH113929).