Tejas Sankar1, M Mallar Chakravarty2, Agustin Bescos3, Monica Lara4, Toshiki Obuchi5, Adrian W Laxton6, Mary Pat McAndrews7, David F Tang-Wai8, Clifford I Workman9, Gwenn S Smith9, Andres M Lozano10. 1. Division of Neurosurgery, University of Alberta, Edmonton, Alberta, Canada. 2. Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Quebec, Canada. 3. Joan XXIII University Hospital of Tarragona, Tarragona, Spain. 4. Son Espases University Hospital, Palma de Mallorca, Mallorca, Spain. 5. Department of Neurosurgery, Nihon University School of Medicine, Tokyo, Japan. 6. Department of Neurosurgery, Wake Forest University, Winston-Salem, NC, USA. 7. Department of Psychology, University of Toronto, Toronto, Ontario, Canada. 8. University Health Network Memory Clinic, Toronto, Ontario, Canada; Division of Neurology, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada. 9. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 10. Division of Neurosurgery, University of Toronto, Toronto, Ontario, Canada. Electronic address: lozano@uhnresearch.ca.
Abstract
BACKGROUND: Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. OBJECTIVE/HYPOTHESIS: We hypothesized that DBS applied to the fornix in patients with Alzheimer's Disease (AD) could have an effect on brain structure. METHODS: In six AD patients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism. We also compared volumetric changes to those in an age-, sex-, and severity-matched group of AD patients (n = 25) not receiving DBS. RESULTS: We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophy was significantly slower in the DBS group compared to the matched AD group, and no matched AD patients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. CONCLUSION: We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.
BACKGROUND: Deep Brain Stimulation (DBS) is thought to improve the symptoms of selected neurological disorders by modulating activity within dysfunctional brain circuits. To date, there is no evidence that DBS counteracts progressive neurodegeneration in any particular disorder. OBJECTIVE/HYPOTHESIS: We hypothesized that DBS applied to the fornix in patients with Alzheimer's Disease (AD) could have an effect on brain structure. METHODS: In six ADpatients receiving fornix DBS, we used structural MRI to assess one-year change in hippocampal, fornix, and mammillary body volume. We also used deformation-based morphometry to identify whole-brain structural changes. We correlated volumetric changes to hippocampal glucose metabolism. We also compared volumetric changes to those in an age-, sex-, and severity-matched group of ADpatients (n = 25) not receiving DBS. RESULTS: We observed bilateral hippocampal volume increases in the two patients with the best clinical response to fornix DBS. In one patient, hippocampal volume was preserved three years after diagnosis. Overall, mean hippocampal atrophy was significantly slower in the DBS group compared to the matched AD group, and no matched ADpatients demonstrated bilateral hippocampal enlargement. Across DBS patients, hippocampal volume change correlated strongly with hippocampal metabolism and with volume change in the fornix and mammillary bodies, suggesting a circuit-wide effect of stimulation. Deformation-based morphometry in DBS patients revealed local volume expansions in several regions typically atrophied in AD. CONCLUSION: We present the first in-human evidence that, in addition to modulating neural circuit activity, DBS may influence the natural course of brain atrophy in a neurodegenerative disease.
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