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Donald M. Whiting, Nestor D. Tomycz, Julian Bailes, Lilian de Jonge, Virgile Lecoultre, Bryan Wilent, Dunbar Alcindor, E. Richard Prostko, Boyle C. Cheng, Cynthia Angle, Diane Cantella, Benjamin B. Whiting, J. Scott Mizes, Kirk W. Finnis, Eric Ravussin and Michael Y. Oh

Object

Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity. The authors present the 2-year safety results as well as early efficacy and metabolic effects in 3 patients undergoing bilateral LHA DBS in the first study of this approach in humans.

Methods

Three patients meeting strict criteria for intractable obesity, including failed bariatric surgery, underwent bilateral implantation of LHA DBS electrodes as part of an institutional review board– and FDA-approved pilot study. The primary focus of the study was safety; however, the authors also received approval to collect data on early efficacy including weight change and energy metabolism.

Results

No serious adverse effects, including detrimental psychological consequences, were observed with continuous LHA DBS after a mean follow-up of 35 months (range 30–39 months). Three-dimensional nonlinear transformation of postoperative imaging superimposed onto brain atlas anatomy was used to confirm and study DBS contact proximity to the LHA. No significant weight loss trends were seen when DBS was programmed using standard settings derived from movement disorder DBS surgery. However, promising weight loss trends have been observed when monopolar DBS stimulation has been applied via specific contacts found to increase the resting metabolic rate measured in a respiratory chamber.

Conclusions

Deep brain stimulation of the LHA may be applied safely to humans with intractable obesity. Early evidence for some weight loss under metabolically optimized settings provides the first “proof of principle” for this novel antiobesity strategy. A larger follow-up study focused on efficacy along with a more rigorous metabolic analysis is planned to further explore the benefits and therapeutic mechanism behind this investigational therapy.

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Bennet Omalu, Jennifer L. Hammers, Julian Bailes, Ronald L. Hamilton, M. Ilyas Kamboh, Garrett Webster and Robert P. Fitzsimmons

Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.

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Introduction

Sports-related neurosurgical injuries

Julian Bailes, Joseph Maroon and Shenandoah Robinson

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Bengt Karlsson, Ingmar Lax, Masaaki Yamamoto, Michael Söderman, Hidefumi Jokura, Charles Rosen and Julian Bailes

Object

The authors sought to assess the relationship between obliteration rate and different dose parameters following fractionated radiotherapy for arteriovenous malformations (AVMs). A comparison of the results of radiosurgery and radiotherapy for AVMs was made to calculate the best fit α/β value, which would then be used as a model for predicting the treatment outcome, independent of the number of fractions applied.

Methods

Data from 1453 patients were analyzed: 1154 treated with radiosurgery and 300 with fractionated radiotherapy. The relationships between dose and obliteration rate after 3 years were calculated, and the best fit curve to the empirical results was defined. The higher the dose per fraction, biologically effective dose, and the lower the total dose, the higher the obliteration rate. The isoeffective doses when comparing radiotherapy and radiosurgery independent of the α/β value could not be defined. The dose per fraction had the best predictive value, independent of the number of fractions.

Conclusions

Dose per fraction seems to be the decisive parameter for the treatment response following both radiotherapy and radiosurgery. A larger number of fractions did not increase the obliteration rate. The data indicate that higher doses per fraction should be used when irradiating AVMs.