Wakefulness-promoting effects of lateral hypothalamic area deep brain stimulation in traumatic brain injury-induced comatose rats: Upregulation of α1-adrenoceptor subtypes and downregulation of gamma-aminobutyric acid b receptor expression via the orexins pathway

Abstract BACKGROUND: Severe traumatic brain injury (TBI) damages the frontal lobes and connecting networks, which impairs executive functions, including the ability to self-regulate. Despite significant disabling effects, there are few treatment options in the chronic phase after injury. OBJECTIVE: To investigate the safety and potential effectiveness of deep brain stimulation (DBS) for individuals with chronic, disabling TBI and problems of behavioral and emotional self-regulation. METHODS: This study was an open-label, prospective design with serial assessments of behavioral outcomes and positron emission tomography 2 years after DBS implantation. Four participants 6 to 21 years after severe TBIs from automobile crashes were included. Although alert and volitional, all experienced significant executive impairments, including either impulsivity or reduced initiation. DBS implants were placed bilaterally in the nucleus accumbens and anterior limb of the internal capsule to modulate the prefrontal cortex. RESULTS: The procedure was safe, and all participants had improved functional outcomes. Two years after implantation, 3 met a priori criteria for improvement on the Mayo-Portland Adaptability Inventory-4. Improvement was due largely to better emotional adjustment, although 1 participant showed marked increases in multiple domains. Significant improvement in a composite score of functional capacity indicated improved independence in self-care and activities of daily living. The pattern of change in cognition corresponded with changes in activation of the prefrontal cortex observed in serial scanning. CONCLUSION: This first study of DBS to this target for severe TBI supports its safety and suggests potential effectiveness to improve function years after injury. The primary impact was on behavioral and emotional adjustment, which in turn improved functional independence. Supplemental Digital Content is Available in the Text. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.neurosurgery-online.com).

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Anesthesia for deep brain stimulation in traumatic brain injury‐induced hemidystonia

Clinical Case Reports ◽

10.1002/ccr3.289 ◽

2015 ◽

Vol 3 (6) ◽

pp. 492-495 ◽

Cited By ~ 1

Author(s):

Jill M. Jani ◽

Chima O. Oluigbo ◽

Srijaya K. Reddy

Keyword(s):

Traumatic Brain Injury ◽

Deep Brain Stimulation ◽

Brain Injury ◽

Brain Stimulation ◽

Deep Brain

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Deep brain stimulation for the treatment of disorders of consciousness and cognition in traumatic brain injury patients: a review

Neurosurgical FOCUS ◽

10.3171/2018.5.focus18168 ◽

2018 ◽

Vol 45 (2) ◽

pp. E14 ◽

Cited By ~ 11

Author(s):

Bornali Kundu ◽

Andrea A. Brock ◽

Dario J. Englot ◽

Christopher R. Butson ◽

John D. Rolston

Keyword(s):

Traumatic Brain Injury ◽

Executive Function ◽

Deep Brain Stimulation ◽

Brain Injury ◽

Brain Stimulation ◽

Minimally Conscious State ◽

Disorders Of Consciousness ◽

Future Research ◽

Attention And Memory ◽

Deep Brain

Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.

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Lateral hypothalamic area deep brain stimulation for refractory obesity: a pilot study with preliminary data on safety, body weight, and energy metabolism

Journal of Neurosurgery ◽

10.3171/2013.2.jns12903 ◽

2013 ◽

Vol 119 (1) ◽

pp. 56-63 ◽

Cited By ~ 71

Author(s):

Donald M. Whiting ◽

Nestor D. Tomycz ◽

Julian Bailes ◽

Lilian de Jonge ◽

Virgile Lecoultre ◽

...

Keyword(s):

Weight Loss ◽

Deep Brain Stimulation ◽

Energy Metabolism ◽

Pilot Study ◽

Brain Stimulation ◽

Lateral Hypothalamic Area ◽

Hypothalamic Area ◽

Lateral Hypothalamic ◽

Deep Brain

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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