Deep brain stimulation in the treatment of obesity.

Obesity is a growing global health problem frequently intractable to current treatment options. Recent evidence suggests that deep brain stimulation (DBS) may be effective and safe in the management of various, refractory neuropsychiatric disorders, including obesity. The authors review the literature implicating various neural regions in the pathophysiology of obesity, as well as the evidence supporting these regions as targets for DBS, in order to explore the therapeutic promise of DBS in obesity. The lateral hypothalamus and ventromedial hypothalamus are the appetite and satiety centers in the brain, respectively. Substantial data support targeting these regions with DBS for the purpose of appetite suppression and weight loss. However, reward sensation associated with highly caloric food has been implicated in overconsumption as well as obesity, and may in part explain the failure rates of conservative management and bariatric surgery. Thus, regions of the brain's reward circuitry, such as the nucleus accumbens, are promising alternatives for DBS in obesity control. The authors conclude that deep brain stimulation should be strongly considered as a promising therapeutic option for patients suffering from refractory obesity.

Mechanical failure of the electrode wire in deep brain stimulation.

The feasibility and efficacy of deep brain stimulation (DBS) has offered new possibilities for treatment of movement disorders. Mechanical failure of the DBS system is a potential complication. Here we report five patients who presented with mechanical failure of the DBS system. Radiographs of the skull and cervical spine were analyzed for disruptions. Seven instances of lead breakage near the connection of the DBS electrode with the extension wire were identified. In one patient this was in the paramastoid area over the skull, while in all others were in the supraclavicular location. The patients consisted of three men and two women ranging in age from 24 to 78 (at the time of first operation), one person suffering three breakages. The length of spanned time from implantation to presentation ranged from 8 to 32 months. Palpation of the electrode lead wire in the neck for breakage proved unreliable. Radiography localized the site of breakage in all but one patient who required intraoperative exploration, which revealed that although the lead wire was disrupted, the two ends remained in contact. The fact that all breakages occurred near the connection wire suggests that to-and-fro motion of the DBS electrode with repeated head turning leads to fatigue and eventual disruption.

Endovascular microcoil gene delivery using immobilized anti-adenovirus antibody for vector tethering.

BACKGROUND AND PURPOSE: Endovascular microcoils are widely used in interventional procedures to treat cerebral aneurysms. In the present study we report for the first time successful use of an endovascular microcoil as a gene delivery system. METHODS: Anti-adenoviral monoclonal antibodies were covalently attached to the collagen-coated surface of either platinum or polyglycolic acid microcoils. These antibodies were used to tether replication-deficient adenovirus (Ad-GFP [encoding green fluorescent protein] or Ad-LacZ [encoding beta-galactosidase]). Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the coil. Platinum coils coated with Ad-GFP were implanted into the ligated common carotid artery (CCA) of adult rats in a model of arterial stasis and pressurization. After 7 days, CCA segments were harvested, and coils were removed for histopathology and GFP expression studies, while organs were evaluated by polymerase chain reaction to assess viral biodistribution. RESULTS: In cell culture studies, GFP-positive smooth muscle cells were detected only on the platinum coil surface, while LacZ-positive cells were detected only on the polyglycolic acid coil surface, thus demonstrating localized gene delivery. After 7-day implantation, GFP (according to fluorescence microscopy and confirmed with immunohistochemistry) was detected on the harvested platinum coil and in the organizing thrombus within the CCA but not in the arterial wall. Morphometric analyses revealed that 13.3+2.0% of cells within the organized thrombus were transduced with Ad-GFP via the gene delivery system. However, arterial smooth muscle cells were negative for GFP according to fluorescence microscopy and immunohistochemistry. Ad-GFP was not detectable by polymerase chain reaction in lung, liver, or kidney. CONCLUSIONS: It is concluded that catheter deployment of platinum or biodegradable gene delivery endovascular microcoils represents an interventional device-based gene therapy system that can serve as a suitable platform for either single or multiple gene therapy vectors.