Disease Stabilization of DYT1-Positive Primary Generalized Dystonia With Deep Brain Stimulation of the Globus Pallidus Interna: A 15-Year Follow-up.

BACKGROUND AND IMPORTANCE: Primary generalized dystonia (PGD) is a genetic form of dystonia that frequently displays pharmacological resistance and progresses quickly after onset. Deep brain stimulation (DBS) has been used successfully to treat refractory dystonia, specifically globus pallidus interna (GPi) DBS for DYT1-positive PGD patients. Long-term follow-up of the safety and efficacy falls short of the longevity seen in other diseases treated with DBS. CASE PRESENTATION: A male patient presented for neurosurgical evaluation with scapular winging, hand contractures, and violent truncal spasms, which forced him to be bedridden. After failing conservative therapy, the 18-yr-old patient was implanted with bilateral GPi-DBS. DBS parameter adjustments were made primarily within the first 3 yr after implantation, with nominal changes thereafter. Initial settings were contact of 3 + 0-, amplitude of 4.9 V, frequency of 185 Hz, and pulse width of 270 µsec on the left and 3 + 0-, 2.8 V, 185 Hz, and 120 µsec on the right. Current settings are 3 + 2 + 1-, 5.2 V, 130 Hz, 330 µsec on the left and 3 + 0-, 3.5 V, 185 Hz, and 180 µsec on the right and have been relatively unchanged in the past 4 yr. Unified dystonia rating scale scores reveal a significant decrease in dystonic symptoms. CONCLUSION: While prior reports have shown that GPi-DBS is effective for dystonia, this is the first with 15 yr of long-term follow-up showing disease stabilization, suggesting that stimulation is efficacious and can potentially prevent disease progression. This report reaffirms previous reports that recommend early surgical intervention before the onset of permanent musculoskeletal deficits.

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

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.

Mapping of microstimulation evoked responses and unit activity patterns in the lateral hypothalamic area recorded in awake humans. Technical note.

Major contributions to the understanding of human brain function have come from detailed clinical reports of responses evoked by electrical stimulation and specific brain regions during neurosurgical procedures in awake humans. In this study, microstimulation evoked responses and extracellular unit recordings were obtained intraoperatively in 3 awake patients undergoing bilateral implantation of deep brain stimulation electrodes in the lateral hypothalamus. The microstimulation evoked responses exhibited a clear anatomical distribution. Anxiety was most reliably evoked by stimulation directed ventromedially within or adjacent to the ventromedial nucleus of the hypothalamus, nausea was most reliably evoked by stimulation directed at the center of the lateral hypothalamus, and paresthesias were most reliably evoked by stimulation at the border of the lateral hypothalamus and basal nuclei. Regarding the unit recordings, the firing rates of individual neurons did not have an anatomical distribution, but a small subpopulation of neurons located at the border of the lateral hypothalamus and basal nuclei exhibited a fast rhythmically bursting behavior with an intraburst frequency of 200-400 Hz and an interburst frequency of 10-20 Hz. Based on animal studies, the lateral hypothalamic area and surrounding hypothalamic nuclei are putatively involved with a variety of physiological, behavioral, and sensory functions. The lateral hypothalamus is situated to play a dynamic and complex role in human behavior and this report further shows that to be true. In addition, this report should serve as a valuable resource for future intracranial work in which accurate targeting within this region is required.

Induction of panic attack by stimulation of the ventromedial hypothalamus.

Panic attacks are sudden debilitating attacks of intense distress often accompanied by physical symptoms such as shortness of breath and heart palpitations. Numerous brain regions, hormones, and neurotransmitter systems are putatively involved, but the etiology and neurocircuitry of panic attacks is far from established. One particular brain region of interest is the ventromedial hypothalamus (VMH). In cats and rats, electrical stimulation delivered to the VMH has been shown to evoke an emotional "panic attack-like" escape behavior, and in humans, stimulation targeting nuclei just posterior or anterior to the VMH has reportedly induced panic attacks. The authors report findings obtained in an awake patient undergoing bilateral implantation of deep brain stimulation electrodes into the hypothalamus that strongly implicates the VMH as being critically involved in the genesis of panic attacks. First, as the stimulating electrode progressed deeper into the VMH, the intensity of stimulation required to evoke an attack systematically decreased; second, while stimulation of the VMH in either hemisphere evoked panic, stimulation that appeared to be in the center of the VMH was more potent. Thus, this evidence supports the role of the VMH in the induction of panic attacks purported by animal studies.