OBJECT Anterior nuclear (AN) stimulation has been reported to reduce the frequency of seizures, in some cases dramatically; however, it has not been approved by the US Food and Drug Administration. The anterior nucleus is difficult to target because of its sequestered location, partially surrounded by the ventricle. It has traditionally been targeted by using transventricular or lateral transcortical routes. Here, the authors report a novel approach to targeting the anterior nucleus and neurophysiologically confirming effective stimulation of the target, namely evoked potentials in the hippocampus. METHODS Bilateral AN 3389 electrodes were placed in a novel trajectory followed by bilateral hippocampal 3391 electrodes from a posterior trajectory. Each patient was implanted bilaterally with a Medtronic Activa PC+S device under an investigational device exemption approval. Placement was confirmed with CT. AN stimulation-induced hippocampal evoked potentials were measured to functionally confirm placement in the anterior nucleus. RESULTS Two patients had implantations by way of a novel AN trajectory with concomitant hippocampal electrodes. There were no lead misplacements. Postoperative stimulation of the anterior nucleus with a PC+S device elicited evoked potentials in the hippocampus. Thus far, both patients have reported a > 50% improvement in seizure frequency. CONCLUSIONS Placing AN electrodes posteriorly may provide a safer trajectory than that used for traditionally placed AN electrodes. In addition, with a novel battery that is capable of electroencephalographic recording, evoked potentials can be used to functionally assess the Papez circuit. This treatment paradigm may offer increased AN stimulation efficacy for medically intractable epilepsy by assessing functional placement more effectively and thus far has proven safe.

Deep brain stimulation (DBS) of the thalamic centromedian/parafascicular (CM-Pf) complex has been reported as a promising treatment for patients with severe, treatment resistant Tourette syndrome (TS). In this study, safety and clinical outcomes of bilateral thalamic CM-Pf DBS were reviewed in a series of twelve consecutive patients with medically refractory TS, eleven of whom met the criteria of post-surgical follow-up at our institution for at least two months. Five subjects were followed for a year or longer. Consistent with many TS patients, all subjects had psychiatric co-morbidities. Tic severity and frequency was measured by the Yale Global Tic Severity Scale (YGTSS) over time (average 26 months) in ten subjects. One subject was tested at two weeks follow-up only and thus was excluded from group YGTSS analysis. Final YGTSS scores differed significantly from preoperative baseline. The average (n=10) improvement relative to baseline in the Total Score was 54% (95% confidence interval (CI): 37–70); average improvement relative to baseline in the YGTTS Motor tic, Phonic tic, and Impairment subtests was 46% (95% CI: 34–64), 52% (95% CI: 34–72), and 59% (95% CI: 39–78), respectively. There were no intraoperative complications. Following surgery, one subject underwent wound revision due to a scalp erosion and wound infection; the implanted DBS system was successfully salvaged with surgical revision and combined antibiotic therapy. Stimulation-induced adverse-effects did not prevent the use of the DBS system, although one subject is undergoing a trial period with the stimulator off. This surgical series adds to the literature on CM-Pf DBS and supports its use as an effective and safe therapeutic option for severe refractory TS.

A 31-year-old woman was admitted for fever and altered mentation of unclear etiology 16 months after a renal transplant. This was her third admission in 4 months for fever of unclear etiology, but the current admission differed in that she also demonstrated short-term memory loss, dramatic mood swings, agitation, and paranoid delusions. Other significant medical history included nonHodgkin lymphoma in childhood for which she underwent 2 allogeneic stem cell transplants, chemotherapy, and whole-body radiation. She also developed postradiation kidney failure which necessitated a cadaveric kidney transplant followed by immunosuppression with tacrolimus 2 mg BID and mycophenolate 1 g BID. Questions for consideration:

Background and objectivesDeep brain stimulation (DBS) of the thalamus is a promising therapeutic alternative for treating medically refractory Tourette syndrome (TS). However, few human studies have examined its mechanism of action. Therefore, the networks that mediate the therapeutic effects of thalamic DBS remain poorly understood.MethodsFive participants diagnosed with severe medically refractory TS underwent bilateral thalamic DBS stereotactic surgery. Intraoperative fMRI characterized the blood oxygen level-dependent (BOLD) response evoked by thalamic DBS and determined whether the therapeutic effectiveness of thalamic DBS, as assessed using the Modified Rush Video Rating Scale test, would correlate with evoked BOLD responses in motor and limbic cortical and subcortical regions.ResultsOur results reveal that thalamic stimulation in TS participants has wide-ranging effects that impact the frontostriatal, limbic, and motor networks. Thalamic stimulation induced suppression of motor and insula networks correlated with motor tic reduction, while suppression of frontal and parietal networks correlated with vocal tic reduction. These regions mapped closely to major regions of interest (ROI) identified in a nonhuman primate model of TS.ConclusionsOverall, these findings suggest that a critical factor in TS treatment should involve modulation of both frontostriatal and motor networks, rather than be treated as a focal disorder of the brain. Using the novel combination of DBS-evoked tic reduction and fMRI in human subjects, we provide new insights into the basal ganglia-cerebellar-thalamo-cortical network-level mechanisms that influence the effects of thalamic DBS. Future translational research should identify whether these network changes are cause or effect of TS symptoms.