Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications?

Chronic consumption of alcohol represents one of the greatest health and socioeconomic problems worldwide. We report on a 54-year-old patient with a severe anxiety disorder and secondary depressive disorder in whom bilateral deep brain stimulation (DBS) of the nucleus accumbens was carried out. Despite the absence of desired improvement in his primary disorder, we observed a remarkable although not primarily intended alleviation of the patient's comorbid alcohol dependency. Our case report demonstrates the extremely effective treatment of alcohol dependency by means of DBS of the nucleus accumbens and may reveal new prospects in overcoming therapy resistance in dependencies in general.

Subcutaneous Peripheral Nerve Field Stimulation for the Treatment of Chronic Back Pain: Patient Selection and Technical Aspects.

A wide variety of therapeutic options are available for the treatment of chronic back pain, a very common condition in Western countries with high related social and economic costs. Nevertheless, it is not always possible to achieve adequate long-term pain relief in spite of intensive analgesic therapies. Subcutaneous peripheral nerve field stimulation (sPNFS) is a newly approved neuromodulative treatment for back pain. In previously reported case series, it has provided encouraging results on long-term pain relief, improvement in quality of life, and a reduced need for analgesic drugs. Although the surgical technique is simple, there is neither consensus for patient management nor a standardized procedure for the implantation procedure. After consideration of our personal experience and the published literature, a basic recommendation has now been developed. This represents the first step toward planning prospective studies and standardization of this treatment and will permit comparison of this technique and the results with sPNFS.

Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a highly effective surgical treatment in patients with advanced Parkinson's disease (PD). Because the STN has been shown to represent an important relay station not only in motor basal ganglia circuits, the modification of brain areas also involved in non-motor functioning can be expected by this intervention. To determine the impact of STN-DBS upon the regional cerebral metabolic rate of glucose (rCMRGlc), we performed positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) in eight patients with advanced PD before surgery as well as in the DBS on- and off-conditions 4 months after electrode implantation and in ten age-matched healthy controls. Before surgery, PD patients showed widespread bilateral reductions of cortical rCMRGlc versus controls but a hypermetabolic state in the left rostral cerebellum. In the STN-DBS on-condition, clusters of significantly increased rCMRGlc were found in both lower thalami reaching down to the midbrain area and remote from the stimulation site in the right frontal cortex, temporal cortex, and parietal cortex, whereas rCMRGlc significantly decreased in the left rostral cerebellum. Therefore, STN-DBS was found to suppress cerebellar hypermetabolism and to partly restore physiologic glucose consumption in limbic and associative projection territories of the basal ganglia. These data suggest an activating effect of DBS upon its target structures and confirm a central role of the STN in motor as well as associative, limbic, and cerebellar basal ganglia circuits.

The nucleus accumbens: a target for deep brain stimulation in obsessive-compulsive- and anxiety-disorders.

We considered clinical observations in patients with obsessive-compulsive- and anxiety-disorders, who underwent bilateral anterior capsulotomy, as well as anatomical and pathophysiological findings. Based on these considerations, we choose the shell region of the right nucleus accumbens as target for deep brain stimulation (DBS) in a pilot-series of four patients with severe obsessive-compulsive- and anxiety-disorders. Significant reduction in severity of symptoms has been achieved in three of four patients treated. Clinical results as well as a 15-O-H(2)O-PET study, perfomed in one patient during stimulation, speak in favour of the following hypothesis. As a central relay-structure between amygdala, basal ganglia, mesolimbic dopaminergic areas, mediodorsal thalamus and prefrontal cortex, the accumbens nucleus seems to play a modulatory role in information flow from the amygdaloid complex to the latter areas. If disturbed, imbalanced information flow from the amygdaloid complex could yield obsessive-compulsive- and anxiety-disorders, which can be counteracted by blocking the information flow within the shell region of the accumbens nucleus by deep brain stimulation.

Bilateral high-frequency stimulation in the subthalamic nucleus for the treatment of Parkinson disease: correlation of therapeutic effect with anatomical electrode position.

OBJECT: The goal of this study was to relate the degree of clinical improvement and that of energy consumption to the anatomical position of electrode poles used for long-term stimulation. METHODS: The authors conducted a retrospective analysis of 15 consecutive patients in whom targeting of the subthalamic nucleus (STN) had been performed using ventriculography, three-dimensional (3D) magnetic resonance (MR) imaging, and 3D computerized tomography, together with macrostimulation and teleradiographic control of the electrode position. In these patients the follow-up period ranged from 6 to 12 months. Postoperative improvement in contralateral motor symptoms, which was assessed by assigning a lateralized motor subscore of the Unified Parkinson's Disease Rating Scale (UPDRS), and stimulus intensity required for optimal treatment results were correlated with the intracerebral position of the active electrode pole. Bilateral high-frequency stimulation of the STN improved the UPDRS motor score during the medication-off period by an average of 60.5% compared with that at baseline. Repeated transfer of stereotactic coordinates from postoperative teleradiography to treatment-planning MR images documented the proper localization of the most distal electrode pole (pole 0) in the targeted STN. Nevertheless, in most cases the best clinical improvement was achieved using electrode poles that were located several millimeters above the electrode tip. If the relative improvement in motor symptoms was correlated with the required electrical energy for chronic stimulation, the best coefficient was observed for active electrode poles projecting onto white matter dorsal to the STN. CONCLUSIONS: This observation makes blocking or activation of large fiber connections arising in the STN or running nearby more likely than electrical interference with cell bodies inside the STN. Anatomical correlates may be the pallidothalamic bundle (including Field H of Forel and the thalamic fascicle), the pallidosubthalamic tract, and/or the zona incerta.

Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: valuable therapeutic implications?

Chronic consumption of alcohol represents one of the greatest health and socioeconomic problems worldwide. We report on a 54-year-old patient with a severe anxiety disorder and secondary depressive disorder in whom bilateral deep brain stimulation (DBS) of the nucleus accumbens was carried out. Despite the absence of desired improvement in his primary disorder, we observed a remarkable although not primarily intended alleviation of the patient's comorbid alcohol dependency. Our case report demonstrates the extremely effective treatment of alcohol dependency by means of DBS of the nucleus accumbens and may reveal new prospects in overcoming therapy resistance in dependencies in general.

Transient Manic-like Episode Following Bilateral Deep Brain Stimulation of the Nucleus Accumbens and the Internal Capsule in a Patient With Tourette Syndrome.

Objective. Deep brain stimulation (DBS) increasingly attracts attention as a potential treatment of mental disorders. Beside depression and obsessive-compulsive disorders, DBS has already been shown to be beneficial for Tourette syndrome (TS). Clinical Presentation/Method. The authors report on the outcome of a patient with treatment-resistant TS who underwent bilateral DBS of the nucleus accumbens and the internal capsule. Results. Within the 10-month follow-up, a substantial reduction of tics has been observed. Yet, as a side-effect of DBS, the patient developed a transient manic-like episode when primarily stimulated by the most proximally contact in the internal capsule. Conclusions. This case supports the hypothesis that DBS of the nucleus accumbens and the internal capsule represents an effective therapeutic alternative for otherwise treatment-resistant TS. Yet, future controlled studies are needed to determine optimal stimulation parameters and to reduce negative side-effects such as transient hypomanic episodes.

Clinical protocols for titrating constant flow implantable pumps in patients with pain or spasticity.

Objectives The objective of this paper is to report the clinical protocols that we have developed and used for titrating constant flow implantable pumps to an effective dose in de novo pain and spasticity pump patients and, thereby, highlight the similarities and differences in our techniques. As a group, we have implanted over 1600 pumps and currently manage over 800 pump patients. Materials and Methods We used our collective experience of implanting over 1600 pumps to create protocols for performing the drug trial and the initial titration of constant flow implantable pumps in de novo patients. Results In creating our protocols, we found that constant flow pumps can be titrated to an effective dose with two to six adjustments over a period of 1-6 months. This compares favorably to reports of programmable pumps requiring 5.3 ± 3.5 adjustments over a period of 3-6 months to reach an effective dose. Conclusions A comparison of our protocols shows that after an initial stabilization period, dose adjustments can be made at subsequent refill, that it is not necessary to adjust the dose by prematurely emptying and filling constant flow pumps, and that it is not necessary to adjust the dose as often as has been done with programmable pumps.

Deep brain stimulation of the subthalamic nucleus does not increase the striatal dopamine concentration in parkinsonian humans.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) has become an effective treatment option in advanced Parkinson's disease (PD). Recent animal studies showed an increase of neuronal firing in dopaminergic neurons under effective STN-DBS. Increased striatal dopamine levels may also contribute to the stimulation's mechanism of action in humans. We investigated the striatal dopamine release in 6 patients with advanced PD under effective bilateral STN-DBS with positron emission tomography (PET) of the reversible dopamine-D2/3-receptor ligand [(11)C]raclopride (RACLO). Although STN-DBS proved to be a highly effective treatment in these subjects, we found no significant difference of the striatal RACLO binding between the STN-DBS-on and -off condition. The changes of radioligand binding did not correlate with the patients' improvement in clinical rating scales or with the stimulation amplitudes. Therefore, our PET data in living parkinsonian humans do not provide evidence for an increased striatal dopamine concentration under effective STN-DBS. We conclude that the modulation of dopaminergic activity does not seem to play a crucial role for the stimulation's mechanisms of action in parkinsonian humans.