Athanasios Koulousakis

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.

Deep-brain stimulation: long-term analysis of complications caused by hardware and surgery—experiences from a single centre

Objective: To determine the surgery-related and hardware-related complications of deep-brain stimulation (DBS) at a single centre. Methods: 262 consecutive patients (472 electrodes) operated for DBS in our department from February 1996 to March 2003 were retrospectively analysed to document acute adverse events (30 days postoperatively). The data of 180 of these patients were additionally revised to assess long-term complications (352 electrodes, mean follow-up 36.3 (SD 20.8) months). Results: The frequency of minor intraoperative complications was 4.2% (11/262 patients). Transient (0.2%) or permanent (0.4%) neurological deficits, and in one case asymptomatic intracranial haemorrhage (0.2%), were registered as acute severe adverse events caused by surgery. Among minor acute complications were subcutaneous bleeding along the extension wire (1.2%) and haematoma at the pulse generator implantation site (1.2%). Skin infection caused by the implanted material was registered in 15 of 262 patients (5.7%). The infection rate during the first observation period was 1.5% (4/262 patients) and the late infection rate was 6.1% (11/180 patients). Partial or complete removal of the stimulation system was necessitated in 12 of 262 (4.6%) patients because of skin infection. During the long-term observation period, hardware-related problems were registered in 25 of 180 (13.9%) patients. Conclusions: Stereotactic implantation of electrodes for DBS, if performed with multiplanar three-dimensional imaging and advanced treatment planning software, is a safe procedure with no mortality and low morbidity. The main causes for the patients’ prolonged hospital stay and repeated surgery were wound infections and hardware-related complications.

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 Parkinsons 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 nonmotor 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.

Deep brain stimulation of the nucleus accumbens and the internal capsule in therapeutically refractory Tourette-syndrome

Sirs: Tourette Syndrome (TS) is a neuropsychiatric disorder with typical onset in childhood, characterized by the chronic occurrence of motor and vocal tics. High rates of comorbidity with other psychiatric disorders, such as obsessive compulsive disorders (OCD) are to be found. OCD symptoms, which almost always accompany TS, are even discussed as constituting an integral component of the phenomenology of the disorder. Pharmacological treatment of the tics of TS centres predominantly on the use of neuroleptics. Patients with comorbid OCD can additionally benefit from clomipramine and selective serotonin reuptake inhibitors. Despite maximum dosage and combination of all known therapeutic approaches, a number of seriously affected individuals fail to experience satisfactory treatment results. In light of initially successful experimental treatment of TS using deep brain stimulation (DBS) it is hoped that this approach may, in the future, provide an alternative therapeutic option for pharmacologically refractory individuals. We report on a 26 year old male patient suffering, from puberty onwards, from a serious TS. The disorder is characterized by a broad spectrum of high-frequency simple and complex motor and vocal tics. Massive impairment is especially induced by autoaggressive and automutilative tics, as well as repetitive spitting and coprolalia. The disorder is additionally complicated by a severe OCD. The case history of the patient documents the unsuccessful administration of maximum doses and combinations of established treatments. The gravity of the disorder is substantiated by the fact that the patient has found himself in continuous in-patient psychiatric treatment since puberty. Furthermore, the patient has for the most part of this treatment period been physically restrained in order to prevent self injury. On account of this history, we considered a therapeutic trial using DBS to be indicated. Based on our experiences and the beneficial results gained in a pilot series of patients with intractable OCD and anxiety disorders [15], we selected the region of the nucleus accumbens (NA) as primary target for DBS in our patient with TS and comorbid OCD. Access and electrode trajectories were determined by a computer-supported image fusion of MRI and intraoperative CT. 3-D coordinates for localisation of the target point were as follows: 2,5 mm rostral anterior border of AC, 6,5 mm lateral of midline, 4,5 mm ventral AC. Stereotactically guided implantation of quadripolar electrodes (Medtronic 3387; Medtronic, Inc., Minneapolis, MN) was carried out under general anaesthetic. The correct positioning of these was postoperatively confirmed by means of CT and conventional x-ray procedures (pole 0,1: fundus subventricularis medialis of the nucleus accumbens; pole 2,3: anterior limb of the internal capsule). A pulse generator (Kinetra, Medtronic, Inc., Minneapolis, MN) connected to the electrodes was implanted inferior to the clavicles. During a post-operative phase of adjustment lasting a few months, the following settings appeared most effective: ()0,)1,)2,)3 anode; + case cathode; pulse width 90 ls, 130 Hz, 7 V); although these parameter settings also resulted in an extremely high energy consumption. Under application of DBS with the aforementioned parameters, the patient showed a significant reduction in both the frequency and gravity of his tics over the course of a two and half year observation period. Remission rates of 41% and 50% were found based on measurements with the Yale Global Tic Severity Scale [12] and the Modified Rush Video Rating Scale [7] respectively (Figure 1). Tics involving self injury were especially reduced and symptoms of coprolalia disapJ. Kuhn, MD (&) Æ W. Huff, MD S.-H. Lee, MD Æ J. Klosterkoetter, MD Dept. of Psychiatry and Psychotherapy University of Cologne Kerpener Strasse 62 50924 Cologne, Germany Tel.: +49-221/478-4005 E-Mail: Jens.Kuhn@uk-koeln.de

Drug Adverse Events and System Complications of Intrathecal Opioid Delivery for Pain: Origins, Detection, Manifestations, and Management

Intrathecal drug delivery is effective for the treatment of cancer and nonmalignant pain in patients who do not respond well to oral opioids, in patients who cannot tolerate the side effects associated with opioids, or in patients who show a large, permanent increase in dosage. Although intrathecal drug delivery is associated with pharmacological side effects and complications, its benefits far outweigh its risks. There are three main categories of potential adverse events associated with intrathecal drug delivery: pharmacologic side effects, surgical complications, and device‐related complications. Prevention, early recognition, and prompt management of adverse events will optimize patient outcomes. Many adverse events either resolve on their own or can be managed with dosage or device adjustment. More serious complications may require surgical intervention or discontinuation of therapy. This paper will provide an overview of adverse events and complications, their origins, detection, manifestations, and management.

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).

Deep brain stimulation for Parkinson's disease.

Indications for the treatment of Parkinsons disease (PD) with deep brain stimulation (DBS) are severe, therapy refractory tremor and complications of long-term levodopa uptake. Since its first application DBS has become a standard therapy for these patients. Theoretically, the ventrolateral part of the internal pallidum (GPI) or the subthalamic nucleus (STN) are suitable targets in order to treat all cardinal symptoms of patients in an advanced stage of PD stereotactically. Although clinical efficacy of both GPI or STN stimulation is obviously comparable, it has become widely accepted to prefer STN over GPI DBS. If PD-associated, medically intractable tremor is the most disabling symptom, stimulation of the ventrolateral motor thalamus can be an alternative. Anatomical targets for DBS are small and located in critical brain areas. Furthermore, this type of surgery is highly elective. As a consequence, high resolution multiplanar imaging and adequate treatment planning software are indispensable prerequisites for DBS surgery. Currently, commercially available impulse generators deliver a permanent high frequency periodic pulse train stimulation that interacts rather unspecifically with the firing pattern of both normal and pathological neurons. Prospectively, the development of more specific stimulation paradigms may help to improve the efficacy of this treatment modality.

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.

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.

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.