Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: psychopathological and neuropsychological outcome in three cases.

OBJECTIVE: Investigation of deep brain stimulation (DBS) as a last-resort treatment alternative to capsulotomy in treatment-refractory obsessive-compulsive disorder (OCD). METHOD: Prospective single-case based design with evaluation of DBS impact on emotions, behaviour, personality traits and executive function in three patients with OCD. RESULTS: Two patients experienced sustained improvement of OCD symptoms with DBS. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) dropped 12 points and 23 points to baseline and Y-BOCS self-rating scale (Y-BOCS-SRS) and Profile of Mood States (POMS) for depression and tension decreased with increasing stimulation amplitude. Total Maladjustment Score on the Brief Psychiatric Rating Scale reduced with 44 and 59% to baseline. Reduction in psychopathology was sustained under continuous stimulation. No deleterious impact of DBS on neuropsychological testing or personality traits measured on a self-rated personality inventory was detected. CONCLUSION: These preliminary findings demonstrate that DBS may have important therapeutic benefits on psychopathology in OCD. No harmful side-effects were detected during follow-up (33/33/39 months, respectively).

Effect of the serotonin agonist 8-OH-DPAT on the sensorimotor system of the rat.

8-Hydroxy-2-(di-n-propylamino)-tetralin hydrobromide (8-OH-DPAT, 2 mg/kg) is used to induce perseverative behavior in rats in a T-maze as a model for obsessive-compulsive disorder (OCD). Using the open-field test, radiant heat test, and the test with von Frey filaments, we examined whether alterations in sensorimotor functioning could contribute to the perseverative tendencies in this model by measuring differences in left versus right hind paw reactions after 8-OH-DPAT administration (2 mg/kg, sc). Also, the effect of repeated 8-OH-DPAT administration on sensorimotor functioning was tested every third day. 8-OH-DPAT administration induced a significantly decreased sensorimotor performance in the open-field test, an increased threshold for noxious thermal stimulation (increased withdrawal latency, WL, and decreased elevation time, ET) in the radiant heat test, and a decreased nociceptive threshold for mechanical stimulation in the test with von Frey filaments. All changes in sensorimotor functioning were similar for left and right hind paws suggesting that, these changes as measured with the tests in the present study, are not likely to contribute to the perseverative behavior of rats in a T-maze. Further, repeated administration of 8-OH-DPAT had no effect in the radiant heat test and the test with the Frey filaments, but produced a tolerance effect in the open-field test.

Thalamic stimulation in neuropathic pain: 27 years later.

An overview is given of CNS mechanisms which are behind the beneficial effects of VPL-VPM thalamic stimulation in the treatment of neuropathic pain. Further research in this field is urgently needed and the recent possibility to combine Deep Brain Stimulation with positron emission tomography (PET) will certainly help to unravel the brain circuitry implicated in stimulation-produced analgesia. Brain stimulation is an artificial way to activate nervous tissue that is reversible and, when correctly applied, has few complications. The clinical results warrant a continued dissemination of brain stimulation as a treatment in well selected cases of neuropathic pain.

Electrical stimulation of the brain for psychiatric disorders.

Despite advances in therapies, there remain psychiatric patients who are extremely ill and cannot be helped by classic psychiatric treatments, including psychotherapy and drug therapy. Certain of these patients may be helped by use of bilateral brain lesioning. The complication rate of standard stereotactic psychosurgery techniques is very low. The main rationale for the continued experimental use of deep brain stimulation (DBS) in neurosurgery for mental disorders is its reversibility. This reversibility is not an advantage in terms of the benefits obtained, but rather if side effects emerge. In addition, electrical stimulation may provide patients with some autonomy for their treatment. The first, very preliminary results of electrical stimulation for obsessive-compulsive disorder and for a small heterogeneous group of patients with other psychiatric disorders have been published. Electrical stimulation of the brain for psychiatric disorders may become a new treatment option for certain intractable psychiatric disorders. Nevertheless, the mechanism of action of DBS in psychiatric disorders is unknown, and the experience with this modality is extremely limited. The first results look promising, but this treatment option may prove unusable for some time because of a lack of knowledge of appropriate brain stimulation targets and technical problems such as the availability of sufficient current supply.

Targeting the basal ganglia for deep brain stimulation in Parkinson's disease.

The revitalization of surgery for Parkinson's disease (PD) has fueled discussion about the best methodology to define the target. Placement of electrodes for deep brain stimulation (DBS) requires the usual stereotactic technique but the argument is mainly centered on whether or not microrecording neuronal activity is necessary. We compared the accuracy of calculating the coordinates X (medio-lateral) and Y (rostro-caudal) considered by the classic stereotactic method, i.e., definition of the AC-PC intercomissural line by MRI and a digitized version of the Schaltenbrand's atlas, with final electrode placement according with microrecording and microstimulation in 21 patients. For both the globus pallidum internum (GPi) (n = 21) and the subthalamic nucleus (STN) (n = 36) there was, respectively, a 43% and 45% mismatching of more than 3 mm between the theoretic coordinates and the final site of electrode location. This applies to both the X and Y planes. Accuracy was not improved in patients (n = 11) in whom the bilateral procedure was undertaken in a single day. We conclude that proper electrode positioning of the STN and GPi requires fine electrophysiologic assessment.

Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder.

Chronic electrical stimulation instead of bilateral capsulotomy was done in four selected patients with long-standing treatment-resistant obsessive-compulsive disorder. In three of them beneficial effects were observed.

[The placebo effect: classes of explanation]. / Het placebo-effect: klassen van verklaring.

The placebo effect is a frequent phenomenon in medicine, but very little is known about its mechanisms. An overview is given of the different classes of explanation of the placebo effect in analgesia and in particular the role of endogenous opioids, classical conditioning and expectations. Then the question is raised which are the properties of placebo for which a theory has to provide answers in order to be coherent. These properties are, between others, the efficacy of placebo in a variety of conditions, in individuals with different personality characteristics, etc. Finally, the difficulty of observing individual placebo is emphasized and problems concerning the diagnostic and therapeutic use of placebo are mentioned.

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography.

Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J. Neurophysiol. 80: 3326-3330, 1998. Stimulation of the somatosensory thalamus was used for more than 2 decades to treat chronic pain in the human. However, despite clinical reports of successful results, little is known about the actual mechanisms mediating this form of stimulation-produced analgesia. To reveal possible neuronal pathways evoked by thalamic stimulation, we measured regional changes in cerebral blood flow (rCBF) in five patients who received successful long-term relief of chronic pain with somatosensory thalamic stimulation. Positron emission tomography during thalamic stimulation revealed significant activation of the thalamus in the region of the stimulating electrodes as well as activation of the insular cortex ipsilateral to the thalamic electrodes (contralateral to the patients' clinical pain). For these patients, thalamic stimulation also evoked paresthesiae that included thermal sensations in addition to tingling sensations. Results of this study indicate that in some cases somatosensory thalamic stimulation may activate a thalamocortical pain modulation circuit that involves thermal pathways. These results are consistent with other recent reports suggesting that activation of thermal pathways may contribute to modulation of nociceptive information.

Estimation of fiber diameters in the spinal dorsal columns from clinical data.

Lack of human morphometric data regarding the largest nerve fibers in the dorsal columns (DC's) of the spinal cord has lead to the estimation of the diameters of these fibers from clinical data retrieved from patients with a new spinal cord stimulation (SCS) system. These patients indicated the perception threshold of stimulation induced paresthesia in various body segments, while the stimulation amplitude was increased. The fiber diameters were calculated with a computer model, developed to calculate the effects of SCS on spinal nerve fibers. This computer model consists of two parts: 1) a three-dimensional (3-D) volume conductor model of a spinal cord segment in which the potential distribution due to electrical stimulation is calculated and 2) an electrical equivalent cable model of myelinated nerve fiber, which uses the calculated potential field to determine the threshold stimulus needed for activation. It is shown that the largest fibers in the medial DC's are significantly smaller than the largest fibers in the lateral parts. This finding is in accordance with the fiber distribution in cat, derived from the corresponding propagation velocities. Moreover, it is shown that the mediolateral increase in fiber diameter is mainly confined to the lateral parts of the DC's. Implementation of this mediolateral fiber diameter distribution of the DC's in the computer model enables the prediction of the recruitment order of dermatomal paresthesias following increasing electrical stimulation amplitude.

Clinical evaluation of paresthesia steering with a new system for spinal cord stimulation.

OBJECTIVE: The goal was to evaluate, in a clinical study, the predicted performance of the transverse tripolar system for spinal cord stimulation, particularly the steering of paresthesia, paresthesia coverage, and the therapeutic range of stimulation. METHODS: Six transverse tripolar electrodes were implanted in the lower thoracic region in four patients experiencing chronic neuropathic pain. Electrode positions, relative to the spinal cord, were estimated from computed tomographic scans. A dual-channel stimulator was used for initial percutaneous tests, and an implanted single-channel stimulator was used for follow-up test sessions. Nine "balance" settings and several cathode-anode combinations were used with the dual-channel and single-channel stimulator, respectively. In each test, the increase of paresthesia coverage from the perception threshold to the discomfort threshold was registered on a body map and the corresponding voltages were recorded. RESULTS: Paresthesia steering occurred in all but one patient. The normalized steering score, enabling quantitative comparisons of paresthesia steering among tests and patients, showed that maximum paresthesia steering occurred when the electrode was at least 3 mm dorsal to the spinal cord and centered <2 mm from its midline. Paresthesia coverage included 70 to 100% of the body up to the electrode level, unless the electrode migrated or had broken wires. The therapeutic range, defined as the discomfort/perception of paresthesia threshold ratio, varied from 1.6 to 4.0. CONCLUSION: The clinical performance of transverse tripolar stimulation is in accordance with the characteristics predicted by computer modeling. It enables finer control of paresthesia than that achieved by polarity changes in conventional spinal cord stimulation systems.

[Image-guided surgery]. / Beeldgestuurde chirurgie.

Initially, stereotactic surgery was developed to treat functional brain diseases only. The localisation of targets was based on stereotactic atlases and radiographs. The introduction of computer based imaging techniques, such as CT and MRI, have offered the possibility to "see" anomalies and to approach them stereotactically. The working principle of such a procedure consists of three steps. It is assumed that brain tissue does not move with respect to the skull. 1. Acquisition of the images and their registration with the patient, usually based on a series of reference points (fiducials) that belong to a stereotactic localizer attached to the base ring of the stereotactic frame, 2. planning and simulation of the surgical intervention, mostly based on two-dimensional (2D) images resliced along arbitrary directions, and 3. intra-operative guidance of the instruments mounted onto the stereotactic frame. This procedure has continuously been updated by new image acquisition techniques, 3D visualization and frameless stereotaxy. 1. PET, MRI and angiography (DSA, MRA) have been used in addition to CT. Moreover, such images of different modalities can automatically be fused without using a stereotactic frame or other artificial fiducials. 2. 3D images for surgery planning have become available, a feature that has proved to be very useful for the cerebral blood vessels. 3. The stereotactic frame can be replaced by a robot arm or an optical guidance system. Registration of the instruments with the patient is then performed by using markers in the cranial bone or on the scalp, or by means of intra-operative images such as radiographs or video images. Recently the use of registered video images has resulted in a number of experiments with "improved reality" and telesurgery. The same working principle has shown to be useful for bone and bone related surgery. As in brain surgery, the prerequisites of rigidity and immobility with respect to a reference are satisfied. Because bone structures are rigid and can easily be outlined in CT images, 3D graphical as well as stereolithographic representations can be produced for the purpose of planning and even for navigation. Unfortunately, for most organs or soft tissue the above conditions of inflexibility and fixed position with respect to a reference are not fulfilled. Real time imaging, partly due to the introduction of the "open" MR scanner, may offer a solution. It can be expected that interventional diagnostic imaging will become increasingly important in the future, also for neurosurgery.

Production of tumor necrosis factor in spinal cord following traumatic injury in rats.

Production of tumor necrosis factor (TNF) in the spinal cord following traumatic injury has been studied. In these experiments, the level of TNF was examined in the homogenate of the spinal cord, cerebrospinal fluid (CSF) and serum (n = 56). TNF could be detected in the injured spinal cord but not in the normal spinal cord. The TNF level increased in the spinal cord after the injury. At the lesion site, a maximal TNF concentration was observed 1 h after the injury, and the TNF concentration remained at this level until 8 h after the injury. Thereafter, it decreased gradually. However, TNF still could be detected 72 h after the injury. No TNF could be detected in the CSF and serum, collected from rats both with and without spinal cord injury (SCI). This study thus suggests that TNF is produced locally in the spinal cord following traumatic injury, and this TNF production is caused by the injury. The present results also demonstrate that TNF production is an acute and rapid reaction in the spinal cord following traumatic injury.

The use of magnetic resonance angiography in stereotactic neurosurgery.

The authors discuss the advantages and disadvantages of the use of magnetic resonance (MR) angiography images in stereotactic neurosurgery. Current computer programs designed to assist the neurosurgeon in the planning of stereotactic neurosurgical interventions use intraarterial digital subtraction angiography images to visualize the blood vessels. Magnetic resonance angiography is a recent technique with a number of advantages over the digital subtraction method: it is less invasive and less prone to complications; it provides truly three-dimensional data sets that can be viewed from any direction; and it can visualize both stationary and flowing tissues with the same imaging device and localizer frame. Although digital subtraction images are still superior in contrast and vascular detail, state-of-the-art high-resolution MR angiography sequences provide sufficient vascular detail for planning surgery. Contrast-enhanced MR angiography images were acquired using adapted gradient-echo sequences to compensate for flow-induced distortions; postacquisition distortion correction was not necessary. Five methods to integrate and inspect a possible trajectory in the MR angiography data are discussed. Initial clinical experience with eight patients led to the conclusion that MR angiography is a valuable imaging modality that can be integrated reliably into a stereotactic neurosurgery planning procedure.

The consumption of fentanyl is increased in rats with nociceptive but not with neuropathic pain.

The question whether opioids relieve neuropathic pain remains a controversial issue. Experimental as well as clinical studies report contradictory results. This study investigated the consumption of fentanyl, a short-acting opioid, in rats with neuropathic pain, induced by partial sciatic nerve injury. The experiment consisted of a drug choice procedure in which the animals could choose between a solution containing 0.008 mg/ml of fentanyl and a highly palatable sweet solution. It was reasoned that if opioids have an analgesic effect in neuropathic pain, this will reinforce the intake of fentanyl more so in rats with neuropathic pain than in pain-free controls. This protocol was previously already used by Colpaert et al. (1982) in a rat model of chronic pain of nociceptive origin, namely polyarthritis. No significant differences were found in the relative oral intake of the fentanyl solution in mononeuropathic and pain-free control rats. In contrast, rats with nociceptive pain, adjuvant monoarthritis, drank significantly more of the fentanyl solution than did control rats. These data give experimental support for the clinical findings that opioids have a poor analgesic effect in neuropathic pain.

Protocol for the clinical functionality assessment of a workstation for stereotactic neurosurgery.

The objective of this study is to establish a protocol for the technical and clinical evaluation of a workstation for the planning of stereotactic neurosurgical interventions that has been developed in the framework of a joint European research project. Although several such workstations have been proposed before, they lacked the final and most important step, that of clinical validation. They failed to rigorously prove that their product was useful. The authors present a new method that is applicable to the evaluation of a wide range of medical technologies. Their protocol basically assesses the clinical relevance of the user requirements that are at the root of the development of the new technology. The evaluation consists of two stages. During functional specification, iterative prototyping is used to establish the clinical requirements and to assure the quality of the final product. A case study design is used in a second stage that assesses the clinical usability. A before-after study gives a first indication of cost effectiveness and improvement of health care quality.

[Pain of autonomic nervous system origin]. / Les douleurs d'origine neurovégétative.

Reflex sympathetic dystrophy (algodystrophy) is a descriptive term used to designate a clinical phenomenology, which appears after a trauma, often a minor one; it is thought that the sympathetic nervous system plays an important role in its physiopathology. The same applies to sympathetic maintained pain appearing after a lesion of a peripheral nerve (causalgia). There is no agreement as to which are the criteria necessary to make the diagnosis and as to what is the physiopathology of these syndromes. Research in this field is very active today.

How does the stereotactic workstation help the neurosurgeon?

At the KUL University of Leuven a workstation for the planning of neurosurgical stereotactic procedures has been developed. Its benefits are illustrated in three exemplary cases. The CT and/or MR images, acquired under stereotactic conditions, are transmitted via a PACS network (picture archiving and communication systems) directly to the stereotactic workstation in the operating theater. Target and entry point can be accurately defined on zoomed images. The trajectory can be checked and modified on all registered data sets and on resliced images along any plane. Maximum intensity projection of magnetic resonance angiography data sets along any arbitrary direction show the relative position of the blood vessels and the trajectory. During the preceding 32 months 29 patients were operated on using the stereotactic workstation. Postoperatively no new neurological deficit was observed in any of these patients. The workstation improves patient safety and increases the accuracy of neurosurgical stereotactic operations, because it helps the neurosurgeon to avoid blood vessels and/or important functional areas.