Deep brain stimulation for treatment-resistant major depressive disorder: a comparison of two targets and long-term follow-up.

We previously found that electrical stimulation in the anterior limb of the internal capsule/bed nucleus of the stria terminalis (IC/BST) alleviates depressive symptoms in severe treatment-resistant obsessive-compulsive disorder (OCD) patients. Here we tested the hypothesis that electrical stimulation in either IC/BST or in the inferior thalamic peduncle (ITP) effectively reduces depressive symptoms in treatment-resistant major depressive disorder (TRD). In a double-blind crossover design, the effects of electrical stimulation at both targets were compared in TRD patients. The 17-item Hamilton Depression Rating scale (HAM-D) was the primary outcome measure. During the first crossover, patients received IC/BST stimulation versus no stimulation in random order (2 × 1 weeks). During the second crossover (3 × 2 months), patients received IC/BST versus ITP versus no stimulation. Patients and evaluators were blinded for stimulation conditions. All patients (n=7) were followed up for at least 3 years (3-8 years) after implantation. Six patients completed the first crossover and five patients completed the second. During the first crossover, mean (s.d.) HAM-D scores were 21.5 (2.7) for no stimulation and 11.5 (8.8) for IC/BST stimulation. During the second crossover, HAM-D scores were 15.4 (7.5) for no stimulation, 7.6 (3.8) for IC/BST stimulation and 11.2 (7.5) for ITP stimulation. The final sample size was too small to statistically analyze this second crossover. At last follow-up, only one patient preferred ITP over IC/BST stimulation. Two patients, with a history of suicide attempts before implantation, committed suicide during the follow-up phases of this study. Our data indicate that, in the long term, both ITP and IC/BST stimulation may alleviate depressive symptoms in patients suffering from TRD.

Spinal cord stimulation modulates cerebral function: an fMRI study.

INTRODUCTION: Although spinal cord stimulation (SCS) is widely used for chronic neuropathic pain after failed spinal surgery, little is known about the underlying physiological mechanisms. This study aims to investigate the neural substrate underlying short-term (30 s) SCS by means of functional magnetic resonance imaging in 20 patients with failed back surgery syndrome (FBSS). METHODS: Twenty patients with FBSS, treated with externalized SCS, participated in a blocked functional magnetic resonance imaging design with stimulation and rest phases of 30 s each, repeated eight times in a row. During scanning, patients rated pain intensity over time using an 11-point numerical rating scale with verbal anchors (0 = no pain at all to 10 = worst pain imaginable) by pushing buttons (left hand, lesser pain; right hand, more pain). This scale was back projected to the patients on a flat screen allowing them to manually direct the pain indicator. To increase the signal-to-noise ratio, the 8-min block measurements were repeated three times. RESULTS: Marked deactivation of the bilateral medial thalamus and its connections to the rostral and caudal cingulate cortex and the insula was found; the study also showed immediate pain relief obtained by short-term SCS correlated negatively with activity in the inferior olivary nucleus, the cerebellum, and the rostral anterior cingulate cortex. CONCLUSIONS: Results indicate the key role of the medial thalamus as a mediator and the involvement of a corticocerebellar network implicating the modulation and regulation of averse and negative affect related to pain. The observation of a deactivation of the ipsilateral antero-medial thalamus might be used as a region of interest for further response SCS studies.

The subthalamic region is activated during valence-related emotional processing in patients with Parkinson's disease.

Visual stimuli are judged for their emotional significance based on two fundamental dimensions, valence and arousal, and may lead to changes in neural and body functions like attention, affect, memory and heart rate. Alterations in behaviour and mood have been encountered in patients with Parkinson's disease (PD) undergoing functional neurosurgery, suggesting that electrical high-frequency stimulation of the subthalamic nucleus (STN) may interfere with emotional information processing. Here, we use the opportunity to directly record neuronal activity from the STN macroelectrodes in patients with PD during presentation of emotionally laden and neutral pictures taken from the International Affective Picture System (IAPS) to further elucidate the role of the STN in emotional processing. We found a significant event-related desynchronization of STN alpha activity with pleasant stimuli that correlated with the individual valence rating of the pictures. Our findings suggest involvement of the human STN in valence-related emotional information processing that can potentially be altered during high-frequency stimulation of the STN in PD leading to behavioural complications.

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).

Deep brain stimulation in treatment refractory obsessive compulsive disorder.

Obsessive-compulsive disorder is a worldwide psychiatric disorder with a lifetime prevalence of 2% and mainly characterized by obsessional ideas and compulsive behaviors and rituals. Many patients show improvement under cognitive behavioral and/or pharmacological treatment. A minority of patients is refractory to all available therapy and may benefit from capsulotomy. This study aims to investigate deep brain stimulation (DBS) as a last resort treatment alternative to capsulotomy in treatment refractory obsessive-compulsive disorder. Eight patients have been implanted bilaterally in the anterior limbs of the internal capsules with a quadripolar electrode. This paper presents the results of the first 4 operated patients. Acute deep brain stimulation displays an immediate improvement of the speech, mood, eye contact and motor function. Chronic deep brain stimulation improves significantly the obsessional and compulsive symptomatology in three out of the four patients. This study definitely needs replication, but the results are promising. Reversible deep brain stimulation may improve the symptomatology of treatment refractory OCD patients, without significant side effects.

Chronaxie calculated from current-duration and voltage-duration data.

To determine the rheobase and the chronaxie of excitable cells from strength-duration curves both constant-current pulses and constant-voltage pulses are applied. Since the complex impedance of the electrode-tissue interface varies with both the pulsewidth and the stimulation voltage, chronaxie values estimated from voltage-duration measurements will differ from the proper values as determined from current-duration measurements. To allow a comparison of chronaxie values obtained by the two stimulation methods, voltage-duration curves were measured in human subjects with a deep brain stimulation electrode implanted, while the current and the load impedance of the stimulation circuit were determined in vitro as a function of both stimulation voltage and pulsewidth. Chronaxie values calculated from voltage-duration data were shown to be 30-40% below those estimated from current-duration data. It was also shown that in the normal range of stimulation amplitudes (up to 7 V) the load impedance increases almost linearly with the pulsewidth. This result led us to present a simple method to convert voltage-duration data into current-duration data, thereby reducing the error in the calculated chronaxie values to approximately 6%. For this purpose voltage-duration data have to be measured for pulses up to 10-20 times the expected chronaxie.

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.

Functional MRI of the brain: localisation of eloquent cortex in focal brain lesion therapy.

The aim of this study was to assess the feasibility of functional MRI (fMRI) in a clinical environment on a large patient group, and to evaluate the pretherapeutic value of localisation of eloquent cortex. Forty patients with focal brain lesions of different origin were studied using fMRI. Functional information was obtained using motor, somatosensory, auditory and phonological stimuli depending on the localisation of the lesions. To obtain information about the spatial accuracy of fMRI, the results were compared with postoperative electrocortical stimulation. Two patients with secondary trigeminal neuralgia were scanned using a motor protocol and were implanted with an extradural plate electrode. Imaging was successful in 40 of 42 patients (including the 2 with trigeminal neuralgia). These patients were analysed for strength of activation, the relation of the lesion to activation sites and the presence of mass effect. The correlation between these data and surgical findings provided significant additional clinical information. Functional MRI can be accurately performed in patients with focal brain lesions using a dedicated approach. Functional MRI offers important clinical information as a contribution to a decrease in posttherapeutic morbidity. The accuracy of the technique can be confirmed by other modalities, including invasive cortical electrostimulation.

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.

Therapeutic stereotactic procedures on the thalamus for pain.

Thalamotomy and electrical stimulation of a thalamic target as treatment for persistent pain are discussed. Thalamotomy is only rarely performed these days according to a questionnaire, given to some colleagues, about the type and the number of operations they performed in the years 1984, 1985 and 1986. The need for stimulation in the periventricular or periaqueductal grey for nociceptive pain is decreasing due to the advent of intraspinal and intraventricular administration of opioids. Nowadays medial and lateral ventro-posterior thalamic nuclei are frequently stimulated for treatment of deafferentation pain. Of 36 patients with deafferentation pain, 22 initially had benefit from this stimulation, but long-term success was only achieved in 11 (30%) of them. It was a general trend that the patients with an initial high pain relief score obtained the best long-term results.