[Networkmodulation through deep brain stimulation]. / Netwerkmodulatie door diepe hersenstimulatie.

BACKGROUND: Deep brain stimulation (DBS) is widely performed since 1987, mainly in the realm of movement disorders. AIM: To provide an overview of the current state of DBS in various neuropsychiatric disorders and to provide an overview of new developments. METHOD: Narrative review of recent literature. RESULTS: Several studies have shown the potential of DBS for carefully selected patients suffering from refractory neuropsychiatic indications such as Tourette syndrome, obsessive-compulsive disorder, depression, and Alzheimer’s disease. Applying for a CE or FDA approval by the implant manufacturer by means of double-blinded controlled trials has become highly cumbersome because of the new stricter European medical device regulation. For these RCTs to be successful, a sufficiently long follow-up time and the neurosurgeon’s knowledge of the most optimal stimulation point are required. The latest technical advances focussing on network stimulation have greatly added to defining this optimal stimulation point per disease. CONCLUSION: DBS is a safe technique with a proven effect on more than 200,000 patients with movement disorders. Trials into the application of DBS for the most important psychiatric and cognitive indications are important.

Beneficial effects of bilateral subthalamic stimulation on alexithymia in Parkinson's disease.

BACKGROUND AND PURPOSE: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL) and motor and non-motor symptoms in advanced Parkinson's disease (PD). However, its effect on alexithymia and its relationship to other neuropsychiatric symptoms and QoL in PD is unclear. METHODS: In this prospective, observational study of 39 patients with PD undergoing STN-DBS, we examined the Parkinson's Disease Questionnaire-8 (PDQ-8), 20-item Toronto Alexithymia Scale (TAS-20), Hospital Anxiety and Depression Scale (HADS), Self-Report Manic Inventory (SRMI), Apathy Evaluation Scale (AES), Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living, UPDRS motor examination and UPDRS complications (UPDRS-II/-III/-IV) and levodopa-equivalent daily dose (LEDD) pre-operatively and at 5-month follow-up. Outcome changes were tested with Wilcoxon signed-rank or paired t-test when parametric tests were applicable and corrected for multiple comparisons. The relationship between outcome changes was explored with bivariate correlations. Additionally, partial correlations between PDQ-8 and TAS-20 were computed controlling for HADS, SRMI and AES change scores. Predictor analyses for PDQ-8 improvement were calculated for all baseline parameters. RESULTS: The baseline prevalence of alexithymia was 17.9%. We observed significant beneficial effects of STN-DBS on PDQ-8, TAS-20, HADS, UPDRS-II, -III and -IV scores and significant LEDD reduction. The correlation between TAS-20 and PDQ-8 improvements remained significant after controlling for all other aforementioned outcomes. Predictor analyses for PDQ-8 improvement were significant for PDQ-8 and TAS-20. CONCLUSIONS: This is the first report of beneficial effects of STN-DBS on alexithymia. Alexithymia was significantly associated with QoL outcome independent of anxiety, depression, mania and apathy. Our study highlights the importance of alexithymia for holistic assessments of DBS outcomes.

Adaptive Deep Brain Stimulation in Parkinson's Disease: A Delphi Consensus Study.

Importance: If history teaches, as cardiac pacing moved from fixed-rate to on-demand delivery in in 80s of the last century, there are high probabilities that closed-loop and adaptive approaches will become, in the next decade, the natural evolution of conventional Deep Brain Stimulation (cDBS). However, while devices for aDBS are already available for clinical use, few data on their clinical application and technological limitations are available so far. In such scenario, gathering the opinion and expertise of leading investigators worldwide would boost and guide practice and research, thus grounding the clinical development of aDBS. Observations: We identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to aDBS. A 5-point Likert scale questionnaire along with a Delphi method was employed. 42 questions were submitted to the panel, half of them being related to technical aspects while the other half to clinical aspects of aDBS. Experts agreed that aDBS will become clinical practice in 10 years. In the present scenario, although the panel agreed that aDBS applications require skilled clinicians and that algorithms need to be further optimized to manage complex PD symptoms, consensus was reached on aDBS safety and its ability to provide a faster and more stable treatment response than cDBS, also for tremor-dominant Parkinson's disease patients and for those with motor fluctuations and dyskinesias. Conclusions and Relevance: Despite the need of further research, the panel concluded that aDBS is safe, promises to be maximally effective in PD patients with motor fluctuation and dyskinesias and therefore will enter into the clinical practice in the next years, with further research focused on algorithms and markers for complex symptoms.

Physical therapy in patients with Parkinson's disease treated with Deep Brain Stimulation: a Delphi panel study.

Although deep brain stimulation of the subthalamic nucleus (STN-DBS) induces motor benefits in people with Parkinson's disease (PwPD), the size and duration of the effects of STN-DBS on motor axial (e.g., postural instability, trunk posture alterations) and gait impairments (e.g., freezing of gait - FOG) are still ambiguous. Physical therapy (PT) effectively complements pharmacological treatment to improve postural stability, gait performance, and other dopamine-resistant symptoms (e.g. festination, hesitation, axial motor dysfunctions, and FOG) in PwPD who are non-surgically treated. Despite the potential for positive adjuvant effects of PT following STN-DBS surgery, there is a paucity of science available on the topic. In such a scenario, gathering the opinion and expertise of leading investigators worldwide was pursued to study motor rehabilitation in PwPD following STN-DBS. After summarizing the few available findings through a systematic review, we identified clinical and academically experienced DBS clinicians (n=21) to discuss the challenges related to PT following STN-DBS. A 5-point Likert scale questionnaire was used and based on the results of the systematic review along with a Delphi method. Thirty-nine questions were submitted to the panel - half related to general considerations on PT following STN-DBS, half related to PT treatments. Despite the low-to-moderate quality, the few available rehabilitative studies suggested that PT could improve dynamic and static balance, gait performance and posture. Similarly, panellists strongly agreed that PT might help in improving motor symptoms and quality of life, and it may be possibly prescribed to maximize the effects of the stimulation. The experts agreed that physical therapists could be part of the multidisciplinary team taking care of the patients. Also, they agreed on prescribing of conventional PT, but not massage or manual therapy. Our results will inform the rehabilitation and the DBS community to engage, publish and deepen this area of research. Such efforts may spark guidelines for PT following STN-DBS.

Directional DBS leads show large deviations from their intended implantation orientation.

OBJECTIVE: Lead orientation is a new degree of freedom with directional deep brain stimulation (DBS) leads. We investigated how prevalent deviations from the intended implantation direction are in a large patient cohort. METHODS: The Directional Orientation Detection (DiODe) algorithm to determine lead orientation from postoperative CT scans was implemented into the open-source Lead-DBS toolbox. Lead orientation was analyzed in 100 consecutive patients (198 leads). Different anatomical targets and intraoperative setups were compared. RESULTS: Deviations of up to 90° from the intended implantation direction were observed. Deviations of more than 30° were seen in 42% of the leads and deviations of more than 60° in about 11% of the leads. Deviations were independent from the neuroanatomical target and the stereotactic frame but increased depending on which microdrive was used. DISCUSSION: Our results indicate that large deviations from the intended implantation direction are a common phenomenon in directional leads. Postoperative determination of lead orientation is thus mandatory for investigating directional DBS.

Buspirone induced acute and chronic changes of neural activation in the periaqueductal gray of rats.

5-HT(1A) modulation within the midbrain periaqueductal gray (PAG) is closely associated with anxiety- or panic-like behavior. Several findings have demonstrated that the properties of buspirone (a 5-HT(1A) partial agonist) would function as either anxiolytic or panicolytic in both clinical and laboratory animal research. In this study, we have investigated the neuronal activity occurring within the different regions of the PAG induced by buspirone treatment. Twenty-eight albino Wistar rats (350-400 g) were injected with either acute or chronic saline/buspirone (each, n=7), respectively. Our results show that buspirone treatment reduced locomotor activity, body weight and fecal boli, particularly in the chronic buspirone group. Two-way ANOVA revealed a significant decrease of c-Fos-immunoreactive (ir) cells expression in all regions of the rostral PAG after both acute and chronic buspirone (acute buspirone (AB) and chronic buspirone (CB), respectively) treatment. However, no effects on c-Fos-ir were detected in the caudal lateral periaqueductal gray (lPAG) and ventrolateral periaqueductal gray (vlPAG) in both the AB and CB groups, and in the dorsolateral periaqueductal gray (dlPAG) of the CB group. Interestingly, c-Fos-ir cells in the dorsomedial periaqueductal gray (dmPAG) column were reduced consistently in both the rostral and caudal PAG in both AB and CB groups. Besides, in all regions the number of c-Fos-ir cells was higher in the AB than in the CB group with exception of the rostral lPAG. In conclusion, the main anxiolytic effect of buspirone was specifically localized in all regions of the rostral PAG and in the caudal dmPAG. However, the caudal dlPAG, lPAG and vlPAG were found to be ineffective to buspirone treatment, probably due to their distinctive function in mediating higher level of anxiety in defensive behavior. This indicates that the longitudinal anatomical structure of the PAG possesses a different level of receptor sensitivity of 5-HT(1A) in the pathophysiology of anxiety and panic disorder.

Surgery for temporal lobe epilepsy after cerebral malaria.

The most common indication for epilepsy surgery is temporal lobe epilepsy (TLE) which usually is divided into two categories, mesial and lateral TLE. The commonest pathology underlying mesial temporal lobe epilepsy (MTLE) is mesial temporal sclerosis (MTS); we report on a 50-year-old male patient, who contracted cerebral malaria and developed MTLE shortly thereafter. Magnetic resonance imaging (MRI) showed MTS. Surgical treatment was an anteromedial temporal lobe resection with amygdalohippocampectomy. The patient is seizure free, 36 months after surgical treatment. This is the first report describing MTLE-onset subsequent to cerebral malaria and discussing the potential pathophysiological relationship between cerebral malaria and MTS.

Dysarthria in pallidal Deep Brain Stimulation in dystonia depends on the posterior location of active electrode contacts: a pilot study.

BACKGROUND: Pallidal Deep Brain Stimulation (GPi-DBS) is an efficient treatment for primary dystonia. We investigated stimulation-induced dysarthria, which is the most frequent side-effect of GPi-DBS. METHODS: Speech was recorded while reading a standard text, and performing rapid syllable repetitions ON and OFF DBS in ten dystonia patients (6 men; 3 cervical, 4 segmental, 3 generalized, unselected for DBS-related speech impairments). Speech and articulation rate, pauses, and syllable repetition rates were extracted via acoustic analysis. Locations of active stimulation contacts and volumes of tissue activated (VTA) were calculated. RESULTS: The number of pauses increased significantly ON vs. OFF stimulation (Wilcoxon test, p < 0.05). More posteriorly localized active contacts were associated with slower syllable repetition (Pearson correlation, p < 0.05). VTA size did not correlate with any measure of dysarthria. CONCLUSION: Using quantitative acoustic signal analysis, this study demonstrates that GPi-DBS alters motor aspects of speech. Both inadvertent stimulation of parts of the internal capsule, or interference with GPi function and outflow are possible causes. Understanding causes of GPi-DBS-induced speech changes can improve DBS programming.

High frequency stimulation of the subthalamic nucleus improves speed of locomotion but impairs forelimb movement in Parkinsonian rats.

The subthalamic nucleus (STN) plays an important role in motor and non-motor behavior in Parkinson's disease, but its involvement in gait functions is largely unknown. In this study, we investigated the role of the STN on gait in a rat model of PD using the CatWalk method. Parkinsonian rats received bilateral high frequency stimulation (HFS) with different stimulation amplitudes of the STN. Rats were rendered parkinsonian by bilateral injections of 6-hydroxydopamine (6-OHDA) into the striatum. One group of 6-OHDA animals was implanted bilaterally with stimulation electrodes at the level of the STN. Stimulations were performed at 130 Hz (frequency), 60 micros (pulse width) and varying amplitudes of 0, 3, 30 and 150 microA. Rats were evaluated in an automated quantitative gait analysis method (CatWalk method). After behavioral evaluations, rats were killed and the brains processed for histological stainings to determine the impact of the dopaminergic lesion (tyrosine hydroxylase immunohistochemistry) and the localization of the electrode tip (hematoxylin-eosin histochemistry). Results show that bilateral 6-OHDA infusion significantly decreased (70%) the number of dopaminergic cells in the substantia nigra pars compacta (SNc). Due to 6-OHDA treatment, the gait parameters changed considerably. There was a general slowness. The most pronounced effects were seen at the level of the hind paws. Due to implantation of STN electrodes the step pattern changed. STN electrical stimulation improved the general slowness but induced slowing of the forelimb movement. Furthermore, we found that HFS with a medium amplitude significantly changed speed, the so-called dynamic aspect of gait. The static features of gait were only significantly influenced with low amplitude. Remarkably, STN stimulation affected predominantly the forepaws/limbs.

DBS in tourette syndrome: rationale, current status and future prospects.

Tourette syndrome is a neuropsychiatric disorder with onset in early childhood and characterized by tics, often associated with behavioural abnormalities. Symptoms often disappear before or during adulthood. Treatment consists of psychotherapy or pharmacotherapy. A small percentage of patients is treatment refractory. After the introduction of deep brain stimulation (DBS) of the thalamus as a new therapeutical approach in 1999, several other brain nuclei have been targeted in a small number of patients, like the globus pallidus internus, anteromedial and ventroposterolateral part, and the nucleus accumbens. In the published reports, a tic reduction rate of at least 66% is described. The effects of DBS on associated behavioural disorders are more variable. The number of treated patients is small and it is unclear whether the effects of DBS are dependent on the target nucleus. The pathophysiology of Tourette syndrome is not well understood. On the basis of our current knowledge of cortico-basal ganglia-thalamocortical circuits, an explanation for the beneficial effects of DBS on tics is proposed. It is concluded that a meticulous evaluation of the electrode position, and a blinded assessment of the clinical effects on tics and behavioural disorders, is absolutely mandatory in order to identify the best target of DBS for Tourette syndrome.

German registry of paediatric deep brain stimulation in patients with childhood-onset dystonia (GEPESTIM).

BACKGROUND: Data on paediatric deep brain stimulation (DBS) is limited, especially for long-term outcomes, because of small numbers in single center series and lack of systematic multi-center trials. OBJECTIVES: We seek to systematically evaluate the clinical outcome of paediatric patients undergoing DBS. METHODS: A German registry on paediatric DBS (GEPESTIM) was created to collect data of patients with dystonia undergoing DBS up to the age of 18 years. Patients were divided into three groups according to etiology (group 1 inherited, group 2 acquired, and group 3 idiopathic dystonia). RESULTS: Data of 44 patients with a mean age of 12.8 years at time of operation provided by 6 German centers could be documented in the registry so far (group 1 n = 18, group 2 n = 16, group 3 n = 10). Average absolute improvement after implantation was 15.5 ± 18.0 for 27 patients with pre- and postoperative Burke-Fahn-Marsden Dystonia Rating scale movement scores available (p < 0.001) (group 1: 19.6 ± 19.7, n = 12; group 2: 7.0 ± 8.9, n = 8; group 3: 19.2 ± 20.7, n = 7). Infection was the main reason for hardware removal (n = 6). 20 IPG replacements due to battery expiry were necessary in 15 patients at 3.7 ± 1.8 years after last implantation. DISCUSSION: Pre- and postoperative data on paediatric DBS are very heterogeneous and incomplete but corroborate the positive effects of DBS on inherited and acquired dystonia. Adverse events including relatively frequent IPG replacements due to battery expiry seem to be a prominent feature of children with dystonia undergoing DBS. The registry enables collaborative research on DBS treatment in the paediatric population and to create standardized management algorithms in the future.

Deep Brain Stimulation of the internal globus pallidus in refractory Tourette Syndrome.

OBJECTIVE: Deep Brain Stimulation in psychiatric disorders is becoming an increasingly performed surgery. At present, seven different targets have been stimulated in Tourette Syndrome, including the internal globus pallidus. We describe the effects on tics and comorbid behavioral disorders of Deep Brain Stimulation of the anterior internal globus pallidus in five patients with refractory Tourette Syndrome. METHODS: This study was performed as an open label study with follow-up assessment between 12 and 38 months. Patients were evaluated twice, one month before surgery and at long-term follow-up. Primary outcome was tic severity, assessed by several scales. Secondary outcomes were comorbid behavioral disorders, mood and cognition. The final position of the active contacts of the implanted electrodes was investigated and side effects were reported. RESULTS: Three males and two females were included with a mean age of 41.6 years (SD 9.7). The total post-operative score on the Yale Global Tic Severity Scale was significantly lower than the pre-operative score (42.2±4.8 versus 12.8±3.8, P=0.043). There was also a significant reduction on the modified Rush Video-Based Tic Rating Scale (13.0±2.0 versus 7.0±1.6, P=0.041) and in the total number of video-rated tics (259.6±107.3 versus 49.6±24.8, P=0.043). No significant difference on the secondary outcomes was found, however, there was an improvement on an individual level for obsessive-compulsive behavior. The final position of the active contacts was variable in our sample and no relationship between position and stimulation effects could be established. CONCLUSION: Our study suggests that Deep Brain Stimulation of the anterior internal globus pallidus is effective in reducing tic severity, and possibly also obsessive-compulsive behavior, in refractory Tourette patients without serious adverse events or side-effects.

Voxel-based dose calculation in radiocolloid therapy of cystic craniopharyngiomas.

Very high doses are administered in radiocolloid therapy of cystic craniopharyngiomas. However individual dose planning is not common yet mainly due to insufficient image resolution. Our aim was to investigate whether currently available high-resolution image data can be used for voxel-based dose calculation for short-ranged ß-emitters ((32)P,(90)Y,(186)Re) and to assess the achievable accuracy. We developed a convolution algorithm based on voxelized dose activity distributions and dose-spread kernels. Results for targets with 5-40 mm diameter were compared with high-resolution Monte Carlo calculations in spherical phantoms. Voxel size was 0.35 mm. Homogeneous volume and surface activity distributions were used. Dose-volume histograms of targets and shell structures were compared and γ index (dose tolerance 5%, distance to agreement 0.35 mm) was calculated for dose profiles along the principal axes. For volumetric activity distributions 89.3% ± 11.9% of all points passed the γ test (mean γ 0.53 ± 0.16). For surface distributions 33.6% ± 14.8% of all points passed the γ test (mean γ 2.01 ± 0.60). The shift of curves in dose-volume histograms was -1.7 Gy ± 7.6 Gy (-4.4 Gy ± 24.1 Gy for (186)Re) in volumetric distributions and 46.3% ± 32.8% in surface distributions. The results show that individual dose planning for radiocolloid therapy of cystic craniopharyngiomas based on high-resolution voxelized image data is feasible and yields highly accurate results for volumetric activity distributions and reasonable dose estimates for surface distributions.

Effects of deep brain stimulation on prepulse inhibition in obsessive-compulsive disorder.

Owing to a high response rate, deep brain stimulation (DBS) of the ventral striatal area has been approved for treatment-refractory obsessive-compulsive disorder (tr-OCD). Many basic issues regarding DBS for tr-OCD are still not understood, in particular, the mechanisms of action and the origin of side effects. We measured prepulse inhibition (PPI) in treatment-refractory OCD patients undergoing DBS of the nucleus accumbens (NAcc) and matched controls. As PPI has been used in animal DBS studies, it is highly suitable for translational research. Eight patients receiving DBS, eight patients with pharmacological treatment and eight age-matched healthy controls participated in our study. PPI was measured twice in the DBS group: one session with the stimulator switched on and one session with the stimulator switched off. OCD patients in the pharmacologic group took part in a single session. Controls were tested twice, to ensure stability of data. Statistical analysis revealed significant differences between controls and (1) patients with pharmacological treatment and (2) OCD DBS patients when the stimulation was switched off. Switching the stimulator on led to an increase in PPI at a stimulus-onset asynchrony of 200 ms. There was no significant difference in PPI between OCD patients being stimulated and the control group. This study shows that NAcc-DBS leads to an increase in PPI in tr-OCD patients towards a level seen in healthy controls. Assuming that PPI impairments partially reflect the neurobiological substrates of OCD, our results show that DBS of the NAcc may improve sensorimotor gating via correction of dysfunctional neural substrates. Bearing in mind that PPI is based on a complex and multilayered network, our data confirm that DBS most likely takes effect via network modulation.

Changes in Nutritional Status after Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer's Disease--Results of a Phase I Study.

OBJECTIVE: The progression of Alzheimer's disease (AD) is associated with impaired nutritional status. New methods, such as deep brain stimulation (DBS), are currently being tested to decrease the progression of AD. DBS is an approved method in the treatment of Parkinson's disease, and its suitability for the treatment of AD patients is currently under experimental investigation. To evaluate the advantages and disadvantages of this new treatment, it is important to assess potential side effects of DBS regarding the nucleus basalis of Meynert; this new treatment is thought to positively affect cognition and might counteract the deterioration of nutritional status and progressive weight loss observed in AD. This study aims to assess the nutritional status of patients with AD before receiving DBS of the nucleus basalis of Meynert and after 1 year, and to analyze potential associations between changes in cognition and nutritional status. DESIGN: A 1-year phase I proof-of-concept study. SETTING: The Department of Psychiatry and Psychotherapy at the University of Cologne. PARTICIPANTS: We assessed a consecutive sample of patients with mild to moderate AD (n=6) who fulfilled the inclusion criteria and provided written informed consent. INTERVENTION: Bilateral low-frequency DBS of the nucleus basalis of Meynert. MEASUREMENTS: Nutritional status was assessed using a modified Mini Nutritional Assessment, bioelectrical impedance analysis, a completed 3-day food diary, and analysis of serum levels of vitamin B12 and folate. RESULTS: With a normal body mass index (BMI) at baseline (mean 23.75 kg/m²) and after 1 year (mean 24.59 kg/m²), all but one patient gained body weight during the period of the pilot study (mean 2.38 kg, 3.81% of body weight). This was reflected in a mainly stable or improved body composition, assessed by bioelectrical impedance analysis, in five of the six patients. Mean energy intake increased from 1534 kcal/day (min 1037, max 2370) at baseline to 1736 kcal/day (min 1010, max 2663) after 1 year, leading to the improved fulfillment of energy needs in four patients. The only nutritional factors that were associated with changes in cognition were vitamin B12 level at baseline (Spearman's rho = 0.943, p = 0.005) and changes in vitamin B12 level (Spearman's rho = -0.829, p = 0.042). CONCLUSION: Patients with AD that received DBS of the nucleus basalis of Meynert demonstrated a mainly stable nutritional status within a 1-year period. Whether DBS is causative regarding these observations must be investigated in additional studies.

Tic related local field potentials in the thalamus and the effect of deep brain stimulation in Tourette syndrome: Report of three cases.

OBJECTIVE: Three patients with intractable Tourette syndrome (TS) underwent thalamic deep brain stimulation (DBS). To investigate the role of thalamic electrical activity in tic generation, local field potentials (LFP), EEG and EMG simultaneously were recorded. METHODS: Event related potentials and event related spectral perturbations of EEG and LFP, event related cross-coherences between EEG/LFP and LFP/LFP were analyzed. As time locking events, the tic onsets were used. Spontaneous tics were compared to voluntary tic mimicking. The effect of tic suppression and DBS on thalamic LFPs was evaluated. RESULTS: All three patients showed time-locked and prior to onset of spontaneous motor tics thalamic synchronization and thalamo-cortical cross-coherence. Also in three patients, not time-locked to motor tics, increased intra-thalamic coherences in the 1-8Hz frequency band were found. In one patient it was demonstrated that voluntary mimicked tics were preceded by premotor cortical and thalamic potentials. In this patient unilateral thalamic DBS contralaterally decreased the background thalamic activity. CONCLUSIONS: The present study in three cases with TS shows that spontaneous tics in TS are preceded by repetitive coherent thalamo-cortical discharges, indicating that preceding a tic the basal ganglia circuits are "charged up", ultimately leading to a motor tic. SIGNIFICANCE: Thalamic LFP recording may lead to more insight in underlying pathophysiological mechanisms in TS.

Thalamus and penile erection.

Penile erection is a complex neurovascular event. The neuronal system involved is often divided into a spinal (generator) and supraspinal (controller) network. Little is known about the supraspinal control. The recent finding of changes in penile erection following deep brain stimulation of the thalamus in two patients has raised the question as to what extent the thalamus is involved in erectile function. The thalamus has generally been regarded as a group of relay nuclei that served as a 'gate' for sexual information from the spinal cord towards higher centres. Recent evidence, however, suggests a more integrated regulatory function. Our review of the literature from 1960 until 2003 revealed 13 reports describing original data (preclinical and clinical). Various thalamic regions, varying from the midline thalamus to the posterior thalamus, have been reported to be activated during erection. The majority of the reports, however, showed that mainly the mediodorsal (MD) nucleus and the centromedian-parafascicular nucleus (Cm-Pf complex) are involved in penile erection. MD is the second largest nuclear aggregation located within the medial part of the thalamus. Anatomically, the MD is closely related to the Cm-Pf complex. The Cm-Pf complex is one of the most important relay stations in which the anterolateral spinothalamic pathway is further processed. This pathway is thought to transmit peripheral sexual sensations. On the whole, the present data on the role of the thalamus in erection are far from complete and future experiments are required to delineate its involvement.

Deep brain stimulation in movement disorders. The applications reconsidered.

In this study the role of DBS in advanced Parkinson disease (PD) is re-evaluated and new indications in the field of movement disorders are explored. The authors performed unilateral pallidal stimulation in 26 patients with advanced PD. At long-term follow-up review, the motor effect is unsatisfying. The authors conclude that unilateral pallidal stimulation is not a favourable treatment option for patients with advanced PD. Bilateral subthalamic nucleus stimulation was performed in twenty patients with advanced PD. After a minimum follow-up of 4 years, there was still a significant improvement in motor function and functional performance in all patients. One side-effect of the stimulation was however rather concerning: four patients presented with stimulation-induced hypomanic to manic characteristics. Bilateral subthalamic stimulation was performed in four patients with multiple system atrophy-parkinsonism. At long-term follow-up, the patients fared better with than without stimulation. The authors finally present a completely new indication for DBS: Tourette syndrome (TS). They review the literature on surgical procedures performed in TS, all of which consisted of making lesions. Three TS patients are presented on which bilateral thalamic stimulation was performed. At long-term follow-up, all major tics had disappeared, as well as associated behavioral disturbances.

[Manipulation of mental competence: an ethical problem in case of electrical stimulation of the subthalamic nucleus for severe Parkinson's disease]. / Manipuleerbare wilsbekwaamheid: een ethisch probleem bij elektrostimulatie van de nucleus subthalamicus voor ernstige ziekte van Parkinson.

Three years after the implantation of electrodes in the subthalamic nucleus (STN) and the start of deep brain stimulation (DBS) for advanced Parkinson's disease, a 62-year-old man was admitted because of a stimulation-related manic state that did not respond to treatment with a mood stabiliser and that led to chaotic behaviour, megalomania, serious financial debts and mental incompetence. Although adjustment of the stimulation parameters resulted in a normophoric state with a return of insight and capacity to judge, this was only at the cost of a serious exacerbation of his motor symptoms that left the patient bedridden. There was no therapeutic margin between the two states. Ultimately, there seemed to be only two alternatives: to admit the patient to a nursing home because of serious invalidity, but mentally in good condition, or to admit the patient to a chronic psychiatric ward because of a manic state, but with acceptable motor capacity and ADL functions. Thorough ethical evaluation followed. When not being stimulated, the patient was considered competent to decide about his own treatment; in this condition the patient chose for the second option. In accordance with his own wishes he was therefore legally committed to a chronic ward in the regional psychiatric hospital. The current ethical views on mental competence do not consider the potential influence of modern methods of treatment such as STN-DBS on this capacity.