Refractory Parkinson's Disease Research Articles

Dopamine Release in the Nonhuman Primate Caudate and Putamen Depends upon Site of Stimulation in the Subthalamic Nucleus

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for medically refractory Parkinson's disease. Although DBS has recognized clinical utility, its biologic mechanisms are not fully understood, and whether dopamine release is a potential factor in those mechanisms is in dispute. We tested the hypothesis that STN DBS-evoked dopamine release depends on the precise location of the stimulation site in the STN and the site of recording in the caudate and putamen. We conducted DBS with miniature, scaled-to-animal size, multicontact electrodes and used functional magnetic resonance imaging to identify the best dopamine recording site in the brains of nonhuman primates (rhesus macaques), which are highly representative of human brain anatomy and circuitry. Real-time stimulation-evoked dopamine release was monitored using in vivo fast-scan cyclic voltammetry. This study demonstrates that STN DBS-evoked dopamine release can be reduced or increased by redirecting STN stimulation to a slightly different site. Electrical stimulation of deep structures of the brain, or deep brain stimulation (DBS), is used to modulate pathological brain activity. However, technological limitations and incomplete understanding of the therapeutic mechanisms of DBS prevent personalization of this therapy and may contribute to less-than-optimal outcomes. We have demonstrated that DBS coincides with changes in dopamine neurotransmitter release in the basal ganglia. Here we mapped relationships between DBS and changes in neurochemical activity. Importantly, this study shows that DBS-evoked dopamine release can be reduced or increased by refocusing the DBS on a slightly different stimulation site.

Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Correlates

Background: The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. Methods: Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. Results: Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. Conclusions: The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain.

State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective.

Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective.

Current Topics in Deep Brain Stimulation for Parkinson Disease.

There is a long history of surgical treatment for Parkinson disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment option for patients with medically refractory PD. However, there are still many problems and controversies associated with DBS. In this review, we discuss current issues in DBS for PD, including patient selection, clinical outcomes, complications, target selection, long-term outcomes, management of axial symptoms, timing of surgery, surgical procedures, cost-effectiveness, and new technology.

Spatial Topographies of Unilateral Subthalamic Nucleus Deep Brain Stimulation Efficacy for Ipsilateral, Contralateral, Midline, and Total Parkinson Disease Motor Symptoms

Subthalamic nucleus (STN) deep brain stimulation is a successful intervention for medically refractory Parkinson disease, although its efficacy depends on optimal electrode placement. Even though the predominant effect is observed contralaterally, modest improvements in ipsilateral and midline symptoms are also observed. To elucidate the role of contact location of unilateral deep brain stimulation on contralateral, ipsilateral, and axial subscores of Parkinson disease motor symptoms. Eighty-six patients receiving first deep brain stimulation STN electrode placements were identified, yielding 73 patients with 3-month follow-up. Total preoperative and postoperative Unified Parkinson Disease Rating Scale Part III scores were obtained and divided into contralateral, ipsilateral, and midline subscores. Contact location was determined on immediate postoperative magnetic resonance imaging. A 3-dimensional ordinary "kriging" algorithm generated spatial interpolations for total, ipsilateral, contralateral, and midline symptom categories. Interpolative reconstructions were performed in the axial planes (z = -0.5, -1.0, -1.5, -3.5, -4.5, -6.0) and a sagittal plane (x = 12.0). Interpolation error and significance were quantified by use of a cross-validation technique and quantile-quantile analysis. There was an overall reduction in Unified Parkinson Disease Rating Scale Part III symptoms: total = 37.0 ± 24.11% (P < .05), ipsilateral = 15.9 ± 51.8%, contralateral = 56.2 ± 26.8% (P < .05), and midline = 26.5 ± 34.7%. Kriging interpolation was performed and cross-validated with quantile-quantile analysis with high correlation (R2 > 0.92) and demonstrated regions of efficacy for each symptom category. Contralateral symptoms demonstrated broad regions of efficacy across the peri-STN area. The ipsilateral and midline regions of efficacy were constrained and located along the dorsal STN and caudal zona incerta. We provide evidence for a unique functional topographic window in which contralateral, ipsilateral, and midline structures may achieve the best efficacy. Although there are overlapping regions, laterality demonstrates distinct topographies. Surgical optimization should target the intersection of optimal regions for these symptom categories.

2014 Lasker-DeBakey Clinical Medical Research Award.

2014 Lasker-DeBakey Clinical Medical Research Award.

Subthalamic Nuclear Tissue Contrast in Inversion Recovery MRI Decreases with Age in Medically Refractory Parkinson's Disease

MRI appearance of subthalamic nucleus (STN) boundaries in Parkinson's patients is often unreliable and not well understood. An objective comparison between FSE T2 and inversion recovery (FSTIR) sequences for stereotactic placement of deep brain stimulators is presented to advance current understanding of STN tissue contrast for refractory Parkinson's disease (PD). We imaged 12 PD (age 53-82) and 12 control patients (age 48-77) using T2 and FSTIR sequences at 1.5 T. To avoid MR contrast variation from hardware and patient dependent sources we used an internal thalamic tissue standard to normalize STN signal intensity and correlated it with patient age for these two groups. Normalized FSTIR-weighted STN contrast decreased with increasing age for PD patients (Spearman Rank correlation = -.5) while remained virtually unchanged for controls with age (Spearman Rank coefficient ≈ 0). T2-weighted STN contrast did not show appreciable changes with age for both the groups (Spearman correlation ≈ -.1). STN, a common stimulation target, shows an age dependent trend for normalized FSTIR MRI contrast. Although larger patient pools are needed, our work points to tissue relaxation-based changes in STN that may provide insight in early stages of brain pathology involving DBS targets in medically refractory Parkinson's disease.

Application of Describing Function Analysis to a Model of Deep Brain Stimulation

Deep brain stimulation effectively alleviates motor symptoms of medically refractory Parkinson's disease, and also relieves many other treatment-resistant movement and affective disorders. Despite its relative success as a treatment option, the basis of its efficacy remains elusive. In Parkinson's disease, increased functional connectivity and oscillatory activity occur within the basal ganglia as a result of dopamine loss. A correlative relationship between pathological oscillatory activity and the motor symptoms of the disease, in particular bradykinesia, rigidity, and tremor, has been established. Suppression of the oscillations by either dopamine replacement or DBS also correlates with an improvement in motor symptoms. DBS parameters are currently chosen empirically using a "trial and error" approach, which can be time-consuming and costly. The work presented here amalgamates concepts from theories of neural network modeling with nonlinear control engineering to describe and analyze a model of synchronous neural activity and applied stimulation. A theoretical expression for the optimum stimulation parameters necessary to suppress oscillations is derived. The effect of changing stimulation parameters (amplitude and pulse duration) on induced oscillations is studied in the model. Increasing either stimulation pulse duration or amplitude enhanced the level of suppression. The predicted parameters were found to agree well with clinical measurements reported in the literature for individual patients. It is anticipated that the simplified model described may facilitate the development of protocols to aid optimum stimulation parameter choice on a patient by patient basis.

Anaesthetic management of a patient with deep brain stimulation implant for radical nephrectomy.

A 63-year-old man with severe Parkinson's disease (PD) who had been implanted with deep brain stimulators into both sides underwent radical nephrectomy under general anaesthesia with standard monitoring. Deep brain stimulation (DBS) is an alternative and effective treatment option for severe and refractory PD and other illnesses such as essential tremor and intractable epilepsy. Anaesthesia in the patients with implanted neurostimulator requires special consideration because of the interaction between neurostimulator and the diathermy. The diathermy can damage the brain tissue at the site of electrode. There are no standard guidelines for the anaesthetic management of a patient with DBS electrode in situ posted for surgery.

Where are we with surgical therapies for Parkinson's disease?

Surgical therapies are now widely accepted in the treatment of medically refractory Parkinson's disease or levodopa-related side effects. Neuromodulation using deep brain stimulation (DBS) is currently the most well known surgical treatment, however other developing technologies are emerging. We briefly review active research areas in the field of DBS including timing of surgery, target selection and localization under general anesthesia and developments in closed loop stimulation systems. We then describe other evolving modalities such as lesioning using MR guided focused ultrasound and biological therapies.

Risks of common complications in deep brain stimulation surgery: management and avoidance

Deep brain stimulation (DBS) surgery is increasingly prominent in the treatment of various disorders refractory to medication. Despite the procedure's efficacy, the community at large continues to be hesitant about presumed associated risks. The main object of this study was to assess the incidence of various surgical complications occurring both during and after DBS device implantation in a large population of patients with movement disorders in an effort to better quantify patient risk, define management plans, and develop methods for risk avoidance. A second aim was to corroborate the low procedural complication risk of DBS reported by others, which in light of the procedure's efficacy is needed to promote its widespread acceptance. All patients who had undergone new DBS device implantation surgery between 2002 and 2010 by a single surgeon were entered into a database after being verified by cross-referencing manufacturer implantation records. All surgical records and charts were reviewed to identify intraoperative, perioperative, and long-term surgical complications, including any characteristics predictive of an adverse event. Seven hundred twenty-eight patients received 1333 new DBS electrodes and 1218 new internal pulse generators (IPGs) in a total of 1356 stereotactic procedures for the treatment of movement disorders. Seventy-eight percent of the patients had staged lead and IPG implantations. Of the 728 patients, 452 suffered from medically refractory Parkinson disease; in the other patients, essential tremor (144), dystonia (64), mixed disease (30), and other hyperkinetic movement disorders (38) were diagnosed. Severe intraoperative adverse events included vasovagal response in 6 patients (0.8%), hypotension in 2 (0.3%), and seizure in 2 (0.3%). Postoperative imaging confirmed asymptomatic intracerebral hemorrhage (ICH) in 4 patients (0.5%), asymptomatic intraventricular hemorrhage in 25 (3.4%), symptomatic ICH in 8 (1.1%), and ischemic infarction in 3 (0.4%), associated with hemiparesis and/or decreased consciousness in 13 (1.7%). Long-term complications of DBS device implantation not requiring additional surgery included hardware discomfort in 8 patients (1.1%) and loss of desired effect in 10 (1.4%). Hardware-related complications requiring surgical revision included wound infections in 13 patients (1.7%), lead malposition and/or migration in 13 (1.7%), component fracture in 10 (1.4%), component malfunction in 4 (0.5%), and loss of effect in 19 (2.6%). The authors confirmed that the overall risk of both procedure- and hardware-related adverse events is acceptably low. They offer advice on how to avoid the most common complications.

Subthalamic Nucleus Deep Brain Stimulation: An Invaluable Role for MER

Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the main surgical procedure for medically refractory Parkinson's disease. The benefit of intra-operative microelectrode recording (MER) for the purpose of neurophysiological localization and mapping of the STN continues to be debated. A retrospective review of the charts and operative reports of all patients receiving STN DBS implantation for Parkinson's disease at our institution from January 2004 to March 2011 was done. Data from 43 of 44 patients with Parkinson's disease treated with STN DBS were reviewed. The average number of tracts on the left was 2.4, versus 2.3 on the right. The average dorsal and ventral anatomical boundaries of the STN based on Schaltenbrand's Stereotactic Atlas were estimated to be at -5.0 mm above and +1.4 mm below target respectively. The average dorsal and ventral boundaries of the STN using MER were -2.6 mm above and +2.0 mm below target respectively. The average dorsal-ventral distance of the STN as predicted by Stereotactic Atlas was 6.4 mm, compared to 4.6 mm as determined by MER. MER demonstrated the average dorsal and ventral boundaries on the left side were -2.6 mm and +2.2 mm from target respectively, while the average dorsal and ventral boundaries on the right side were -2.5 mm and +1.8 mm from target respectively with MER. MER in STN DBS surgery demonstrated measurable difference between stereotactic atlas/MRI STN target and neurophysiologic STN localization.

Underlying Neurobiology and Clinical Correlates of Mania Status After Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Review of the Literature

Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson's disease (PD). The authors review the current literature to identify the clinical correlates associated with subthalamic nucleus (STN) DBS-induced hypomania/mania in PD patients. Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (&gt;3 V), male sex, and/or early-onset PD. STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanisms of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight toward development of future DBS mood-stabilization therapies.

Temporary deterioration of executive function after subthalamic deep brain stimulation in Parkinson's disease

ObjectiveSelective impairment of executive function has been shown in Parkinson's Disease (PD) patients undergoing Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN). However, some patients experience difficulties in daily life, such as dissension in interpersonal relationships or a loss of lifestyle balance, in the short term after surgery. Our hypothesis is that these difficulties might be related to executive dysfunction. To elucidate the involvement of executive dysfunction in these difficulties, we assessed motor and executive function in the short term and long term after surgery. MethodsWe examined motor function and executive function in 30 patients who underwent bilateral STN–DBS for medically refractory PD. Patients were evaluated for executive function 1 month before surgery, 1 month after surgery, and 12 months after surgery using the Trail Making Test (TMT), the Modified Stroop Color Word Interference Test (MST) and tests of Verbal Fluency (VF). ResultsTMT-B, TMT (B/A), MST-B, VF-phonemic and VF-semantic scores were significantly poorer 1 month after STN–DBS. TMT-B, TMT (B/A) and VF-phonemic recovered to preoperative levels by 12 months after surgery. A reduction in dopaminergic medication 1 month after surgery was significantly correlated with deterioration of TMT (B/A). ConclusionTemporary deterioration of executive function may occur in the short term after STN–DBS, whereas motor function is usually improved. PD patients undergoing STN–DBS should be managed during this period to better predict temporary executive dysfunction. Excessive reduction of dopaminergic medication after surgery might, at least in part, result in this deterioration of executive function.

The Need for a Multifactorial Approach to Raise the Standard in Deep Brain Stimulation Reporting

Deep brain stimulation (DBS) has been demonstrated to be an effective therapeutic strategy for the treatment of pharmacologically refractory Parkinson disease (PD) ( 1. Kleiner-Fisman G Herzog J Fisman DN et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord. 2006; 21: S290-S304 Crossref Scopus (761) Google Scholar ). Since its renaissance in 1987 ( 2. Benabid AL Pollak P Louveau A Henry S de Rougemont J Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol. 1987; 50: 344-346 PubMed Google Scholar , 3. Hariz MI Blomstedt P Zrinzo L Deep brain stimulation between 1947 and 1987: the untold story. Neurosurg Focus. 2010; 29: E1 Crossref Scopus (150) Google Scholar ), it has become widely accepted in the movement disorders community with more than 33,000 patients currently implanted. Targets have evolved from the ventral intermediate nucleus of the thalamus ( 2. Benabid AL Pollak P Louveau A Henry S de Rougemont J Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Appl Neurophysiol. 1987; 50: 344-346 PubMed Google Scholar , 4. Benabid AL Pollak P Gervason C et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991; 337: 403-406 Abstract PubMed Scopus (1393) Google Scholar ) to the globus pallidus internus ( 5. Siegfried J Lippitz B Bilateral chronic electrostimulation of ventroposterolateral pallidum: a new therapeutic approach for alleviating all parkinsonian symptoms. Neurosurgery. 1994; 35 (discussion 1129–1130): 1126-1129 Crossref PubMed Scopus (409) Google Scholar ), subsequently to the subthalamic nucleus (STN) ( 6. Pollak P Benabid AL Gross C et al. [Effects of the stimulation of the subthalamic nucleus in Parkinson disease]. Rev Neurol (Paris). 1993; 149: 175-176 PubMed Google Scholar ), and recently to the pedunculopontine nucleus ( 7. Stefani A Lozano AM Peppe A et al. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson’s disease. Brain. 2007; 130: 1596-1607 Crossref PubMed Scopus (636) Google Scholar ). While debate exists with respect to the optimal therapeutic target ( 8. Okun MS Foote KD Subthalamic nucleus vs globus pallidus interna deep brain stimulation, the rematch: will pallidal deep brain stimulation make a triumphant return?. Arch Neurol. 2005; 62: 533-536 Crossref PubMed Scopus (64) Google Scholar , 9. Minguez-Castellanos A Escamilla-Sevilla F Pallidal vs subthalamic deep brain stimulation for Parkinson disease: winner and loser or a sharing of honors?. Arch Neurol. 2005; 62 (author reply 1643): 1642-1643 Crossref Google Scholar ), DBS of STN is the most common surgical intervention for PD ( 10. Benabid AL Chabardes S Mitrofanis J Pollak P Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol. 2009; 8: 67-81 Abstract Full Text Full Text PDF PubMed Scopus (971) Google Scholar ). DBS of the STN has resulted in substantial motor improvements and often leads to a significant reduction in levodopa administration ( 11. Molinuevo JL Valldeoriola F Tolosa E et al. Levodopa withdrawal after bilateral subthalamic nucleus stimulation in advanced Parkinson disease. Arch Neurol. 2000; 57: 983-988 Crossref PubMed Scopus (191) Google Scholar ). Now that these major advances in motor function have been achieved, the apparent limbic side-effects of DBS have come into greater focus ( 12. Okun MS Green J Saben R Gross R Foote KD Vitek JL Mood changes with deep brain stimulation of STN and GPi: results of a pilot study. J Neurol Neurosurg Psychiatry. 2003; 74: 1584-1586 Crossref PubMed Scopus (93) Google Scholar ).

Transgressing the Ventricular Wall During Subthalamic Deep Brain Stimulation Surgery for Parkinson Disease Increases the Risk of Adverse Neurological Sequelae

Deep brain stimulation (DBS) at the subthalamic nucleus (STN) is an effective treatment for the motor manifestations of advanced medically refractory Parkinson disease. Because of the medial location of the target, surgical trajectories to the STN may violate the ipsilateral lateral ventricle. To determine whether violating the ventricle during STN DBS surgery is associated with postoperative confusion. A retrospective chart review of all STN implantation procedures for Parkinson disease performed by 1 surgeon between January 2005 and September 2008 was performed. Postoperative magnetic resonance imaging was performed in all cases, and each scan was reviewed for evidence of ventricular wall violation. All charts were reviewed for postoperative confusion and/or increased length of hospital stay. A total of 145 leads were implanted in 81 patients over 102 admissions. Forty-three patients underwent contemporaneous bilateral lead implantation; 23 underwent unilateral implantation; and 18 underwent staged bilateral implantation. The cases of 8 patients were complicated by postoperative confusion and increased length of stay. Sixteen magnetic resonance imaging scans demonstrated evidence of ventricular wall violation including all 8 patients with postoperative confusion. The relative risk of having postoperative confusion after traversing the ventricle is 87 (P < .001). Violating the ventricular system during STN DBS surgery correlated significantly with postoperative altered mental status and subsequent increased length of hospital stay. This finding may explain why cognitive complications are observed more frequently in Parkinson disease patients undergoing DBS at the STN compared with the internal globus pallidus.

Simultaneous Use of Neurostimulators in Patients With a Preexisting Cardiovascular Implantable Electronic Device

Neurostimulation is widely accepted for the treatment of refractory Parkinson's disease, essential tremor, and chronic pain. The presence of a cardiovascular implantable electronic device (CIED) might be considered a contraindication for neurostimulators due to the possible interaction between the two devices. The purpose of this study is to report the feasibility and safety of concomitant use of neurostimulators and CIED, and to review surgical and clinical precautions needed to avoid possible interference between the two systems. A retrospective institutional review board approved chart review of six patients having both a neurostimulator(s) and a CIED was performed. Diagnosis included Parkinson's disease (two) and intractable pain (four). All implantable cardiac devices were set on bipolar sensing mode and bipolar stimulation was chosen for the neurostimulators. In general, both systems were implanted at sites seven inches apart. Electrocardiogram monitoring was observed throughout implantation. Patients were followed up for a mean period of 31.7 months (ranging from 14 to 67 months). An extensive chart review was done and cases from previous reports were compiled. In all six patients, no acute events occurred during surgery with no interaction or interference noted during implantation of the second device. Subsequent follow-up visits continued to exhibit a lack of interference between the two systems, including normal electrocardiogram studies. Both systems were noted to function at optimal levels. An extensive literature review revealed 57 unique cases previously published reporting the simultaneous use of neurostimulators and a CIED in the same patient. A table summarizing previously cited cases from the literature is provided. The concomitant use of neurostimulator(s) and permanent pacemaker(s) can be safely performed. Permanent pacemaker should not be considered a general contraindication for neurostimulation therapy. Current literature lacks evidence to determine the safety of concomitant use of neurostimulator(s) and implantable cardioverter defibrillator(s).

Complications of Subthalamic Nucleus Stimulation in Parkinson's Disease

Subthalamic nucleus deep brain stimulation (STN-DBS) is effective for medically refractory Parkinson's disease. We retrospectively analyzed complications in 180 consecutive patients who underwent bilateral STN-DBS. Surgery-related complications were symptomatic intracerebral hemorrhage in 2, chronic subdural hematoma in 1, and transient deterioration of medication-induced psychosis in 2 patients. Device-related complications involved device infection in 5, skin erosion in 5, and implantable pulse generator malfunction in 2 patients. All of these patients required surgical repair. Surgery and device-related complications could be reduced with increased surgical experience and the introduction of new surgical equipment and technology. Treatment or stimulation-related complications were intractable dyskinesia/dystonia in 11, problematic dysarthria in 7, apraxia of eyelid opening (ALO) in 11, back pain in 10, and restless leg syndrome in 6 patients. Neuropsychiatric complications were transient mood changes in some, impulse control disorder in 2, severe depression related to excessive reduction of dopaminergic medications in 2, rapid progression of dementia in 1, and suicide attempts in 2 patients. Most complications were mild and transient. Dysarthria and ALO were the most frequent permanent sequelae after STN-DBS. Treatment-related adverse events may be caused not only by the effect of stimulation effect but also excessive reduction of dopaminergic medication, or progression of the disease. In conclusion, STN-DBS seems to be a relatively safe procedure. Although serious complications with permanent sequelae are rare, significant incidences of adverse effects occur. Physicians engaged in this treatment should have a comprehensive understanding of the probable complications and how to avoid them.

Deep brain stimulation for camptocormia in dystonia and Parkinson’s disease

Camptocormia, or "bent spine syndrome", may occur in various movement disorders such as primary dystonia or idiopathic Parkinson's disease (PD). Although deep brain stimulation (DBS) is an established treatment in refractory primary dystonia and advanced PD, few data are available on the effect of DBS on camptocormia comparing these two conditions. Seven patients (4 with dystonia, 3 with PD; mean age 60.3years at surgery, range 39-73years) with camptocormia were included in the study. Five patients underwent bilateral GPi DBS and two patients underwent bilateral STN DBS guided by CT-stereotactic surgery and microelectrode recording. Pre- and postoperative motor assessment included the BFM in the dystonia patients and the UPDRS in the PD patients. Severity of camptocormia was assessed by the BFM subscore for the trunk at the last available follow-up at a mean of 17.3months (range 9-36months). There were no surgical complications. In the four patients with dystonia there was a mean improvement of 53% in the BFM motor score (range 41-79%) and of 63% (range 50-67%) in the BFM subscore for the trunk at the last available follow-up (mean 14.3months, range 9-18months). In the three patients with camptocormia in PD who underwent bilateral STN DBS (2 patients) or pallidal DBS (1 patient), the PD symptoms improved markedly (mean improvement in the UPDRS motor subscore stimulation on/medication off 55%, range 49-61%), but there was no or only mild improvement of camptocormia in the two patients who underwent STN DBS, and only moderate improvement in the patient with GPi DBS at the last available follow-up (mean 21months, range 12-36months). GPi DBS is an effective treatment for camptocormia in dystonia. The response of camptocormia to chronic STN or GPi DBS in PD is more heterogenous. The latter may be due to a variety of causes and needs further clarification.

Preserved cognition after deep brain stimulation (DBS) in the subthalamic area for Parkinson's disease: a case report

At present, subthalamic nucleus (STN) stimulation is the preferred procedure for the amelioration of motor symptoms in medication refractory Parkinson's disease. Results are however impaired by negative impacts on mood, cognition, incentive, and social judgment. Alternative targets are therefore explored. We describe a case with stimulation of subthalamic fibre tracts that showed clear improvement of cognitive and social abilities. Avoiding the STN may be advantageous in progressive Parkinson's disease to avoid non-motor complications and enhance quality of life.