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BACKGROUND: Although it is well established that surgically treated patients with cervical degenerative myelopathy (CDM) improve irrespective of the anterior decompression technique used, no consensus exists on what technique is superior in terms of neurological recovery. A general concern exists that anterior cervical discectomy with arthroplasty (ACDA) leads to less favorable outcomes in CDM due to microtrauma caused by preserved mobility. It is remarkable that current literature mainly uses pain scores to assess clinical outcomes after anterior decompression surgery, especially considering that pain may not be the most relevant outcome for CDM. This systematic review evaluated the literature concerning neurological outcomes in patients with CDM treated with anterior decompression surgery and assessed by validated myelopathy scores.METHODS: Systematic searches were carried out in PubMed, EMBASE, Web of Science, CINAHL, and the Cochrane Library. Prospective studies were included when patients with isolated CDM were treated with anterior decompression surgery, and a validated myelopathy outcome score was used.RESULTS: A total of 11 studies were included from the 16,032 identified studies. All studies used the modified Japanese Orthopedic Association (JOA) outcome score and showed improvement for all anterior techniques. The mean improvement in anterior cervical discectomy and fusion (ACDF) was 4.80 and 3.64 for the modified JOA and JOA outcome scores, respectively. The JOA for ACDA showed a mean improvement of 5.51. The overall quality of the included articles was low to moderate according to the Cochrane tool.CONCLUSION: Neurological recovery of CDM is similar after all anterior decompression techniques, including ACDA when compared with ACDF.CLINICAL RELEVANCE: The current literature gives no reason to dissuade the use of ACDA in cervical myelopathy.LEVEL OF EVIDENCE: 3

Background Around 20% of patients undergoing spinal fusion surgery have persistent back or leg pain despite surgery. Pain catastrophizing is the strongest psychological predictor for chronic postsurgical pain. Psychological variables are modifiable and could be target for intervention. However, randomized controlled trials evaluating the effectiveness of psychological interventions to reduce chronic pain and disability after spinal fusion in a population of patients with high preoperative pain catastrophizing scores are missing. The aim of our study is to examine whether an intervention targeting pain catastrophizing mitigates the risk of chronic postsurgical pain and disability. Our primary hypothesis is that targeted perioperative cognitive behavioral therapy decreases the risk of chronic postsurgical pain and disability after spinal fusion surgery in high catastrophizing patients. Methods We will perform a two-center prospective, single-blind, randomized, controlled study comparing lumbar spinal fusion surgery outcome between 2 cohorts. Adult patients selected for lumbar spinal fusion with decompression surgery and a minimum score of 24 on the pain catastrophizing scale will be randomized with 1:1 allocation for either perioperative cognitive behavioral therapy (intervention group) or a perioperative education plus progressive exercise program (control group). Patients randomized to the intervention group will receive six individual sessions of cognitive behavioral therapy, two sessions before the operation and four after. Primary outcome is the Core Outcome Measures Index at 12 months. Secondary outcomes include pain, disability, depression and quality of life. Discussion This is the first trial that evaluates the effectiveness of cognitive behavioral therapy as a perioperative tool to improve pain and disability after spinal fusion surgery in comparison with an educational/exercise control intervention, in patients with high levels of pain catastrophizing. If perioperative cognitive behavioral therapy proves to be effective, this might have important clinical implications, reducing the incidence of chronic postsurgical pain and improving outcome after spinal fusion surgery. Trial registration Clinicaltrials (NCT03969602). Registered 31 May 2019

IntroductionTo date, there is no consensus on which anterior surgical technique is more cost-effective in treating cervical degenerative disc disease (CDDD). The most commonly used surgical treatment for patients with single- or multi-level symptomatic CDDD is anterior cervical discectomy with fusion (ACDF). However, new complaints of radiculopathy and/or myelopathy commonly develop at adjacent levels, also known as clinical adjacent segment pathology (CASP). The extent to which kinematics, surgery-induced fusion, natural history and progression of disease play a role in the development of CASP remain unclear. Anterior cervical discectomy with arthroplasty (ACDA) is another treatment option that is thought to reduce the incidence of CASP by preserving motion in the operated segment. While ACDA is often discouraged, as the implant costs are higher while the clinical outcomes are similar to ACDF, preventing CASP might be a reason for ACDA to be a more cost-effective technique in the long-term.Methods and analysisIn this randomized controlled trial, patients will be randomized to receive ACDF or ACDA in a 1:1 ratio. Adult patients with single- or multi-level CDDD and symptoms of radiculopathy and/or myelopathy will be included. The primary outcome is cost-effectiveness and cost-utility of both techniques from a healthcare and societal perspective. Secondary objectives are the differences in clinical and radiological outcomes between the two techniques, as well as the qualitative process surrounding anterior decompression surgery. All outcomes will be measured at baseline, and every six months until four years post-surgery.DiscussionHigh-quality evidence regarding the cost-effectiveness of both ACDA and ACDF is lacking; to date, there are no prospective trials from a societal perspective. Considering the ageing of the population and the rising healthcare costs, there is an urgent need for a solid clinical cost-effectiveness trial addressing this question.

Background: Deep brain stimulation (DBS) is an accepted treatment for patients with medication-resistant Tourette syndrome (TS). Sedation is commonly required during electrode implantation to attenuate anxiety, pain, and severe tics. Anesthetic agents potentially impair the quality of microelectrode recordings (MER). Little is known about the effect of these anesthetics on MER in patients with TS. We describe our experience with different sedative regimens on MER and tic severity in patients with TS. Methods: The clinical records of all TS patients who underwent DBS surgery between 2010 and 2018 were reviewed. Demographic data, stimulation targets, anesthetic agents, perioperative complications, and MER from each hemisphere were collected and analyzed. Single-unit activity was identified by filtering spiking activity from broadband MER data and principal component analysis with K-means clustering. Vocal and motor tics which caused artifacts in the MER data were manually selected using visual and auditory inspection. Results: Six patients underwent bilateral DBS electrode implantation. In all patients, the target was the anterior internal globus pallidus. Patient comfort and hemodynamic and respiratory stability were maintained with conscious sedation with one or more of the following anesthetic drugs: propofol, midazolam, remifentanil, clonidine, and dexmedetomidine. Good quality MER and clinical testing were obtained in 9 hemispheres of 6 patients. In 3 patients, MER quality was poor on one side. Conclusion: Cautiously applied sedative drugs can provide patient comfort, hemodynamic and respiratory stability, and suppress severe tics, with minimal interference with MER.

Background: Several case reports about spinal cord compression due to hyperostosis at the craniocervical junction are available. However, compression at C1-C2 solely due to ossification of the posterior longitudinal ligament (OPLL) is rare. Case Description: A 50-year-old Asian male, with a history of lumbar spinal canal stenosis, presented with a progressive quadriparesis within 3 months. Imaging showed central OPLL at the C1-C2 level contributing to severe spinal cord compression. The patient improved neurologically after a C1-C2 laminectomy. Conclusion: A patient presented with a progressive Brown-Séquard syndrome due to OPLL at the craniocervical junction (C1-C2 level) and improved following a decompressive laminectomy.

Tourette syndrome (TS) is a complex childhood-onset neuropsychiatric disorder characterized by multiple motor tics, plus one or more vocal tics, lasting longer than 1 year. The prevalence of TS in childhood is estimated at 0.3–0.9%, and overall TS has a favorable prognosis. About one third of children with TS will experience a significant decrease in tics during adolescence, and another third of children will become completely tic free. Yet a small proportion of patients do not experience this remission. There is no cure for TS, and treatment aims to reduce or alleviate tics and other comorbid symptoms. Behavioral therapy and pharmacological treatment may provide relief, but some patients remain refractory or experience unbearable side effects. For those patients, deep brain stimulation (DBS) can be considered. The first TS patient was treated with DBS of the thalamus in 1999; since then, approximately 270 patients have been operated. A key factor in attaining optimal results from this surgery is target selection, a topic still under debate due to the complex clinical profile presented by TS patients. Nine separate brain areas have been targeted so far: the medial part of the thalamus (three different areas), the internal globus pallidus (GPi) (anterior and posterior part), the external globus pallidus (GPe), the nucleus accumbens (NA), the anterior limb of the internal capsule (ALIC), and the subthalamic nucleus (STN). Interfering with DBS at the level of one of the main output or relay stations of the basal ganglia seems to result in clinical benefits in refractory TS patients. Overall, DBS results in a significant short-term improvement of 53% on the Yale Global Tic Severity Scale (YGTSS) on all targets. The degree of tic improvement appears to be most robust for the thalamic and the GPi targets. Further research should provide more clarity in selection of the optimal stimulation target, stimulation parameters, and the effectiveness of this treatment.

Objective Thalamic deep brain stimulation (DBS) is effective in reducing tics in patients with refractory Tourette syndrome at the short-term. Here, we report on the long-term outcome. Materials and Methods Seven patients underwent bilateral DBS between 2001 and 2008. The target was the centromedian nucleus, substantia periventricularis and nucleus ventro-oralis internus cross point of the thalamus. The effect on tics and side effects were evaluated with a variable follow-up duration of 12 to 78 months. Results Patient 1 and 2 showed good tic improvements of 81.6% (60 months) and 50% (36 months), respectively. However, side effects like reducing levels of energy and visual disturbances increased. In patient 1, the target was changed to the anterior part of the internal pallidum and patient 2 switched the stimulator permanently off. Patient 3 experiences still satisfying results with a tic improvement of 88.9% (78 months). Patient 4 and 7 showed minor tic improvements of 34% (16 months) and 9% (60 months), respectively. In both patients side effects became more severe and the target was changed to the anterior part of the internal pallidum. Patient 5 showed a tic improvement of 27.5% (12 months) and went abroad for stimulation of the external globus pallidus. Patient 6 developed cerebellar atrophy. He experienced several nonstimulation related side effects and turned the stimulator off. Conclusions There seems to be an increasing disbalance of therapeutic effects and side effects at long-term follow-up, often leading to either switching the stimulator off or new surgery with a different neuro-anatomic target.

Background: Tourette syndrome is a hyperkinetic neurodevelopmental disorder characterized by tics. Objective: Assess the neuronal changes in the associative/limbic GP associated with Tourette syndrome. Methods: Neurophysiological recordings were performed from the anterior (associative/limbic) GPe and GPi of 8 awake patients during DBS electrode implantation surgeries. Results: The baseline firing rate of the neurons was low in a state-dependent manner in both segments of the GP. Tic-dependent transient rate changes were found in the activity of individual neurons of both segments around the time of the tic. Neither oscillatory activity of individual neurons nor correlations in their interactions were observed. Conclusions: The results demonstrate the involvement of the associative/limbic pathway in the underlying pathophysiology of Tourette syndrome and point to tonic and phasic modulations of basal ganglia output as a key mechanisms underlying the abnormal state of the disorder and the expression of individual tics, respectively. © 2017 International Parkinson and Movement Disorder Society

Deep brain stimulation is invasive and used in selected patients with intractable Tourette Syndrome. The anaesthetic technique of first choice during implantation of the electrodes is an awake technique with local anaesthetics and conscious sedation. The anaesthetic management can be challenging, especially in Tourette Syndrome patients due to sudden movements. The anaesthetic goal is to have a comfortable patient during the procedure with minimal influence of pharmacological agents on microelectrode recordings. Here, we describe our experience with the use of an intravenous dexmedetomidine infusion during deep brain stimulation in a patient with Tourette Syndrome. We discuss the effects on the microelectrode recordings and clinical testing. Finally, we describe the advantages of dexmedetomidine as a sedative agent in Tourette Syndrome patients during deep brain stimulation and the pharmacological effects of dexmedetomidine on the basal ganglia.

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.

This thesis describes new insights into deep brain stimulation in otherwise treatment-resistant patients with Tourette Syndrome. Although the exact cause of Tourette Syndrome is largely unknown, it is shown that basal ganglia dysfunction plays a role. Deep brain stimulation activates certain areas within the basal ganglia. We found that thalamus stimulation has marked short-term tic-reducing effects. In the long-term, however, the tic-reducing effects are outweighed by the side effects. Therefore, we switched to globus pallidus stimulation, which is shown to have marked short-term and long-term tic-reducing effects.

Tourette Syndrome (TS) is a childhood onset disorder characterized by vocal and motor tics and often remits spontaneously during adolescence. For treatment refractory patients, Deep Brain Stimulation (DBS) may be considered. We discuss ethical problems encountered in two adolescent TS patients treated with DBS and systematically review the literature on the topic. Following surgery one patient experienced side effects without sufficient therapeutic effects and the stimulator was turned off. After a second series of behavioural treatment, he experienced a tic reduction of more than 50%. The second patient went through a period of behavioural disturbances that interfered with optimal programming, but eventually experienced a 70% tic reduction. Sixteen DBS surgeries in adolescent TS patients have been reported, none of which pays attention to ethical aspects. Specific ethical issues arise in adolescent TS patients undergoing DBS relating both to clinical practice as well as to research. Attention should be paid to selecting patients fairly, thorough examination and weighing of risks and benefits, protecting the health of children and adolescents receiving DBS, special issues concerning patient's autonomy, and the normative impact of quality of life. In research, registration of all TS cases in a central database covering a range of standardized information will facilitate further development of DBS for this indication. Clinical practice should be accompanied by ongoing ethical reflection, preferably covering not only theoretical thought but providing also insights in the views and perspectives of those concerned, that is patients, family members and professionals.

Introduction Thalamic deep brain stimulation is effective in reducing tics in patients with severe Tourette syndrome at the short-term. Here, we report on the long-term outcome. Methods Seven patients with refractory Tourette syndrome were referred to the Maastricht University Medical Centre and underwent bilateral thalamic deep brain stimulation between 2001 and 2008. The target was the centromedian nucleus-substantia periventricularis-nucleus ventro-oralis internus cross point of the thalamus. During the visits to the outpatient clinic, effects on tics, side-effects and stimulations parameters were evaluated. The follow-up duration varied between 12 to 78 months. Results Patient 1 showed an improvement on tics of 81.6% after 60 months, but due to higher voltage stimulation after some years needed to suppress the tics, side-effects became more severe and the target was changed to the anterior part of the internal pallidum. Patient 2 showed a tic improvement of 50% after 36 months, but due to increasing side-effects, he switched the stimulator permanently off. In patient 3 the stimulator is still active and showed satisfying results with an improvement on tics of 88.9% after 78 months. Patient 4 experienced a tic improvement of 34% after 16 months. However, side-effects became more severe, and when the whole system had to be removed due to a persisting hardware infection after six years, the target was changed to the anterior part of the internal pallidum. Patient 5 showed a minor tic improvement of 27.5% after 12 months. He was unsatisfied and went to abroad for stimulation of the external globus pallidus. Patient 6 developed cerebral atrophy due to a neurodegenerative disease and experienced several non-stimulation related side-effects. His tic improvement was 34% on the YGTSS after 26 months and he decided to turn the stimulator off. The positive effect on tics in patient 7 decreased over time until an improvement of only 9% at 60 months of follow-up. The target was changed to the anterior part of the internal pallidum. Conclusion Thalamic deep brain stimulation in patients with severe Tourette syndrome is effective in reducing tics, at least at the short-term. At the long-term only in one patient the stimulator is still active, in three patients the target was changed to the anterior part of the internal pallidum due to side-effects and three were unsatisfied and turned off their stimulator. There seems to be an increasing disbalance of effects versus side effects leading to either switching off the stimulator or re-surgery changing the target. These clinical cases reflect the strong heterogeneity of the disease, with serious comorbity, interfering with effects and side-effects of deep brain stimulation.

Introduction Patients with severe Tourette syndrome are potential candidates for deep brain stimulation (DBS). We have shown that bilateral thalamic as well as pallidal stimulation can be effective in reducing the severity of motor and vocal tics. However, one of the challenges is the anesthetic approach in this type of surgery. During surgery there is an ’awake’ and an ’asleep’ phase. In the ’awake’ phase, anesthesia has three goals. First, to reduce the intraoperative tics to avoid the dislocation of the stereotactic frame. Second, adequate level of consciousness to allow intraoperative testing of stimulation effects. Third, avoid interference with the single-unit electrophysiological recordings. To date there is no consensus on how to reach these goals. In this study, we report our own experience in the past 15 years. In the ‘asleep’ phase there is the internalization of the extension leads and pulsgenerator. Methods From 1999 to 2015 surgery was performed in 15 patients (12 males and 3 females) with severe Tourette syndrome. Eight patients were operated in the thalamic target (cross point of the centromedian nucleus-substantia periventricularis-nucleus ventro-oralis internus) and 7 in the pallidal target (the anteromedial part of the internal globus pallidus). During the procedure different short-acting anesthetic regimens were used. In the ’awake’ phase we used a combination of propofol and remifentanil, remifentanil and clonidine, and remifentanil as a single anesthetic. In the asleep phase all patients were intubated and received a combination of propofol and remifentanil. Results With our awake-asleep anesthetic protocols, none of the patients experienced dislocation of the stereotactic frame during surgery. In the awake phase, all patients were cooperative and neuropsychological testing was possible. Moreover, stimulation related side effects could be screened. We obtained adequate single-unit recordings from the thalamic and pallidal neurons. Conclusion Tailored anesthetic techniques with low-dose sedation make it possible to achieve adequate tic reduction in the ‘awake’ phase, allowing intraoperative clinical testing, and obtain good neurophysiological recordings.