Subthalamic nucleus stimulation improves Parkinsonian gait via brainstem locomotor centers.

BACKGROUND: Subthalamic deep brain stimulation (STN-DBS) can ameliorate gait disturbances in Parkinson's disease (PD). Using motor imagery and positron emission tomography (PET), we investigated how STN-DBS interacts with supraspinal locomotor centers in PD. METHODS: Ten PD patients with bilateral STN-DBS actually walked or stood still under STN-DBS ON or OFF conditions. Directly thereafter, subjects imagined walking or standing while changes in regional cerebral blood flow were measured by PET. RESULTS: Independent of STN-DBS, imagined walking distance correlated with imagery duration. Compared with STN-DBS OFF, STN-DBS ON improved actual gait and increased imagined walking distance. Imagery of gait (vs. stance) induced activity in the supplementary motor area and the right superior parietal lobule for both STN-DBS conditions. The improvement of imagined gait during STN-DBS ON led to activity changes in the pedunculopontine nucleus/mesencephalic locomotor region (PPN/MLR). CONCLUSIONS: Data suggest that STN-DBS improves Parkinsonian gait by modulating PPN/MLR activity.

Production of ß-ionone by combined expression of carotenogenic and plant CCD1 genes in Saccharomyces cerevisiae.

BACKGROUND: Apocarotenoids, like the C13-norisoprenoids, are natural compounds that contribute to the flavor and/or aroma of flowers and foods. They are produced in aromatic plants-like raspberries and roses-by the enzymatic cleavage of carotenes. Due to their pleasant aroma and flavour, apocarotenoids have high commercial value for the cosmetic and food industry, but currently their production is mainly assured by chemical synthesis. In the present study, a Saccharomyces cerevisiae strain that synthesizes the apocarotenoid ß-ionone was constructed by combining integrative vectors and high copy number episomal vectors, in an engineered strain that accumulates FPP. RESULTS: Integration of an extra copy of the geranylgeranyl diphosphate synthase gene (BTS1), together with the carotenogenic genes crtYB and crtI from the ascomycete Xanthophyllomyces dendrorhous, resulted in carotenoid producing cells. The additional integration of the carotenoid cleavage dioxygenase gene from the plant Petunia hybrida (PhCCD1) let to the production of low amounts of ß-ionone (0.073 ± 0.01 mg/g DCW) and changed the color of the strain from orange to yellow. The expression of the crtYB gene from a high copy number plasmid in this former strain increased ß-ionone concentration fivefold (0.34 ± 0.06 mg/g DCW). Additionally, the episomal expression of crtYB together with the PhCCD1 gene in the same vector resulted in a final 8.5-fold increase of ß-ionone concentration (0.63 ± 0.02 mg/g DCW). Batch fermentations with this strain resulted in a final specific concentration of 1 mg/g DCW at 50 h, which represents a 15-fold increase. CONCLUSIONS: An efficient ß-ionone producing yeast platform was constructed by combining integrative and episomal constructs. By combined expression of the genes BTS1, the carotenogenic crtYB, crtI genes and the plant PhCCD1 gene-the highest ß-ionone concentration reported to date by a cell factory was achieved. This microbial cell factory represents a starting point for flavor production by a sustainable and efficient process that could replace current methods.

Physiological and anatomical decomposition of subthalamic neurostimulation effects in essential tremor.

Postural tremor is the leading symptom in essential tremor, but in some cases intention tremor and limb ataxia emerge and can become highly disabling features. Deep brain stimulation of the thalamus or subthalamic white matter improve tremor and ataxia; however, the underlying network mechanisms are enigmatic. To elucidate the mechanisms of deep brain stimulation in essential tremor, we pursued a multimodal approach combining kinematic measures of reach-to-grasp movements, clinical assessments, physiological measures of neuronal excitability and probabilistic tractography from diffusion tensor imaging. Seven patients with essential tremor (age 62.9 ± 10.3 years, two females) received thalamic deep brain stimulation and a clinical examination of severity of limb tremor and ataxia at off stimulation, using therapeutic and supratherapeutic stimulation parameters. A reach-to-grasp task based on acoustic cues was also performed. To examine the electrical properties of target structures, we determined the chronaxie of neural elements modulated. A control group of 13 healthy subjects (age 56 ± 7.6 years, five females) underwent whole-brain diffusion tensor imaging at 3 T. Probabilistic tractography was applied in healthy subjects from seeds in cerebellum and midbrain to reconstruct the connectivity pattern of the subthalamic area. The positions of stimulation electrodes in patients were transferred into probability maps and connectivity values were correlated to clinical outcome measures. Therapeutic stimulation improved ataxia and tremor mainly during the target period of the reaching paradigm (63% reduction compared with off stimulation). Notably the acceleration (29%) and deceleration periods (41%) were improved. By contrast, supratherapeutic stimulation worsened ataxia during the deceleration period with a 55% increase of spatial variability, while maintaining near complete suppression of tremor. Chronaxie measures were in the range of rapidly-conducting myelinated fibres with significantly different values for the anti-tremor effect of therapeutic stimulation (27 s) and the pro-ataxic effect of supratherapeutic stimulation (52 s). The degree of connectivity to the dentato-thalamic tract at the stimulating electrode correlated significantly with the reduction of tremor in the therapeutic condition. Our data suggest that stimulation induced tremor reduction and induction of ataxia by supratherapeutic stimulation are mediated by different fibre systems. Probalistic tractography identified the dentato-thalamic tract as a likely target of tremor suppression. Stimulation-induced ataxia may be caused by additional recruitment of adjacent fibre systems at higher amplitudes. Stimulation with short pulse duration may help to increase the therapeutic window and focus on the anti-tremor effect.

Arthroscopic-assisted hook plate fixation for acromioclavicular joint dislocation.

PURPOSE: We present a new technique of arthroscopic-assisted AC-hook plate fixation for acromioclavicular joint dislocation with all the advantages of minimally invasive surgery and the possibility to treat concomitant pathologies. METHODS: Initially a glenohumeral arthroscopy is performed to address concomitant intra-articular injuries. Under subacromial visualisation the drill hole for the hook of the plate can be exactly positioned in the acromion. The hook plate is put in place under visual control. RESULTS: The initial results (n = 3) are promising with good to excellent results in the Constant score [90.5 (range 82-100)] in all cases studied. The cross-body test was slightly positive in one case. The median follow-up time after the index procedure was seven months (range five to ten). CONCLUSIONS: In conclusion, arthroscopic-assisted reconstruction of acromioclavicular joint separation is feasible and may provide patients with all the benefits of AC-hook fixation with decreased risks related to open surgery. The described technique is recommended for all surgeons familiar with arthroscopic surgery.

Lactate based caproate production with Clostridium drakei and process control of Acetobacterium woodii via lactate dependent in situ electrolysis.

Syngas fermentation processes with acetogens represent a promising process for the reduction of CO2 emissions alongside bulk chemical production. However, to fully realize this potential the thermodynamic limits of acetogens need to be considered when designing a fermentation process. An adjustable supply of H2 as electron donor plays a key role in autotrophic product formation. In this study an anaerobic laboratory scale continuously stirred tank reactor was equipped with an All-in-One electrode allowing for in-situ H2 generation via electrolysis. Furthermore, this system was coupled to online lactate measurements to control the co-culture of a recombinant lactate-producing Acetobacterium woodii strain and a lactate-consuming Clostridium drakei strain to produce caproate. When C. drakei was grown in batch cultivations with lactate as substrate, 1.6 g·L-1 caproate were produced. Furthermore, lactate production of the A. woodii mutant strain could manually be stopped and reinitiated by controlling the electrolysis. Applying this automated process control, lactate production of the A. woodii mutant strain could be halted to achieve a steady lactate concentration. In a co-culture experiment with the A. woodii mutant strain and the C. drakei strain, the automated process control was able to dynamically react to changing lactate concentrations and adjust H2 formation respectively. This study confirms the potential of C. drakei as medium chain fatty acid producer in a lactate-mediated, autotrophic co-cultivation with an engineered A. woodii strain. Moreover, the monitoring and control strategy presented in this study reinforces the case for autotrophically produced lactate as a transfer metabolite in defined co-cultivations for value-added chemical production.

Novel synthetic co-culture of Acetobacterium woodii and Clostridium drakei using CO2 and in situ generated H2 for the production of caproic acid via lactic acid.

Acetobacterium woodii is known to produce mainly acetate from CO2 and H2, but the production of higher value chemicals is desired for the bioeconomy. Using chain-elongating bacteria, synthetic co-cultures have the potential to produce longer-chained products such as caproic acid. In this study, we present first results for a successful autotrophic co-cultivation of A. woodii mutants and a Clostridium drakei wild-type strain in a stirred-tank bioreactor for the production of caproic acid from CO2 and H2 via the intermediate lactic acid. For autotrophic lactate production, a recombinant A. woodii strain with a deleted Lct-dehydrogenase complex, which is encoded by the lctBCD genes, and an inserted D-lactate dehydrogenase (LdhD) originating from Leuconostoc mesenteroides, was used. Hydrogen for the process was supplied using an All-in-One electrode for in situ water electrolysis. Lactate concentrations as high as 0.5 g L-1 were achieved with the AiO-electrode, whereas 8.1 g L-1 lactate were produced with direct H2 sparging in a stirred-tank bioreactor. Hydrogen limitation was identified in the AiO process. However, with cathode surface area enlargement or numbering-up of the electrode and on-demand hydrogen generation, this process has great potential for a true carbon-negative production of value chemicals from CO2.

An Examination of the Number of Adolescent Scoliotic Curves That Are Braceable at First Presentation to a Scoliosis Service.

Adolescent idiopathic scoliosis (AIS) affects between 0.5% and 5.2% of adolescents and is progressive in two-thirds of cases. Bracing is an effective non-operative treatment for AIS and has been shown to prevent up to 72% of curves from requiring surgery. This paper explores the presentation of AIS in the UK and identifies who would be suitable for bracing, as per guidelines published by the Scoliosis Research Society (SRS) and British Scoliosis Society (BSS), through curve severity and skeletal maturity at presentation. There were 526 patients with AIS eligible for inclusion across three tertiary referral centres in the UK. The study period was individualised to each centre, between January 2012 and December 2021. Only 10% were appropriate for bracing via either SRS or BSS criteria. The rest were either too old, skeletally mature or had a curve size too large to benefit. By the end of data collection, 38% had undergone surgery for their scoliosis. In the UK, bracing for AIS is only suitable for a small number at presentation. Future efforts to minimise delays in specialist review and intervention will increase the number of those with AIS suitable for bracing and reduce the number and burden of operative interventions for AIS in the UK.

Stimulation site within the MRI-defined STN predicts postoperative motor outcome.

High-frequency stimulation of the subthalamic nucleus (STN-HFS) is highly effective in treating motor symptoms in Parkinson's disease (PD) and medication side effects as well as in improving quality of life. Despite preoperative screening for patients as eligible candidates for this treatment, electrode position may furthermore influence treatment quality. Here, we investigated the relationship between the anatomical site of stimulation within the MRI-defined STN and the outcome of PD patients after STN-HFS. In 30 PD patients with bilateral STN stimulation, we retrospectively defined the boundaries of the STN within the axial target plane of the stereotactic T2-weighted MRI and determined the position of the active electrode contact in relation to the border of the STN. The position of the active contact within the STN was the only variable to predict the outcome of STN stimulation. In contrast, covariates such as age, disease duration, symptom severity, and response to levodopa had no effect. The lateral position of the stimulation contact within the STN led to significantly better clinical improvement, lower stimulation parameters, and less need for postoperative dopaminergic medication. The outcome of patients with stimulation contacts within the medial region of the STN was significantly worse. Precise targeting of the lateral region of the STN is essential for achieving sufficient stimulation efficacy. Preoperative T2-weighted MRI might be a useful component of the targeting procedure to improve the outcome of PD patients.

The atypical subthalamic nucleus--an anatomical variant relevant for stereotactic targeting.

BACKGROUND: The improvement of PD motor symptoms by DBS of the STN depends on exact targeting. METHODS: A combination of MRI and multitrajectory microrecordings was used for localization of the STN in a group of 228 consecutive PD patients. RESULTS: In 1% of our cases, the STN was consistently shifted in the anterior (3.3 ± 0.8mm) and medial (3.0 ± 0.9 mm) direction within the target plane, compared to controls. Adjustment of the original target coordinates after intraoperative reevaluation of the MRI and confirmation by typical subthalamic neuronal recordings along the deviant trajectory allowed the implantation of clinically effective electrodes in all cases. The relative improvement of the motor UPDRS at 6-months follow-up in patients with an atypical and typical STN was comparable. CONCLUSION: An atypical position of the STN does not need to complicate DBS surgery, if detected by a combination of MRI-based targeting and electrophysiological guidance.

Dual modality of vertebral body tethering : anterior scoliosis correction versus growth modulation with mean follow-up of five years.

AIMS: Vertebral body tethering (VBT) is a non-fusion technique to correct scoliosis. It allows correction of scoliosis through growth modulation (GM) by tethering the convex side to allow concave unrestricted growth similar to the hemiepiphysiodesis concept. The other modality is anterior scoliosis correction (ASC) where the tether is able to perform most of the correction immediately where limited growth is expected. METHODS: We conducted a retrospective analysis of clinical and radiological data of 20 patients aged between 9 and 17 years old, (with a 19 female: 1 male ratio) between January 2014 to December 2016 with a mean five-year follow-up (4 to 7). RESULTS: There were ten patients in each group with a total of 23 curves operated on. VBT-GM mean age was 12.5 years (9 to 14) with a mean Risser classification of 0.63 (0 to 2) and VBT-ASC was 14.9 years (13 to 17) with a mean Risser classification of 3.66 (3 to 5). Mean preoperative VBT-GM Cobb was 47.4° (40° to 58°) with a Fulcrum unbend of 17.4 (1° to 41°), compared to VBT-ASC 56.5° (40° to 79°) with 30.6 (2° to 69°)unbend. Postoperative VBT-GM was 20.3° and VBT-ASC Cobb angle was 11.2°. The early postoperative correction rate was 54.3% versus 81% whereas Fulcrum Bending Correction Index (FBCI) was 93.1% vs 146.6%. The last Cobb angle on radiograph at mean five years' follow-up was 19.4° (VBT-GM) and 16.5° (VBT-ASC). Patients with open triradiate cartilage (TRC) had three over-corrections. Overall, 5% of patients required fusion. This one patient alone had a over-correction, a second-stage tether release, and final conversion to fusion. CONCLUSION: We show a high success rate (95%) in helping children avoid fusion at five years post-surgery. VBT is a safe technique for correction of scoliosis in the skeletally immature patient. This is the first report at five years that shows two methods of VBT can be employed depending on the skeletal maturity of the patient: GM and ASC. Cite this article: Bone Jt Open 2022;3(2):123-129.

Dynamic Radiographs in Assessing Stability of Cervical Spine Fractures: A Multicentre Study.

BACKGROUND: In the management of a trauma patient with cervical spine injury, the need for accurate diagnostic imaging is key to ensure correct management. Different classification systems have been developed including the Subaxial Injury Classification (SLIC) system and AO cervical spine fracture classification. Through a multicentre study, we have identified a group of cases where the use of CT alone to classify fractures by either SLIC or AO score may be deficient and the use of dynamic cervical spine radiographs could help identify instability. METHODS: Three level 1 trauma centers retrospectively reviewed patients with cervical spine injuries. Cervical spine radiographs (AP and lateral) were undertaken in collar, in all patients with suspected cervical spine injury within 2 weeks, followed by reanalysis of scoring systems. RESULTS: Eleven cases were identified in total, and 72% were male with a mean age of 65 years, with approximately 54% being older than 70 years. All patients reported their pain as severe using the Visual Analogue Scale scale. The predynamic radiograph mean SLIC score was 0.73, which is in contrast to the postdynamic radiograph mean SLIC score of 6. The statistical significance (P = 0.004) was found using the Wilcoxon signed-rank test. CONCLUSION: Supine imaging eliminates the gravitational loads normally exerted on the c-spine. The cases show assumed cervical stability based on CT, but dynamic c-spine radiographs subsequently demonstrated instability. Therefore, we suggest a combination of SLIC and AO classification using radiologic imaging to classify fracture and correlate clinical symptoms with persistent neck pain, which warrants a Miami-J collar and dynamic c-spine radiograph to assess stability with re-evaluation of scoring.

Modulation of gait coordination by subthalamic stimulation improves freezing of gait.

The effect of subthalamic deep brain stimulation on gait coordination and freezing of gait in patients with Parkinson's disease is incompletely understood. The purpose of this study was to investigate the extent to which modulation of symmetry and coordination between legs by subthalamic deep brain stimulation alters the frequency and duration of freezing of gait in patients with Parkinson's disease. We recruited 13 post-subthalamic deep brain stimulation patients with Parkinson's disease with off freezing of gait and evaluated them in the following 4 conditions: subthalamic deep brain stimulation on (ON) and stimulation off (OFF), 50% reduction of stimulation voltage for the leg with shorter step length (worse side reduction) and for the leg with longer step length (better side reduction). Gait analysis was performed on a treadmill and recorded by an optoelectronic analysis system. We measured frequency and duration of freezing of gait episodes. Bilateral coordination of gait was assessed by the Phase Coordination Index, quantifying the ability to generate antiphase stepping. From the OFF to the ON state, freezing of gait improved in frequency (2.0 ± 0.4 to 1.4 ± 0.5 episodes) and duration (12.2 ± 2.6 to 2.6 ± 0.8 seconds; P = .005). Compared with the ON state, only better side reduction further reduced freezing of gait frequency (0.2 ± 0.2) and duration of episodes (0.2 ± 0.2 seconds; P = .03); worse side reduction did not change frequency (1.3 ± 0.4) but increased freezing of gait duration (5.2 ± 2.1 seconds). The better side reduction-associated improvements were accompanied by normalization of gait coordination, as measured by phase coordination index (16.5% ± 6.0%), which was significantly lower than in the other 3 conditions. Reduction of stimulation voltage in the side contralateral to the leg with longer step length improves frequency and duration of freezing of gait through normalization of gait symmetry and coordination in subthalamic deep brain stimulation patients with Parkinson's disease. This identifies poor leg coordination as a risk factor for causing freezing of gait.

Long-term clinical outcome in meige syndrome treated with internal pallidum deep brain stimulation.

Deep brain stimulation of the globus pallidus internus (GPi DBS) is effective in the treatment of primary segmental and generalized dystonia. Although limb, neck, or truncal dystonia are markedly improved, orofacial dystonia is ameliorated to a lesser extent. Nevertheless, several case reports and small cohort studies have described favorable short-term results of GPi DBS in patients with severe Meige syndrome. Here, we extend this preliminary experience by reporting long-term outcome in a multicenter case series, following 12 patients (6 women, 6 men) with Meige syndrome for up to 78 months after bilateral GPi DBS. We retrospectively assessed dystonia severity based on preoperative and postoperative video documentation. Mean age of patients at surgery was 64.5 ± 4.4 years, and mean disease duration 8.3 ± 4.4 years. Dystonia severity as assessed by the Burke-Fahn-Marsden Dystonia Rating Scale showed a mean improvement of 45% at short-term follow-up (4.4 ± 1.5 months; P < 0.001) and of 53% at long-term follow-up (38.8 ± 21.7 months; P < 0.001). Subscores for eyes were improved by 38% (P = 0.004) and 47% (P < 0.001), for mouth by 50% (P < 0.001) and 56% (P < 0.001), and for speech/swallowing by 44% (P = 0.058) and 64% (P = 0.004). Mean improvements were 25% (P = 0.006) and 38% (P < 0.001) on the Blepharospasm Movement Scale and 44% (P < 0.001) and 49% (P < 0.001) on the Abnormal Involuntary Movement Scale. This series, which is the first to demonstrate a long-term follow-up in a large number of patients, shows that GPi DBS is a safe and highly effective therapy for Meige syndrome. The benefit is preserved for up to 6 years.

Gait ataxia in essential tremor is differentially modulated by thalamic stimulation.

Patients with advanced stages of essential tremor frequently exhibit tandem gait ataxia with impaired balance control and imprecise foot placement, resembling patients with a cerebellar deficit. Thalamic deep brain stimulation, a surgical therapy for otherwise intractable cases, has been shown to improve tremor, but its impact on cerebellar-like gait difficulties remains to be elucidated. Eleven patients affected by essential tremor (five females; age 69.8 ± 3.9 years; disease duration 24.4 ± 11.2 years; follow-up after surgery 24.7 ± 20.3 months) were evaluated during the following conditions: stimulation off, stimulation on and supra-therapeutic stimulation. Ten age-matched healthy controls served as the comparison group. Locomotion by patients and controls was assessed with (i) overground gait and tandem gait; (ii) balance-assisted treadmill tandem gait and (iii) unassisted treadmill gait. The two treadmill paradigms were kinematically analysed using a 3D opto-electronic motion analysis system. Established clinical and kinesiological measures of ataxia were computed. During stimulation off, the patients exhibited ataxia in all assessment paradigms, which improved during stimulation on and worsened again during supra-therapeutic stimulation. During over ground tandem gait, patients had more missteps and slower gait velocities during stimulation off and supra-therapeutic stimulation than during stimulation on. During balance-assisted tandem gait, stimulation on reduced the temporospatial variability in foot trajectories to nearly normal values, while highly variable (ataxic) foot trajectories were observed during stimulation off and supra-therapeutic stimulation. During unassisted treadmill gait, stimulation on improved gait stability compared with stimulation off and supra-therapeutic stimulation, as demonstrated by increased gait velocity and ankle rotation. These improvements in ataxia were not a function of reduced tremor in the lower limbs or torso. In conclusion, we demonstrate the impact of thalamic stimulation on gait ataxia in patients with essential tremor with improvement by stimulation on and deterioration by supra-therapeutic stimulation, despite continued control of tremor. Thus, cerebellar dysfunction in these patients can be differentially modulated with optimal versus supra-therapeutic stimulation. The cerebellar movement disorder of essential tremor is due to a typical cerebellar deficit, not to trembling extremities. We hypothesize that deep brain stimulation affects two major regulating circuits: the cortico-thalamo-cortical loop for tremor reduction and the cerebello-thalamo-cortical pathway for ataxia reduction (stimulation on) and ataxia induction (supra-therapeutic stimulation).

Online survey among maritime pilots: job-related stress and strain and the effects on their work ability.

BACKGROUND: Maritime pilots often navigate ships through challenging waterways. The required 24 h standby rotation system (ROS) poses a stressful working situation. This study aims to describe the current job-related stress and strain among maritime pilots and the effects on their work ability, taking into account the different rotation systems. METHODS: Within a cross-sectional survey, pilots of all German pilots' associations were asked to complete an online questionnaire. The 1-week ROS (port pilots) was compared with the 4-month ROS (sea and canal pilots). The pilots' subjective perception of stress and strain was assessed using an established ship-specific questionnaire. Daily sleepiness and work ability were examined respectively using the Epworth Sleepiness Scale (ESS) and the Work Ability Index (WAI). RESULTS: The study group consisted of 401 male German pilots with an average age of 48.5 years (participation rate 46.9%). More than 50% of the pilots evaluated irregular working hours as the main stressor in their job. 79.8% of the pilots (especially 4-month ROS) experienced high psychological demands in their workplace. 83.3% stated having regularly neglected their private obligations due to job assignments. Pilots from the 4-month ROS experienced insufficiently predictable free time and long operation times at a stretch as stressors (p < 0.001 and p = 0.037). Elevated daily sleepiness was found in 41.9% of the pilots. The overall evaluation of the WAI questionnaire showed good to very good work ability at 77.3%. Additionally, no significant differences in the daily sleepiness or the work ability were observed between the pilots of the different two ROS. CONCLUSIONS: Due to their subjectively higher job-related mental demands, their disturbed work-life balance, and their long operation times at a stretch, it is likely that pilots from the 4-month ROS have significantly higher job stress compared to those in the 1-week ROS. However, this does not lead to more sleepiness or reduced work ability, which suggests that the pilots of this ROS are highly adapted to their working situation. Nevertheless, intervention measures with shortened ROS amongst sea and canal pilots' associations should be tested in respect of benefit, practicability and acceptance by the pilots.

Managing Known Difficult Airways in Obstetric Patients Using a Flexible Bronchoscope and IRRIS: A Case-Illustrated Guide for Nonexpert Anesthesiologists, without Surgical Backup.

Pregnancy is associated with anatomical and physiological changes leading to potential difficult airway management. Some pregnant women have known difficult airways and cannot be intubated even with a hyperangulated videolaryngoscope. If neuraxial techniques are also impossible, awake tracheal intubation with a flexible bronchoscope may be one of the few available options to avoid more invasive techniques. The Infrared Red Intubation System (IRRIS) may help nonexpert anesthesiologists in such situations and may enhance the chance of successful intubation increasing safety for the mother and the fetus, especially in hospitals without the ear, nose, and throat surgical backup.

Influence of deep brain stimulation and levodopa on sensory signs in Parkinson's disease.

To examine the effects of levodopa (L-dopa) and deep brain stimulation of the subthalamic nucleus (STN-DBS) on sensory symptoms and signs in Parkinson's disease (PD). Seventeen patients with PD were included. (1) Presence of sensory symptoms and (2) effects of L-dopa and STN-DBS on sensory symptoms and signs [assessed by quantitative sensory testing (QST)] were examined 6 months after starting STN-DBS. In addition, in 12 of these patients, presence of sensory symptoms prior and post STN-DBS was compared. Pain was most frequently nociceptive. In about 30-40%, pain and sensory symptoms were associated with PD motor symptoms. In most of these cases, pain responded to L-dopa. Intensity of pain was reduced post STN-DBS compared to pre STN-DBS. L-Dopa had no influence on detection thresholds, whereas STN-DBS improved thermal detection thresholds. However, thermal and mechanical pain thresholds were uninfluenced by L-dopa or STN-DBS. Although some patients reported an improvement of pain with STN-DBS or L-dopa, objectively pain sensitivity as assessed by QST was not altered by STN-DBS or L-dopa suggesting that there is no evidence for a direct modulation of central pain processing by L-dopa or STN-DBS.

Chronic deep brain stimulation in patients with tardive dystonia without a history of major psychosis.

Tardive dystonia usually occurs with a delay after neuroleptic exposure in patients with major psychosis. A subgroup of patients, however, is given such medication for "mild depression" or "neurasthenia." Tardive dystonia, in general, may respond favorably to pallidal deep brain stimulation (DBS). Nevertheless, it remains unclear thus far whether or not similar beneficial outcome is achieved with pallidal DBS in different subgroups of patients with tardive dystonia. Four women (mean age 59 years at surgery) underwent stereotactic pallidal DBS in the frame of an observational study. Tardive dystonia occurred secondary to medication with fluspirilene and haloperidol, and injection of long-acting depot neuroleptics prescribed for mild depression or "nervousness." Assessment included the Burke-Fahn-Marsden (BFM) scale preoperatively and at 12 months follow-up. Extended follow-up was available at a mean of 27.3 months postoperatively (range 16-36 months). There were no surgically related complications. All 4 patients experienced sustained statistically significant benefit from pallidal DBS. Mean improvement at 12 months was 77% for the BFM motor score (range, 45-91%; P = 0.043), and 84% at the last available follow-up (range, 70-91%; P = 0.03). This was paralleled by improvement of the BFM disability score. Chronic pallidal DBS in patients with tardive dystonia without a history of major psychosis provides sustained improvement which is similar to that in other subgroups of patients with tardive dystonia. This effect is stable on extended follow-up for up to 3 years.

A randomised controlled trial of lidocaine infusion on post-operative opioid consumption in patients undergoing robotic colorectal surgery.

INTRODUCTION: Intravenous lidocaine has been shown to have analgesic effects leading to a reduced post-operative opiate need, but this effect is still debated in various surgical populations. We investigated whether this effect could be demonstrated in robot-assisted colorectal surgery. METHODS: A total of 60 adult patients undergoing robot-assisted colorectal surgery were randomly assigned to two groups in this prospective, double-blinded trial. The lidocaine group was treated with intravenous lidocaine. Treatment was initiated before induction of anaesthesia with a bolus of 1.5 mg/kg and immediately followed by infusion of 1.5 mg/kg/h continued until 2 h after end of surgery. The control group received placebo treatment with an equal volume and a dosing of 0.9% saline. The follow-up period was 72 h. RESULTS: No significant difference between groups in the median cumulated morphine consumption at 24 and 72 h was observed. Nor were there any differences in pain score, use of antiemetics, time until flatus and/or defecation or length of hospital stay. CONCLUSIONS: In this randomised, double-blinded, prospective study using intravenous lidocaine versus 0.9% saline in robot-assisted colorectal surgery, we found no significant difference in post-operative cumulated morphine consumption at 24 or at 72 h. FUNDING: The study received funding from DASAIMs Forskningsinitiativ (2016) and DASAIMs Smerteforskningspris (2016). TRIAL REGISTRATION: The trial is registered with EudraCT (2014-003466-25) and ClinicalTrials.gov (ID: NCT03044808).

A randomized trial of deep-brain stimulation for Parkinson's disease.

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).