Peak wall rupture index is associated with risk of rupture of abdominal aortic aneurysms, independent of size and sex.

BACKGROUND: Information on the predictive determinants of abdominal aortic aneurysm rupture from CT angiography are scarce. The aim of this study was to investigate biomechanical parameters in abdominal aortic aneurysms and their association with risk of subsequent rupture. METHODS: In this retrospective study, the digital radiological archive was searched for 363 patients with ruptured abdominal aortic aneurysms. All patients who underwent at least one CT angiography examination before aneurysm rupture were included. CT angiography results were analysed to determine maximum aneurysm diameter, aneurysm volume, and biomechanical parameters (peak wall stress and peak wall rupture index). In the primary survival analysis, patients with abdominal aortic aneurysms less than 70 mm were considered. Sensitivity analyses including control patients and abdominal aortic aneurysms of all sizes were performed. RESULTS: A total of 67 patients who underwent 109 CT angiography examinations before aneurysm rupture were identified. The majority were men (47, 70%) and the median age at the time of CTA examination was 77 (71-83) years. The median maximum aneurysm diameter was 56 (interquartile range 46-65) mm and the median time to rupture was 2.13 (interquartile range 0.64-4.72) years. In univariable analysis, maximum aneurysm diameter, aneurysm volume, peak wall stress, and peak wall rupture index were all associated with risk of rupture. Women had an increased HR for rupture when adjusted for maximum aneurysm diameter or aneurysm volume (HR 2.16, 95% c.i. 1.23 to 3.78 (P = 0.007) and HR 1.92, 95% c.i. 1.06 to 3.50 (P = 0.033) respectively). In multivariable analysis, the peak wall rupture index was associated with risk of rupture. The HR for peak wall rupture index was 1.05 (95% c.i. 1.03 to 1.08) per % (P < 0.001) when adjusted for maximum aneurysm diameter and 1.05 (95% c.i. 1.02 to 1.08) per % (P < 0.001) when adjusted for aneurysm volume. CONCLUSION: Biomechanical factors appear to be important in the prediction of abdominal aortic aneurysm rupture. Women are at increased risk of rupture when adjustments are made for maximum aneurysm diameter alone.

Seeing Is Believing: Photon Counting Computed Tomography Clearly Images Directional Deep Brain Stimulation Lead Segments and Markers After Implantation.

BACKGROUND AND OBJECTIVES: Directional deep brain stimulation (DBS) electrodes are increasingly used, but conventional computed tomography (CT) is unable to directly image segmented contacts owing to physics-based resolution constraints. Postoperative electrode segment orientation assessment is necessary because of the possibility of significant deviation during or immediately after insertion. Photon-counting detector (PCD) CT is a relatively novel technology that enables high resolution imaging while addressing several limitations intrinsic to CT. We show how PCD CT can enable clear in vivo imaging of DBS electrodes, including segmented contacts and markers for all major lead manufacturers. MATERIALS AND METHODS: We describe postoperative imaging and reconstruction protocols we have developed to enable optimal lead visualization. PCD CT images were obtained of directional leads from the three major manufacturers and fused with preoperative 3T magnetic resonance imaging (MRI). Radiation dosimetry also was evaluated and compared with conventional imaging controls. Orientation estimates from directly imaged leads were compared with validated software-based reconstructions (derived from standard CT imaging artifact analysis) to quantify congruence in alignment and directional orientation. RESULTS: High-fidelity images were obtained for 15 patients, clearly indicating the segmented contacts and directional markers both on CT alone and when fused to MRI. Our routine imaging protocol is described. Ionizing radiation doses were significantly lower than with conventional CT. For most leads, the directly imaged lead orientations and depths corresponded closely to those predicted by CT artifact-based reconstructions. However, unlike direct imaging, the software reconstructions were susceptible to 180° error in orientation assessment. CONCLUSIONS: High-resolution photon-counting CT can very clearly image segmented DBS electrode contacts and directional markers and unambiguously determine lead orientation, with lower radiation than in conventional imaging. This obviates the need for further imaging and may facilitate anatomically tailored directional programming.

Three-dimensional growth and biomechanical risk progression of abdominal aortic aneurysms under serial computed tomography assessment.

Growth of abdominal aortic aneurysms (AAAs) is often described as erratic and discontinuous. This study aimed at describing growth patterns of AAAs with respect to maximal aneurysm diameter (Dmax) and aneurysm volume, and to characterize changes in the intraluminal thrombus (ILT) and biomechanical indices as AAAs grow. 384 computed tomography angiographies (CTAs) from 100 patients (mean age 70.0, standard deviation, SD = 8.5 years, 22 women), who had undergone at least three CTAs, were included. The mean follow-up was 5.2 (SD = 2.5) years. Growth of Dmax was 2.64 mm/year (SD = 1.18), volume 13.73 cm3/year (SD = 10.24) and PWS 7.3 kPa/year (SD = 4.95). For Dmax and volume, individual patients exhibited linear growth in 87% and 77% of cases. In the tertile of patients with the slowest Dmax-growth (< 2.1 mm/year), only 67% belonged to the slowest tertile for volume-growth, and 52% and 55% to the lowest tertile of PWS- and PWRI-increase, respectively. The ILT-ratio (ILT-volume/aneurysm volume) increased with time (2.6%/year, p < 0.001), but when adjusted for volume, the ILT-ratio was inversely associated with biomechanical stress. In contrast to the notion that AAAs grow in an erratic fashion most AAAs displayed continuous and linear growth. Considering only change in Dmax, however, fails to capture the biomechanical risk progression, and parameters such as volume and the ILT-ratio need to be considered.

Biomechanics and early sac regression after endovascular aneurysm repair of abdominal aortic aneurysm.

Background: Sac regression after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) is regarded as a marker of successful response to treatment. Several factors influence sac behavior after EVAR, yet little is known about the value of preoperative biomechanics. The aim of this study was to investigate the difference in aortic biomechanics between patients with and without sac regression. Methods: Patients treated with standard EVAR for infrarenal AAA at the Karolinska University Hospital between 2009 and 2012 with one preoperative and a minimum of two postoperative computed tomography angiography (CTA) scans were considered for inclusion in this single-center retrospective cohort study. Biomechanical indices such as AAA wall stress and wall stress-strength ratio as well as intraluminal thrombus (ILT) thickness and stress were measured preoperatively in A4ClinicRE (VASCOPS GmbH). AAA diameter and volume were analyzed on preoperative, 30-day, and 1-year CTAs. Patients were dichotomized based on sac regression, defined as a ≥ 5 mm decrease in maximal AAA diameter between the first two postoperative CTA scans. Multivariable logistic regression was used for analysis of factors associated with early sac regression. Results: Of the 101 patients treated during the inclusion period, 64 were included. Thirty-nine (61%) demonstrated sac regression and 25 (39%) had a stable sac or sac increase. The mean patients age (73 years vs 76 years), male sex (85% vs 96%), and median AAA diameter (58 mm vs 58.5 mm) did not differ between patients with and without sac regression. Although no difference in preoperative biomechanics was seen between the groups, multivariable logistic regression revealed that a larger AAA diameter (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.06-1.51; P = .009) and smoking (OR, 22.1; 95% CI, 2.78-174; P = .003) were positively associated with sac regression. In contrast, the lumen diameter (OR, 0.87; 95% CI, 0.77-0.98; P = .023), ILT thickness (OR, 0.85; 95% CI, 0.75-0.97; P = .013), aspirin or direct-acting oral anticoagulant use (OR, 0.11; 95% CI, 0.02-0.61; P = .012), and mean ILT stress (OR, 0.35; 95% CI, 0.14-0.87; P = .024) showed a negative association. Patients with sac regression had fewer reinterventions (log-rank P = .010) and lower mortality (log-rank P = .012) at the 5-year follow-up. Conclusions: This study, characterizing preoperative biomechanics in patients with and without sac regression, demonstrated a negative association between mean ILT stress and ILT thickness with a change in sac diameter after EVAR. Given that the ILT is a highly dynamic entity, further studies focusing on the role of the thrombus are needed. Furthermore, patients presenting with early sac regression had improved outcomes after EVAR.

Deep Brain Stimulation and Levodopa Affect Gait Variability in Parkinson Disease Differently.

BACKGROUND: Both dopaminergic medication and subthalamic nucleus (STN) deep brain stimulation (DBS) can improve the amplitude and speed of gait in Parkinson disease (PD), but relatively little is known about their comparative effects on gait variability. Gait irregularity has been linked to the degeneration of cholinergic neurons in the pedunculopontine nucleus (PPN). OBJECTIVES: The STN and PPN have reciprocal connections, and we hypothesized that STN DBS might improve gait variability by modulating PPN function. Dopaminergic medication should not do this, and we therefore sought to compare the effects of medication and STN DBS on gait variability. MATERIALS AND METHODS: We studied 11 patients with STN DBS systems on and off with no alteration to their medication, and 15 patients with PD without DBS systems on and off medication. Participants walked for two minutes in each state, wearing six inertial measurement units. Variability has previously often been expressed in terms of SD or coefficient of variation over a testing session, but these measures conflate long-term variability (eg, gradual slowing, which is not necessarily pathological) with short-term variability (true irregularity). We used Poincaré analysis to separate the short- and long-term variability. RESULTS: DBS decreased short-term variability in lower limb gait parameters, whereas medication did not have this effect. In contrast, STN DBS had no effect on arm swing and trunk motion variability, whereas medication increased them, without obvious dyskinesia. CONCLUSIONS: Our results suggest that STN DBS acts through a nondopaminergic mechanism to reduce gait variability. We believe that the most likely explanation is the retrograde activation of cholinergic PPN projection neurons.

Longitudinal changes of early motor and cognitive symptoms in progressive supranuclear palsy: the OxQUIP study.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative condition characterised by a range of motor and cognitive symptoms. Very little is known about the longitudinal change in these symptoms over time. Moreover, the effectiveness of clinical scales to detect early changes in PSP is still a matter of debate. OBJECTIVE: We aimed to determine longitudinal changes in PSP features using multiple closely spaced follow-up time points over a period of 2 years. Methods 28 healthy control and 28 PSP participants, with average time since onset of symptoms of 1.9 years, were prospectively studied every 3 months for up to 24 months. Changes from baseline scores were calculated at each follow-up time point using multiple clinical scales to identify longitudinal progression of motor and cognitive symptoms. RESULTS: The Montreal Cognitive Assessment, but not the Mini-Mental State Examination, detected cognitive decline at baseline. Both scales revealed poor longitudinal sensitivity to clinical change in global cognitive symptoms. Conversely, the Movement Disorders Society Unified Parkinson's disease Rating Scale - part III and the PSP Rating Scale (PSPRS) reliably detected motor decline less than 2 years after disease onset. The 'Gait/Midline' PSPRS subscore consistently declined over time, with the earliest change being observed 6 months after baseline assessment. CONCLUSION: While better cognitive screening tools are still needed to monitor cognitive decline in PSP, motor decline is consistently captured by clinical rating scales. These results support the inclusion of multiple follow-up time points in longitudinal studies in the early stages of PSP.

Geometric and biomechanical modeling aided by machine learning improves the prediction of growth and rupture of small abdominal aortic aneurysms.

It remains difficult to predict when which patients with abdominal aortic aneurysm (AAA) will require surgery. The aim was to study the accuracy of geometric and biomechanical analysis of small AAAs to predict reaching the threshold for surgery, diameter growth rate and rupture or symptomatic aneurysm. 189 patients with AAAs of diameters 40-50 mm were included, 161 had undergone two CTAs. Geometric and biomechanical variables were used in prediction modelling. Classifications were evaluated with area under receiver operating characteristic curve (AUC) and regressions with correlation between observed and predicted growth rates. Compared with the baseline clinical diameter, geometric-biomechanical analysis improved prediction of reaching surgical threshold within four years (AUC 0.80 vs 0.85, p = 0.031) and prediction of diameter growth rate (r = 0.17 vs r = 0.38, p = 0.0031), mainly due to the addition of semiautomatic diameter measurements. There was a trend towards increased precision of volume growth rate prediction (r = 0.37 vs r = 0.45, p = 0.081). Lumen diameter and biomechanical indices were the only variables that could predict future rupture or symptomatic AAA (AUCs 0.65-0.67). Enhanced precision of diameter measurements improves the prediction of reaching the surgical threshold and diameter growth rate, while lumen diameter and biomechanical analysis predicts rupture or symptomatic AAA.

Limb Graft Occlusion Following Endovascular Aneurysm Repair for Infrarenal Abdominal Aortic Aneurysm with the Zenith Alpha, Excluder, and Endurant Devices: a Multicentre Cohort Study.

OBJECTIVE: Limb graft occlusion (LGO) is a serious complication after endovascular aneurysm repair (EVAR) and while device development enables treatment of increasingly complex aortic anatomy, little is known about how endograft type affects the risk of occlusion. This observational study aimed to explore the incidence of LGO after EVAR for three major endograft systems. METHODS: All patients with standard EVAR as the primary intervention for infrarenal abdominal aortic aneurysm (AAA), between January 2012 and December 2018, at five Swedish vascular surgery centres, were included in this multicentre retrospective cohort study. LGO was defined as a total limb occlusion regardless of symptoms, or a treated significant stenosis. A nested case control (NCC) design with incidence density sampling of 1:3 was used for analysis of potential per-operative and morphological risk factors. Conditional logistic regression was used to estimate multivariable odds ratios (OR) with 95% confidence intervals (CI) RESULTS: A total of 924 patients were included. The majority were male (84%), the mean age was 76 years (± 7.5 SD), and median AAA diameter was 59 mm (IQR 55, 67). Patients were treated with Zenith Alpha (n = 315, ZISL limbs), Excluder (n = 152, PLC/PXC limbs), and Endurant (n = 457, ETLW/ ETEW limbs). During median follow up of 37 months (IQR 21, 62), 55 occlusions occurred (5.9%); 39 with Zenith Alpha (12.4%), one with Excluder (0.7%), and 15 with Endurant (3.3%). In the NCC analysis, the Zenith Alpha device (OR 5.31, 95% CI 1.97 - 14.3), external iliac artery (EIA) landing (OR 5.91, 95% CI 1.30 - 26.7), and EIA diameter < 10 mm (OR 4.99, 95% CI 1.46 - 16.9) were associated with an increased risk of LGO. CONCLUSION: Endograft device type is an independent risk factor for LGO after EVAR. Specifically, the Zenith Alpha demonstrated an increased risk of LGO compared with the Endurant and Excluder devices. In addition, a narrow EIA and landing zone in EIA are also risk factors for LGO.

Sex hormones in men with abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysms (AAAs) primarily affect elderly men. The effect of sex on aneurysm development has been associated with the effects of sex hormones through mechanisms that are not fully understood. The present study examined the association between the levels of sex hormones and the occurrence of AAAs in elderly men. METHODS: A prospective case-control study was conducted of 452 men aged 65 years participating in screening for AAAs from 2013 to 2019. Of the 452 men, 230 had an AAA and 222 an aortic diameter of <30 mm (control group). Questionnaires and blood samples were collected and stored consecutively. The serum levels of total testosterone, estradiol, progesterone, luteinizing hormone, and sex hormone-binding globulin were analyzed using electrochemiluminescent immunoassays. Multivariable logistic regression analysis was used to assess the association between sex hormones and AAA. RESULTS: The median aneurysm diameter was 33 mm. Men with AAA had greater estradiol (93 pmol/L vs 84 pmol/L; P =.003) and progesterone (0.41 nmol/L vs 0.17 nmol/L; P < .001) levels compared with the controls. The testosterone levels were lower in the AAA group than in the control group (13 nmol/L vs 14 nmol/L; P = .026). AAA was associated with detectable levels of progesterone (odds ratio [OR], 6.69; 95% confidence interval [CI], 3.86-11.47), smoking (OR, 5.26; 95% CI, 3.12-8.85), coronary heart disease (OR, 4.06; 95% CI, 1.92-8.58), and a body mass index >25 kg/m2 (OR, 2.26; 95% CI, 1.34-3.82). CONCLUSIONS: The observed higher estradiol and progesterone levels in men with an AAA suggest an effect of sex hormones on aneurysm development. The association between progesterone levels and the aortic diameter stresses the importance of focusing on the potential effect of this unconsidered female sex hormone on aneurysm formation.

Low-grade fibromyxoid sarcoma of the liver: A case report.

BACKGROUND: Low grade fibromyxoid sarcoma (LGFMS) is a rare and benign mesenchymal tumor with indolent course, most commonly found in young or middle-aged men. The majority of the LGFMSs are located in the trunk and deep soft tissue of the lower extremities. They appear as well circumscribed, although not encapsulated, which often leads to incomplete surgical resection. Despite their seemingly benign appearance, these tumors have aggressive behavior with high metastatic and recurrence rates. Accurate histopathologic examination of the specimen and its immunohistochemical analysis are mandatory for a precise diagnosis. CASE SUMMARY: We report a case of a 38 year-old-man who presented with jaundice and upper abdominal discomfort. Multi-detector computed tomography and magnetic resonance imaging showed a large left liver tumor mass, extending to the hepatoduodenal ligament. Left hepatectomy was performed with resection and reconstruction of hepatic artery and preservation of middle hepatic vein. Histopathologic examination confirmed the tumor being a low-grade fibromyxoid sarcoma. Three and a half years after surgery, the patient died after being diagnosed with spine metastasis. CONCLUSION: Due to poor response to all modalities of adjuvant treatment, we consider that the focus of treatment should be on surgery as the only option for curing the disease.

Revisiting the rules for anatomical targeting of ventralis intermediate nucleus.

Indirect targeting of the Ventralis Intermedius Nucleus (Vim) is widely used for functional neurosurgical procedures to treat essential tremor (ET). Here, we review if the laterality of the Vim depends on the diameter of the third ventricle and if a targeting approach that incorporates this correlation can facilitate targeting and yields accurate lead placement. We analyzed 15 consecutive ET patients. Vim targeting was adapted according to the width of the third ventricle and the lateral distance to the internal capsule (IC). Postoperative outcome was assessed 12 months post-OP based on the Bain-Findley score. Application of this targeting approach resulted in mean target coordinates of LAT 12.8 ±â€¯1.5; AP -3.6 ±â€¯1.0 and VERT 0 ±â€¯0 mm and which projected onto the Vim. The laterality of IC and Vim are correlated to the width of the third ventricle. The mean postoperative tremor reduction was 63.0%. In summary, adjusting the lateral coordinate according to the width of the third ventricle leads to accurate targeting and effective tremor reduction.

Exercise response in Parkinson's disease: insights from a cross-sectional comparison with sedentary controls and a per-protocol analysis of a randomised controlled trial.

OBJECTIVES: To investigate the acute and adaptation cardiovascular and metabolic training responses in people with Parkinson's disease (pwP). DESIGN: (1) A cross-sectional study of exercise response of pwP compared with sedentary controls and (2) an interventional study of exercise training in pwP. SETTING: Community leisure facilities. PARTICIPANTS: pwP (n=83) and sedentary controls (n=55). INTERVENTIONS: Study 1 included participants from a two-arm-parallel single-blind phase II randomised controlled trial (RCT), that undertook a baseline maximal incremental exercise test and study 2 included those randomised to the exercise group in the RCT, who completed a 6-month weekly exercise programme (n=37). The intervention study 2 was a prescribed exercise program consisting of sessions lasting 60 min, two times a week over a 6-month period. The control group followed the same protocol which derived the same cardiorespiratory parameters, except that they were instructed to aim for a cadence of ~60 revolutions per minute and the unloaded phase lasted 3 min with an initial step of 25 W. PRIMARY AND SECONDARY OUTCOME MEASURES: Stepwise incremental exercise test to volitional exhaustion was the primary outcome measure. RESULTS: Study 1 showed higher maximum values for heart rate (HR), VO2 L/min, VCO2 L/min and ventilation L/min for the control group; respiratory exchange ratio (RER), perceived exertion and O2 pulse (VO2 L/min/HR) did not differ between groups. In study 2, for pwP who adhered to training (n=37), RER increased significantly and although there was no significant change in aerobic capacity or HR response, reduced blood pressure was found. CONCLUSIONS: An abnormal cardiovascular response to exercise was observed in pwP compared to controls. After the exercise programme, metabolic deficiencies remained for pwP. These observations add to the pathogenic understanding of PD, acknowledge an underling metabolic contribution and support that certain cardiovascular symptoms may improve as a result of this type of exercise.

A long-term self-managed handwriting intervention for people with Parkinson's disease: results from the control group of a phase II randomized controlled trial.

OBJECTIVE: To report on the control group of a trial primarily designed to investigate exercise for improving mobility in people with Parkinson's disease (pwP). The control group undertook a handwriting intervention to control for attention and time spent practising a specific activity. DESIGN: Secondary analysis of a two-arm parallel phase II randomized controlled trial with blind assessment. SETTING: Community. PARTICIPANTS: PwP able to walk ⩾100 m and with no contraindication to exercise were recruited from the Thames Valley, UK, and randomized (1:1) to exercise or handwriting, via a concealed computer-generated list. INTERVENTION: Handwriting was undertaken at home and exercise in community facilities; both were delivered through workbooks with monthly support visits and involved practice for 1 hour, twice weekly, over a period of six months. MAIN MEASURES: Handwriting was assessed, at baseline, 3, 6 and 12 months, using a pangram giving writing speed, amplitude (area) and progressive reduction in amplitude (ratio). The Movement Disorder Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS) item 2.7 measured self-reported handwriting deficits. RESULTS: In all, 105 pwP were recruited (analysed: n = 51 handwriting, n = 54 exercise). A total of 40 pwP adhered to the handwriting programme, most completing ⩾1 session/week. Moderate effects were found for amplitude (total area: d = 0.32; 95% confidence interval (CI): -0.11 to 0.7; P = 0.13) in favour of handwriting over a period of12 months; effects for writing speed and ratio parameters were small ≤0.11. Self-reported handwriting difficulties also favoured handwriting (UPDRS 2.7: odds ratio (OR) = 0.55; 95% CI: 0.34 to 0.91; P = 0.02). No adverse effects were reported. CONCLUSION: PwP generally adhere to self-directed home handwriting which may provide benefit with minimal risk. Encouraging effects were found in writing amplitude and, moreover, perceived ability.

Standard versus extended lymphadenectomy in radical surgical treatment for pancreatic head carcinoma.

PURPOSE: The primary aim of this study was to evaluate the benefit of extended lymphadenectomy in pancreaticoduodenectomy (PD) and to estimate its impact on long-term survival in patients with pancreatic head carcinoma. Secondary endpoints included perioperative mortality, postoperative morbidity and predictors of survival in patients undergoing standard versus extended lymphadenectomy for pancreatic head carcinoma. METHODS: From January 2007 to December 2010, 60 patients with potentially resectable pancreatic head carcinoma were operated using pylorus-preserving pancreatoduodenectomy (PPPD) at the Clinic for Digestive Surgery, Clinical Center of Serbia, Belgrade. Intraoperatively patients were randomly stratified into two groups: the first group (N1=30) underwent PPPD with standard lymphadenectomy whilst the second group (N2=30) was operated with PPPD with extended lymphadenectomy. None of the patients received adjuvant treatments. RESULTS: The number of retrieved lymph nodes, mean operating time and postoperative hospital stay were greater in patients with extended lymphadenectomy . Cox regression analysis showed that stage and lymph node metastasis were independent prognostic factors for survival. CONCLUSION: Extended lymphadenectomy in PPPD did not improve long-term survival in patients with resectable pancreatic head carcinoma and led to comparable and similar morbidity and mortality rates to those after standard lymphadenectomy.

Functional Connectivity of the Pedunculopontine Nucleus and Surrounding Region in Parkinson's Disease.

Deep brain stimulation of the pedunculopontine nucleus and surrounding region (PPNR) is a novel treatment strategy for gait freezing in Parkinson's disease (PD). However, clinical results have been variable, in part because of the paucity of functional information that might help guide selection of the optimal surgical target. In this study, we use simultaneous magnetoencephalography and local field recordings from the PPNR in seven PD patients, to characterize functional connectivity with distant brain areas at rest. The PPNR was preferentially coupled to brainstem and cingulate regions in the alpha frequency (8-12 Hz) band and to the medial motor strip and neighboring areas in the beta (18-33 Hz) band. The distribution of coupling also depended on the vertical distance of the electrode from the pontomesencephalic line: most effects being greatest in the middle PPNR, which may correspond to the caudal pars dissipata of the pedunculopontine nucleus. These observations confirm the crucial position of the PPNR as a functional node between cortical areas such as the cingulate/ medial motor strip and other brainstem nuclei, particularly in the dorsal pons. In particular they suggest a special role for the middle PPNR as this has the greatest functional connectivity with other brain regions.

Phase II randomised controlled trial of a 6-month self-managed community exercise programme for people with Parkinson's disease.

BACKGROUND: Evidence for longer term exercise delivery for people with Parkinson's disease (PwP) is deficient. AIM: Evaluate safety and adherence to a minimally supported community exercise intervention and estimate effect sizes (ES). METHODS: 2-arm parallel phase II randomised controlled trial with blind assessment. PwP able to walk ≥100 m and with no contraindication to exercise were recruited from the Thames valley, UK, and randomised (1:1) to intervention (exercise) or control (handwriting) groups, via a concealed computer-generated list. Groups received a 6-month, twice weekly programme. Exercise was undertaken in community facilities (30 min aerobic and 30 min resistance) and handwriting at home, both were delivered through workbooks with monthly support visits. Primary outcome was a 2 min walk, with motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS III), fitness, health and well-being measured. RESULTS: Between December 2011 and August 2013, n=53 (n=54 analysed) were allocated to exercise and n=52 (n=51 analysed) to handwriting. N=37 adhered to the exercise, most attending ≥1 session/week. Aerobic exercise was performed in 99% of attended sessions and resistance in 95%. Attrition and adverse events (AEs) were similar between groups, no serious AEs (n=2 exercise, n=3 handwriting) were related, exercise group-related AEs (n=2) did not discontinue intervention. Largest effects were for motor symptoms (2 min walk ES=0.20 (95% CI -0.44 to 0.45) and MDS-UPDRS III ES=-0.30 (95% CI 0.07 to 0.54)) in favour of exercise over the 12-month follow-up period. Some small effects were observed in fitness and well-being measures (ES>0.1). CONCLUSIONS: PwP exercised safely and the possible long-term benefits observed support a substantive evaluation of this community programme. TRIAL REGISTRATION NUMBER: NCT01439022.

Reward sensitivity deficits modulated by dopamine are associated with apathy in Parkinson's disease.

Apathy is a debilitating and under-recognized condition that has a significant impact in many neurodegenerative disorders. In Parkinson's disease, it is now known to contribute to worse outcomes and a reduced quality of life for patients and carers, adding to health costs and extending disease burden. However, despite its clinical importance, there remains limited understanding of mechanisms underlying apathy. Here we investigated if insensitivity to reward might be a contributory factor and examined how this relates to severity of clinical symptoms. To do this we created novel ocular measures that indexed motivation level using pupillary and saccadic response to monetary incentives, allowing reward sensitivity to be evaluated objectively. This approach was tested in 40 patients with Parkinson's disease, 31 elderly age-matched control participants and 20 young healthy volunteers. Thirty patients were examined ON and OFF their dopaminergic medication in two counterbalanced sessions, so that the effect of dopamine on reward sensitivity could be assessed. Pupillary dilation to increasing levels of monetary reward on offer provided quantifiable metrics of motivation in healthy subjects as well as patients. Moreover, pupillary reward sensitivity declined with age. In Parkinson's disease, reduced pupillary modulation by incentives was predictive of apathy severity, and independent of motor impairment and autonomic dysfunction as assessed using overnight heart rate variability measures. Reward sensitivity was further modulated by dopaminergic state, with blunted sensitivity when patients were OFF dopaminergic drugs, both in pupillary response and saccadic peak velocity response to reward. These findings suggest that reward insensitivity may be a contributory mechanism to apathy and provide potential new clinical measures for improved diagnosis and monitoring of apathy.media-1vid110.1093/brain/aww188_video_abstractaww188_video_abstract.

Tremor Reduction by Deep Brain Stimulation Is Associated With Gamma Power Suppression in Parkinson's Disease.

OBJECTIVES: Rest tremor is a cardinal symptom of Parkinson's disease (PD), and is readily suppressed by deep brain stimulation (DBS) of the subthalamic nucleus (STN). The therapeutic effect of the latter on bradykinesia and rigidity has been associated with the suppression of exaggerated beta (13-30 Hz) band synchronization in the vicinity of the stimulating electrode, but there is no correlation between beta suppression and tremor amplitude. In the present study, we investigate whether tremor suppression is related to suppression of activities at other frequencies. MATERIALS AND METHODS: We recorded hand tremor and contralateral local field potential (LFP) activity from DBS electrodes during stimulation of the STN in 15 hemispheres in 11 patients with PD. DBS was applied with increasing voltages starting at 0.5 V until tremor suppression was achieved or until 4.5 V was reached. RESULTS: Tremor was reduced to 48.9% ± 10.9% of that without DBS once stimulation reached 2.5-3 V (t14 = -4.667, p < 0.001). There was a parallel suppression of low gamma (31-45 Hz) power to 92.5% ± 3% (t14 = -2.348, p = 0.034). This was not seen over a band containing tremor frequencies and their harmonic (4-12 Hz), or over the beta band. Moreover, low gamma power correlated with tremor severity (mean r = 0.43 ± 0.14, p = 0.008) within subjects. This was not the case for LFP power in the other two bands. CONCLUSIONS: Our findings support a relationship between low gamma oscillations and PD tremor, and reinforce the principle that the subthalamic LFP is a rich signal that may contain information about the severity of multiple different Parkinsonian features.

Complementary roles of different oscillatory activities in the subthalamic nucleus in coding motor effort in Parkinsonism.

The basal ganglia may play an important role in the control of motor scaling or effort. Recently local field potential (LFP) recordings from patients with deep brain stimulation electrodes in the basal ganglia have suggested that local increases in the synchronisation of neurons in the gamma frequency band may correlate with force or effort. Whether this feature uniquely codes for effort and whether such a coding mechanism holds true over a range of efforts is unclear. Here we investigated the relationship between frequency-specific oscillatory activities in the subthalamic nucleus (STN) and manual grips made with different efforts. The latter were self-rated using the 10 level Borg scale ranging from 0 (no effort) to 10 (maximal effort). STN LFP activities were recorded in patients with Parkinson's Disease (PD) who had undergone functional surgery. Patients were studied while motor performance was improved by dopaminergic medication. In line with previous studies we observed power increase in the theta/alpha band (4-12 Hz), power suppression in the beta band (13-30 Hz) and power increase in the gamma band (55-90 Hz) and high frequency band (101-375 Hz) during voluntary grips. Beta suppression deepened, and then reached a floor level as effort increased. Conversely, gamma and high frequency power increases were enhanced during grips made with greater effort. Multiple regression models incorporating the four different spectral changes confirmed that the modulation of power in the beta band was the only independent predictor of effort during grips made with efforts rated <5. In contrast, increases in gamma band activity were the only independent predictor of effort during grips made with efforts ≥5. Accordingly, the difference between power changes in the gamma and beta bands correlated with effort across all effort levels. These findings suggest complementary roles for changes in beta and gamma band activities in the STN in motor effort coding. The latter function is thought to be impaired in untreated PD where task-related reactivity in these two bands is deficient.