Search

Background Motor and sensory evoked potentials (EP) are potential candidate biomarkers for clinical trials in multiple sclerosis. Objective To determine test -retest reliability of motor EP (MEP) and sensory EP (SEP) and associated EP-scores in patients with multiple sclerosis. Methods In three centres, 16 relapsing and five progressive multiple sclerosis patients had MEPs and SEPs 1–29 days apart. Five neurophysiologists independently marked latencies by central reading. By variance component analysis, we estimated the critical difference (absolute reliability) for cross-sectional group comparison, comparison of longitudinal group changes, within-subject minimal detectable change and defined within-subject improvement. Results Cortical SEP responses and cortico-muscular MEP latencies were more reliable than central conduction times. For comparison of 20 subjects per arm, cross-sectional group difference ranged from 0.7 to 3.9 ms and 1.1 to 1.7, group difference in longitudinal changes from 0.4 to 1.8 ms and 0.36 to 0.62, within-subject minimal detectable change from 1.2 to 5.8 ms and 1.2 to 2.0, within-subject improvement from 0.8 to 3.8ms and 0.8 to 1.3, for single EP modalities and EP scores, respectively. Conclusions Multicentre EP assessment with central EP reading is feasible and reliable. The critical difference is reasonably low to detect significant group changes and to define responders. The results support the concept of using EP and EP-scores as candidate response biomarkers for quantification of disease progression and for studying remyelination in multiple sclerosis.

In this paper we present a new population-based implant design methodology, which advances the state-of-the-art approaches by combining shape and bone quality information into the design strategy. The method may enhance the mechanical stability of the fixation and reduces the intra-operative in-plane bending which might impede the functionality of the locking mechanism. The computational method is presented for the case of mandibular locking fixation plates, where the mandibular angle and the bone quality at screw locations are taken into account. The method automatically derives the mandibular angle and the bone thickness and intensity values at the path of every screw from a set of computed tomography images. An optimization strategy is then used to optimize the two parameters of plate angle and screw position. The method was applied to two populations of different genders. Results for the new design are presented along with a comparison with a commercially available mandibular locking fixation plate (MODUS(®) TriLock(®) 2.0/2.3/2.5, Medartis AG, Basel, Switzerland). The proposed designs resulted in a statistically significant improvement in the available bone thickness when compared to the standard plate. There is a higher probability that the proposed implants cover areas of thicker cortical bone without compromising the bone mineral density around the screws. The obtained results allowed us to conclude that an angle and screw separation of 129° and 9 mm for females and 121° and 10 mm for males are more suitable designs than the commercially available 120° and 9 mm.

Background DBS is commonly used to treat Parkinson's disease (PD). DBS is not considered to cause major cognitive side effects, but some research groups have reported that it can cause decreased verbal fluency. The influence of age on DBS cognitive outcome is unclear. We investigated the possible influence of patients' age, level of education, disease duration, disease progression, depression, and levodopa equivalent dose (LED) on verbal fluency performance in patients with PD who underwent DBS of the subthalamic nucleus (STN-DBS). In this article, we investigated the influence of demographic and clinical parameters, especially age, on cognitive performance post-DBS in PD patients. Methods Forty-three patients with PD and without major psychiatric illness (according to Diagnostic and Statistical Manual of Mental Disroders, Fourth Edition) were enrolled in the study. Median age was 64.0 years (range, 46–77). In 21 patients, the indication for DBS was established on clinical grounds in keeping with international guidelines; these patients underwent STN-DBS, and the remaining 22 did not. Cognitive performance in both groups was assessed by standard neuropsychological test batteries at baseline and after median follow-up of 7 months. Results A statistically significant decline in the semantic category of verbal fluency task was found in the STN-DBS group (P < 0.01). Linear regression model revealed an influence of age (P < 0.01) and disease duration (P < 0.01) in relation to this decline. Conclusions This study confirms previous findings that verbal fluency declines after STN-DBS in PD patients in comparison to PD patients without DBS. This decline is related to age and disease duration.

OBJECTIVE: Mild cognitive impairment in Parkinson's disease (PD-MCI) is diagnosed based on the results of a standardized set of cognitive tests. We investigate whether quantitative EEG (qEEG) measures could identify differences between cognitively normal PD (PD-CogNL) and PD-MCI patients. METHODS: High-resolution EEG was recorded in 53 patients with Parkinson's disease (PD). Relative power in five frequency bands was calculated globally and for ten regions. Peak and median frequencies were determined. qEEG results were compared between groups. Effect sizes of all variables were calculated. The best separating variable was used to demonstrate subject-wise classification. RESULTS: Lower mean values were observed in global alpha1 power and alpha1 power in five brain regions (left hemisphere: frontal, central, temporal, occipital; right hemisphere: temporal, P > 0.05), differentiating between PD-CogNL and PD-MCI groups. Effect sizes were high, ranging from 0.79 to 0.87. Median frequency was 8.56 ± 0.74 Hz and was not different between the groups. The variable with the best subject-wise classification was the power in the alpha1 band in the right temporal region. The area under the corresponding receiver operating characteristic (ROC) curve was 0.72. The optimal classification threshold yielded a sensitivity of 65.9% and a specificity of 66.7%. The positive and negative predictive values were 87.1% and 36.4%, respectively. INTERPRETATION: Reduction in alpha1 band power in nondemented PD patients, particularly in the right temporal region, is highly indicative of MCI in PD patients. The results might be used to assist in time-efficient diagnosis of PD-MCI and avoid the drawbacks of test-retest effect in repeated neuropsychological testing.

Objective To compare the reliability of a newly developed Matlab® toolbox for the fully automated, pre- and post-processing of resting state EEG (automated analysis, AA) with the reliability of analysis involving visually controlled pre- and post-processing (VA). Methods 34 healthy volunteers (age: median 38.2 (20–49), 82% female) had three consecutive 256-channel resting-state EEG at one year intervals. Results of frequency analysis of AA and VA were compared with Pearson correlation coefficients, and reliability over time was assessed with intraclass correlation coefficients (ICC). Results Mean correlation coefficient between AA and VA was 0.94 ± 0.07, mean ICC for AA 0.83 ± 0.05 and for VA 0.84 ± 0.07. Conclusion AA and VA yield very similar results for spectral EEG analysis and are equally reliable. AA is less time-consuming, completely standardized, and independent of raters and their training. Significance Automated processing of EEG facilitates workflow in quantitative EEG analysis.

Introduction Sensory and motor evoked potentials (SEP; MEP) can be used to measure quantitatively the extent of delayed signal conduction in multiple sclerosis (MS). They may be useful to monitor disease course and even serve as biomarkers in clinical trials (Hardmeier et al., 2017). Here we estimate the detectable differences in group means and in longitudinal group changes for different sample sizes accounting for physiological and rater-related variability. Methods 15 healthy subjects were evaluated twice within 30 days with median and tibial SEP and upper (UL) and lower limb (LL) MEP in three centers 1-3 according to a common standardized protocol in keeping with IFCN recommendations. Four neurophysiologists (FJ, MH, PA, PF) independently marked all curves blinded to their previous ratings using a web-based tool (EPMark; HB, MH, PF). N20, P40, shortest and mean cortico-muscular-latencies (CML) were analyzed; central (motor) conduction times were omitted due to lower test-retest-reliability. In addition, the sum of the z-transformed results from each test was divided by number of tests to yield a quantitative EP-score (qEPS). Mixed effect models using results of time-points 1 and 2 as combined outcomes were employed to calculate the standard error (SE) of a group mean of cross-sectional measurements or longitudinal changes. The respective SE formulas were used to calculate the difference d detectable with a power of 90% [d = (1.96 + 1.28) ∗ sqrt( SE 1 2 + SE 2 2 ) -2CoV] as a function of group size assuming a central reading center. Covariance between group means by common influence of raters on both groups was ignored for a more conservative estimate. Results For a sample size of n = 60, cross-sectional group mean difference (d1) is estimated to range from 0.6 to 2.1 ms (N20: 0.6, P40: 1.5; CML-UL [shortest/ mean]: 1.4/1.2; CML-LL: 1.7/2.1), and longitudinal mean group difference (d2) from 0.4 to 2.7 ms (N20: 0.4, P40: 1.0; CML-UL: 1.1/0.8; CML-LL: 1.6/2.7). For a sample size of n = 100, d1 ranged from 0.5 to 2.0 ms (N20: 0.5, P40: 1.2; CML-UL: 1.1/1.0; CML-LL: 1.4/2.0), and d2 from 0.4 to 2.6 ms (N20: 0.4, P40: 0.8; CML-UL: 0.9/0.7; CML-LL: 1.5/2.6). For qEPS [including shortest or mean CML], d1 was 0.5/0.4 ms for n = 60, and 0.4/0.3 ms for n = 100; d2 was 0.3/0.2 ms for n = 60 and 0.2/0.2 for n = 100. Conclusion Quantitative evaluation of combined SEP and MEP is possible in a multicenter setting with an independent reading center and allows reliable detection of significant differences in small groups of subjects. When evaluating an intervention, significant changes of EP results at an individual level help to identify responders, while significant changes at a group level may help to determine the biological effectiveness of an intervention. However, variability may be higher in patients and thus, consecutively, estimates of sample size. Supported by an unconditional research grant from Biogen Inc. MA, USA, which had no influence in planning the study or data analysis.

Introduction Sensory and motor evoked potentials (SEP; MEP) can be used to measure quantitatively the extent of delayed signal conduction in multiple sclerosis (MS). They may be useful to monitor disease course and even serve as biomarkers in clinical trials (Hardmeier et al., 2017). Here we evaluate physiological and rater-related variability to determine the minimal significant change between two measurements intra-individually. Methods 15 healthy subjects were evaluated twice within 30 days with median and tibial SEP and upper (UL) and lower limb (LL) MEP in three centers1–3 according to a common standardized protocol in keeping with IFCN recommendations. Four neurophysiologists (FJ, MH, PA, PF) independently marked all curves blinded to their previous ratings using a web-based tool (EPMark; HB, MH, PF). In SEP, N13, N20 and N22, P40, in MEP, cortico-muscular- (CML) and spinal-muscular-latencies were marked. N20, P40, shortest and mean CML, and central (motor) conduction times (CCT; CMCT) were analyzed. Mixed effect models were calculated using results of (a) 1st and 2nd rating of identical baseline curves (model 1), and (b) 1st baseline and follow-up rating (model 2) as combined outcomes. Based on model 2, confidence intervals (CI) were calculated for the difference of a repeated measurement of the same curve. Results Intra-class-correlation coefficient (ICC) for intra-and inter-rater reliability (model 1) was very high in median SEP (N20: 0.97; CCT: 0.85) and tibial SEP (P40: 0.95; CCT: 0.89). In MEP, ICC was higher when mean CML (UL: 0.94; LL: 0.90) or mean CMCT (UL: 0.88; LL: 0.91) was used instead of shortest CML (UL: 0.80; LL: 0.78) or shortest CMCT (UL: 0.65; LL: 0.81). As CCT and CMCT showed lower ICC, only CML, N20 and P40 were further analyzed. Total variance in model 2 ranged from 0.9 to 6.4 ms (N20: 0.9, P40: 6.4; CML-UL [shortest/mean]: 4.8/4.1; CML-LL: 5.8/3.7), mainly accounted for by inter-subject variability (64–79%); estimation of center effects was unreliable. 80%-CI ranged from 0.4 to 1.5 ms (N20: 0.4, P40: 1.3; CML-UL: 1.5/1.1; CML-LL: 1.1/0.9), 95%-CI from 0.7 to 3.0 ms (N20: 0.7, P40: 2.6; CML-UL: 3.0/2.2; CML-LL: 2.2/1.7). Conclusion Main SEP components (N20, P40) and MEP cortico-muscular latencies show higher reliability than central conduction times. Mean instead of shortest CML further improves reliability. Intra-subject differences in individual tracts exceeding 0.4 to 3.0 ms (depending on test and CI level) most likely reflect true underlying changes. These numbers may be used to define responders to remyelinating therapies in MS. However, these confidence intervals may be higher in patients and have to be validated in a larger sample. In group level analyses, variability is much less important as over- and underestimation counterbalance each other. Supported by an unconditional research grant from Biogen Inc. MA, USA , which had no influence in planning the study or data analysis.

Various techniques for defect reconstruction after oncologic orthopaedics surgery exist, and the use of each technique vary depending on the complexity of the case. Biological reconstruction in great defects is a huge challenge for orthopaedics due to the high complication rate. However, bone allografts are highly recommended for major defects especially in younger patients. Clinical reports propose that this technique preserves the durability of bone stock and limb functionality plus a responsible handling of bone banks decreases loss of the usually scarce cadaver bone stock. Access to allografts has been improved owing to centralised bone banks, which develop threedimensional copies for storage and use them for the selection process. Virtual modelling has been recently demonstrated to be a potential predictor to select adequate allograft in preoperative virtual planning. Moreover, shape matching is the foremost method for proper allograft selection.

Deficits in executive functions occur in up to 93% of patients with Parkinson's disease (PD). Apathy, a reduction of motivation and goal-directed behavior is an important part of the syndrome; affecting both the patients as well as their social environment. Executive functions can be subdivided into three different processes: initiation, shifting and inhibition. We examined the hypotheses, (1) that apathy in patients with Parkinson's disease is only related to initiation and not to shifting and inhibition, and (2) that depression and severity of motor signs correlate with apathy. Fifty-one non-demented patients (19 = female) with PD were evaluated for apathy, depression and executive functions. Executive function variables were summarized with an index variable according to the defined executive processes. Linear regression with stepwise elimination procedure was used to select significant predictors. The significant model (R2 = 0.41; p < 0.01) revealed influences of initiation (b = −0.79; p < 0.01), gender (b = −7.75; p < 0.01), age (b = −0.07; p < 0.05) and an age by gender interaction (b = 0.12; p < 0.01) on apathy in Parkinson's disease. Motor signs, depression and level of education did not influence the relation. These results support an association of apathy and deficits of executive function in PD. Initiation strongly correlates with apathy, whereas depression does not. We conclude, that initiation dysfunction in a patient with Parkinson's disease heralds apathy. Apathy and depression can be dissociated. Additionally, apathy is influenced by age and gender: older age correlates with apathy in men, whereas in women it seems to protect against it.

Background Deep brain stimulation (DBS) is commonly used in the treatment of Parkinson’s disease (PD). Various research groups have reported that DBS is associated with decreased verbal fluency. We investigated the possible confounding effects of patients’ age, disease duration and levodopa equivalent daily dose (LEDD) on verbal fluency performance after DBS in patients with PD. Methods 43 patients with PD and without major psychiatric illness (according to DSM-IV) were enrolled in the study, median age 63.4 years, range 39–76. Subjects were allocated to two groups: the first were scheduled to bilateral DBS-STN (n = 21), the second comprised patients without DBS surgery (n = 22). Verbal fluency performance in both groups was assessed with Controlled Oral Word Association Test at baseline and eight months later. Results Decline in semantic fluency performance was found in the DBS group (p = 0.03). No confounding effect of age, disease Duration and LEDD was found in relation to this decline. Conclusions This restrospective observation confirms previous findings showing a decline in verbal fluency after DBS-STN in PD patients when compared with PD patients without surgery. Verbal fluency decline is unrelated to age, disease duration and LEDD.

Background: Cognitive deficits in Parkinson's disease (PD) are heterogeneous and can be classified into cognitive domains. Quantitative EEG is related to and predictive of cognitive status in PD. In this cross-sectional study, the relationship of cognitive domains and EEG slowing in PD patients without dementia is investigated. Methods: A total of 48 patients with idiopathic PD were neuropsychologically tested. Cognitive domain scores were calculated combining Z-scores of test variables. Slowing of EEG was measured with median EEG frequency. Linear regression was used for correlational analyses and to control for confounding factors. Results: EEG median frequency was significantly correlated to cognitive performance in most domains (episodic long-term memory, rho = 0.54; overall cognitive score, rho = 0.47; fluency, rho = 0.39; attention, rho = 0.37; executive function, rho = 0.34), but not to visuospatial functions and working memory. Conclusion: Global EEG slowing is a marker for overall cognitive impairment in PD and correlates with impairment in the domains attention, executive function, verbal fluency, and episodic long-term memory, but not with working memory and visuospatial functions. These disparate effects warrant further investigations.

In this paper we present a new population-based implant design methodology, which advances the state-of-the-art approaches by combining shape and bone quality information into the design strategy. The method enhances the mechanical stability of the fixation and reduces the intra-operative in-plane bending which might impede the functionality of the locking mechanism. The method is presented for the case of mandibular locking fixation plates, where the mandibular angle and the bone quality at screw locations are taken into account. Using computational anatomy techniques, the method automatically derives, from a set of computed tomography images, the mandibular angle and the bone thickness and intensity values at the path of every screw. An optimisation strategy is then used to optimise the two parameters of plate angle and screw position. Results for the new design are presented along with a comparison with a commercially available mandibular locking fixation plate. A statistically highly significant improvement was observed. Our experiments allowed us to conclude that an angle of 126 degrees and a screw separation of 8 mm is a more suitable design than the standard 120 degrees and 9 mm.

This paper presents a firsthand comparative evaluation of three different existing methods for selecting a suitable allograft from a bone storage bank. The three examined methods are manual selection, automatic volume-based registration, and automatic surface-based registration. Although the methods were originally published for different bones, they were adapted to be systematically applied on the same data set of hemi-pelvises. A thorough experiment was designed and applied in order to highlight the advantages and disadvantages of each method. The methods were applied on the whole pelvis and on smaller fragments, thus producing a realistic set of clinical scenarios. Clinically relevant criteria are used for the assessment such as surface distances and the quality of the junctions between the donor and the receptor. The obtained results showed that both automatic methods outperform the manual counterpart. Additional advantages of the surface-based method are in the lower computational time requirements and the greater contact surfaces where the donor meets the recipient.

International audience; In this paper we present a new population-based implant design methodology, which advances the state-of-the-art approaches by combining shape and bone quality information into the design strategy. The method enhances the mechanical stability of the fixation and reduces the intra-operative in-plane bending which might impede the functionality of the locking mechanism. The method is presented for the case of mandibular locking fixation plates, where the mandibular angle and the bone quality at screw locations are taken into account. Using computational anatomy techniques, the method automatically derives, from a set of computed tomography images, the mandibular angle and the bone thickness and intensity values at the path of every screw. An optimisation strategy is then used to optimise the two parameters of plate angle and screw position. Results for the new design are presented along with a comparison with a commercially available mandibular locking fixation plate. A statistically highly significant improvement was observed. Our experiments allowed us to conclude that an angle of 126 degrees and a screw separation of 8 mm is a more suitable design than the standard 120 degrees and 9 mm.

Objective To examine the hypothesis that apathy in patients with PD is related to frontal and temporal changes in EEG frequencies. We expected apathy to correlate with slowing of general EEG background activity, with decrease of alpha power and with increase of theta power in frontal and temporal regions of the brain. Methods 37 non-demented patients with idiopathic PD were recruited from the Movement Disorder Outpatient Clinic Basel (age: Median 69y; from 50y to 84y; 14 females). The Apathy Evaluation Scale (AES) (Marin, 1991) in informant version (AES-I) were completed by relatives of the patients.256-channel EEGs with quantitative semi-automatic analyses were used to detect alpha total-frequencies alpha 1-, alpha 2- and theta-in frontal and temporal regions. In addition, slowing of EEG was measured with Median Peak frequency. For statistics, a general linear model with backward elimination procedure was conducted. We controlled for confounding factors: age, gender, education, severity of motor symptoms, levodopa equivalent dose, depression and cognition. Results In this sample, the patients were only slightly affected by apathy ( Median =24; from 18 to 39; cut off value: 38). The resulting model was significant ( R 2 = 0.39 ; p b =−3.74; p =0.08). Relevant variables in the resulting model were alpha total, temporal right ( b =76.493; p b =−58.37; p b =−13.07; p r =−0.40), whereas in females there was no correlation between alpha total and the number of apathy symptoms ( r =0.04). Conclusions Slowing of EEG is correlated with apathy in patients with PD. This correlation is significant even in PD patients with little or no depression. This fact helps to separate the two neuropsychiatric entities. In accordance with our hypothesis, beginning apathy in PD might be related to an alpha 1 decrease the frontal left part of the brain. In contrast, alpha total of the right hemisphere positively correlates with apathy. In addition, however, the results in male gender are consistent with our expectation, but have to be replicated in a larger sample of PD patients with more severe apathy.