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Background: Currently, there are several studies showing that wearable inertial sensors are highly sensitive in the detection of gait disturbances in people with multiple sclerosis (PwMS), showing excellent reliability within one or 7-14 days. However, it is not known how stable these gait parameters remain over a longer period of time. This is surprising, because many treatments last longer than two weeks. Thus, the purpose of the current study was to examine gait parameters obtained by means of wearable inertial sensors during a 6-min walk and to reassess these parameters after a period of one year., Methods: Fifty PwMS (without a relapse or a recent change in the Expanded Disability Status Scale (EDSS) or treatment) and 20 healthy participants were examined at two assessment points (interval between assessments: 14.4 ± 6.6 months). At each assessment point, all participants had to complete a 6-min walking test, an observer-rater test (Berg Balance Scale, BBS) and a Timed-up and Go Test (TUG). To measure mean gait parameters (i.e. walking speed, stride length, stride time, the duration of the stance and swing phase and minimum toe-to-floor distance), as well as the intraindividual standard deviation of each mean gait parameter, wearable inertial sensors were utilized., Results: We found that even after one year all mean gait parameters showed excellent Intraclass Correlation Coefficients (ICC between 0.75 and 0.95) in PwMS. Looking at MS subgroups, the ICCs were slightly higher in MS subgroup 2 (EDSS 2.0-5.0) than those in MS subgroup 1 (EDSS 0.0-1.5) and healthy controls. Compared to the mean gait parameters, parameters of gait variability showed only good-to-fair ICC values in PwMS. Concerning BBS and TUG, the ICC values after one year were close to the ICC values of the measured mean gait parameters., Conclusions: Due to the excellent stability of mean gait parameters after one year, these sensor-based gait parameters can be identified as clinically relevant markers to evaluate treatment effects over a longer (several months) period of time in MS., (© 2023. The Author(s).)

Background: Diagnostics of Alzheimer's Disease (AD) require a multimodal approach. Neuropsychologists examine the degree and etiology of dementia syndromes and results are combined with those of cerebrospinal fluid markers and imaging data. In the diagnostic process, neuropsychologists often rely on anamnestic and clinical information, as well as cognitive tests, prior to the availability of exhaustive etiological information. The congruency of this phenomenological approach with results from FDG-PET/CT examinations remains to be explored. The latter yield highly accurate diagnostic information., Method: A mixed sample of N = 127 hospitalized neurological patients suspected of displaying a dementia syndrome underwent extensive neuropsychological and FDG-PET/CT examinations. Neuropsychological examinations included an anamnestic and clinical interview, and the CERAD cognitive test battery. Two decisional approaches were considered: First, routine diagnostic results were obtained, i.e. the final clinical decision of the examining neuropsychologist (AD Clinical vs. non-AD Clinical ). Secondly, a logistic regression model was implemented, relying on CERAD profiles alone. CERAD subscales that best predicted AD based on FDG-PET/CT were identified and a nominal categorization obtained (AD Test vs. non-AD Test ). Congruency of results from both approaches with those of the FDG-PET/CT (AD PET vs. non-AD PET ) were estimated with Cohen's Kappa (κ) and Yule's Y coefficient of colligation. Descriptive estimates of accuracy, sensitivity and specificity of CERAD relative to FDG-PET/CT diagnostics were derived., Results: AD PET patients constituted N = 33/127 (26%) of the sample. The clinical decision approach (AD Clinical vs. non-AD Clinical ) showed substantial agreement with the FDG-PET/CT classification (κ = .69, Y = .72) involving good accuracy (84.2%), moderate sensitivity (75.8%) and excellent specificity (92.6%). In contrast, the decisional approach that relied on CERAD data alone (AD Test vs. non-AD Test ) involved only moderate agreement with the FDG-PET/CT (κ = .54, Y = .62) with lower accuracy (74.8%), attributable to decreased sensitivity (56.3%) and comparable specificity (93.3%)., Conclusions: It is feasible to identify AD through a comprehensive neuropsychological examination in a mixed sample of neurological patients. However, within the boundaries of methods applied here, decisions based on cognitive test results alone appear limited. One may conclude that the clinical impression based on anamnestic and clinical information obtained by the neuropsychological examiner plays a crucial role in the identification of AD patients in routine clinical practice., (© 2022. The Author(s).)

Objectives: Persons with MS (PwMS) are frequently affected by fatigue and depression. Mindfulness-based interventions may reduce these symptoms in PwMS and consequently their application has been extended to various settings. Only few efforts have been made to explore effects of short-term mindfulness training during brief periods of hospitalization. In the current study, the feasibility and potential effects of short-term mindfulness training on depression, fatigue, rumination and cognition were explored in PwMS in an acute-care hospital setting. Based on previous work, it was further examined whether the relation between trait mindfulness and fatigue prior to and following the intervention was mediated by depression and whether a mediation effect was also observable throughout the intervention., Methods: A short-term mindfulness training protocol was developed, tailored to the requirements of the acute-care setting. Subsequently, 30 PwMS were recruited sequentially and received mindfulness training during the routine clinical process (median duration in hospital: eight days, number of sessions: four). Participants completed relevant self-report measures (depression, fatigue, rumination) and a neuropsychological assessment before and after training., Results: Participants reported significantly increased trait mindfulness and decreased depression and fatigue following the intervention. Respective change scores were highly correlated so that increased trait mindfulness was associated with decreased symptoms. In the rumination domain, patients reported a tendency for an increased adaptive ability to engage in distractive behavior during arising negative mood. Other measures of trait rumination and cognition remained relatively stable. Results of the mediation analyses indicated that depression mediated the negative relationship between trait mindfulness and fatigue symptoms at pre and post assessments. With regards to the change scores, an association between mindfulness and cognitive fatigue ceased to be significant when depression was controlled, albeit in this case, the mediation effect did not reach significance., Conclusion: Results of the current study indicate that short-term mindfulness training during brief periods of hospitalization may be beneficial for PwMS. They further complement previous work by identifying depression as a potential mediator of the antagonistic relationship between mindfulness and fatigue. Based on the current exploratory study, future trials are warranted to address this mechanism of mindfulness training in more detail., (© 2021. The Author(s).)

Background: The aim of the current study was to examine multiple gait parameters obtained by wearable inertial sensors and their sensitivity to clinical status in early multiple sclerosis (MS). Further, a potential correlation between gait parameters and subjective fatigue was explored., Methods: Automated gait analyses were carried out on 88 MS patients and 31 healthy participants. To measure gait parameters (i.e. walking speed, stride length, stride duration, duration of stance and swing phase, minimal toe-to-floor distance), wearable inertial sensors were utilized throughout a 6-min 25-ft walk. Additionally, self-reported subjective fatigue was assessed., Results: Mean gait parameters consistently revealed significant differences between healthy participants and MS patients from as early as an Expanded Disability Status Scale (EDSS) value of 1.5 onwards. Further, MS patients showed a significant linear trend in all parameters, reflecting continuously deteriorating gait performance throughout the test. This linear deterioration trend showed significant correlations with fatigue., Conclusions: Wearable inertial sensors are highly sensitive in the detection of gait disturbances, even in early MS, where global scales such as the EDSS do not provide any clinical information about deviations in gait behavior. Moreover, these measures provide a linear trend parameter of gait deterioration that may serve as a surrogate marker of fatigue. In sum, these results suggest that classic timed walking tests in routine clinical practice should be replaced by readily and automatically applicable gait assessments, as provided by inertial sensors., (© 2021. The Author(s).)

Objectives: Persons with MS (PwMS) often display symptoms of depression and fatigue. Mindfulness-based interventions are known to counteract these symptoms. However, to-date the exact relations between trait mindfulness, depression and fatigue remain to be examined. Fatigue is generally regarded as a symptom immanent to the disease and as a direct neurobiological consequence of increased cytokine levels and cortical atrophy. In depression on the other hand, psychosocial factors in the context of adaptation difficulties are probably of higher relevance. Hence, one may argue that mindfulness, as a trait that promotes successful adaption, may show a strong negative association with depression and a relatively minor negative association with fatigue in PwMS., Methods: In the current study, the association between self-reported trait mindfulness, fatigue and depression was examined in a sample of 69 PwMS., Results: Trait mindfulness showed highly significant negative correlations with both, depression and fatigue. Mediation analyses however, revealed that depression mediated the relation between mindfulness and fatigue., Conclusion: It may be concluded that in PwMS, trait mindfulness shows a genuine negative association with depression, but that it is only secondarily associated with fatigue. Implications for mindfulness-based interventions in MS are discussed. Based on the results of the current study, it may be feasible to promote the acceptance of default fatigue symptoms, instead of an actual reduction of fatigue symptoms.

Background: Cognitive deficits are common in multiple sclerosis (MS) and require continuous monitoring. In routine examinations, screening instruments such as the Brief Repeatable Battery (BRB) may serve this purpose. It was suggested that even a shortened version of the BRB, comprising the Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT) and Selective Reminding Test (SRT), may be feasible. However, an evaluation of sensitivity and specificity of the short BRB in comparison to an independent battery of established tests has not yet occurred. Therefore in the current study, this short version of the BRB was matched against the gold standard of an extensive test battery comprehensively assessing neuropsychological functions., Methods: 127 MS-patients were tested with a short version of the BRB and an extensive procedure. The latter served as the gold standard for defining sensitivity and specificity., Results: For subtests of the short BRB, estimates of sensitivity (38-44 %) and specificity (81-94 %) were obtained. Combining subtests into a single indicator of cognitive deficits yielded increased sensitivity (78 %), while reducing specificity (65 %)., Conclusion: The short BRB is reasonably sensitive and specific in detecting cognitive deficits. However, these qualities only emerge, if the short BRB is administered as a whole, whereas sensitivity is considerably lower than suggested by previous work, when relying on subtests separately (SDMT, PASAT, SRT). While the short BRB may not be regarded as conclusive as an extensive test battery, it represents a valid and economic screening instrument.

Background: Impaired walking capacity is a frequent confinement in Multiple Sclerosis (MS). Patients are affected by limitations in coordination, walking speed and the distance they may cover. Also abnormal dynamic walking patterns have been reported, involving continuous deceleration over time. Fampridine (4-aminopyridine), a potassium channel blocker, may improve walking in MS. The objective of the current study was to comprehensively examine dynamic walking characteristics and improved walking capacity in MS patients treated with fampridine., Methods: A sample of N = 35 MS patients (EDSS median: 4) underwent an electronic walking examination prior to (Time 1), and during treatment with fampridine (Time 2). Patients walked back and forth a distance of 25 ft for a maximum period of 6 min (6-minute 25-foot-walk). Besides the total distance covered, average speed on the 25-foot distance and on turns was determined separately for each test minute, at Time 1 and Time 2., Results: Prior to fampridine administration, 27/35 patients (77 %) were able to complete the entire 6 min of walking, while following the administration, 34/35 patients (97 %) managed to walk for 6 min. In this context, walking distance considerably increased and treatment was associated with faster walking and turning across all six test minutes (range of effect sizes: partial eta squared = .34-.72). Importantly, previously reported deceleration across test minutes was consistently observable at Time 1 and Time 2., Discussion: Fampridine administration is associated with improved walking speed and endurance. Regardless of a treatment effect of fampridine, the previously identified, abnormal dynamic walking feature, i.e. the linear decline in walking speed, may represent a robust feature., Conclusions: The dynamic walking feature might hence be considered as a candidate for a new outcome measure in clinical studies involving interventions other than symptomatic treatment, such as immune-modulating medication., Trial Registration: DRKS00009228 (German Clinical Trials Register). Date obtained: 25.08.2015.

Background: Patients suffering from Multiple Sclerosis (MS) experience a wide array of symptoms, including balance problems, mobility impairment, fatigue and depression. Physical exercise has recently been acknowledged as a treatment option complementary to medication. However, information regarding putative effects of structured exercise programs on neurological symptoms is sparse. Tai Chi, a Chinese martial art incorporating physical exercise and mindfulness training, has been shown to yield health benefits in various neurological groups. It seems particularly suitable for patients with motoric deficits as it challenges coordination and balance. The purpose of the current study was to explore the therapeutic value of structured Tai Chi training for coordination, balance, fatigue and depression in mildly disabled MS patients., Methods: A sample of 32 MS patients (Expanded Disability Status Scale, EDSS < 5) was examined. A structured Tai Chi course was devised and a Tai Chi group participated in two weekly sessions of 90 minutes duration for six months, while a comparison group received treatment as usual (TAU). Both groups were examined prior to and following the six-months interval with regards to balance and coordination performance as well as measures of fatigue, depression and life satisfaction., Results: Following the intervention, the Tai Chi group showed significant, consistent improvements in balance, coordination, and depression, relative to the TAU group (range of effect-sizes: partial η2 = 0.16 - 0.20). Additionally, life satisfaction improved (partial η2 = 0.31). Fatigue deteriorated in the comparison group, whereas it remained relatively stable in the Tai Chi group (partial η2 = 0.24)., Conclusions: The consistent pattern of results confirms that Tai Chi holds therapeutic potential for MS patients. Further research is needed to determine underlying working mechanisms, and to verify the results in a larger sample and different MS subgroups.

Background: Physical disability in multiple sclerosis (MS) is frequently characterized by impaired ambulation. Although walking tests have been successfully employed to assess walking ability in MS patients, data analytic procedures have predominantly relied on result-oriented parameters (e.g. total distance covered during a given amount of time), whereas process-oriented, dynamic walking patterns have mostly been ignored. This is striking, since healthy individuals have been observed to display a stereotypical U-shaped pattern of walking speed during timed walking, characterized by relatively high speed during the initial phase, subsequent slowing and final acceleration. Objective of the current study was to test the utility of the 6 min Walk (6MW) and the 12 min Walk (12MW) for revealing putatively abnormal temporal dynamic features of walking in MS., Methods: A group of 37 MS patients was divided into subgroups with regard to their level of disability analyzed with the Expanded Disability Status Scale (EDSS; Mild MS Group, n = 20, EDSS 0-3.5; Moderate MS Group, n = 17, EDSS 4-5). Subsequently, both groups were compared to age-matched healthy controls (n = 25) on both tests with regard to result-oriented characteristics (mean walking speed), as well as dynamic features (mean decline in walking speed, degree of observed U-shape)., Results: Both MS groups showed a significantly lower mean walking speed than healthy controls, independent of test duration. Compared to controls, the Moderate MS Group also slowed down more rapidly throughout both tests. The same pronounced decline in walking speed was observed for the Mild MS Group in case of the 12MW. Additionally, for both MS groups an attenuated U-shaped velocity pattern was observed relative to controls in the 6MW. Patients' subjective fatigue scores were more strongly correlated with the decline in walking speed than with the common parameter of mean walking speed in the 6MW., Conclusions: MS patients display abnormal dynamics in their walking patterns. A pronounced linear decline in walking speed can be identified with the 12MW even in MS patients with seemingly mild disability. Similarly, the 6MW can be used to assess an abnormal walking profile. Particularly the linear decline in walking speed on this test shows a more robust association with subjective fatigue than mean walking speed. Dynamic walking parameters may hence represent valuable clinical features, serving as surrogate measures of motor fatigue. Future studies are needed to verify their prognostic value.