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Introduction: The patho-psychological mechanisms of persistent posturalperceptual dizziness (PPPD) appear to be very complex, and a multimodal, multidisciplinary approach is suggested for treating patients with PPPD. The aim of this review was to provide a comprehensive overview of non-pharmacological treatments and their comparative effectiveness in patients with PPPD. Methods: Scopus, Web of Science, PsycINFO, Medline, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov were searched in April 2022 with a search update in August 2023. Only randomized controlled trials (RCTs) were included. There was no restrictions regarding publication date. Two reviewers independently identified eligible trials, extracted data, double-checked all extracted information from the included articles and assessed the risk of bias using the Cochrane risk of bias tool. A qualitative synthesis was performed, considering methodological heterogeneity between trials. Finally, an effect size analysis was performed for each treatment comparison. The standardized mean differences (SMD) and their corresponding 95% confidence intervals (95%CI) were calculated for each trial using Review Manager 5.4. Results: Thirteen RCTs (618 patients with moderate or mild dizziness) out of 1,362 references describing seven different non-pharmacological comparisons were selected. Nine trials included patients with PPPD, and four trials included patients with functional dizziness. The trials used different interventions that were classified as: (1) psychotherapeutic interventions (cognitive behavioral therapy, patient education), (2) physiotherapeutic interventions/training (vestibular rehabilitation, optokinetic stimulation), (3) stimulation procedures (vagus nerve stimulation, transcranial direct current stimulation) and (4) device application (visual desensitization using personalized glasses). However, most of the trials investigated the effects of single interventions, rather than multimodal interdisciplinary treatment of patients with PPPD. The SMD for dizziness handicap and severity was between 0.04 and 0.52 in most trials. In one trial using visual desensitization, the SMD was 1.09 (strong effect on the severity of dizziness) and 1.05 (strong effect on dizziness handicap). Discussion: Several individual interventions have shown benefits in the treatment of patients with PPPD with small to moderate effects. However, the multimodal treatment or a combination of vestibular rehabilitation with visual desensitization, cognitive behavioral therapy including patient education, and medication support should be further investigated. Future trials should include a large sample size with severe dizziness, and provide a longer follow-up period. [ABSTRACT FROM AUTHOR]

Background: The majority of stroke survivors experience long-term impairments. Regular physical activity and other lifestyle modifications play an important role in rehabilitation. Outpatient rehabilitation using telemedicine might be suitable to improve functional ability and long-term secondary prevention. The Strokecoach Intervention Program (SIP, Strokecoach GmbH, Cologne, Germany) comprises training, coaching and monitoring with the aim of improving or at least maintaining functional independence and preventing further stroke through more targeted physical activity. The SIP is provided as blended care, which refers to the integrated and coordinated delivery of healthcare services that combines traditional in-person interactions with technology-mediated interventions, optimizing the use of both face-to-face and virtual modalities to enhance patient outcomes. Objective: The aim of this study was to evaluate the acceptance of the SIP by the participants and its practical application, as well as to obtain initial indications of effects of the SIP on the basis of patient-related outcome measures, blood pressure measurements and recording of physical activity in parallel with the intervention. Methods: Data from individuals with stroke participating in the SIP were analyzed retrospectively. Within the SIP, participants received an application-based training program, were instructed to measure their blood pressure daily and to wear an activity tracker (pedometer). During the intervention period of either 6 or 12 weeks, the participants were supported and motivated by a personal coach via a messenger application. The primary outcomes of the analysis were recruitment, acceptance of and satisfaction with the SIP. Secondary outcomes included functional measures, mobility and health-related quality of life. Results: A total of 122 individuals with stroke could be recruited for the SIP. A total of 96 out of 122 were able to start the program (54% female, mean age 54.8 (SD = 13.1), 6.1 (SD = 6.6) years after stroke onset) and 88 completed the SIP. Participants wore the activity tracker on 66% and tracked their blood pressure on 72% of their intervention days. A further analyzed subgroup of 38 participants showed small improvements in patient-reported outcomes such as health-related quality of life (SF-36) with an increase of 12 points in the subdomain mental health, vitality (12.6) and physical functioning (9.1). However, no statistically significant improvements were found in other performance-based measures (Timed Up and Go test, gait speed). Conclusions: This study showed that a blended therapy approach for stroke survivors with mild to moderate impairments in the chronic phase is feasible and was highly accepted by participants, who benefitted from the additional coaching. [ABSTRACT FROM AUTHOR]

Background: Persistent postural-perceptual dizziness (PPPD) is a functional disorder of the nervous system and currently one of the most common types of chronic dizziness. Currently existing questionnaires do not fully assess patients' specific symptoms of PPPD. The Japanese Niigata PPPD Questionnaire (NPQ) was recently developed following consensus-based diagnosis criteria. The aim of this study was to translate it into German, evaluate its content with the help of experts and patients and, if necessary, revise the original version to allow for a comprehensive assessment of patients' PPPD-related symptoms. Methods: A 3-round expert Delphi survey and semi-structured patient interviews were conducted. 28 experts from Switzerland, Germany and Austria working in hospitals or outpatient centres were asked to complete a first questionnaire on various aspects of PPPD, on the translated, original NPQ and their own related experiences (Round one), a second questionnaire with statements regarding PPPD they could agree or disagree with using a 6-point Likert-scale (Round two), and a third survey to finally reach a consensus on statements to be integrated into the NPQ. In addition, eleven patients (mean age of 64.6±12.6 years; 6 females) were selected according to the criteria for the diagnosis of PPPD proposed by the Bárány Society and participated in a semi-structured interview asking for their opinion on the content of the original NPQ. All collected data were analysed using a descriptive evaluation and a qualitative content analysis based on verbatim transcripts. Results: Seven new items were added to the NPQ based on expert and patient comments and ratings. Its revised version (NPQ-R) comprises 19 items divided into five subscales using a 7-point Likert-scale with two additional subscales relating to associated symptoms and symptom behaviour in PPPD. The new maximal score is 114 points compared to 72 for the NPQ. Conclusion: The NPQ-R is the first patient-reported outcome measurement for patients with PPPD in German. It should help to provide a comprehensive assessment of the intensity of PPPD in affected patients. [ABSTRACT FROM AUTHOR]

Introduction: It is suggested that eye movement recordings could be used as an objective evaluationmethod of motor imagery (MI) engagement. Our investigation aimed to evaluate MI engagement in patients after stroke (PaS) compared with physical execution (PE) of a clinically relevant unilateral upper limbmovement task of the patients' affected body side. Methods: In total, 21 PaS fulfilled the MI ability evaluation [Kinaesthetic and Visual Imagery Questionnaire (KVIQ-10), body rotation task (BRT), and mental chronometry task (MC)]. During the experiment, PaS moved a cup to distinct fields while wearing smart eyeglasses (SE) with electrooculography electrodes integrated into the nose pads and electrodes for conventional electrooculography (EOG). To verifyMI engagement, heart rate (HR) and oxygen saturation (SpO2) were recorded, simultaneously with electroencephalography (EEG). Eye movements were recorded during MI, PE, and rest in two measurement sessions to compare the SE performance between conditions and SE's psychometric properties. Results: MI and PE correlation of SE signals varied between r = 0.12 and r = 0.76. Validity (cross-correlation with EOG signals) was calculated for MI (r = 0.53) and PE (r = 0.57). The SE showed moderate test-retest reliability (intraclass correlation coefficient) with r = 0.51 (95% CI 0.26-0.80) for MI and with r = 0.53 (95% CI 0.29 - 0.76) for PE. Event-related desynchronization and event-related synchronization changes of EEG showed a large variability. HR and SpO2 recordings showed similar values during MI and PE. The linear mixed model to examine HR and SpO2 between conditions (MI, PE, rest) revealed a significant difference in HR between rest and MI, and between rest and PE but not for SpO2. A Pearson correlation between MI ability assessments (KVIQ, BRT, MC) and physiological parameters showed no association between MI ability and HR and SpO2. Conclusion: The objective assessment of MI engagement in PaS remains challenging in clinical settings. However, HR was confirmed as a reliable parameter to assess MI engagement in PaS. Eye movements measured with the SE during MI did not resemble those during PE, which is presumably due to the demanding task. A re-evaluation with task adaptation is suggested. [ABSTRACT FROM AUTHOR]

Background: Spinal cord (SC) gray and white matter pathology plays a central role in multiple sclerosis (MS). Objective: We aimed to investigate the extent, pattern, and clinical relevance of SC gray and white matter atrophy in vivo. Methods: 39 relapsing–remitting patients (RRMS), 40 progressive MS patients (PMS), and 24 healthy controls (HC) were imaged at 3T using the averaged magnetization inversion recovery acquisitions sequence. Total and lesional cervical gray and white matter, and posterior (SCPH) and anterior horn (SCAH) areas were automatically quantified. Clinical assessment included the expanded disability status scale, timed 25-foot walk test, nine-hole peg test, and the 12-item MS walking scale. Results: PMS patients had significantly reduced cervical SCAH — but not SCPH — areas compared with HC and RRMS (both p < 0.001). In RRMS and PMS, the cervical SCAH areas increased significantly less in the region of cervical SC enlargement compared with HC (all p < 0.001). This reduction was more pronounced in PMS compared with RRMS (both p < 0.001). In PMS, a lower cervical SCAH area was the most important magnetic resonance imaging (MRI)-variable for higher disability scores. Conclusion: MS patients show clinically relevant cervical SCAH atrophy, which is more pronounced in PMS and at the level of cervical SC enlargement. [ABSTRACT FROM AUTHOR]

Background and purpose: In an era of individualized multiple sclerosis (MS) patient management, biomarkers for accurate prediction of future clinical outcomes are needed. We aimed to evaluate the potential of short‐term magnetic resonance imaging (MRI) atrophy measures and serum neurofilament light chain (sNfL) as predictors of the dynamics of disability accumulation in relapse‐onset MS. Methods: Brain gray and white matter, thalamic, striatal, pallidal and cervical spinal cord volumes, and lesion load were measured over three available time points (mean time span 2.24 ± 0.70 years) for 183 patients (140 relapsing‐remitting [RRMS] and 43 secondary‐progressive MS (SPMS); 123 female, age 46.4 ± 11.0 years; disease duration 15.7 ± 9.3 years), and their respective annual changes were calculated. Baseline sNfL was also measured at the third available time point for each patient. Subsequently, patients underwent annual clinical examinations over 5.4 ± 3.7 years including Expanded Disability Status Scale (EDSS) scoring, the nine‐hole peg test and the timed 25‐foot walk test. Results: Higher annual spinal cord atrophy rates and lesion load increase predicted higher future EDSS score worsening over time in SPMS. Lower baseline thalamic volumes predicted higher walking speed worsening over time in RRMS. Lower baseline gray matter, as well as higher white matter and spinal cord atrophy rates, lesion load increase, baseline striatal volumes and baseline sNfL, predicted higher future hand dexterity worsening over time. All models showed reasonable to high prediction accuracy. Conclusion: This study demonstrates the capability of short‐term MRI metrics to accurately predict future dynamics of disability progression in a real‐world relapse‐onset MS cohort. The present study represents a step towards the utilization of structural MRI measurements in patient care. [ABSTRACT FROM AUTHOR]

Background: Considerable spinal cord (SC) atrophy occurs in multiple sclerosis (MS). While MRI-based techniques for SC cross-sectional area (CSA) quantification have improved over time, there is no common agreement on whether to measure at single vertebral levels or across larger regions and whether upper SC CSA can be reliably measured from brain images. Aim: To compare in a multicenter setting three CSA measurement methods in terms of repeatability at different anatomical levels. To analyze the agreement between measurements performed on the cervical cord and on brain MRI. Method: One healthy volunteer was scanned three times on the same day in six sites (three scanner vendors) using a 3T MRI protocol including sagittal 3D T1-weighted imaging of the brain (covering the upper cervical cord) and of the SC. Images were analyzed using two semiautomated methods [NeuroQLab (NQL) and the Active Surface Model (ASM)] and the fully automated Spinal Cord Toolbox (SCT) on different vertebral levels (C1–C2; C2/3) on SC and brain images and the entire cervical cord (C1–C7) on SC images only. Results: CSA estimates were significantly smaller using SCT compared to NQL and ASM (p < 0.001), regardless of the cord level. Inter-scanner repeatability was best in C1–C7: coefficients of variation for NQL, ASM, and SCT: 0.4, 0.6, and 1.0%, respectively. CSAs estimated in brain MRI were slightly lower than in SC MRI (all p ≤ 0.006 at the C1–C2 level). Despite protocol harmonization between the centers with regard to image resolution and use of high-contrast 3D T1-weighted sequences, the variability of CSA was partly scanner dependent probably due to differences in scanner geometry, coil design, and details of the MRI parameter settings. Conclusion: For CSA quantification, dedicated isotropic SC MRI should be acquired, which yielded best repeatability in the entire cervical cord. In the upper part of the cervical cord, use of brain MRI scans entailed only a minor loss of CSA repeatability compared to SC MRI. Due to systematic differences between scanners and the CSA quantification software, both should be kept constant within a study. The MRI dataset of this study is available publicly to test new analysis approaches. [ABSTRACT FROM AUTHOR]

There is evidence that multiple sclerosis (MS) pathology leads to distinct patterns of volume loss over time (VLOT) in different central nervous system (CNS) structures. We aimed to use such patterns to identify patient subgroups. MS patients of all classical disease phenotypes underwent annual clinical, blood, and MRI examinations over 6 years. Spinal, striatal, pallidal, thalamic, cortical, white matter, and T2‐weighted lesion volumes as well as serum neurofilament light chain (sNfL) were quantified. CNS VLOT patterns were identified using principal component analysis and patients were classified using hierarchical cluster analysis. 225 MS patients were classified into four distinct Groups A, B, C, and D including 14, 59, 141, and 11 patients, respectively). These groups did not differ in baseline demographics, disease duration, disease phenotype distribution, and lesion‐load expansion. Interestingly, Group A showed pronounced spinothalamic VLOT, Group B marked pallidal VLOT, Group C small between‐structure VLOT differences, and Group D myelocortical volume increase and pronounced white matter VLOT. Neurologic deficits were more severe and progressed faster in Group A that also had higher mean sNfL levels than all other groups. Group B experienced more frequent relapses than Group C. In conclusion, there are distinct patterns of VLOT across the CNS in MS patients, which do not overlap with clinical MS subtypes and are independent of disease duration and lesion‐load but are partially associated to sNfL levels, relapse rates, and clinical worsening. Our findings support the need for a more biologic classification of MS subtypes including volumetric and body‐fluid markers. [ABSTRACT FROM AUTHOR]

Objective: To determine the levels of brain‐derived neurotrophic factor (BDNF) in the serum of patients suffering from multiple sclerosis (MS) to evaluate the potential of serum BDNF as a biomarker for MS. Methods: Using a recently validated enzyme‐linked immunoassay (ELISA) we measured BDNF in patients with MS (pwMS), diagnosed according to the 2001 McDonald criteria and aged between 18 and 70 years, participating in a long‐term cohort study with annual clinical visits, including blood sampling, neuropsychological testing, and brain magnetic resonance imaging (MRI). The results were compared with an age‐ and sex‐matched cohort of healthy controls (HC). Correlations between BDNF levels and a range of clinical and magnetic resonance imaging variables were assessed using an adjusted linear model. Results: In total, 259 pwMS and 259 HC were included, with a mean age of 44.42 ± 11.06 and 44.31 ± 11.26 years respectively. Eleven had a clinically isolated syndrome (CIS), 178 relapsing remitting MS (RRMS), 56 secondary progressive MS (SPMS), and 14 primary progressive MS (PPMS). Compared with controls, mean BDNF levels were lower by 8 % (p˂0.001) in pwMS. The level of BDNF in patients with SPMS was lower than in RRMS (p = 0.004). Interpretation: We conclude that while the use of comparatively large cohorts enables the detection of a significant difference in BDNF levels between pwMS and HC, the difference is small and unlikely to usefully inform decision‐making processes at an individual patient level. [ABSTRACT FROM AUTHOR]

Background: To date, little is known about the presence and extent of cerebellar cortical pathology in early stages of MS. Objective: The aims of this study were to (i) investigate microstructural changes in the normal-appearing cerebellar cortex of early MS patients by using 7 T MRI and (ii) evaluate the influence of those changes on clinical performance. Methods: Eighteen RRMS patients and nine healthy controls underwent quantitative T1 and T2* measurement at 7 T MRI using high-resolution MP2RAGE and multi-echo gradient-echo imaging. After subtracting lesion masks, average T1 and T2* maps were computed for three layers in the cerebellar cortex and compared between groups using mixed effects models. Results: The volume of the cerebellar cortex and its layers did not differ between patients and controls. In MS patients, significantly longer T1 values were observed in all vermis cortical layers and in the middle and external cortical layer of the cerebellar hemispheres. No between-group differences in T2* values were found. T1 values correlated with EDSS, SDMT and PASAT. Conclusions: We found MRI evidence of damage in the normal-appearing cerebellar cortex at early MS stages and before volumetric changes. This microstructural alteration appears to be related to EDSS and cognitive performance. [ABSTRACT FROM AUTHOR]

In multiple sclerosis (MS), cortical atrophy is correlated with clinical and neuropsychological measures. We aimed to examine the differences in the temporospatial evolution of cortical thickness (CTh) between MS‐subtypes and to study the association of CTh with T2‐weighted white matter lesions (T2LV) and clinical progression. Two hundred and forty‐three MS patients (180 relapsing–remitting [RRMS], 51 secondary‐progressive [SPMS], and 12 primary‐progressive [PPMS]) underwent annual clinical (incl. expanded disability status scale [EDSS]) and MRI‐examinations over 6 years. T2LV and CTh were measured. CTh did not differ between MS‐subgroups. Higher total T2LV was associated with extended bilateral CTh‐reduction on average, but did not correlate with CTh‐changes over time. In RRMS, CTh‐ and EDSS‐changes over time were negatively correlated in large bilateral prefrontal, frontal, parietal, temporal, and occipital areas. In SPMS, CTh was not associated with the EDSS. In PPMS, CTh‐ and EDSS‐changes over time were correlated in small clusters predominantly in left parietal areas. Increase of brain lesion load does not lead to an immediate CTh‐reduction. Although CTh did not differ between MS‐subtypes, a dissociation in the correlation between CTh‐ and EDSS‐changes over time between RRMS and progressive‐MS was shown, possibly underlining the contribution of subcortical pathology to clinical progression in progressive‐MS. [ABSTRACT FROM AUTHOR]

Background: Little is known on longer term changes of spinal cord volume (SCV) in primary progressive multiple sclerosis (PPMS). Objective: Longitudinal evaluation of SCV loss in PPMS and its correlation to clinical outcomes, compared to relapse-onset multiple sclerosis (MS) subtypes. Methods: A total of 60 MS age-, sex- and disease duration-matched patients (12 PPMS, each 24 relapsing-remitting (RRMS) and secondary progressive MS (SPMS)) were analysed annually over 6 years of follow-up. The upper cervical SCV was measured on 3D T1-weighted magnetization-prepared rapid gradient-echo (MPRAGE) images using a semi-automatic software (CORDIAL), along with the total brain volume (TBV), brain T2 lesion volume (T2LV) and Expanded Disability Status Scale (EDSS). Results: PPMS showed faster SCV loss over time than RRMS (p < 0.01) and by trend (p = 0.066) compared with SPMS. In contrast to relapse-onset MS, in PPMS SCV loss progressed independent of TBV and T2LV changes. Moreover, in PPMS, SCV was the only magnetic resonance imaging (MRI) measurement associated with EDSS increase over time (p < 0.01), as opposed to RRMS and SPMS. Conclusion: SCV loss is a strong predictor of clinical outcomes in PPMS and has shown to be faster and independent of brain MRI metrics compared to relapse-onset MS. [ABSTRACT FROM AUTHOR]

Neuro-axonal injury is a key factor in the development of permanent disability in multiple sclerosis. Neurofilament light chain in peripheral blood has recently emerged as a biofluid marker reflecting neuro-axonal damage in this disease. We aimed at comparing serum neurofilament light chain levels in multiple sclerosis and healthy controls, to determine their association with measures of disease activity and their ability to predict future clinical worsening as well as brain and spinal cord volume loss. Neurofilament light chain was measured by single molecule array assay in 2183 serum samples collected as part of an ongoing cohort study from 259 patients with multiple sclerosis (189 relapsing and 70 progressive) and 259 healthy control subjects. Clinical assessment, serum sampling and MRI were done annually; median follow-up time was 6.5 years. Brain volumes were quantified by structural image evaluation using normalization of atrophy, and structural image evaluation using normalization of atrophy, cross-sectional, cervical spinal cord volumes using spinal cord image analyser (cordial). Results were analysed using ordinary linear regression models and generalized estimating equation modelling. Serum neurofilament light chain was higher in patients with a clinically isolated syndrome or relapsing remitting multiple sclerosis as well as in patients with secondary or primary progressive multiple sclerosis than in healthy controls (age adjusted P < 0.001 for both). Serum neurofilament light chain above the 90th percentile of healthy controls values was an independent predictor of Expanded Disability Status Scale worsening in the subsequent year (P < 0.001). The probability of Expanded Disability Status Scale worsening gradually increased by higher serum neurofilament light chain percentile category. Contrast enhancing and new/enlarging lesions were independently associated with increased serum neurofilament light chain (17.8% and 4.9% increase per lesion respectively; P < 0.001). The higher the serum neurofilament light chain percentile level, the more pronounced was future brain and cervical spinal volume loss: serum neurofilament light chain above the 97.5th percentile was associated with an additional average loss in brain volume of 1.5% (P < 0.001) and spinal cord volume of 2.5% over 5 years (P = 0.009). Serum neurofilament light chain correlated with concurrent and future clinical and MRI measures of disease activity and severity. High serum neurofilament light chain levels were associated with both brain and spinal cord volume loss. Neurofilament light chain levels are a real-time, easy to measure marker of neuro-axonal injury that is conceptually more comprehensive than brain MRI. [ABSTRACT FROM AUTHOR]

Pediatric onset multiple sclerosis (POMS) is a rare disease with an incidence of 0.07 to 2.9/100'000 children per year. It follows a relapsing-remitting disease course and is characterized by rapid accrual of inflammatory lesions, high relapse frequency, and early cognitive impairment. Magnetic resonance imaging (MRI) plays a pivotal role in the diagnosis of POMS, and in the exclusion of other disorders mimicking POMS. Furthermore, MRI aids in disease monitoring, and in the evaluation of therapeutic efficacy in both clinical practice and clinical trials. Volumetric MRI studies, diffusion tensor imaging, resting-state, and task-based functional MRI provide deeper insight into the impact of POMS on maturing neural networks. This review article aims to highlight the importance of MRI in the care of POMS patients and to provide an overview on the different MRI techniques used in the management of POMS. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 62-year-old man, who was admitted with acute inflammation, arthralgia, and fever. The patient was started on antibiotics, but after lack of response, this was changed to prednisolone, leading to rapid improvement and treatment phase out. Further histologic analysis revealed pronounced amyloid deposits immunohistochemically positive for the transthyretin (TTR) subtype; a mutation in the gene encoding TTR was confirmed.