Expert consensus recommendations for improving and standardising the assessment of patients with generalised myasthenia gravis.

BACKGROUND: Regular and consistent disease assessment could provide a clearer picture of burden in generalised myasthenia gravis (gMG) and improve patient care; however, the use of assessment tools in practice lacks standardisation. This modified Delphi approach was taken to review current evidence on assessment tool use in gMG and develop expert-derived consensus recommendations for good practice. METHODS: A European expert panel of 15 experienced gMG neurologists contributed to development of this consensus, four of whom formed a lead Sub-committee. The PICO (Population, Intervention, Control, Outcomes) framework was used to define six clinical questions on gMG assessment tools, a systematic literature review was conducted, and evidence-based statements were developed. According to a modified Delphi voting process, consensus was reached when ≥70% of the experts rated agreement with a statement as ≥8 on a scale of 1-10. RESULTS: Eighteen expert- and evidence-based consensus statements based on six themes were developed. Key recommendations include: consistent use of the Myasthenia Gravis Activities of Daily Living score (MG-ADL) across clinical settings, followed by a simple question (e.g., Patient Acceptable Symptom State [PASS]) or scale to determine patient satisfaction in clinical practice; use of a Quantitative Myasthenia Gravis [QMG] or quality of life [QoL] assessment when the MG-ADL indicates disease worsening; and consideration of symptom state to determine the timing and frequency of recommended assessments. Expert panel consensus was reached on all 18 statements after two voting rounds. CONCLUSIONS: This process provided evidence- and expert consensus-based recommendations for the use of objective and subjective assessment tools across gMG research and care to improve management and outcomes for patients.

Burden of disease in Lambert-Eaton myasthenic syndrome: taking the patient's perspective.

BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disorder leading to muscle weakness, autonomic dysregulation and hyporeflexia. Psychosocial well-being is affected. Previously, we assessed burden of disease for Myasthenia gravis (MG). Here, we aim to elucidate burden of disease by comparing health-related quality of life (HRQoL) of patients with LEMS to the general population (genP) as well as MG patients. METHODS: A questionnaire-based survey included sociodemographic and clinical data along with standardized questionnaires, e.g. the Short Form Health (SF-36). HRQoL was evaluated through matched-pairs analyses. Participants from a general health survey served as control group. RESULTS: 46 LEMS patients matched by age and gender were compared to 92 controls from the genP and a matched cohort of 92 MG patients. LEMS participants showed lower levels of physical functioning (SF-36 mean 34.2 SD 28.6) compared to genP (mean 78.6 SD 21.1) and MG patients (mean 61.3 SD 31.8). LEMS patients showed lower mental health sub-scores compared to genP (SF-36 mean 62.7 SD 20.2, vs. 75.7 SD 15.1) and MG patients (SF-36 mean 62.7 SD 20.2, vs. 66.0 SD 18.). Depression, anxiety and fatigue were prevalent. Female gender, low income, lower activities of daily living, symptoms of depression, anxiety and fatigue were associated with a lower HRQoL in LEMS. DISCUSSION: HRQoL is lower in patients with LEMS compared to genP and MG in a matched pair-analysis. The burden of LEMS includes economic and social aspects as well as emotional well-being. TRIAL REGISTRATION INFORMATION: drks.de: DRKS00024527, submitted: February 02, 2021, https://drks.de/search/en/trial/DRKS00024527 .

Guideline adherence in speech and language therapy in stroke aftercare. A health insurance claims data analysis.

BACKGROUND: Impairments to comprehension and production of speech (aphasia, dysarthria) and swallowing disorders (dysphagia) are common sequelae of stroke, reducing patients' quality of life and social participation. Treatment oriented on evidence-based guidelines seems likely to improve outcomes. Currently, little is known about guideline adherence in stroke aftercare for the above-mentioned sequelae. This study aims to analyse guideline adherence in the treatment of aphasia, dysarthria and dysphagia after stroke, based on suitable test parameters, and to determine factors that influence the implementation of recommended therapies. METHODS: Six test parameters were defined, based on systematic study of guidelines for the treatment of speech impairments and swallowing disorders (e.g. comprehensive diagnostics, early initiation and continuity). Guideline adherence in treatment was tested using claims data from four statutory health insurance companies. Multivariate logistic and linear regression analyses were performed in order to test the outcomes. RESULTS: 4,486 stroke patients who were diagnosed with specific disorders or received speech therapy were included in the study. The median age was 78 years; the proportion of women was 55.9%. Within the first year after the stroke, 90.3% of patients were diagnosed with speech impairments and swallowing disorders. Overall, 44.1% of patients received outpatient speech and language therapy aftercare. Women were less frequently diagnosed with specific disorders (OR 0.70 [95%CI:0.55/0.88], p = 0.003) and less frequently received longer therapy sessions (OR 0.64 [95%CI:0.43/0.94], p = 0.022). Older age and longer hospitalization duration increased the likelihood of guideline recommendations being implemented and of earlier initiation of stroke aftercare measures. CONCLUSIONS: Our observations indicate deficits in the implementation of guideline recommendations in stroke aftercare. At the same time, they underscore the need for regular monitoring of implementation measures in stroke aftercare to address group-based disparities in care.

Burden of disease in myasthenia gravis: taking the patient's perspective.

BACKGROUND: Myasthenia gravis (MG) leads to exertion-dependent muscle weakness, but also psychological and social well-being are limited. We aim to describe the burden of disease in MG including sociodemographic, economical, psychosocial as well as clinical aspects, to compare health-related quality of life (HRQoL) of patients with MG to the general population (genP) and to explore risk factors for a lower HRQoL. METHODS: This case-control study was conducted with MG patients of the German Myasthenia Association. A questionnaire-based survey included sociodemographic and clinical data as well as standardized questionnaires, e.g. the Short Form Health (SF-36). HRQoL was compared to genP in a matched-pairs analysis. Participants of the German Health Interview and Examination Survey for Adults (DEGS1) served as control group. RESULTS: In our study, 1660 MG patients participated and were compared to 2556 controls from the genP. Patients with MG showed lower levels of physical functioning (SF-36 mean 56.0, SD 30.3) compared to the genP (mean 81.8, SD 22.1, adjusted difference: 25, 95% CI 22-29) and lower mental health sub-score (SF-36 mean 67.3, SD 19.8, vs. 74.1, SD 16.7, adjusted difference: 5, 95% CI 2-8). Female gender, higher age, low income, partnership status, lower activities of daily life, symptoms of depression, anxiety and fatigue and self-perceived low social support were associated with a lower HRQoL in MG patients. DISCUSSION: HRQoL is lower in patients with MG compared to genP. The burden of MG on patients includes economic and social aspects as well as their emotional well-being. New therapies must achieve improvements for patients in these areas. TRIAL REGISTRATION INFORMATION: Clinicaltrials.gov, NCT03979521, submitted: June 7, 2019, first patient enrolled: May 1, 2019, https://clinicaltrials.gov/ct2/show/NCT03979521.

Cost-effectiveness of patient navigation programs for stroke patients-A systematic review.

OBJECTIVE: Stroke remains a leading cause of premature death, impairment and reduced quality of life. Its aftercare is performed by numerous different health care service providers, resulting in a high need for coordination. Personally delivered patient navigation (PN) is a promising approach for managing pathways through health care systems and for improving patient outcomes. Although PN in stroke care is evolving, no summarized information on its cost-effectiveness in stroke survivors is available. Hence, the aim of this systematic review is to analyze the level of evidence on the cost-effectiveness of PN for stroke survivors. METHODS: A systematic literature search without time limitations was carried out in PubMed, EMBASE, CENTRAL, CINAHL as well as PsycINFO and supplemented by a manual search. Randomized controlled trials published prior to April 2020 in English or German were considered eligible if any results regarding the cost-effectiveness of PN for stroke survivors were reported. The review was conducted according to PRISMA guidelines. Quality of included studies was assessed with the RoB2 tool. Main study characteristics and cost-effectiveness results were summarized and discussed. RESULTS: The search identified 1442 records, and two studies met the inclusion criteria. Quality of included studies was rated moderate and high. Programs, settings and cost-effectiveness results were heterogeneous, with one study showing a 90% probability of being cost-effective at a willingness to pay of $25600 per QALY (health/social care perspective) and the other showing similar QALYs and higher costs. CONCLUSIONS: Since only two studies were eligible, this review reveals a large gap in knowledge regarding the cost-effectiveness of PN for stroke survivors. Furthermore, no conclusive statement about the cost-effectiveness can be made. Future attempts to evaluate PN for stroke survivors are necessary and should also involve cost-effectiveness issues.

Quantitative grip force assessment of muscular weakness in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: In patients suffering from Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) disease severity is assessed by Medical Research Counsil (MRC) Scale or Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. However, none of these methods is appropriate to objectively assess muscle weakness or to detect very small subclinical changes. More objective and quantitative measures are needed in order to evaluate treatment efficiency or to detect subclinical affection of upper limps for early diagnosis. The goal of our study was to objectively quantify muscular weakness in CIDP patients with the non-invasive Quantitative Motor (Q-Motor) test of Grip Force Assessment (QGFA) as well as the Involuntary Movement Assessment (QIMA) and to search for differences between typical and atypical CIDP variants. In addition, we hypothesized that Q-Motor findings correlate with disease severity scales such as MRC or INCAT score. METHODS: In this cross-sectional exploratory proof-of-concept study subjects with confirmed diagnosis of typical or atypical CIDP were examined and compared to healthy controls (HC). For Q-Motor tests all subjects had to lift a device (250 g and 500 g) equipped with an electromagnetic sensor that measured grip force (GF) and three-dimensional changes in position and orientation. The measures "grip force variability" (GFV), "position index" (PI) and "orientation index" (OI) were provided to assess involuntary movements due to muscular weakness. RESULTS: 33 patients with CIDP and 28 HC were included. All measures were significantly elevated in CIDP patients for both devices in the right and left hand compared to healthy controls. Subgroup analysis revealed no differences between typical and atypical CIDP variants. INCAT score only weakly correlated with OI and PI. However, there was a stronger correlation between MRC and QIMA parameters in both hands. CONCLUSION: Q-Motor assessments were capable to objectively assess muscular weakness in CIDP. In particular, QIMA measures detected subclinical generalized muscle weakness even in patients with milder disability. Sensitivity and rater-independence of Q-Motor assessments support a further exploration of QIMA measures as potential endpoints for future clinical trials in CIDP.

Identifying unmet needs in long-term stroke care using in-depth assessment and the Post-Stroke Checklist - The Managing Aftercare for Stroke (MAS-I) study.

INTRODUCTION: Detailed data on the long-term consequences and treatment of stroke are scarce. We aimed to assess the needs and disease burden of community-dwelling stroke patients and their carers and to compare their treatment to evidence-based guidelines by a stroke neurologist. METHODS: We invited long-term stroke patients from two previous acute clinical studies (n = 516) in Berlin, Germany to participate in an observational, cross-sectional study. Participants underwent a comprehensive interview and examination using the Post-Stroke Checklist and validated standard measures of: self-reported needs, quality of life, overall outcome, spasticity, pain, aphasia, cognition, depression, secondary prevention, social needs and caregiver burden. RESULTS: Fifty-seven participants (median initial National Institutes of Health Stroke Scale score 10 interquartile range 4-12.75) consented to assessment (median 41 months (interquartile range 36-50) after stroke. Modified Rankin Scale was 2 (median; interquartile range 1-3), EuroQoL index value was 0.81 (median; interquartile range 0.70-1.00). The frequencies for disabilities in the major domains were: spasticity 35%; cognition 61%; depression 20%; medication non-compliance 14%. Spasticity (p = 0.008) and social needs (p < 0.001) had the strongest impact on quality of life. The corresponding items in the Post-Stroke Checklist were predictive for low mood (p < 0.001), impaired cognition (p = 0.015), social needs (p = 0.005) and caregiver burden (p = 0.031). In the comprehensive interview, we identified the following needs: medical review (30%), optimization of pharmacotherapy (18%), outpatient therapy (47%) and social work input (33%). CONCLUSION: These results suggest significant unmet needs and gaps in health and social care in long-term stroke patients. Further research to develop a comprehensive model for managing stroke aftercare is warranted.Clinical Trial Registration: clinicaltrials.gov NCT02320994.

Quantitative motor assessment of muscular weakness in myasthenia gravis: a pilot study.

BACKGROUND: Muscular weakness in myasthenia gravis (MG) is commonly assessed using Quantitative Myasthenia Gravis Score (QMG). More objective and quantitative measures may complement the use of clinical scales and might detect subclinical affection of muscles. We hypothesized that muscular weakness in patients with MG can be quantified with the non-invasive Quantitative Motor (Q-Motor) test for Grip Force Assessment (QGFA) and Involuntary Movement Assessment (QIMA) and that pathological findings correlate with disease severity as measured by QMG. METHODS: This was a cross-sectional pilot study investigating patients with confirmed diagnosis of MG. Data was compared to healthy controls (HC). Subjects were asked to lift a device (250 and 500 g) equipped with electromagnetic sensors that measured grip force (GF) and three-dimensional changes in position and orientation. These were used to calculate the position index (PI) and orientation index (OI) as measures for involuntary movements due to muscular weakness. RESULTS: Overall, 40 MG patients and 23 HC were included. PI and OI were significantly higher in MG patients for both weights in the dominant and non-dominant hand. Subgroup analysis revealed that patients with clinically ocular myasthenia gravis (OMG) also showed significantly higher values for PI and OI in both hands and for both weights. Disease severity correlates with QIMA performance in the non-dominant hand. CONCLUSION: Q-Motor tests and particularly QIMA may be useful objective tools for measuring motor impairment in MG and seem to detect subclinical generalized motor signs in patients with OMG. Q-Motor parameters might serve as sensitive endpoints for clinical trials in MG.

A circle-monitor for computerised assessment of visual neglect in peripersonal space.

UNLABELLED: Current assessment of visual neglect involves paper-and-pencil tests or computer-based tasks. Both have been criticised because of their lack of ecological validity as target stimuli can only be presented in a restricted visual range. This study examined the user-friendliness and diagnostic strength of a new "Circle-Monitor" (CM), which enlarges the range of the peripersonal space, in comparison to a standard paper-and-pencil test (Neglect-Test, NET). METHODS: Ten stroke patients with neglect and ten age-matched healthy controls were examined by the NET and the CM test comprising of four subtests (Star Cancellation, Line Bisection, Dice Task, and Puzzle Test). RESULTS: The acceptance of the CM in elderly controls and neglect patients was high. Participants rated the examination by CM as clear, safe and more enjoyable than NET. Healthy controls performed at ceiling on all subtests, without any systematic differences between the visual fields. Both NET and CM revealed significant differences between controls and patients in Line Bisection, Star Cancellation and visuo-constructive tasks (NET: Figure Copying, CM: Puzzle Test). Discriminant analyses revealed cross-validated assignment of patients and controls to groups was more precise when based on the CM (hit rate 90%) as compared to the NET (hit rate 70%). CONCLUSION: The CM proved to be a sensitive novel tool to diagnose visual neglect symptoms quickly and accurately with superior diagnostic validity compared to a standard neglect test while being well accepted by patients. Due to its upgradable functions the system may also be a valuable tool not only to test for non-visual neglect symptoms, but also to provide treatment and assess its outcome.

Association between socioeconomic status and functional impairment 3 months after ischemic stroke: the Berlin Stroke Register.

BACKGROUND AND PURPOSE: We aimed to analyze the association between patient socioeconomic status and functional impairment 3 months after ischemic stroke and to identify factors that influence this association. METHODS: Data were obtained from the Berlin Stroke Register, a network of 14 stroke units in Berlin. Ischemic stroke patients consecutively admitted to 1 of the hospitals in the Berlin Stroke Register between June 2010 and September 2011, were followed-up 3 months after the index event by postal or telephone interview. We used multivariable logistic regression to examine the association between highest education as marker of socioeconomic status and functional impairment after stroke defined by Barthel Index categories. We adjusted for age, sex, prestroke dependency, stroke severity, functional deficit after stroke onset, and comorbidities as possible confounding factors. RESULTS: A total of 1688 ischemic stroke patients who were alive at 3 months and completed the questionnaire were included in the analysis; 40% of the patients were female and 50% of the patients were 70 years or older. Age, prestroke dependency, stroke severity, and the absence of comorbidities were significantly associated with good functional outcome at 3 months. In multivariable analysis, a higher probability of good outcome was observed in patients with college or university degree (odds ratio, 2.18; 95% confidence interval, 1.39-3.42) compared with patients with no completed education. CONCLUSIONS: Patients with lower education have considerably lower rates of good functional outcome after stroke that cannot be fully explained by variations in the patients' clinical and demographic characteristics.

Serial analysis of gene expression identifies metallothionein-II as major neuroprotective gene in mouse focal cerebral ischemia.

We applied serial analysis of gene expression (SAGE) to study differentially expressed genes in mouse brain 14 hr after the induction of focal cerebral ischemia. Analysis of >60,000 transcripts revealed 83 upregulated and 94 downregulated transcripts (more than or equal to eightfold). Reproducibility was demonstrated by performing SAGE in duplicate on the same starting material. Metallothionein-II (MT-II) was the most significantly upregulated transcript in the ischemic hemisphere. MT-I and MT-II are assumed to be induced by metals, glucocorticoids, and inflammatory signals in a coordinated manner, yet their function remains elusive. Upregulation of both MT-I and MT-II was confirmed by Northern blotting. MT-I and MT-II mRNA expression increased as early as 2 hr after 2 hr of transient ischemia, with a maximum after 16 hr. Western blotting and immunohistochemistry revealed MT-I/-II upregulation in the ischemic hemisphere, whereas double labeling demonstrated the colocalization of MT with markers for astrocytes as well as for monocytes/macrophages. MT-I- and MT-II-deficient mice developed approximately threefold larger infarcts than wild-type mice and a significantly worse neurological outcome. For the first time we make available a comprehensive data set on brain ischemic gene expression and underscore the important protective role of metallothioneins in ischemic damage of the brain. Our results demonstrate the usefulness of SAGE to screen functionally relevant genes and the power of knock-out models in linking function to expression data generated by high throughput techniques.