Long-term monitoring of stimulated lower leg skeletal muscle forces compared with voluntary contractions in myopathy patients - A five-year follow-up report on 5 adults.

OBJECTIVE: Long-term assessments of lower leg muscle forces in ambulant patients with distal myopathies. METHODS AND MATERIALS: Over a five-year period, we measured involuntary, nerve-stimulated, isometric torques of the ankle dorsiflexors in a group of ambulant patients with myopathies and compared results with voluntary Manual Muscle Tests (MMT). RESULTS: From ten recruited patients, five could finish the five-year protocol. Twenty-seven force measurements sessions (one per year; 1,5 hours duration each) were performed. These patients exhibited low, stable torques or increased minimally (0.2 Newtonmeter, versus 0.1 Nm, ns; 0.7 vs. 1.0, ns; 3.4 vs. 3.5, ns; 0.2 vs. 0.1, ns; 0.8 vs. 1.5, P 0.0004 initial values vs. 5-year values, [norm: 3.9-5.7 Nm]). A 6th patient, eliciting low torque values (0.1 Nm) early passed away. Contraction times inversely correlated with MMT. MMT provided similar overall force abilities. CONCLUSIONS: Long-term monitoring of lower leg muscle forces in ambulant patients is limited by the patient's health status. In a small group of patients, stimulated lower leg forces did not worsen over many years relative to their diagnosed myopathies. Tracking involuntary forces, could be a useful monitoring providing phenotypic information, in addition to MMT. Future devices should be small and be simply self-applying, designed for subjects' domestic use and web-based data transfer. CLINICALTRIALS: gov NCT00735384.

Cervical and thoracic spinal cord gray matter atrophy is associated with disability in patients with amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In amyotrophic lateral sclerosis (ALS), there is an unmet need for more precise patient characterization through quantitative, ideally operator-independent, assessments of disease extent and severity. Radially sampled averaged magnetization inversion recovery acquisitions (rAMIRA) magnetic resonance imaging enables gray matter (GM) and white matter (WM) area quantitation in the cervical and thoracic spinal cord (SC) with optimized contrast. We aimed to investigate rAMIRA-derived SC GM and SC WM areas and their association with clinical phenotype and disability in ALS. METHODS: A total of 36 patients with ALS (mean [SD] age 61.7 [12.6] years, 14 women) and 36 healthy, age- and sex-matched controls (HCs; mean [SD] age 63.1 [12.1] years, 14 women) underwent two-dimensional axial rAMIRA imaging at the inter-vertebral disc levels C2/3-C5/C6 and the lumbar enlargement level Tmax. ALS Functional Rating Scale-revised (ALSFRS-R) score, muscle strength, and sniff nasal inspiratory pressure (SNIP) were assessed. RESULTS: Compared to HCs, GM and WM areas were reduced in patients at all cervical levels (p < 0.0001). GM area (p = 0.0001), but not WM area, was reduced at Tmax. Patients with King's Stage 3 showed significant GM atrophy at all levels, while patients with King's Stage 1 showed significant GM atrophy selectively at Tmax. SC GM area was significantly associated with muscle force at corresponding myotomes. GM area at C3/C4 was associated with ALSFRS-R (p < 0.001) and SNIP (p = 0.0016). CONCLUSION: Patients with ALS assessed by rAMIRA imaging show significant cervical and thoracic SC GM and SC WM atrophy. SC GM area correlates with muscle strength and clinical disability. GM area reduction at Tmax may be an early disease sign. Longitudinal studies are warranted.

Supportive needs of informal caregivers of people with amyotrophic lateral sclerosis in Switzerland: a qualitative study.

OBJECTIVE: This study explores the supportive needs of informal caregivers of people with amyotrophic lateral sclerosis (ALS) in Switzerland. METHOD: We conducted semi-structured interviews with nine informal caregivers currently providing care to a person with ALS, 14 bereaved informal caregivers, and 13 healthcare professionals. Interviews were recorded on digital audio and analysed using an inductive thematic analysis within a realist framework. RESULT: Informal caregivers discussed five themes of support needs relating to being overburdened by administrative demand, in contact with healthcare providers, home support, especially during the terminal phase, and having or lacking social support. Healthcare professionals discussed three themes of support needs of informal caregivers which related to the general institutional support for informal caregivers, their own work as caring for informal caregivers, and the challenges in healthcare for families with ALS they encountered. SIGNIFICANCE OF RESULTS: Informal caregiving for people with ALS can be demanding. This study provides evidence for improvements in supporting informal caregivers. It shows administrative needs of informal caregivers, stresses their needs regarding advance care planning early in the context of ALS, and underlines the importance of social support, be it in peer-groups or community care.

Diagnosis and treatment of neurogenic dysphagia - S1 guideline of the German Society of Neurology.

INTRODUCTION: Neurogenic dysphagia defines swallowing disorders caused by diseases of the central and peripheral nervous system, neuromuscular transmission, or muscles. Neurogenic dysphagia is one of the most common and at the same time most dangerous symptoms of many neurological diseases. Its most important sequelae include aspiration pneumonia, malnutrition and dehydration, and affected patients more often require long-term care and are exposed to an increased mortality. Based on a systematic pubmed research of related original papers, review articles, international guidelines and surveys about the diagnostics and treatment of neurogenic dysphagia, a consensus process was initiated, which included dysphagia experts from 27 medical societies. RECOMMENDATIONS: This guideline consists of 53 recommendations covering in its first part the whole diagnostic spectrum from the dysphagia specific medical history, initial dysphagia screening and clinical assessment, to more refined instrumental procedures, such as flexible endoscopic evaluation of swallowing, the videofluoroscopic swallowing study and high-resolution manometry. In addition, specific clinical scenarios are captured, among others the management of patients with nasogastric and tracheotomy tubes. The second part of this guideline is dedicated to the treatment of neurogenic dysphagia. Apart from dietary interventions and behavioral swallowing treatment, interventions to improve oral hygiene, pharmacological treatment options, different modalities of neurostimulation as well as minimally invasive and surgical therapies are dealt with. CONCLUSIONS: The diagnosis and treatment of neurogenic dysphagia is challenging and requires a joined effort of different medical professions. While the evidence supporting the implementation of dysphagia screening is rather convincing, further trials are needed to improve the quality of evidence for more refined methods of dysphagia diagnostics and, in particular, the different treatment options of neurogenic dysphagia. The present article is an abridged and translated version of the guideline recently published online ( https://www.awmf.org/uploads/tx_szleitlinien/030-111l_Neurogene-Dysphagie_2020-05.pdf ).

Differentiating needs of informal caregivers of individuals with ALS across the caregiving course: a systematic review.

BACKGROUND: Informal caregivers of people with amyotrophic lateral sclerosis (ALS) experience a range of needs across the course of the disease. For the provision of adequate support, an examination of the empirical evidence is necessary. AIM: The purpose of the systematic review was to synthesize evidence of needs of informal caregivers of people with ALS at different stages of caregiving. METHOD: Systematic review of empirical research on needs of ALS informal caregivers in both English and German, from January 2000 to August 2018. We searched the databases EMBASE, MEDLINE (PubMed), PsycINFO, and CINAHL. Study selection, quality assessment, and data extraction was performed independently. Both quantitative and qualitative studies were included. Of the included studies, we additionally screened citing literature in Google Scholar (citation tracking). We linked the narrative synthesis to four stages of caregiving described by Williams and colleagues and used descriptive inductive thematic analysis to structure data within the stages. RESULTS: From 3275 abstracts screened, 48 manuscripts met our inclusion criteria. Our data analysis shows that needs differ across the four caregiving stages. While the stage of bereavement (stage 4) includes too little data for separate themes, themes for needs after diagnosis (stage 1), and terminal stage (stage 3) could be specified. As the maintenance (stage 2) stage comprised of themes relevant across the caregiving course, it became an overall stage. DISCUSSION: Healthcare professionals need to pay attention to current caregiving stages to provide support for informal caregivers. Further research is needed to tease out support needs for the bereavement phase.

Safety and clinical impact of FEES - results of the FEES-registry.

BACKGROUND: At present, the flexible endoscopic evaluation of swallowing (FEES) is one of the most commonly used methods for the objective assessment of swallowing. This multicenter trial prospectively collected data on the safety of FEES and also assessed the impact of this procedure on clinical dysphagia management. METHODS: Patients were recruited in 23 hospitals in Germany and Switzerland from September 2014 to May 2017. Patient characteristics, professional affiliation of the FEES examiners (physicians or speech and language therapists), side-effects and cardiorespiratory parameters, severity of dysphagia and clinical consequences of FEES were documented. RESULTS: 2401 patients, mean age 69.8 (14.6) years, 42.3% women, were included in the FEES-registry. The most common main diagnosis was stroke (61%), followed by Parkinson's disease (6.5%). FEES was well tolerated by patients. Complications were reported in 2% of examinations, were all self-limited and resolved without sequelae and showed no correlation to the endoscopist's previous experience. In more than 50% of investigations FEES led to changes of feeding strategies, in the majority of cases an upgrade of oral diet was possible. DISCUSSION: This study confirmed that FEES, even when performed by less experienced clinicians is a safe and well tolerated procedure and significantly impacts on the patients' clinical course. Implementation of a FEES-service in different clinical settings may improve dysphagia care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03037762, registered January 31st 2017.

Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation: a large multinational screening study.

A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting RP-PCR data. Our objective was to determine the properties of these sequence variations with regard to prevalence, the range of variation, and effect on disease prognosis. We screened a multi-national cohort (n = 6981) for the HREM and samples with deviant RP-PCR curves were identified. The deviant samples were subsequently sequenced to determine sequence alteration. Our results show that in the USA and European cohorts (n = 6508) 10.7% carried the HREM and 3% had a sequence variant, while no HREM or sequence variants were observed in the Japanese cohort (n = 473). Sequence variations were more common on HREM alleles; however, certain population specific variants were associated with a non-expanded allele.In conclusion, we identified 38 different sequence variants, most located within the first 50 bp downstream of the HREM region. Furthermore, the presence of an HREM was found to be coupled to a lower age of onset and a shorter disease survival, while sequence variation did not have any correlation with these parameters.

Isometric skeletal muscle force measurement in primary myopathies.

INTRODUCTION: In myopathy patients, it is useful to measure skeletal muscle forces. Conventional methods require voluntary muscle activation, which can be unreliable. We evaluated a device for nonvoluntary force assessment. METHODS: We tested 8 patients (unknown myopathy n = 2, inflammatory myopathy, facioscapulohumeral muscular dystrophy, mitochondrial myopathy, dysferlinopathy, multi-minicore disease, Becker-Kiener muscular dystrophy, n = 1 each). Isometric twitch torques of ankle dorsiflexors were measured after fibular nerve stimulation. RESULTS: Six patients had decreased torques vs. 8 controls (men: median Newton-meter 1.6 vs. 5.7, women: 0.2 vs. 3.9, both P < 0.0001). Values correlated with Manual Muscle Test results (r = 0.73; r(2) = 0.53; P < 0.0001). In weak dorsiflexors, torque could be measured despite lower signal-to-noise ratios. In 2 patients with hypertrophy, we measured increased torques. CONCLUSIONS: Nonvoluntary muscle force assessment can be used in patients with myopathies, and values correlate with voluntary forces determined by traditional methods. Muscle Nerve 53: 913-917, 2016.

Nerve ultrasound for differentiation between amyotrophic lateral sclerosis and multifocal motor neuropathy.

Ultrasound is useful for non-invasive visualization of focal nerve pathologies probably resulting from demyelination, remyelination, edema or inflammation. In patients with progressive muscle weakness, differentiation between multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS) is essential regarding therapy and prognosis. Therefore, the objective of this study was to investigate whether nerve ultrasound can differentiate between ALS and MMN. Systematic ultrasound measurements of peripheral nerves and the 6th cervical nerve root (C6) were performed in 17 patients with ALS, in 8 patients with MMN and in 28 healthy controls. Nerve conduction studies of corresponding nerves were undertaken in MMN and ALS patients. Electromyography was performed in ALS patients according to revised El-Escorial criteria. ANOVA and unpaired t test with Bonferroni correction revealed significant differences in cross-sectional areas (CSA) of different nerves and C6 diameter between the groups. Nerve enlargement was found significantly more frequently in MMN than in other groups (p < 0.001). Receiver operating characteristics analysis revealed detection of enlarged nerves/roots in at least four measurement points to serve as a good marker to differentiate MMN from ALS with a sensitivity of 87.5% and a specificity of 94.1%. Ultrasonic focal nerve enlargement in MMN was often not colocalized with areas of conduction blocks found in nerve conduction studies. Systematic ultrasound measurements in different nerves and nerve roots are valuable for detecting focal nerve enlargement in MMN, generally not found in ALS and thus could serve as a diagnostic marker to differentiate between both entities in addition to electrodiagnostic studies.

Contribution of nerve biopsy to unclassified neuropathy.

OBJECTIVES: To evaluate the diagnostic yield of nerve biopsy in patients with peripheral neuropathy of undetermined cause despite extensive diagnostic workup. METHODS: From November 2001 through January 2004, 38 patients underwent nerve biopsy because of unclassified neuropathy. RESULTS: The etiology of the neuropathies could be defined in 14 patients (37%), i.e. in 15% of chronic symmetric, 30% of chronic asymmetric, 50% of subacute symmetric and 62.5% of subacute asymmetric neuropathies. The biopsy was diagnostic in 6 patients (16%), where it showed a vasculitis, and supportive in 8 patients (21%). CONCLUSIONS: The contribution of nerve biopsy to the diagnosis of peripheral neuropathy was highest in acute and subacute asymmetric forms of neuropathy and lowest in chronic symmetric forms. The main indication for nerve biopsy remains the diagnosis of vasculitic neuropathy, a potentially treatable disorder.