Patients' and caregivers' perception of multidimensional and palliative care in amyotrophic lateral sclerosis - protocol of a German multicentre study.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an inevitably fatal condition that leads to a progressive loss of physical functioning, which results in a high psychosocial burden and organizational challenges related to medical care. Multidimensional and multiprofessional care is advised to meet the complex needs of patients and their families. Many healthcare systems, including Germany, may not be able to meet these needs because non-medical services such as psychological support or social counselling are not regularly included in the care of patients with ALS (pwALS). Specialised neuropalliative care is not routinely implemented nor widely available. Caregivers of pwALS are also highly burdened, but there is still a lack of support services for them. METHODS: This project aims to assess the perceptions and satisfaction with ALS care in Germany in pwALS and their caregivers. This will be achieved by means of a cross-sectional, multicentre survey. The examination will assess, to which extend the patients' needs in the six domains of physical, psychological, social, spiritual, practical and informational are being met by current care structures. This assessment will be linked to mental well-being, subjective quality of life, attitudes toward life-sustaining measures and physician-assisted suicide, and caregiver burden. The study aims to recruit 500 participants from nationwide ALS centres in order to draw comprehensive conclusions for Germany. A total of 29 centres, mostly acquired via the clinical and scientific German Network for Motor Neuron Diseases (MND-NET), will take part in the project, 25 of which have already started recruitment. PERSPECTIVE: It is intended to provide data-based starting points on how current practice of care in Germany is perceived pwALS and their caregivers and how it can be improved according to their needs. Planning and initiation of the study has been completed. TRIAL REGISTRATION: The study is registered at ClinicalTrails.gov; NCT06418646.

[EMG phenomena of myogenic hyperexcitability]. / EMG-Phänomene myogener Übererregbarkeit.

The type, distribution pattern and time course of spontaneous muscular activity are important for the diagnostics of neuromuscular diseases in the clinical practice. In neurogenic lesions with motor axonal involvement, pathologic spontaneous activity (PSA) is usually reliably detectable by needle electromyography (EMG) 2-4 weeks after occurrence of the lesion. The distribution pattern correlates with the lesion location. The focus of the present work is the description of the different forms of PSA in myogenic diseases.

Historical Profiling of Dry Eye Patients - Potential Trigger Factors and Comorbidities.

PURPOSE: Dry eye syndrome (DES) is one of the most common diseases of the ocular surface. Affected persons suffer from different subjective complaints, with sometimes severe impairment in the quality of life. The aetiology and pathogenesis are multifactorial, multifaceted, and not yet fully understood. The present study is intended to provide deeper insights into possible triggering factors and correlating comorbidities. MATERIALS AND METHODS: In German ophthalmological practices, 306 persons (174 women, 132 men, age: 18 - 87 years) were interviewed by questionnaire on concomitant diseases and possible further triggering factors. DES was diagnosed by an ophthalmologist in 170 cases. The statistical comparative analysis between persons with and without DES was carried out using the chi-squared test (SPSS statistical software). RESULTS: DES occurred with significantly (p < 0.05) increased frequency in women over 40 years of age, as well as in persons exposed to screen work, air conditioning, persons with chronic ocular inflammation, myomas (hysterectomy), dry skin, arterial hypertonicity in need of medication, cardiac arrhythmias, fatty liver, gastric ulcer, appendicitis, cholecystectomy, depression, hyperlipidaemia, hyperuricaemia, osteoporosis, and nephrolithiasis. CONCLUSION: Some of the known comorbidities and DES risk factors, e.g., computer work or depression, were confirmed. In contrast, the higher prevalence of hyperlipidaemia, hyperuricaemia, osteoporosis, nephrolithiasis, and fibroids among DES patients has not previously been reported. Additional studies should be performed on causal connections between DES and specific comorbidities.

Jitter patterns in conventional concentric needle electromyography recordings of regenerating motor units.

BACKGROUND: The time interval between two potential components of the same motor unit potential (MUP) is measured for jitter analysis. Enhanced jitter is generally thought to result from impaired neuromuscular transmission as occurs in myasthenia gravis or during reinnervation. METHODS: Within a database of conventional video-electromyography (EMG) recordings 4 MUP with peculiar jitter patterns were identified. In 1 spontaneously discharging MUP, massive and chaotic jitter was seen with a mean consecutive difference (MCD) of 9.3 ms. In 2 spontaneously discharging MUP a certain potential subgroup jittered relative to the other part(s) of the MUP (MCD 2.0 and 3.3 ms). A jittering satellite was detected in a fourth voluntarily recruited MUP (MCD 0.6 ms). RESULTS: These different jitter patterns recorded with conventional EMG technique may mainly result from dysmyelination. CONCLUSIONS: A new look at the contribution of dysmyelination to abnormal jitter is also warranted in single fiber EMG recordings.

Complex Repetitive Discharges: A Sign of Motor Axonal Reinnervation?

Complex repetitive discharges (CRDs) are poorly understood phenomena in needle electromyography (EMG) recordings. The data presented here suggest that CRDs may mainly be a sign of motor unit reinnervation. EMG "video" data of 108 CRDs from neurogenic (ND, n = 39) and myogenic (MD, n = 14) disorders were retrospectively analyzed for cycle duration, potential-free time intervals, spike components (SC), maximum amplitudes, blockade, and increased jitter. CRD-SC in ND disorders (9.3 ± 7.8) outnumbered those in MD disorders (6.3 ± 6.2). The CRD cycle duration was correlated with SC and silent periods (p each < 0.000001). Blockade was observed in 36% and increased jitter in 27% of the CRDs. A higher number of CRD-SC in ND vs. MD fits the known differences in motor unit dimensions. Blockade and increased jitter are known features of diseased neuromuscular junctions, such as during reinnervation. The SC patterns of single CRD cycles resemble reinnervation potentials. Thus, CRDs may result from myo-axonal re-excitation in sprouting motor units. The purpose of this investigation was to better understand the circumstances under which CRDs may occur and eventually to contribute to the understanding of their pathogenesis.

Severe CIDP-MGUS responsive to Rituximab.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a relatively rare disease with progressive limb weakness and sensory loss. A few patients show a severely progressing course without major response to intravenous immunoglobulin or plasma exchange therapy. CIDP-MGUS (monoclonal gammopathy of undetermined significance) is a seldom CIDP variant that has been rarely addressed in therapeutic studies. In the presented CIDP-MGUS case, B cell depletion with rituximab had a favourable effect on the disease course, clinically and in nerve conduction studies.

Basilar artery thrombosis during sexual intercourse.

An ischemic stroke during sexual intercourse is very rare. A basilar artery thrombosis during sexual intercourse has not been described previously. We report a young woman with a life-threatening basilar artery thrombosis during sexual intercourse, with a resulting locked-in syndrome. The positive high intensity transient signals (HITS) diagnosis showed a right-to-left shunt and is in line with paradoxic embolism. The molecular genetics revealed a homozygosity 4G/4G in the region PAI1, -675 (promoter polymorphism) as a risk factor for ischemic stroke. Sexual intercourse is a possible, albeit unusual stroke cause, especially in young people.

Spontaneous continuous motor unit single discharges.

INTRODUCTION: Motor unit hyperexcitability (MUH) may become manifest in needle electromyography (EMG) recordings as fasciculation potentials, myokymic discharges, or neuromyotonic discharges. Here, we describe a further MUH phenomenon. METHODS: Needle EMG recordings of the Neurology Hospital of Halle (Saale) stored in a video mode as .wav data between 2000 and 2015 were screened for spontaneous continuous motor unit single discharges (SCMUSD). RESULTS: We identified 23 video needle EMG waveforms from 14 patients with SCMUSD. The corresponding motor units discharged at a rate of about 6 H Z (6.3 ± 4.0; range, 1.3-18.1). The coefficient of variation of the discharge rate was 3.5% ± 1.7%. Neurogenic disorders were diagnosed in 12 patients, limb girdle muscle dystrophy was diagnosed in one patient, and stiff-limb syndrome was diagnosed in one patient. DISCUSSION: Spontaneous continuous motor unit single discharge, as described here, widens the spectrum of MUH phenomena.

Myositis in Lewis rats induced by the superantigen Staphylococcal enterotoxin A.

The aetiology of inflammatory myopathies is not clearly known. A predominance of activated Cd8+ T lymphocytes in inflammatory infiltrates has already been detected. Superantigens activate lymphocytes in an oligoclonal manner. In the present investigation, we investigated local effects after injection of the superantigen (Sag) Staphylococcus enterotoxin A (SEA) in the quadriceps femoris muscle of Lewis rats. Histopathology and gene expression profiling was performed after injection of SEA or saline (control group) after one, three and 10 days. Histology revealed focal myositis predominated by Cd8+ T lymphocytes with a perimysial, endomysial and perivascular distribution, peaking 3 days after SEA injection. Using DNA microarray analysis (Affymetrix Rat Genome 230 2.0) genes that were differentially over-expressed at least 15 times at days one, three or ten after SEA injection were further analysed. One day after SEA injection over-expressed genes were related to the immune response (e.g. Fcnb, CD8a) but also to cell proliferation, differentiation and migration (e.g. Mpp2). Three days after SEA injection, differentially overexpressed genes were mainly related to the immune reaction with a clear signature for a Cd8+ T lymphocyte response (e.g. Cd3d, Cd8, Prf1, Gzmb). Ten days after SEA injection, the differentially overexpressed genes were again associated with the immune reaction (e.g. Cd3d, Il2) but also with regenerative processes and wound healing (e.g. Tgfa, Tpm1, Ripply1). The inflammatory response induced by SEA in Lewis rats shares histological and molecular similarities to polymyositis in humans. Therefore, SEA induced myositis can be taken as a new and apt model for polymyositis.

Quantification of surfactant proteins in tears of patients suffering from dry eye disease compared to healthy subjects.

PURPOSE: To quantify and compare the amounts of surfactant proteins SP-A, SP-B, SP-C and SP-D in the tear fluid collected from patients with dry eye syndrome and from individuals with a healthy ocular surface. METHODS: Schirmer strips were used to collect tear fluid from both eyes of 241 volunteers (99 men, 142 women; age range: 18-87 years). Dry eye syndrome was diagnosed by ophthalmologists in 125 patients, whereas the healthy control group comprised 116 individuals. The total protein concentration was determined via Bradford assay. The relative concentration of surfactant proteins SP-A through -D was measured by enzyme-linked immuno-sorbent assay (ELISA). RESULTS: The mean relative concentrations of SP-A, SP-C and SP-D were significantly higher in the dry eye group as compared to the healthy controls (p<0.05, one-way ANOVA). SP-B was also detected at a higher concentration in the dry eye group, but the difference to the control group was not statistically significant. CONCLUSIONS: The upregulation of SP-A and SP-D in the dry eye group is probably related to these proteins' known antimicrobial and immunomodulatory effects at the ocular surface. It may represent a pathophysiological response to the inflammatory condition of the ocular surface in dry eye. The upregulation of SP-B and SP-C may represent an effort of the lacrimal system to reduce surface tension and thus to counteract the increased tendency of the tear film to tear in dry eye.

Motor unit potentials of the erector spinae muscle by concentric needle electromyography.

INTRODUCTION: The needle electromyography (EMG) serves to supply additional information in patients with suspected neuromuscular disorders. We aimed to provide motor unit potential (MUP) data by concentric needle EMG in the erector spinae (ES) in comparison with biceps brachii (BB) and lateral vastus (LV). METHODS: Electromyography MUP data (n) were obtained in ES (517), BB (539), and LV (627) in 32 healthy volunteers (16f). RESULTS: Motor unit potential data: amplitude (µV) 393 ± 174 (ES), 375 ± 162 (BB), and 577 ± 304 (LV); duration (ms) 10.4 ± 2.4 (ES), 10.1 ± 2.1 (BB), and 11.1 ± 2.3 (LV), area (µV × ms) 585 ± 327 (ES), 538 ± 267 (BB), and 881 ± 492 (LV); phase number 3.23 ± 0.94 (ES), 2.98 ± 0.76 (BB), and 3.19 ± 0.81 (LV); size index 0.60 ± 0.56 (ES), 0.51 ± 0.53 (BB), and 0.96 ± 0.55 (LV). LV displayed higher values (p at least <.001) for MUP amplitude, duration, area, and size index as compared to both, BB and ES. CONCLUSION: Concentric needle EMG investigations in healthy adult human subjects revealed similar MUP parameters in the ES and BB muscles, while in the LV muscle MUP amplitude, duration, area, and size index were significantly larger. Different neuromuscular disorders display a predominant involvement of proximally located muscles such as truncal muscles. The present results given here may facilitate the diagnosis of neuromuscular disorders.

Dysautonomic polyneuropathy as a variant of chronic inflammatory "demyelinating" polyneuropathy?

This report describes the clinical course over almost one decade of a male patient presenting with immune-mediated pure autonomic neuropathy resembling a distinct variant of chronic dysimmune polyneuropathies. We suppose autoantibodies directed against epitopes on autonomic axons or neurons causative for the symptoms.

[Each person has to make their own individual decision - arguments for physician assisted suicide]. / Jeder Mensch muss eine individuelle Entscheidung treffen dürfen.

Since November 2015, businesslike assisted suicide is punishable in Germany. But who acts businesslike? The majority of the German population prefers to make own decisions about the circumstances of their arriving death, and many of them would also accept (physician) assisted suicide if necessary. Only a minority of physicians plead for prohibiting assisted suicide in general. In the end everyone should be able to take position on his own. No one is obliged to use or execute assisted suicide.

Schirmer strip vs. capillary tube method: non-invasive methods of obtaining proteins from tear fluid.

Human tear fluid is a complex mixture containing over 500 solute proteins, lipids, electrolytes, mucins, metabolites, hormones and desquamated epithelial cells as well as foreign substances from the ambient air. Little is known to date about the function of most tear components. The efficient and gentle collection of tear fluid facilitates closer investigation of these matters. The objective of the present paper was to compare two commonly used methods of obtaining tear fluid, the capillary tube and Schirmer strip methods, in terms of usefulness in molecular biological investigation of tear film. The comparative protein identification methods Bradford and Western Blot were used in the analyses to this end. The surfactant proteins (SP) A-D recently described as present on the eye surface were selected as the model proteins. Both methods feature sufficient uptake efficiency for proteins in or extraction from the sampling means used (capillary tube/Schirmer strip). The total protein concentration can be determined and the proteins in the tears can be detected - besides the hydrophilic SP-A and D also the non-water-soluble proteins of smaller size such as SP-B and C. Thus both methods afford a suitable basis for comparative analysis of the physiological processes in the tear fluid of healthy and diseased subjects. On the whole, the Schirmer strip has several advantages over the capillary tube.

Functional relationship between cationic amino acid transporters and beta-defensins: implications for dry skin diseases and the dry eye.

The ocular surface, constantly exposed to environmental pathogens, is particularly vulnerable to infection. Hence an advanced immune defence system is essential to protect the eye from microbial attack. Antimicrobial peptides, such as beta-defensins, are essential components of the innate immune system and are the first line of defence against invaders of the eye. High concentrations of L-arginine and L-lysine are necessary for the expression of beta-defensins. These are supplied by epithelial cells in inflammatory processes. The limiting factor for initiation of beta-defensin production is the transport of L-arginine and L-lysine into the cell. This transport is performed to 80% by only one transporter system in the human, the y(+)-transporter. This group of proteins exclusively transports the cationic amino acids L-arginine, L-lysine and L-ornithine and is also known under the term cationic amino acid transporter proteins (CAT-proteins). Various infections associated with L-arginine deficiency (for example psoriasis, keratoconjuctivitis sicca) are also associated with an increase in beta-defensin production. For the first time, preliminary work has shown the expression of human CATs in ocular surface epithelia and tissues of the lacrimal apparatus indicating their relevance for diseases of the ocular surface. In this review, we summarize current knowledge on the human CATs that appear to be integrated in causal regulation cascades of beta-defensins, thereby offering novel concepts for therapeutic perspectives.