Caregiver burden and health-related quality of life in idiopathic dystonia patients under botulinum toxin treatment: a cross-sectional study.

Dystonia is a chronic movement disorder that is associated with a reduction in health-related quality of life (HR-QoL) and restriction of activities of daily living. Botulinum neurotoxin (BT) improves disease-specific HR-QoL by reducing abnormal movements, postures, and pain. We examined the burden of the corresponding primary caregiver as a potential important factor for disease management and HR-QoL of dystonia patients under treatment with BT. 114 patients with focal, segmental, or generalized dystonia were recruited, together with 93 corresponding caregivers, whose burden was investigated using the Caregiver Burden Inventory. In addition, all participants were assessed for cognitive impairment, depression, anxiety, alexithymia, and HR-QoL. Only a small proportion of caregivers suffered from caregiver burden. Despite BT therapy, patients' HR-QoL was decreased compared to the age-matched general German population. Psychological symptoms, notably anxiety, and depression correlated significantly with reduced HR-QoL. Our data imply that caregiver burden emerged to be an issue in subgroups of dystonia patients. Furthermore, HR-QoL of dystonia patients is reduced even under optimized BT treatment in a specialized center.

Dyspnea in amyotrophic lateral sclerosis: The Dyspnea-ALS-Scale (DALS-15) essentially contributes to the diagnosis of respiratory impairment.

BACKGROUND: Dyspnea is a cardinal but often underestimated symptom in amyotrophic lateral sclerosis (ALS). The newly developed Dyspnea-ALS-Scale (DALS-15) is highly relevant for therapeutic decisions because dyspnea is a separate criterion to consider noninvasive ventilation (NIV) in ALS. In comparison to the limited effects of neuroprotective compounds, NIV has the greatest impact on survival and improves quality of life. OBJECTIVE: To investigate whether dyspnea corresponds to parameters of respiratory status mainly used in clinical neurological practice. We also investigated if the DALS-15 could help identify patients for consideration of NIV in whom neither spirometry nor blood gas parameters indicate the need for NIV (forced vital capacity (FVC) < 50% or probable <75%, pCO2 ≥45  mmHg). METHODS: Seventy ALS patients with dyspnea according to the DALS-15 obtained blood gas analysis and spirometry (FVC in sitting and supine positions). The supine decline in FVC was calculated. RESULTS: There was no linear relationship between dyspnea and spirometry as well as blood gases. 83% of our patients had an upright FVC still greater than 50% and no daytime hypercapnia. CONCLUSIONS: Our study clearly shows that dyspnea can occur independently of objective indicators of respiratory impairment like spirometry or blood gases. Hence, the DALS-15 covers another aspect of respiratory impairment than these tests and refers to the subjective component of respiratory impairment. It detects dyspnea in a considerable proportion of patients in whom NIV should thus be considered although their spirometric and blood gas results do not point towards NIV. The DALS-15 therefore may help to improve the stratification of patients with respiratory impairment for more efficient symptom management and timely coordination of care.

Diagnostic criteria for amyotrophic lateral sclerosis: A multicentre study of inter-rater variation and sensitivity.

OBJECTIVE: This study assesses inter-rater agreement and sensitivity of diagnostic criteria for amyotrophic lateral sclerosis (ALS). METHODS: Clinical and electrophysiological data of 399 patients with suspected ALS were collected by eleven experienced physicians from ten different countries. Eight physicians classified patients independently and blinded according to the revised El Escorial Criteria (rEEC) and to the Awaji Criteria (AC). Inter-rater agreement was assessed by Kappa coefficients, sensitivity by majority diagnosis on 350 patients with follow-up data. RESULTS: Inter-rater agreement was generally low both for rEEC and AC. Agreement was best on the categories "Not-ALS", "Definite", and "Probable", and poorest for "Possible" and "Probable Laboratory-supported". Sensitivity was equal for rEEC (64%) and AC (63%), probably due to downgrading of "Probable Laboratory-supported" patients by AC. However, AC was significantly more effective in classifying patients as "ALS" versus "Not-ALS" (p < 0.0001). CONCLUSIONS: Inter-rater variation is high both for rEEC and for AC probably due to a high complexity of the rEEC inherent in the AC. The gain of AC on diagnostic sensitivity is reduced by the omission of the "Probable Laboratory-supported" category. SIGNIFICANCE: The results highlight a need for initiatives to develop simpler and more reproducible diagnostic criteria for ALS in clinical practice and research.

[Provision of assistive devices in amyotrophic lateral sclerosis. Analysis of 3 years case management in an internet-based supply network]. / Hilfsmittelversorgung bei der amyotrophen Lateralsklerose. Analyse aus 3 Jahren Fallmanagement in einem internetunterstützten Versorgungsnetzwerk.

BACKGROUND: The provision of assistive devices (PAD) is a key element of care in amyotrophic lateral sclerosis (ALS). Since 2011, assistive devices (AD) have been coordinated in an internet-supported care network at university-based ALS centers in Berlin, Bochum, Hannover and Jena. The digitization of PAD processes has facilitated the evaluation of real-life ALS care. OBJECTIVES: Orthotics (OT), augmentative and alternative communication (AAC), supported treadmill (ST) and powered wheelchair (PW) were the PAD groups analyzed for delivery rates (proportion of delivered AD vs. medically indicated AD), rejection by patients and payers and latency of provision of care. RESULTS: Between June 2011 and October 2014 a total of 1479 patients and 12,478 AD were coordinated, among which 3313 PAD were related to OT, AAC, ST or EM. The median delivery rate was 64.3 %. The mean rejection rate by patients was 9.8 % (OT 5.4 %, AAC 9.8 %, ST 10.2 % and PW 15.6 %). Marked differences were noted in the rejection rate by payers and in care provision latency: OT (16.2 %, 68 days, n = 734), AAC (30.4 %, 96 days, n = 392), ST (34.8 %, 113 days, n = 164) and PW (35.6 %, 129 days, n = 259). Analysis of rejection rates showed significant differences among insurers. CONCLUSION: Only two thirds of the medically indicated AD reached the patients. Rejection rates by patients and payers and latency of provision of care were high. The PAD can substantially vary among health insurance companies. The establishment of consented criteria for PAD and their integration into treatment regimens and guidelines are crucial tasks for the future.

Prevalence and prognostic impact of comorbidities in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is characterized by rapidly progressive paralysis of striated muscles due to the loss of upper and lower motor neurons. The disease leads to death within 2-5 years, mainly due to respiratory failure. The pathogenesis of ALS is still unexplained for the most part. In this study, we aimed to determine the prevalence of different cardiovascular, metabolic, and neuropsychiatric comorbidities in a large ALS cohort and to evaluate their influence on the disease course. METHODS: A cohort of 514 patients with ALS of our ALS outpatient clinic was investigated retrospectively with reference to known prognostic factors and comorbidities. The prevalence of concomitant diseases was compared with the data from the German general population. Uni- and multivariate survival analyses were performed using the Cox proportional hazards model and Kaplan-Meier analysis. RESULTS: The prevalence of cardiovascular diseases and cardiovascular risk factors was significantly lower in patients with ALS compared to the German general population, whilst the prevalence of dementia, parkinsonism, and depressive symptoms was significantly higher in the ALS cohort. None of the investigated comorbidities had an influence on the disease course or on the survival of patients. CONCLUSIONS: Persons with cardiovascular diseases or risk factors seem to be at lower risk of ALS. Although these diseases are apparently somehow protective regarding ALS susceptibility, their presence did not modify disease progression and survival in patients with ALS. Our study further confirms the well-known continuum between ALS and dementia. It also suggests a link with other neurodegenerative diseases such as Parkinson's disease.

[Carpal tunnel syndrome in children with mucopolysaccharidosis type 1H: diagnosis and therapy in an interdisciplinary centre]. / Karpaltunnelsyndrom bei Kindern mit Mukopolysaccharidose Typ 1H. Diagnostik und Therapie im Rahmen eines interdisziplinären Zentrums.

Carpal tunnel syndrome is common in children with mucopolysaccharidosis type 1H (MPS type 1H). Clinical signs of carpal tunnel syndrome are frequently absent in these children and it is often very difficult to perform and interpret neurophysiological investigations. In this article we wish to present our experience and results regarding the diagnosis and postoperative results after decompression of the median nerve.In an interdisciplinary set-up we are currently treating 11 MPS type 1H children following blood stem cell transplantation. 7 patients were operated 12 times (5 bilateral operations) because of a carpal tunnel syndrome (age at the time of operation 83,3 months, (43-143 months), 2 male, 5 female). 6 patients had a follow up after 23,7 months (9-59 months). 6 patients had a histological analysis of the flexor retinaculum. Three patients had a postoperative neurophysiological investigation.Each of the operated patients had at least 1 preoperative clinical sign of a carpal tunnel syndrome. We found at least 1 pathological finding in motor and sensory nerve conduction studies in each patient. 6 of the 7 children operated on were symptom-free at postoperative follow-up. 1 of the 3 patients with a postoperative neurophysiological follow up showed a deterioration of the nerve conduction studies. This patient was free of symptoms postoperatively. Biopsy of the flexor retinaculum confirmed abundant proteoglycan deposition. We had neither postoperative complications nor were revisional operations necessary.The Diagnosis of a carpal tunnel syndrome in children with MPS Typ 1H needs a thorough medical history, the correct interpretation of the clinical symptoms and sophisticated nerve conduction studies. Wether the improvement of the postoperative clinical situation lasts has to be evaluated in a long term investigation especially because in one patient in our group we saw a deterioration of the nerve conduction studies postoperatively.

Long-term treatment of spasticity with botulinum toxin type A: an analysis of 1221 treatments in 137 patients.

OBJECTIVES: Spasticity is a complex disorder that causes significant disability in affected patients. We here present long-term results of botulinum toxin type A (BoNT-A) treatment in spasticity of various etiologies in the upper and lower limbs. PATIENTS AND METHODS: We evaluated long-term results of BoNT-A treatment with Dysport and Botox for up to 12 years in 137 patients with spasticity of various etiologies. The focus was laid on efficacy, dosage, safety and side effects over time in a retrospective analysis of the database of our movement disorder clinic. RESULTS: The mean clinical benefit, latency and duration of response were comparable for both products. Side effects were generally mild and comparable for the two products. We found a significant negative correlation between time from onset of spasticity to start of BoNT-A treatment and degree of improvement after treatment. CONCLUSION: Our data confirm the safety and efficacy of BoNT-A treatment of spasticity of different etiologies over a long period of time. Furthermore, the data imply that BoNT-A treatment should be started early after appearance of spasticity to obtain better treatment response.

A long-term follow-up of botulinum toxin A in cervical dystonia.

OBJECTIVE: Cervical dystonia (CD) is the most common form of adult-onset focal dystonia, and botulinum toxin A (BoNT-A) has become the first-line treatment for this condition. METHODS: In this work, we present data of 207 CD patients treated with BoNT-A for 6.7 +/- 3.5 years. One hundred and sixty-three patients were treated with Dysport (mean dose, 389 +/- 144 U) and 44 with Botox (mean dose, 145 +/- 44 U). RESULTS: The mean clinical benefit, based on a 0-3 scale (0=no effect, 1=slight, 2=moderate and 3=marked improvement) was similar for Dysport (2.5 +/- 0.3) and Botox (2.2 +/- 0.4). Adverse events were mild and similar for both products. Fewer than 2% of the patients developed neutralizing antibodies. DISCUSSION: These data confirm the efficacy and safety of BoNT-A treatment in CD over an extended period of up to 14 years.

[Amyotrophic lateral sclerosis. Current clinical trials and underlying pathomechanisms]. / Amyotrophe Lateralsklerose. Aktuelle klinische Studien und ihr pathogenetischer Hintergrund.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to death after 3 to 5 years. The glutamate antagonist Riluzole currently is the only drug with marginal therapeutic benefit, but its effect on survival is modest, with an average increase of only 3-4 months. Therefore symptomatic treatment still is the most important. Further neuroprotective agents are currently under investigation, both in transgenic animal models of ALS and clinical trials in ALS patients. This review summarizes the current state of clinical studies in ALS patients in the context of underlying therapeutic mechanisms.

EFNS task force on management of amyotrophic lateral sclerosis: guidelines for diagnosing and clinical care of patients and relatives.

Despite being one of the most devastating diseases known, there is little evidence for diagnosing and managing patients with amyotrophic lateral sclerosis (ALS). Although specific therapy is lacking, correct early diagnosis and introduction of symptomatic and specific therapy can have a profound influence on the care and quality of life of the patient and may increase survival time. This document addresses the optimal clinical approach to ALS. The final literature search was performed in the spring of 2005. Consensus recommendations are given graded according to the EFNS guidance regulations. Where there was lack of evidence but consensus was clear we have stated our opinion as good practice points. People affected with possible ALS should be examined as soon as possible by an experienced neurologist. Early diagnosis should be pursued and a number of investigations should be performed with high priority. The patient should be informed of the diagnosis by a consultant with a good knowledge of the patient and the disease. Following diagnosis, the patient and relatives should receive regular support from a multidisciplinary care team. Medication with riluzole should be initiated as early as possible. PEG is associated with improved nutrition and should be inserted early. The operation is hazardous in patients with vital capacity < 50%. Non-invasive positive pressure ventilation improves survival and quality of life but is underused. Maintaining the patients ability to communicate is essential. During the entire course of the disease, every effort should be made to maintain patient autonomy. Advance directives for palliative end of life care are important and should be fully discussed early with the patient and relatives respecting the patients social and cultural background.

Reconstitution of the erythrocyte anion transport system: recent progress.

The anion transport system of the human erythrocyte membrane was reconstituted in phosphatidylcholine vesicles by a new procedure. The reconstituted system shows all major properties of the sulfate transport system found in the erythrocyte membrane (Scheuring, U., K. Kollewe, W. Haase, and D. Schubert: J. Membrane Biol. 90, 123-135 (1986)). Modifications of the reconstitution method have now led to increased values of the internal volumes of the protein-lipid vesicles and of the average turnover number of the transport protein (which is now larger than in the erythrocyte membrane). Gel filtration on Sephacryl S-1000 has allowed the isolation of vesicles of a narrow size distribution.

A new method for the reconstitution of the anion transport system of the human erythrocyte membrane.

The anion transport protein of the human erythrocyte membrane, band 3, was solubilized and purified in solutions of the non-ionic detergent Triton X-100. It was incorporated into spherical lipid bilayers by the following procedure: Dry phosphatidylcholine was suspended in the protein solution. Octylglucopyranoside was added until the milky suspension became clear. The sample was dialyzed overnight against detergent-free buffer. Residual Triton X-100 was removed from the opalescent vesicle suspension by sucrose density gradient centrifugation and subsequent dialysis. Sulfate efflux from the vesicles was studied, under exchange conditions, using a filtration method. Three vesicle subpopulations could be distinguished by analyzing the time course of the efflux. One was nearly impermeable to sulfate, and efflux from another was due to leaks. The largest subpopulation, however, showed transport characteristics very similar to those of the anion transport system of the intact erythrocyte membrane: transport numbers (at 30 degrees C) close to 20 sulfate molecules per band 3 and min, an activation energy of approx. 140 kJ/mol, a pH maximum at pH 6.2, saturation of the sulfate flux at sulfate concentrations around 100 mM, inhibition of the flux by H2DIDS and flufenamate (approx. KI-values at 30 degrees C: 0.1 and 0.7 microM, respectively), and "right-side-out" orientation of the transport protein (as judged from the inhibition of sulfate efflux by up to 98% by externally added H2DIDS). Thus, the system represents, for the first time, a reconstitution of all the major properties of the sulfate transport across the erythrocyte membrane.