C. Münch

Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature.

Background: Neuromyelitis optica (NMO, Devic syndrome) and myasthenia gravis (MG) are rare antibody-mediated autoimmune disorders. Concurrent incidence has been reported in only few patients, mostly non-Caucasians. Objective: To report on ten Caucasian patients with NMO spectrum disorders (NMOSD) and MG and to provide a comprehensive review of the literature. Method: Retrospective study. Results: In total, 26 patients (m:f = 1:12; Caucasian in 12) with MG (generalized in 17) and NMOSD (NMO in 21, longitudinally extensive transverse myelitis in five) were identified from the authors’ own files (n = 10) and the previous literature (n = 16). MG preceded NMOSD in 24/25 cases (96%). AQP4-Ab were tested in 20 patients and were positive in 17 (85%). Twenty out of 25 patients (80%) had been treated with thymectomy or thymic irradiation, which preceded NMOSD in all cases (median latency, 12 years; range, 0.3–32). At last follow-up, complete remission of MG was reported in 15/22 (68%), and MG was well controlled with pyridostigmine in three. Co-existing autoimmune disorders or autoimmune antibodies were reported in 17 patients. Conclusion: Our study demonstrates that i) AQP4-Ab-positive NMOSD are more commonly associated with MG in Caucasians than previously thought; ii) MG precedes NMOSD in most cases, often by more than a decade; iii) NMOSD almost exclusively occur in females with juvenile or early-onset MG; and iv) MG frequently takes an unusually mild course in patients with NMOSD. A history of thymectomy could be a possible risk factor for the later development of NMOSD. We recommend testing for AQP4-Ab in MG patients presenting with atypical motor or optic symptoms.

Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. Recently, missense variants in the angiogenin gene (ANG), an angiogenic factor expressed in ventral horn motor neurons that is up-regulated by hypoxia, have been found in ALS patients of Irish/Scottish, North American, Italian, French and Dutch descent. To investigate the role of ANG in the German population, we screened for mutations by sequencing the entire coding region of the ANG gene in a large sample of 581 German ALS cases and 616 sex- and age-matched healthy controls. We identified two heterozygous missense variants, F(−13)L and K54E, in two German sporadic ALS cases but not in controls. Both missense variants are novel and have not been previously found in ALS cases. Our results suggest that missense variants in the ANG gene play a role in ALS in the German population and provide further evidence to support the hypothesis that angiogenic factors up-regulated by hypoxia are involved in the pathophysiology of ALS.

Online assessment of ALS functional rating scale compares well to in-clinic evaluation: A prospective trial

Abstract Self-assessment of symptom progression in chronic diseases is of increasing importance in clinical research, patient management and specialized outpatient care. Against this background, we developed a secure internet platform (ALShome.de) that allows online assessment of the revised ALS Functional Rating Scale (ALSFRS-R) and other established self-assessment questionnaires. We developed a secure and closed internet portal to assess patient reported outcomes. In a prospective, controlled and stratified study, patients conducted a web-based self-assessment of ALSFRS-R compared to on-site assessment. On-site and online assessments were compared at baseline (n = 127) and after 3.5 months (n = 81, 64%). Results showed that correlation between on-site evaluation and online testing of ALSFRS-R was highly significant (r = 0.96; p < 0.001). The agreement of both capturing methods (online vs. on-site) was excellent (mean interval, 8.8 days). The adherence to online rating was high; 75% of patients tested on-site completed a follow-up online visit (mean 3.5 months, SD 1.7). We conclude that online self-assessment of ALS severity complements the well-established face-to-face application of the ALSFRS-R during on-site visits. The results of our study support the use of online administration of ALSFRS-R within clinical trials and for managing the care of ALS patients.

Contribution of spinal cord biopsy to diagnosis of aquaporin-4 antibody positive neuromyelitis optica spectrum disorder

Longitudinally extensive transverse myelitis is characteristic but not pathognomonic for neuromyelitis optica spectrum disorders (NMOSDs) and may mimic local tumors. In this retrospective study based on a cohort of 175 NMOSD patients we identified seven patients who initially presented with a longitudinally extensive spinal cord lesion and underwent spinal cord biopsy due to magnetic resonance imaging (MRI)-suspected malignancies. Remarkably, routine neuropathology was inconclusive and did not guide the diagnostic process to anti-aquaporin-4 (AQP4)-seropositive NMOSD. Serious postoperative complications occurred in 5/7 patients and persisted during follow-up in 2/7 patients (29%). Considering these sequelae, AQP4-antibody testing should be mandatory in patients with inconclusive longitudinally extensive spinal cord lesions prior to biopsy.

Clinical characteristics and course of dying in patients with amyotrophic lateral sclerosis withdrawing from long-term ventilation.

Abstract Non-invasive ventilation (NIV) or tracheotomy with invasive ventilation (TIV) are treatment options in ALS. However, a proportion of patients receiving long-term ventilation decide to have it withdrawn. The objective of this study was to analyse the clinical characteristics and palliative approaches in ALS patients withdrawing from long-term ventilation (WLTV). In a cohort study, two different palliative concepts in WLTV were studied: (1) augmented symptom control (ASC; sedation not intended) in patients with ventilator-free tolerance; (2) continuous deep sedation (CDS; sedation intended) in patients without ventilator-free tolerance. Results showed that WLTV was realised in 49 ALS patients (NIV = 13; TIV = 36). Mean daily ventilation was 23.4 h. The ALS Functional Rating Scale (ALSFRS-R) was low (5.6 of 48). Forty-one per cent of patients (n = 20) presented with ophthalmoplegia. ASC was performed in 20 patients, CDS in 29 patients. The mean time to death following disconnection was 32 (0.3–164) h during ASC and 0.3 (0.2–0.6) h in CDS. In conclusion, a low ALSFRS-R, high incidence of ophthalmoplegia and extended ventilator dependency were found before WLTV. The presence or absence of ventilator-free tolerance determined the approach to the management of symptoms, the setting for immediate end-of-life care and the course of dying in WLTV.

[Provision of assistive devices in amyotrophic lateral sclerosis. Analysis of 3 years case management in an internet-based supply network].

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.

Hilfsmittelversorgung bei der amyotrophen Lateralsklerose

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.

Provision of assistive technology devices among people with ALS in Germany: a platform-case management approach

Abstract Objective: The procurement of assistive technology devices (ATD) is an essential component of managed care in ALS. The objective was to analyze the standards of care for ATD and to identify challenges in the provision process. Methods: A cohort study design was used. We investigated the provision of 11,364 ATD in 1494 patients with ALS at 12 ALS centers in Germany over four years. Participants were patients that entered a case management program for ATD including systematic assessment of ATD on a digital management platform. Results: Wheelchairs (requested in 65% of patients), orthoses (52%), bathroom adaptations (49%), and communication devices (46%) were the most needed ATD. There was a wide range in the number of indicated ATD per patient: 1 to 4 ATD per patient in 45% of patients, 5 to 20 ATD in 48%, and >20 ATD in 7% of patients. Seventy percent of all requested ATD were effectively delivered. However, an alarming failure rate during procurement was found in ATD that are crucial for ALS patients such as powered wheelchairs (52%), communication devices (39%), or orthoses (21%). Leading causes for not providing ATD were the refusal by health insurances, the decision by patients, and the death of the patient before delivery of the device. Conclusions: The need for ATD was highly prevalent among ALS patients. Failed or protracted provision posed substantial barriers to ATD procurement. Targeted national strategies and the incorporation of ATD indication criteria in international ALS treatment guidelines are urgently needed to overcome these barriers.

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

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.