Peter Linke

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.

Thalidomide causes sinus bradycardia in ALS

ObjectiveNeuroinflammation contributes to motor neuron degeneration in ALS. Thalidomide (THL) shows potent anti-inflammatory properties and increased the lifespan in ALS transgenic mice. Thalidomide was therefore suggested as atherapeutic intervention for the treatment of ALS.We conducted a pilot, randomized clinical trial of THL in patients with ALS to assess safety, feasibility, and preliminary estimates of treatment efficacy.MethodsPatients were randomized to THL in combination with riluzole (n = 18) or riluzole alone (n = 19). THL was initiated at 100 mg per day for 6 weeks. Thereafter, the dose was increased every week by 50 mg until reaching the dose of 400 mg per day and planned to continue for another 12 weeks.ResultsWithin 12 weeks of THL treatment, nine THL patients (50%) developed bradycardia defined as a heart rate below 60 beats per minute (bpm) and ranged from 46 to 59 bpm. Mean heart rate dropped by 17 bpm with THL treatment. Severe symptomatic bradycardia of 30 bpm occurred in one patient. A further patient died from sudden unexpected death. The study was terminated prematurely for safety concerns. The secondary outcome variables showed similar results for both groups.ConclusionBradycardia was the most common adverse event of THL treatment in ALS. THL-related bradycardia does not appear to be ALS-specific. It is conceivable, however, that the unexpected frequency and severity of THL-induced bradycardia may be related to subclinical involvement of the autonomic nervous system in ALS. The cardiac toxicity discourages further clinical trials and compassionate use of THL in ALS. ClinicalTrials.gov Identifier: NCT00231140.

Severe loss of appetite in amyotrophic lateral sclerosis patients: online self-assessment study.

Background Undesirable loss of weight is a major challenge in amyotrophic lateral sclerosis (ALS). However, little is known about loss of appetite in ALS patients. Objective We investigated loss of appetite in ALS patients by means of an online self-assessment and whether ALS-related symptoms were associated with it. Methods Loss of appetite in 51 ALS patients was assessed using the Council on Nutrition Appetite Questionnaire (CNAQ). Loss of appetite is defined as a CNAQ-score of 28 or less with a predicted weight loss of at least 5% within 6 months. We developed an Internet portal to facilitate self-assessment. Results Approximately half of the ALS patients (47%, 24/51) suffered from severe loss of appetite; after 6 months this increased to nearly two-thirds (65%, 22/34). An average weight loss of 5% was found in the group with severe loss of appetite as compared to only 2% of patients with normal appetite. Interestingly, loss of appetite was associated with respiratory dysfunction (P=.001, R2=.223). Conclusions Loss of appetite was more common and more severe than expected. It was found to be an independent risk factor for unintended weight loss and may be related to dyspnea. The impact of severe loss of appetite on survival and quality of life should be established in further studies.

Progressive muscle atrophy with hypokalemic periodic paralysis and calcium channel mutation

A family with hypokalemic periodic paralysis (HypoPP) and motor neuron degeneration is reported. In conjunction with HypoPP, the index patient developed progressive muscle atrophy. The calcium channel gene CACNA1S showed a mutation encoding p.R528H, which has been related previously to HypoPP. We propose that CACNA1S mutations may comprise a previously unrecognized genetic risk factor in a greater spectrum of motor unit disorders including amyotrophic lateral sclerosis. Muscle Nerve, 2007

Elective termination of respiratory therapy in amyotrophic lateral sclerosis

BACKGROUND Due to the growing use of artificial respiration in amyotrophic lateral sclerosis (ALS), physicians are increasingly confronted with patients seeking discontinuation of therapy. Yet there are few systematic investigations of the withdrawal of ventilation therapy. PATIENTS AND METHODS In a retrospective investigation of nine German ALS patients, clinical data were recorded from the discontinuation of noninvasive ventilation (n=4) and mechanical ventilation (n=5). RESULTS In cases of residual spontaneous breathing, intensified symptom control of dyspnea and anxiety was possible with intravenous morphine sulfate at a low dose rate (10 mg/h) but high cumulative dose (185-380 mg). The terminal phase after removing the mask was protracted (22:10 h to 28:00 h). In cases of minimal or absent spontaneous breathing the disconnection was realized in deep sedation, which required a moderate total dose of morphine sulfate (120 mg) but a high dosage rate (up to 300 mg/h). The terminal phase in deep sedation was short (15-80 min). CONCLUSION The elective termination of ventilation requires differentiated pharmacologic palliative care. More controlled studies are required in order to establish evidence-based guidelines for the termination of ventilation.

Differences in pain perception during open muscle biopsy and Bergstroem needle muscle biopsy

Purpose Open surgical muscle biopsy (OB) and percutaneous Bergstroem needle muscle biopsy (NB) are equally accepted procedures. However, there are no data comparing intraprocedural pain for both techniques. We designed this prospective trial to test the hypothesis that the less invasive NB causes less intraprocedural pain than OB. Methods In a two-center prospective trial, 33 patients underwent both procedures in one session. All patients quantified intraprocedural pain using the numeric rating scale (NRS). Mean NRS values were calculated along with the difference in NRS values (ΔNRS) between both types of biopsies. Results Mean NRS values were 4.5 (±2.7 standard deviation [SD]) for NB and 3.2 (±2.1) for OB (P=0.02). Of the patients, 57.6% described the ΔNRS as ≤2 NRS points. Regarding the pain categories “mild” (NRS 0–3), “moderate” (NRS 4–7), and “severe” (NRS 8–10), no significant difference was observed between NB and OB. Patients who found NB to be more uncomfortable were more likely to quantify the ΔNRS as >2 NRS points than patients finding OB more uncomfortable. Conclusion Our results do not support the hypothesis that intraprocedural pain in NB is less than in OB. When informing the patient about both types of muscle biopsies, the amount of intraprocedural pain should not serve as a differentiating characteristic.

Elektive Termination der Beatmungstherapie bei der amyotrophen Lateralsklerose@@@Elective termination of respiratory therapy in amyotrophic lateral sclerosis

BACKGROUND Due to the growing use of artificial respiration in amyotrophic lateral sclerosis (ALS), physicians are increasingly confronted with patients seeking discontinuation of therapy. Yet there are few systematic investigations of the withdrawal of ventilation therapy. PATIENTS AND METHODS In a retrospective investigation of nine German ALS patients, clinical data were recorded from the discontinuation of noninvasive ventilation (n=4) and mechanical ventilation (n=5). RESULTS In cases of residual spontaneous breathing, intensified symptom control of dyspnea and anxiety was possible with intravenous morphine sulfate at a low dose rate (10 mg/h) but high cumulative dose (185-380 mg). The terminal phase after removing the mask was protracted (22:10 h to 28:00 h). In cases of minimal or absent spontaneous breathing the disconnection was realized in deep sedation, which required a moderate total dose of morphine sulfate (120 mg) but a high dosage rate (up to 300 mg/h). The terminal phase in deep sedation was short (15-80 min). CONCLUSION The elective termination of ventilation requires differentiated pharmacologic palliative care. More controlled studies are required in order to establish evidence-based guidelines for the termination of ventilation.