In a large cohort of 1034 patients with the diagnosis of definite or probable amyotrophic lateral sclerosis (ALS), the association of forced vital capacity (FVC) at baseline with (a) time to progression of 20 points in Appel ALS (AALS) score or (b) tracheostomy free survival was investigated. The median survival of ALS patients with baseline FVC<75% was 2.91 years, compared with 4.08 years for patients with baseline FVC >75% (p<0.001). Patients with baseline FVC <75% progressed more rapidly (taking 8.0 months to progress 20 AALS points) compared with patients with baseline FVC >75% (10.0 months, p<0.001). Moreover, FVC at first examination was identified as a significant predictor of survival and disease progression in both univariate and multivariate Cox regression models, after adjustment for age, sex, site of onset, diagnostic delay, riluzole therapy, and use of bilateral positive airway pressure and percutaneous endoscopic gastrostomy (p<0.001). We conclude that a single FVC value obtained at an initial visit may serve as a clinically meaningful predictor of survival and disease progression in ALS.

IntroductionThe Glasgow Coma Scale (GCS) is the most widely used scoring system for comatose patients in intensive care. Limitations of the GCS include the impossibility to assess the verbal score in intubated or aphasic patients, and an inconsistent inter-rater reliability. The FOUR (Full Outline of UnResponsiveness) score, a new coma scale not reliant on verbal response, was recently proposed. The aim of the present study was to compare the inter-rater reliability of the GCS and the FOUR score among unselected patients in general critical care. A further aim was to compare the inter-rater reliability of neurologists with that of intensive care unit (ICU) staff.MethodsIn this prospective observational study, scoring of GCS and FOUR score was performed by neurologists and ICU staff on 267 consecutive patients admitted to intensive care.ResultsIn a total of 437 pair wise ratings the exact inter-rater agreement for the GCS was 71%, and for the FOUR score 82% (P = 0.0016); the inter-rater agreement within a range of ± 1 score point for the GCS was 90%, and for the FOUR score 92% (P = ns.). The exact inter-rater agreement among neurologists was superior to that among ICU staff for the FOUR score (87% vs. 79%, P = 0.04) but not for the GCS (73% vs. 73%). Neurologists and ICU staff did not significantly differ in the inter-rater agreement within a range of ± 1 score point for both GCS (88% vs. 93%) and the FOUR score (91% vs. 88%).ConclusionsThe FOUR score performed better than the GCS for exact inter-rater agreement, but not for the clinically more relevant agreement within the range of ± 1 score point. Though neurologists outperformed ICU staff with regard to exact inter-rater agreement, the inter-rater agreement of ICU staff within the clinically more relevant range of ± 1 score point equalled that of the neurologists. The small advantage in inter-rater reliability of the FOUR score is most likely insufficient to replace the GCS, a score with a long tradition in intensive care.

The identification of younger age, limb site of onset and longer diagnostic delay as predictors of prolonged survival in ALS clinic population supports the findings of several, earlier studies that were based on smaller groups of patients. More significantly, several additional variables assessed at the first examination predict longer survival: lower baseline AALSS, lower AALSS- preslope and higher baseline FVC. All of these parameters are of value in patient management and in clinical trial development.

We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease.

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, and Switzerland).