Prevalence and impact of comorbidities in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of multifaceted nature and variable progression that poses considerable challenges to our understanding of its evolution and interplay with different comorbid conditions. The etiopathogenesis of ALS is still unexplained and multimorbidity is common, but its influence on the ALS susceptibility and disease course is a matter of discussion. This study using medical databases tries to find diseases associated with ALS and their impact on disease onset and progression. Diseases associated with the risk of ALS include diabetes mellitus, dyslipidemias and cardiovascular comorbidities that may play an important role in the prognosis of ALS. Hypometabolic disorders and cardiovascular diseases may have a protective effect on ALS incidence, while coronary heart disease and hypertension have a negative effect on disease progression. Other comorbidities include Parkinson disease, TDP-43 pathology, progressive supranuclear palsy, progressive aphasia, myasthenia gravis, cancer and autoimmune disorders, while there is no evidence for a shared genetic background of common risk variants in ALS and multiple sclerosis. Among non-motor manifestations of ALS, cognitive and behavioral impairments are important. Other comorbidities include sleep disorders, traumatic encephalopathy, sarcoidosis, prionopathies, schizophrenia, cervical spondylotic myelopathy, psoriasis and others. The tremendous heterogeneity of concomitant pathologies and comorbidities observed across the ALS spectrum may be caused by a complex interplay between genetic, pathogenetic, inflammatory and other risk factors that are still poorly understood. Further research should provide increasing insight into their relationship with motor system disorders in order to find better diagnostic tools and probable effective therapies for these disease-modifying comorbidities.