Israel Medical Association Journal

Background: There is an unmet need for real-world data regarding laboratory results, co-morbidities, and medication use prior to the first symptoms of amyotrophic lateral sclerosis (ALS). Researchers must identify specific subpopulations at risk for developing ALS and understand pathogenic mechanisms preceding the clinical presentation of ALS as well as possible subclinical disease manifestations.

Objectives: To valuate the role of laboratory results, co-morbidities, and medication use prior to the first symptoms of patients with ALS in Israel so that specific subpopulations at risk for developing ALS can be identified and for possible subclinical disease manifestations. To understand pathogenic mechanisms preceding the clinical presentation of ALS.

Methods: At the ALS clinic at Tel Aviv Sourasky Medical Center, 259 ALS patients insured by Maccabi Healthcare Services and seen between January 1998 and December 2017 were included. Comparisons of demographics, co-morbidities, medications taken, history of trauma, and laboratory tests prior to disease onset were performed between patients and 1295 matched controls.

Results: Prior to disease presentation, ALS patients had a higher frequency of hypertension and cardiovascular disease; presented more frequently with trauma and viral infections; more frequently used analgesics, non-steroidal anti-inflammatory drugs, narcotics, antibiotics, and antiviral medications; and had higher creatine kinase levels.

Conclusions: ALS patients showed higher frequency of cardiovascular disease prior to diagnosis, as well as higher frequency of trauma, infections, and pain medication usage.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive death of motor neurons leading to fatal paralysis. The causes of ALS remain unknown; however, evidence supports the presence of autoimmune mechanisms contributing to pathogenesis. Although several environmental factors have been proposed, the only established risk factors are older age, male gender, and a family history of ALS. To date, there are no diagnostic test for ALS, and clinicians rely on the combination of upper motor neuron and lower motor neuron signs in the same body region. The aim of this paper was to provide a comprehensive review of current clinical literature with special focus on the role of autoimmunity in ALS, differential diagnosis, and available therapeutic approaches. Current evidence suggests a contribution of the innate immune system in ALS, with a role of microglial cell activation at the sites of neurodegeneration. The median time from symptom onset to diagnosis of ALS is 14 months, and this time estimate is mainly based on specific clinical signs and exclusion of ALS-like conditions. Several therapeutic approaches have been proposed, including immunosuppressive drugs, to reduce disease progression. Riluzole has been established as the only, although modestly effective, disease modifying therapy, extending mean patient survival by 3to 6 months. Recent advances in understanding the pathophysiology mechanisms of ALS encourage realistic hope for new treatment approaches. To date, the cornerstones of the management of patients with ALS are focused on symptom control, maintaining quality of life and improving survival.