Neuromuscular and Microvascular Changes in Intrinsic Tongue Muscles of Patients with Various Forms of ALS

Sammanfattning: The study objective was to investigate whether amyotrophic lateral sclerosis (ALS) affects the intrinsic tongue muscles differently when the symptoms begin in cranial or lower limb muscles. Muscle fiber area, myosin heavy chain (MyHC) composition and vascularization were analyzed in the anterior and posterior region of the tongue with immunohistochemistry and morphometric techniques in 7 patients with classical ALS (limb onset) and 5 patients with progressive bulbar ALS (cranial onset). Samples from 5 previously healthy subjects were used as controls. The morphological results were correlated to the clinical data for each patient. The results showed that the ALS samples had various degrees of pathological changes in both the anterior and posterior region of the tongue. The fiber area and number of capillaries around fibers was decreased by approximately 50% compared to controls. In both anterior and posterior regions, there was a shift against fibers co-expressing slow and fast MyHC isoforms. Although both classical and bulbar forms of ALS affected the muscles, there were also important differences between the two. In the bulbar form of ALS, the proportion of MyHCI fibers were decreased, a finding in contrast with classical ALS where MyHCII fibers have been reported to be affected preferentially. The slow contracting MyHCI fibers in the bulbar form of ALS differed also by being better supplied by capillaries. Conclusively, ALS had a large impact on the tongue muscle morphology, but both the form of the ALS and inherent factors seem to influence the disease process.