An approach to non–motor symptoms of patients with amyotrophic lateral sclerosis : an update on clinical management

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult–onset, relentlessly progressive motor neuron disease characterized by dominantly involving cortical neurons in frontotemporal lobe and motor neurons in brainstem and spinal cord, but ultimately leading to multisystem neurodegeneration. As motor symptoms progress, muscle wasting with weakness in the limbs and trunk, bulbar palsy, and respiratory muscle paralysis appear. In addition, non–motor symptoms such as cognitive decline, mood disorders, pseudobulbar affect, sleep disturbances, fatigue, pain, and weight loss due to hypermetabolism may occur. However, each symptom may not occur in all cases. Disease–associated hypometabolism and multisystem involvement, particularly in the advanced stages after the introduction of tracheostomy invasive ventilation (TIV), may lead to other non–motor symptoms including autonomic disturbance, glucose intolerance, and macroglossia. Although lack of sufficient evidence in therapeutic intervention and underlying pathomechanism essentially limit concrete recommendations, I will review here an update on clinical management of non–motor symptoms in patients with ALS.