Ectopic Motor Unit Activity in Motor Neuron Disease

Abstract

Motor neuron disease (MND) is characterized by the progressive loss of motor neurons that control voluntary muscles. Due to its progressive nature, the muscles gradually lose their function leading to paralysis and, ultimately, death. The most common variant of MND is amyotrophic lateral sclerosis (ALS). Of all the people diagnosed with ALS, 50% die within approximately two to three years after their first symptoms arise and only about 20% live longer than 5 years [1]. Onset is typically around 50 - 70 years of age, but in some patients the onset may be much earlier, around the age of 20 - 30 years. Incidence is higher among men than women, estimated at 2:1 [2-4]. The first symptoms usually occur in the limbs, but muscle weakness may also begin in the bulbar region. Progressive weakness of the respiratory muscles leading to respiratory failure is the most common cause of death. Before the first clinical signs of muscle weakness become apparent, more than 50% of the motor neurons innervating a muscle may already be lost [5]. In the Netherlands, approximately 1,700 people (prevalence 10.3 per 100,000) suffer from ALS [2]. Every year, approximately 500 people (incidence 2.8 per 100,000) in the Netherlands are diagnosed with ALS [2], and about the same number of persons dies every year. In comparison, approximately 570 people in the Netherlands died in traffic accidents in 2013 [6]. The term ALS was first described in 1874 by Jean-Martin Charcot [7]. Despite the tremendous technological progress that has been made in the last 140 years and despite numerous studies that have been conducted to unravel the mechanisms that may cause this deadly disease, relatively little is known about the mechanisms that cause ALS and the progressive degeneration of motor neurons is often unpredictable. The great majority of patients is classified as having sporadic ALS, and only 5 - 10% of the patients have a familial history of this disease. A complex interaction between genetic and environmental factors is believed to contribute to the development of the disease. Several genes have been identified and their discovery gave new insights into the underlying pathophysiological mechanisms. At present, no cure is available, and the only approved and widely used medication (Riluzole) can only marginally slow down the progression of the disease by approximately 3 months [8]. In this section, first the concept of a motor unit as a crucial component being affected by MND will be introduced, together with some basics on how motor units are affected in this condition. Next, one of the most obvious clinical signs, fasciculations, will be discussed, followed by the varying clinical phenotypes. Subsequently, the difficulties in the diagnostic process and the prognosis will be described. Currently, both can be very difficult, especially in the early stages of the disease, even with a thorough clinical and electrodiagnostic examination.