Motor neuron disease: Causes, classification and treatments

Motor Neuron Disease (MND) is the most common chronic neurodegenerative disorder of the motor system in adults. It is a relatively rare disease with a reported population incidence of between 1.5 and 2.5 per 100,000 per year worldwide. The only established risk factors are age and family history, with age being the most important factor. The disease occurs throughout adult life, with the peak incidence between 50 to 75 years of age. MND occurs more commonly in men than in women in a ratio of 3:2. MND is characterized by the loss of motor neurons in the cortex, brain stem, and spinal cord, manifested by upper and lower motor neuron signs and symptoms affecting bulbar, limb, and respiratory muscles. Death usually results from respiratory failure and follows on average two to four years after onset, but some may survive for a decade or more. Whilst the aetiology of MND is unknown, current evidence suggests that multiple interacting factors contribute to motor neuron injury in MND. The working hypothesis is that MND, like many other chronic diseases, is a complex genetic condition and the relative contribution of individual environmental and genetic factors is likely to be small. The three key pathogenetic hypotheses are genetic factors, oxidative stress and glutamatergic toxicity, which result in damage to critical target proteins such as neurofilaments and organelles such as mitochondria. The symptoms in MND are diverse and challenging and include weakness, spasticity, limitations in mobility and activities of daily living, communication deficits and dysphagia, and in those with bulbar involvement, respiratory compromise, fatigue and sleep disorders, pain and psychosocial distress. Hence, the burden of disease and economic impact of MND upon patients, their caregivers (often family members) and on society is substantial, often beginning long before the actual diagnosis is made, and increasing with increasing disability and the need for medical equipment and assisted care. At present, the only approved drug treatment for MND in the USA, Australia and in many European countries is riluzole, which is thought to prolong median survival by about two to three months. In the absence of a cure or indeed any medical intervention, which might stop the progression of MND, the management relies mostly on symptomatic, rehabilitative and palliative therapy, which is the focus of this chapter. An update in the symptomatic and disability management of MND is provided, covering the interface between neurology, rehabilitation and palliative care and incorporates issues encountered over the spectrum of disease, including activity and pain related issues, respiratory and dysphagia issues and psychosocial changes. Recent trends, developments and future research in rehabilitation approaches that maintain and restore functional independence and quality of life will be presented