What are Motor Neuron Diseases (MND)?

From the Guidelines

Motor neuron diseases are a group of progressive neurological disorders characterized by the degeneration and death of motor neurons, leading to muscle weakness, atrophy, and eventually paralysis, with Amyotrophic Lateral Sclerosis (ALS) being the most common type. These diseases cause the selective affection of motor neurons, the nerve cells responsible for controlling voluntary muscle movement. The most common type, ALS, is a complex neurodegenerative disorder characterized by progressive loss of motor neurons, resulting in progressive atrophy of skeletal muscles, including the respiratory muscles, as described in the ESPEN guideline on clinical nutrition in neurology 1. Symptoms typically begin with muscle weakness, cramps, twitching, and difficulty with fine movements, progressing to more severe disability affecting speech, swallowing, and breathing.

Some of the key factors associated with the risk of malnutrition in ALS patients include the degeneration of bulbar neurons, which manifests as difficulty in chewing, oral preparation, time required to complete a meal, and dysphagia 1. While there is no cure for motor neuron diseases, treatments focus on symptom management and improving quality of life. Medications like riluzole and edaravone for ALS can modestly slow disease progression. Multidisciplinary care involving neurologists, physical therapists, respiratory specialists, and speech therapists is essential. The diseases occur when motor neurons in the brain and spinal cord deteriorate due to genetic mutations, protein misfolding, oxidative stress, or other mechanisms that disrupt normal cellular function, though the exact causes remain incompletely understood for many forms of MND.

Key aspects of motor neuron diseases include:

• Progressive loss of motor neurons
• Muscle weakness, atrophy, and paralysis
• Difficulty with speech, swallowing, and breathing
• Malnutrition due to bulbar neuron degeneration
• Treatment focusing on symptom management and quality of life improvement
• Multidisciplinary care for optimal patient outcomes, as supported by the ESPEN guideline on clinical nutrition in neurology 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE Riluzole tablets is indicated for the treatment of amyotrophic lateral sclerosis (ALS).

Motor neuron diseases are not directly defined in the provided drug labels. However, Amyotrophic Lateral Sclerosis (ALS) is mentioned as an indication for the use of Riluzole tablets. ALS is a type of motor neuron disease.

• Key points:
  • Riluzole tablets are indicated for the treatment of ALS.
  • ALS is a type of motor neuron disease.
• Conclusion: While the drug labels do not directly define motor neuron diseases, they imply that ALS is a type of motor neuron disease, and Riluzole is used to treat ALS 2.

From the Research

Definition and Overview of Motor Neuron Diseases

• Motor neuron diseases (MNDs) are rare and frequently fatal neurological disorders characterized by the slow death of motor neurons within the brainstem and spinal cord regions 3.
• MNDs are primarily caused by genetic mutations, with over 100 different mutant genes discovered in humans thus far 3.
• The diseases affect motor neurons in the brain, brainstem, and spinal cord, leading to progressive muscle weakness, muscle atrophy, and eventual paralysis 4, 5.

Types of Motor Neuron Diseases

• Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motor neuron disease, resulting in the destruction and ultimate death of neurons that control muscles 4, 6.
• Other types of MNDs include spinal muscular atrophy (SMA), spinal bulbar muscle atrophy (SBMA), and hereditary spastic paraplegia (HSP) 3.
• ALS is a clinical diagnosis without a unique biomarker, and its diagnosis relies on electrodiagnostic examinations, such as electromyography (EMG) and nerve conduction studies (NCS) 4.

Symptoms and Treatment

• MNDs affect patients' speech, mobility, and respiratory function, and care of patients with MND is complex and involves various healthcare professionals and services 7.
• The current mainstay of treatment for ALS remains symptom management and palliation, particularly in the setting of a multidisciplinary clinic 6.
• There is a need to discuss symptom management and promote palliative and end of life care from the point of diagnosis to ensure appropriate holistic care is provided 7.

Pathophysiology and Genetics

• The mechanisms for motor neuron degeneration in ALS are not fully understood, but recent studies have identified that the degeneration of motor neurons in ALS is a form of apoptotic cell death 5.
• The discovery of genes associated with familial and sporadic ALS has provided a deeper understanding of the mechanisms of motor neuron failure in ALS 6.
• Areas of particular interest include the role of transactive response DNA-binding protein 43 and other RNA-processing proteins in the development of disease 6.