Motor Neuron Disorders (MNDs) are a group of progressive neurological disorders that attack and destroy the upper and lower motor neurons. Motor neurons are the cells that control voluntary essential muscle activity like speaking, walking, breathing, and swallowing. Upper motor neurons send signals from the brain to the medulla or spinal cord. The lower motor neurons send signals from the spinal cord to the muscles of the body.
MNDs occur in both adults and children. In adults, MNDs are more prevalent in men than women with symptoms usually appearing at age 40, with the highest incidence occurring between ages 50-70. In children, especially those with the familial or inherited forms of the disease, symptoms can appear at birth or when the child starts to walk.
Pathogenesis & Clinical Features
Some MNDs are inherited though the causes are unknown. In sporadic MNDs, environmental, toxic, viral or genetic factors may be implicated.
There are no specific tests to diagnose most MNDs, and symptoms vary greatly among individuals. Initially, physical and neurological exams are performed, and depending on the outcome of these, tests to rule out other diseases may follow, including blood & urine tests, electromyography (EMG), MRI, muscle and/or nerve biopsies, transcranial magnetic stimulation (TMS). Some of the more common MNDs include:
Amyotrophic Lateral Sclerosis (ALS)
Also known as Lou Gehrig’s disease. This is a progressive disorder that disrupts the signals to all voluntary muscles. Symptoms usually affect arms, hands, legs and swallowing muscles first. Muscle weakness and atrophy affects both sides of the body. Affected individuals lose strength and ability to move their arms and legs, and to hold the body upright. Other symptoms include spasms, muscle cramps, slurred speech. The disease does not usually impair an individual’s mind or personality though studies suggest that some individuals may develop cognitive problems affecting memory and decision-making. Most cases are sporadic, with only 10% of cases considered familial. 10 genes have been identified to date though these account for a very small number of cases.
Primary Lateral Sclerosis (PLS)
Affects the upper motor neurons of the arms, legs and face. Often, legs are affected first followed by the trunk, arms, and hands, and finally the bulbar muscles. Initially, the legs and arms become stiff, slow and weak resulting in an inability to walk, and difficulty with balance. Speech may become affected as will fine motor coordination. PLS is at times considered a type of ALS but PLS does not affect the lower motor neurons, it has a slow progression rate, and though it’s not considered fatal, quality of life is affected.
Progressive Muscular Atrophy
Affects only the lower motor neurons, and is more prevalent in men than women. The degeneration is slow but progressive and in many cases, the disease will develop into ALS.
Spinal Muscular Atrophy (SMA)
This is an autosomal recessive disorder caused by defects in the SMN1 gene. The degeneration of the lower motor neurons is caused by low levels of the SMN protein. SMA manifests in various degrees of severity though all include general muscle wasting and mobility impairment. SMA is the most common genetic cause of death in infants.
Progressive Bulbar Palsy
Affects the lower motor neurons in the brain stem used for swallowing, chewing, speaking, etc. Affected individuals have an increased risk of choking, and aspiration pneumonia. They are also affected by emotional lability (laughing or crying outbursts). Most ALS-affected persons show progressive bulbar palsy symptoms.
Is very similar to progressive bulbar palsy though it affects the upper motor neurons transmitting signals to the lower motor neurons in the brain stem. Affected individuals exhibit the same symptoms as those with progressive bulbar palsy.
Post-polio Syndrome (PPS)
Polio is a virus that attacks motor neurons. Due to the aggressive vaccinations, this virus has been virtually eradicated. However, those who have had the disease sometimes complain of weakness known as PPS. The disorder affects older people who have previously been affected with polio and is not life-threatening.
Current Therapies/Future Aims
At present, there are no cures or standard treatment for MNDs. Supportive treatment helps affected individuals maintain their quality of life. Riluzole is the only FDA-approved drug used to treat ALS. It may slow the progression and extend life by 2-3 months. Other drugs used to treat symptoms include muscle relaxants, anti-depressants, as well as opiates in the palliative stages of the diseases. Physical therapy, occupational therapy and rehabilitation often help improve joint mobility, muscle strength and atrophy.
The prognosis varies depending on the MND and the age of onset. Some MNDs progress slowly and are not fatal. Others like ALS, and early onset SMAs, are fatal.
Currently, there are several clinical trials testing different drugs for efficacy in slowing down disease progression. Other groups are looking for a better understanding of the mechanisms involved in the degeneration of the motor neurons. Neural stem cell therapies are also being investigated through FDA-approved clinical trials.