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Motor Neuron Diseases (ALS, SMA, PBP, PLS)

Motor Neuron Diseases (MNDs) are a group of progressive neurological disorders that destroy motor neurons, the cells that control essential voluntary muscle activities such as speaking, walking, breathing and swallowing. Normally, messages from nerve cells in the brain, called upper motor neurons, are transmitted to nerve cells in the brainstem and spinal cord called lower motor neurons and from there to particular muscles. Upper motor neurons direct lower motor neurons to produce movements such as walking or chewing. Lower motor neurons control movement in the arms, legs, chest, face, throat and tongue. When upper motor neurons are affected the manifestations include spasticity or stiffness of limb muscles and overactivity of tendon reflexes such as knee and ankle jerks. When lower motor neurons are affected the results include gradual weakening and wasting away of the muscles and fasciculations (rapid twitching of muscles). Motor neuron disease is more common in men than in women.

A number of MNDs can be diagnosed:

a. Amyotrophic Lateral Sclerosis (ALS) is also called Lou Gehrig’s disease and is a progressive, ultimately fatal disorder that eventually disrupts signals to all voluntary muscles. Both upper and lower motor neurons are affected. Approximately 75% of patients with classic ALS also develop weakness and wasting of the bulbar muscles, which control speech, swallowing and chewing. Symptoms are usually noticed first in the arms and hands, legs or swallowing muscles. Muscle weakness and atrophy occur disproportionately on both sides of the body. Patients lose strength and the ability to move the arms, legs and body while other symptoms include spasticity, exaggerated reflexes, muscle cramps, fasciculations, and problems with swallowing and forming words. When muscles of the diaphragm and chest wall fail to function properly patients lose the ability to breathe without mechanical support. A number of recent studies suggest that some ALS patients may have alterations in cognitive functioning such as problems with decision-making and memory. Most cases of ALS occur sporadically, meaning that there is no identifiable cause. The most frequent cause of death is from respiratory failure usually within three to five years from the onset of symptoms.

b. Progressive Bulbar Palsy (PBP) involves the bulb shaped brainstem that controls lower motor neurons needed for swallowing, speaking, chewing and other functions. Symptoms include pharyngeal muscle weakness (muscles that are involved in swallowing), weak facial muscles, progressive loss of speech, and tongue muscle atrophy. Limb weakness with both lower and upper motor neuron signs is almost always evident but is less prominent than in ALS. Affected persons have outbursts of laughing or crying that are unrelated to anything that is going on around them. They eventually become unable to eat or speak and are at increased risk for choking and aspiration pneumonia.

c. Pseudobulbar Palsy shares many of the symptoms of progressive bulbar palsy and is characterized by upper motor neuron degeneration and progressive loss of the ability to speak, chew and swallow. Progressive weakness of facial muscles leads to an expressionless face. Patients may also develop a gravelly voice and an increased gag reflex. The tongue may become immobile and unable to protrude from the mouth. Patients may also experience emotional instability.

d. Primary Lateral Sclerosis (PLS) affects only upper motor neurons and is nearly twice as common in men as in women. Onset is generally after age 50 with unknown causes. It occurs when specific nerve cells in the cerebral cortex (the grey matter of the brain) that control voluntary movement gradually degenerate, causing the muscles under their control to weaken. The disorder progresses gradually over years and usually affects the legs first, followed by the trunk, arms and hands and finally the bulbar muscles. Symptoms may include difficulty with balance, weakness and stiffness in the legs, clumsiness, spasticity in the legs which produces slowness and stiffness of movement, dragging of the feet and facial involvement resulting in dysarthria. The major difference between ALS and PLS are the motor neurons involved and the rate of the disease progression. The disorder is not fatal but may affect quality of life and often develops into ALS.

e. Progressive Muscular Atrophy (PMA) is marked by slow but progressive degeneration of only the lower motor neurons. It largely affects men with onset earlier than other MNDs. Weakness is typically seen first in the hands and then spreads into the lower body, where it can be severe. Symptoms may include muscle wasting, clumsy hand movements, fasciculations and muscle cramps. The trunk muscles and respiration may be affected and the disease develops into ALS in many patients.

f. Spinal Muscular Atrophy (SMA) is a hereditary (genetically transmitted) disease affecting the lower motor neurons. Weakness and wasting of the skeletal muscles is caused by progressive degeneration of the anterior horn cells of the spinal cord. The weakness is often more severe in the legs than in the arms. SMA has various forms, with different ages of onset, patterns of inheritance and progression of symptoms.

i. SMA type I is evident by the time by the time a child is six months old. Symptoms may include hypotonia, diminished limb movements, lack of tendon reflexes, fasciculations, tremors, swallowing and feeding difficulties and impaired breathing. Some children may develop scoliosis or curvature of the spine or other skeletal abnormalities. Affected children never sit or stand and the vast majority usually die of respiratory failure before the age of two years.

ii. SMA type II has symptoms which usually begin after the child is six months of age. Features may include inability to stand or walk, respiratory problems, hypotonia, decreased tendon reflexes, and fasciculations. These children may learn to sit but not stand. Life expectancy varies but some patients live into adolescence or later.

iii. SMA type III appears between two and 17 years of age and includes abnormal gait, difficulty running, climbing steps, rising from a chair, and fine tremor of the fingers. Lower extremities are more often affected. Complications include scoliosis and joint contractures, chronic shortening of muscles or tendons around joints that is caused by abnormal muscle tone and weakness, which prevents the joints for moving freely.

iv. Fazio-Londe disease appears between one and 12 years of age and may include facial weakness, dysphagia, stridor, difficulty speaking, and paralysis of the eye muscles. Most patients die from breathing complications.

v. Kennedy disease, also known as progressive spinal bulbar muscular atrophy, is an X-linked recessive disease. Daughters of patients with Kennedy disease are carriers and have a 50% chance of having a son affected with the disease. Onset occurs between 15 and 60 years of age. Symptoms include weakness of the facial and tongue muscles, hand tremor, muscle cramps, dysphagia, dysarthria and gynecomastia. Weakness usually begins in the pelvis before spreading to the legs. Some patients develop non-insulin-dependent diabetes mellitus. The course of the disorder varies but is generally slowly progressive. Individuals tend to remain ambulatory until late in the disease and life expectancy is usually normal.

vi. Congenital SMA with arthrogryposis is a rare disorder that involves persistent contracture of the joints with fixed abnormal posture of the limb. Manifestations include severe contractures, scoliosis, joint deformity, respiratory problems, micrognathia (small mouth) and ptosis (drooping eyes).

Post-Polio Syndrome (PPS) is a condition that can strike polio survivors decades after their recovery from poliomyelitis. PPS is believed to occur when injury, illness, weight gain or the aging process damages or kills spinal cord lower motor neurons that remain functional after the initial polio attack. Some scientists believe PPS is a delayed weakness among muscles previously affected by poliomyelitis and not a new MND. Symptoms include fatigue, slowly progressive muscle weakness, muscle atrophy, fasciculations, cold intolerance and muscle and joint pain. Symptoms typically appear in those muscle groups that were initially affected by the poliomyelitis. Additional symptoms can include skeletal deformities such as scoliosis and difficulty breathing, swallowing or sleeping. PPS is not usually life-threatening.

There is no cure or standard of treatment for most of the diseases in this domain. Symptomatic and supportive treatment can help patients live more comfortablely while maintaining their quality of life. Riluzole is an FDA approved medication that can prolong life in individuals with ALS by two to three months but does not relieve symptoms. It reduces the body’s natural production of the neurotransmitter glutamate, which is believed to have an excitotoxic effect on the motor neurons. Muscle relaxants such as baclofen, tizanidine and the benzodiazepines may reduce spasticity. Glycopyrrolate and atropine may reduce the flow of saliva. Quinine or phenytoin may decrease cramps. Anticonvulsants and nonsteroidal anti-inflammatory drugs may help relieve pain.

For more information, contact Dr. Rozenblatt at (866) 840-9790 or