Progressive Muscular Atrophy (PMA)

What happens in PMA

Motor neurons come in two types:

• upper motor neurons in the brain, which send signals down the spinal cord
• lower motor neurons in the spinal cord and brainstem, which connect to the muscles

In amyotrophic lateral sclerosis (ALS), both types degenerate. In PMA, only the lower motor neurons are affected; in primary lateral sclerosis, only the upper. When lower motor neurons die, the muscles they supply lose their nerve signal, weaken and waste.

PMA makes up a small proportion of motor neuron disease cases. Over time, a substantial number of people with PMA develop upper motor neuron signs, and autopsy studies show ALS-type changes in many, so PMA is often considered part of the ALS spectrum.

Symptoms

• weakness, often starting in one hand (difficulty with buttons, keys, gripping) or one foot (tripping, foot drop)
• visible muscle wasting, such as thinning of the hand muscles between the thumb and index finger
• twitching under the skin (fasciculations)
• muscle cramps
• reduced or absent reflexes
• floppy (low tone) rather than stiff muscles
• fatigue
• later: weakness spreading to other limbs, neck, swallowing and breathing muscles

Sensation, bladder and bowel control, and thinking are typically unaffected.

PMA vs ALS and other conditions

Distinguishing PMA from treatable mimics such as multifocal motor neuropathy is a key goal of testing.

Diagnosis

Diagnosis is clinical and by exclusion:

• neurological examination for patterns of weakness, wasting and reflexes
• electromyography (EMG) and nerve conduction studies showing widespread denervation with normal sensory nerves and no conduction block
• MRI of the spine and brain to exclude compression, tumors or other structural causes
• blood tests: CK, thyroid, B12, protein electrophoresis, anti-GM1 antibodies, and genetic testing for Kennedy's disease, SMA and ALS genes when relevant
• sometimes lumbar puncture

Treatment and care

There is no cure. Management is best delivered by a multidisciplinary motor neuron disease clinic:

• Riluzole may be offered, as it modestly slows ALS progression; evidence specifically for PMA is limited.
• Physical therapy: maintaining range of motion and safe activity.
• Occupational therapy: aids for hand function, mobility and home adaptations.
• Orthoses: splints and ankle-foot orthoses for foot drop.
• Speech and swallowing therapy: diet changes and, if needed, a feeding tube to maintain nutrition.
• Respiratory care: monitoring lung function, non-invasive ventilation (BiPAP) when breathing muscles weaken, cough assist devices.
• Medicines for cramps and other symptoms.
• Psychological support and advance care planning.

Outlook

PMA progression varies widely. On average it progresses more slowly than classic ALS, and some people live many years. Survival depends largely on whether and when breathing muscles become affected and whether upper motor neuron signs develop.

Frequently asked questions

What is progressive muscular atrophy?

It is a rare motor neuron disease in which the nerve cells connecting the spinal cord to muscles gradually die, causing weakness, muscle wasting, twitching and cramps. It affects movement but usually not sensation or thinking.

How is PMA different from ALS?

PMA affects only lower motor neurons, causing floppy weakness and wasting with reduced reflexes. ALS affects both lower and upper motor neurons, adding stiffness and brisk reflexes. PMA usually progresses more slowly, though some people later develop ALS features.

What is the life expectancy with progressive muscular atrophy?

It varies considerably. Many people live longer than the average for ALS, sometimes many years. Breathing muscle involvement is the main factor affecting survival, and respiratory support can extend life.

Is progressive muscular atrophy inherited?

Most cases are not inherited. A small number of people have genetic changes linked to motor neuron disease, and genetic testing may be offered, especially with a family history.