Narrowing of the spinal canal due to a buildup of proteins — transthyretin (TTR) amyloid deposits — was reported in a rare case of familial amyloid polyneuropathy (FAP).
The case was described by researchers from the U.K. in the study, “Spinal Stenosis in Familial Transthyretin Amyloidosis,” published at the Journal of Neuromuscular Diseases.
This rare manifestation of FAP “highlights the need for awareness of the heterogeneous neurological” presentation of this disease to promote early diagnosis, “especially now that disease modifying therapies are available,” the researchers stated.
FAP, also known as transthyretin amyloidosis (ATTR), is a rare inherited disorder caused by genetic mutations in the TTR gene, and consequent accumulation of TTR protein amyloid clumps in nerve cells. Progressive degeneration of sensory and motor nerve cells results, leading to a broad range of symptoms.
The patient in this case, a woman of German ancestry, had FAP confirmed at the age 42 upon detection of a TTR mutation.
Her family had a strong history of systemic amyloidosis, with her mother, maternal uncle, and older brother having carpal tunnel syndrome, peripheral neuropathy (nerve damage), and restrictive cardiomyopathy (heart disease).
Following the diagnosis she was closely monitored in a specialized center, and two years later TTR accumulation was further confirmed in carpal tunnel release surgery.
For about 10 years she had experienced worsening symptoms of carpal tunnel syndrome, such as hand and finger numbness or tingling. But she reported no other symptoms of peripheral neuropathy, or other common FAP symptoms.
Systemic and neurological examinations confirmed no other alterations, with exception of reduced sensory nerve signal conduction in the wrist. Heart evaluation suggested only early signs of TTR accumulation there.
She started taking the nonsteroidal anti-inflammatory agent Dolobid (diflunisal), and in the following four years her disease remained stable with no sign of progression.
At age 47, she developed numbness on the dorsum of her left foot (the mid-foot and forefoot) and pain in her lower back that spread to both thighs and knees. These new symptoms got progressive worse in the following 12 months, and she also started to having problems with incontinence.
A neurological examination revealed that her low back and limbs symptoms were consistent with a diagnosis of cauda equine syndrome. This condition is characterized by compression of lower end of the spinal cord, most commonly caused by narrowing of the spinal canal — clinically, it’s identified as spinal stenosis.
Magnetic resonance imaging (MRI) scans showed that the spinal cord was being compressed due to enlargement of ligaments. Surgery to remove the altered tissues were removed to decompress the nerves confirmed that accumulation of TTR clumps caused the ligament enlargement.
Six weeks after the surgery her neurological symptoms were almost completely resolved. Her pain had significantly eased and she had much greater tolerance to exercise and better lower limb sensation.
“This is the first reported case of (…) confirmed mutant ATTR-associated spinal stenosis,” the researchers stated.
As “recent gene therapy trials showed improvement in the neuropathy in TTR amyloidosis” the team believes that confirmation of diagnosis by tissue analysis is an important step to achieving the best outcome, particularly for “patients where a high suspicion of ATTR amyloidosis exists.”
“Early diagnosis of ATTR amyloidosis is likely to be increasingly important,” the researchers added.