Most late-onset FAP patients have pain due to nerve damage: Study
Life quality affected by neuropathic pain that's often not eased with treatment
Most people with late-onset familial amyloid polyneuropathy (FAP) experience pain as a result of nerve damage, referred to as neuropathic pain, a recent study highlights.
Findings suggest that neuropathic pain is linked to worse life quality, and many patients do not experience relief from this type of pain even with treatment. Researchers stressed that it’s important for clinicians to address pain in people with FAP.
The study, “Neuropathic pain experience in symptomatic and presymptomatic subjects carrying a transthyretin gene mutation,” was published in the journal Frontiers in Neurology.
Neuropathic pain is known symptom in early-onset FAP
FAP is caused by mutations in the TTR gene, resulting in the production of an abnormal transthyretin protein that forms toxic clumps in body tissues.
Based on the age at which symptoms first appear, FAP can be broadly divided into early-onset (starting at 50 years or younger) or late-onset (after age 50). Early-onset disease is generally more common, particularly in certain parts of the world such as Portugal where FAP is endemic.
Neuropathic pain is a well-documented symptom in early-onset FAP, but its occurrence and impact on patients with late-onset disease are less well-characterized.
To learn more, a team of scientists in Italy conducted detailed neurological examinations and pain assessments on 102 people who carried a TTR mutation associated with late-onset FAP.
Among the participants, 78 had FAP symptoms, while the remaining 24 were presymptomatic, meaning they were not yet displaying overt symptoms of the disease. As expected, symptomatic patients were older than presymptomatic ones (mean age of 68.1 vs. 49 years).
“To our knowledge, this is the first systematic assessment of pain in a large cohort of late-onset TTR-mutated subjects encompassing both symptomatic patients and presymptomatic carriers,” the researchers wrote.
About three-quarters of the participants reported significant pain, although pain was significantly more frequent among symptomatic (85.9%) versus presymptomatic patients (41.6%). Pain was most commonly generalized (affecting the whole body), or distal (affecting the hands and/or feet) in symptomatic FAP patients.
Assessment of neuropathic pain may be a useful strategy to monitor disease progression in symptomatic patients and may be suitable to identify early manifestation of the disease in presymptomatic relatives who carry a TTR gene mutation.
Neuropathic pain was identified in majority of patients with symptoms
Neuropathic pain was identified in more than two-thirds (69.2%) of the patients with active symptoms. This type of pain was most frequently described as an “electric shock” sensation; some patients also described feelings of burning or extreme cold. Neuropathic pain almost always co-occurred with other unusual sensations like tingling, itching, numbness, or pins and needles.
Neuropathic pain was also identified in two (8.3%) presymptomatic carriers.
“This finding raises the question of whether presymptomatic carriers who complain of neuropathic pain should instead be considered symptomatic patients and, consequently, be able to access the available therapies,” the researchers wrote, noting that further testing should be conducted in such cases.
FAP patients and carriers who experienced neuropathic pain were significantly older (mean age of 66.5 vs. 60.1 years), and tended to have worse overall pain scores than those without this specific type of pain. Individuals with neuropathic pain also generally had worse scores on measures of disease severity.
These data suggest that neuropathic pain tends to worsen as FAP develops and progresses, the researchers noted. As such, “assessment of neuropathic pain may be a useful strategy to monitor disease progression in symptomatic patients and may be suitable to identify early manifestation of the disease in presymptomatic relatives who carry a TTR gene mutation,” they wrote.
Neuropathic pain was significantly linked to worse quality of life
In statistical models, the presence of neuropathic pain was significantly associated with significantly worse scores on measures of life quality and ability to perform day-to-day activities. Neuropathic pain was also associated with autonomic involvement — damage to the parts of the nervous system responsible for regulating unconscious bodily processes such as breathing, heartbeat, and digestion.
Of note, while most patients received some form of treatment to ease neuropathic pain (most commonly anti-seizure medicines), less than half (45.9%) reported satisfactory pain relief, and 40.5% reported persistent neuropathic pain despite treatment.
In late-onset FAP, “pain and its treatment could be overlooked if clinicians are more focused on motor disability,” the researchers wrote. “Clinicians should not neglect the pain experience when evaluating [FAP] patients or presymptomatic relatives who carry a TTR gene mutation.”