FAP Nerve Function Found to Deteriorate Faster Than Other Disorders

Nerve function deteriorates more rapidly in people with familial amyloid polyneuropathy (FAP) than in those with other peripheral nerve disorders, a literature review has found. 

These findings may improve the understanding of the natural history of nerve damage in FAP and contribute to its early diagnosis, the researchers said.

The results also could guide the development of new targeted therapies.

The review study, “Rate of neuropathic progression in hereditary transthyretin amyloidosis with polyneuropathy and other peripheral neuropathies: a systematic review and meta-analysis,” was published in the journal BMC Neurology.

FAP, also known as hereditary transthyretin amyloidosis with polyneuropathy, is a progressive disease characterized by the buildup of abnormal protein deposits of transthyretin (amyloid) around peripheral nerves — those found outside the brain and spinal cord.

Over time, this process causes nerve damage and nerve function deterioration, leading to a condition known as peripheral neuropathy. 

Indirect comparisons have suggested that nerve disease progresses faster in people with FAP than in those with other peripheral neuropathies, such as diabetic peripheral neuropathy (DPN), in which diabetes causes nerve damage. 

However, no direct comparison of neuropathic progression rates between patients with FAP and those with other peripheral neuropathies has been conducted to date.

Further, as it is difficult to distinguish in the early stages between FAP and DPN or idiopathic peripheral neuropathy (IPN), which has an unknown cause,  a direct comparison of neuropathic progression rates may facilitate an early diagnosis.

To fill in this gap, scientists at QualityMetric and their colleagues conducted a review and analysis of published studies to assess and compare nerve disease progression in people with FAP with that of patients with other peripheral neuropathies. 

“The objective of this study, then, was to better understand the natural history of peripheral neuropathy across different conditions, and to provide an interpretive context for the time-course of neuropathic degeneration in [FAP] that could potentially reduce misdiagnosis of this condition,” the team wrote. 

Among the peripheral neuropathy conditions compared in this analysis were FAP, DPN, IPN, small fiber neuropathy, and Charcot-Marie-Tooth disease (CMT). Following a database search and selection process, 15 studies were included in the final analyses. 

The neuropathic impairment score (NIS), a clinician-rated measure that captures neuropathic progression symptoms across a range of different diseases, was used as the primary outcome measure. The NIS-lower leg (NIS-LL) score, a subset of NIS items specific to the lower limbs, also was used. In both outcome measures, higher scores reflect a higher degree of neuropathic impairment.

Among the selected studies, the patients’ mean age ranged from 33 to 69, with 24-90% being men. Follow-up duration ranged from 160 days (just under six months) to four years, except for three studies that had varying follow-up periods for individual participants. 

Based on NIS score changes from 11 studies, the mean annual rate of neuropathic impairment in people with FAP was 11.77 points per year. Among those with CMT, NIS scores increased 1.41 points per year, while in patients with DPN scores dropped 1.96 points per year. Rates in IPN and small fiber peripheral neuropathy were not assessed, as there was only one study with NIS scores for each disorder.

In both FAP and DPN, NIS scores were highly variable, compared with CMT studies, “which may be due to there being only three studies in this group, with one of those studies having a much larger sample size than the other two, thus dominating the weighting,” the scientists wrote. 

A statistical analysis found that, on average, patients with FAP had a 12.45-point higher annual rate of NIS change (nerve function worsening), compared with people with other peripheral neuropathies. After adjusting for NIS scores at the initial assessment, the results remained statistically significant with an estimated score change of 11.97 points per year. 

From nine studies reporting NIS-LL scores, the mean annual rate of change was 5.68 points per year in patients with FAP and -2.31 points per year among those with DPN. The team did not perform the same analysis for patients with IPN or CMT, since there was only one study published with NIS-LL scores for each disease. Similar to NIS scores, NIS-LL scores were highly variable. 

On average, studies of people with FAP had a 6.96-point higher annual rate of NIS-LL impairment compared to studies with patients with other peripheral neuropathies. After adjustments, the rate was still significant at 6.47 points per year. 

“In conclusion, this systematic review and meta-analysis provides empirical evidence suggesting that patients with [FAP] have more rapid neuropathic progression than patients with other peripheral neuropathies,” the authors wrote.

“These findings could help clinicians differentiate [FAP] from other types of peripheral neuropathies, usually with more common and benign [causes], and to evaluate patient response to treatment in [FAP],” they wrote.

The researchers also noted that data from this study “may be used to guide the development of new assessment tools and therapies” to tackle the rapid progression of FAP.