hATTR Polyneuropathy in Russia

Since the increasing number of treatments available to help slow the progression of neuropathy it is critical to timely identify and diagnose the ATTR-PN. Early identification and intervention are also crucial to improve patient outcomes because newly available treatments have been shown to have maximum therapeutic benefit when started in the early stages of the disease.

Identification of ATTRv amyloidosis with PN can be challenging, particularly in non-endemic regions, and a high level of suspicion is required to diagnose patients as early as possible.

Previously proposed suspicion index of ATTRv amyloidosis was based on disease's red flags, that is, on the presence of a progressive polyneuropathy in addition to at least one red flag symptom suggestive of multi-systemic involvement. However, sometimes the demonstration of a progressive neuropathy requires follow-up evaluations, risking wasting time. Moreover, some red flags (e.g., cardiomyopathy or vitreous opacities) need specialist evaluations that could be often lacking during the first neurological evaluation.

Patients can present with heterogeneous symptoms and variable levels of disease severity, which often leads to a misdiagnosis. Early and accurate diagnosis may also be confounded by a lack of family history and the presence of various phenotypes common to multiple disease conditions such as GI disorders. In fact, CIAP still represents a common misdiagnosis for ATTRv patients.

Study is planned to determine the principal differences between the hATTR-PN and CIAP patients and valorize them in a compound score which can help clinician through a specific cut-off to recognize patients deserving TTR genetic analysis. The application of the compound score in patients with sensory-motor neuropathy may have a major role, representing a screening tool to avoiding wasting time and therefore shortening the time to reach a correct diagnosis.

Previously reported compound score included presence of muscle weakness and CTS history as clinical parameters and amplitude of Sensory action potential (SAP), Compound muscular action potential (CMAP) of the median and ulnar nerves, CMAP of the tibial nerve as electrophysiological parameters. Electrophysiological findings in this study showed that ATTRv patients, although they had the same disease duration of CIAP patients, had a greater reduction of amplitude of potentials in all nerves with a more frequently absence of potential at lower limbs and reduction at upper limbs.

At the same time, the landscape of mutations and phenotypes of ATTR amyloidosis are very different between countries, which does not allow extrapolating the results from Italian study, and there are no comprehensive epidemiological data on patients with hATTR-PN and CIAP in the Russian Federation.

Therefore, there is a need to conduct a large-scale observational study in the Russian population to obtain information on clinical, electrophysiological and demographic characteristics of patients with hATTR-PN and CIAP. Obtaining the study data will help to identify the patients with axonal polyneuropathy, who deserve TTR gene sequencing, and therefore to allow early treatment and potentially modify disease progression in patients.

Inclusion criteria

• Patients with hATTR-PN or CIAP ;
• The diagnosis of hATTR-PN or CIAP was established between the 1st January 2017 and the 1st March 2024;
• Presence of at least 1 month between the date of hATTR-PN or CIAP diagnosis and the date of inclusion;
• Age ≥ 18 years at the time of hATTR-PN or CIAP diagnosis.

Exclusion criteria

• The participation in any clinical trial with investigational product from the moment of diagnosis of ATTR PN or CIAP until the end of retrospective follow-up period.