Hereditary Transthyretin Amyloidosis Polyneuropathy in Patients With Carpal Tunnel Syndrome in Russia

Overview

This is a multicenter observational study consisting of retrospective and prospective phases. The retrospective phase will entail secondary data collection from electronic or paper medical records of patients who underwent surgery for CTS to assess their probability of having ATTR PN.

Description

ATTR PN is a genotypically, phenotypically and geographically variable disease with a poor prognosis, albeit available disease-modifying drugs can change the disease trajectory. Thus country-specific epidemiologic data collection and identification of early stage PN, including previously misdiagnosed patients, is crucial to improve outcomes and quality of life. However, no observational studies on the epidemiology of ATTR PN in the whole Russian population, or in patients with CTS, have been performed.

Therefore, there is a need to conduct a large-scale observational study to determine the prevalence of ATTR PN in Russia, obtain information on patients' clinical characteristics, and determine their medical needs.

The approaches to diagnosis of ATTR PN in Russia over the past few years have been characterized by the use of heterogenous methods, partially explained by the lack of availability of molecular genetic testing, which is essential to diagnose the presence of pathogenic mutation in patients with hereditary ATTR PN. Thus, recent introduction of such tests into routine clinical practice may allow to assess reliable epidemiologic data including estimation of true ATTR PN prevalence among patients with CTS, which can often be the first manifestation of the disease. Earlier recognition, in turn, may lead to timely treatment initiation and change in the prognostic outlook of ATTR PN patients.

In order to assess the prevalence of ATTR PN in patients undergoing surgery for CTS in Russia this study will retrospectively include patients with the diagnosis of CTS undergoing surgery between the 1st January 2021 and the 1st September 2024. Suspicion of ATTR PN will be assessed in each case, and diagnostic tests (comprehensive neurological examination including nerve conduction study (NCS) combined with molecular genetic testing) to confirm or exclude the disease will be conducted prospectively in eligible patients. In addition to that, clinical features, concomitant manifestations, and diagnosed genotypes will be analyzed to examine characteristic ATTR PN patient profiles in the Russian Federation.

Eligibility

Inclusion Criteria:

for the retrospective phase are:

1. Patients with the established diagnosis of CTS undergoing surgical intervention between the 1st January 2021 and the 1st September 2024.
2. Age ≥ 18 years at the time of surgery.

   Additional inclusion criteria for the prospective phase are:

3. Provided written informed consent for the prospective phase of the study (including molecular genetic testing).
4. Bilateral CTS;
5. Presence of ≥1 of the following features (red flags):
   1. CIDP or polyneuropathy of unknown etiology in the family history;
   2. Spinal canal stenosis of the lumbar region;
   3. Autonomic dysfunction, defined by the presence of ≥1 of the following symptoms:
   4. gastrointestinal complaints (constipation, chronic diarrhea, or both); ii. erectile dysfunction; iii. orthostatic hypotension;
   5. Gait disorders;
   6. Sweating disorders, anhidrosis.
   7. Paresthesia and burning of the skin of the distal extremities
   8. Distal symmetrical paresis
   9. Hypotrophy and hypotension of limb muscles, areflexia
   10. Biceps tendon rupture
   11. Aortic valve stenosis
   12. Diagnosis of HFpEF
   13. Unexplained weight loss ≥5 kilos at any timepoint since the onset of symptoms of CTS;
   14. Left ventricular hypertrophy (based on electro- or echocardiographic criteria documented in the patient's medical record);
   15. Heart rhythm disorders;
   16. Renal abnormalities, defined by ≥1 of the following features - i. documented diagnosis of chronic kidney disease (CKD); ii. decreased estimated glomerular filtration rate (eGFR <60 mL/min/1.73m2); iii. increased serum creatinine (SCr) above reference range of the local laboratory; iv. albuminuria (≥30 mg/g of creatinine or ≥30 mg/24h ); v. proteinuria (according to urinalysis results).
   17. Ophthalmology disorder defined by ≥1 of the following features - i. vitreous body inclusions (opacification); ii. Glaucoma; iii. pupillary disorders; iv. vitrectomy
6. Absence of previously established ATTR PN diagnosis (ICD-10 code Е85.1, "Neuropathic

   hereditary familial amyloidosis").

Exclusion Criteria:

for the retrospective phase are:

1. Participation in any interventional trial within the period since surgical intervention until the end of current study.

   Additional exclusion criteria for the prospective phase are:

2. Previously performed TTR genetic testing;
3. Verified B12 deficiency;
4. History of alcohol abuse according to the patient's medical record.