Utility of Neuropathy Screening for Wild-Type Transthyretin Amyloidosis Patients

Abstract

Background: Wild-type transthyretin amyloidosis (wtATTR) is an important cause of heart failure (HF); however, the prevalence and clinical significance of neurologic complications remains uncertain. Methods: This analysis reports findings from a single-centre experience of routine neuropathy screening at the time of wtATTR diagnosis by nerve conduction studies and neurologist assessment, compared with age-matched controls. Results: Forty-one wtATTR patients were included, 39 (95%) males, mean age 78.4 ± 7.7 years, 22 (54%) New York Heart Association (NYHA) class III–IV HF, along with 15 age-matched controls (mean age 77.1 ± 4.2 years, 80% male). Twenty-one (51%) wtATTR patients were diagnosed with polyneuropathy, 15 (37%) with spinal stenosis, 36 (88%) with carpal tunnel syndrome (CTS) and 14 (34%) with ulnar neuropathy. Comparison diagnoses among controls were 1 (7%), 0, 1 (7%) and 3 (20%), respectively. Among patients with NYHA class III–IV HF, 16 (73%) had polyneuropathy compared with 5 (26%) with class I–II (p < 0.01), odds ratio of 7.5 (95% confidence interval 1.9–29.9). After neuropathy screening, 19 (46%) patients were offered neurologic therapy and/or additional diagnostic evaluation. This included CTS release surgery (16, 39%), neuropathic pain medication (3, 7%), nerve block (1, 2%), wrist splinting (2, 5%) and foot care (1, 2%). Spine imaging was performed for 3 (7%) patients, and deltoid muscle and sural nerve biopsy for 1 (2%) patient. Conclusions: Screening of wtATTR patients for neurologic complications resulted in a management change for nearly half. CTS, polyneuropathy and ulnar neuropathy were common. This approach warrants consideration as part of routine assessment for newly diagnosed wtATTR patients.

Hereditary transthyretin amyloidosis: a case report

“…A mild normocytic anemia is not uncommon [ 4 ]. In contrast, wtATTR commonly causes cardiomyopathy in older patients and may include neurologic involvement in the form of carpal tunnel syndrome and spinal stenosis [ 5 , 6 ]. Neuropathy, when present in wtATTR, is typically mild [ 4 ].…”

“…Globally, hATTR is a rare disease, but is endemic in certain regions such as Portugal, Sweden, and Japan [ 5 ]; thus, a high index of suspicion should be maintained in adult patients with compatible symptoms and ancestry. Recently, genetic testing has become the diagnostic test of choice for patients presenting with neuropathy, given the low sensitivity of many sites of tissue biopsy, although tissue confirmation with mass spectrometry may be helpful in certain settings [ 5 , 7 ]. Additionally, the PYP scan is a relatively novel tool that has a high sensitivity for cardiac ATTR, although it does not differentiate between hATTR and wtATTR [ 3 ].…”

“…A multidisciplinary approach is essential both to manage symptoms and to help rule out other conditions. Recent guidelines outline the importance of this approach, with early referral to cardiology and neurology being strongly recommended along with involvement from hematology, when appropriate, to rule out plasma cell disorders [ 5 , 7 ].…”

Assessment and Management of Older Patients With Transthyretin Amyloidosis Cardiomyopathy: Geriatric Cardiology, Frailty Assessment and Beyond

“…Peripheral neuropathy is a hallmark feature of some ATTRh genotypes, notably the pV50M mutation ( 30 ). Recently it has been recognized that ATTRwt patients can also develop peripheral neuropathy ( 31 , 32 ). Similar to cardiovascular manifestations, symptoms of peripheral neuropathy can also be associated with other more common conditions that increase in prevalence with age, such as diabetes, thyroid dysfunction, monoclonal gammopathy and vitamin deficiencies, making clinical recognition of ATTR challenging, particularly in early stages of disease ( 33 ).…”

Peripheral Neuropathy in Wild-Type Amyloidosis: The More You Look, the More You Will Find

“…The retrospective cohort study by Russel et al 5 in this issue of the journal reports the type and frequency of peripheral nerve complications in ATTRwt. Consecutive ATTRwt cardiomyopathy patients seen in their multidisciplinary amyloid clinic were offered a complete neurologic evaluation through standardized physical and neurophysiologic examinations.…”