A new screening tool for early recognition of ATTRv polyneuropathy in clinical practice: AmyloScan®

Abstract

Hereditary transthyretin (ATTRv) amyloidosis is a progressive multisystem disorder, mainly characterized by cardiac dysfunction and polyneuropathy. Due to its rarity and heterogeneous presentation, diagnosis is often delayed, which has a direct impact on the initiation of treatment and, therefore, span and quality of life. To facilitate early disease recognition, we aimed to develop and validate a new screening tool for early identification of ATTRv amyloidosis with polyneuropathy (AmyloScan^®). Potential disease characteristics were identified via literature screening, interviews and detailed examination of ATTRv amyloidosis patients (n = 10) and controls (CIDP: chronic inflammatory demyelinating polyneuropathy, n = 15; diabetic polyneuropathy, n = 15) using validated questionnaires, and autonomic and sensory testing. The preliminary AmyloScan® was developed and validated in patients with polyneuropathy caused by ATTRv amyloidosis (n = 21), CIDP (n = 19), or others (n = 43). By sensitivity and discriminant analyses, we determined the most characteristic item combinations for ATTRv amyloidosis. Cut-off values were defined by Receiver Operator Curves. The final AmyloScan® includes 12 questions and two sensory bedside tests. All items require simple yes/no answers, resulting in a total score of 0-14 points and two cut-off values: A value of ≥ 4 indicates an increased chance (sensitivity: 95.2%, specificity: 72.6%); a value of ≥ 6 indicates a high chance of ATTRv polyneuropathy (sensitivity: 81.0%, specificity: 93.5%). The AmyloScan^® is a simple time- and cost-efficient screening tool with a high discriminative value. Regular use in clinical practice might enable an earlier diagnosis with impact on treatment considerations and quality of life.

Keywords: Bedside sensory test; CIDP; Hereditary transthyretin amyloidosis; Red flags; TTR silencers; TTR stabilizers.

Fig. 1

Study schedule. ATTRv amyloidosis, hereditary transthyretin amyloidosis; CIDP, chronic inflammatory demyelinating polyneuropathy; PNP, polyneuropathy; diabPNP, diabetic polyneuropathy; HRV, heart rate variability; lQST, laboratory quantitative sensory testing; bQST, bedside quantitative sensory testing; PROMs, patient-reported outcome measures. *one drop out per group

Fig. 2

Frequencies of autonomic symptoms in ATTRv amyloidosis (n = 10) vs. CIDP (n = 15) and diabPNP (n = 15). * ATTRv vs. CIDP (*p < 0.05; **p < 0.01)

Fig. 3

Profiles with selected bQST items of patients with ATTRv amyloidosis (n = 21) versus CIDP (n = 19) and PNP (n = 43) a) bQST parameters that were assessed using a 0–10 numerical rating scale (NRS), b) pressure pain threshold (PPT) in mL, c) vibration detection threshold (VDT) in x/8. Shown are the mean values and the standard error of the mean. BZ = border zone area. # ATTRv vs. PNP (#p < 0.05; ##p < 0.01)

Fig. 4

Frequencies of selected dichotomized bQST parameters (perception/pain: yes/no) of patients with ATTRv amyloidosis (n = 21) versus CIDP (n = 19) and PNP (n = 43). Shown are the frequencies of patients with gain of function (positive values, i.e., stimulus perceived/painful) and loss of function (negative values, i.e., stimulus not perceived/not painful). MPT mechanical pain threshold. PPT pressure pain threshold. CDT cold detection threshold. BZ border zone area. * ATTRv vs. CIDP (*p < 0.05); # ATTRv vs. PNP (#p < 0.05)

Fig. 5

ROC curves for the final AmyloScan^® total score. Light gray curve = discriminant function; dashed black curve = simple function; red dotted curve = reference line