Type of noninvasive techniques | Details | Indices to detect disease progression | Feasibility to perform in neurology clinicsa | References |
---|---|---|---|---|
Peripheral neuropathy assessments | ||||
 Items necessary to suspect disease onset | Upper limb numbness, pain in extremities, dissociated sensory disturbance | – |  +  +  +  | [1] |
 Nerve conduction study | Measure the amplitude and velocity of sural and peroneal nerve conduction at left, right, or both sides of the body | SNAP amplitude ≤ 19 μV, sensory nerve conduction velocity ≤ 50 m/s, CMAP amplitude ≤ 16 mV, or motor nerve conduction velocity ≤ 51 m/s 50% reduction in CMAP amplitude within the normal range Reduction of CMAP or SNAP below the lower limit of normal range |  +  +  | [49] |
 QST | Evaluate sensory loss (hypesthesia, hypoalgesia) and gain (hyperalgesia, allodynia) for thermal and mechanical stimuli | – |  +  | [50] |
 NIS | Assess the degree of neuropathic symptoms (muscle weakness, reflexes, and sensation at specific sites) as a composite score | 7- to 16-point increase in the total score |  +  | [16] |
 NIS-LL | Subset of the NIS specific to neuropathy in the lower limbs |  ≥ 2-point worsening in the total score |  +  | [73] |
Autonomic function assessments | ||||
 Items necessary to suspect disease onset | Urinary disturbance, erectile dysfunction, orthostatic intolerance, diarrhea, constipation, alternating episodes of diarrhea and constipation, persistent nausea and vomiting, orthostatic hypotension, abnormal metaiodobenzylguanidine myocardial scans | – |  +  +  +  | [1] |
 Supine versus orthostatic blood pressure | Assess orthostatic hypotension |  ≥ 20-mmHg decrease in SBP or ≥ 10-mmHg decrease in DBP after standing up from a sitting or supine position |  +  +  +  | [82] |
Sudomotor test (Sudoscan™) | Quantify sudomotor function through local conductance using chloride in the sweat | Feet ESC ≤ 66 µS |  +  | [51] |
 HRDB, heart rate variability | Detect cardiac autonomic dysfunction through a paced breath test | – |  +  | [52] |
Cardiac symptom assessments | ||||
 Items necessary to suspect disease onset | Edema, conduction disorders with syncope, ventricular wall thickness and/or low voltage, elevated plasma BNP or NT-proBNP levels, abnormal cardiac accumulation in 99mtechnetium-labeled tracer scintigraphy | – |  +  +  +  | [1] |
 Echocardiography | Monitor cardiac involvement | Increased ventricular wall thickness (> 12 mm) |  +  +  | [83] |
 ECG | Monitor cardiac involvement | Low QRS voltage, conduction disturbance, arrhythmia |  +  +  | [83] |
 BNP, NT-proBNP, troponin T, troponin I | Monitor cardiac function | Elevation in BNP, NT-proBNP, troponin T, or troponin I |  +  +  | [84] |
 NYHA functional classification | Classify the severity of heart failure symptoms (class I, II, III, or IV) | Class II or above |  +  +  | [83] |
Cardiac MRI | Monitor cardiac involvement | Late gadolinium enhancement |  +  | [83] |
 Myocardial scintigraphy using 99mtechnetium-labeled tracers | Monitor cardiac amyloidosis | Grade 2 (moderate uptake, equal to rib uptake) or grade 3 (high uptake, greater than rib uptake) myocardial uptake with planar imaging |  +  | [85] |
CTS | ||||
 Phalen’s test | Monitor the development of CTS by putting pressure on the carpal tunnel | Exacerbation of dysesthesia after keeping the wrists flexed for 1 min |  +  +  | [67] |
 Reverse Phalen’s test | Monitor the development of CTS by putting pressure on the carpal tunnel | Exacerbation of dysesthesia after keeping the wrists extended for 1 min |  +  +  | [67] |
 Tinel’s sign test | Monitor the development of CTS by tapping the carpal tunnel with a hammer | Tingling pain |  +  +  | [67] |
 Nerve conduction study | Measure the amplitude and velocity of median nerve conduction at left, right, or both sides of the body | Sensory nerve conduction velocity of the median nerve across the carpal tunnel < 45 m/s; difference between the latencies of sensory potentials of median nerve determined at the fourth finger after equidistant stimulation of ulnar and median nerve > 0.5 ms; or distal motor latency > 4.4 ms for a stimulus applied 8 cm away from active motor electrode |  +  +  | [87] |
Nutritional status | ||||
 Items necessary to suspect disease onset | Unexplained weight loss | – |  +  +  +  | [1] |
 mBMI | Monitor nutritional status and detect unexplained weight loss | mBMI < 1000 |  +  +  +  | [76] |
Renal assessments | ||||
 eGFR and urinary protein | Monitor renal dysfunction due to amyloidosis | eGFR < 60 mL/min/1.73 m2, abnormal urinary protein excretion (> 150 mg/24 h), or albuminuria (> 30 mg/24 h or mg/g creatinine) |  +  +  +  | [4] |
PRO instruments | ||||
 Norfolk QoL-DN | Assess neuropathy-specific changes in patients’ quality of life | Norfolk QoL-DN score of ≥ 48 |  +  +  | |
 EQ-5D | Measure general health status | Utility value of ≤ 0.5 |  +  +  | [92] |
 COMPASS-31 | Assess patients’ autonomic functions | Total COMPASS-31 score of ≥ 30 |  +  +  | [78] |