Table 5.

Evaluation of disease progression at initial screening and follow-up

	Evaluation	Purpose	References
Neurologic manifestations
A. Sensory motor neuropathy	Questionnaire		[61]
	Paresthesia, neurogenic pain	Small fiber loss
	Gait disability	Large fiber loss
	NIS (0–244)
	Weakness in LL and UL	Large fiber loss
	Sensory loss in toes and fingers	Small and large fiber loss
	Tendon reflex loss in the four limbs	Large fiber loss
	Examination
	Pain and thermal sensory loss in the extremities in LL and UL (extension)	Small fiber loss
Disability	Modified Norris test	Sensorimotor neuropathy	[62]
	FAP-RODS RODS	Overall disability Overall disability	[63] [86]
Locomotion	PND score	Autonomy to walk
B. Autonomic neuropathy	CADT* (24-0)	Overall dysfunction	[62]
	COMPASS 31		[64]
	Sudoscan	Denervated sweat glands of the soles and palms
	Orthostatic hypotension		[87]
	MIBG scintigraphy	Sympathetic cardiac denervation
	Heart rate variability tests	Sympathetic and parasympathetic
Non-neurologic manifestations
C. Cardiac	ECG, Holter-ECG Cardiac staging	Looking for conduction block or arrhythmia
	ECHO (strain)	Cardiac involvement
	Cardiac MRI	Cardiac involvement
	DPD, PYP, and HMDP scintigraphy	Cardiac amyloidosis
	NT-proBNP	Cardiomyocyte stress
	Cardiac troponin	Cardiomyocyte death
	NYHA class	Extent of heart failure
	NYHA class	Stage the extent of cardiac damage	[65]
D. Ocular	Slit-lamp examination Intraocular pressure Schirmer test Visual acuity	Vitreous opacities Ocular hypertension Dry eye (sicca syndrome)
E. Kidney	Proteinuria eGFR	Renal dysfunction Renal insufficiency
F. General condition	Weight mBMI	Nutritional status Nutritional status
Quality of life	Norfolk QOL-DN	Disease-specific changes in QOL	[66]
	SF-36 QOL	Non-disease-specific changes in QOL	[67]
Overall scale for ATTR disease	Kumamoto neurologic scale	Sensory disturbances, motor weakness, autonomic dysfunction, and visceral organ impairment	[68, 69]
Sensory motor deficit in the limbs and autonomic dysfunction	NIS + 7, mNIS + 7	Composite score for clinical trial only	[70] [71]

CADT Compound Autonomic Dysfunction Test, COMPASS Composite Autonomic Symptom Score, DN diabetic neuropathy, DPD diphosphono-1,2-propanodicarboxylic acid, ECG electrocardiography, ECHO echocardiography, eGFR estimated glomerular filtration rate, FAP-RODS Familial Amyloid Polyneuropathy-Specific Rasch-built Overall Disability Scale, HMDP hydroxymethylene diphosphonate, LL lower limb, mBMI modified body mass index, MIBG metaiodobenzylguanidine, MRI magnetic resonance imaging, mNIS modified Neuropathy Impairment Score, NIS Neuropathy Impairment Score, NT-proBNP N-terminal fragment of the probrain natriuretic peptide, NYHA New York Heart Association, PND polyneuropathy disability, PYP pyrophosphate, QOL quality of life, SF-36 36-Item Short Form Survey, UL upper limb