WEAKNESS

REFLEXES

SENSATION

NIS SCORENORFOLKPND/FAPKARNOFSKYCOMPASS 31RODS

Because ATTRv amyloidosis is a systemic disease, physicians should be aware of manifestations other than those of the peripheral nervous system, such as cardiac, ocular, and renal manifestations. A multidisciplinary approach is required to assess whether, through effects of autonomic dysfunction or amyloid deposition, other organs and systems are likely to be affected 1,2,3

Autonomic dysfunction

Autonomic dysfunction occurs in approximately 73% of patients with ATTR amyloidosis with PN and affects the gut, bladder sphincter, genital nerves, and cardiovascular system.1

Evaluation of the spread of the disease

Assessment of the spread of the disease is crucial for the detection of accompanying organ damage and requires a multidisciplinary approach.1 This is essential because the involvement of most organs, other than the nervous system, is latent but may have potentially major consequences—heart blocks, restrictive cardiomyopathy, glaucoma, renal insufficiency— for patients.1

Grading of the disease

Grading of the disease in each organ system involved is important for the follow-up of these patients. Grading allows detection of eventual disease progression and of organ complications that will require specific management (Table 1). The frequency of examinations should be determined by the severity and the systemic nature of the disease in each patient.1

Follow‑up

Patients with confirmed diagnoses should be routinely followed up to monitor for disease progression .1 Assessments should evaluate somatic neuropathy with locomotion (polyneuropathy disability score), severity of sensory motor neuropathy (NIS), autonomic dysfunction, manifestations with cardiac insufficiency (NYHA), biomarkers (ECG, ECHO, NT-proBNP), BMI, renal dysfunction with eGFR, and proteinuria (Table 1).1

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Evaluation Purpose References
Neurologic manifestations A. Sensory motor neuropathy Questionnaire [4]
 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 [5]
FAP-RODS RODS Overall disability [6] [7]
 Locomotion PND score Autonomy to walk
 B. Autonomic neuropathy CADT* (24-0) Overall dysfunction [8]
COMPASS 31 [9]
Sudoscan Denervated sweat glands of the soles and palms
Orthostatic hypotension [10]
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 [11]
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
Quality of life Norfolk QOL-DN Disease-specific changes in QOL [12]
SF-36 QOL Non-disease-specific changes in QOL [13]
Overall scale for ATTR disease Kumamoto neurologic scale Sensory disturbances, motor weakness, autonomic dysfunction, and visceral organ impairment [14, 15]
Sensory motor deficit in the limbs and autonomic dysfunction NIS + 7, mNIS + 7 Composite score for clinical trial only [16] [17]


Ref. Table 5 from Adams D. (2020) Evaluation of disease progression at initial screening and follow-up
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 fltration rate, FAP-RODS Familial Amyloid Polyneuropathy-Specifc Rasch-built Overall Disability Scale, HMDP hydroxymethylene diphosphonate, LL lower limb, mBMI modifed body mass index, MIBG metaiodobenzylguanidine, MRI magnetic resonance imaging, mNIS modifed 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
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