Measure of peripheral neuropathy: neuropathic impairment score (NIS)

The NIS is a widely used, clinician-rated measure that captures the symptoms and signs of neuropathic progression across different disease types that manifest in peripheral neuropathy. The NIS was originally developed for assessing neuropathic progression and response to treatment in DPN, but this instrument and its related measures have also been utilized in other types of peripheral neuropathy [7, 17–19]. In particular, variations of the measure have been used as primary endpoint measures in pivotal RCTs of patients with ATTRv-PN [6, 9], because of its high sensitivity in tracking progression of neuropathy over relatively short time periods [12]. Therefore, the NIS can be used to compare the rate of neuropathic progression between ATTRv-PN and other disease types manifesting in peripheral neuropathy.

The NIS uses a composite clinical scoring system, with a trained neurologist evaluating muscle weakness, reflexes, and sensation at specific sites bilaterally [20]. NIS total score is graded on a scale of 0–244, with higher scores indicating greater impairment [18]. The NIS-LL is a subset of NIS items specific to neuropathy in the lower limbs. NIS-LL total score ranges from 0 to 88, with higher scores indicating greater impairment. Other variants of the NIS (e.g., modified NIS + 7 [mNIS + 7] scale) have been used in studies of patients with ATTRv-PN [6, 9].