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showed a significant correlation with the decrease in tail NCV
(
18
). The present findings are in keeping with previous stud-
ies after sciatic nerve injury in rats (
12, 17
) and with experi-
mental neuropathy in mice (
39
). The linear correlation
between neurophysiologic examination, which represents a
primary outcome measure in experimental neuropathies, and
IENF quantification strengthens the potential usefulness of
skin biopsy as a tool in experimental trials.
7. We chose to examine cutaneous innervation of rat instead of
mouse hind paw because of the availability of a well-character-
ized model of neuropathy in our laboratory in which (as above
described) behavioral and neurophysiologic methods can be
easily performed.
8. Interobserver agreement was significant for IENF counts
(
r
= 0.818,
p
< 0.01). This study demonstrated that the proto-
col used to quantify the density of IENF, which is the same
used in human clinical practice (
40, 41
), is reliable, as shown
by the high interobserver agreement obtained by two blinded
expert examiners in healthy and neuropathic rats.
9. An exact count of the number of nerve fibers should
not
be
expected. The counts cannot provide more than an estimated
range of the IENF density at a particular site. It is also impor-
tant to note that some cases can be much more difficult to
quantify than others, due to the sheer number of variables
involved. There will be situations in which the determination is
ambiguous or involves conflicting information. It is in these
cases that the experience or practice of the measurer plays a
critical role in making the final decision whether a stained
profile is or is not an IENF. Through experience with an already
trained measurer, the beginning measurer will be able to deter-
mine when to apply which rules and hints most effectively.
More importantly, consistency and reliability will be estab-
lished between the measurer's own style and that of the trained
measurer. The measuring process requires skills and acquired
experiences.
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