Improving the clinical usefulness of skin biopsy in small fiber neuropathy: examining the intraepidermal nerve fiber density dynamic longitudinally and the importance of adding the proximal/distal ratio

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 280

Inclusion Criteria

Group 1 (n=40) Idiopathic SFN, with normal IENFD:
a) Male and female subjects of 18 years or older.
b) >=2 positive answers on the SFN-SIQ, not otherwise explained.
c) Normal IENFD and abnormal TTT, according to the international normative
values,3,23 during the regular visit in our clinical center at least one year
ago.
d) Written informed consent.Group 2 (n = 40) Sodium channelopathy-related SFN,
with normal IENFD:
a) Male and female subjects of 18 years or older.
b) >=2 positive answers on the SFN-SIQ, not otherwise explained.
c) Normal IENFD and abnormal TTT, according to the international normative
values,3,23 during the regular visit in our clinical center at least one year
ago.
d) Possibly pathogenic, probably pathogenic or pathogenic NaV1.7, Nav1.8 and/or
NaV1.9 variant
a) Written informed consent.Group 3 (n=140) Healthy subjects (only
proximal/distal IENFD ratio study)
a) Male and female subjects of 18 years or older.
b) Written informed consent.Group 4 (n = 20) Idiopathic SFN, with abnormal
IENFD (only proximal/distal IENFD ratio study)
a) Male and female subjects of 18 years or older.
b) >=2 positive answers on the SFN-SIQ, not otherwise explained.
c) Abnormal IENFD, according to the international normative values, during the
regular visit in our clinical center at least one year ago.
d) Written informed consent.When it appears that the proximal/distal ratio is
abnormal in patients with an abnormal TTT, but normal IENFD, the study will be
extended with an extra group of patients:Group 5 (n=40) Idiopathic clinical
SFN, with both normal IENFD and TTT
a) Male and female subjects of 18 years or older.
b) >=5 positive answers on the SFN-SIQ, not otherwise explained.
c) Patients with a normal IENFD and normal TTT, according to the international
normative values, during the regular visit in our clinical center at least one
year ago.

Exclusion Criteria

All patient groups:
a) Underlying cause of SFN (diabetes, hypothyroidism, renal failure, vitamin
B12 deficiency, monoclonal gammopathy, alcohol abuse (more than 5 IU/day),
malignancies, drugs that cause neuropathy (e.g. chemotherapy, amiodarone,
propafenone)).
b) Large nerve fiber involvement (i.e. weakness, loss of vibration sense,
hypo-/areflexia, abnormal nerve conduction studies).Groups 1, 4 and 5
a) Possibly pathogenic, probably pathogenic or pathogenic NaV1.7, Nav1.8 and/or
NaV1.9 variant.Healthy subjects
a) >1 positive answer on the SFN-SIQ.
b) A history of peripheral neuropathy.
c) Signs of peripheral neuropathy in neurological examination.nt claCC

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Current IENFD at the ankle compared with the IENFD that has been taken during<br /><br>the regular visit, at least one year before. The degree of IENFD decrease or<br /><br>increase over time (corrected for expected age-dependent decline) will be<br /><br>computed. Furthermore, the percentage of IENFD results that turn from normal<br /><br>into abnormal will be calculated.<br /><br>- Proximal/distal IENFD ratio normative values.<br /><br>- The proximal/distal IENFD ratio compared between SFN patients and healthy<br /><br>subjects.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Change in number of complaints on the SFN-SIQ related to IENFD alteration.<br /><br>- Number of complaints on the SFN-SIQ related to proximal/distal IENFD ratio.<br /><br>- Change in VAS related to IENFD alteration.<br /><br>- VAS-score related to proximal/distal IENFD ratio.<br /><br>- Changes on NPS related to IENFD alteration.<br /><br>- NPS-score related to proximal/distal IENFD ratio.<br /><br>- The value of abnormal TTT at baseline as predictor of abnormal IENFD in<br /><br>future.</p><br>