In this study, we will determine the IENFD after at least one year since the first skin biopsy was taken, in patients with the diagnosis of SFN based on the clinical picture and abnormal TTT, but with a normal IENFD at presentation. A biopsy will be…
ID
Source
Brief title
Condition
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Current IENFD at the ankle compared with the IENFD that has been taken during
the regular visit, at least one year before. The degree of IENFD decrease or
increase over time (corrected for expected age-dependent decline) will be
computed. Furthermore, the percentage of IENFD results that turn from normal
into abnormal will be calculated.
- Proximal/distal IENFD ratio normative values.
- The proximal/distal IENFD ratio compared between SFN patients and healthy
subjects.
Secondary outcome
- Change in number of complaints on the SFN-SIQ related to IENFD alteration.
- Number of complaints on the SFN-SIQ related to proximal/distal IENFD ratio.
- Change in VAS related to IENFD alteration.
- VAS-score related to proximal/distal IENFD ratio.
- Changes on NPS related to IENFD alteration.
- NPS-score related to proximal/distal IENFD ratio.
- The value of abnormal TTT at baseline as predictor of abnormal IENFD in
future.
Background summary
Small fiber neuropathy (SFN) is a condition in which the smallest nerve fibers
are affected, characterized by neuropathic pain and autonomic dysfunction.
According to the international criteria, the diagnosis SFN is based on clinical
symptoms in combination with abnormal temperature threshold testing (TTT)
levels and/or reduced intraepidermal nerve fiber density (IENFD) in skin
biopsy. The IENFD reflects the severity of axonal degeneration and is an
objective and reliable tool. However, it has a moderate sensitivity to confirm
the diagnosis SFN, resulting in false negative findings. It is known that IENFD
decreases with age, but only one study has been performed to monitor IENFD
during disease course. It is conceivable the decrease of IENFD occurs faster in
SFN than in healthy people. Besides, at the moment only the distal IENFD is
used to establish the diagnosis SFN. This location is chosen because of the
length-dependent general acceptance of its pattern, although non-length
dependent forms have been published. To show the length-dependency the
proximal/distal IENFD ratio could be used. It is hypothesized that this ratio
might be higher in SFN than in healthy subjects. Both follow-up of IENFD and
determination of the proximal/distal IENFD ratio may have implications for the
diagnostic strategy in patients with possible SFN, because IENFD may be normal
at presentation and decrease to abnormal over time, or will remain within the
normal range, but might show an increased proximal/distal ratio compared with
healthy people.
Study objective
In this study, we will determine the IENFD after at least one year since the
first skin biopsy was taken, in patients with the diagnosis of SFN based on the
clinical picture and abnormal TTT, but with a normal IENFD at presentation. A
biopsy will be taken at the ankle and at the thigh of the same leg. We will
differentiate between patients with idiopathic SFN and patients with a sodium
channelopathy related SFN. Since no proximal/distal IENFD ratio normative
values are present, we will include a healthy age-/gender-stratified control
group. Second, we will investigate the relationship between the change of
IENFD, proximal/distal IENFD ratio and the amount and severity of SFN
complaints (reported with the SFN-symptom inventory questionnaire, visual
analogue scale for pain and neuropathic pain scale), and the TTT results.
Sensitivity and specificity comparison studies will be performed to determine
which technique or combination of findings will yield the highest clinically
applicable method.
Study design
The study is a non-randomized, longitudinal study.
Study burden and risks
The estimated time of duration for the examination is maximal 60 minutes.
During this time, the subjects will be asked about their actual complaints and
neurological examination will be conducted. Also, the subjects need to fill out
questionnaires and will undergo a skin biopsy. Patients also need to travel
to/from our hospital.
Oxfordlaan 10 Oxfordlaan 10
AZ 6201
NL
Oxfordlaan 10 Oxfordlaan 10
AZ 6201
NL
Listed location countries
Age
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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL54704.068.16 |