Recently mutations in sodium channel genes were found in a subset of patients with small fibre neuropathy. These sodium channels are involved in the generation of pain signals that are transmitted to the brain.
The PROPANE-study (Probing the role of sodium channels in painful neuropathies) is an international study, supported by the EU FP7 Framework, aiming to investigate the role of sodium channels in painful neuropathy. The objective of this study is to find more pain genes involved in the development of painful neuropathy, as well as to find possible new treatment strategies, based on these genes. Patients with small fibre neuropathy or with painful or non-painful diabetic neuropathy can be included in this study. Study inclusion ends by Oktober 2016.
The diagnosis of small fibre neuropathy is often difficult. Temperature threshold testing may also be abnormal in other conditions (i.e. lacks specificity), whereas the nerve fibre density in a skin biopsy is not decreased in every patient.
Therefore, we want to investigate whether other tests can be helpful in determining dysfunction and damage of small nerve fibres.
Cornea confocal microscopy
Cornea confocal microscopy is a non-invasive test to determine the density of small nerve fibres in the cornea of the eye. This test has shown reduced small nerve fibres in patients with diabetic neuropathy. We aim to investigate whether the test is useful in the diagnosis of small fibre neuropathy.
Skin Wrinkling Test
Several centres use the Skin Wrinkling Test, that determines the degree of wrinkling of the finger tips after holding the hands in water, or after application of crème. Currently, the degree of wrinkling is visually determined, and this does not seem to be very reliable. We are therefore developing an automated and more optimized method to determine skin wrinkling.
Pain signals are transmitted to the brain. Functional MRI (fMRI) of the brain can visualize functional activity in the brain. We aim to investigate whether the functional activity of the brain is different in patients with small fibre neuropathy compared to healthy persons
Small fibre neuropathy and itch
Recently, attention has been drawn to the troublesome symptom of itch in small fibre neuropathy. We use digital questionnaires to study the presence and characteristics of itch, and to investigate factors that may influence itch.
Optimisation of outcome measures and questionnaires
To increase the knowledge of small fibre neuropathy, we ask patients to fill in questionnaires. These questionnaires can also be used as outcome measure, for example to determine therapeutic efficacy. We investigate how to optimize these outcome measures. Therefore, sometimes we ask our patients to fill in the same questionnaire at two time points.
In the lacosamide-trial the effect of the drug lacosamide that blocks certain sodium channels will be investigated. Patients with small fibre neuropathy and a mutation in the sodium channel NaV1.7 were included in this study. If the drug has a beneficial affect, it may eventually also be tested in other patients with small fibre neuropathy. The last patient of the study was included in July 2016. The first results are expected in the beginning of 2017.
Intravenous immunoglobulins study
This study started in July 2016. Patients with small fibre neuropathy without underlying cause will be treated with intravenous immunoglobulins or placebo. Immunoglobulins are proteins that play a role in the immune system. There are indications that immunoglobulins may be effective in small fibre neuropathy, but this has never been systematically investigated. Sixty patients will be enrolled in this study, and only patients living in the Netherlands or Belgium can participate in the study. The results will be available after the last patients have finished their treatment period.
In 2016 a study will start with a neurostimulator as treatment for pain in patients with small fibre neuropathy. The neurostimulator will be implanted in the back, with an electrode stimulating the spinal cord. This may diminish the pain in the feet and legs. Only patients with pain predominantly in feet and legs can participate in this study. The study is conducted with the pain clinic of the Maastricht UMC+.