TY  - JOUR
A1  - Burlina, Alessandro P.
A1  - Sims, Katherine B.
A1  - Politei, Juan M.
A1  - Bennett, Gary J.
A1  - Baron, Ralf
A1  - Sommer, Claudia
A1  - Moller, Anette Torvin
A1  - Hilz, Max J.
T1  - Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel
JF  - BMC Neurology
N2  - Background: 

Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. 

Methods: 

An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. 

Results: 

We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e. g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. 

Conclusions: 

Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate.
KW  - Enzyme replacement therapy
KW  - Quality of life
KW  - Small-fiber neuropathy
KW  - Rochester diabetic neuropathy
KW  - Randomized controlled trial
KW  - Agalsidase beta therapy
KW  - Outcome survey
KW  - Pharmacological management
KW  - Clinical manifestations
KW  - Alpha galactosidase
KW  - Diagnosis
KW  - Fabry
KW  - Disease
KW  - Neuropathy
KW  - Pain
KW  - Treatment
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135309
VL  - 11
IS  - 61
ER  - 
TY  - JOUR
A1  - Simon, Christian M.
A1  - Rauskolb, Stefanie
A1  - Gunnersen, Jennifer M.
A1  - Holtmann, Bettina
A1  - Drepper, Carsten
A1  - Dombert, Benjamin
A1  - Braga, Massimiliano
A1  - Wiese, Stefan
A1  - Jablonka, Sibylle
A1  - Pühringer, Dirk
A1  - Zielasek, Jürgen
A1  - Hoeflich, Andreas
A1  - Silani, Vincenzo
A1  - Wolf, Eckhard
A1  - Kneitz, Susanne
A1  - Sommer, Claudia
A1  - Toyka, Klaus V.
A1  - Sendtner, Michael
T1  - Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy
JF  - Acta Neuropathologica
N2  - Diabetic neuropathy (DNP), afflicting sensory and motor nerve fibers, is a major complication in diabetes.The underlying cellular mechanisms of axon degeneration are poorly understood. IGFBP5, an inhibitory binding protein for insulin-like growth factor 1 (IGF1) is highly up-regulated in nerve biopsies of patients with DNP. We investigated the pathogenic relevance of this finding in transgenic mice overexpressing IGFBP5 in motor axons and sensory nerve fibers. These mice develop motor axonopathy and sensory deficits similar to those seen in DNP. Motor axon degeneration was also observed in mice in which the IGF1 receptor(IGF1R) was conditionally depleted in motoneurons, indicating that reduced activity of IGF1 on IGF1R in motoneurons is responsible for the observed effect. These data provide evidence that elevated expression of IGFBP5 in diabetic nerves reduces the availability of IGF1 for IGF1R on motor axons, thus leading to progressive neurodegeneration. Inhibition of IGFBP5 could thus offer novel treatment strategies for DNP.
KW  - Motor nerve biopsy
KW  - Diabetic polyneuropathy
KW  - Neuropathy
KW  - Neurotrophic factors
KW  - Axonal degeneration
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154569
VL  - 130
SP  - 373
EP  - 387
ER  -