Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 75

Abstract

Monoclonal IgM antibodies against myelin‐associated glycoprotein (MAG) are associated with a chronic demyelinating neuropathy characterized by predominant involvement of large sensory fibers, although nerve conduction study reveals preferential demyelination of distal motor fibers. In sural nerve biopsy, deposits of monoclonal IgM are found at sites of MAG localization such as Schmidt‐Lanterman incisures and paranodal loops, but also on the surface of myelinated nerve fibers (mesaxon). Distal involvement in sensory fibers cannot be assessed by routine studies. Therefore, we investigated sensory fibers by skin biopsy in 13 patients with anti‐MAG neuropathy. Patients with CIDP (n = 8) and with IgM anti‐MAG negative paraproteinemic neuropathy (n = 3) were used as diseased controls. Skin biopsy was performed using a 3 mm punch at the proximal thigh (n = 20), at the distal leg (n = 21), at the hand or arm or fingertip (n = 23). Specimens were processed to quantify the density of intra‐epidermal nerve fibers (IENF) using the anti‐protein gene product 9.5 (PGP 9.5). Both anti‐MAG patients and CIDP patients showed a proximal‐distal gradient in IENF density decrease, indicating a length‐dependent fiber loss, as typically seen in other neuropathies. Further, we investigated anti‐MAG immunoreactivity and the presence of IgM deposits in dermal myelinated fibers by confocal microscopy. IgM deposits were detected on the surface of MAG positive fibers in the dermis of 11 anti‐MAG patients (85%), but not in diseased controls. IgM deposits were also located at paranodal loops. Our study shows that small myelinated fibers in the skin are involved in anti‐MAG neuropathy, and that IgM deposits can be demonstrated in terminal sensory fibers. Skin biopsy provides a useful, minimally traumatic method for early diagnosis as well as for follow‐up studies of anti‐MAG neuropathy. Supported by a Fellowship of the European Neurological Society.