Cryoglobulinaemic neuropathy. A clinical, morphological and immunocytochemical study of 8 cases.
Clinical, pathological and immunocytochemical studies are described for 8 patients with cryoglobulinaemia and peripheral neuropathy: 5 had essential cryoglobulinaemia and 3 secondary cryoglobulinaemia. The cryoglobulins in 2 cases were type II (mixed cryoglobulins with a monoclonal component), type III (mixed polyclonal cryoglobulins) in 2 others, and were not characterized in 4. In all patients the neuropathy had an acute or subacute onset and in 7 it was initially asymmetric but, during the illness, in 3 it gradually progressed to a symmetric sensorimotor polyneuropathy. All patients had sural nerve biopsies. In 4 there was widespread vasculitis with necrosis of vessel walls and perivascular inflammatory cells. In another 2, thickening of vessel walls and luminal narrowing without inflammatory cell infiltration, together with loss of myelinated fibres from single fascicles or focally within fascicles, suggested that the neuropathy was of vascular origin. In all patients the main pathological damage was axonal degeneration. Signs of axonal regeneration were rare. The total number of myelinated fibres was reduced in all cases, from 24 to 95% below the lower limit of normal control values. Large diameter fibres were lost preferentially in 7 patients, being below 16.5% of the total number. Several possible pathogenetic mechanisms have been suggested for cryoglobulinaemic neuropathy, including immunologically mediated demyelination and ischaemic injury due to intravascular deposits of cryoglobulins or vasculitis. Our observations therefore confirm a major role for ischaemic factors, secondary to inflammatory vascular destruction, in the pathogenesis of peripheral neuropathy in most cases of types II and III cryoglobulinaemia.
Nemni
R
R
Department of Neurology, University of Milan, Istituto Scientifico San Raffaele, Italy.
Corbo
M
M
Fazio
R
R
Quattrini
A
A
Comi
G
G
Canal
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003449:Cryoglobulinemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007120:Immunochemistry; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008854:Microscopy, Electron; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D013497:Sural Nerve / Q000473:pathology / Q000648:ultrastructure
D007074:Immunoglobulin G; D007075:Immunoglobulin M