Journal of Neurological Sciences 152 (1997) 218–223 Cryoglobulinaemic neuropathy manifesting with restless legs syndrome * Franco Gemignani , Adriana Marbini, Guido Di Giovanni, Sultan Salih, Francesco P. Margarito, Giovanni Pavesi, Mario Giovanni Terzano Institute of Neurology, University of Parma, Parma, Italy Received 29 November 1996; received in revised form 21 May 1997; accepted 24 May 1997 Abstract In a series of 12 patients with essential mixed cryoglobulinaemia (EMC) and peripheral neuropathy as main feature of the disease, restless legs syndrome (RLS) was a major manifestation in four women, aged 55–65 years. In one patient RLS was a presenting manifestation of the disease, and in another patient the diagnosis of EMC was made investigating RLS and polyneuropathy, although prior rheumatological symptoms were retrospectively recognized. All patients with RLS had symmetrical sensory polyneuropathy, but non-RLS patients had also other forms of peripheral neuropathy, and symmetrical sensory polyneuropathy only in two of eight cases ( P50.03). Neurophysiological study showed that sensory action potentials of the sural nerve were more often inelicitable in non-RLS patients (six of eight) than in RLS patients (none of three). Sural nerve biopsy had no distinctive features in three RLS patients, with regard to other patients with cryoglobulinaemic neuropathy. RLS seems not uncommon in cryoglobulinaemic neuropathy, and significantly associated with symmetrical sensory polyneuropathy, whereas patients with other subtypes of cryoglobulinaemic neuropathy do not develop RLS; thus, a disorder of the sensory inputs may be important in the pathogenesis of RLS. The occurrence of RLS, especially in middle-aged women, should prompt investigations for peripheral neuropathy focusing on cryoglobulinaemic neuropathy.  1997 Elsevier Science B.V. Keywords: Cryoglobulinaemic neuropathy; Restless legs syndrome; Sensory neuropathy 1. Introduction manifestations may occur secondarily to other diseases, and in particular in association with various forms of The restless legs syndrome (RLS) is characterized by peripheral neuropathy (Gorman et al., 1965; Callaghan, irresistible urge to move the legs, accompanied or preceded 1966; Heinze et al., 1967; Matchey, 1971; Ekbom, 1987; by dysesthetic sensations deep inside the legs, especially Walters and Hening, 1987; Salvi et al., 1990; Rutkove et when sitting or lying down (Ekbom, 1945). The nature of al., 1996), and in some patients with apparently idiopathic neural mechanisms involved in RLS is still controversial, RLS, axonopathic changes have been demonstrated by although it is usually considered of central origin, possibly sural nerve biopsy (Iannaccone et al., 1995). Nevertheless, related to a pacemaker located in the reticular formation RLS is still overlooked as a manifestation of peripheral (Lugaresi et al., 1972), and it is also unclear if the primary neuropathy. We report the occurrence of RLS as an event is represented by the motor or the sensory mani- outstanding feature in patients with cryoglobulinaemic festations or both (Pelletier et al., 1992; Trenkwalder et al., neuropathy. 1996). RLS may be idiopathic, or associated with several medical conditions, including systemic diseases (Ekbom, 1987). Although most studies were dedicated to the 2. Patients and methods idiopathic form of RLS, it is well known that identical Clinical manifestations were reviewed in a series of 21 * Corresponding author. Tel.: 139 521 259511; fax: 139 521 282776. consecutive patients (19 women, 2 men) with peripheral 0022-510X / 97 / $17.00  1997 Elsevier Science B.V. All rights reserved. PII S0022-510X(97)00187-1