J Neurol (2011) 258:212–217 of Ranvier and the node that is next to be activated. First, paranodal demyelination results in current leakage at the node-to-be-activated, so that less current is available to depolarize this node [11]. Secondly, raising temperature will decrease sodium-channel open time at the active node [6, 21]. This yields a further decrease in the current available to depolarize the node-to-be-activated. If there is just sufﬁcient current available to sustain action potential propagation at a demyelinated internode, an additional decrease in current due to rising temperature may, there- fore, induce conduction block as was shown in single demyelinated internodes [19]. In the authors’ experience, however, patients with peripheral nervous system disorders often state that weakness during cold increases. This cold paresis is not consistent with the above-described mechanism because that would lead to less weakness in cold. Whether or not cold paresis is really common and if it is related to speciﬁc disorders has not been investigated. Furthermore, the mechanisms of cold paresis are not clear. Cold paresis was only reported in single cases of multifocal motor neurop- athy (MMN) and in patients with Hirayama disease [11, 23]. To explain cold paresis in MMN, Kaji hypothesized the existence of inﬂammatory nerve lesions with perma- nently depolarized axons that only just conduct at normal temperature [11]. At lower temperatures, Na/K-pump activity decreases due to the thermal reduction of its ATP-ase activity; this may cause additional depolarization, yielding depolarizing conduction block and weakness [9–11]. Recent ﬁndings from our group supported the hypothesis of Kaji by showing that cooling indeed induced depolariza- tion of human motor axons, and that this depolarization was best explained by decreased pump-activity [7]. Since, in the future, such axons may possibly be saved from degeneration by neuroprotective treatment, cold paresis may become an important symptom [13, 22, 30]. The present study was not conducted to investigate the mechanism of cold paresis but to assess if symptoms of cold paresis are common in MMN and if they are speciﬁc for MMN. If cold paresis were a common symptom, it may instigate further research into its mechanisms. If cold Table 1 Baseline characteristics 213 paresis were speciﬁc for MMN, it may form a clue for the pathogenesis of MMN, which is currently unknown. We investigated the frequency of symptoms of cold paresis and heat paresis in a large group of patients with MMN. Con- trol groups included CIDP, sporadic progressive spinal muscular atrophy (PSMA), and chronic idiopathic axonal polyneuropathy (CIAP). Materials and methods Patients A cross-sectional study was performed by sending a ques- tionnaire to 60 patients with MMN, 60 with CIDP, 50 with sporadic PSMA, and 35 patients with CIAP. All patients had weakness in arm or leg muscles on neurological examina- tion. The questionnaire was returned by 83% of MMN, 80% of CIDP, 70% of PSMA, and 71% of CIAP patients. For each group, the patients who did not return the questionnaire did not differ signiﬁcantly from the patients who returned the questionnaire with respect to sex, age, and disease duration (data not shown). Patient characteristics are presented in Table 1. Two patients in the PSMA group had Hirayama disease. The patients attended the outpatient clinics of the University Medical Center in Utrecht, a tertiary referral center for neuromuscular disorders in the Netherlands. Diagnoses were based on criteria sets for MMN [28], CIDP [1], sporadic PSMA [29], and CIAP [16]. In these sets, the criteria for conduction block were adapted [27, 28]. All MMN patients were on intravenous immunoglobulins (IVIg) maintenance treatment. Twenty-eight patients with CIDP were treated with IVIg, with 20 patients responding favor- ably. Twelve patients with CIDP were treated with steroids, with 11 patients responding favorably. Of the remaining CIDP patients, two were successfully treated with cyclo- phosphamide and six were not treated. None of the patients had concomitant diseases of the central or peripheral nervous system. All participants gave informed consent to participate in the study, which was approved by the Medical Ethical Committee of the University Medical Center Utrecht. Patient group MMN (n = 50) CIDP (n = 48) PSMA (n = 35) CIAP (n = 25) Male (%) 82 58 86 80 Age (years) 51 (33–74) 54 (22–82) 61 (35–83) 75 (61–89) Disease duration (years) 10 (2–39) 4 (0–32) 12 (4–30) 13 (4–21) Weakness arm (%) 100 88 86 28 Weakness leg (%) 68 96 51 100 Age and disease duration are given as median (range) CB conduction block; MMN multifocal motor neuropathy; CIDP chronic inﬂammatory demyelinating polyneuropathy; PSMA progressive spinal muscular atrophy; CIAP chronic idiopathic axonal polyneuropathy CB arm nerves (%) CB leg nerves (%) 68 44 0 0 24 19 0 0 123