J Neurol (2011) 258:212–217 Table 4 Percentage of patients reporting cold and heat paresis Patient group Cold paresis Heat paresis p value p value – \0.001 0.001 0.002 18 26 6 17 – ns ns ns MMN CIDP PSMA CIAP 83 44 50 44 p values refer to comparison with MMN MMN multifocal motor neuropathy; CIDP chronic inﬂammatory demyelinating polyneuropathy; PSMA progressive spinal muscular atrophy; CIAP chronic idiopathic axonal polyneuropathy; ns not signiﬁcant PSMA patients (Tables 2, 3). Exposure to warming was more common than exposure to cooling and cold weather was the most common exposure to cooling. Despite this, patients reported cold paresis more often than heat paresis (Table 4). Cold paresis in arms or legs was reported more fre- quently in MMN than in CIDP, PSMA, and CIAP (Table 4). Multivariate analysis showed that these differences were independent of sex, age, and disease duration, except for CIAP (Table 5). Patients with MMN had a ﬁvefold higher risk of symptoms of cold paresis than patients with CIDP, and a sixfold higher risk than patients with PSMA. Multi- variate analysis for symptoms of cold paresis in arms and legs separately, showed that these differences were still signiﬁcant for the arms but not for the legs (Table 5). Heat paresis in arms or legs was not signiﬁcantly more or less frequently reported in MMN than in CIDP, PSMA and CIAP (Table 4). Neither univariate nor multivariate analysis showed any signiﬁcant differences between MMN and the other patient groups (data not shown). Discussion Patient groups MMN–CIDP MMN–PSMA MMN–CIAP The present study demonstrated that cold paresis was experienced by a substantial proportion of patients with Table 5 Risk of cold paresis in MMN versus other disorders 215 MMN, CIDP, PSMA, and CIAP. Cold paresis was more frequently reported than heat paresis. Cold paresis was more frequently reported in MMN than in CIDP, PSMA, or CIAP. Multivariate analysis indicated that MMN patients had a 4- to 6-fold greater risk of experiencing cold paresis than CIDP or PSMA patients. Because MMN predomi- nantly affects arm nerves [27], we analyzed symptoms of cold paresis in arms and legs separately; this showed that these differences were still signiﬁcant for the arms but not for the legs. In MMN, electrophysiological, pathological, and immunological studies suggest that several mechanisms may be involved in the unique process that results in asymmetric loss of strength and muscular atrophy. Motor nerve conduction studies may show conduction block and slowing consistent with demyelination in the same seg- ment; however, conduction velocity may also be normal in segments with motor conduction block [27, 28]. Some pathological studies of nerve branches containing motor and sensory axons showed demyelination but others only showed loss of axons [2, 5, 12, 24]. Needle electromyog- raphy studies showed extensive neurogenic abnormalities in non-atrophic as well as in atrophic muscles [26]. Excitability studies showed focal depolarization or hyper- polarization of motor axons of which the signiﬁcance is not clear [14, 17]. In many MMN patients, antibodies against epitopes presented on the axolemma are found, and a recent study showed that these anti-GM1 antibodies are associated with loss of motor axons [3]. Thus, whereas demyelination clearly occurs in MMN, mechanisms lead- ing to primary axonal degeneration may possibly occur as well. It is not clear if the conduction block is due to unfavorable effects of paranodal demyelination, blocking of impulse generation at the node, or both. Because MMN may lead to demyelination as well as loss of motor axons, we have chosen CIDP, PSMA, and CIAP as control groups in order to make a comparison to peripheral nervous sys- tem disorders that are also characterized by weakness: CIDP is characterized mainly by demyelination of motor p value \0.001 0.005 0.03 0.04 123 Arm and leg Univariate Multivariate Univariate Multivariate Univariate Multivariate Odds ratio 6.3 (2.4–16.6) 4.7 (1.7–13.4) 5.0 (1.8–13.8) 5.7 (1.8–18.1) 6.3 (1.9–20.8) 4.0 (0.4–36.5) p value \0.001 0.003 0.002 0.003 0.003 ns Arm Univariate Multivariate Univariate Multivariate Odds ratio 6.9 (2.4–20.0) 5.3 (1.7–16.7) 3.4 (1.1–10.3) 3.8 (1.04–14.3) Odds ratios are given with 95% conﬁdence intervals. Multivariate analysis was adjusted for age, sex, and disease duration. Cold paresis in arm muscles in the CIAP group was not analyzed because only two patients had upper limb weakness and were exposed to cold MMN multifocal motor neuropathy; CIDP chronic inﬂammatory demyelinating polyneuropathy; PSMA progressive spinal muscular atrophy; CIAP chronic idiopathic axonal polyneuropathy; ns not signiﬁcant