Cold paresis in multifocal motor neuropathy

Abstract

Increased weakness during cold (cold paresis) was reported in single cases of multifocal motor neuropathy (MMN). This was unexpected because demyelination is a feature of MMN and symptoms of demyelination improve, rather than worsen, in cold. It was hypothesized that cold paresis in MMN does not reflect demyelination only, but may indicate the existence of inflammatory nerve lesions with permanently depolarized axons that only just conduct at normal temperature, but fail at lower temperatures. We investigated symptoms of cold paresis in 50 MMN patients, 48 chronic inflammatory demyelinating polyneuropathy (CIDP) patients, 35 progressive spinal muscular atrophy (PSMA) patients, and 25 chronic idiopathic axonal polyneuropathy patients. We also investigated symptoms of increased weakness during warmth (heat paresis). Cold paresis was reported more often than heat paresis. Cold paresis was most frequently reported in MMN. Multivariate analysis indicated that MMN patients had a 4- to 6-fold higher risk of reporting cold paresis than CIDP or PSMA patients. Because cold paresis is not consistent with demyelination, the lesions in MMN may involve other mechanisms than demyelination only. In conclusion, symptoms of cold paresis are common in peripheral nervous system disorders, particularly in MMN. This supports the above-described hypothesis.

The pathogenesis of multifocal motor neuropathy and an update on current management options

“…Patients frequently experience an exacerbation of weakness with cold, in line with the disruption of nodal sodium-channel clusters and dysfunction of nodal sodium channels, suggested above as possible underlying mechanisms [Straver et al 2011a]. In addition, a marked motor deficit with no or slight amyotrophy may probably be considered a hallmark of the disease and the clinical expression of CB [van Schaik et al 2010] Interestingly, the extent of sensory signs and symptoms has been reconsidered and the development of electrophysiological sensory changes, with or without sensory signs and symptoms over the course of MMN, has been reported (see below) [Lievens et al 2009;Delmont et al 2009].…”

Multifocal motor neuropathy

“…29 Despite the fact that in most demyelinating disorders, symptoms worsen in heat, in MMN, 'cold paresis' with worsening of weakness in cold temperature has been reported. 30 One study suggested a 4-6 fold increased risk of cold paresis in MMN compared with chronic inflammatory demyelinating polyneuropathy (CIDP). 30 Whether this is because MMN is caused by a channelopathy at the node of Ranvier rather than demyelination remains unclear (see below).…”

Conducting processes in simulated chronic inflammatory demyelinating polyneuropathy at 20°C–42°C

“…Other studies of the e®ects of temperature on the conduction block in human arm or leg nerves (median nerve, ulnar nerve, radial nerve and musculocutaneous nerve up to the lower neck and the peroneal and tibial nerves up to the knee) focused on either cooling (cold paresis) or warming (heat paresis) in patients with MMN and CIDP (Van Asseldonk et al, 2003;Straver et al, 2011;Straver, 2013). Conduction block in limb nerves is found in all investigated MMN patients and in 82% of CIDP patients, as patients report cold paresis more often than heat paresis.…”

“…In this so-called heat paresis, weakness of the limbs increases. Patients with peripheral nervous disorders, such as chronic in°ammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN), often state that weakness also increases during cold and a conduction block of depolarized action potentials in the so-called cold paresis is observed (Straver, 2013;Straver et al, 2011). In these studies, cold paresis is reported more often than heat paresis.…”

“…14, No. 1 (2015) demyelinating neuropathies (Chaudhry et al, 1993;Franssen et al, 1999;Kaji, 2003;Rutkove, 2001;Straver, 2013;Straver et al, 2011). In this so-called heat paresis, weakness of the limbs increases.…”