To document short-term and long-term responses to a single type of intravenous immunoglobulin (IVIg) in a large cohort of patients with multifocal motor neuropathy (MMN).
A retrospective study was ...conducted in 40 patients with MMN included on ENMC Workshop criteria, and treated with periodic IVIg infusions between 1995 and 2003. The short-term response was defined as improvement of at least 1 point on the MRC score in at least two affected muscles at 6 months. The population comprised 22 treatment-naïve patients (who had never received IVIg before inclusion), and 18 previously treated patients. For the long-term evaluation (>6 months), the patients were classified into three groups according to the dependency or not on periodic IVIg. In addition, changes in conduction block (CB) and predictive criteria for response to IVIg were explored.
The MRC score significantly improved (p<0.0001) in 14 (70%; 95% CI 0.46 to 0.88) of the 20 treatment-naïve patients (missing data for 2 patients). None of the predictive criteria studied were found to be significant. At the end of follow-up (mean of 2.2+/-2.0 years), only 8 of the 40 patients (22%) had significant remission, whereas 25 patients (68%) were dependent on periodic IVIg infusions. The number of CBs decreased or remained unchanged in 12 treatment-naïve patients and increased in 2 such patients.
This study confirmed a significantly high short-term response to IVIg of patients with MMN, but showed contrasted results in long-term follow-up. No predictive factors for response to IVIg were found.
Variation in genetic-based coloration is widespread among vertebrates, yet the underlying mechanisms explaining this polymorphism maintenance remain poorly known. Gene-by-environment interactions on ...fitness traits in a fluctuating environment are often invoked to explain the maintenance of such color diversity. According to this hypothesis, variation in coloration could signal alternative life-history strategies to cope with variable environmental conditions. However, empirical studies testing this hypothesis are still rare. Here, we aimed at comparing the variation of body mass maintenance behavior and reproductive traits between differently colored individuals in alternative environments. We exposed differently colored captive feral pigeons to different food conditions and immune challenges and measured their investment in body mass maintenance, egg laying, and offspring quality. Under food restriction, darker eumelanic females had a higher egg production, but darker adults tended to lose more body mass than paler conspecifics. Moreover, offspring reared in food-limited conditions had a higher body mass at fledging when sired by darker biological fathers, suggesting a positive genetic effect of a darker eumelanic coloration in harsh food conditions. In contrast, when food was abundant, pale- and dark-colored females had a similar egg production, but darker adults lost significantly less body mass than paler conspecifics. The immune challenge had no effect on adult body mass maintenance and reproduction. Differently colored individuals may thus display alternative reaction norms to different food conditions, suggesting that eumelanin-based coloration reflects how animals cope with variations in food availability. Spatiotemporal heterogeneity of food availability in natural systems may thus play a central role in the evolution of melanin-based coloration in wild animal populations.
Lewis–Sumner syndrome (LSS) is a dysimmune peripheral nerve disorder, characterized by a predominantly distal, asymmetric weakness mostly affecting the upper limbs with sensory impairment, and by the ...presence of multifocal persistent conduction blocks. The nosological position of this neuropathy in relation to multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is still debated. We report the clinical, biological and electrophysiological features, the course and the response to treatment in 23 LSS patients. The initial symptoms started in the distal part of an upper limb in 70% of patients. They were sensorimotor in 65% and purely sensory in 35% of patients. A cranial nerve involvement was observed in 26% of patients and a distal limb amyotrophy in 52%. The CSF protein level was normal in 67% of patients and mildly elevated in the remainder. None had serum anti-GM1 antibodies. There were multiple motor conduction blocks (average of 2.87/patient), predominantly located in the forearm, whereas demyelinating features outside the blocked nerves were rare. Abnormal distal sensory potentials were found in 87% of patients. The electrophysiological pattern suggests a very focal motor fibre demyelination sparing the nerve endings, whereas sensory fibre involvement was widespread. The course was chronic progressive in 71% of patients and relapsing–remitting in the others. During the follow-up study (median duration of 4 years), half of the patients progressed with a multifocal pattern and the distribution of the motor deficit remained similar to the initial presentation. The other patients showed a progression to the other limbs, suggesting a more diffuse process. Fifty-four percent of the patients treated with intravenous immunoglobulin showed an improvement, compared with 33% of the patients treated with oral steroids. Overall, 73% of patients had a positive response to immune-mediated therapy. LSS may be distinguished from MMN by the presence of sensory involvement, the absence of serum anti-GM1 antibodies and, in some cases, a positive response to steroids. In some of the patients in our study, LSS evolved into a more diffuse neuropathy sharing similarities with CIDP. Others had a clinical course characterized by a striking multifocal neuropathy, which suggests underlying mechanisms different from CIDP. Overall, whatever the clinical course, LSS responded to immune-mediated treatment in a manner similar to CIDP.
Background and purpose
Charcot−Marie−Tooth (CMT) 1C due to mutations in LITAF/SIMPLE is a rare subtype amongst the autosomal dominant demyelinating forms of CMT. Our objective was to report the ...clinical and electrophysiological characteristics of 18 CMT1C patients and compare them to 20 patients with PMP22 mutations: 10 CMT1A patients and 10 patients with hereditary neuropathy with liability to pressure palsies (HNPP).
Methods
Charcot−Marie−Tooth 1C patients were followed‐up in referral centres for neuromuscular diseases or were identified by familial survey. All CMT1A and HNPP patients were recruited at the referral centre for neuromuscular diseases of Pitié‐Salpêtrière Hospital.
Results
Two phenotypes were identified amongst 18 CMT1C patients: the classical CMT form (‘CMT‐like’, 11 cases) and a predominantly sensory form (‘sensory form’, seven cases). The mean CMT neuropathy score was 4.45 in CMT1C patients. Motor nerve conduction velocities in the upper limbs were significantly more reduced in CMT1A than in CMT1C patients. On the other hand, the motor nerve conduction velocity of the median nerve was significantly lower in CMT1C compared to the HNPP group. Distal motor latency was significantly more prolonged in CMT1A patients compared to the CMT1C and HNPP groups, the latter two groups having similar distal motor latency values. Molecular analysis revealed five new LITAF/SIMPLE mutations (Ala111Thr, Gly112Ala, Trp116Arg, Pro135Leu, Arg160Cys).
Conclusions
Our study delineates CMT1C as mostly a mild form of neuropathy, and gives clinical and electrophysiological clues differentiating CMT1C from CMT1A and HNPP. Delineating phenotypes in CMT subtypes is important to orient molecular diagnosis and to help to interpret complex molecular findings.
Several diagnostic criteria for multifocal motor neuropathy have been proposed in recent years and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs ...has been suggested in several trials and uncontrolled studies. The objectives were to prepare consensus guidelines on the definition, investigation and treatment of multifocal motor neuropathy. Disease experts and a patient representative considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements which were agreed in an iterative fashion. The Task Force agreed good practice points to define clinical and electrophysiological diagnostic criteria for multifocal motor neuropathy and investigations to be considered. The principal recommendations and good practice points were: (i) IVIg (2 g/kg given over 2–5 days) should be considered as the first line treatment (level A recommendation) when disability is sufficiently severe to warrant treatment. (ii) Corticosteroids are not recommended (good practice point). (iii) If initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2–4 weeks or 2 g/kg every 4–8 weeks (good practice point). (iv) If IVIg is not or not sufficiently effective then immunosuppressive treatment may be considered. Cyclophosphamide, ciclosporin, azathioprine, interferon beta1a, or rituximab are possible agents (good practice point). (v) Toxicity makes cyclophosphamide a less desirable option (good practice point).
Thalidomide is effective in several cutaneous diseases. Peripheral neuropathy is the most important adverse event limiting its use. Its incidence rate and its relation to thalidomide doses remain ...unclear. We prospectively monitored 135 patients treated with thalidomide for various dermatologic diseases for 2 y in order to estimate the annual incidence rate and risk factors for neuropathy. Patients underwent standardized neurologic examination and nerve conduction studies prior to, and regularly during treatment. Risk factors for neuropathy were assessed using a Cox proportional-hazards model. Clinical and electrophysiologic evidence of a thalidomide-induced neuropathy were present in 25.2% of the patients; however, when considering all potential cases, this rate reached 55.6%. The incidence rate was maximal during the first year of treatment (20%). The risk of neuropathy was related to the daily dose whatever the duration of treatment (p<10-3). Considering a daily dose ≤50 mg per day as reference, the relative risk for thalidomide neuropathy was 8.2 for a daily dose comprised between 50 and 75 mg per day and 20.2 for a daily dose >75 mg per day (p<10-3). No neuropathy occurred for daily doses ≤25 mg per day. The neuropathy was subclinical in nearly a quarter of patients with such an adverse event. These data confirm the high rate of thalidomide neuropathy and identify the daily dose as the main risk factor. The risk of neuropathy seems to be negligible for doses less than 25 mg per day, whatever the duration of therapy.
Summary Objective This paper describes a new electrode placement for recording compound muscle action potentials (CMAPs) of the first dorsal interosseous muscle (FDI) to determine the distal motor ...latency (DML) and study nerve conduction of the ulnar nerve across the wrist. Methods The DML to the FDI was evaluated bilaterally in 90 subjects after stimulation 1 cm proximal to the distal wrist crease and at the palm. The CMAP was recorded with a pair of disposable surface electrodes fixed over the FDI and wrist. Results The CMAP never exhibited a positive initial deflection, with a gain of 0.5 mV per division. DML to the FDI was 2.65 ± 0.26 ms (mean ± SD), and CMAP amplitude was 14.7 ± 3.3 mV. A prolonged DML was taken as 3.4 ms (mean + 3 standard deviation SD). Conclusions This new electrode placement offers more reproducible results for determining the DML to the FDI as it provides the shortest DML, and the tightest SD values. Significance This result is obtained through the respect of fundamental rules for CMAP recording, as it shows no positive wave at the onset of the CMAP of the FDI. Its use should improve the diagnosis of ulnar nerve lesions at the wrist and more especially of the deep motor branch.
Background. Paraprotein‐associated neuropathies have heterogeneous clinical, neurophysiological, neuropathological and haematological features. Objectives. To prepare evidence‐based and consensus ...guidelines on the clinical management of patients with both a demyelinating neuropathy and a paraprotein (paraproteinaemic demyelinating neuropathy, PDN). Methods. Search of MEDLINE and the Cochrane library, review of evidence and consensus agreement of an expert panel. Recommendations. In the absence of adequate data, evidence based recommendations were not possible but the panel agreed the following good practice points: (1) Patients with PDN should be investigated for a malignant plasma cell dyscrasia. (2) The paraprotein is more likely to be causing the neuropathy if the paraprotein is immunoglobulin (Ig)M, antibodies are present in serum or on biopsy, or the clinical phenotype is chronic distal sensory neuropathy. (3) Patients with IgM PDN usually have predominantly distal and sensory impairment, with prolonged distal motor latencies, and often anti‐myelin associated glycoprotein antibodies. (4) IgM PDN sometimes responds to immune therapies. Their potential benefit should be balanced against their possible side‐effects and the usually slow disease progression. (5) IgG and IgA PDN may be indistinguishable from chronic inflammatory demyelinating polyradiculoneuropathy, clinically, electrophysiologically, and in response to treatment. (6) For POEMS syndrome, local irradiation or resection of an isolated plasmacytoma, or melphalan with or without corticosteroids, should be considered, with haemato‐oncology advice.
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