Phenotypic spectrum of Charcot-Marie-Tooth disease due to LITAF/SIMPLE mutations: a study of 18 patients.

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.

Challenges in the treatment of chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic idiopathic demyelinating polyradiculoneuropathy (CIDP) is a rare disease, the most frequent one within the spectrum of the so-called "chronic immune-mediated neuropathies". Challenges in the treatment of CIDP firstly concern its diagnosis, which may be difficult, mainly for the atypical forms. Secondly, challenges encompass the choice of the first-line treatment, such as corticosteroids, intravenous immunoglobulins (IVIg), and plasma exchanges (PE) that have been proven as efficacious by several randomized controlled trials (RCT). Recent reports have focused on both different regimens of corticosteroids, and the occurrence of relapses following treatment with either corticosteroids or IVIg. These data may be helpful for the choice of the first-line treatment and may result in changing the guidelines for treatment of CIDP in clinical practice. The third and more difficult challenge is to manage long-term treatment for CIDP, since no immunomodulatory treatment has to date been proven as efficacious in this situation. Lastly, challenges in the treatment concern the choice of the best outcome measure for CIDP in RCT and clinical practice. The aim of this article is to overview the results of the more recently reported published trials for CIDP, and to give some insights for the current and future management of CIDP.