Analysis of mutations in 17p 11.2 region in patients with Charcot-Marie-Tooth type 1 disease and patients with tomaculose neuropathy

Charcot-Marie-Tooth type 1Α disease (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are common inherited disorders of the peripheral nervous system associated with duplication and deletion respectively, of the 17p11.2 segment including the gene of peripheral myelin protein 22. We studied 48 subjects belonging to 29 families with clinical and electrophysiological signs of definite CMT1, 20 patients with suspected CMT phenotype, and 17 patients and healthy members of their families with HNPP. Blood sampling and DNA isolation, PCR, restriction analysis, southern blotting were performed using standard procedures. Of 48 patients with diagnosis of definite CMT1 in 25 (52%) we found a 1.5 Mb tandem duplication in chromosome 17p11.2. These duplications were not found in any of 20 sporadic cases with the clinical phenotype of CMT but without reliable electrophysiological data. Only 13 (44.8%)of 29 unrelated CMT1 patients from the first group had 17p11.2 duplications. Three of 4 sporadic cases (75%) with definite CMT1 had 17p11.2 duplications. Of 17 patients from 6 families with HNPP deletion of 17p11.2 segment was found in 15 (88.2%), as well as in 5 (83.3%) of six unrelated cases. Detection of CMT1A/HNPP recombination hotspot is a simple and reliable DNA diagnostic method, which is useful only for the patients with clinically already verified CMT1, and HNPP for further genetic counseling of patients and members of their families

A controlled trial of combination of methionine and antioxidants in ALS patients

We assessed a combination of methionine, vitamin E and selenium, as Alsemet(R) in a double blind, placebo controlled trial in 28 out patients with amyotrophic lateral sclerosis. After 12 months, 50% of patients in the placebo group were still alive as compared to 81.3% in the Alsemet(R) group (p<0.05). The rate of deterioration, limb and bulbar-function scores (p<0.05) and muscle-testing score (p<0.025) were significantly lower in the Alsemet(R) group than in the placebo group at the end of a sixth month treatment. We noted a significant increase in GSH-Px activity (p<0.05), as well as an increase in the amount of Vit E (p<0.05) in the Alsemet(R) group in comparison to the placebo group during the clinical trial.nul

Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients

Recent findings indicate that nitric oxide (NOcenter dot) over-production might be an important factor in the pathogenesis of sporadic amyotrophic lateral sclerosis (SALS). We measured significantly higher concentrations of uric acid and thiol group-containing molecules (R-SH groups) in the cerebrospinal fluid (CSF) from SALS patients compared to controls. The above factors, together with a slightly increased free iron concentration found in the CSF, favour conditions necessary for the formation of the dinitrosyl iron complex, capable of NOcenter dot bio-transformation. Thus, we performed ex vivo saturation of CSF ( from both SALS patients and controls) with NOcenter dot. A decrease in the level of R - SH was found. This was more pronounced in the CSF from SALS patients. In the CSF from SALS patients the production of nitrite and hydroxylamine was greater than that observed in the CSF from controls. Moreover, we also found increased Cu, Zn-SOD activity in the CSF from SALS patients ( when compared to control subjects) but no activity corresponding to Mn-SOD in any CSF samples. As Cu, Zn-SOD can react with nitroxyl forming NOcenter dot, the conditions for a closed, but continuous, loop of NOcenter dot biotransformation are present in the CSF of ALS patients.nul

Diagnosis and Treatment of Chronic Immune-mediated Neuropathies

The chronic autoimmune neuropathies are a diverse group of disorders, whose diagnosis and classification is based on the clinical presentations and results of ancillary tests. In chronic inflammatory demyelinating polyneuropathy, controlled therapeutic trials demonstrated efficacy for intravenous gamma-globulins, corticosteroids, and plasmaphereis. In multifocal motor neuropathy, intravenous gamma-globulins have been shown to be effective. In the other immune-mediated neuropathies, there are no reported controlled therapeutic trials, but efficacy has been reported for some treatments in non-controlled trials on case studies. Choice of therapy in individual cases is based on reported efficacy, as well as severity, progression, coexisting illness, predisposition to developing complications, and potential drug interactions