How to distinguish Guillain-Barré syndrome from nitrous oxide-induced neuropathy: A 2-year, multicentric, retrospective study.

BACKGROUND: Recreational use of nitrous oxide (N2 O) has dramatically increased in recent years, resulting in numerous cases of acute sensorimotor tetraparesis secondary to nitrous oxide-induced neuropathy (N2 On). Challenging clinical features can mimic Guillain-Barré syndrome (GBS), the main differential diagnosis upon admission. The most sensitive biomarkers for distinguishing between these two conditions remain to be determined. METHODS: Fifty-eight N2 On patients from three referral centers were retrospectively included over a 2-year period and compared to GBS patients hospitalized during the same timeframe (47 patients). Collected demographic, clinical, biological, and electrophysiological data were compared between the two groups. RESULTS: The typical N2 On clinical pattern included distal sensorimotor deficit in lower limbs with absent reflexes, proprioceptive ataxia, and no cranial involvement (56.7% of our cohort). Misleading GBS-like presentations were found in 14 N2 On patients (24.1%), and 13 patients (22.4%) did not report N2 O use during initial interview. Only half the N2 On patients presented with reduced vitamin B12 serum levels upon admission. A slightly increased cut-off (<200 pmol/L) demonstrated 85.1% sensitivity and 84.5% specificity in distinguishing N2 On from GBS. Only 6.9% of N2 On patients met the criteria for primary demyelination (p < 0.01), with only one presenting conduction blocks. A diagnostic algorithm combining these two biomarkers successfully classified all GBS-like N2 On patients. CONCLUSIONS: Vitamin B12 serum level < 200 pmol/L cut-off and conduction blocks in initial electrophysiological study are the two most sensitive biomarkers for rapidly distinguishing N2 On from GBS patients. These two parameters are particularly useful in clinically atypical N2 On with GBS-like presentation.

[First meeting of the French CEIP (centres d'évaluation et d'information sur la pharmacodépendance). Assessment of the abuse and pharmacodependence potential during drug development]. / Premières journées nationales de pharmacodépendance (CEIP). Place de la pharmacodépendance dans l'évaluation du médicament.

The French system for the evaluation of abuse and dependence created in 1990 was definitely implemented in 1999 with the decree no99-249 making in particular mandatory the reporting of all serious cases of abuse or dependence to psychoactive drugs. This decree was also important to define the role of each party (regulatory agencies, pharmaceutical companies, health professionals and the network of the regional Centres for Evaluation and Information of Pharmacodependence) for all marketed psychoactive drugs in France. The first meeting on pharmacodependence was organized during the last annual congress of the French Society of Therapeutic Pharmacology and Physiology (P2T) held in Toulouse in April 2007. The aim of this meeting was that the role of the French system for the evaluation of abuse and dependence during the different steps of drug approval and after marketing in the context of real life would be better known. The French approach includes classical data obtained from experimental and clinical trials, but also and mainly data obtained from the specific tools installed since the creation of the CEIP.

Ascorbic acid inhibits PMP22 expression by reducing cAMP levels.

Charcot-Marie-Tooth [CMT] syndrome is the most common hereditary peripheral neuropathy. CMT1A, which accounts for 50% of all CMT cases, usually results from triploidy of the PMP22 gene. Preclinical trials using an animal model show that disabled mice force-fed with high doses of ascorbic acid partially recover muscular strength after a few months of treatment, and suggest that high doses of ascorbic acid repress PMP22 expression. In this study, we demonstrated that ascorbic acid represses PMP22 gene expression by acting on intracellular cAMP levels and adenylate cyclase activity. This action is dose dependent and specific to ascorbic acid, since repression is not observed after treatment with other antioxidants. The new properties of ascorbic acid are discussed, along with the implications of these findings for CMT disease treatment.

[Pharmacologic criteria for medical substitution in opiate dependence]. / Critères pharmacologiques d'un médicament pour la substitution de la pharmacodépendance aux opiacés.

Our goal was to establish new pharmacological criteria for a drug to be used in the treatment of opioid dependence. We propose the following six pharmacodynamic and pharmacokinetic criteria: (i) the same pharmacodynamic properties as the drug being substituted; (ii) a long duration of action (minimum 24 hours, not requiring several daily doses) in order to prevent fluctuations in effect and especially withdrawal symptoms; (iii) few euphoric effects together with a minimal reinforcing effect for the drug itself and other drugs; (iv) oral or sublingual administration without any special affinity for other routes, especially the intravenous; (v) a New Drug Application (NDA) in this indication, after submission of a dossier including both clinical randomised comparative trials and security data; and (vi) compatibility with a socially satisfying quality of life. These criteria were applied to methadone, buprenorphine and other drugs that were proposed in the treatment of opioid dependence (such as morphine or codeine).