[New biological and radiological markers in amyotrophic lateral sclerosis].
The only specific marker of sporadic amyotrophic lateral sclerosis (ALS), that represent about 90% of all cases, is neuropathological and based on the demonstration of motoneuronal degeneration associated with typical inclusions positive for ubiquitine and TDP-43. The gene encoding the superoxide dismutase 1 (SOD1) is implicated in about 10-20% of familial ALS. A mutation in the SOD1 gene can be considered as a genetic marker of ALS, and not a polymorphism, if the mutation has been shown to be pathogenic or to segregate to the disease in familial cases. Studies in blood or cerebral spinal fluid have shown biological changes involving different physiopathological pathways (oxidative stress, inflammation, excitotoxicity...). These abnormalities are neither sensitive nor specific enough to provide a diagnostic tool. The ectopic expression of Nogo-A in muscle biopsy is a promising marker but further studies are needed to demonstrate its value as a diagnostic tool in ALS. Studies in series of ALS patients have shown that MR-spectroscopy and diffusion tensor imaging can detect cortico-spinal degeneration. However, because of an overlap between patients and normal subjects, spectroscopic and DTI-parameters cannot be used as diagnostic tool in individual patients. In the future, a combination of biological, radiological and electrophysiological markers, rather than a single marker, may provide diagnostic tool for the diagnosis and follow-up of ALS patients.
Pradat
Pierre-François
PF
Fédération des maladies du système nerveux, Centre référent maladie rare SLA, APHP, Hôpital de la Pitié-Salpêtrière, F-75651 Paris Cedex 13, France. pierre-francois.pradat@psl.aphp.fr
D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D001921:Brain / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis; D003937:Diagnosis, Differential; D003952:Diagnostic Imaging; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D009046:Motor Neurons / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D009185:Myelin Proteins / Q000235:genetics; D009460:Neurologic Examination; D000070798:Nogo Proteins; D012680:Sensitivity and Specificity; D013116:Spinal Cord / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014452:Ubiquitins / Q000032:analysis
D015415:Biomarkers; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000606290:SOD1 protein, human; D014452:Ubiquitins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1