[A critical review of the current pathogenesis of multiple sclerosis and possible future trends].
BACKGROUND
Multiple sclerosis (MS) is a disorder in which the pathogenesis is not clearly understood, but where the disability caused and its progression determine the seriousness of the condition. At present, inflammation due to T lymphocytes is thought to be the cause of the clinical features and resulting disability. The main feature is demyelination, but it has not been possible to show by immunology studies, neuroimaging studies or therapeutic trials that the binomial inflammation-demyelination correlates with the disability. Therefore other possibilities of pathogenesis which provide a better explanation for the clinical findings in MS may be considered.


METHODS
We may start with the hypothesis of the existence of gliotoxic and neurotoxic factors in a patient with MS. These, by means of electrical inhibition mechanisms, autoimmune phenomena and loss of the normal neurone-oligodendrocyte-astrocyte relationship, or a non-specific immune response may give place to inflammation with secondary demyelination on the one hand and to axonopathy with alterations in the mechanisms of remyelination due to alterations in the signals between the axon and the oligodendrocyte on the other.


CONCLUSIONS
When these three factors are considered, a better explanation is found for the factors which determine the progression of the disability, exhaustion of the inflammatory response, deficient remyelination and the poor correlation between demyelination and the progression of the disease. At the same time, new possibilities for approaches to the treatment and investigation of MS appear.
Casanova
B
B
Servei de Neurologia, Hospital Universitari La Fe, Valencia, España. bcasanovae@meditex.es
Burgal
M
M
Coret
F
F
D001253:Astrocytes / Q000473:pathology; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology*; D003711:Demyelinating Diseases / Q000473:pathology; D005544:Forecasting; D006801:Humans; D009103:Multiple Sclerosis / Q000473:pathology*; D009410:Nerve Degeneration / Q000473:pathology; D009836:Oligodendroglia / Q000473:pathology; D012106:Research / Q000639:trends
Revisión crítica de la patogenia actual de la esclerosis múltiple y futuras direcciones posibles.