Pathologie und Pathogenese der progredienten Multiplen Sklerose: Konzepte und Kontroversen

Zusammenfassung

Die Multiple Sklerose (MS) ist eine entzündliche Erkrankung des zentralen Nervensystems, die in der Frühphase oft von schubförmig auftretenden, häufig reversiblen neurologischen Ausfällen dominiert wird. Mit zunehmender Erkrankungsdauer werden diese Krankheitsschübe in der Regel mehr und mehr von einem progredienten Krankheitsprozess überlagert, der zu einem irreversibel fortschreitenden Verlust der motorischen, sensiblen und kognitiven Leistungsfähigkeit führt. Diese progrediente Phase der Multiplen Sklerose ist bis heute nur unzureichend verstanden und therapierbar. Ausgehend von aktuellen Befunden zur Pathologie und Pathogenese versuchen wir ein umfassendes pathomechanistisches Konzept der progredienten MS zu entwerfen und auf dessen Grundlage Stellung zu aktuellen Kontroversen zu beziehen. So diskutieren wir, inwieweit neurodegenerative oder entzündliche Krankheitsprozesse die entscheidenden Antreiber der Progression sind, hinterfragen, ob die Aufteilung in primär und sekundär progrediente MS pathomechanistisch sinnvoll ist, und untersuchen, welche Therapiestrategien am ehesten geeignet sind, der fortschreitenden Behinderung der betroffenen Patienten entgegenzuwirken.

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system that initially is often dominated by relapsing-remitting neurological symptoms. With increasing disease duration, these relapses are more and more superimposed by a progressive disease process that leads to irreversible accumulation of motor, sensory and cognitive deficits. This progressive phase of MS is still only incompletely understood and by and large refractory to therapy. Here we aim to use recent pathological and pathomechanistic insights to outline a unifying pathomechanistic concept of progressive MS. Based on this view of the disease, we examine current controversies surrounding progressive MS. We discuss whether neurodegenerative or inflammatory processes drive progression, and whether the classification of primary and secondary progressive MS is all that useful; we also consider which therapeutic strategies are best suited to limit the insidious decline of progressive MS-patients.

Schlüsselwörter

Multiple Sklerose - Pathologie der weißen Substanz - Pathologie der grauen Substanz - chronische Entzündung - Neurodegeneration

Key words

multiple sclerosis - white matter pathology - grey matter pathology - chronic inflammation - neurodegeneration

^* Diese Autoren haben in gleichem Umfang zu dieser Arbeit beigetragen.

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