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Multiple sclerosis intra-blood-brain-barrier IgG synthesis: effect of pulse intravenous and intrathecal corticosteroids

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Abstract

Nine severely disabled clinically definite chronic progressive multiple sclerosis (MS) patients who had at least one determination of intra-blood-brain-barrier (BBB) IgG synthesis rate of greater than 7 mg/day (upper limit of normal=3.3) participated in this study. Seven patients were given 1 gram of methylprednisolone sodium succinate (MP) by intravenous infusion over 30 minutes once a day for 3 days. Statistically significant (p<.05) reduction in intra-BBB IgG synthesis (mg/day) was seeen in 4/7 patients, but in only 2 were normal levels of synthesis rate (<3.3 mg/day) attained. Rebound of IgG synthesis to premedication rates occurred within 30 days in 2/4 patients. There was no change in intensity or pattern of cerebrospinal fluid (CSF) oligoclonal IgG bands by isoelectric focusing, immunofixation, and silver staining. A subsequent course of intrathecal methylprednisolone acetate (MPA) (80 mg twice a week for 5 weeks) was given to 5 of the 7 patients and to 2 additional patients not previously treated. In spite of signs of subarachnoid inflammation, a statistically significant depression of intra-BB synthesis, which far exceeded that from the pulse treatment occurred in all 7, including the 2 patients whose intra-BBB IgG synthesis rates were previously resistant to pulse steroid administration. Normal levels of synthesis were rapidly reached in 4/7 patients; however, an IgG synthesis rebound occurred in 3/7 patiens which was just as rapid. One out of 7 patients showed a temporary reduction in the number of cathodic IgG oligoclonal bands in the CSF. Two patients required discontinuation of treatment due to aseptic meningitis in one and progressive weakness in the other. Clinically, these severely afflicted patients with fixed deficits remained unchanged with either treatment protocol. While MPA and ACTH have similar initial effect on the central nervous systems (CNS) inflammatory response in MS, the well documented risk of serious adversities with MPA prohibit its clinical use in MS in its present form.

Sommario

9 pazienti affetti da una forma avanzata di MS definita come progressiva cronica che avevano almeno una determinazione dell'indice di sintesi delle IgG di barriera emato-encefalica (BBB) superiore a 7 mg. pro die (limite superiore al normale=3.3) hanno partecipato a questa ricerca. A 7 pazienti è stato somministrato 1 g. di metilprednisolone sodio succinato per via endovenosa per la durata di 30 minuti una volta al giormo per 3 giorni.

In 4 su 7 pazienti è stata vista una riduzione statisticamente significativa della BBB mentre solo in due pazienti si raggiunsero i normali livelli di sintesi. In 2 su 4 pazienti il ritorno ai valori pre medicazione avvenne in 30 giorni. Non vi è stata variante delle bande oligoglonali IgG studiate col focusing isoelettrico, l'immunofissazione e la colorazione argentica. Successivamente è stato somministrato del metilprednisolone acetato (MPA) per via intratecale alla dose di 80 mg. due volte alla settimana per cinque settimane a 5 dei 7 pazienti e a 2 pazienti addizionali non trattati prima. Nonostante segni di infiammazione subaracnoidea è stata constatata una importante depressione della sintesi di IgG in tutti e 7 i pazienti compresi i due resistenti alla somministrazione per via venosa. Normali livelli di sintesi sono stati raggiunti rapidamente in 4 pazienti su 7 mentre negli altri 3 si ebbe un rapido ritorno ai valori di partenza. 1 dei 7 pazienti ha dimostrato una temporanea riduzione nel numero delle bande oligoclonali IgG catodiche nel liquor. 2 pazienti hanno dovuto sospendere il trattamento per il verificarsi di una meningite asettica in uno e di un progressivo adinamismo nell'altro. Non vi sono state variazioni del quadro clinico. Si conclude che il metilprednisolone e l'ACTH hanno un effetto iniziale simile sulle risposte infiammatorie del sistema nervoso centrale nei casi di MS, ma il ben documentato rischio di seri controeffetti col MPA ne proibisce l'uso clinico nella MS con le modalità descritte.

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  1. Wadsworth Division, Neurology and Research Services, VAMC West Los Angeles, Los Angeles, California

    Baumhefner R. W. M.D., Tourtellotte W. W., Syndulko K., Staugaitis A. & Shapshak P.

  2. Department of Neurology, Reed Neurological Research Center, University of California at Los Angeles, Los Angeles, California

    Baumhefner R. W. M.D., Tourtellotte W. W., Syndulko K. & Shapshak P.

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Baumhefner, R.W., Tourtellotte, W.W., Syndulko, K. et al. Multiple sclerosis intra-blood-brain-barrier IgG synthesis: effect of pulse intravenous and intrathecal corticosteroids. Ital J Neuro Sci 10, 19–32 (1989). https://doi.org/10.1007/BF02333869

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