Effects of Intravenous Physostigmine and Lecithin on Memory Loss in Multiple Sclerosis: Report of a Pilot Study

Abstract

This paper reports the results of a pilot study designed to assess the efficacy of intravenous physostigmine and dietary lecithin for treating memory loss in patients with multiple sclerosis (MS). Four patients with definite MS participated in a two-phase (dose-finding and crossover), double-blind clinical trial. In the dose-finding phase, all patients exhibited an improvement in verbal memory (as assessed by the Selective Reminding Test) at the highest of four doses (1.0 mg). In the double-blind, crossover phase, patients were administered placebo or physostigmine (1.0 mg). A significant improvement in verbal memory was observed in three of four patients during the drug condition. None of the patients reported significant medication side effects. This study provides preliminary evidence that cholinergic pharmacotherapy may be useful in treating memory disturbance in MS.

Keywords

Multiple sclerosis Memory loss Physostigmine Lecithin.

References

Charcot JM Lectures on the diseases of the nervous system. London : New Sydenham Society, 1877 .

Peyser JM , Poser CM Neuropsychological correlates of multiple sclerosis. In: Filskov SB , Boll TJ , eds. Handbook of clinical neuropsychology, vol 2. New York: Wiley, 1986:364-97.

Rao SM Neuropsychology of multiple sclerosis: a critical review. J Clin Exp Neuropsychol 1986;8:503-42.

Rao SM , Glatt S. , Hammeke TA , et al. Chronic progressive multiple sclerosis: relationship between cerebral ventricular size and neuropsychological impairment. Arch Neurol 1985;42:678-82.

Drachman DA

Memory and cognitive function in man: does the cholinergic system have a specific role?

Neurology 1977:27:783-90.

Deutsch JA The cholinergic synapse and the site of memory. Science 1971;174:788-94.

Drachman DA , Leavitt J. Human memory and the cholinergic system: a relationship to aging? Arch- Neurol 1974;30:113-21.

Safer DJ , Allen RP The central effects of scopolamine in man. Biol Psychiatry 1971;3:347-55.

Crow TJ , Grove-White IG An analysis of the learning deficit following hyoscine administration to man . Br J Pharmacol 1973;49:322-7.

10.

Caine ED , Weingartner H. , Ludlow CL , Cudahy EA , Wehry S. Qualitative analysis of scopolamine-induced amnesia. Psychopharmacology 1981;74:74-80.

11.

Colquhoun WP Effects of hyoscine and meclozine on vigilance and short-term memory. Br J Industr Med 1962 ;19:287-95.

12.

Whitehouse PJ , Price DL , Struble RG , Clark AW , Coyle JT , DeLong MR Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 1982;215:1237-9.

13.

Coyle JT , Price DL , DeLong MR Alzheimer's disease: a disorder of cortical cholinergic innervation . Science 1983;219:1184-90.

14.

Whitehouse PJ , Price DL , Clark AW , Coyle JT , DeLong MR Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 1981;10:122-6.

15.

Dysken M. A review of recent clinical trials in the treatment of Alzheimer's dementia . Psychiatr Ann 1987;17: 178-91.

16.

Corkin S. , Davis KL , Growden JH , Usdin E. , Wurtman RJ Alzheimer's disease: a report of progress in research. New York: Raven Press, 1982.

17.

Jorm AF Effects of cholinergic enhancement therapies on memory function in Alzheimer's disease: a meta-analysis of the literature. Aust NZ J Psychiatry 1986;20:237-40.

18.

Harbaugh RE , Roberts DW , Coombs DW , Saunders RL , Reeder TM Preliminary report: intracranial cholinergic drug infusion in patients with Alzheimer's disease . Neurosurgery 1984;15:514-18.

19.

Bruno G. , Mohr E. , Gillespie M. , Fedio P. Chase TN Muscarinic agonist therapy of Alzheimer's disease: a clinical trial of RS-86 . Arch Neurol 1986;43:659-61.

20.

Poser CM , Paty DW , Scheinberg L. , et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983;13:227-31.

21.

Buschke H. , Fuld PA Evaluating storage, retention, and retrieval in disordered memory and learning . Neurology 1974;24:1019-25.

22.

Levin HS , Benton AL , Grossman RG Neurobehavioral consequences of closed head injury. New York: Oxford University Press, 1982 .

23.

Pavio A. , Yuille JC , Madigan SA Concreteness, imagery, and meaningfulness values for 925 nouns. J Exp Psychol Monogr 1968;76 (1,Pt. 2):1-25.

24.

Kucera N. , Francis WN Computational analysis of present-day American English. Providence, RI: Brown University Press, 1967.

25.

Christian J. , Bickley W. , Tarka M. , Clayton K. Measures of free recall of 900 English nouns: correlations with imagery, concreteness, meaningfulness, and frequency. Memory Cognition 1978;6:379-90.

26.

Mohs RC , Davis BM , Greenwald BS , et al. Clinical studies of the cholinergic deficit in Alzheimer's disease. II. Psychopharmacologic studies. J Am Geriatr Soc 1985;33:749-57.

27.

Thal LJ , Fuld PA , Masur DM , Sharpless NS Oral physostigmine and lecithin improve memory in Alzheimer's disease . Ann Neurol 1983;13:491-6.

28.

Wettstein A. No effect from double-blind trial of physostigmine and lecithin in Alzheimer's disease. Ann Neurol 1983;13:210-12.

29.

Thal LJ , Fuld PA Memory enhancement with oral physostigmine in Alzheimer's disease. N Engl J Med 1983;308:720.

30.

Beller SA , Overall JE , Swann AC Efficacy of oral physostigmine in primary degenerative dementia: a double-blind study of response to different dose level. Psychopharmacology 1985;87:147-51.

31.

Mohs RC , Davis BM , Johns CA , et al. Oral physostigmine treatment of patients with Alzheimer's disease . Am J Psychiatry 1985;142:28-33.

32.

Thal LJ , Masur DM , Sharpless NS , Fuld PA , Davies P. Acute and chronic effects of oral physostigmine and lecithin in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 1986;10:627-36.

33.

Peters BH , Levin HS Chronic oral physostigmine and lecithin administration in memory disorders of aging. In: Corkin S , Davis KL , Growdon JH , Usdin E , Wurtman RJ , eds. Alzheimer's disease: a report of progress in research. New York: Raven Press, 1982:421-426.

34.

Catsman-Berrevoets CE , Van Harskamp F , Appelhof A. Beneficial effect of physostigmine on clinical amnesic behaviour and neuropsychological test results in a patient with a post-encephalitic amnesic syndrome [letter]. J Neurol Neurosurg Psychiatry 1986; 49:1088-90.

35.

Goldberg E. , Gerstman LJ , Mattis S. , Hughes Jeo , Bilder RM , Sirio CA Effects of cholinergic treatment on post-traumatic anterograde amnesia. Arch Neurol 1982;39: 581.

36.

Rogers JD , Brogan D. , Mirra SS The nucleus basalis of Meynert in neurological disease: a quantitative morphological study. Ann Neurol 1985;17:163-70.

37.

Squire LR Mechanisms of memory. Science 1986 ;232: 1612-19.

38.

Ruberg M. , Villageois A. , Bonnet A. , Pillon B. , Rieger F. , Agid Y. Acetylcholinesterase and butyrylcholinesterase activity in the cerebrospinal fluid of patients with neurodegenerative diseases involving cholinergic systems . J Neurol Neurosurg Psychiatry 1987;50:538-43.