Pharmacopsychiatry 2000; 33(1): 28-37
DOI: 10.1055/s-2000-7966
Original Paper
Georg Thieme Verlag Stuttgart · New York

Amantadine Influences Cognitive Processing in Patients with Multiple Sclerosis

M. Sailer, H.-J. Heinze, M. A. Schoenfeld, U. Hauser, H. G.O.M. Smid
  • Department of Neurology II, Otto-von-Guericke University, Magdeburg, Germany
Further Information

Publication History

Publication Date:
31 December 2000 (online)

We investigated the effect of amantadine on cognitive processing in patients with multiple sclerosis (MS) and fatigue with objective electrophysiological measures. Behavioral methods (Reaction Time, RT) and two different Event Related Potential (ERP) components measuring i) stimulus selection (Selection Negativity, SN) and ii) response selection (Lateralized Readiness Potential, LRP) were employed. Twentyfour patients with clinical definite MS (10 relapsing remitting and 14 secondary progressive) and confirmed fatigue in the past three months (Fatigue Severity Scale (FSS) > 4) were included. Patients were randomized in a double-blind, placebo-controlled cross-over design. We found a difference between the two treatments for ERP measures to stimuli with relevant colour starting at about 200 ms. This negativity had a higher amplitude during amantadine treatment regardless of treatment order. The RT did not differ significantly between the treated and untreated groups. Additional analysis indicated that patients with a disease duration of less than 7 years had a significant test position (practice effect), but no treatment effect, while patients with a longer MS duration showed no practice effect, but rather an improved reaction speed and increased ERP amplitude effects when treated with amantadine. The present findings suggest that amantadine exerts beneficial effects on early cognitive processes in patients with MS, but appears to be limited to subjects with a longer duration of the disease.

References

  • 1 The Canadian MS Research Group . A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis.  Can J Neurol Sci. 1987;  14 273-278
  • 2 Beatty W W, Goodkin D E, Hertsgaard D, Monson N. Clinical and demographic predictors of cognitive performance in multiple sclerosis. Do diagnostic type, disease duration, and disability matter?.  Arch Neurol. 1990;  47 305-308
  • 3 Birbaumer N, Roberts L E, Lutzenberger W, Rockstroh B, Elbert T. Area-specific self-regulation of slow cortical potentials on the sagittal midline- and its effects on behavior.  Electroencephalogr Clin Neurophysiol. 1992;  84 353-361
  • 4 Brunia C H. Waiting in readiness: gating in attention and motor preparation.  Psychophysiology. 1993;  30 327-339
  • 5 Cohen R A, Fisher M. Amantadine treatment of fatigue associated with multiple sclerosis.  Arch Neurol. 1989;  46 676-680
  • 6 DeLuca J, Johnson S K, Beldowicz D, Natelson B H. Neuropsychological impairments in chronic fatigue syndrome, multiple sclerosis, and depression.  J Neurol Neurosurg Psychiatry. 1995;  58 38-43
  • 7 Feinstein A, Ron M, Thompson A. A serial study of psychometric and magnetic resonance imaging changes in multiple sclerosis.  Brain. 1993;  116 569-602
  • 8 Fisk J D, Pontefract A, Ritvo P G, Archibald C J, Murray T J. The impact of fatigue on patients with multiple sclerosis.  Can J Neurol Sci. 1994;  21 9-14
  • 9 Geisler M W, Sliwinski M, Coyle P K, Masur D M, Doscher C, Krupp L B. The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis.  Arch Neurol. 1996;  53 185-188
  • 10 Huber T J, Dietrich D E, Emrich H M. Possible use of amantadine in depression.  Pharmacopsychiat. 1999;  32 47-55
  • 11 Krupp L B, Alvarez L A, LaRocca N G, Scheinberg L C. Fatigue in multiple sclerosis.  Arch Neurol. 1988;  45 435-437
  • 12 Krupp L B, Coyle P K, Doscher C, Miller A, Cross A H, Jandorf L, Halper J, Johnson B, Morgante L, Grimson R. Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo.  Neurology. 1995;  45 1956-1961
  • 13 Krupp L B, LaRocca N G, Muir N J, Steinberg A D. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus.  Arch Neurol. 1989;  46 1121-1123
  • 14 Kujala P, Portin R, Ruutiainen J. The progress of cognitive decline in multiple sclerosis. A controlled 3-year follow-up.  Brain. 1999;  120 289-297
  • 15 Kurtzke J F. Rating neurological impairement in multiple sclerosis: an expanded disability status scale (EDSS).  Neurology. 1983;  33 -1452
  • 16 Miller J, Riehle A, Requin J. Effects of preliminary perceptual output on neuronal activity of the primary motor cortex.  Journal of Experimental Psychology: Human Perception and Performance. 1992;  18 1121-1138
  • Mulder G, Wijers A A, Brookhuis K A, Smid H GOM, Mulder L JM. Selective visual attention: Selective cueing, selective cognitive processing, and selective response processing. In: Heinze H-J, Münte TF, Mangun GR (eds) Cognitive Electrophysiology. Boston; Birkhäuser 26-80
  • 18 Murray T J. Amantadine therapy for fatigue in multiple sclerosis.  Can J Neurol Sci. 1985;  52 251-254
  • 19 Parsons C G, Quack G, Bresink I, Baran L, Przegalinski E, Kostowski W, Krzascik P, Hartmann S, Danysz W. Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo.  Neuropharmacology. 1995;  34 -1258
  • 20 Poser C M, Patty D. New diagnostic criteria for multiple sclerosis: Guide lines for researchers protocols.  Ann Neurol. 1983;  13 227-231
  • 21 Rao S, Leo G, Haughton V, St. Aubin-Foubert P, Bernardin L. Correlation of magnetic resonance imaging with neurophysiological testing in multiple sclerosis.  Neurology. 1989;  39 161-166
  • 22 Rockstroh B, Ehlert T, Canavan A GMT, Lutzenberger W, Birbaumer N. Slow cortical potentials and behaviour. München; Urban and Schwarzenberg 1989
  • 23 Sandroni P, Walker C, Starr A. Fatigue in patients with multiple sclerosis.  Arch Neurol. 1992;  49 517-524
  • 24 Sheean G L, Murray N M, Rothwell J C, Miller D H, Thompson A J. An electrophysiological study of the mechanism of fatigue in multiple sclerosis.  Brain. 1997;  120 299-315
  • 25 Semlitsch H V, Anderer P, Saletu B. Topographic mapping of long latency “cognitive” event-related potentials (P300): a double blind, placebo-controlled study with amantadine in mild dementia.  J Neural Transm Park Dis Dement Sect. 1992;  4 19-36
  • 26 Smets E MA, Garssen B, Bonke B, De Haes J CJM. The multidimensional fatigue inventory (MFI) psychometric qualities of an instrument to assess fatigue.  J Psychosom Res. 1995;  39 315-325
  • 27 Smid H G, Bocker K B, van Touw T D, Mulder G, Brunia C H. A psychophysiological investigation of the selection and the use of partial stimulus information in response choice.  J Exp Psychol Hum Percept Perform. 1996;  22 3-24
  • 28 Smid H G, Lamain W, Hogeboom M M, Mulder G, Mulder L J. Psychophysiological evidence for continuous information transmission between visual search and response processes.  J Exp Psychol Hum Percept Perform. 1991;  17 696-714
  • 29 Smid H G, Mulder G, Mulder L J, Brands G J. A psychophysiological study of the use of partial information in stimulus-response translation.  J Exp Psychol Hum Percept Perform. 1992;  18 1101-1119
  • 30 Tucker D M, Williams P A. Asymmetric neural control system in human self-regulation.  Psychol Rev. 1984;  91 185-215
  • 31 Volkow N D, Gur R C, Wang G J, Fowler J S, Moberg P J, Ding Y S, Hitzemann R, Smith G, Logan J. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals.  Am J Psychiatry. 1998;  155 -349
  • 32 Wickens C D. The structure of attention resources. Nickerson R. Attention and Performance 1980; 239 - 257. Hillsdale NJ, Erlbaum. Wijers AA, Mulder G, Okita T, Mulder LJ, Scheffers MK. Attention to color: an analysis of selection, controlled search, and motor activation, using event-related potentials.  Psychophysiology. 1989;  26 89-109
  • 33 Wijers A A, Mulder G, Okita T, Mulder L J, Scheffers M K. Attention to color: an analysis of selection, controlled search, and motor activation, using event-related potentials.  Psychophysiology. 1989;  26 89-109

Dr. med. PD Michael Sailer

Department of Neurology II Otto-von-Guericke University

Leipziger Straße 44

D-39120 Magdeburg

Germany

Email: michael.sailer@medizin.uni-magdeburg.de