Clinical and electrophysiological follow-up of modafinil treatment for multiple sclerosis patients with fatigue symptom

Year 2020, Volume: 6 Issue: 4, 326 - 336, 04.07.2020

Özlem Akdoğan , Cemile Haki , Ömer Faruk Turan , Özlem Taşkapılıoğlu

https://doi.org/10.18621/eurj.493073

Abstract

Objectives: In our study, we investigated the effects of modafinil therapy on clinical and neurophysiological tests of multiple sclerosis (MS) patients with fatigue.

Methods: The study was performed on 18 MS patients (16 females, 2 males) at Uludağ University School of Medicine, Department of Neurology, who are followed up according to Mc Donald’s criteria, who had 36 points or above based on the fatigue assesment scala (FAS), whose Beck depression inventory points were 16 and below, whose thyroid, liver and renal functions were evaluated as normal, and who had no systemic disorder. All patients had neurological examination and their expanded disability status scale (EDSS), fatigue impact scala (FIS) and multiple sclerosis quality of life (MSQoL-54) were evaluated. Somatosensory evoked potential (SEP), visual evoked potential (VEP), brainstem auditory evoked potential (BAEP), visual event related evoked potential (visual P300) were performed in our neurophysiology laboratory. After that the patients were given modafinil 100 mgr 1×1 (morning) for 1 week, the following weeks 2×1 (morning and noon). At the end of the 6 weeks of therapy the patients were called to the neurology polyclinic, and their neurological examinations, EDSS, FIS, MSQoL-54, SEP, VEP, BAEP and visual P300 were repeated.

Results: When the patients’ previous and subsequent FIS and MSQoL-54 total scores were compared, a significant statistical difference was found. When all 3 subgroups of FIS (consciousness, physical and social) were evaluated after the modafinil therapy, a significant statistical decrease in previous and successive scores were found. It is found out that modafinil therapy improves life quality which is evaluated due to MSQoL-54 (p < 0.05). A significant statistical relation between the number of MS disease attacks and the three subgroups of MFIS was not figured out (p > 0.05). There were no statistically significant relation between the FAS, EDSS and Beck depression inventory scores before the modafinil therapy had been applied (p > 0.05). There was a statistically correlation between Beck depression inventory score and FIS’s social subgroup (p = 0.017). When the patient’s SEP, VEP, BAEP, visual P300 average test values before and after the modafinil therapy were compared, a statistically significant difference was not observed.

Conclusions: In our study, it is found that modafinil therapy, which is used against fatigue, one of the MS disase’s most common symptom, has a positive impact on MS life quality and patients’ clinical symptoms of fatigue, although it has no effect on patients’ evoked potential methods (BAEP, SEP, VEP, visual P300) performed in neurophysiology laboratory. 

Keywords

multiple sclerosis, fatigue, modafinil, evoked potential, fatigue severity scala

References

• 1. Ozakbas S, Cagiran I, Ormeci B, Idiman E. Correlations between multiple sclerosis functional composite, expanded disability status scale and health-related quality of life durin and after treatment of relapses in patients with multiple sclerosis. J Neurol Sci 2004;218:3-7.
• 2. Kurtzke JF. Rating neurological impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology 1983;33:1444-52.
• 3. Freal JE, Kraft GH, Coryell JK. Symptomatic fatigue in multiple sclerosis. Arch Phys Med Rehabil 1984;65:135-8.
• 4. Krupp LB. Fatigue in Multiple Sclerosis A Guide to Diagnosis and Management, Demos Medical Publishing Inc 2004.
• 5. Michielsen HJ, De Vries J, Van Heck GL. Psychometric qualities of a brief self-ratedfatigue measure: The Fatigue Assessment Scale (FAS). J Psychosom Res 2003;54:345-52.
• 6. Mathiowetz V. Test-retest reliability and convergent validity of the Fatigue Impact Scale for persons with multiple sclerosis. Am J Occup Ther 2003;57:389-95.
• 7. Vicrey BG, Hays RD, Harooni R, Myers LW, Ellison GW. A health-related quality of life measure for multiple sclerosis. Qual Life Res 1995;4:187-206.
• 8. Türkdoğan D. Olaya İlişkin Endojen Potansiyeller. Akyüz G. (Ed): Elektrodiagnoz. Bölüm:24. Ankara, 2003: pp. 411-21.
• 9. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561-71.
• 10. Kargarfard M, Eetemadifar M, Mehrabi M, Maghzi AH, Hayatbakhsh MR. Fatigue, depression, and health-related quality of life in patients with multiple sclerosis in Isfahan, Iran. Eur J Neurol 2012;19:431-7.
• 11. Pellicano C, Gallo A, Li X, Ikonomidou VN, Evangelou IE, Ohayon JM, et al. Relationship of cortical atrophy to fatigue inpatients with multiple sclerosis. Arch Neurol 2010;67:447-53.
• 12. Tedeschi G, Dinacci D, Lavorgna L, Prinster A, Savettieri G, Quattrone A, et al. Correlation between fatigue and brainatrophy and lesion load in multiple sclerosis patients inde-pendent of disability. J Neurol Sci 2007;263:15-9.
• 13. Mills R J, Young CA. The relationship between fatigue and other clinical features of multiple sclerosis. Mult Scler 2011;17:604-12.
• 14. Schreurs KM, de Ridder DT and Bensing JM. Fatigue in multiple sclerosis: reciprocal relationships with physical disabilities and depression. J Psychosom Res 2002;53:775-81.
• 15. Lerdal A, Celius EG, Moum T. Fatigue and its association with sociodemographic variables among multiple sclerosis patients. Mult Scler 2003;9:509-14.
• 16. Tedeschi G, Dinacci D, Lavorgna L, Prinster A, Savettieri G, Quattrone A, et al. Correlation between fatigue and brain atrophy and lesion load in multiple sclerosis patients independent of disability. J Neurol Sci 2007;263:15-9.
• 17. Figved N, Klevan G, Myhr KM, Glad S, Nyland H, Larsen JP, et al. Neuropsychiatric symptoms in patients with multiple sclerosis. Acta Psychiatr Scand 2005;112:463-8.
• 18. Scott TF, Allen D, Price TR, McConnell H, Lang D. Characterization of major depression symptoms in multiple sclerosis patients. J Neuropsychiatry Clin Neurosci 1996;8:318-23.
• 19. Schreurs KM, de Ridder DT, Bensing JM. Fatigue in multiple sclerosis: reciprocal relationships with physical disabilities and depression. J Psychosom Res 2002;53:775-81.
• 20. Bakshi R, Shaikh ZA, Miletich RS, Czarnecki D, Dmochowski J, Henschel K, et al. Fatigue in multiple sclerosis and its relationship to depression and neurologic disability. Mult Scler 2000;6:181-5.
• 21. Koch M, Mostert J, Heerings M, Uyttenboogaart M, De Keyser J. Fatigue, depression and disability accumulation in multiple sclerosis: a cross-sectional study. Eur J Neurol 2009;16:348-52.
• 22. Vercoulen JH, Hommes OR, Swanink CM, Jongen PJ, Fennis JF, Galama JM, et al. The measurement of fatigue in patients with multiple sclerosis. A multidimensional comparison with patients with chronic fatigue syndrome and healthy subjects. Arch Neurol 1996;53:642-9.
• 23. Iriarte J, Carreno M, de Castro P. [Fatigue and functional system involvement in multiple sclerosis]. Neurologia 1996;11:210-5. [Article in Spanish]
• 24. Flachenecker P, Kümpfel T, Kallmann B, Gottschalk M, Grauer O, Rieckmann P, et al. Fatigue in multiple sclerosis: a comparison of different rating scales and correlation to clinical parameters. Mult Scler 2002;8:523-6.
• 25. Mohr DC, Hart SL and Goldberg A. Effects of treatment for depression on fatigue in multiple sclerosis. Psychosom Med 2003;65:542-7.
• 26. Daly E, Komaroff AL, Bloomingdale K, Wilson S, Albert MS. Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression. Appl Neuropsychol 2001;8:12-22.
• 27. Moller A, Wiedemann G, Rohde U, Backmund H, Sonntag A. Correlates of cognitive impairment and depressive mood disorder in multiple sclerosis. Acta Neurol Scand 1994;89:117-21.
• 28. Türkbay T, Yıldırım Y, Özakbaş S, Uzunel F. Multiple Sklerozlu Hastalarda Yorgunluk ve Yorgunluğun Etkisinin Değerlendirilmesi. Türk Nöroloji Dergisi 2004;10:515-20.
• 29. van der Werf SP, Jongen PJ, Lycklama à Nijeholt GJ, Barkhof F, Hommes OR, Bleijenberg G. Fatigue in multiple sclerosis: interrelations between fatigue complaints, cerebral MRI abnormalities andneurological disability. J Neurol Sci 1998;160:164-70.
• 30. Pittion-Vouyovitch S, Debouverie M, Guillemin F, Vanden-berghe N, Anxionnat R, Vespignani H. Fatigue in multiplesclerosis is related to disability, depression and quality of life. J Neurol Sci 2006;243:39-45.
• 31. Yaldizli Ö, Glassl S, Sturm D, Papadopoulou A, Gass A, Tet-tenborn B, et al. Fatigue and progression of corpus callosumatrophy in multiple sclerosis. J Neurol 2011;258:2199-205.
• 32. Shaygannejad V, Janghorbani M, Ashtari F, Zakeri H. Com-parison of the effect of aspirin and amantadine for thetreatment of fatigue in multiple sclerosis: a randomized,blinded, crossover study. Neurol Res 2012;34:854-8.
• 33. Cruz Gómez ÁJ, Ventura Campos N, Belenguer A, Ávila C, Forn C. Regional brain atrophy and functional connectivitychanges related to fatigue in multiple sclerosis. PloS One 2013;8:e77914.
• 34. Ayache SS, Chalah MA. Fatigue in multiple sclerosis -- insights into evaluation and management. Neurophysiol Clin 2017;47:139-71.
• 35. Johansson S, Ytterberg C, Hillert J, Widen Holmqvist L, von Koch L. A longitudinal study of variations in and predictors of fatigue in multiple sclerosis. J Neurol Neurosurg Psychiatry 2008;79:454-7.
• 36. Debouverie M, Pittion-Vouyovitch S, Brissart H, Guillemin F. Physical dimension of fatigue correlated with disability change over time in patients with multiple sclerosis. J Neurol 2008;255:633-6.
• 37. Merkelbach S, Konig J, Sittinger H. Personality traits in multiple sclerosis (MS) patients with and without fatigue experience. Acta Neurol Scand 2003;107:195-201.
• 38. Rammohan KW, Rosenberg JH, Lynn DJ, Blumenfeld AM, Pollak CP, Nagaraja HN. Efficacy and safety of modafinil (Provigil ®) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study. J Neurol Neurosurg Psychiatry 2002;72:179-83.
• 39. Lange R, Volkmer M, Heesen C, Liepert J. Modafinil effects in multiple sclerosis patients with fatigue. J Neurol 2009;256:645-50.
• 40. Sangal B, Sangal M, Belisle C. Visual P300 latency predicts treatment response to modafinil in patients with narcolepsy. Clin Neurophysiol 1999;110:1041-7.