BACKGROUND: Neuropsychiatric symptoms and reduced health-related quality of life (HRQoL) are frequent in multiple sclerosis, where are associated with structural brain changes, but have been less studied in clinically isolated syndrome (CIS). OBJECTIVE: To characterize HRQoL, neuropsychiatric symptoms (depressive symptoms, anxiety, apathy and fatigue), their interrelations and associations with structural brain changes in CIS. METHODS: Patients with CIS (n = 67) and demographically matched healthy controls (n = 46) underwent neurological and psychological examinations including assessment of HRQoL, neuropsychiatric symptoms and cognitive functioning, and MRI brain scan with global, regional and lesion load volume measurement. RESULTS: The CIS group had more, mostly mild, depressive symptoms and anxiety, and lower HRQoL physical and social subscores (p≤0.037). Neuropsychiatric symptoms were associated with most HRQoL subscores (β≤-0.34, p≤0.005). Cognitive functioning unlike clinical disability was associated with depressive symptoms and lower HRQoL emotional subscores (β≤-0.29, p≤0.019). Depressive symptoms and apathy were associated with right temporal, left insular and right occipital lesion load (ß≥0.29, p≤0.032). Anxiety was associated with lower white matter volume (ß = -0.25, p = 0.045). CONCLUSION: Mild depressive symptoms and anxiety with decreased HRQoL are present in patients with CIS. Neuropsychiatric symptoms contributing to decreased HRQoL are the result of structural brain changes and require complex therapeutic approach in patients with CIS.

Department of Neurology Charles University 2nd Faculty of Medicine Motol University Hospital Prague Czech Republic

Department of Radiology Charles University 2nd Faculty of Medicine Motol University Hospital Prague Czech Republic

Zobrazit více v PubMed

Nygaard GO, Walhovd KB, Sowa P, Chepkoech JL, Bjornerud A, Due-Tonnessen P, et al. Cortical thickness and surface area relate to specific symptoms in early relapsing-remitting multiple sclerosis. Multiple sclerosis. 2015;21(4):402–14. doi: 10.1177/1352458514543811 . PubMed DOI

Klevan G, Jacobsen CO, Aarseth JH, Myhr KM, Nyland H, Glad S, et al. Health related quality of life in patients recently diagnosed with multiple sclerosis. Acta neurologica Scandinavica. 2014;129(1):21–6. doi: 10.1111/ane.12142 . PubMed DOI

Nourbakhsh B, Julian L, Waubant E. Fatigue and depression predict quality of life in patients with early multiple sclerosis: a longitudinal study. European journal of neurology. 2016;23(9):1482–6. doi: 10.1111/ene.13102 . PubMed DOI

D'Alisa S, Miscio G, Baudo S, Simone A, Tesio L, Mauro A. Depression is the main determinant of quality of life in multiple sclerosis: a classification-regression (CART) study. Disability and rehabilitation. 2006;28(5):307–14. doi: 10.1080/09638280500191753 . PubMed DOI

Stuke H, Hanken K, Hirsch J, Klein J, Wittig F, Kastrup A, et al. Cross-Sectional and Longitudinal Relationships between Depressive Symptoms and Brain Atrophy in MS Patients. Frontiers in human neuroscience. 2016;10:622 doi: 10.3389/fnhum.2016.00622 ; PubMed Central PMCID: PMC5159697. PubMed DOI PMC

Zorzon M, Zivadinov R, Nasuelli D, Ukmar M, Bratina A, Tommasi MA, et al. Depressive symptoms and MRI changes in multiple sclerosis. European journal of neurology. 2002;9(5):491–6. . PubMed

Damasceno A, Damasceno BP, Cendes F. Atrophy of reward-related striatal structures in fatigued MS patients is independent of physical disability. Multiple sclerosis. 2016;22(6):822–9. doi: 10.1177/1352458515599451 . PubMed DOI

Berg D, Supprian T, Thomae J, Warmuth-Metz M, Horowski A, Zeiler B, et al. Lesion pattern in patients with multiple sclerosis and depression. Multiple sclerosis. 2000;6(3):156–62. doi: 10.1177/135245850000600304 . PubMed DOI

Pandey K, Lublin FD. Clinically isolated syndrome and multiple sclerosis: rethinking the arsenal. Current treatment options in neurology. 2009;11(3):193–202. . PubMed

Anhoque CF, Biccas-Neto L, Domingues SC, Teixeira AL, Domingues RB. Cognitive impairment is correlated with reduced quality of life in patients with clinically isolated syndrome. Arquivos de neuro-psiquiatria. 2013;71(2):74–7. . PubMed

Anhoque CF, Domingues SC, Carvalho T, Teixeira AL, Domingues RB. Anxiety and depressive symptoms in clinically isolated syndrome and multiple sclerosis. Arquivos de neuro-psiquiatria. 2011;69(6):882–6. . PubMed

Simioni S, Ruffieux C, Bruggimann L, Annoni JM, Schluep M. Cognition, mood and fatigue in patients in the early stage of multiple sclerosis. Swiss medical weekly. 2007;137(35–36):496–501. 2007/35/smw-11874. . PubMed

Di Legge S, Piattella MC, Pozzilli C, Pantano P, Caramia F, Pestalozza IF, et al. Longitudinal evaluation of depression and anxiety in patients with clinically isolated syndrome at high risk of developing early multiple sclerosis. Multiple sclerosis. 2003;9(3):302–6. doi: 10.1191/1352458503ms921oa . PubMed DOI

Anhoque CF, Biccas-Neto L, Domingues SC, Teixeira AL, Domingues RB. Cognitive impairment and optic nerve axonal loss in patients with clinically isolated syndrome. Clinical neurology and neurosurgery. 2013;115(7):1032–5. doi: 10.1016/j.clineuro.2012.10.025 . PubMed DOI

Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of neurology. 2011;69(2):292–302. doi: 10.1002/ana.22366 ; PubMed Central PMCID: PMC3084507. PubMed DOI PMC

Dufek M. Léčba roztroušené sklerózy v České republice–možnosti a realita. Neurol praxi 2014;(15(1)):31–5.

Association AP. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 2013.

Benedict RH, Cox D, Thompson LL, Foley F, Weinstock-Guttman B, Munschauer F. Reliable screening for neuropsychological impairment in multiple sclerosis. Multiple sclerosis. 2004;10(6):675–8. doi: 10.1191/1352458504ms1098oa . PubMed DOI

Beck AT, Beamesderfer A. Assessment of depression: the depression inventory. Modern problems of pharmacopsychiatry. 1974;7(0):151–69. . PubMed

Beck AT, Epstein N, Brown G, Steer RA. An inventory for measuring clinical anxiety: psychometric properties. Journal of consulting and clinical psychology. 1988;56(6):893–7. . PubMed

Marin RS, Biedrzycki RC, Firinciogullari S. Reliability and validity of the Apathy Evaluation Scale. Psychiatry research. 1991;38(2):143–62. . PubMed

Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Archives of neurology. 1989;46(10):1121–3. . PubMed

Ware JE Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Medical care. 1992;30(6):473–83. 1593914. PubMed

Smith A. Symbol digit modalities test: Manual. Los Angeles: Western Psychological Service; 1982.

Parmenter BA, Weinstock-Guttman B, Garg N, Munschauer F, Benedict RH. Screening for cognitive impairment in multiple sclerosis using the Symbol digit Modalities Test. Multiple sclerosis. 2007;13(1):52–7. doi: 10.1177/1352458506070750 . PubMed DOI

Rao SM, Martin AL, Huelin R, Wissinger E, Khankhel Z, Kim E, et al. Correlations between MRI and Information Processing Speed in MS: A Meta-Analysis. Multiple sclerosis international. 2014;2014:975803 doi: 10.1155/2014/975803 ; PubMed Central PMCID: PMC3984845. PubMed DOI PMC

Smith SM, Zhang Y, Jenkinson M, Chen J, Matthews PM, Federico A, et al. Accurate, robust, and automated longitudinal and cross-sectional brain change analysis. NeuroImage. 2002;17(1):479–89. . PubMed

Jenkinson M, Bannister P, Brady M, Smith S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage. 2002;17(2):825–41. . PubMed

Jenkinson M, Smith S. A global optimisation method for robust affine registration of brain images. Medical image analysis. 2001;5(2):143–56. . PubMed

Winkler AM, Ridgway GR, Webster MA, Smith SM, Nichols TE. Permutation inference for the general linear model. NeuroImage. 2014;92:381–97. doi: 10.1016/j.neuroimage.2014.01.060 ; PubMed Central PMCID: PMC4010955. PubMed DOI PMC

Figved N, Klevan G, Myhr KM, Glad S, Nyland H, Larsen JP, et al. Neuropsychiatric symptoms in patients with multiple sclerosis. Acta psychiatrica Scandinavica. 2005;112(6):463–8. doi: 10.1111/j.1600-0447.2005.00624.x . PubMed DOI

Runia TF, Jafari N, Siepman DA, Hintzen RQ. Fatigue at time of CIS is an independent predictor of a subsequent diagnosis of multiple sclerosis. Journal of neurology, neurosurgery, and psychiatry. 2015;86(5):543–6. doi: 10.1136/jnnp-2014-308374 . PubMed DOI

Ghajarzadeh M, Jalilian R, Eskandari G, Sahraian MA, Azimi A, Mohammadifar M. Fatigue in multiple sclerosis: relationship with disease duration, physical disability, disease pattern, age and sex. Acta neurologica Belgica. 2013;113(4):411–4. doi: 10.1007/s13760-013-0198-2 . PubMed DOI

Putzki N, Fischer J, Gottwald K, Reifschneider G, Ries S, Siever A, et al. Quality of life in 1000 patients with early relapsing-remitting multiple sclerosis. European journal of neurology. 2009;16(6):713–20. . PubMed

Gavelova M, Nagyova I, Rosenberger J, Krokavcova M, Gdovinova Z, Groothoff JW, et al. Importance of an individual's evaluation of functional status for health-related quality of life in patients with multiple sclerosis. Disability and health journal. 2015;8(3):372–9. doi: 10.1016/j.dhjo.2015.02.006 . PubMed DOI

Lynch SG, Kroencke DC, Denney DR. The relationship between disability and depression in multiple sclerosis: the role of uncertainty, coping, and hope. Multiple sclerosis. 2001;7(6):411–6. doi: 10.1177/135245850100700611 . PubMed DOI

Langdon DW, Benedict RH, Wicklein EM, Beckmann K, Fredrikson S. Reports of patients and relatives from the CogniCIS study about cognition in clinically isolated syndrome: what are our patients telling us? European neurology. 2013;69(6):346–51. doi: 10.1159/000345698 . PubMed DOI

Patel VP, Zambrana A, Walker LA, Herrmann N, Swartz RH, Feinstein A. Distractibility in multiple sclerosis: The role of depression. Multiple sclerosis journal—experimental, translational and clinical. 2016;2:2055217316653150. doi: 10.1177/2055217316653150 ; PubMed Central PMCID: PMC5433422. PubMed DOI PMC

Pujol J, Bello J, Deus J, Cardoner N, Marti-Vilalta JL, Capdevila A. Beck Depression Inventory factors related to demyelinating lesions of the left arcuate fasciculus region. Psychiatry research. 2000;99(3):151–9. . PubMed

Audoin B, Zaaraoui W, Reuter F, Rico A, Malikova I, Confort-Gouny S, et al. Atrophy mainly affects the limbic system and the deep grey matter at the first stage of multiple sclerosis. Journal of neurology, neurosurgery, and psychiatry. 2010;81(6):690–5. doi: 10.1136/jnnp.2009.188748 . PubMed DOI

Hyncicova E, Vyhnalek M, Kalina A, Martinkovic L, Nikolai T, Lisy J, et al. Cognitive impairment and structural brain changes in patients with clinically isolated syndrome at high risk for multiple sclerosis. Journal of neurology. 2017;264(3):482–93. doi: 10.1007/s00415-016-8368-9 . PubMed DOI

Feinstein A, O'Connor P, Feinstein K. Multiple sclerosis, interferon beta-1b and depression A prospective investigation. Journal of neurology. 2002;249(7):815–20. doi: 10.1007/s00415-002-0725-0 . PubMed DOI

Mohr DC, Likosky W, Dwyer P, Van Der Wende J, Boudewyn AC, Goodkin DE. Course of depression during the initiation of interferon beta-1a treatment for multiple sclerosis. Archives of neurology. 1999;56(10):1263–5. . PubMed

Spatial navigation in early multiple sclerosis: a neglected cognitive marker of the disease?