Utility of routine neuropsychological assessment for early identification of cognitive impairment in MS.
Multiple sclerosis (MS), a demyelinating and degenerative disease of the central nervous system, causes not only physical disability, but also neuropsychological (NP) impairment. Cognitive impairment affects between 45-60% of patients with MS. (1,2) Depression is equally common (3,4) and influences susceptibility to relapses. (5-7) Affective disorders, such as euphoria and pseudobulbar affect, are less common, but are found in up to about 10% of patients during the course of illness. (8-10) Such symptoms are often missed in routine neurological examinations, as these deficits can be relatively subtle in the context of physical signs and symptoms and impairment of ambulation. (11) However, NP impairment has a significant impact on social functioning, (12-14) overall quality of life (15) and is the most common reason for the discontinuation of employment. (12) Thus, greater attention to NP impairment through routine screening and assessment, and its progression over time is necessary.
NP Defects in MS
In patients with MS, the most frequently observed cognitive impairments are on tests of information-processing speed, working memory, and episodic memory. (16,17) Verbal fluency and executive function can also be involved, but less frequently. (18) In contrast, general intelligence and central language abilities are relatively spared. (1) Defecits in these domains are strongly related to measures of whole brain volume, (19) enlargement of the ventricles, (20,21) and atrophy of the cerebral cortex on magnetic resonance imaging (MRI). (22,23) White-matter atrophy may be more strongly correlated with deficits in processing speed and working memory, whereas grey-matter atrophy predicts memory deficits and neuropsychiatric conditions such as euphoria. (24) Depression has a lifetime prevalence of approximately 40-50% in MS patients, (3,4) and is more common in this disease than in other chronic neurological illness accompanied by comparable physical disability. (25-27) Anxiety is also common in MS patients, often co-occurring with depression, but remains relatively understudied in this population. (28) Although the prevalence of depression is influenced by psychosocial stressors and medication side-effects, mood may also be affected by structural changes due to neuropathology. For example, depression is associated with lesion burden, global atrophy, (29) decreased grey-matter volume and increased cerebrospinal fluid (CSF) volume in the left anterior temporal region. (30)
In contrast, much less is known regarding the underlying pathophysiology of subtle personality changes in MS. Personality broadly refers to individual traits that define the manner in which an individual tends to respond to his or her environment thus, impacting psychosocial functioning. (31) In the context of neurodegenerative MS, the adverse impact on personality has not been thoroughly investigated. Studies have shown that affect disorders are associated with changes in personality traits in MS patients. (9,32) Additionally, personality may impact disease course indirectly by influencing mood states that in turn influence health behaviours and psychosocial support. Research has shown correlations between personality disorder and frontal lobe lesions, (33) as well as with brain atrophy; (34) these studies show a particularly strong association between increasing brain pathology and personality/behavioural changes, particularly disinhibition and irritability. However, in the future, we may find that more subtle changes in personality can be measured in MS and may have an impact on the early course of the illness.
Personality traits can be reliably assessed in medical and psychological research using the NEO Five Factor Inventory (NEO-FFI). (35) This self-report instrument evaluates five personality domains: neuroticism, extraversion, openness, agreeableness and conscientiousness. Neuroticism refers to emotional reactivity and the tendency toward negative mood states and worry. Extraversion is the degree to which a person depends on external stimulation for arousal, and one's inclination toward positive mood states and sensation seeking. Openness is the desire for new or novel knowledge, ideas, and experiences. Agreeableness refers to the desire for social cooperation, honesty, and altruism as opposed to competition. Finally, conscientiousness refers to the degree to which a person is task-oriented, achievement focused, dependable, deliberate, and organized. (35) Benedict et al (36) found significant associations between lower volume of the cerebral cortex and decreases in the traits of extroversion, openness, and conscientiousness. In a separate study, MS patients with cognitive impairment exhibited higher levels of neuroticism and lower levels of extraversion, agreeableness, and conscientiousness than healthy controls. (37) Johnson et al (38) reported that MS patients have significantly higher levels of neuroticism compared with patients with chronic fatigue syndrome. Further research is needed to clarify the potential reciprocal relationship between personality and NP impairment in MS.
NP assessment is a clinical procedure involving psychiatric interview, gross mental status examination, and psychometric testing. Psychometric testing is unique to the field of clinical neuropsychology (or psychology) and is a reliable and valid approach to objectively defining cognitive capacity across various domains. (39,40) Specialized testing batteries have been designed and validated for MS, allowing for relatively brief testing sessions. The Brief Repeatable Neuropsychological Battery (BRNB) (41) requires approximately 45 minutes and consists of five tests; the Stroop conflict task (42) may be added as a measure of response modulation. The Minimal Assessment of Cognitive Function in MS (MACFIMS) (43) requires approximately 90 minutes and consists of seven tests. These batteries differ in the tests used to assess auditory/verbal memory and visual/spatial memory. A recent study comparing these batteries found they were comparable in distinguishing MS patients from healthy controls. (4) 4 However, while auditory/verbal assessments demonstrated similar sensitivity across batteries, the Brief Visuospatial Memory Test, Revised (BVMTR), (45,46) which is part of the MACFIMS battery, was more sensitive than the Spatial Recall Test (10/36) used in the BRNB. Both the MACFIMS and BRNB have alternate forms to allow for repeat testing in monitoring cognitive decline.
Value of Early and Routine Assessment
The ideal timing for NP assessment in MS patients is not well established. Currently, many patients are not evaluated until significant deficits are readily apparent. By the time cognitive impairment is appreciated by a patient or caregiver, they may already be experiencing marked changes in instrumental activities of daily living or at the workplace. In our clinical experience we see many patients who have been either dismissed or discouraged from work, circumstances that are contrary to protection guaranteed by the Americans with Disabilities Act. Recent evidence suggests that cognitive impairment may be detectable soon after MS diagnosis, (15,47,48) or even after a single demyelinating episode suggestive of MS. (49-53) Early detection may therefore prevent maltreatment in the vocational sphere and help patients and family members cope more actively and adaptively with this important aspect of neurological disability.
Another way in which early NP testing may be beneficial is in disease-course monitoring. Natural-history studies show that while the course and trajectory of cognitive impairment in MS is more heterogeneous and slower than in, for example, Alzheimer's disease, (8) progression of these deficits are a reliable marker of neurological decline. (15,54,55) A 10-year longitudinal study revealed that, in addition to the presence of cognitive deficits in the initial stages of MS, deficits continued to emerge and progress in patients over time. In the later stages of the disease, neurological and cognitive status are more likely to converge and constitute the strongest predictors of disability in patients with MS. (56)
Finally, there is growing interest in the predictive value of early and/or routine NP assessment. Benign MS (BMS) is classified based on a clinical course of low-level physical and neurological disability for at least 15 years following disease onset. However, evidence shows that even in the context of minimal physical disability, cognitive impairment can be present. (57,58) In fact, Portaccio et al (58) found that the disease course in BMS was predicted by both cognitive impairment and MRI measures of T1 lesion burden at baseline, as the risk of disease progression was predicted by these factors. Rovaris et al (59) proposed that cognitive functioning be considered in distinguishing BMS from other disease courses, as it is clear that evaluating only physical and neurological features is insufficient. Given the potential predictive role of cognitive functioning, Benedict and Fazekas (60) highlight the importance of screening and monitoring for cognitive impairment in detecting early deficits and preventing worsening in patients who appear to be clinically stable. The authors acknowledge that further research is necessary in determining the sensitivity and specificity of repeated assessments in monitoring for decline. At a minimum, there is a clear case for the implementation of a more comprehensive evaluation of MS patients presenting with a benign disease course.
Screening for NP impairment
Despite the numerous benefits of NP assessment, it remains impractical to recommend NP testing for all MS patients. Thus, reliable and valid screening tools for cognitive and neuropsychiatric impairment in MS are needed. Presently, there are no fully validated screening tools available, although there are some promising studies that may guide clinician efforts to triage patients and guide future research.
The Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) (61) is a self-administered, 15-item questionnaire designed to be completed by patients prior to medical appointments, with little need for supervision. The questionnaire has self- and informant-report forms assessing behaviours related to memory, attention, processing speed, executive function, and control of emotion. Higher scores reflect greater degrees of perceived impairment. While the informant-report form is significantly correlated with brain imaging, NP testing, and neuropsychiatric symptoms, (62) the self-report form varies in its correlation with NP testing, and is confounded by depression. (61) Many studies have shown that self-reported impairment is more strongly related to depression than to objective testing in MS patients, potentially due to negative thoughts and self-appraisal, or to misattribution of cognitive difficulties secondary to depression to MS-related change. (62-65) Accuracy of self-reported cognitive impairment increases in non-depressed MS patients and in patients effectively treated for depression. (63)
In addition to the influence of mood on self-perception of cognitive impairment, part of what might be obscuring the accuracy of self-report screening instruments in identifying cognitive and neuropsychiatric impairment is the frequency of concrete experiences in which such abilities are tested. The workplace is an environment that allows for reflection on relatively concrete and specific behaviours and provides opportunity for error. We tested this hypothesis with 314 MS patients to examine whether vocational status influences accuracy of self-reported impairment. Subjects were classified as 'impaired' or 'unimpaired' based on the MACFIMS criteria; (2) 175 were employed at the time of testing, and 139 were not. Fisher's z statistic revealed a markedly stronger relationship (z = -3.10, P < 0.01) between the Symbol Digit Modalities Test (SDMT) performance and MSNQ in employed versus unemployed patients, and similar results were found with tests of visual/spatial memory and executive function. Asking patients to reflect on their workplace activity might provide more concrete and specific behaviours for consideration, and thus, greater accuracy in self-report of cognitive function. This presents a unique opportunity for the direction of new screening measures for NP impairment in MS with potential for increasing the effectiveness of self-report measures.
In the interim, there is interest in using easily administered brief cognitive performance tests such as the Symbol Digit Modalities Test (SDMT). (64,66,67) The SDMT is a brief test measuring information or cognitive processing speed and is administered by giving the subject 90 seconds to voice the number associated with target symbols based on a grid printed at the top of a page. There are many studies showing that it is highly sensitive when administered to MS patients (2,44,68) and performance on the SDMT is associated with vocational capacity. (69) A decrease on the SDMT of 4 points, or differentiated between MS subjects who remained employed versus those who did not over time. (70) Additionally, performance on the SDMT is strongly associated with lesion burden, (71) ventricle enlargement, (21,72,73) cortical atrophy, (23) deep grey-matter atrophy, (71) informant-reported cognitive problems, (62) and unemployment. (69) Benedict et al (74) recently demonstrated that the SDMT and MSNQ can be reliably administered at monthly intervals with minimal practice effects in MS. Used together, these tests can potentially identify patients at risk for objective NP impairment with higher reliability and validity than when administered in isolation. Additionally, both the SMDT and MSNQ require minimal time, equipment, and training.
NP evaluation remains underutilized in the care of MS patients despite the high prevalence of cognitive impairment and disorders of mood and affect. As cognitive impairment is associated with future problems in work and social function, (14) and can have significant impact on overall quality of life in MS patients and their families, its early identification is clearly important. Additionally, comprehensive NP assessment can provide clarity with regard to psychiatric status and level of functioning in social and vocational domains. In the near future, research regarding personality traits might also provide insight into disease progression, particularly related to cognition, mood, and affect in patients with MS, and perhaps even strategies for preventive care, though more investigation is needed in this area.
As we learn more about potential precipitating and perpetuating factors of cognitive impairment, such as personality traits, and disorders of mood and affect in MS, the benefits of undergoing routine NP assessment will continue to increase. Furthermore, relationships currently under investigation in personality research in MS could increase our understanding of overall neurological disability status and its impact on individual patients. Until then, in the absence of routine NP assessment and prior to readily identifying possible impairment (e.g., through job loss, disruptions in relationships, etc.), patients with MS are vulnerable to undetected NP impairment. Early identification of impairment is particularly important with the advent of new symptomatic and disease-modifying therapies. As such, greater attention is necessary to the development of reliable, valid, and brief screening and monitoring for NP impairment in MS.
* Patients with MS are vulnerable to cognitive impairment and disorders of mood and affect, which have a negative effect on many aspects of health-related quality of life.
* Cognitive impairment can be difficult to detect during routine office visits and is often only recognized once the symptoms are severe.
* Despite the high frequency of cognitive impairment in MS, routine NP testing is uncommon; sensitive, brief screening measures are needed.
* Early identification of cognitive impairment is becoming increasingly important with the advent of new symptomatic and disease-modifying therapies for MS patients.
Received:10 November 2009
Accepted: 27 January 2010
(1.) Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology 1991;41: 685-691.
(2.) Benedict RH, Cookfair D, Gavett R, Gunther M, Munschauer F, Garg N, et al. Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS). J Int Neuropsychol Soc 2006;12: 549-558.
(3.) Chwastiak L, Ehde DM, Gibbons LE, Sullivan M, Bowen JD, Kraft GH. Depressive symptoms and severity of illness in multiple sclerosis: epidemiologic study of a large community sample. Am J Psychiatry 2002;159: 1862-1868.
(4.) Minden SL, Schiffer RB. Affective disorders in multiple sclerosis. Review and recommendations for clinical research. Arch Neurol 1990;47: 98-104.
(5.) Mohr DC, Goodkin DE, Gatto N, Van der WJ. Depression, coping and level of neurological impairment in multiple sclerosis. Multiple Sclerosis. 1997;3: 254-258.
(6.) Mohr DC, Goodkin DE, Likosky W, Gatto N, Baumann KA, Rudick RA. Treatment of depression improves adherence to interferon beta-1b therapy for multiple sclerosis. Archives of Neurology. 1997;54: 531-533.
(7.) Mohr DC, Goodkin DE, Bacchetti P, Boudewyn AC, Huang L, Marrietta P, et al. Psychological stress and the subsequent appearance of new brain MRI lesions in MS. Neurology 2000;55: 55-61.
(8.) Benedict RH, Bobholz JH. Multiple sclerosis. Semin Neurol 2007;27: 78-85.
(9.) Fishman I, Benedict RH, Bakshi R, Priore R, Weinstock-Guttman B. Construct validity and frequency of euphoria sclerotica in multiple sclerosis. J Neuropsychiatry Clin Neurosci 2004;16: 350-356.
(10.) Feinstein A, Feinstein K, Gray T, O'Connor P. Prevalence and neurobehavioral correlates of pathological laughing and crying in multiple sclerosis. Arch Neurol 1997;54: 1116-1121.
(11.) Benedict RH. Integrating cognitive function screening and assessment into the routine care of multiple sclerosis patients. CNS Spectr 2005;10: 384-391.
(12.) Rao SM, Leo GJ, Ellington L, Nauertz T, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning. Neurology 1991;41: 692-696.
(13.) Foley FW, Dince WM, Bedell JR, LaRocca NG. Psychoremediation of communication skills for cognitively impaired persons with multiple sclerosis. Journal of Neurologic Rehabilitation 1994;8: 165-176.
(14.) Benedict RH, Shapiro A, Priore R, Miller C, Munschauer F, Jacobs L. Neuropsychological counseling improves social behavior in cognitively-impaired multiple sclerosis patients. Mult Scler 2000;6: 391-396.
(15.) Amato MP, Ponziani G, Pracucci G, Bracco L. Cognitive impairment in early-onset multiple sclerosis: Pattern, predictors, and impact on everyday life in a 4-year follow-up. Archives of Neurology 1995;52: 168-172.
(16.) Rao SM. Neuropsychology of multiple sclerosis. Curr Opin Neurol 1995;8: 216-220.
(17.) Benedict RH, Fischer JS, Archibald CJ, Arnett PA, Beatty WW, Bobholz J et al. Minimal neuropsychological assessment of MS patients: a consensus approach. Clin Neuropsychol 2002;16: 381-397.
(18.) Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple sclerosis. Lancet Neurol 2008;7: 1139-1151.
(19.) Zivadinov R, Sepcic J, Nasuelli D, De Masi R, Bragadin LM, Tommasi MA et al. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2001;70: 773-780.
(20.) Christodoulou C, Krupp LB, Liang Z, Huang W, Melville P, Roque C et al. Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients. Neurology 2003;60: 1793-1798.
(21.) Benedict RHB, Weinstock-Guttman B, Fishman I, Sharma J, Tjoa CW, Bakshi R. Prediction of neuropsychological impairment in multiple sclerosis: comparison of conventional magnetic resonance imaging measures of atrophy and lesion burden. Archives of Neurology 2004;61: 226-230.
(22.) Amato MP, Bartolozzi ML, Zipoli V, Portaccio E, Mortilla M, Guidi L et al. Neocortical volume decrease in relapsing-remitting MS patients with mild cognitive impairment. Neurology 2004;63: 89-93.
(23.) Benedict RH, Bruce JM, Dwyer MG, Abdelrahman N, Hussein S, Weinstock-Guttman B et al. Neocortical atrophy, third ventricular width, and cognitive dysfunction in multiple sclerosis. Arch Neurol 2006;63: 1301-1306.
(24.) Sanfilipo MP, Benedict RH, Weinstock-Guttman B, Bakshi R. Gray and white matter brain atrophy and neuropsychological impairment in multiple sclerosis. Neurology 2006;66: 685-692.
(25.) Wells KB, Golding JM, Burnam MA. Psychiatric disorder in a sample of the general population with and without chronic medical conditions. Am J Psychiatry 1988;145: 976-981.
(26.) Ron MA, Logsdail SJ. Psychiatric morbidity in multiple sclerosis: a clinical and MRI study. Psychol Med 1989;19: 887-895.
(27.) Schubert DS, Foliart RH. Increased depression in multiple sclerosis patients. A metaanalysis. Psychosomatics 1993;34: 124-130.
(28.) Feinstein A. The clinical neuropsychiatry of multiple sclerosis. New York: Cambridge University Press; 1999.
(29.) Bakshi R, Czarnecki D, Shaikh ZA, Priore RL, Janardhan V, Kaliszky Z et al. Brain MRI lesions and atrophy are related to depression in multiple sclerosis. Neuroreport 2000;11: 1153-1158.
(30.) Feinstein A, Roy P, Lobaugh N, Feinstein K, O'Connor P, Black S. Structural brain abnormalities in multiple sclerosis patients with major depression. Neurology 2004;62: 586-590.
(31.) Mischel W. Toward an integrative science of the person. Annual Review of Psychology 2004;55: 1-22.
(32.) Finger S. A happy state of mind: a history of mild elation, denial of disability, optimism, and laughing in multiple sclerosis. Arch Neurol 1998;55: 241-250.
(33.) Arnett PA, Rao SM, Bernardin L, Grafman J, Yetkin FZ, Lobeck L. Relationship between frontal lobe lesions and Wisconsin Card Sorting Test performance in patients with multiple sclerosis. Neurology 1994;44: 420-425.
(34.) Benedict RH, Carone DA, Bakshi R. Correlating brain atrophy with cognitive dysfunction, mood disturbances, and personality disorder in multiple sclerosis. J Neuroimaging 2004;14: 36S-45S.
(35.) Costa PT, & McCrae, R.R. Professional Manual for the Revised NEO Personality Inventory and NEO Five-Factor Inventory. Odessa, FL.: Psychological Assessment Resources, Inc.; 1992.
(36.) Benedict RH, Hussein S, Englert J, Dwyer MG, Abdelrahman N, Cox JL et al. Cortical atrophy and personality in multiple sclerosis. Neuropsychology 2008;22: 432-441.
(37.) Benedict RH, Priore RL, Miller C, Munschauer F, Jacobs L. Personality disorder in multiple sclerosis correlates with cognitive impairment. J Neuropsychiatry Clin Neurosci 2001;13: 70-76.
(38.) Johnson SK, DeLuca J, Natelson BH. Personality dimensions in the chronic fatigue syndrome: a comparison with multiple sclerosis and depression. J Psychiatr Res 1996;30: 9-20.
(39.) Lezak M. Neuropsychological Assessment (2nd Ed). New York, NY: Oxford University Press; 1995.
(40.) Kolb B, Wishaw, I. Fundamentals of Human Neuropsychology. (2nd Ed). New York, NY: W.H. Freeman; 1985.
(41.) Rao SM. A Manual for the brief, repeatable battery of neuropsychological tests in multiple sclerosis. 1991 (unpublished paper).
(42.) Stroop JR. Studies of interference in serial verbal reactions. Journal of Experimental Psychology 1935;28: 643-662.
(43.) Benedict RHB, Fischer JS, Archibald CJ, Arnett PA, Beatty WW, Bobholz J et al. Minimal Neuropsychological Assessment of MS Patients: A Consensus Approach. Clinical Neuropsychologist 2002;16: 381.
(44.) Strober L, Englert J, Munschauer F, Weinstock-Guttman B, Rao S, Benedict RHB. Sensitivity of conventional memory tests in multiple sclerosis: comparing the Rao Brief Repeatable Neuropsychological Battery and the Minimal Assessment of Cognitive Function in MS. Mult Scler 2009;15:1077-1084.
(45.) Benedict RHB, Schretlen D. Revision of the Brief Visuospatial Memory Test: Studies of normal performance, reliability. Psychological Assessment 1996;8: 145.
(46.) Benedict R. Brief visuospatial memory test - revised: professional manual. Odessa, Florida: Psychological Assessment Resources, Inc; 1997.
(47.) Olivares T, Nieto A, Sanchez MP, Wollmann T, Hernandez MA, Barroso J. Pattern of neuropsychological impairment in the early phase of relapsing-remitting multiple sclerosis. Mult Scler 2005;11: 191-197.
(48.) Deloire MS, Salort E, Bonnet M, Arimone Y, Boudineau M, Amieva H, et al. Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 2005;76: 519-526.
(49.) Callanan MM, Logsdail SJ, Ron MA, Warrington EK. Cognitive impairment in patients with clinically isolated lesions of the type seen in multiple sclerosis. A psychometric and MRI study. Brain 1989;112 (Pt 2): 361374.
(50.) Feinstein A, Kartsounis LD, Miller DH, Youl BD, Ron MA. Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric, and MRI follow up study. J Neurol Neurosurg Psychiatry 1992;55: 869-876.
(51.) Feinstein A, Youl B, Ron M. Acute optic neuritis. A cognitive and magnetic resonance imaging study. Brain 1992;115 (Pt 5): 1403-1415.
(52.) Pelosi L, Geesken JM, Holly M, Hayward M, Blumhardt LD. Working memory impairment in early multiple sclerosis. Evidence from an event-related potential study of patients with clinically isolated myelopathy. Brain 1997;120 (Pt 11): 2039-2058.
(53.) Achiron A, Barak Y. Cognitive impairment in probable multiple sclerosis. J Neurol Neurosurg Psychiatry 2003;74: 443-446.
(54.) Kujala P, Portin R, Ruutiainen J. The progress of cognitive decline in multiple sclerosis. Brain 1997;120: 289-297.
(55.) Amato MP, Zipoli V, Portaccio E. Mulitple-sclerosis related cognitive changes: A review of cross-sectional and longitudinal studies. Journal of the Neurological Sciences 2006;245: 41-46.
(56.) Amato MP, Ponziani G, Siracusa G, Sorbi S. Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years. Arch Neurol 2001;58: 1602-1606.
(57.) Ruggieri RM, Palermo R, Vitello G, Gennuso M, Settipani N, Piccoli F. Cognitive impairment in patients suffering from relapsing-remitting multiple sclerosis with EDSS < or = 3.5. Acta Neurol Scand 2003;108: 323-326.
(58.) Portaccio E, Stromillo ML, Goretti B, Zipoli V, Siracusa G, Battaglini M, et al. Neuropsychological and MRI measures predict short-term evolution in benign multiple sclerosis. Neurology 2009;73: 498-503.
(59.) Rovaris M, Barkhof F, Calabrese M, De Stefano N, Fazekas F, Miller DH, et al. MRI features of benign multiple sclerosis: toward a new definition of this disease phenotype. Neurology 2009;72: 1693-1701.
(60.) Benedict RHB, Fazekas F. Benign or not benign MS. A role for routine neuropsychological assessment? Neurology 2009;73:494-495
(61.) Benedict RH, Cox D, Thompson LL, Foley F, Weinstock-Guttman B, Munschauer F. Reliable screening for neuropsychological impairment in multiple sclerosis. Mult Scler 2004;10: 675-678.
(62.) Benedict RH, Zivadinov R. Predicting neuropsychological abnormalities in multiple sclerosis. J Neurol Sci 2006;245: 67-72.
(63.) Julian L, Merluzzi NM, Mohr DC. The relationship among depression, subjective cognitive impairment, and neuropsychological performance in multiple sclerosis. Mult Scler 2007;13: 81-86.
(64.) Christodoulou C, Melville P, Scherl WF, Morgan T, MacAllister WS, Canfora DM, et al. Perceived cognitive dysfunction and observed neuropsychological performance: longitudinal relation in persons with multiple sclerosis. J Int Neuropsychol Soc 2005;11: 614-619.
(65.) Gold SM, Schulz H, Monch A, Schulz KH, Heesen C. Cognitive impairment in multiple sclerosis does not affect reliability and validity of self-report health measures. Multiple Sclerosis. 2003;9: 404-410.
(66.) Deloire MS, Bonnet MC, Salort E, Arimone Y, Boudineau M, Petry KG et al. How to detect cognitive dysfunction at early stages of multiple sclerosis? Mult Scler 2006;12: 445-452.
(67.) Smith A. Symbol Digit Modalities Test: Manual. Los Angeles: Western Psychological Services; 1982.
(68.) Parmenter BA, Weinstock-Guttman B, Garg N, Munschauer F, Benedict RH. Screening for cognitive impairment in multiple sclerosis using the Symbol digit Modalities Test. Mult Scler 2007;13: 52-57.
(69.) Benedict RHB, Wahlig E, Bakshi R, Fishman I, Munschauer F, Zivadinov R, et al. Predicting quality of life in multiple sclerosis: Accounting for physical disability, fatigue, cognition, mood disorder, personality, and behavior change. Journal of the Neurological Sciences 2005: 29-34.
(70.) Morrow SA, Drake A, Zivadinov R, Munchauer FE, Weinstock-Guttman B, Benedict RHB. Longitudinal analysis of neuropsychological data and employment in MS: Clinically meaningful cognitive decline. Clin Neuropsychol 2009; Submitted 2010.
(71.) Houtchens MK, Benedict RH, Killiany R, Sharma J, Jaisani Z, Singh B, et al. Thalamic atrophy and cognition in multiple sclerosis. Neurology 2007;69: 1213-1223.
(72.) Christodoulou C, Krupp LB, Liang Z, Huang W, Melville P, Roque C, et al. Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients. Neurology 2003;60: 1793-1798.
(73.) Bermel RA, Bakshi R, Tjoa C, Puli SR, Jacobs L. Bicaudate ratio as a magnetic resonance imaging marker of brain atrophy in multiple sclerosis. Arch Neurol 2002;59: 275-280.
(74.) Benedict RH, Duquin JA, Jurgensen S, Rudick RA, Feitcher J, Munschauer FE, et al. Repeated assessment of neuropsychological deficits in multiple sclerosis using the Symbol Digit Modalities Test and the MS Neuropsychological Screening Questionnaire. Mult Scler 2008;14: 940-946.
M Hoogs, S Morrow, RHB Benedict
SUNY Buffalo School of Medicine, Jacobs Neurological Institute, Buffalo, New York, USA
Address for Correspondence
Ralph HB Benedict, SUNY Buffalo School of Medicine, Jacobs Neurological Institute, 101 High Street, Buffalo, New York, USA
Tel: +1 7168 591 403
Fax: +1 7168 591 419
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||NP Assessment in MS|
|Author:||Hoogs, M.; Morrow, S.; Benedict, R.H.B.|
|Publication:||The International MS Journal|
|Date:||Mar 1, 2010|
|Previous Article:||Diagnosing depression in MS in the face of overlapping symptoms.|
|Next Article:||Cyclophosphamide Treatment of MS: current therapeutic approaches and treatment regimens.|