Importancia del BICAMS en la evaluacion del paciente con EM
Ralph HB Benedict, PhD ABPP-CN
Professor of Neurology, Psychiatry, Psychology
University at Buffalo, State University of New York
“[In] most of the patients affected by multi-locular sclerosis whom I have had occasion to observe … there is marked enfeeblement of the memory; conceptions are formed slowly; the intellectual and emotional faculties are blunted in their totality. The dominant feeling in the patients appears to be a sort of almost stupid [cheerful] indifference in reference to all things. J Charcot, 1877
Cognitive Impairment in MS: Occurs in at least 50% of patients Robust correlate of WM pathology and GM atrophy Primary cause of ↓ ADLs and job loss Benedict & Zivadinov,
MS Neuropsicológica Screening Cuestionario
Benedict 2004
- Test-retest reliability 0.90 - 0.93
- Self Report r w NPT 0.37, DEP 0.61
- Informant Report r w NPT 0.57
Vanotti 2009
- Self Report r with NPT not significant
- Informant Report r with NPT 0.36
Performance Based Neuropsychological Testing
Standardization and Normative Data
Reliability – test/retest
Reliability – inter-rater
Validity – Predicts Cognitive Impairment
Validity – Predicts MRI
Validity – Predicts Disease
Validity – Predicts Behavior (eg vocational function, ADLs)
Validity – Predicts Disease Progression
70
85
130
115
30-35%
30-35%
Overall Impairment: 40-50% in RRMS, 50-60% in SPMS
6
7
8
Caceres, Vanotti, et al, 2014, MSARD; 3:335-340
Argentina, Chile, Colombia, Mexico, Uruguay, Venezuela
Multicenter Study To Assess Cognitive and Neuropsychiatric Disorders in Multiple
Sclerosis Patients from Latin America (RELACCEM Study)
MS n=110 HC n=34 p d
M SD M SD
7/24 Total Recall 28.30 5.944 31.38 5.377 .001 0.6
7/24 Delayed recall 5.65 1.710 6.29 1.244 .000 1.0
BVMTR Total Learning 18.50 7.468 25.32 6.143 .000 1.1
BVMTR Delayed recall 7.09 2.583 10.03 1.487 .000 1.8
Cognitive Impairment 35%
Depression 29%
Neuropsychiatric Symptoms 21%
Test-Retest reliability
N = 34 MS patients
Age = 42.2+8.9 years
Mean EDSS = 2.5
Pts examined 2x separated by 1-2 weeks
Random assignment to same vs alt form condition
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Argentina Lithuania Australia Mexico Belgium Netherlands Brazil Norway Canada Oman Czech Rep Peru Denmark Poland Egypt Portugal Estonia Romania Germany Russia Greece Serbia Hungary Slovenia India Spain Iran Sweden Italy Turkey Ireland Finland Israel Switzerland Latvia UK Lebanon USA
BICAMS Validation Projects: Various Stages of Development from Planning to Publication
Brief Screening Tools: MMSE; MOCA; BICAMS recommended for Assessment
Nurses should work with the patient, care partner, and other members of the interdisciplinary team to develop an appropriate cognitive management program and reevaluate on an ongoing basis
Patients should be provided with verbal and written instructions regarding the need to reduce distractions and implement safety measures
Talk to people with MS and their family members or carers about the possibility that the condition might lead to cognitive problems
Consider referring people with MS and persisting memory or cognitive problems to a neuropsychologist or memory service
Consider involving an occupational therapist in managing cognitive problems in people with MS
Recent Validation
• Correlation with Brain MRI
• Discriminative Validity
• Reliability
• Clinical Relevance
Houtchens, Benedict et al. Neurology, 2007
MS n = 367; NC n = 134.
Matched on demographics
24 Benedict et al. MSJ. 2012; 18:1320–1325
660 pts, 109 sites in 21 countries
Translated into 14 languages
MS Baseline to Month 6 Change d = 0.2
P = 0.029
P = 0.090
Clinically Meaningful Change During Cognitive Relapses in Multiple Sclerosis
Ralph H B Benedict PhD, Sarah Morrow MD, Jonathan Rodgers PhD, David Hojnacki
MD, Margaret Ann Bucello NP and Bianca Weinstock-Guttman MD
MSJ, in press
All but one Relapse patient had supratentorial GdE+ lesions No effects for T25FW, NHPT, PASAT or BVMTR MSNQ p = 0.088
Interaction Effect p = 0.004
Disease Activity Free Status [DAFS] No Evidence of Disease Activity [NEDA]
Depiction of disease activity free status domains from Kieseier &
Stuve 2011, Nature Neurology Reviews
Vocational
Status
Fatigue
Age,
Education,
etc
Disease
Features
Physical
Disability
Cognitive
Function
Mood
Disorder Personality
Behavior
Disorder
MSQOL-54
Benedict et al. J Neurol Sci. 2005;231;29-34
Linear regression analysis in 120 MS patients
Model Predicting disabled/employed status,
conservatively defined (n=102)
Model Predicting disabled/employed status, liberally defined (n=162)
Odds* Ratio
95% Confidence
Interval p Odds* Ratio
95% Confidence
Interval p
Depression† 2.30 0.95- 5.54 0.065 2.70 1.45 - 5.04 0.002
Disease Course†† 5.79 1.88 – 17.8 0.002 5.00 2.20 – 11.4 <0.001
CVLT2-DR 3.20 1.19 - 8.63 0.022 2.82 1.41 – 5.66 0.003
BVMTR-DR ns ns
PASAT 4.34 1.63 - 11.6 0.003 ns
SDMT ns ns
DKEFS ns 2.27 1.03 - 5.01 0.042
Tridimensional Personality Questionnaire (TPQ)
• Job Description: # hours, income, tasks, etc
• Negative Work Events: days missed, reprimands from employer, complaints about work quality, errors not reported, etc
• Accommodations: ONET categories and room to report others used not listed, indicated is related to medical condition, provided by employer, etc
• Disclosure Status
Employed MS (n=438)
Employed Healthy Controls (n=61)
Measure Mean SD Mean SD Group Effect
Age, years 44.7 10.0 43.7 12.0 0.576
Education, years 15.3 2.5 15.9 3.0 0.177
Years worked for employer 12.1 9.7 7.7 9.3 0.005
Motor
Timed 25 foot walk 5.1 2.9 4.4 1.0 <.001
NHPT mean both hands 21.7 4.3 19.8 2.4 0.001
Cognition
CVLT2 Total Learning 54.6 10.5 58.4 10.0 0.029
CVLT2 Delayed Recall 12.2 2.8 12.8 2.7 0.1
BVMTR Total Learning 24.4 6.2 25.7 5.1 0.151
BVMTR Delayed Recall 9.4 2.2 9.9 2.0 0.091
SDMT 57.2 11.0 61.6 9.2 0.007
PASAT 46.1 11.4 48.6 10.7 0.243
BDIFS 2.3 2.7 1.0 1.6 0.001
MSNQ 20.8 11.5 14.7 7.0 <0.001
MS w Work
Problems (n=15) MS without
Problems (n=123)
Measure Mean SD Mean SD Group Effect
Age, years 44.9 10.0 44.6 10. 0.911
Education, years 14.7 3.2 15.3 2.4 0.328
Years worked for primary employer 10.1 8.4 12.4 9.8 .390
Motor
Timed 25 foot walk 6.2 1.9 5.0 1.3 .002
NHPT mean both hands 24.1 5.8 21.5 4.1 0.023
Cognition
CVLT2 Total Learning 50.1 9.0 55.2 10.5 0.072
CVLT2 Delayed Recall 11.3 2.9 12.3 2.9 0.167
BVMTR Total Learning 22.1 4.0 24.7 6.3 0.121
BVMTR Delayed Recall 8.0 1.9 9.5 2.2 0.011
SDMT 52.7 8.5 57.7 11.3 0.104
PASAT 40.1 13.0 47.2 10.4 0.016
BDIFS 4.8 3.8 2.0 2.4 <0.001
MSNQ 29.8 11.2 19.7 11.1 0.001
Disclosure of Disease Status among Employed Multiple Sclerosis Patients: Association with Negative Work Events and Accommodations SE Frndak, V Kordovski, D Cookfair, J Rodgers, B Weinstock-Guttman, RHB Benedict MS Journal, in press
Never Disclosed
(n=30)
Past Disclosure
(n=113) P value
Age, ave. ± SD 45.65 ± 11.87 45.79 ± 10.48 .951
Years of Education, ave. ± SD 15.70 ± 3.01 15.27 ± 2.35 .399
Sex (% Female) 73.33% 83.19% .220
Years in Current Position, ave. ± SD 7.72 ± 7.93 9.95 ± 8.19 .088
Total Years with Employer, ave. ± SD 8.88 ± 9.06 13.27 ± 9.32 .007
Median Income $40000.00 $45000.00 .089
Number of Paid Hours, ave. ± SD 33.60 ± 9.91 37.29 ± 8.08 .036
Number of Accommodations, ave. ± SD 0.43 ± 1.36 1.5 ± 2.28 .001
Number of Problems, ave. ± SD 0.27 ± 0.52 0.50 ± 0.84 .232
BICAMS is related to work capacity, but not to disclosure – an invisible disability
Physical features
NP test outcomes lack of Face Validity.
Statistically significant association within a group does not identify a point at which the predictor is important or relevant in individual patients.
Confusion of terminology [eg minimally important difference], statistically meaningful change [SEm; test-retest r, RCI] is not clinically meaningful change.
Co-Primary Outcomes, NP test and clinician impression of change
OR
Research on meaningful anchors with relevance to patients that designate either cross-sectional scale points, or anchors for change scores [raw, %ile]
MS sample = 97 patients, mean interval of 42 months [range 12-90]
Morrow et al. [Clin Neuropsychologist, 2011]
Isolated Cognitive Relapse: transient decline in SDMT of 4 points, as per Morrow et al no clinical or subjective evidence of other new symptoms [EDSS]
ICR n = 17
Stable Group n = 82
Retrospective Study of 99
RRMS patients
All with +Gd MRI
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Conclusions BICAMS research shows that routine assessment of cognitive function is
feasible in MS, both in the clinical and research setting.
Cognitive impairments may be transient or chronic, related to inflammation/demyelination and neurodegeneration, respectively. Baseline exams are needed to appreciate both aspects of cognitive deterioration.
CVLT learning
BVMT learning
25FW
9HPT
SDMT
BDIFS/MSNQ
CVLT delay
BVMT delay
Work Status Monitoring
Acknowledgements:
Co-I Bianca Weinstock-Guttman MD
Co-I Robert Zivadinov MD
Co-I Murali Ramanathan PhD
Channa Kolb MD, David Hojnacki MD, Meg Bucello NP
Audrey Smerbeck PhD, Seth Frndek BS, Carrie Fisher BA, Allison Drake BA, Victoria Kordovski BA, Claire Modica BS, Joy Parrish PhD
Funding:
NIH, National MS Society, Association for Research in MS, Bayer, Biogen Idec, Novartis