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