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Psychotherapy in MS Patients with Dementia and Personality Changes

Ralph HB Benedict, PhD

Professor of Neurology

University at Buffalo, State University of New York

Research Support from the NIH, National MS Society, and Industry

Acknowledgements:

Bianca Weinstock‐Guttman MD

Robert Zivadinov MD

Murali Ramanathan PhD

Channa Kolb MD, David Hojnacki MD, Meg Bucello NP

Jonathan Rodgers PhD, Audrey Smerbeck PhD, Adam Booth MA, Seth Frndek BS, Carrie Fisher BA, Allison Drake BA, Victoria Kordovski BA, Claire Modica BS, Maria Pollack, Kelly Couglin, Joy Parrish PhD

Disclosures:Accorda, Bayer, Biogen Idec, EMD Serono, Genzyme, Genentech, Novartis, Questor

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[In] most of the patients affected by multi-locularsclerosis 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 cheerful indifferencein reference to all things.

Jean-Martin Charcot (1877)

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Benedict & Bobholz. Seminars in Neurology, Vol 27, 78-85

Age 51; Male; 16 years Education EDSS = 3.0; nystagmus and ataxia

CASE CG

• Year 1 - 51 YO c PP MS, EDSS = 1.0

• Year 3 - neurologist suspects cognitive impairment

• Year 3 - wife discovers losing $40,000

• Year 4 - EDSS = 3.0

• Year 5 - NP testing shows severe cognitive impairment

• Year 6 - paroxetine

• Year 6 - social security disability

• Year 7 - wife complains of euhphoria and pers dis

• Year 7 - neuropsychological counseling

• Year 8 - valproic acid, risperdone

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SCOREBaseline

%ile SCORE Year 5

%ile INTERPRETATION

Estimated Premorbid Intelligence

Barona Regression Formula 102 55 102 55 average

Language

Cont Oral Word Association NA ‐‐ 11 <1 severe defect

Spatial Abilities

Judgment of Line Orientation 22 22 16 4 impaired, declined

Learning and Memory

CVLT List A, Trial 5 11 16 5 <1 severe defect, declined

CVLT List B, Trial 6 4 2 2 2 impaired, unchanged

CVLT List A, Trial 7 5 2 2 2 impaired, unchanged

CVLT List A, 20 min Delay 10 50 2 2 impaired, declined

CVLT Recognition 89% 16 1.3 6 impaired, declined

BVMT‐R Trial 1 3 7 1 1 severe defect, declined

BVMT‐R Trial 3 3 <1 6 3 impaired, unchanged

BVMT‐R 20 min Delay 3 <1 4 1 severe defect, declined

BVMT‐R Recognition 5 11‐16 3 1‐2 severe defect, declined

Executive Control

PASAT, 2.0 sec pacing 14 <1 0 <1 severe defect, declined

WCST Categories 5 >50 1 2‐5 impaired, declined

WCST Perseverative Responses 22 42 118 <1 severe defect, declined

“….. cheerful …. almost stupid indifference in reference to all things.”Charcot (1877)

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Hoffman [1904] Agrees with Charcot that euphoria is commonly seen in MS

Cottrell [1927] Of 100 consecutive cases, 63 Dx with euphoria

Ombredane [1929] Of 50 patients, 36 impaired cognitively and of these 30/36 have 

disturbance of affect

Surridge [1969] Euphoria defined as “cheerful complacency out of context to 

total situation, not always borne out by patient’s account of 

feelings”

Of 108 patients, 26 euphoric, all but 2 of whom “impaired 

intellectually”

Majority of euphoric patients exhibit “denial of disability” and 

“increased sexuality”

Euphoria and intellectual decline result in “great distress to 

relatives”

Subsequent Reports of Personality Changes in MS

“….. cheerful …. almost stupid indifference in reference to all things.”Charcot (1877)

Hoffman (1904); The 1921: 1st international conference on MS (NY, NY); Cottrell and Wilson (1926); Cottrell (1927); Runge (1928); Ombredane (1929); Surridge (1969); Rabins et al (1986); Feinstein et al (1997); Finger (1998)

euphoria = persistently cheerful mood (‘mental well-being‘)

eutonia = lack of awareness or concern about physical disability (‘physical well-being‘)

Prevalence 0 –60%

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NeuroticExtrovert

OpenAgreeable

ConsciEmpathic

MS

30

35

40

45

50

55

60

65

MS Normal

Methods: 35 referred patientsComprehensive NP BatteryPersonality testing.  

Results:   Executive Function Defects predict low Agreeableness (p=.02), Empathy (p=.009), Conscientiousness Discrepancy (p=.001)

Benedict et al. JNCN. 2001; 13:70-76

Neuropsychiatric Interview (NPI), Cummings et al, 1994

Factor 1:

Agitation/Aggression .85

Euphoria* .87

Disinhibition .78

Irritability/Lability .66

Factor 2:

Dysphoria/Depression .73

Anxiety .70

Apathy .73

N=34, most with SP course and cognitive impairment, median EDSS = 3.0

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Results of the regression analysis:

• SP course

• elevated MSNQ

• low agreeableness

Eutonia/Euphoria

R2 = .56

F = 25.34, p < .001

R2 = .16, p = .05

R2 = .48, p < .001

R2 = .38, p < .001

Fishmen et al, 2004

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RHB Benedict, et al. (2004).  J Neuroimaging; 14:36S‐46S 

31 MS patients from Benedict et al (AN; 2004) also had informant report Neuropsychiatric Inventory profiles

Depression Euphoria* Disinhibition*

TVW -- .46 .46

BPF -- -.43 -.34

Replicates early CT study by Rabins et al. 1986. STRUCTURAL BRAIN CORRELATES OF EMOTIONAL DISORDER IN MULTIPLE SCLEROSIS.  Brain, 109:585‐597

Neuropsychological Counseling

Goals:

Enhance Insight – Cognitive Defects and Behavioral Changes due to Neurological Disorder

Improve Interpersonal Empathy – Reduce Egocentric Speech

Reduce Frequency of Disruptive Behaviors

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Neuropsychological Counseling

1. PSYCHOEDUCATION: Enhance Insight‐ review MRI‐ review NP Testing‐ agree on defects‐memorize defects

2.  SOCIAL SKILLS TRAINING: Improve social skills and interpersonal empathy‐ caregiver monitoring of target behavior frequency‐ attentive listening‐ empathy‐ conversation skills

3.  BEHAVIOR THERAPY: Diminish frequency of disruptive outbursts‐ identify precipitants to target behavior‐ stress inoculation techniques

Benedict et al. Multiple Sclerosis. 2000; 6:391-396

Social Aggression Scale: Range 0 - 248 subscales including emotional episodes, inappropriate social behavior, anger outbursts, risk-taking behavior, excessive speech

0   not at all present

1   occurs infrequently, less than once per week2   occurs frequently, 1‐2 times per week3   occurs very frequently, more than 2 times per week

Poorly controlled anger outbursts. Patient loses temper and says something mean that is out of character; may throw objects or breaks things; threaten another person; use profanity.

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SAS Total Scores

Normal MS

01

23

45

67

89

1011

1213

1415

1617

1819

2021

0

2

4

6

8

10

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Active PlaceboMean SD Mean SD t p

Beck Depression Inventory - 2.4 9.3 -0.3 7.6 0.5 ns

Hogan Empathy Scale 1.9 4.5 -0.4 2.4 1.2 ns

NEO Personality Inventory Altruism 2.9 9.8 -1.7 7.9 0.9 ns Competence 4.6 8.8 -1.3 6.3 1.4 ns Dutifulness 3.4 10.7 -9.0 7.2 2.6 .03

Social Aggression Scale - 6.1 2.8 -1.4 2.9 3.2 <.01

Notes: All comparisons by t test .

Pre- and Post-Treatment Change Scores

Benedict et al. MS. 2000; 6:391-396

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0

2

4

6

8

10

12

14

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Exam 1 Exam 2

NormalNCNSP

SAS Scores

VocationalStatus

FatigueAge,

Education, etc

DiseaseFeatures

PhysicalDisability

Cognitive Function

MoodDisorder

PersonalityBehavior Disorder

MSQOL-54

Benedict et al. J Neurol Sci. 2005;231;29‐34

Linear regression analysis in 120 MS patients

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Tridimensional Personality Questionnaire (TPQ)

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Conscientiousness explains how GMV leads to euphoria in al MS pts

GMV → Euphoria effect is influenced by Neuro cism only in high Neuroticism patients. High neuroticism induces chronically high emotionality and dysregulation of the hypothalamic‐pituitary‐adrenal axis.

Conclusions

There are psychometric tests for personality and neuropsychiatric symptoms in MS: NEOFFI, and NPI

Personality is markedly affected in some MS patients, but far fewer than once thought

Neuropsychologically focused CBT may be a viable approach for treatment

↑ in Neuro cism and ↓ in Extraversion and Conscientiousness are risk factors for poor adaptation

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Thank You

Bianca Weinstock-Guttman MD

Robert Zivadinov MD; Murali Ramanathan PhD

David Hojnacki MD; Channa Kolb MD

Margaret Bucello NP; Audrey Smerbeck PhD

Jonathan Rodgers PhD, Natalie Emmert BA