Mood and Cognition in MS:
The Patient’s Challenges & Ours
Rosalind Kalb, PhD
Jean-Martin Charcot
Second Lecture on Multiple Sclerosis, 1868
There is marked enfeeblement of the memory; conceptions are
formed slowly; the intellectual and emotional faculties are
blunted in their totality…. It is not rare to see them give way
to foolish laughter for no cause, and sometimes, on the
contrary, to melt into tears for no reason. Nor is it rare,
amid this state of mental depression, to find psychic disorders
arise which assume one or other of the classic forms of
mental alienation.
Multiple Sclerosis: A [Very] Brief Overview
What does MS look like?
What does MS really look like?
• Julia—a 35yo white married mother of 3 who is exhausted
all the time and can’t drive because of vision problems and
numbness in her feet
• Jackson—a 25yo African-American man who stopped
working because he can’t control his bladder or remember
what he read in the morning paper
• Maria—a 10yo Hispanic girl who falls down a lot and whose
parents just told her she has MS
• Loretta—a 47yo white single woman who moved into a
nursing home because she can no longer care for herself
• Geoff—a 24yo single white man who is severely depressed
and worried about losing his job because of his MS
diagnosis
What MS Is:
• MS is thought to be a disease of the immune system.
• The primary targets of the immune attack are the
myelin coating around the nerves in the central
nervous system (CNS—brain, spinal cord, and optic
nerves) and the nerve fibers themselves.
• Its name comes from the scarring caused by
inflammatory attacks at multiple sites in the central
nervous system.
What MS Is Not:
• MS is not:
 Contagious
 Directly inherited
 Always severely disabling
 Fatal—except in fairly rare instances
• Being diagnosed with MS is not a reason to:
 Stop working
 Stop doing things that one enjoys
 Not have children
What causes MS?
Genetic
Predisposition
Environmental
Trigger
Immune Attack
Loss of myelin
& nerve fiber
What happens in MS?
“Activated” T cells...
...cross the blood-brain barrier…
…launch attack on myelin & nerve fibers...
…to obstruct nerve signals
myelinated nerve fiber
myelinated nerve fiber
What happens to the myelin and nerve fibers?
Who gets MS?
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Usually diagnosed between 20 and 50
 Occasionally diagnosed in young children and older
adults
More common in women than men (2-3:1)
Most common in those of Northern European ancestry
 More common in Caucasians than Hispanics or African
Americans; rare among Asians
More common in temperate areas (further from the equator)
Why does a person get MS?
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We do not know why one person gets MS and another does not.
We do not know of anything:
 The person did to cause MS.
 The person could have done to prevent it.
There is no way to predict who will get it and who will not.
What is the genetic factor?
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The risk of getting MS is approximately:
 1/750 for the general population
 1/40 for person with a close relative with MS
 1/4 for an identical twin
20% of people with MS have a blood relative with MS
The risk is higher in any family in which there are several family
members with the disease (aka multiplex families)
What are possible symptoms?
• Fatigue (most common)
• Bladder/bowel
dysfunction
• Sensory problems
(numbness, tingling)
• Vision problems
• Pain (neurogenic)
• Sexual problems
• Breathing difficulties
• Dizziness/vertigo
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Balance problems
Weakness
Stiffness (spasticity)
Speech/swallowing
problems
• Tremor
• Emotional changes
• Cognitive problems
Our focus today
Visible to others
How is MS treated?
• While we continue to look for the cure, MS treatment needs
to be comprehensive and interdisciplinary:
 Treating relapses (aka exacerbations, flare-ups, attacks)
 Slowing disease progression
 Managing symptoms
 Maintaining/improving function
 Enhancing quality of life for individuals and their families
Who is on the MS “Treatment Team”?
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Neurologist
Nurse
Physiatrist
Physical therapist
Occupational therapist
Speech/language pathologist
Neuropsychologist
Social worker/Care manager
Psychotherapist
Psychiatrist/psychiatric nurse practitioner
Urologist
Neuro-ophthalmologist
It takes a village….
Primary Challenges for People Living with MS
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Chronicity—most will live with MS for decades
Unpredictability—each person’s outcome is uncertain
Change and Loss—most will need to grieve over major
changes in their lives
Expense—large direct and indirect costs
Multiple Choices with no “correct” answers—treatments,
disclosure, employment, family planning
Risk Tolerance—varies among family members
Contrasting Then and Now
THEN
NOW
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“Diagnose & Adios”
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“You should go home and rest.”
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“Women with MS should never
have children
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“There is a lot we can do to
manage your MS.”
“People with MS can continue to
work as long as they want to and
feel able.”
Women and men with MS can be
happy parents of healthy kids.”
So what do we know about MS?
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MS is a chronic, unpredictable disease.
The cause is still unknown.
MS affects each person differently; symptoms vary
widely.
MS is not fatal, contagious, directly inherited, or always
disabling.
Early diagnosis and treatment are important:
 Significant, irreversible damage can occur early on.
 Treatment reduces the number of relapses and may
slow progression.
Treatment includes: attack management, symptom
management, disease modification, rehabilitation,
emotional support.
Mood Changes in MS
Why are mood issues so important?
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Affect cognitive function
Compromise quality of life
Are associated with time lost from work
Interfere with self-care/adherence to treatment
Adversely affect relationships
May be triggered by medications
Depression—Setting the Stage1
• Depression
 Is more common in MS than in other chronic
conditions.
 Is under-diagnosed and under-treated in MS patients.
 Impacts quality of life
 Interferes with a person’s ability to participate
actively in his or her own MS care
 Impacts cognition (and vice versa)
 Is the greatest risk factor for suicide
1Feinstein,
2007
Prevalence of Depression in MS
• Lifetime prevalence estimates range from 20-50% in
clinic populations, with a similarly high rate in
community samples.1
• Depression can occur at any time over the disease
course.
• People are at greatest risk for depression at major
transition points:3
 Following the diagnosis
 Following significant loss of function, departure
from the workforce
1 Minden
& Schiffer, 1990; Patten et al., 2003; 2Feinstein, 2007
Meet Joseph
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60 yo man with SPMS
Married with two children
Employed full-time as a college professor
Triplegic
Low-key, creative, warm, wry sense of humor
Etiology of Depression in MS
• Evidence points to a multifactorial etiology1
 Brain pathology2,3
 Psychosocial factors:
• Unpredictability
• Psychosocial stressors (marital problems;
economic pressures, etc.)
• Emotion-centered coping style4
• Learned helplessness vs. self-efficacy
 Abnormalities in the hypothalamic-pituitaryadrenal axis5
1Feinstein,
1995; 2Gold et al, 2010; 3Feinstein et al, 2004; 4Lynch
et al., 2001; 5Wei & Lightman, 1997
Diagnosis of Depression in MS: The Challenges
• Of 9 DSM-IV symptoms of depression, 4 are symptoms of MS1
 Depressed mood most of the day nearly every day
 Markedly diminished pleasure in most or all activities
 Significant weight change (>5% up or down in a month)
 Inability to sleep or sleeping too much
 Motor agitation or significant slowing
 Fatigue or loss of energy
 Problems with thinking or concentrating
 Feelings of worthlessness/excessive guilt
 Recurrent thoughts of death
1Mohr
et al., 1997
Diagnosis of Depression in MS: The Challenges,
cont’d
• Patients may be reluctant to report mood changes
• Depression in MS often presents with
irritability/frustration rather than the more typical
withdrawal, apathy, and guilt1
• The common – but incorrect – assumption that it is
“normal” for a person with a devastating chronic
illness to be depressed
• Depression can be difficult to distinguish from the
grieving process that is part of life with MS2
1Minden
et al., 1987; Feinstein & Feinstein; 2001; 2Kalb & Miller, 2008
What is normal grieving in MS?
Kalb, 2008
Undiagnosed Depression: The Consequences
• The result of these challenges is that many people with
MS are living with an unnecessary amount of emotional
pain, a reduced quality of life, and a greatly increased
risk of suicide:1
 In one study, two-thirds of MS patients with
depression within a neurology clinic received no
antidepressant treatment.2
 Of those who were treated, only 25% were given an
adequate dose.
1Feinstein,
2007; Sadovnick et al., 1991; Stenager & Stenager, 1992;
2Mohr et al., 2006
Suicide among Patients with MS
• Suicide is more common in MS than in other
neurological disorders.1
 Swedish epidemiological study: significantly
elevated risk of suicide in MS, particularly in
males and those diagnosed before age 30.2
 Canadian review of death certificates (1972-1988):
suicide listed as cause of death in 15% of MS
clinic attendees (7.5x greater than age-matched
population).3
• Anxiety co-morbid with depression increases the
risk for self-harm.4
1Stenager
& Stenager, 1992; 2Stenager et al., 1992; 3Sadovnick et
al., 1991; 4Feinstein et al., 1999
Tools for Assessing Depression in MS
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Beck Depression Inventory (BDI)
Beck Fast Screen for Medically Ill Patients (B-FS)*
Hamilton Rating Scale for Depression (HDRS)
[http://healthnet.umassmed.edu/mhealth/HAMD.pdf]
• Psychiatric interview
*Recommended by the Goldman Consensus Statement on Depression in
Multiple Sclerosis (Goldman Consensus Group, 2005)
Assessment Tools, cont’d
• Two-question screening tool validated in MS1
 260 MS patients screened using the MDD module of
the DSM-IV Structured Clinical Interview
 Each participant also given two screening questions:
1. During the past two weeks, have you often been
bothered by feeling down, depressed, or hopeless?
2. During the past two weeks, have you often been
bothered by little interest or pleasure in doing things?
 Using at least one affirmative response on either
question as the criterion identified 98.5% of patients
meeting the criteria for MDD based on the structured
diagnostic interview.
1Mohr
et al., 2007
Depression: Treatment Recommendations
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Psychotherapy + antidepressant medication is
the treatment of choice1
 Cognitive behavior therapy
 Psychoeducation (problem-focused coping
skills)2
 SSRI antidepressants
Exercise3
ECT is recommended under limited
circumstances4
Note: Support groups/chat rooms/bulletin boards are not
adequate for treating significant depression
1Feinstein,
2007; Mohr et al., 2001b; 2Dennison et al., 2009; Goretti et al., 2009;
3 Dalgas et al., 2010; Stroud & Minahan, 2009; Petajan et al., 1996; 4Feinstein, 2007
Challenges to Treating Depression in MS
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1Mohr
Patients’ resistance to treatment (“I take enough
pills already!”)
Neurologists’ lack of time/lack of training
May require unusual/unexpected antidepressant
dosages1
Non-adherence because of side effects (Rates of
sexual dysfunction may be as high as 70% in a
population that already experiences significant
sexual dysfunction)2
Insufficient number of psychiatrists who are
interested/accessible/covered
et al., 2006; 2Feinstein, 2007; Zorzon et al., 2001
Meet Cassandra
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43 yo woman with PPMS
Dynamic, funny, and smart
Employed in a high-power job
In a committed relationship
Gradually increasing mobility impairment
Responded so well to medication that she thought
she didn’t need it any more—3 times
Mood stabilized on maintenance dose
Meet Anna
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49 yo woman diagnosed with RRMS
Employed as a teacher
In a committed relationship
Minimally physically disabled
Bubbly, motivated, creative, clingy, dependent
Became depressed following the diagnosis
Pressured by her friends to seek treatment
Successfully treated with antidepressant medication
(“happy pills”) and intermittent psychotherapy for
past 15 years
So, what is the reality in MS?
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Depression in general tends to be under-diagnosed.
Two-thirds of MS patients with major depression within
neurological clinics receive no antidepressant treatment.
Three-quarters of those treated are given an inadequate
dose.
Many people with MS are living with more distress and
discomfort than they need to.
Other Emotional Disorders in MS
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Bipolar disorder
Mood swings
Anxiety
Pseudobulbar affect
Euphoria
What do we know about bipolar disorder in
MS?
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Relatively rare in MS, but more common than in the
general population1,2,3
May share a common genetic predisposition with MS
Likely related to white matter changes
Responds to standard treatment (mood stabilizers +
antipsychotic medication as needed)
Steroid Alert
1Feinstein,
2007; 2Hutchinson et al., 1993; 3Schiffer et al., 1986
What do we know about mood swings in MS?
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Moderate to severe shifts in mood may occur
May shift between happiness, sadness, irritability,
and/or rage
Affects self-esteem and the sense of personal control
Strains relationships at home and at work
May be treated with a combination of psychotherapy
and mood-stabilizing medications
Steroid Alert
Meet Norman
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55 yo man diagnosed with PPMS
Minimally physically-disabled
Married with two children
Professional  retired because of MS fatigue
Warm, funny, feisty, irritable, moody
One Child’s Description of MS Moods
Anxiety in People Living with MS
• Anxiety is more common than depression, especially
among females, particularly right after diagnosis.1
• Like depression, anxiety is under-diagnosed and
under-treated.
• Anxiety is the best predictor of excessive alcohol
consumption in people with MS.2
• Lifetime prevalence of generalized anxiety disorder in
MS patients found to be 18.6% vs. 5.1% in general
population.3
1Feinstein
et al., 1999; Zorzon et al., 2001; 2Quesnel & Feinstein, 2004;
3Korostil & Feinstein, 2007
Pseudobulbar Affect (PBA) in MS
• Characterized by episodes of uncontrolled
laughing and or crying1
 Inappropriate to both external circumstances
and internal mood states
• PBA may be mediated by damaged to the prefrontal cortex2
• Occurs in approximately 10% of MS patients2
• Generally associated with longer disease course,
greater disability, and more cognitive impairment2
1Poeck,
1969; 2Feinstein et al., 1997
PBA, cont’d
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1Schiffer
Has been treated successfully with amitriptyline1
and SSRI antidepressants2
Neudexta® (dextromethorphan + quinidine)
approved in 2010 to treat PBA3
& Pope, 1985; 2Seliger et al., 1989; 3Pioro et al., 2010
Euphoria in MS
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Once thought to be a hallmark of MS
Persistent unrealistic optimism in spite of harsh
realities and lack of insight
Fixed rather than fluctuating—like a personality
change
Associated with progressive course, widespread
lesions on MRI, significant cognitive impairment
Devastating for families
No treatment available
Meet Erica
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30 yo woman with SPMS
Diagnosed with RRMS at age 14
In a long-term committed relationship
Initial symptoms were cognitive changes that
progressed rapidly
Today, minimal physical symptoms but unable to
function/live independently because of cognitive
limitations
Warm, cheerful, unconcerned about her status and
future
Take-Aways about Common Mood Issues
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Significantly affect quality of life and healthcare
May be related to disease process itself and/or
altered life circumstances
May overlap with other MS symptoms
Are often under-diagnosed or mis-diagnosed
Respond best to medication + counseling
Depression and anxiety are more common
in caregivers as well
Cognitive Changes in MS
Cognition and Other Disease Characteristics1
• Cognitive function correlates with number of
lesions and lesion area on MRI, as well as brain
atrophy.
• Cognitive dysfunction can occur at any time but is
more common later in the disease.
• Cognitive dysfunction can occur with any disease
course, but is slightly more likely in progressive
MS.
• Being in an exacerbation is a risk factor for
cognitive dysfunction.
• Depression can worsen cognition, particularly
executive functions.
1Feinstein,
2007; LaRocca & Kalb, 2006
Prevalence of Cognitive Changes1
Severity of Cognitive Changes
in Multiple Sclerosis
None
50%
Mild
40%
Moderate to
severe
10%
1LaRocca
& Kalb, 2006
Impact of Cognitive Impairment on Employment1
45
40
% Employed
35
30
25
20
15
10
5
0
1Rao
et al. 1991
Impaired
Not Impaired
Cognitive Functions Affected in MS1
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Memory - acquisition and retrieval
Attention and concentration
Speed of information processing
Executive Functions (planning, prioritizing, organizing,
decision-making)
• Visual/spatial organization
• Verbal fluency - word finding
1DeLuca,
2006
Cognitive Functions Unaffected in MS1
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1DeLuca,
General intellect
Long-term (remote) memory
Recognition memory
Conversational skill
Reading comprehension
2006
The Psychosocial Impact of Cognitive Changes1
• The ability to think, remember, and reason is central
to a person’s identity. Changes in cognitive abilities:
 Threaten the sense of self
 Damage self-esteem and self-confidence
• Cognitive abilities impact interactions with others.
• Cognitive impairments:
 Alter communication patterns
 Impact other people’s perceptions
 Interfere with role performance
 Affect the balance and intimacy in a partnership
 Have an interrelationship with depression
1Kalb,
2006
Guidelines for Treatment (for now)1
• Symptomatic Treatments – slow progress
 Not much of real value has emerged; as of 2012 no
agents have demonstrated efficacy in controlled
clinical trials
• Disease Modifying Agents – may be most important
 Modest results so far, but if they can slow or halt
accumulation of cerebral lesions . . .
• Cognitive Rehabilitation – common-sense help
 Disappointing data thus far but common-sense
points to compensatory measures as best strategy
 Address affective and social issues related to MS
Implications for patient care
Even mild cognitive dysfunction can impact treatment:
• Your patients may not:
 Show up on time for appointments
 Follow complex explanations
 Remember what they’ve been told
 Follow through on treatment plans
• You may want to:
 Provide informational brochures
 Provide appointment reminders
 Write down specific instructions
 Remind patients to write down their questions
 Invite patients to bring a family member or friend to
appointments
Multiple Sclerosis Neuropsychological
Screening Questionnaire (MSNQ)1
• 15-item self-report questionnaire
(http://mscare.org/cmsc/images/pdf/MSNQ.pdf)
 Includes versions for both patient and informant
 Takes approximately 5 minutes
 Reliable and predicts neuropsychological impairment
• Both self- and informant reports correlated with
cognitive dysfunction and depression scales,
however:
• Self-reports may be exaggerated in depressed
patients
• Self-reports may under-estimate impairment in
severely impaired patients
Benedict et al., 2003; Benedict et al., 2004
NMSS Resources for Clinicians
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MS Clinical Care Network
(www.nationalMSsociety.org/MSClinicalCare;
healthprof_info@nmss.org;
 Clinical consultations with MS specialists
 Literature search services
 Professional publications (Clinical Bulletins; Expert Opinion
Papers; Talking with Your MS Patients about Difficult Topics;
Pamela Cavallo Education Series for nurses, rehab
professionals, mental health professionals, and pharmacists
 Professional Education Programs (Nursing, Rehab,
Mental Health)
 Consultation on insurance and long-term care issues
NMSS Resources for Your Patients
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40+ chapters around the country
Newly-designed Web site (www.nationalmssociety.org)
Access to information, referral, support (1-800-344-4867)
Educational programs (in-person, online)
Support programs (self-help groups, peer and
professional counseling, friendly visitors)
Consultation (legal, employment, insurance, long-term
care
Financial assistance