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Title: Mood and Cognition in MS: The Patient


1
Mood and Cognition in MSThe Patients
Challenges OursRosalind Kalb, PhD
2
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.
3
  • Multiple Sclerosis A Very Brief Overview

4
What does MS look like?
5
What does MS really look like?
  • Juliaa 35yo white married mother of 3 who is
    exhausted all the time and cant drive because of
    vision problems and numbness in her feet
  • Jacksona 25yo African-American man who stopped
    working because he cant control his bladder or
    remember what he read in the morning paper
  • Mariaa 10yo Hispanic girl who falls down a lot
    and whose parents just told her she has MS
  • Lorettaa 47yo white single woman who moved into
    a nursing home because she can no longer care for
    herself
  • Geoffa 24yo single white man who is severely
    depressed and worried about losing his job
    because of his MS diagnosis

6
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 (CNSbrain, 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.

7
What MS Is Not
  • MS is not
  • Contagious
  • Directly inherited
  • Always severely disabling
  • Fatalexcept in fairly rare instances
  • Being diagnosed with MS is not a reason to
  • Stop working
  • Stop doing things that one enjoys
  • Not have children

8
What causes MS?
Genetic Predisposition
Environmental Trigger
Immune Attack
Loss of myelin nerve fiber
9
What happens in MS?
Activated T cells...
...cross the blood-brain barrier
launch attack on myelin nerve fibers...
to obstruct nerve signals
10
What happens to the myelin and nerve fibers?
11
Who gets MS?
  • Usually diagnosed between 20 and 50
  • Occasionally diagnosed in young children and
    older adults
  • More common in women than men (2-31)
  • 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)

12
Why does a person get MS?
  • 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.

13
What is the genetic factor?
  • 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)

14
What are possible symptoms?
  • Balance problems
  • Weakness
  • Stiffness (spasticity)
  • Speech/swallowing problems
  • Tremor
  • Emotional changes
  • Cognitive problems
  • Fatigue (most common)
  • Bladder/bowel

    dysfunction
  • Sensory problems

    (numbness, tingling)
  • Vision problems
  • Pain (neurogenic)
  • Sexual problems
  • Breathing difficulties
  • Dizziness/vertigo

Our focus today Visible to others
15
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

16
Who is on the MS Treatment Team?
  • 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.

17
Primary Challenges for People Living with MS
  • Chronicitymost will live with MS for decades
  • Unpredictabilityeach persons outcome is
    uncertain
  • Change and Lossmost will need to grieve over
    major changes in their lives
  • Expenselarge direct and indirect costs
  • Multiple Choices with no correct
    answerstreatments, disclosure, employment,
    family planning
  • Risk Tolerancevaries among family members

18
Contrasting Then and Now
  • THEN
  • Diagnose Adios
  • You should go home and rest.
  • Women with MS should never have children
  • NOW
  • 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.

19
So what do we know about MS?
  • 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.

20
  • Mood Changes in MS

21
Why are mood issues so important?
  • 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

22
DepressionSetting 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 persons 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
23
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 points3
  • Following the diagnosis
  • Following significant loss of function, departure
    from the workforce

1 Minden Schiffer, 1990 Patten et al., 2003
2Feinstein, 2007
24
Meet Joseph
  • 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

25
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-pituitary-adrena
    l axis5

1Feinstein, 1995 2Gold et al, 2010 3Feinstein
et al, 2004 4Lynch et al., 2001 5Wei
Lightman, 1997
26
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 (gt5 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
27
Diagnosis of Depression in MS The Challenges,
contd
  • 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
28
What is normal grieving in MS?
Kalb, 2008
29
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 suicide1
  • 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
30
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
31
Tools for Assessing Depression in MS
  • 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)

32
Assessment Tools, contd
  • 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
33
Depression Treatment Recommendations
  • 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
34
Challenges to Treating Depression in MS
  • 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

1Mohr et al., 2006 2Feinstein, 2007 Zorzon et
al., 2001
35
Meet Cassandra
  • 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 didnt need it any more3 times
  • Mood stabilized on maintenance dose

36
Meet Anna
  • 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

37
So, what is the reality in MS?
  • 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.

38
Other Emotional Disorders in MS
  • Bipolar disorder
  • Mood swings
  • Anxiety
  • Pseudobulbar affect
  • Euphoria

39
What do we know about bipolar disorder in MS?
  • 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
40
What do we know about mood swings in MS?
  • 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

41
Meet Norman
  • 55 yo man diagnosed with PPMS
  • Minimally physically-disabled
  • Married with two children
  • Professional ?? retired because of MS fatigue
  • Warm, funny, feisty, irritable, moody

42
One Childs Description of MS Moods
43
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
44
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 pre-frontal
    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
45
PBA, contd
  • Has been treated successfully with amitriptyline1
    and SSRI antidepressants2
  • Neudexta (dextromethorphan quinidine) approved
    in 2010 to treat PBA3

1Schiffer Pope, 1985 2Seliger et al., 1989
3Pioro et al., 2010
46
Euphoria in MS
  • Once thought to be a hallmark of MS
  • Persistent unrealistic optimism in spite of harsh
    realities and lack of insight
  • Fixed rather than fluctuatinglike a personality
    change
  • Associated with progressive course, widespread
    lesions on MRI, significant cognitive impairment
  • Devastating for families
  • No treatment available

47
Meet Erica
  • 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

48
Take-Aways about Common Mood Issues
  • 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

49
  • Cognitive Changes in MS

50
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
51
Prevalence of Cognitive Changes1
1LaRocca Kalb, 2006
52
Impact of Cognitive Impairment on Employment1
1Rao et al. 1991
53
Cognitive Functions Affected in MS1
  • 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
54
Cognitive Functions Unaffected in MS1
  • General intellect
  • Long-term (remote) memory
  • Recognition memory
  • Conversational skill
  • Reading comprehension

1DeLuca, 2006
55
The Psychosocial Impact of Cognitive Changes1
  • The ability to think, remember, and reason is
    central to a persons 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 peoples perceptions
  • Interfere with role performance
  • Affect the balance and intimacy in a partnership
  • Have an interrelationship with depression

1Kalb, 2006
56
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

57
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 theyve 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

58
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
59
NMSS Resources for Clinicians
  • MS Clinical Care Network
    (www.nationalMSsociety.org/MSClinicalCare
    healthprof_info_at_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

60
NMSS Resources for Your Patients
  • 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
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