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Advanced clinical neuropsychology > Topic 2: Fatigue > Flashcards

Topic 2: Fatigue Flashcards

1
Q

What is MS (multiple sclerosis)

A

An inflammatory disease of the central nervous system that results in myelin destruction and axonal degeneration in the brain and spinal cord.

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2
Q

The relapsing-remitting MS subtype is characterized by ..

A

clearly defined episodes of neurological dysfunction (relapse) separated by periods of relative clinical stability (remissions).

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3
Q

The majority of untreated cases of relapsing-remitting MS evolve into a …

A

secondary-progressive phase

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4
Q

A secondary progressive phase in MS is characterized by …

A

a gradual, insidious deterioration, usually in the form of paraparesis, hemiparesis, or dementia.

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5
Q

The primary-progressive subtype of MS is characterized by …

A

a slow deterioration in neurologic function from onset, without distinct relapses

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6
Q

What is the effect of therapies for the management of MS?

A

these therapies can decrease the frequency of clinical relapses and new radiological lesion formation. However, non of these therapies reverse preexistig tissue damage of control chronic symptoms such as fatigue, that are common to all MS subtypes.

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7
Q

What is considered to be one of the main causes of impaired quality of life among MS patients?

A

Fatigue, independent of depression or disability.

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8
Q

Fatigue in MS remains poorly understood and often underemphasized for several reasons.

A
  1. fatigue is a subjective symptom without a unified definition
  2. Ambiguity arises because no gold standard exists by which to measure fatigue
  3. whereas questionnaires can be helpful to rate the level of fatigue, most do not include questions to qualify or define the fatigue.
  4. fatigue in MS patients may be multifactorial
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9
Q

The most commonly proposed primary mechanisms of fatigue in MS involve the immune system or sequelae from central nervous system damage. Specific causes are thought to include:

A
  • proinflammatory cytokines
  • endocrine influences
  • axonal loss
  • altered patterns of cerebral activation
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10
Q

What is known about cytokine influences in fatigue in MS

A

Cytokines implicated in the disease are thought to be strong mediators of fatigue. interferon-gamma and TNF-alpha are the most studied. These cytokines are significantly increased in fatigued MS patients compared to non-fatigued patients. Both cytokines are relatively nonspecific and may be elevated in a variety of inflammatory conditions

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11
Q

What is known about endocrine influences in fatigue in MS?

A

The HPA-axis and the hormone DHEA are most studied. Both low cortisol and low DHEA levels have been implicated in CFS, and low DHEA levels are found in patients with lupus and rheuma. Lower levels of DHEA have been demonstrated in MS patients with sustained fatigue than their non-fatigued counterparts.

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12
Q

What is evidence for possible hormonal influence in fatigue in MS?

A

the fact that many MS patients report increased energy while taking corticosteroids as treatment for their neurologic symptoms further supports a possible hormonal influence.

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13
Q

Why are steroids not advocated as treatment for fatigue in MS?

A

because of the chronic nature of fatigue and risks of long-term steroid use

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14
Q

PET demonstrates decreased regional glucose metabolism in various brain structures of fatigued MS patients, which structures?

A

decreased regional glucose metabolism in the frontal cortex and basal ganglia

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15
Q

Fatigue in MS also can arise from associated conditions or accumulation of disease burden. Specific causes to consider include …

A
  • sleep disorders
  • depression
  • disability status
  • MS subtype
  • iatrogenicity
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16
Q

Which sleep disorders may affect MS patients?

A
  • RLS
  • periodic limb movement disorder
  • chronic insomnia
  • circadian rhythm disturbances
  • sleep disordered breathing
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17
Q

What is the prevalence of RLS in MS patients?

A

The prevalence of RLS among MS patients is approximately 3-5 times that of the general population

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18
Q

Risk for chronic insomnia may arise secondary to ..

A
  • pain
  • spasticity
  • depression
  • anxiety
  • nocturia
  • medication effects
  • RLS
  • periodic limb movement disorder
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19
Q

What is the prevalence of depression in MS patients?

A

50%

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20
Q

In which MS subtype is fatigue most severe?

A

Fatigue appears to be most severe in patients with progressive subtypes of MS, but this observation may in part be confounded by disability levels

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21
Q

The Chalder Fatigue Scale was created for ..

A

CFS patients

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22
Q

The Chalder Fatigue Scale quantifies fatigue intensity in terms of ..

A

physical and mental domains

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23
Q

Advantages of the Chalder Fatigue Scalre include ..

A

its ease of use and brevity. Although it has demonstrated good internal consistency in patients with CFS, MS-specific assessments of validity and consistency for this instruments are lacking.

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24
Q

Krupp’s Fatigue Severity Scale is designed ..

A

to identify common features of fatigue in both MS and lupus patients, the FSS assesses the impact of fatigue on multiple outcomes, with a physical focus.

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25
Q

the FSS can differentiate between …

A

subgroups of MS, CFS, and primary depression

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26
Q

The Modified Fatigue Impact Scale contains only 21 items and offers a more multidimensional assessment:

A

physical, cognitive and psychosocial functioning

27
Q

Besides its multidimensional features, other advantages of the MFIS include …

A
  • ease of use
  • good reproducibility
  • strong correlation with FSS results
  • reliable tool
28
Q

What is the diagnostic approach to fatigue in MS?

A
  1. inital questioning
  2. sleepiness assessment: epworth sleepiness scale (ESS) & Pittsburgh Sleep Quality Index (PSQI)
  3. depression screening: Beck Depression Inventory (BDI) & Zung Self-Rating Depression Scale
  4. fatigue quantification - FSS or MFIS
  5. other medical conditions
29
Q

Which drugs are used to treat fatigue in MS?

A
  • Amantadine -> used for PD and influenza, it also remains the most extensively studied for MS related fatigue
  • Pemoline -> central nervous stimulant with dopaminergic effects. Pemoline has been associated with liver toxicity that has limited its use.
  • Modafinil -> wake-promoting agents
30
Q

Non-pharmacologic treatments in MS

A
  • CBT

- Relaxation Therapy

31
Q

Fatigue in a clinical setting is typically described als …

A

A pervasive complaint of individuals with significant health problems of medical, psychiatric or neurologic origin

32
Q

A good deal of research has been devoted to elucidating the mechanisms involved in such fatigue, particularly in certain disorders such as …

A

MS, TBI & depression

33
Q

Fatigue remains a poorly understood symptom whose management strategies, whether behavioral or pharmacological, are only partially effective. Why?

A

Because there is a lack of a widely accepted conceptual framework of fatigue.
First, there is no universally accepted definition of fatigue.
Second, fatigue continues to be conceptualized as a unitary construct rather than a multifaceted symptom, with components potentially arising from distinct mechanisms of origin.

34
Q

The multidimensional nature of fatigue often leads to …

A

Confusion and miscommunication between professionals as well as with patients

35
Q

The primary approach to measuring fatigue today is by …

A

Subjective patient reporting

36
Q

Self reports measuring fatigue have been known to …

A

To correlate poorly with actual physical performance or measures of disease activity

37
Q

How is the relationship between subjective fatigue and cognitive dysfunction

A

There is no relationship found between subjective fatigue and cognitive dysfunction

38
Q

What is mental fatigue?

A

A time-related deterioration in the ability to perform certain mental tasks

39
Q

Studies examining mental fatigue over the course of an experimental induction of fatigue, using four general principles …

A
  1. Cognitive fatigue can be conceptualized as decreased performance over a prolonged period of time
  2. Cognitive fatigue could be viewed as decreased performance during acute but sustained mental effort.
  3. Cognitive fatigue after challenging mental exertion
  4. Cognitive fatigue after challenging physical exertion
40
Q

What did studies on cognitive fatigue during prolonged effort find?

A

Studies of prolonged effort in clinical samples show little to no discernable effect on actual cognitive performance. While prolonged cognitive effort produced an increase in the subjective experience of fatigue in these samples, this increase did not translate into observable cognitive performance deficits

41
Q

What did studies on cognitive fatigue during sustained mental effort found?

A

The method of documenting change in performance during sustained cognitive activity appears to be fruitful in objectively documenting cognitive fatigue and its effect on measures of sustained attention or processing speed. Overall, indices of subjective fatigue are not reliably correlated with objective measures of cognitive fatigue.

42
Q

What did studies on cognitive fatigue after challenging physical exertion find?

A

The data suggesting that physical exertion affects later cognitive performance is mixed, and thus inconclusive. Yet the lack of any relationship between subjective fatigue and objective performance was universal

43
Q

What are possible mechanisms of cognitive fatigue?

A
  1. Metabolic disturbances : fluctuations in glucose metabolism may be the final common pathway leading to cognitive decline.
  2. Central fatigue is caused by an increase in tryptophan levels in the brain, leading to an increased level of the neurotransmitter serotonin in the brain.
  3. A third and more recent model for the subjective experience of cognitive fatigue is its association with levels of functional cerebral activity.
44
Q

MS patients have been shown to experience dysregulation of the …

A

HPA axis, and HPA axis dysregulation mat be related to cognitive performance. However, the relationship with fatigue is fairly low.

45
Q

Functional imaging studies suggest that the perception of cognitive fatigue may be a result of…

A

Increased cerebral effort required to perform the same amount of cognitive work

46
Q

During a complex working memory task, healthy controls showed cerebral activation primarily in ….. In contrast,TBI subjects displayed ……

A

Healthy controls showed cerebral activation primarily in the left hemisphere of the brain, involving the frontal and temporal lobes, as well as bilateral parietal lobe activation. TBI subjects displayed bilateral activation that was more lateralized, primarily to homologous regions of the right hemisphere relative to controls. In addition, TBI subjects showed a pattern of more dispersed activation within both the ipsilatersal left no contralateral hemispheres

47
Q

What are the two primary misconceptions regarding central fatigue?

A
  1. There must be an association between subjective and objective measures of fatigue
  2. Performance decrement a will result from cognitive fatigue.
48
Q

Definition of CSF

A

Persistent fatigue lasting for at least 6 months not due to ongoing exertion, not substantially relieved by rest, and not caused by other medical conditions

49
Q

Fatigue can be conceptualized as …

A
  • a subjective feeling

- a performance decrement

50
Q

What is peripheral fatigue?

A

Failure to sustain force or power output because of neuromuscular dysfunction outside of the central nervous system

51
Q

What is central fatigue?

A

Resulting from failure to achieve and maintain the recruitment of high-treshold motor units, implicating dysfunction in the CNS

52
Q

Fatigue is a multidimensional construct, name 4 constructs.

A
  • behavior (effects on performance)
  • feeling (subjective experience)
  • mechanism (physiological and psychological)
  • context (environment)
53
Q

What are the primary mechanisms of fatigue?

A
  • basal ganglia
  • frontal lobes
  • HPA axis
  • pro inflammatory cytokines affecting neural metabolism
54
Q

What is the difference between ms patients with fatigue and without fatigue?

A

Ms patients with fatigue show reduced glucose metabolism in the prefrontal cortex and basal ganglia, suggesting a dysfunction of cortical-subcortical circuits

55
Q

What are the general sites of pathology in central fatigue?

A
  • basal ganglia: Parkinson’s disease
  • hypothalamus: narcolepsy
  • subcortical gray and white matter disease: stroke and demyelination
  • limbic system: limbic encephalitis
  • thalamus and ras: stroke and tumors
  • brain stem nuclei: myotonic dystrophy
  • posterior fossa: Chiari malformation
56
Q

What is myotonic dystrophy?

A

Inherited disorder of muscle function which also can affect other body systems

57
Q

What is Chiari malformation?

A

Downward displacement of cerebellum (cerebellar tonsils) through for amen magnum

58
Q

What is primary fatigue?

A

Fatigue caused by its primary neural mechanisms

59
Q

What is secondary fatigue?

A

Includes factors perpetuating or exacerbating its effects

60
Q

How is fatigue treated?

A
  • psychotherapy
  • pharmacotherapy
  • physical exercise
61
Q

Our understanding of the behavioral correlates of fatigue has been hindered by two flawed assumptions:

A
  1. Subjective report of fatigue and objective measures are correlated
  2. The idea that cognitive fatigue necessarily results in a performance decrement
62
Q

What problems are associated with defining cognitive fatigue based on self-report?

A
  • assessments instruments focus on a small subset of potential sources of fatigue perception, while there are several factors associated with subjective fatigue.
  • construct contamination: constructs known to be independent of fatigue are often included in such questionnaires, raising questions about validity and reliability of such subjective reports.
63
Q

How can psychiatric and neurological underpinnings of fatigue be disentangled?

A

By means of tryptophan. Increase in tryptophan leads to increase in serotonin. Serotonin is known to be involved in sleep regulation, and excessive serotonin may lead to tiredness or fatigue

Advanced clinical neuropsychology (7 decks)

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