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Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis (an evidence-based review)

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Title: Practice Parameter update: The care of the patient with amyotrophic lateral sclerosis (an evidence-based review)


1
Practice Parameter update The care of the
patient with amyotrophic lateral sclerosis (an
evidence-based review)
  • Report of the Quality Standards Subcommittee of
    the American Academy of Neurology
  • R. G. Miller, MD, FAAN C. E. Jackson, MD, FAAN
    E. J. Kasarskis, MD, PhD, FAAN J. D. England,
    MD, FAAN D. Forshew, RN W. Johnston, MD S.
    Kalra, MD J. S. Katz, MD H. Mitsumoto, MD,
    FAAN J. Rosenfeld, MD, PhD, FAAN C. Shoesmith,
    MD, BSc M. J. Strong, MD S. C. Woolley, PhD

2
If you have questions, comments, or feedback
regarding this slide presentation, or would like
to modify the contents for presentation in a
lecture, please contact guidelines_at_aan.com
3
Presentation Objectives
  • To review the evidence on care of the patient
    with amyotrophic lateral sclerosis (ALS)
  • Drug, nutritional, and respiratory therapies
  • Multidisciplinary care, symptom management, and
    cognitive/behavioral impairment
  • To present evidence-based recommendations

4
Overview
  • Background
  • Gaps in care
  • AAN guideline process
  • Analysis of evidence, conclusions,
    recommendations
  • Recommendations for future research

5
Background
  • In 1999, the American Academy of Neurology (AAN)
    published an evidence-based practice parameter
    for managing patients with amyotrophic lateral
    sclerosis (ALS).1
  • Since that publication, there have been some
    important new studies, including a randomized
    controlled trial of noninvasive ventilation (NIV)
    in ALS.2
  • Although only one drug, riluzole, has shown
    modest benefit and received US Food and Drug
    Administration (FDA) approval, there have been
    advances in symptomatic treatment for patients
    with this disease.
  • This revision updates the riluzole practice
    advisory and addresses other management issues
    for care of patients with ALS.

6
Gaps in Care
  • As of the publication of this guideline update,
    only one drug, riluzole, has received FDA
    approval.
  • The evidence for recent advances in symptomatic
    treatment for patients with ALS was not
    systematically examined before this parameter
    update.
  • Consensus-based general principles of ALS
    management have been developed to guide
    clinicians in managing patients with ALS.

7
AAN Guideline Process
  • Clinical Question
  • Evidence
  • Conclusions
  • Recommendations

8
Clinical Questions
  • The first step in developing guidelines is to
    clearly formulate questions to be answered.
  • Questions address areas of controversy,
    confusion, or variation in practice.
  • Questions must be answerable with data from the
    literature.
  • Answering the question must have the potential to
    improve care/patient outcomes.

9
Literature Search/Review
Rigorous, Comprehensive, Transparent

10
AAN Classification of Evidence
  • All studies rated Class I, II, III, or IV
  • Five different classification systems
  • Therapeutic
  • Randomization, control, blinding
  • Diagnostic
  • Comparison to gold standard
  • Prognostic
  • Screening
  • Causation

11
AAN Level of Recommendations
  • A Established as effective, ineffective or
    harmful (or established as useful/predictive or
    not useful/predictive) for the given condition in
    the specified population.
  • B Probably effective, ineffective or harmful
    (or probably useful/predictive or not
    useful/predictive) for the given condition in the
    specified population.
  • C Possibly effective, ineffective or harmful
    (or possibly useful/predictive or not
    useful/predictive) for the given condition in the
    specified population.
  • U Data inadequate or conflicting given current
    knowledge, treatment (test, predictor) is
    unproven.
  • Note that recommendations can be positive or
    negative.

12
Translating Class to Recommendations
  • A Requires at least two consistent Class I
    studies.
  • B Requires at least one Class I study or two
    consistent Class II studies.
  • C Requires at least one Class II study or two
    consistent Class III studies.
  • U Studies not meeting criteria for Class I
    through Class III.

13
Translating Class to Recommendations, cont.
  • In exceptional cases, one convincing Class I
    study may suffice for an A recommendation if 1)
    all criteria are met, 2) the magnitude of effect
    is large (relative rate improved outcome gt5 and
    the lower limit of the confidence interval is
    gt2).

14
Applying This Processto the Issue
  • We will now turn our attention to the guidelines.

15
Clinical Questions
  • 1. Does riluzole prolong survival or slow
    disease progression in ALS?
  • 2. Does lithium carbonate prolong survival or
    slow disease progression in ALS?
  • What is the effect of enteral nutrition
    administered via percutaneous endoscopic
    gastrostomy (PEG) on weight stability?
  • When is PEG indicated in ALS?
  • What is the efficacy of nutritional support via
    PEG in prolonging survival?
  • What is the effect of enteral nutrition delivered
    via PEG on quality of life (QOL)?

16
Clinical Questions, cont.
  • What is the efficacy of vitamin and nutritional
    supplements on prolonging survival or QOL?
  • What are the optimal pulmonary tests to detect
    respiratory insufficiency?
  • Does NIV improve respiratory function or increase
    survival?
  • How do invasive ventilation and NIV affect QOL?
  • What factors influence acceptance of invasive
    ventilation and NIV?
  • What is the efficacy of targeted respiratory
    interventions for clearing secretions?

17
Clinical Questions, cont.
  • How should a physician tell patients that they
    have ALS?
  • Does multidisciplinary management improve
    outcomes?
  • What are the most effective treatments for
    sialorrhea?
  • What pharmacologic measures reduce pseudobulbar
    affect?
  • What pharmacologic interventions reduce fatigue?
  • What interventions reduce cramps?
  • What interventions reduce spasticity?
  • What pharmacologic interventions reduce
    depression?

18
Clinical Questions, cont.
  • What pharmacologic interventions reduce anxiety?
  • What pharmacologic interventions reduce insomnia?
  • What is the prevalence and natural history of
    cognitive and behavioral impairment in ALS?
  • How is cognitive or behavioral impairment in ALS
    diagnosed?
  • What is the effect of cognitive or behavioral
    impairment on management of patients with ALS?
  • What treatments are effective for cognitive or
    behavioral impairment in ALS?
  • What treatments for dysarthria optimize
    communication in ALS?

19
Clinical Questions, cont.
  • What treatments reduce pain and dyspnea in the
    terminal phase of ALS?
  • Do hospice care, spiritual interventions, or
    advance directives improve quality of life in the
    terminal phase of ALS?
  • What is the optimal method of withdrawing both
    NIV and invasive ventilation in ALS?

20
Methods
  • OVID, MEDLINE EMBASE, CINAHL, Science Citation
    Index, BIOETHICSLINE, International
    Pharmaceutical Abstracts (IPAB), OVID Current
    contents, Medline-ProQuest, EIFL, and INVEST
  • 1998 through September 2007
  • Relevant, fully published, peer-reviewed articles

21
Methods, cont.
  • Search terms
  • Combined the words ALS, Lou Gehrig's disease, and
    motor neuron disease with the following words
    using AND
  • respiratory, respiratory failure, respiratory
    insufficiency
  • nutrition, enteral nutrition, malnutrition,
    weight loss, gastrostomy
  • clinical trials
  • mechanical insufflation-exsufflation, high
    frequency chest wall oscillation, Vest, Bipap,
    tracheostomy ventilation, dysphagia, mechanical
    ventilation, noninvasive ventilation,
    hypoventilation,
  • bronchial secretions, sleep-disordered breathing,
    breath stacking
  • sialorrhea, pseudobulbar palsy, pseudobulbar
    affect, emotional lability

22
Methods, cont.
  • Search terms, cont.
  • palliative care, diagnosis, telling the
    diagnosis, breaking the news, advance directives,
    hospice
  • botulinum toxin A, botulinum toxin B, parotid
    irradiation, anticholinergic drugs,
    amitriptyline, glycopyrrolate, benztropine,
    transdermal hyoscyamine, atropine,
    trihexyphenidyl hydrochloride, propranolol,
    metoprolol, dextromethorphan, quinidine, opioids,
    opiates, lorazepam
  • oxygen, dyspnea, pain, anxiety, sleep,
    depression, cramps, spasticity, insomnia, deep
    venous thrombosis, communication devices,
    fatigue, constipation
  • multidisciplinary clinic, specialty clinic
  • cognitive impairment, dementia, frontotemporal
    dementia, executive dysfunction

23
Methods, cont.
  • All panelists reviewed each article for
    inclusion.
  • Risk of bias was determined using the
    classification of evidence for each study
    (Classes IIV).
  • Strength of practice recommendations were linked
    directly to levels of evidence (Levels A, B, C,
    and U).
  • Conflicts of interest were disclosed.

24
Literature Review
  • Inclusion criteria
  • Relevant to the clinical questions
  • Limited to human subjects
  • Randomized controlled trials, cohort studies,
    case control studies, case series, meta-analyses,
    and review papers
  • Exclusion criteria
  • Articles related to postpolio conditions, cancer,
    or non-ALS disease
  • Articles not peer-reviewed

25
AAN Classification of Evidencefor Therapeutic
Intervention
  • Class I A randomized, controlled clinical trial
    of the intervention of interest with masked or
    objective outcome assessment, in a representative
    population. Relevant baseline characteristics are
    presented and substantially equivalent among
    treatment groups or there is appropriate
    statistical adjustment for differences. The
    following are also required a. concealed
    allocation, b. primary outcome(s) clearly
    defined, c. exclusion/inclusion criteria clearly
    defined, d. adequate accounting for drop-outs
    (with at least 80 of enrolled subjects
    completing the study) and cross-overs with
    numbers sufficiently low to have minimal
    potential for bias. e. For non inferiority or
    equivalence trials claiming to prove efficacy for
    one or both drugs, the following are also
    required 1. The authors explicitly state the
    clinically meaningful difference to be excluded
    by defining the threshold for equivalence or
    non-inferiority. 2. The standard treatment used
    in the study is substantially similar to that
    used in previous studies establishing efficacy of
    the standard treatment. (e.g. for a drug, the
    mode of administration, dose and dosage
    adjustments are similar to those previously shown
    to be effective).

26
AAN Classification of Evidencefor Therapeutic
Intervention, cont.
  • 3. The inclusion and exclusion criteria for
    patient selection and the outcomes of patients on
    the standard treatment are comparable to those of
    previous studies establishing efficacy of the
    standard treatment. 4. The interpretation of the
    results of the study is based upon a per protocol
    analysis that takes into account dropouts or
    crossovers.
  • Class II A randomized controlled clinical trial
    of the intervention of interest in a
    representative population with masked or
    objective outcome assessment that lacks one
    criteria ae above or a prospective matched
    cohort study with masked or objective outcome
    assessment in a representative population that
    meets be above. Relevant baseline
    characteristics are presented and substantially
    equivalent among treatment groups or there is
    appropriate statistical adjustment for
    differences.
  • Class III All other controlled trials (including
    well-defined natural history controls or patients
    serving as own controls) in a representative
    population, where outcome is independently
    assessed, or independently derived by objective
    outcome measurement.

27
AAN Classification of Evidencefor Therapeutic
Intervention, cont.
  • Class IV Studies not meeting Class I, II or III
    criteria including consensus or expert opinion.
  • Note that numbers 13 in Class Ie are required
    for Class II in equivalence trials. If any one of
    the three is missing, the class is automatically
    downgraded to Class III.
  • Objective outcome measurement an outcome
    measure that is unlikely to be affected by an
    observers (patient, treating physician,
    investigator) expectation or bias (e.g., blood
    tests, administrative outcome data).

28
AAN Classification of Evidencefor Diagnostic
Accuracy
  • Class I A cohort study with prospective data
    collection of a broad spectrum of persons with
    the suspected condition, using an acceptable
    reference standard for case definition. The
    diagnostic test is objective or performed and
    interpreted without knowledge of the patients
    clinical status. Study results allow calculation
    of measures of diagnostic accuracy.
  • Class II A case control study of a broad
    spectrum of persons with the condition
    established by an acceptable reference standard
    compared to a broad spectrum of controls or a
    cohort study where a broad spectrum of persons
    with the suspected condition where the data was
    collected retrospectively. The diagnostic test is
    objective or performed and interpreted without
    knowledge of disease status. Study results allow
    calculation of measures of diagnostic accuracy.

29
AAN Classification of Evidencefor Diagnostic
Accuracy, cont.
  • Class III A case control study or cohort study
    where either persons with the condition or
    controls are of a narrow spectrum. The condition
    is established by an acceptable reference
    standard. The reference standard and diagnostic
    test are objective or performed and interpreted
    by different observers. Study results allow
    calculation of measures of diagnostic accuracy.
  • Class IV Studies not meeting Class I, II or III
    criteria including consensus, expert opinion or a
    case report.

30
Analysis of Evidence
  • Question 1 Does riluzole prolong survival or
    slow disease progression in ALS?

31
Conclusion/Recommendation
  • Conclusion
  • Riluzole is safe and effective for slowing
    disease progression to a modest degree in ALS
    (four Class I studies).
  • Recommendation
  • Riluzole should be offered to slow disease
    progression in patients with ALS (Level A).

32
Analysis of Evidence
  • Question 2 Does lithium carbonate prolong
    survival or slow disease progression in ALS?

33
Conclusion/Recommendation
  • Conclusion
  • There are inadequate data on the effectiveness of
    lithium carbonate (one Class III study).
  • Recommendation
  • There are insufficient data at this time to
    support or refute treatment with lithium
    carbonate in patients with ALS (Level U).

34
Analysis of Evidence
  • Question 3 What is the effect of enteral
    nutrition administered via PEG on weight
    stability?

35
Conclusion/Recommendation
  • Conclusion
  • Enteral nutrition administered via PEG is
    probably effective in stabilizing body
    weight/body mass index (two Class II, seven Class
    III studies).
  • Recommendation
  • In patients with ALS with impaired oral food
    intake, enteral nutrition via PEG should be
    considered to stabilize body weight (Level B).

36
Analysis of Evidence
  • Question 4 When is PEG indicated in ALS?

37
Conclusion/Recommendation
  • Conclusion
  • There are no studies of ALS-specific indications
    for the timing of PEG insertion, although
    patients with dysphagia will possibly be exposed
    to less risk if PEG is placed when forced vital
    capacity (FVC) is above 50 of predicted (one
    Class III study).3
  • Recommendation
  • There are insufficient data to support or refute
    specific timing of PEG insertion in patients with
    ALS (Level U).3

38
Analysis of Evidence
  • Question 5 What is the efficacy of nutritional
    support via PEG in prolonging survival?

39
Conclusion/Recommendation
  • Conclusion
  • Studies using appropriate controls or
    multivariate analysis demonstrated that PEG is
    probably effective in prolonging survival in ALS,
    although insufficient data exist to quantitate
    the survival advantage (two Class II studies).
  • Recommendation
  • PEG should be considered for prolonging survival
    in patients with ALS (Level B).

40
Analysis of Evidence
  • Question 6 What is the effect of enteral
    nutrition delivered via PEG on QOL?

41
Conclusion/Recommendation
  • Conclusion
  • No evidence exists regarding the effect of
    enteral nutrition on quality of life.
  • Recommendation
  • There are insufficient data to support or refute
    PEG for improving quality of life in patients
    with ALS (Level U).

42
Analysis of Evidence
  • Question 7 What is the efficacy of vitamin and
    nutritional supplements on prolonging survival or
    QOL?

43
Conclusions
  • Conclusions
  • Creatine, in doses of 5-10g daily, is established
    as ineffective in slowing the rate of progression
    or in improving survival in ALS (two Class I
    studies).
  • Vitamin E 5,000 mg/d plus riluzole is probably
    ineffective in improving survival or functional
    outcomes (one Class I study). Vitamin E (1,000
    mg/d plus riluzole) was marginally effective in
    slowing the progression of ALS from milder to
    more severe ALS health states using a single
    measure but is ineffective using multiple other
    measures (one Class I study).

44
Recommendations
  • Recommendations
  • Creatine, in doses of 5-10g daily, should not be
    given as treatment for ALS because it is not
    effective in slowing disease progression (Level
    A).
  • High-dose vitamin E should not be considered as
    treatment for ALS (Level B), while the equivocal
    evidence regarding low-dose vitamin E permits no
    recommendation (Level U).

45
Analysis of Evidence
  • Question 8 What are the optimal pulmonary tests
    to detect respiratory insufficiency?

46
Conclusions
  • Conclusions
  • Nocturnal oximetry and maximal inspiratory
    pressure (MIP) are possibly more effective in
    detecting early respiratory insufficiency than
    erect FVC (two Class III studies).
  • Supine FVC is possibly more effective than erect
    FVC in detecting diaphragm weakness and
    correlates better with symptoms of nocturnal
    hypoventilation (two Class III studies).

47
Conclusions, cont.
  • Conclusions, cont.
  • Sniff transdiaphragmatic pressure (Pdi) and sniff
    nasal pressure (SNP) are possibly effective in
    detecting hypercapnia and nocturnal hypoxemia
    (two Class III studies).

48
Recommendations
  • Recommendations
  • Nocturnal oximetry may be considered to detect
    hypoventilation (regardless of the FVC) (Level
    C).
  • Supine FVC and MIP may be considered useful in
    routine respiratory monitoring, in addition to
    the erect FVC (Level C).
  • SNP may be considered to detect hypercapnia and
    nocturnal hypoxemia (Level C).

49
Analysis of Evidence
  • Question 9 Does NIV improve respiratory
    function or increase survival?

50
Conclusions/Recommendation
  • Conclusions
  • NIV is probably effective in prolonging survival
    (one Class I, three Class III studies).
  • NIV is probably effective in slowing the rate of
    FVC decline (one Class I, one Class III study).
  • Recommendation
  • NIV should be considered to treat respiratory
    insufficiency in ALS, both to lengthen survival
    and to slow the rate of FVC decline (Level B).

51
Analysis of Evidence
  • Question 10 How do invasive ventilation and NIV
    affect QOL?

52
Conclusions
  • Conclusions
  • NIV is possibly effective in raising QOL for
    patients with ALS who have respiratory
    insufficiency (five Class III studies).
  • Tracheostomy invasive ventilation (TIV) is
    possibly effective in preserving QOL for patients
    with ALS, but possibly with a greater burden for
    their caregivers (two Class III studies).

53
Recommendations
  • Recommendations
  • NIV may be considered to enhance QOL in patients
    with ALS who have respiratory insufficiency
    (Level C).
  • TIV may be considered to preserve QOL in patients
    with ALS who want long-term ventilatory support.
    (Level C).

54
Analysis of Evidence
  • Question 11 What factors influence acceptance
    of invasive ventilation and NIV?

55
Conclusions/Recommendation
  • Conclusions
  • Nocturnal oximetry is possibly effective in
    detecting early respiratory insufficiency and the
    early use of NIV possibly increases compliance
    (two Class III studies).
  • Bulbar involvement and executive dysfunction
    possibly lower compliance with NIV (two Class III
    studies).
  • Recommendation
  • NIV may be considered at the earliest sign of
    nocturnal hypoventilation or respiratory
    insufficiency in order to improve compliance with
    NIV in patients with ALS (Level C).

56
Analysis of Evidence
  • Question 12 What is the efficacy of targeted
    respiratory interventions for clearing
    secretions?

57
Conclusions
  • Conclusions
  • Mechanical insufflation/exsufflation (MIE) is
    possibly effective for clearing upper airway
    secretions in patients with ALS who have reduced
    peak cough flow, although the clinically
    meaningful difference is unknown (four Class III
    studies).
  • High frequency chest wall oscillation (HFCWO) is
    unproven for adjunctive airway secretion
    management (two Class III studies with
    conflicting results).

58
Recommendations
  • Recommendations
  • MIE may be considered to clear secretions in
    patients with ALS who have reduced peak cough
    flow, particularly during an acute chest
    infection (Level C).
  • There are insufficient data to support or refute
    HFCWO for clearing airway secretions in patients
    with ALS (Level U).

59
Clinical Context
  • Medications with mucolytics like guaifenesin or
    N-aceylcysteine, a B-receptor antagonist (such as
    metoprolol or propanolol), nebulized saline, or
    an anticholinergic bronchodilator such as
    ipratropium are widely used however, no
    controlled studies exist in ALS.

60
Analysis of Evidence
  • Question 13 How should a physician tell
    patients that they have ALS?

61
Conclusion/Recommendation
  • Conclusion
  • There have been no controlled trials of breaking
    the news in ALS.
  • Recommendation
  • There is insufficient evidence to support or
    refute any specific method of disclosing the
    diagnosis in ALS (Level U).

62
Clinical Context
  • Useful strategies have been developed for
    disclosing a diagnosis of cancer (see appendix
    e-1 of the published guideline).4

63
Analysis of Evidence
  • Question 14 Does multidisciplinary management
    improve outcomes?

64
Conclusions/Recommendations
  • Conclusions
  • Two Class II studies and one Class III study show
    that multidisciplinary clinics specializing in
    ALS care are probably effective in several ways
    increased use of adaptive equipment increased
    utilization of riluzole, PEG, and NIV improved
    quality of life and lengthened survival.
    However, one Class II study with low use of
    treatments found no survival benefit.
  • Recommendations
  • Specialized multidisciplinary clinic referral
    should be considered for patients with ALS to
    optimize health care delivery (Level B) and
    prolong survival (Level B), and may be considered
    to enhance quality of life (Level C).

65
Analysis of Evidence
  • Question 15 What are the most effective
    treatments for sialorrhea?

66
Conclusions/Recommendations
  • Conclusions
  • In patients with medically refractory sialorrhea,
    botulinum toxin B (BTxB) injections into the
    parotid and submandibular glands are probably
    effective (one Class I study). There are
    inadequate data on the effectiveness of botulinum
    toxin A (BTxA) (one Class III study). Low-dose
    irradiation is possibly effective for sialorrhea
    (two Class III studies).
  • Recommendations
  • In patients with ALS who have medically
    refractory sialorrhea, BTxB should be considered
    (Level B) and low-dose radiation therapy to the
    salivary glands may be considered (Level C).

67
Clinical Context
  • In ALS and other diseases, anticholinergic
    medications are generally tried first to reduce
    sialorrhea, although effectiveness is unproven.1
    Botulinum toxin has been effective in controlled
    trials in Parkinsonism as well as ALS.5

68
Analysis of Evidence
  • Question 16 What pharmacologic measures reduce
    pseudobulbar affect?

69
Conclusion/Recommendation
  • Conclusion
  • The combination of dextromethorphan/quinidine
    (DM/Q) is probably effective for pseudobulbar
    affect in ALS (one Class I study), although side
    effects may limit its usefulness.
  • Recommendation
  • If approved by the FDA, and if side effects are
    acceptable, DM/Q should be considered for
    symptoms of pseudobulbar affect in patients with
    ALS (Level B).

70
Analysis of Evidence
  • Question 17 What pharmacologic interventions
    reduce fatigue?

71
Conclusion/Recommendation
  • Conclusion
  • There are no controlled studies of pharmacologic
    agents relieving fatigue in ALS. Riluzole may
    cause fatigue in some patients (two Class III
    studies).
  • Recommendation
  • In patients developing fatigue while taking
    riluzole, once risks of fatigue vs modest
    survival benefits have been discussed,
    withholding the drug may be considered (Level C).

72
Analysis of Evidence
  • Question 18 What interventions reduce cramps?

73
Conclusion/Recommendation
  • Conclusion
  • Studies of gabapentin, vitamin E, and riluzole
    for treating cramps were all negative (Class
    III). There are safety concerns about quinine.
  • Recommendation
  • There are insufficient data to support or refute
    any specific intervention for the treatment of
    cramps in ALS (Level U).

74
Analysis of Evidence
  • Question 19 What interventions reduce
    spasticity?

75
Conclusion/Recommendation
  • Conclusion
  • Evidence is insufficient to recommend exercise or
    medication for treating spasticity in ALS (Class
    III).
  • Recommendation
  • There are insufficient data to support or refute
    exercise or medication for treating spasticity in
    ALS (Level U).

76
Clinical Context
  • In multiple sclerosis and cerebral palsy,
    benzodiazepam, baclofen, dantrolene, and
    tizanidine are effective in reducing
    spasticity-related symptoms.6

77
Analysis of Evidence
  • Question 20 What pharmacologic interventions
    reduce depression?

78
Conclusion/Recommendation
  • Conclusion
  • There have been no controlled trials of treatment
    for depression in ALS.
  • Recommendation
  • There are insufficient data to support or refute
    specific treatments for depression in ALS (Level
    U).

79
Clinical Context
  • There is consensus amongst experts that
    depression should be treated in patients with
    ALS7 however, there are no controlled studies of
    benefit or harm.

80
Analysis of Evidence
  • Question 21 What pharmacologic interventions
    reduce anxiety?

81
Conclusion/Recommendation
  • Conclusion
  • There have been no trials of treatment for
    anxiety in ALS.
  • Recommendation
  • There are insufficient data to support or refute
    specific treatment for anxiety in ALS (Level U).

82
Analysis of Evidence
  • Question 22 What pharmacologic interventions
    reduce insomnia?

83
Conclusion/Recommendation
  • Conclusion
  • There have been no studies of treatment for
    insomnia in ALS.
  • Recommendation
  • There are insufficient data to support or refute
    specific treatment for insomnia in ALS (Level U).

84
Analysis of Evidence
  • Question 23 What is the prevalence and natural
    history of cognitive and behavioral impairment in
    ALS?

85
Conclusion/Recommendation
  • Conclusion
  • A significant proportion of patients with ALS
    demonstrate cognitive impairment and some have
    dementia (two Class II, multiple Class III
    studies). Neither behavioral impairment in ALS
    nor the natural progression of cognitive or
    behavioral impairments have been adequately
    studied.
  • Recommendation
  • Screening for cognitive and behavioral impairment
    should be considered in patients with ALS (Level
    B).

86
Analysis of Evidence
  • Question 24 How is cognitive or behavioral
    impairment in ALS diagnosed?

87
Conclusion/Recommendation
  • Conclusion
  • Neuropsychological assessment is possibly
    effective for identifying cognitive impairment in
    ALS (one Class II, one Class III).
  • Recommendation
  • Screening tests of executive function may be
    considered to detect cognitive impairment in
    patients with ALS prior to confirmation with
    formal neuropsychological evaluation (Level C).

88
Analysis of Evidence
  • Question 25 What is the effect of cognitive or
    behavioral impairment on management of patients
    with ALS?

89
Conclusion/Recommendation
  • Conclusion
  • Insufficient data exist on the effect of
    cognitive or behavioral impairment on the
    management of patients with ALS.
  • Recommendation
  • There are insufficient data to support or refute
    the impact of cognitive and behavioral impairment
    on management in ALS (Level U).

90
Analysis of Evidence
  • Question 26 What treatments are effective for
    cognitive or behavioral impairment in ALS?

91
Conclusion/Recommendation
  • Conclusion
  • Data are inadequate regarding the effect of NIV
    on cognition.
  • Recommendation
  • There are insufficient data to support or refute
    treatment of cognitive or behavioral impairment
    in ALS (Level U).

92
Analysis of Evidence
  • Question 27 What treatments for dysarthria
    optimize communication in ALS?

93
Conclusion/Recommendation
  • Conclusion
  • No controlled studies examined communication in
    ALS.
  • Recommendation
  • There are insufficient data to support or refute
    treatment to optimize communication in ALS (Level
    U).

94
Analysis of Evidence
  • Question 28 What treatments reduce pain and
    dyspnea in the terminal phase of ALS?

95
Conclusion/Recommendation
  • Conclusion
  • No controlled studies examined treating pain or
    dyspnea in late-stage ALS.
  • Recommendation
  • There are insufficient data to support or refute
    specific treatments for pain and dyspnea in
    terminal ALS (Level U).

96
Analysis of Evidence
  • Question 29 Do hospice care, spiritual
    interventions, or advance directives improve
    quality of life in the terminal phase of ALS?

97
Conclusion/Recommendation
  • Conclusion
  • No controlled studies examined hospice, spiritual
    care, or advance directives in ALS.
  • Recommendation
  • There are insufficient data to support or refute
    hospice, spiritual care, or advance directives in
    ALS (Level U).

98
Analysis of Evidence
  • Question 30 What is the optimal method of
    withdrawing both NIV and invasive ventilation in
    ALS?

99
Conclusion/Recommendation
  • Conclusion
  • There are no controlled studies examining
    withdrawal of ventilation in ALS.
  • Recommendation
  • There are insufficient data to support or refute
    specific strategies for withdrawal of ventilation
    in ALS (Level U).

100
Clinical Context
  • Protocols based on consensus for withdrawal of
    mechanical ventilation in intensive care units
    (Class IV)8 include counseling and symptom
    control with opioids, benzodiazepines, and
    anticholinergic medications.9 We could find no
    controlled studies in any disease.

101
Clinical Context
  • This evidence-based review indicates some
    progress in evaluating new therapies for patients
    with ALS. More high-quality studies have been
    reported leading to more confident
    recommendations regarding the value of NIV and
    PEG.

102
Clinical Context
  • It is one thing to publish an evidence-based
    practice parameter for the management of patients
    with ALS, and it is quite another to be able to
    track adherence in practice and to determine
    whether the publication of evidence-based
    guidelines has changed outcomes.

103
Clinical Context, cont.
  • The ALS patient CARE database was developed with
    the hope of standardizing new and effective
    therapies for patients with ALS and tracking
    outcomes to raise the standard of care.10
  • Data obtained from the ALS CARE program have
    shown that the underutilization of many therapies
    (especially PEG and NIV) has persisted in the
    years since the original practice parameter on
    this topic, though there have been gains.

104
Clinical Context, cont.
  • These findings suggest that an evidence-based
    practice parameter may over time become more
    widely accepted and change practice. However, the
    persistent underutilization of therapies that
    improve survival and QOL poses a challenge for
    ALS clinicians to continue to raise the standard
    of care for patients with ALS.

105
Future Research
  • This evidence-based review indicates some
  • progress in evaluating new therapies for
  • patients with ALS. More high-quality studies
  • have been reported leading to more confident
  • recommendations regarding multidisciplinary
  • clinics and symptomatic therapy for
  • pseudobulbar effect and sialorrhea. However,
  • future research in the following areas is still
  • greatly needed.

106
Future Research, cont.
  • Lithium carbonate
  • Study whether lithium slows disease progression
    or prolongs survival in ALS in larger clinical
    trials.
  • Nutrition
  • Develop ALS-specific indications for nutritional
    adequacy in ALS and for PEG and radiologically
    inserted gastrostomy (RIG).
  • Study the optimal timing of nutritional therapy
    administered via PEG or RIG.
  • Conduct clinical studies of novel antioxidants
    and supplements .

107
Future Research, cont.
  • Respiratory Management
  • Evaluate SNP as a criterion for NIV initiation.
  • Evaluate the impact of early NIV initiation on
    survival and quality of life.
  • Assess the impact of executive dysfunction on NIV
    compliance.
  • Evaluate the effect of hypoventilation on
    executive dysfunction.
  • Compare techniques for clearing upper airway
    secretions at various stages of respiratory and
    bulbar dysfunction.
  • Evaluate pulmonary tests, compliance with NIV,
    and outcomes in patients with bulbar dysfunction.

108
Future Research, cont.
  • Breaking the News
  • Validate measures that can be applied to studies
    of diagnostic disclosure.
  • Evaluate attitudes of neurologists and patients
    to strategies for breaking the news.
  • Conduct controlled studies of the effects of
    different disclosure strategies on patient
    satisfaction, preserving hope, and outcomes.
  • Multidisciplinary Clinic
  • Examine referral bias to clinics.
  • Examine factors essential to benefits in clinics,
    optimal visit frequency, cost effectiveness of
    staff, and economic factors in care.

109
Future Research, cont.
  • Symptomatic Management
  • Conduct controlled trials of pharmacologic
    therapy for spasticity, cramps, constipation,
    sialorrhea, pseudobulbar affect, pain,
    depression, anxiety, fatigue, and therapeutic
    exercise.
  • Examine irradiation and botulinum toxin for
    sialorrhea in controlled trials.
  • Cognitive and Behavioral Impairment
  • Develop consensus criteria for cognitive and
    behavioral impairment to ensure consistency in
    diagnosis and research.
  • Identify screening tests for cognitive and
    behavioral impairment.
  • Evaluate the natural history of, and treatments
    for, cognitive and behavioral impairment, and
    their impact on compliance and survival.

110
Future Research, cont.
  • Communication
  • Validate criteria to examine communication
    strategies.
  • Design clinical trials to compare different
    strategies for communication in ALS.
  • Palliative Care
  • Design controlled trials of terminal symptom
    management, advanced directives, hospice, and
    spiritual care.

111
Acknowledgments
  • The authors thank Gary Gronseth, MD Thomas
    Getchius Valerie Cwik, MD Larry Brower and Sid
    Valo for contributions to the practice
    parameters Christina Metzler and Barbara
    Phillips, MS, OTR/L, for their contributions to
    the patient summary versions of the guidelines
    and Sharon J. Matland, RN, MBA, for her
    contributions to both the practice parameters and
    the patient summary versions.

112
References
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    Practice parameter the care of the patient with
    amyotrophic lateral sclerosis (an evidence-based
    review) report of the Quality Standards
    Subcommittee of the American Academy of
    Neurology ALS Practice Parameters Task Force.
    Neurology 1999521311-1323.
  • Bourke SC, Tomlinson M, Williams TL, Bullock RE,
    Shaw PJ, Gibson GJ. Effects of non-invasive
    ventilation on survival and quality of life in
    patients with amyotrophic lateral sclerosis a
    randomised controlled trial. Lancet Neurol
    20065140-147.
  • Kasarskis EJ, Scarlata D, Hill R, Fuller C,
    Stambler N, Cedarbaum JM. A retrospective study
    of percutaneous endoscopic gastrostomy in ALS
    patients during the BDNF and CNTF trials. J
    Neurol Sci 1999169118-125.
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    process of truth disclosure an assessment of the
    results of information during the diagnostic
    phase in patients with cancer. Ann Oncol 2009.
  • 5. Molloy L. Treatment of sialorrhea in
    patients with Parkinson's disease best current
    evidence. Curr Opin Neurol 200720493-498.
  • Abbruzzese G. The medical management of
    spasticity. Eur J Neurol 20029 Suppl 130-34
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References
  • Andersen PM, Borasio GD, Dengler R, et al. EFNS
    task force on management of amyotrophic lateral
    sclerosis guidelines for diagnosing and clinical
    care of patients and relatives. Eur J Neurol
    200512921-938.
  • O'Mahony S, McHugh M, Zallman L, Selwyn P.
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    division and a palliative care service. J Pain
    Symptom Manage 200326954-961.
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    official American Thoracic Society clinical
    policy statement palliative care for patients
    with respiratory diseases and critical illnesses.
    Am J Respir Crit Care Med 2008177912-927.
  • Miller RG, Anderson F, Neelam G, Wei Hea. The ALS
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  • For a complete list of references, please access
    the full guidelines at www.aan.com/guidelines

114
Questions/Comments
115
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