Transcript The Diagnostic Evaluation and Treatment of Trigeminal Neuralgia

Practice Parameter: The diagnostic evaluation
and treatment of trigeminal neuralgia
(an evidence-based review)
Report of the Quality Standards Subcommittee of
the American Academy of Neurology and the
European Federation of Neurological Societies
G. Gronseth, MD, FAAN; G. Cruccu, MD; J. Alksne, MD; C. Argoff, MD; M.
Brainin, MD, FESO; K. Burchiel, MD; T. Nurmikko, MD, PhD; J. M.
Zakrzewska, MD, FDSRCS, FFDRCSI
© 2006 American Academy of Neurology
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© 2006 American Academy of Neurology
Presentation Objectives
• To perform an evidence-based review of
the diagnosis and treatment of trigeminal
neuralgia
• To make evidence-based
recommendations
© 2006 American Academy of Neurology
Overview
•
•
•
•
Background
Gaps in care
AAN guideline process
Analysis of evidence, conclusions,
recommendations
• Recommendations for future research
© 2006 American Academy of Neurology
Background
• Trigeminal neuralgia (TN) is sudden, usually
unilateral, severe, brief, stabbing, recurrent
episodes of pain in the distribution of one or
more branches of the trigeminal nerve.1
• The annual incidence of TN is 4 to 5 in 100,000.2
• Classic TN (CTN) includes cases without an
established etiology, and symptomatic TN (STN)
is diagnosed when investigations identify a
structural abnormality (e.g., MS plaques, tumors,
etc.).
© 2006 American Academy of Neurology
AAN Guideline Process
Clinical Question
Evidence
Conclusions
Recommendations
© 2006 American Academy of Neurology
Clinical Questions
• The first step of 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.
© 2006 American Academy of Neurology
Literature Search/Review
Rigorous, Comprehensive, Transparent
Complete
Search
Review abstracts
Review full text
Select articles
Relevant
© 2006 American Academy of Neurology
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
© 2006 American Academy of Neurology
AAN Level of
Recommendations
• A = Established as effective, ineffective, or harmful for
the given condition in the specified population.
• B = Probably effective, ineffective, or harmful for the
given condition in the specified population.
• C = Possibly effective, ineffective, or harmful for the
given condition in the specified population.
• U = Data is inadequate or conflicting; given current
knowledge, treatment is unproven.
Note that recommendations can be positive or negative.
© 2006 American Academy of Neurology
Translating Class to
Recommendations
• A = Requires two consistent Class I
studies.
• B = Requires one Class I study or two
consistent Class II studies.
• C = Requires one Class II study or two
consistent Class III studies.
• U = Studies not meeting criteria for
Class I through Class III.
© 2006 American Academy of Neurology
Applying This Process
to the Issue
We will now turn our attention to the
guidelines.
© 2006 American Academy of Neurology
Clinical Questions
Diagnostic questions
1. How often does routine neuroimaging (CT,
MRI) identify a structural cause of TN
(excluding vascular contact with compression
of the fifth cranial nerve?
2. Which clinical or laboratory features accurately
identify patients with STN?
3. For patients with CTN, does high-resolution
MRI accurately identify patients with
neurovascular compression?
© 2006 American Academy of Neurology
Clinical Questions
Pharmacologic questions
1. Which drugs effectively treat CTN?
2. Which drugs effectively treat STN?
3. Is there evidence of efficacy of
intravenous drugs in acute exacerbations
of TN?
© 2006 American Academy of Neurology
Clinical Questions
Surgical questions
1. When should surgery be offered?
2. Which surgical technique gives the
longest pain-free period with the fewest
complications and good quality of life?
3. Which surgical techniques should be
used in patients with MS?
© 2006 American Academy of Neurology
Methods
• Medline, EMBASE and Cochrane Library:
– Database creation to December 2007
– Relevant, fully published, peer-reviewed
articles
– Supplemented through manual searches by
panel members
• Search terms:
– Trigeminal neuralgia, tic douloureux,
facial pain, or trigeminal neuropathy
© 2006 American Academy of Neurology
Methods
• At least two panelists reviewed each article for
inclusion. A third panelist was added for
arbitrating disagreements
• Risk of bias determined using the classification
of evidence for each study (Class I–IV).
• Strength of practice recommendations linked
directly to level of evidence (Level A–U).
• Conflicts of interest disclosed.
© 2006 American Academy of Neurology
Literature Review
> 500 abstracts
47 articles
© 2006 American Academy of Neurology
Inclusion criteria:
- Relevant to the
clinical questions
- Limited to human
subjects
-RCT, case control,
cohort studies, case
series > 6, metaanalysis
Exclusion criteria:
-Abstracts, reviews,
and undocumented or
unstated mention of
improvement
AAN Classification of Evidence
for Therapeutic Intervention
• Class I: Randomized, controlled clinical trial 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 required:
a) concealed allocation
b) primary outcome(s) clearly defined
c) exclusion/inclusion criteria clearly defined, and
d) adequate accounting for drop-outs (with at least 80%
of enrolled subjects completing the study) and crossovers with numbers sufficiently low to have minimal
potential for bias.
© 2006 American Academy of Neurology
AAN Classification of Evidence
for Therapeutic Intervention
• Class II: Prospective matched group
cohort study in a representative population
with masked outcome assessment that
meets b-d above OR a randomized
controlled trial in a representative
population that lacks one criteria a-d.
© 2006 American Academy of Neurology
AAN Classification of Evidence
for Therapeutic Intervention
• 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.*
• Class IV: Studies not meeting Class I, II, or III criteria
including consensus, expert opinion, or a case report.
*Objective outcome measurement: an outcome measure
that is unlikely to be affected by an observer’s (patient,
treating physician, investigator) expectation or bias (e.g.,
blood tests, administrative outcome data).
© 2006 American Academy of Neurology
AAN Classification of Evidence
for Screening
• Class I: A statistical, population-based
sample of patients studied at a uniform
point in time (usually early) during the
course of the condition. All patients
undergo the intervention of interest. The
outcome, if not objective, is determined in
an evaluation that is masked to the
patients’ clinical presentations.
© 2006 American Academy of Neurology
AAN Classification of Evidence
for Screening
• Class II: A statistical, non-referral-clinicbased sample of patients studied at a
uniform point in time (usually early) during
the course of the condition. Most patients
undergo the intervention of interest. The
outcome, if not objective, is determined in
an evaluation that is masked to the
patients’ clinical presentations.
© 2006 American Academy of Neurology
AAN Classification of Evidence
for Screening
• Class III: A sample of patients studied
during the course of the condition. Some
patients undergo the intervention of
interest. The outcome, if not objective, is
determined in an evaluation by someone
other than the treating physician.
• Class IV: Studies not meeting Class I, II,
or III criteria including consensus, expert
opinion, or a case report.
© 2006 American Academy of Neurology
AAN Classification of Evidence
for Diagnosis
• 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 patient’s
clinical status. Study results allow
calculation of measures of diagnostic
accuracy.
© 2006 American Academy of Neurology
AAN Classification of Evidence
for Diagnosis
• 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.
© 2006 American Academy of Neurology
AAN Classification of Evidence
for Diagnosis
• 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.
© 2006 American Academy of Neurology
Analysis of Evidence
Question 1: How often does routine
neuroimaging (CT, MRI) identify a
structural cause (excluding vascular
contact with compression of the fifth
cranial nerve)?
© 2006 American Academy of Neurology
Conclusion/Recommendation
Conclusion: For patients with TN, routine
neuroimaging may identify a cause in up to 15%
of patients (four Class III studies). These
reported yields are most representative of those
expected from referral centers.
Recommendation: Weak evidence indicates
that for patients with TN, routine imaging may be
considered to identify a cause in up to 15
percent of patients with STN (Level C).
© 2006 American Academy of Neurology
Clinical Context
• The initial diagnostic evaluation of a
patient with TN naturally focuses on those
clinical characteristics known to identify
patients with symptomatic trigeminal
neuralgia (STN). Those characteristics
include the presence of trigeminal sensory
deficits and bilateral involvement.
© 2006 American Academy of Neurology
Analysis of Evidence
Question 2: Which clinical or
laboratory features accurately identify
patients with STN?
© 2006 American Academy of Neurology
Conclusion/Recommendation
Conclusion: For patients with TN, younger age (one
Class I and three Class II studies) and abnormal
trigeminal nerve evoked potentials (two Class II and two
Class III studies) are probably associated with an
increased risk of STN. However, there is too much
overlap in patients with CTN and STN for these
predictors to be considered clinically useful.
Recommendation: Good evidence indicates that
measuring trigeminal reflexes in a qualified
electrophysiogical laboratory should be considered
useful for distinguishing STN from classic trigeminal
neuralgia (CTN) (Level B).
© 2006 American Academy of Neurology
Clinical Context
• If after the initial evaluation the clinician
remains suspicious of STN, further testing
is desirable. Based upon cost, local
expertise and availability, and patient
preferences, obtaining trigeminal reflex
testing or head imaging are both
reasonable next steps.
© 2006 American Academy of Neurology
Analysis of Evidence
Question 3: Does high-resolution MRI
accurately identify patients with
neurovascular compression?
© 2006 American Academy of Neurology
Conclusion/Recommendation
Conclusion: Because of inconsistency of
results, there is insufficient evidence to support
or refute the usefulness of MRI to identify
vascular contact in CTN or to indicate the most
reliable MRI technique.
Recommendation: There is insufficient
evidence to support or refute the usefulness of
MRI to identify vascular contact in CTN or to
indicate the most reliable MRI technique (Level
U).
© 2006 American Academy of Neurology
Clinical Context
• Because of a high diagnostic accuracy,
MRI might reasonably be foregone in a
patient with normal trigeminal reflexes.
© 2006 American Academy of Neurology
Analysis of Evidence
Question 4: Which drugs effectively
treat CTN pain?
© 2006 American Academy of Neurology
Conclusion/Recommendation
Conclusion: Carbamazepine is established as effective for controlling pain
in patients with CTN (multiple Class I and II studies). Oxcarbazepine is
probably effective for treating pain in CTN (three Class II studies). Baclofen,
lamotrigine, and pimozide are possibly effective for controlling pain in
patients with CTN (single Class II study for each drug). Topical ophthalmic
anesthesia is probably ineffective for controlling pain in patients with CTN
(single Class I study). There is insufficient evidence to support or refute the
efficacy of clonazepam, gabapentin, phenytoin, tizanidine, topical capsaicin,
and valproate for controlling pain in patients with CTN.
Recommendation:
Strong evidence supports that carbamazepine should be offered to treat
CTN pain (Level A).
Good evidence supports that oxcarbazepine should be considered to treat
CTN pain (Level B).
Weak evidence supports that baclofen, lamotrigine, and pimozide may be
considered to treat CTN pain (Level C).
Good evidence supports that topical ophthalmic anesthesia should not be
considered to treat CTN pain (Level B).
© 2006 American Academy of Neurology
Clinical Context
• The two drugs to consider as first-line therapy in TN are
CBZ (200-1200 mg/day) and OXC (600-1800 mg/day).
Although the evidence for CBZ is stronger than for OXC,
the latter may pose fewer safety concerns.
• There is little evidence to guide the clinician on the
treatment of TN patients that who fail first-line therapy.
Some evidence supports add-on therapy with lamotrigine
or a switch to baclofen (pimozide being no longer in
use).
© 2006 American Academy of Neurology
Analysis of Evidence
Question 5. Which drugs effectively
treat STN pain?
© 2006 American Academy of Neurology
Conclusion/Recommendation
Conclusion: There is insufficient evidence
to support or refute the effectiveness of
any medication in treating pain in STN
(Class IV studies).
Recommendation: There is insufficient
evidence to support or refute the
effectiveness of any medication in treating
pain in STN (Level U).
© 2006 American Academy of Neurology
Clinical Context
• The effect of other drugs commonly used
in neuropathic pain is unknown. There are
no published studies directly comparing
polytherapy with monotherapy.
© 2006 American Academy of Neurology
Analysis of Evidence
Question 6: Is there evidence of
efficacy of intravenous administration
of drugs in acute exacerbations of TN?
© 2006 American Academy of Neurology
Conclusion/Recommendation
Conclusion: There is insufficient evidence to
support or refute the efficacy of IV medications
for the treatment of pain from TN (Class IV
study).
Recommendation: There is insufficient
evidence to support or refute the efficacy of
intravenous medications for the treatment of
pain from TN (Level U).
© 2006 American Academy of Neurology
Analysis of Evidence
Question 7: When should surgery be
considered?
© 2006 American Academy of Neurology
Conclusion/Recommendation
Conclusion: There is insufficient evidence
to allow conclusions as to when surgery
should be offered (two Class IV studies).
Recommendation: There is insufficient
evidence to allow conclusions as to when
surgery should be offered (Level U).
© 2006 American Academy of Neurology
Clinical Context
• Referral for a surgical consultation seems
reasonable in TN patients refractory to medical
therapy. Some TN experts believe TN patients
failing to respond to first-line therapy are unlikely
to respond to alternative medications and
suggest early surgical referral.
© 2006 American Academy of Neurology
Analysis of Evidence
Question 8: Which surgical technique
gives the longest pain-free period with
the fewest complications and good
quality of life?
© 2006 American Academy of Neurology
Conclusion/Recommendation
Conclusion: Percutaneous procedures on the
Gasserian ganglion, gamma knife, and microvascular
decompression are possibly effective in the treatment of
TN (multiple Class III studies). The evidence about
peripheral techniques is either negative (two Class I
studies about streptomycin/lidocaine) or insufficient
(Class IV studies for all the other peripheral techniques).
Recommendation: There is weak evidence to support
that early surgical therapy may be considered for
patients with TN refractory medical therapy (Level C).
There is weak evidence to support percutaneous
procedures on the Gasserian ganglion, gamma knife,
and microvascular decompression may be considered
(Level C).
© 2006 American Academy of Neurology
Analysis of Evidence
Question 9. Which surgical techniques
should be used in patients with
multiple sclerosis?
© 2006 American Academy of Neurology
Conclusion/Recommendation
Conclusion: There is insufficient evidence to
support or refute the effectiveness of the surgical
management of TN in patients with MS.
Recommendation: There is insufficient
evidence to support or refute the effectiveness of
the surgical management of TN in patients with
MS (Level U).
© 2006 American Academy of Neurology
Future Research
• To establish a better estimate of the yield of routine brain
imaging in identifying patients with STN, we need a
population-based study of consecutive, newly diagnosed
patients with TN all undergoing head imaging.
• To improve our knowledge of the diagnostic accuracy of
clinical characteristics and electrophysiologic studies to
distinguish STN from CTN, we need prospective cohort
surveys of large populations of patients with TN all
undergoing standardized diagnostic assessments
reported using STARD criteria.3
© 2006 American Academy of Neurology
Future research
• It would also be useful to determine if finding a
neurovascular contact on high-resolution MRI
accurately identifies patients who will respond to
microvascular decompression. This question
could be answered with a prospective study
comparing longterm outcomes in patients with
TN undergoing microvascular decompression
with and without neurovascular contact identified
on preoperative high-resolution MRI.
© 2006 American Academy of Neurology
Future research
• The efficacy of new drugs and, in particular, surgical
interventions, needs to be determined in well-designed
RCTs. Although double-blinded studies are impractical
for surgical trials, randomized treatment allocation and
independent outcome assessment would go a long way
to establish the efficacy of the surgical techniques.
• The optimal timing of surgical referral remains a crucial
question. How many different drugs should be tried
before referring a patient for surgery? What is the
likelihood that a patient with TN failing OXC or CBZ will
respond to alternative drugs? These are questions that
could be answered by a large prospective cohort survey
of patients with TN treated in a standardized, stepwise
fashion.
© 2006 American Academy of Neurology
References
1.
2.
3.
Merskey H, Bogduk N. Classification of Chronic Pain:
Descriptions of Chronic Pain Syndromes and Definitions of Pain
Terms. Seattle: IASP Press; 1994;59–71.
Katusic S, Williams DB, Beard CM, et al. Epidemiology and
clinical features of idiopathic trigeminal neuralgia and
glossopharyngeal neuralgia: similarities and differences,
Rochester, Minnesota, 1945–1984. Neuroepidemiology
1991;10:276–281.
Bossuyt P, Reitsma J, Bruns D, et al. Towards complete
assessment and accurate reporting studies of diagnostic
accuracy: the STARD initiative. Clin Radiol 2003;58:575-580.
For a complete list of references, please access the
full guideline at www.aan.com/guidelines
© 2006 American Academy of Neurology
Questions/Comments
© 2006 American Academy of Neurology
Thank you for your
participation!
© 2006 American Academy of Neurology