Diagnostic Challenges in Craniofacial Pain - Johns Hopkins ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
10/19/2020
Diagnostic Challenges in
Craniofacial Pain
TINA DOSHI, MD, MHS
OCTOBER 16, 2020
1
Disclosures
• Research Support:
• Foundation for Anesthesia Education and Research
• Neurosurgery Pain Research Institute
• Blaustein Pain Research Fund
• Doris Duke Early Clinician Investigator Award
• Biohaven Pharmaceutical
• Consulting: Guidepoint Global
2
1
10/19/2020
Objectives
• To share illustrative cases of diagnostic challenges in
facial pain
• To understand the potential role of biomarkers in
craniofacial pain diagnosis and treatment
3
Is it trigeminal neuralgia?
4
2
10/19/2020
White and Sweet Criteria
Confined to
Paroxysmal trigeminal Unilateral
distribution
Normal
Provoked by
sensory
light touch
examination
White, James Clarke, and William Herbert Sweet. Pain and the
neurosurgeon: a forty-year experience. CC Thomas, 1969.
5
Trigeminal Neuralgia Diagnostic Criteria:
A. Recurrent paroxysms of unilateral facial
pain in the distribution(s) of one or more
divisions of the trigeminal nerve, with no
radiation beyond1, and fulfilling criteria B
and C:
B. Pain has all of the following characteristics: International
A. lasting from a fraction of a second to 2 minutes2 Classification of
B. severe intensity3 Headache Disorders
C. electric shock-like, shooting, stabbing or sharp in (ICHD), 3rd Edition
quality
1. “…pain may radiate to another division…”
C. Precipitated by innocuous stimuli within the “A minority of patients will report attacks
affected trigeminal distribution4 2.
predominantly lasting for >2 minutes.”
D. Not better accounted for by another ICHD-3 3. “Pain may become more severe over time.”
diagnosis. 4. “Some attacks may be, or appear to be,
spontaneous…”
6
3
10/19/2020
International
Association for the
Study of Pain (IASP)
7
Trigeminal Neuralgia Diagnostic Criteria:
1.Pain territory is restricted to ≥1 divisions of the
trigeminal nerve, including the intraoral territories. If the
pain involves 2 trigeminal divisions, they must be
contiguous. The pain does not extend to the posterior
third of the scalp, the back of the ear, or the angle of the
mandible.
2.Pain is paroxysmal, ie, it has an abrupt onset and very
short duration (usually a few seconds).
ACTTION-American
3.Pain paroxysms confined to the trigeminal region
associated with brisk muscle contractions (tics) are Pain Society Pain
elicited by innocuous mechanical stimuli on examination
or by facial or oral movements by the patient. Taxonomy (AAPT)
TN Diagnostic Modifier:
The diagnosis of TN is clinical. Objective tests (usually
MRI) are used to obtain etiologic information and to
define subtypes.
8
4
10/19/2020
Is it trigeminal neuralgia?
(PROBABLY NOT.)
9
Mr. E
• 58 yo with history of cluster headaches referred
for left facial pain, presumed trigeminal neuralgia
• 5 institutions, 16 specialists, dozens of medication
trials, trigeminal blocks, no relief
• 2 years ago: “fever blister” left lower lip
• Burning, continuous pain left face and left ear, with
episodic exacerbations
• Intermittent problems speaking, swallowing,
spitting/drooling
• Loss of taste
• Two weeks ago, choked on some food and “passed
out” for 10 seconds
10
5
10/19/2020
Mr. E
• 58 yo with history of cluster headaches referred
for left facial pain, presumed trigeminal neuralgia
• 5 institutions, 16 specialists, dozens of medication
trials, trigeminal blocks, no relief
• 2 years ago: “fever blister” left lower lip
• Burning, continuous pain left face and left ear, with
episodic exacerbations
• Intermittent problems speaking, swallowing,
spitting/drooling
• Loss of taste
• Two weeks ago, choked on some food and “passed
out” for 10 seconds
11
Mr. E
• Examination
• No facial asymmetry
• Sensation intact to pinprick
and light touch bilateral
face; no hyperalgesia or
allodynia
• Normal neurologic exam
• Pain worsened with
bimanual palpation of the
left styloid process
12
6
10/19/2020
Eagle Syndrome
• Painful sensation in the head and neck
due to elongation of the styloid process
(>30 mm) or calcification of the
stylohyoid ligament
• Elongation/calcification present in ~4% of
the population; about 4% of those
individuals become symptomatic
• Associated symptoms related to
compression of carotid, vagus, and
cranial nerves
• Sore throat, pain radiating to ear, foreign
body sensation in the throat, dysphagia
• Precipitation or exacerbation on turning of
the head/neck
• TIA, syncope, sudden death
13
Mr. E
• Glossopharyngeal nerve
block provided 6 weeks
of benefit
• Referred for
styloidectomy; now with
ongoing pain relief
14
7
10/19/2020
Next case: Mr. A
• 65 yo diagnosed with trigeminal
neuralgia 20 years ago
• MVD (5 and 18 years ago), gamma knife (3
years ago) with good relief
• Developed worsening right-sided head
pain a year later
• “A thousand earthworms moving and a
thousand bees stinging” in right posterior
head and face
• Associated with light/sound sensitivity
• Initially received occipital blocks with
good efficacy, now minimal relief
following
15
Next case: Mr. A
• 65 yo diagnosed with trigeminal
neuralgia 20 years ago
• MVD (5 and 18 years ago), gamma knife (3
years ago) with good relief
• Developed worsening right-sided head
pain a year later
• “A thousand earthworms moving and a
thousand bees stinging” in right posterior
head and face
• Associated with light/sound sensitivity
• Initially received occipital blocks with
good efficacy, now minimal relief
following
16
8
10/19/2020
Migraine: Diagnosis
Pulsatile
4-74 hOurs
Unilateral
Nausea/vomiting
Disabling
Charles AC, Baca SM. Cortical spreading depression and migraine.
Nature Reviews Neurology. 2013 Nov;9(11):637.
17
Migraine: Management
• Combination of abortive and prophylactic treatments,
along with lifestyle modifications
• Our patient:
• Sumatriptan for abortive therapy
• Pregabalin for prophylactic therapy
• Botulinum every three months for prophylaxis
18
9
10/19/2020
Next case: Mrs. C
• 79 yo woman from Puerto Rico with right facial
pain that began after a dental cleaning
• Intermittent pain begins in right cheek and travels
to top and back of head
• Episodes last about 2-5 minutes, at least daily, but
usually every few hours
• Exacerbated by cold, heat, stress; alleviated by ice,
massage
• No phonophobia/photophobia, nausea/vomiting
• MRI with contact of right trigeminal nerve by
overlying vessel
• Diagnosed with trigeminal neuralgia
• Taking carbamazepine and gabapentin for 6
months without relief
19
Next case: Mrs. C
• 79 yo woman from Puerto Rico with right facial
pain that began after a dental cleaning
• Intermittent pain begins in right cheek and travels
to top and back of head
• Episodes last about 2-5 minutes, at least daily, but
usually every few hours
• Exacerbated by cold, heat, stress; alleviated by ice,
massage
• No phonophobia/photophobia, nausea/vomiting
• MRI with contact of right trigeminal nerve by
overlying vessel
• Diagnosed with trigeminal neuralgia
• Taking carbamazepine and gabapentin for 6
months without relief
20
1010/19/2020
Mrs. C
• Physical Examination
• Visible right facial swelling in face
• Noted nasal congestion and eye tearing
• Restless, unable to get comfortable
21
Mrs. C
• Physical Examination
• Visible right facial swelling in face
• Noted nasal congestion and eye tearing
• Restless, unable to get comfortable
A nterior side-locked pain
A utonomic features
A gitation or restlessness
The three A’s of TACs!
22
1110/19/2020
Paroxysmal Hemicrania
• A trigeminal autonomic cephalalgia
(TAC), which includes cluster headache,
SUNCT/SUNA, hemicrania continua
• Paroxysmal hemicrania and hemicrania
continua characterized by absolute
response to indomethacin
• Indomethacin 25 mg TID x 3 days, 50 mg
TID x 3 days, then 75 mg TID x 8 days
• Treatment failure if no response after 2
weeks
23
Last case: Mr. S
• 40 yo with recent hospitalization 1 month
ago for COVID-19 pneumonia, complicated
by PE
• While performing incentive spirometry at
home, developed severe pain over right temple
• Sharp, intermittent, occurs at least daily and
lasts a few seconds at a time
• Exacerbated by chewing, stress, cold, yawning,
opening mouth wide; alleviated by stopping the
offending activity
• ED: prescribed gabapentin and nortriptyline
for presumed trigeminal neuralgia
• Did not start
24
1210/19/2020
Mr. S
• Tenderness to palpation over right
temporalis with reproduction of
pain, spreading to the right cheek,
jaw, and over the ear
• Limited mouth opening and
lateral jaw deviation due to pain
25
Temporomandibular Disorder
• Spectrum of related chronic craniofacial
disorders
• Disorders of the jaw muscles,
temporomandibular joints, and associated
nerves (“the chewing apparatus”)
• TMD Myalgia
• Pain of muscle origin that is affected by jaw
movement, function, or parafunction, and
replication of this pain occurs with
provocation testing of the masticatory
muscles
26
1310/19/2020
27
Self-Care
• Diet
• Habits
• Posture
• Stress management
• Physical activity
• Sleep
Physical
Dentistry Therapy
• Exercises
TMD
• Intraoral appliances
• Orthodontia • Manual therapy
• Graded activity
• Dry needling
Care
Medications/
Psychology Procedures
• Cognitive-behavioral • NSAIDs
therapy • Injections
• Relaxation • Arthroscopy,
• Graded exposure arthrocentesis
• Open surgery
28
1410/19/2020
Why is it so hard to diagnose
craniofacial pain?
29
Why is it so hard to diagnose
craniofacial pain?
IT’S COMPLICATED…
30
1510/19/2020
Challenges in Craniofacial Pain Diagnosis
• Multiple specialists (dentists, ENT, neurology,
neurosurgery, pain medicine, physical medicine,
among others)
• Variable training
• Overlapping treatments with variable treatment
responses
• Concurrent disorders
31
32
1610/19/2020
33
The Role of Biomarkers in Chronic Pain
• Biomarker (FDA/NIH)
• “a defined characteristic that is
measured as an indicator of
normal biological processes,
pathogenic processes, or
responses to an exposure or
intervention, including
therapeutic interventions … not
an assessment of how an
individual feels, functions, or
survives”
Doshi, Tina L., et al. "Biomarkers in temporomandibular disorder and trigeminal neuralgia: A
conceptual framework for understanding chronic pain." Canadian Journal of Pain 4.1 (2020): 1-18.
34
1710/19/2020
Finding a Pain Biomarker
• No validated pain biomarker
• Candidates
• Genetic, “-omic” markers
• Molecular
• Neuroradiological
• Psychophysical (QST)
Doshi, Tina L., et al. "Biomarkers in temporomandibular disorder and trigeminal neuralgia: A
conceptual framework for understanding chronic pain." Canadian Journal of Pain 4.1 (2020): 1-18.
35
Ji, Ru-Rong, Alexander Chamessian, and Yu-Qiu Zhang. "Pain regulation by
non-neuronal cells and inflammation." Science 354.6312 (2016): 572-577.
36
1810/19/2020
Trigeminal Neuralgia: An Inflammatory Condition?
• Neuropathic pain is traditionally considered as distinct from inflammatory or
immune-mediated pain
• Increasing evidence that inflammatory mediators may play a role in the
development of neuropathic pain
• Role of glial cells in normal and abnormal pain signaling
• Potential for diagnostic immunology or immunotherapeutic options for neuropathic pain?
37
Trigeminal Neuralgia: An Inflammatory Condition?
• Increased IL-1β, IL-6, IL-8, and
TNF-α in TN and HFS vs. healthy
controls
• Correlation between IL-6
concentration and TN/HFS
symptom severity
• TNF-α elevated in TN
patients pre- and post-MVD
CSF biomarkers of inflammation in trigeminal neuralgia patients operated
with microvascular decompression compared to all controls
Hans Ericson, Sami Abu Hamdeh, Eva Freyhult, Fredrik Stiger, Emmanuel Bäckryd,
Anders Svenningsson, Torsten Gordh, Kim Kultima
38
1910/19/2020
Cytokine Levels in Trigeminal Neuralgia
• 22 MVD patients, 14 age- and gender-matched controls
• Intraoperative plasma and CSF cytokine levels
• Cytokines identified from review of literature
• IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, MCP-1, TNF- α, and fractalkine
• Controls
• Age- and gender-matched controls from Neurology LP clinic
• No chronic pain disorder
• No known inflammatory condition
Controls Patients P-value
N 14 22
Age in years, mean (SD) 56.4 (22.0) 52.3 (13.3) 0.49
Female, n (%) 10 (71%) 15 (68%) 0.84
39
Preliminary Cytokine Findings: Plasma
Factor Controls Patients p-value
N 14 22
Fractalkine, mean (SD) 110.49 (116.97) 185.23 (190.19) 0.20
IFN-γ, mean (SD) 12.10 (25.61) 47.70 (95.94) 0.19
IL-1β, mean (SD) 11.31 (18.78) 14.19 (27.67) 0.73
IL-2, mean (SD) 6.19 (6.83) 9.02 (13.96) 0.48
IL-4, mean (SD) 94.11 (107.99) 161.35 (339.06) 0.48
IL-6, mean (SD) 32.82 (39.72) 56.33 (114.78) 0.47
IL-8, mean (SD) 18.71 (22.41) 25.30 (46.96) 0.63
IL-10, mean (SD) 18.30 (22.18) 12.63 (12.21) 0.33
IL-12, mean (SD) 18.44 (41.04) 30.86 (74.32) 0.57
IL-13, mean (SD) 49.43 (87.00) 63.23 (197.77) 0.81
IL-17a, mean (SD) 7.83 (11.71) 14.35 (27.47) 0.41
MCP-1, mean (SD) 453.04 (182.71) 191.69 (86.08)10/19/2020
Preliminary Cytokine Findings: CSF
Factor Controls Patients p-value
N 14 22
Fractalkine, mean (SD) 205.03 (51.38) 184.04 (90.47) 0.44
IFN-γ, mean (SD) 3.57 (0.36) 4.30 (2.32) 0.25
IL-1β, mean (SD) 3.43 (0.17) 3.36 (0.18) 0.28
IL-2, mean (SD) 3.04 (1.07) 3.05 (0.86) 0.96
IL-4, mean (SD) 161.93 (182.66) 137.41 (168.94) 0.68
IL-6, mean (SD) 11.25 (6.38) 9.55 (7.05) 0.47
IL-8, mean (SD) 33.42 (17.89) 25.67 (8.35) 0.087
IL-10, mean (SD) 3.06 (0.80) 3.16 (0.34) 0.61
IL-12, mean (SD) 3.41 (0.78) 6.19 (5.83) 0.086
IL-13, mean (SD) 10.07 (5.56) 7.69 (5.55) 0.22
IL-17a, mean (SD) 3.44 (0.34) 3.31 (0.35) 0.28
MCP-1, mean (SD) 1053.22 (486.58) 605.01 (224.68)10/19/2020
MCP-1 (CCL2)
• Recruits monocytes, memory T cells and dendritic
cells to inflammation (i.e., “pro-inflammatory”)
• Expression in glial cells increased in CNS diseases
(epilepsy, brain ischemia, Alzheimer’s, TBI)
• Animal studies
• Increased in acute phase after trigeminal injury
• Expression and induction via TNF receptor in other
animal models of neuropathic pain (e.g., ventral
rhizotomy)
• Do MCP-1 levels observed reflect long-term
versus short-term effects?
43
Limitations of Cytokines
• Variable stability
• High degree of inter- and intra-individual variability
• Alternative molecular biomarkers
• miRNA, lncRNA, and other non-coding RNAs
• Proteomics, metabolomics
• Extracellular vesicles
44
2210/19/2020
Transcriptomic Profiles
• 16 TN patients classified as MVD responders and non-responders
• Proteins quantified
• CSF n=1087 proteins quantified
• Plasma n=1090 proteins quantified
• Not all included have associated gene names or protein accession numbers
• Significant proteins
• CSF n=62 significant in non-responders vs. responders (2-fold and FDR
adjusted p10/19/2020
String Analysis
47
MCODE Analysis
48
2410/19/2020
Diagnostic Challenges in Craniofacial Pain
• Facial pain is challenging to diagnose
• Many similar/overlapping pain syndromes
• Biomarkers may assist in both diagnosis and treatment
selection
• Cytokines, transcriptomes
• Evidence of inflammatory pathways in trigeminal neuralgia
49
THANKS
Ashish, Siona, and Niam Doshi
Neurosurgery Pain Research Institute
Blaustein Pain Research Fund Srinivasa Raja
ACCM StAAR Awards Claudia Campbell
Doris Duke Early Clinician Investigator Fund Michael Lim
Seena Ajit
Foundation for Anesthesia Education and Research Susan Dorsey
Donald Nixdorf
Johns Hopkins Department of Anesthesiology and Carlos Pardo
Critical Care Medicine Abhay Moghekar
Mirinda Anderson-White
Division of Pain Medicine
Elizabeth White
Johns Hopkins School of Public Health Becton Alice Hung
Dickinson Immune Function Laboratory Adela Wu
Institute for Genome Sciences Renuka Bhisetti
Shravya Gogula
Tricia Nilles
50
25You can also read
