Imaging of Chronic Headache

IMAGING OF CHRONIC
HEADACHE
Alexander Wong 1, Adam Dmytriw 2, Eugene Yu 2, Reza Forghani 3, Gordon Sze 4, Colin S. Poon 4
1
University Of British Columbia, Vancouver, BC
2 University Of Toronto, Toronto, ON
3 Jewish General Hospital & McGill University, Montreal, QC
4 Yale University, New Haven, CT
Control Number: 1729
eEdE#: eEdE-214
DISCLOSURE
Neither I nor my immediate family members have a financial relationship with
a commercial organization that may have direct or indirect interest in the
content presented herein.
INTRODUCTION
• Chronic headache is commonly a nonspecific complaint.
• The decision to initiate imaging investigation of chronic headache is difficult due to the low
diagnostic yield.
• Most imaging studies of chronic headache are non-contributory. However, in a small proportion
of cases, headache may be the presenting symptoms of significant diseases. The consequence of
delayed diagnosis can be catastrophic.
• Imaging of chronic headache is therefore a controversial topic.
• To further complicate the controversy, advanced imaging may provide new information that can
re-define the role of neuroimaging in chronic headache
OBJECTIVES
• To review the appropriateness and controversy of costs-versus-benefits for imaging of chronic
headache
• To review diseases presenting as chronic headache, with an emphasis on diseases less
commonly seen
• To review the role of advanced imaging techniques for evaluation of chronic headache
APPROPRIATENESS OF NEUROIMAGING
FOR CHRONIC HEADACHE
THE ARGUMENTS IN FAVOR AND AGAINST
IMAGING OF CHRONIC HEADACHE
BENEFITS
• Identification of significant, treatable
causes
• Patient reassurance
ADVERSE EFFECTS
• Costs
• Harm of neuroimaging (e.g., radiation,
exposure to contrast materials)
• Harm of false positive results (patient
anxiety, additional unwarranted
investigation / treatment)
GUIDELINES OF APPROPRIATENESS OF
NEUROIMAGING
• Guidelines have been developed to facilitate decision making in utilization of imaging
investigation for headache.
• Most guidelines focus on “red flag” symptoms and clinical signs that aim to increase
diagnostic yield of diagnostic imaging.
SUMMARY OF GUIDELINES FOR APPROPRIATENESS OF NEUROIMAGING
(Lester,2012; Frishberg 2000; Douglas 2013; Duncan 2008)
CLINICAL FINDINGS
APPROPRIATENESS
COMMENTS / EVIDENCE
Chronic migraine headache with normal
neurological examination and findings
N
Further CT and MRI studies on normal neurologic
examinations yielded only 0.4% of cases having significant
abnormalities (Evans, 2009).
Long-lasting headache with no
significant change or new feature
N
Neuroimaging only recommended if patient suffering
from anxiety of severe illness or there are ‘red flags’ in
initial examination.
Thunderclap headache
Y
May be seen in subarachnoid hemorrhage and reversible
vasoconstriction syndrome.
Radiating to neck
Y
May be seen in dissection.
Temporal headache in older individuals
Y
May be seen in giant cell arteritis.
Increasing frequency or severity
Y
-
Occurring on the same side
Y
Commonly seen in intracranial tumours.
Not responding to treatment
Y
-
SUMMARY OF GUIDELINES FOR APPROPRIATENESS OF NEUROIMAGING
– CONTD. (Lester,2012; Frishberg 2000; Douglas 2013; Duncan 2008)
CLINICAL FINDINGS
APPROPRIATENESS
COMMENTS / EVIDENCE
Wake patient from sleep
Y
Common in intracranial tumors.
Triggered by Valsalva maneuver,
Y
cough, physical exertion, or sexual
activity
May be seen in intracranial hypotension, intracranial hypertension,
subarachnoid hemorrhage, reversible cerebral vasoconstriction
syndrome, intracranial tumor, hindbrain and occipitocervical junction
abnormality such as Chiari 1 malformation.
New headache in HIV positive
patients
Y
Increased likelihood of intracranial infections due to immunosuppression
(35-82% of patients show abnormalities on neuroimaging studies)
Prior history of cancer, seizures
Y
32% of cancer patients with changing headache pattern have intracranial
metastases.
Pregnancy
Y
Higher probability of intracranial pathologies; 2.7 times greater
probability in patients with abnormal neurologic examinations.
Age > 50
Y
New headache at this age group are at higher risk of intracranial tumor.
THE MAIN PURPOSE OF GUIDELINES IS TO MINIMIZE
UNWARRANTED UTILIZATION AND HEALTH CARE COST
COSTS OF NEUROIMAGING ARE HIGH
Individually(ABIM, 2012):
• CT scan = $340, with contrast agent = $840
• MRI scan = $660, with contrast agent = $970
• Note that these costs do not factor in follow-up treatments or other
Populational (Callaghan, 2014) :
• Total neuroimaging expenditure estimated to be $3.9 billion over 4 years with $1.5 billion from just migraine
visits
• Outpatient headache neuroimaging visits cost nearly $1 billion annually and is increasing
CAUTION ON THE STRICT USE OF GUIDELINES
Hawasli et al. discuss that current guidelines only lead to
diagnosis in a fraction of brain tumor patients who receive
neuroimaging (2015)
• Patients with tumours frequently present with isolated
headaches, minimal symptoms or are even asymptomatic,
which are not taken into account in the guidelines
They recommended more emphasis be put on evaluating each
patient on a case-to-case basis:
RECOMMENDATIONS
POTENTIAL MISSES, n/N (%)
Headache Society/(Loder et
al., 2013)
3/11 (27.3)
American College of
Radiology
7/11 (63.6)
American Academy of
Neurology/(Frishberg et al.,
2006)
3/11 (27.3)
Potential tumours missed with current guideline.
• Though this approach may increase initial healthcare costs
From: Hawasli, A.H., Chicoine, M.R., and Dacey, R.G. (2015).
due to increased neuroimaging utilization, it may ultimately Choosing Wisely: A neurosurgical perspective on
result in more favorable cost - benefit ratio by decreasing the Neuroimaging for headaches. Neurosurgery 76: 1–5.
potential malpractice liability costs
• This approach also reduces delay for treatment in some
cases, which may lead to decrease of total healthcare costs
THE CONSIDERATION OF COST OF
“UNNECESSARY” NEUROIMAGING MAY NOT BE
AS SIMPLE AS IT SOUNDS
“Unnecessary ” neuroimaging studies may be beneficial.
VALUE OF NEGATIVE IMAGING RESULTS
• Many current cost versus benefit analysis studies only take into account the low proportion of
neuroimaging scans with positive findings of neuropathological conditions (i.e. low diagnostic
yield)
• These studies often neglect the fact that neuroimaging itself has the benefit of providing patients
with the reassurance that they do not have severe pathological conditions, ultimately leading to
anxiolytic outcomes
• The conclusion of these studies that negative imaging evaluation places unwarranted economical
burden on the healthcare system may be over-simplistic
• Neuroimaging studies which lead to anxiolytic effects enhance the emotional and mental health
of patients, leading to a greater quality of life, and consequently decrease the total health care
costs in select groups of patients
NEGATIVE IMAGING STUDIES CAN BE COST EFFECTIVE
AND PROVIDE PATIENT REASSURANCE (Howard,2005)
• Some patients with chronic daily headaches who did not receive a magnetic resonance imaging
(MRI) brain scan had significantly higher number of visits to psychiatrists or neurologists,
ultimately leading to increased medical expenditure
• The study used a Hospital Anxiety and Depression Scale (HADS) to stratify the random sample into
two categories: HADS positive (with a score >11) and HADS negative (with a score ≤11)
• A positive result on the HADS scale indicated a patient who had high level of anxiety or depression
• Based on primary care case notes examined at 1 year after the start of the clinical trial, HADS
positive patients who received a scan had a mean cost that was significantly less (-£ 465) than
patients of the same group who did not receive a scan
• However, the benefits do not extend to HADS negative patients
CONSIDERATION OF COST VERSUS BENEFIT IN
NEUROIMAGING
• The study of Howard (2005) showed the favorable cost versus benefit of performing neuroimaging
on patients with chronic headache and high levels of anxiety or depression
• Appropriateness of neuroimaging, in the context of cost versus benefit, should also take into
consideration the patient factors on top of the common existing guidelines which are largely
based on the neurological findings and diagnosis of diseases
HEALTHCARE PRACTITIONER REASSURANCE
FROM NEUROIMAGING (Howard,2005)
• The study of Howard further suggested that negative neuroimaging also provides reassurance for healthcare
practitioners, decreasing the cycle of unnecessary referrals and investigations, resulting in overall decreased
costs of patient care
APPROPRIATENESS OF NEUROIMAGING
• Appropriateness and cost versus benefit analysis of neuroimaging of chronic headache is a
complex issue
• Several practice guidelines are available to facilitate the decision of imaging investigation of
chronic headache
• These guidelines were developed to improve diagnostic yield of neuroimaging
• Decision of imaging investigation needs to be individualized
• Factors of patient and health care practitioner anxiety levels may alter the balance of cost versus
benefit and should also be taken into consideration
DISEASES PRESENTING AS CHRONIC
HEADACHE
COMMON IMAGING DIAGNOSIS THAT MAY
PRESENT AS CHRONIC HEADACHE
NEUROIMAGING FINDING
COMMENTS
Neoplasm
Very commonly presented as headache (71%). Headache is more common in
neoplasm below tentorium cerebelli. It is more prevalent in primary and
intracerebral tumors than extracerebral and metastatic tumors (Suwanwela et
al., 2005).
Arteriovenous Malformation (AVM)
Only a fraction of AVM present with isolated headache. Most present with
hemorrhage.
Arterial aneurysm / Subarachnoid
hemorrhage
30-40% of patients with unruptured aneurysms have intense thunderclap
headache weeks prior to rupture (D’Souza, 2015).
Subdural hemorrhage
Found in 11-25% of patients with thunderclap headache
Cavernous Malformation
Common symptoms include seizures (50%), neurological deficits (25%) while
20% of patients are asymptomatic.
Hydrocephalus
-
Occipitocervical junction abnormality /
Chiari 1 malformation
-
LESS COMMON IMAGING DIAGNOSIS THAT MAY
PRESENT AS CHRONIC HEADACHE
NEUROIMAGING FINDINGS
COMMENTS
Cerebral Venous Thrombosis
Isolated intracranial hypertension is differentiating symptom from classical criteria
for idiopathic intracranial hypertension (Biousse, 1999).
Dissections
Unilateral headaches that radiate down neck and ipsilateral Horner syndrome
symptoms are suspicious of arterial dissection.
Giant Cell Arteritis
Elderly patients with temporal headache and elevated sedimentation rates (Lester,
2012).
Moyamoya Disease
Aneurysms and AVMs are associated findings in 11-14% of cases (Lester, 2012).
Reversible Cerebral Vasoconstriction
Characterized by recurrent thunderclap headaches, seizures, strokes, and
nonaneurysmal subarachnoid hemorrhage.
Intracranial hypotension
Orthostatic and postural headaches, visual or aural changes, cranial nerve
dysfunction and meningismus may indicate intracranial hypotension.
Intracranial hypertension
Characterized by pulsating headache with gradually increasing intensity causing
patient to wake up, pain in a nerve root distribution or ocular pain with eye
movement (specific symptom).
INTRACRANIAL HYPOTENSION
• Most often related to dural
cerebrospinal fluid leak
• Common image findings:
• Bifrontal subdural hygroma
or hematoma, diffuse dural
enhancement and
engorgement, and sagging of
brain stem (40-50% of cases)
Sagittal T1 weighted MRI images. (A) Patient with intracranial hypotension demonstrates sagging of
brainstem, downward displacement of cerebellum and medulla towards the foramen magnum (➨
and →), and enlargement of pituitary gland (➝). Note also flattening of angle of infundibulum and
optic chiasm. The presence of findings in addition to cerebellar tonsillar ectopia distinguishes this
case from Chiari 1 malformation. Contrast the findings with that in normal brain (B) (corresponding
structures shown by same arrows).
INTRACRANIAL HYPOTENSION – SAME PATIENT
• Axial FLAIR image demonstrates dural thickening
and hyperintensity (solid arrow) along the right
cerebral convexity
• The ventricles are decreased in size (open arrow)
INTRACRANIAL HYPOTENSION – DIFFERENT PATIENT
A
B
C
(A & B) Axial FLAIR images demonstrate bilateral subdural hematoma (➨), and decreased size of lateral ventricles
(→). (C) Axial T1-weighted post-gadolinium image demonstrates smooth dural thickening and enhancement in
posterior cranial fossa.
IDIOPATHIC INTRACRANIAL HYPERTENSION
Axial fat saturated T1 weighted MR
image showing prominence of optic
nerve heads (white arrows).
Coronal T2 weighted MRI showing
increased cerebrospinal fluid
surrounding optic nerves (white
arrow).
Axial T2-weighted MRI showing
narrowed slit-like ventricles
(indicated by white arrow).
Sagittal T1 weighted postgadolinium image demonstrates
partially empty sella with
flattening of pituitary gland.
GIANT CELL ARTERITIS (GCA) (Cianco, 2011)
• Primarily affects patients of northern European
descent
• Artery biopsy still remains the most accurate method
of diagnosis, but improved ultrasound and vascular
MRI may allow non-invasive diagnosis
• In ultrasound, dark hypoechoic halo around temporal
artery is most specific to GCA, and indicates
inflammation and thickening of vessel wall
Duplex ultrasonography of left temporal artery showing hypoechoic regions at
vessel wall ( white arrows), which are indicative of giant cell arteritis.
• False-positives: commonly occur when accompanying
vein of GCA-affected artery has no flow and shows a
halo
• False negative: 10% of patients with positive biopsy
have normal ultrasound imaging (may be due to prior
corticosteroid treatment or mild GCA)
Axial (A) and coronal (B) T1-weighted post-contrast fat-saturated MRI showing
asymmetric thickening and enhancement of right superficial temporal artery
walls (arrow).
From: Lester MS and Liu BP, Medical Clinics of N. Am. 2013
CENTRAL NERVOUS SYSTEM VASCULITIS
A
B
C
D
(A). Axial T2 weighted image demonstrates scattered areas of gray and white matter hyperintensity and focal edema. (B).
Diffusion weighted images demonstrate restricted diffusion on many of the involved areas. (C) On T1-weighted postgadolinium images, patchy areas of parenchymal and leptomeningeal enhancement are present. (D) Maximum intensity
projection of MR angiography demonstrates irregular stenosis of bilateral cerebral arteries diffusely (arrows).
• Imaging findings in vasculitis are variable and can be relatively normal. If imaging findings are non-revealing, clinical and
laboratory correlation is required. Biopsy may be required for diagnosis in some cases.
SINUS HEADACHE – THE OFTEN OVERLOOKED
DIAGNOSIS
• Extracranial source of chronic headache (e.g., sinogenic
headache) should be considered
• Kaur’s (2013) study showed that sinogenic headache is
most often localized to the forehead (43.4% of patients).
Other sites include multiple regions (34.7%), glabella
(13.04%), and top of head (8.69%)
• Corollary: some studies suggest 90% of migraines are
misdiagnosed as sinus headaches (Levine, 2014)
• Largely due to trigeminal nerve activation in migraines,
leading to highly similar symptoms to sinus headaches
(including lacrimation and rhinorrhea)
Coronal CT of paranasal sinuses demonstrates
chronic obstruction of right maxillary sinus (shown
by white arrow) in a patient presenting with
chronic headache.
ADVANCED IMAGING FOR CHRONIC HEADACHE
• Many advanced imaging techniques are not routinely used in clinical evaluation of chronic
primary headache, but may provide additional diagnostic information in selective cases.
• Advanced imaging may enhance understanding of pathophysiology of primary headache
disorder and development of therapeutics.
MAJOR HYPOTHESES OF PATHOPHYSIOLOGY OF
MIGRAINE
Vasogenic theory
◦ Cerebral vasoconstriction results in local hypoxia and focal neurologic symptoms.
◦ Subsequent rebound extracranial and intracranial vasodilatation results in pain.
Neurogenic theory
◦ Transient paroxysmal depolarization of cortical neurons results in focal neurologic symptoms and
pain.
TRANSIENT HYPOPERFUSION OF MIGRAINE WITH AURA
CAN BE DETECTED WITH PERFUSION IMAGING
• 24-year old male patient presenting with
aura of acute-onset aphasia, visual
reduction, and right-sided paresthesias
• Initial MR perfusion weighted imaging (A–
D) shows hypoperfusion in left posterior
cerebral hemisphere, demonstrated by
prolonged rMTT (Fig. B) and TTP (Fig. A).
rCBF maps demonstrate decreased blood
flow (Fig. C). In rCBV maps, no significant
hypoperfusion is demonstrated
• Follow-up perfusion imaging after 24 hours
shows complete resolution of
hypoperfusion in all maps (Fig. E to H)
From: Floery D, et al. Acute-onset migrainous aura mimicking acute
stroke: MR perfusion imaging features. AJNR 2012; 33:1546-1552.
fMRI PROVIDES IMPROVED UNDERSTANDING OF
BRAIN ACTIVATION IN MIGRAINEURS (Sprenger, 2012)
• Functional MRI provides effective non-invasive platform for
studying brain activation in response to stimuli
• Allows study of activity in different brain regions based on [O2]
decreases, corresponding to increased brain activity
• Migraineurs with visual auras show increased contralateral
primary sensorimotor cortex activation and a shift in the center of
supplementary motor area activation, which suggests migraines
may be associated with functional reorganization cortex outside
the ictal phase (Llano, 2013).
• Allows study of connectivity between different active brain regions
in migraineurs
• Increased activation of temporal pole in response to trigeminal
pain outside attacks, hyper-excitability even greater during attack
• Increased bilateral structural connectivity between temporal pole
and pulvinar of thalamus
BOLD responses in trigeminal nuclei at various stages of
migraine attack and a healthy control group. A more
negative value indicates a decrease in blood-oxygen level
dependent level signal, which corresponds to greater
activity and O2 consumption of trigeminal nuclei.
From: Stankewitz A, et al. Trigeminal nociceptive
transmission in migraineurs predicts migraine attacks.
The Journal of Neuroscience 2011; 31(6):1937-1943
INCREASED BRAIN ACTIVATION DURING AN ACUTE HEADACHE
ATTACK IN RESPONSE TO OLFACTORY STIMULATION
Migraine patients scanned during head pain (n = 13) showed an increased activation level in the amygdala (Amy), insular
cortex (InsC), temporal pole, superior temporal gyrus (Sup Temp Gyr), rostral pons, and cerebellum (Cereb) compared to
their own data outside migraine attacks (n = 13).
From: Stankewitz A, May A. Increased limbic and brainstem activity during migraine attacks following
olfactory stimulation. Neurology 2011; 77: 476-482
ADVANCED NEUROIMAGING CAN DEMONSTRATE SUBTLE
STRUCTURAL ABNORMALITY IN MIGRAINE PATIENTS
• Voxel-based morphometry demonstrates subtle focal
structural change of brain in migraine patients
• Focal gray matter loss in several areas belonging to the
pain transmitting network may be present in migraine
patients.
• Compared to control subjects, migraine patients
demonstrate subtle gray matter loss in right superior
frontal gyrus, right inferior frontal gyrus, and left
precentral gyrus.
Differences in gray matter between migraine patients and healthy
controls using modulated images. The background is structural T1weighted MRI. The color coding represents T values and describes
reduced gray matter. y and z represent spatial coordinates.
From: Valfrė W, et al. Voxel based morphometry reveals gray
matter abnormalities in migraine. Headache 2008; 48(1):109-117
SUMMARY
• Neuroimaging of chronic headache is a complex issue.
• Headache is a common clinical complaint. Most imaging investigation is non-contributory but
delayed diagnosis in some cases can be catastrophic.
• Appropriateness of neuroimaging and consideration of cost versus benefit:
• Most current guidelines on appropriateness of neuroimaging focuses on “red flag” symptoms and
signs to increase diagnostic yield.
• Decision of imaging investigation should also take into account patient and health care practitioner
anxiety levels and risk of delayed diagnosis, as these factors may alter the balance of total cost versus
benefit.
• Many diseases may present as headache, including extracranial diseases. Familiarity of the wide
spectrum of diseases, including less common diseases such as intracranial hypotension, intracranial
hypertension and vasculitis will help to improve imaging diagnosis.
• Advanced neuroimaging techniques provide new information of chronic headache, and help to improve
understanding of its underlying pathophysiology.
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THE END
Please contact Alexander Wong at [email protected] for any inquiries on the presentation. Thank you.