Cardiac cephalgia:

A treatable form of exertional headache

R.B. Lipton, MD; T. Lowenkopf, MD; Z.H. Bajwa, MD; R.S. Leckie, MD; S. Ribeiro, MD; L.C. Newman, MD;
and M.A. Greenberg, MD

Article abstract-We report two patients with exertional headaches beginning with vigorous exercise and relieved by
rest. Neurologic evaluation and neuroimaging were normal in both. During exercise stress testing, the onset of the
patients’ typical headaches correlated with ECG changes indicative of myocardial ischemia. In both patients coronary
angiography revealed three-vessel disease, and myocardial revascularization procedures were followed by complete reso-
lution of headaches. Based on these patients, and a review of prior similar reports, we conclude that myocardial ischemia
is a rare and treatable cause of exertional headache. Accurate diagnosis is critical to controlling headaches and preventing
myocardial infarction.
NEUROLOGY 1997;49:813-816

The majority of headaches associated with exertion
are benign. Within the International Headache Soci-
ety classification, most exertional headache can be
categorized as “miscellaneous headaches unassoci-
ated with a structural lesion” (reference 1, p. 39).l
Subtypes include benign cough headache, benign ex-
ertional headache, and headaches associated with
sexual activity.l Exertional headaches due to an or-
ganic cause may occur in patients with intracranial
structural p a t h o l ~ g y .We
~ - ~report two unusual cases
of cardiac ischemia presenting as an exertional head-
ache and review prior published reports.
Patient 1. A 57-year-old man presented with a
4-month history of exertional headaches beginning 5
to 10 minutes after the onset of vigorous exercise
and increasing in severity over several minutes. The
pain was maximum at the vertex, sharp or shooting
in quality, and rated as 10 (of 10) in severity. The
pain persisted when he walked or swam, gradually
subsiding over minutes to hours when exercise was
terminated. The headache also occurred with sexual
activity. The pain was accompanied by nausea but
not vomiting. There was no aura, photophobia, or
phonophobia. Headaches were not provoked by
coughing, sneezing, or straining with bowel move-
ments. On a few occasions they were associated with
vague abdominal or chest discomfort but not with
palpitations, dizziness, or diaphoresis.
His history was negative for hypertension, diabe-
tes, and heart disease. He stopped smoking 1 year
prior to evaluation. Family history was positive for
coronary artery disease in both parents.
The patient presented to a neurologist with the
described history. Initial workup included noncon-
From the Department of Neurology (Drs. Lipton, Lowenkopf, Ribeiro. and Newman) and Medicine (Dr. Greenberg), Albert Einstein College of Medicine, The
Headache Unit, Montefiore Medical Center (Drs. Lipton, Lowenkopf, Ribeiro, and Newman), Bronx, NY: and the Department of Neurology (Dr. Bajwal and
Anesthesiology (Drs. Bajwa and Leckie), Beth Israel Hospital, Harvard Medical School, Boston, MA.
Received September 26, 1996. Accepted on final form March 1. 1997.
Address correspondence and reprint requests to Dr. Richard B. Lipton, Department of Neurologymeadache Unit, Montefiore Medical Center, 111 E. 210th
Street, Bronx, NY 10467.
trast CT and MRI of the head, both of which were
normal. Two weeks later he again developed the
rapid onset of severe headache with exertion. He
consulted a second neurologist who performed a lum-
bar puncture to rule out subarachnoid hemorrhage;
CSF was normal. The patient’s internist sent him for
pulmonary function tests, which were also normal. A
resting ECG revealed flattened T waves in V, and
AVL, an inverted T wave in lead V,, and biphasic T
waves in V3,4,6.No specific diagnosis was made.
The patient’s exertional headaches persisted and
he sought a third neurologic opinion at our center.
To assess the possibility that cardiac ischemia
caused his headaches, we referred him for a exercise
stress-thallium test. In stage I1 he developed the
onset of his typical exertional headache accompanied
by ST-segment depression in leads 11, 111, AVF, and
V4-6. A severe reversible perfusion defect was seen
in the mid and distal anterior wall extending to the
apex. The termination of exercise was followed by
the rapid simultaneous resolution of the headache
and ECG changes. The patient was started on dilti-
azem 30 mg four times a day and aspirin 80 mg
every day with some decrease in his exertional head-
aches. Coronary angiography revealed severe three-
vessel disease with hypokinesis and hypertrophy of
the wall of the left ventricle. Following three-vessel
coronary artery bypass surgery, his resting ECG nor-
malized and he has returned to his usual exercise
program without exertional headache.
Patient 2. A 67-year-old man presented with a
9-month history of exertional headache beginning 10
to 15 minutes after the onset of strenuous exercise,
including brisk walking. The headaches consisted of
Copyright 0 1997 by the American Academy of Neurology 813
a bifrontal, squeezing, steady pressure that in-
creased with continuous exercise to a rating of 10 (of
10) in severity. Pain gradually resolved over minutes
to an hour after the termination of exercise. The
headaches were not associated with nausea, vomit-
ing, aura, photophobia, phonophobia, abdominal or
chest discomfort, palpitations, dizziness, diaphoresis,
or shortness of breath. They were not provoked by
coughing, sneezing, or straining with bowel move-
ments. The patient also reported the onset of bilat-
eral calf claudication with walking and stair climb-
ing.
His history was negative for diabetes, heart dis-
ease, and hypercholesteremia. He stopped smoking
30 years prior to presentation and had been physi-
cally active his entire adult life. For the past year he
took nifedipine 30 mg twice a day, metoprolol 50 mg
twice a day, and enalapril 10 mg twice a day for
hypertension, as well as aspirin 80 mg every day.
His family history was positive for diabetes, coronary
artery disease, peripheral vascular disease, and
cancer.
His family physician ordered noncontrast CT of
the head and noninvasive vascular studies of his
lower extremities; both studies were normal. A neu-
rologic consultation did not identify a cause for head-
ache and the patient was referred for a cardiac eval-
uation. His cardiac exam was normal but his ECG
showed sinus bradycardia and a possible old inferior
wall myocardial infarct. During his cardiac exercise
stress-thallium test he developed his typical bifron-
tal headache with simultaneous inferolateral ST-
segment depression and a small area of inferolateral
reversible hypoperfusion. The patient was instructed
to take sublingual nitroglycerin prior to exercise. He
found that this regimen prevented his exertional
headache. On a repeat stress test he again developed
his typical bifrontal headache with inferolateral ST-
segment depression on ECG. The headache and ECG
changes simultaneously reversed with the adminis-
tration of nitroglycerin and the termination of exer-
cise. A coronary angiogram revealed three-vessel dis-
ease with 90% left circumflex artery stenosis. The
patient underwent rotational atherectomy and per-
cutaneous transluminal coronary angioplasty. A re-
peat stress-thallium test 1month after the procedure
failed to reproduce headache or ECG changes consis-
tent with ischemia. The patient continues to exercise
regularly without exertional headache.
Discussion. We summarize the new patients and
five prior reports in table 1. In all seven patients,
exertional headache was the most prominent mani-
festation of well-documented myocardial ischemia.
The onset of headache with exercise, the association
of headache onset with documented simultaneous
myocardial ischemia, and the resolution of headache
with medical (Patients 1, 2, 4, 5, 6, 7) and surgical
(Patients 3, 5, 6, 7) therapy support our contention
that myocardial ischemia may present with exer-
tional headache. We suggest the term “cardiac ceph-
814 NEUROLOGY 49 September 1997
algia” for this disorder. In both our patients, and in
several earlier reports, the diagnosis was delayed by
a failure to recognize cardiac ischemia as a cause of
headache.
As exertional headache has a broad differential,
which includes both secondary and primary head-
ache syndromes, the evaluation of exertional head-
ache should seek to identify or exclude serious treat-
able etiologies. In general, patients with exertional
headache require neuroimaging to rule out struc-
tural disease. Magnetic resonance imaging is the
preferred imaging modality as pathology in exer-
tional headache tends to be in the posterior fossa.l0
Sands et a1.l0 reviewed 233 published cases of exer-
tional or cough headache and found that 22 had
structural disease. Pascual et aL4 reviewed 28 cases
of exercise headache and found 10 with subarach-
noid hemorrhage, one with brain metastases, and
one with pansinusitis. If the exertional headaches
are of recent onset or if the pain is paroxysmal, se-
vere, or long-lasting lumbar puncture is required to
rule out subarachnoid hemorrhage. Occasionally,
pseudotumor cerebri,ll cortical vein thrombosis, or
sagittal sinus thrombosis may present as exertional
headache.12 Once secondary causes are excluded, a
specific primary headache disorder should be diag-
nosed.
The primary headache disorders in the differen-
tial diagnosis of cardiac cephalgia include benign ex-
ertional headache, benign cough headache, and
headache associated with sexual activity.l Exertional
headache caused by angina should be relatively easy
to differentiate from benign cough headache, which
is of sudden onset, generally lasts less than 1
minute, and is usually prevented by ind0metha~in.l~
Raskin13 demonstrated that this disorder also remits
with lumbar puncture. Benign exertional headache
is potentially more problematic, as the headache
may last from 5 minutes to 24 hours. Patients at risk
for cardiac cephalgia may require a cardiac workup
as discussed later. Exertional migraine could present
a diagnostic difficulty in that typical migraine may
begin after a period of strenuous exercise.14
Distinguishing cardiac cephalgia from migraine is
of considerable importance. Both disorders can pro-
duce severe head pain accompanied by nausea and
both can be triggered by exertion.14Vasoconstrictors
(sumatriptan, ergotarnine, and dihydroergotamine)
are indicated in the treatment of migraine but con-
traindicated in patients with cardiac cephalgia due
to their ability to constrict coronary arteries.15 Con-
versely, the vasodilator nitroglycerin can induce
headache in normal subjects, and may have an espe-
cially potent headache-inducing effect in migraine
sufferers.16In four of the patients with cardiac ceph-
algia (see the table), treatment with nitrates relieved
exertional headache.
The key to identifying cardiac cephalgia is the
temporal profile of the pain. The headache typically
begins in close proximity to the onset of vigorous
exercise, and subsides with rest and with antiangi-
Table Patient reports of cardiac cephalgia

Author Headache Result of

(patient agehex) character Cardiac symptoms Workup Treatment therapy

Fleetcroft and Frontal Tightness of chest ECG: 1 ST AVF, Vl-z Isosorbide Headache
Maddocks5 (78IF) dinitrate resolved
nifedipine
Blacky et aL6 (40/M) Bitemporal None Stress-thallium: inferolateral Antianginal Headache
& ST associated with headache; therapy resolved
reversible inferoapical
perfusion defect; cath: left
circumflex obstructed, RCA
stenosis
Lefkowitz and Biller7 Vertex Retrosternal pain E C G anterolateral & ST; stress CABG Headache
(62/M) test: & ST associated with resolved
headache; cath: anterolateral
wall hypokinesia, three-vessel
disease
Vernay et aL8 (71/M) Occipital, Chest tightness ECG. anteroapical J ST; stress Isosorbide Headache
parietal, test: & ST associated with dinitrate resolved
frontal headache
Bowen and Bitemporal, Rare left-arm ECG: anterior 1 ST; cath: RCA Nitroglycerin, Headache
Oppenheimer9(59/M) left-sided painful total occlusion, proximal OM, PTCA resolved
predominance pressure; chest 95% stenosis
pain once
Lipton” (57/M) Severe vertex Occasional ECG: T-wave flattening I, AVF; Diltiazem, Symptoms
pain sensation of biphasic T-wave Vz4; stress- aspirin decreased
chest heaviness/ thallium: anterior & ST CABG Headache
nausea associated with headache; resolved
anterior hypoperfusion defect;
cath: three-vessel disease
Lipton” (67/M) Bifrontal, None Stress-thallium: inferolateral Nitroglycerin, Headache
squeezing & ST, associated with rotational resolved
pressure headache; inferolateral atherectomy,
perfusion defect; cath: three- PTCA
vessel disease
-

:k Current report.
F = female; M = male; AVF = arteriovenous fistula; CABG = coronary artery bypass graft; cath = cardiac catheterization; OM = ob-
tuse marginal; PTCA = percutaneous transluminal coronary angioplasty; RCA = right coronary artery; stress test = cardiac exercise
stress test; J ST = depressed ST segment.

nal treatment. The diagnosis should be suspected in
patients with headache onset after age 50 and in
patients with risk factors for cardiac disease.
Workup with a stress thallium test should usually
confirm or exclude the diagnosis. If cardiac cephalgia
is a possibility, prompt workup is essential before
treatment with vasoactive migraine drugs.
The mechanism of cardiac cephalgia is specula-
tive. Indeed, the bases of ischemic chest pain or pres-
sure and extrathoracic cardiac ischemic pain are
poorly understood.17One possible explanation of car-
diac cephalgia is anatomic: the heart’s sympathetic
fibers are supplied by cervical and thoracic ganglia.
Because fibers from these ganglia also supply struc-
tures of the eye, face, neck, and cerebrovascu1ature,l8
referral of pain along these pathways might account
for headache symptoms. A second possibility is that
the decrease in cardiac output and the increase in
left ventricular and right atrial pressure associated
with anginal9cause a decrease in venous return from
the brain and subsequently an increase in intracra-
nial pressure. Although changes in intracranial pres-
sure during angina have not been documented, head-
ache and increased intracranial pressure have been
described in patients with decreased cranial venous
return secondary to jugular or superior vena caval
obstruction.z0,21Das22reported a patient with head-
ache and a defective cardiac pacemaker. Synchro-
nous atrial and ventricular contraction caused a sud-
den increase in right atrial pressure that was
transmitted intracranially t o produce headache.
Headache from sudden, transient, increased intra-
cranial pressure is also proposed as an explanation
for cough headache. An increase in intra-abdominal
and intrathoracic pressure resulting from the cough
impedes venous return to the right atrium.13
A third explanation for cardiac cephalgia posits an
as yet unidentified mediator released secondary to
cardiac ischemia that might act on intracranial pain-
sensitive structures. Serotonin, bradykinin, hista-
mine, and substance P have been proposed as medi-
ators of ischemic painz3 and might also have distant
September 1997 NEUROLOGY 49 815
intracranial effects. The increase in intracardiac
pressure in angina may also induce atrial natriuretic
peptide (ANP) and brain natriuretic peptide (BNP)
release, a response to increased right atrial and left
ventricular pressure.24ANP and BNP are potent va-
s o d i l a t o r ~ and
, ~ ~ thus
~ ~ ~ could produce headache by
dilation of the cerebrovasculature. Both the head-
ache described by Das22and cough headache might
be explained by this action of these natriuretic car-
diac peptides. Alternatively, cardiac cephalgia may
be a selectively silent form of angina. There are nu-
merous patient reports of typical anginal pain in the
thorax accompanied by h e a d a ~ h e . ~ ~ From
- ~ O this per-
spective the unusual feature of cardiac cephalgia is
not the presence of headache but the absence of the
typical pain of cardiac ischemia.
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 Cardiac cephalgia: A treatable form of exertional headache
R. B. Lipton, T. Lowenkopf, Z. H. Bajwa, et al.
Neurology 1997;49;813-816
DOI 10.1212/WNL.49.3.813

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