Cases & Commentaries

The Worst Headache

Commentary By Jonathan A. Edlow, MD

The Case

A 48-year-old woman with a history of migraine
headaches and hypertension presented to her outpatient clinic with
a 4-day history of headache. While shopping 4 days earlier, she
experienced sudden onset of a severe diffuse headache—"maybe
the worst headache I've ever had." She sat down because of the pain
and associated nausea.

She had presented to clinic later that day, where
a nurse practitioner assessed her symptoms as consistent with her
prior migraines, and recommended that she simply start the regimen
that she had used in the past (ibuprofen and ergotamine
tartrate/caffeine [Cafergot®]).

When her symptoms remained severe, she returned
the following day to the urgent care center. A staff physician
agreed with the nurse's diagnosis and reassured the patient that
there simply had not been enough time for the medications to take
effect. He administered intramuscular ketorolac and oral
prochlorperazine, with substantial improvement in her symptoms. An
appointment was made for her to follow-up with her primary care
physician 3 days later in case symptoms persisted, and also to
discuss initiation of a medication for migraine prophylaxis.

When the patient returned for her clinic visit in
the late afternoon 3 days later, she initially stated that her
symptoms had resolved. On closer questioning, however, she stated
that she continued to experience headaches when straining (eg,
during bowel movements) or bending over. Her physical exam,
including visualization of both retinas, was normal.

The physician regarded the initial acute
presentation as very worrisome for subarachnoid hemorrhage (SAH).
However, her subsequent clinical course seemed too benign, even
with the lingering headaches. Given that he had not completely
ruled out the possibility of hemorrhage, he arranged for her to
have a CT scan and asked the radiologist to page him immediately
with the results. He also gave the patient clear instructions to
call him if her symptoms worsened.

The radiologist paged the primary physician later
that evening to inform him that the head CT was normal. Knowing
that the CT is not 100% sensitive for subarachnoid hemorrhage, the
physician telephoned the patient the next morning to see how she
was doing. She had just woken up, but thanked him for calling and
stated that she felt much better—then the phone went dead. At
first, the physician thought she had simply hung up, but since it
was rather abrupt he called back and received a busy signal. He
called 911.

EMTs found the patient on the floor, arousable
only to painful stimuli. MR angiography in the emergency department
demonstrated a posterior circulation aneurysm (Figure 1),
which was clipped later that day. The patient required a
ventriculoperitoneal shunt, but her postoperative course went well,
with complete neurologic recovery.

The Commentary

Even in this age of ready access to sophisticated
neuro-imaging modalities, misdiagnosis of patients with
non-traumatic subarachnoid hemorrhage occurs in roughly 20%-30% of
cases (1-3) and
results in an inordinate number of malpractice claims.(4) Why is this?
Three recurring explanations may account for this high rate of
misdiagnosis: (i) not considering the diagnosis, (ii) not
understanding the limitations of computed tomography (CT), and
(iii) not performing or correctly interpreting the results of
lumbar puncture (LP).

Failure to Consider the Diagnosis
In the ambulatory setting, headache accounts for about 4% of office
visits and 2% of emergency department (ED) visits.(1,2) Even in
the acuity-skewed ED population, less than 1% of headache patients
have SAH, and only an additional 3%-4% have some other serious
condition that is life, limb, vision, or brain threatening if
untreated (Table 1). The
clinician's principal goal is to distinguish between the 95% of
patients with self-limiting headache syndromes, who require pain
control, and the other 5%, who require emergent diagnosis and
treatment.

The clinician's task may seem sufficiently
similar to finding a needle in a haystack that high rates of
misdiagnosis ought to be expected. However, clinicians operate with
a number of misconceptions about patients with headaches in general
and SAH in particular. First, because migraine and tension headache
are so common, patients with a history of headaches sometimes
develop other types of headache, as occurred in the present case.
Since almost everyone has had a headache at some point, clinicians
must carefully distinguish the index headache from prior ones.

We are not told how the nurse practitioner
"assessed her symptoms as consistent with her prior migraines." A
simple battery of questions will quickly distinguish "familiar" or
chronic headaches from unusual ones. In general, relevant questions
include:

  • Are the quality, duration, severity, and
    onset of pain the same?
  • Are any associated symptoms the
    same?
  • How often and under what circumstances
    have headaches occurred in the past?
  • Has there been any kind of work-up for
    the headaches?
  • Is the current headache responding to
    treatment as in the past?

Many clinicians have the mistaken impression that
patients with SAH invariably exhibit at least one of the following:
severe, acute illness; hard neurological findings such as cranial
nerve palsies; or meningismus. This is simply not true. As with
most diagnoses in medicine, there is a bell-shaped curve of
presentations, and well-appearing patients with normal neurological
examinations represent approximately 30%-40% of patients with
SAH.(1) Reliance on
the classic presentation of any disease opens the door to
misdiagnosis. Moreover, these mildly affected patients, who may
lack classic symptoms and signs, have the most to gain by prompt
correct diagnosis and therapy.

Another misconception is that symptoms begin with
strenuous activity. In fact, in one large study, roughly 50% of
patients with SAH developed their initial symptoms during relaxed
activity or were awakened from sleep.(5)
Similarly, many patients will not describe their pain as "10 out of
10" in severity or characterize it as the "worst headache of my
life." Moreover, some patients report their symptoms as gradual in
onset, rather than describing a "thunderclap" (sudden) onset
headache. However, almost all patients will describe their headache
as unusual or distinctive in terms of severity and/or character.
Even when neck pain dominates the clinical picture, it too tends to
be unusual and distinctive, reinforcing the importance of carefully
characterizing the patient's symptoms, especially when there is a
prior history of headache. Table 2 lists
common misdiagnoses given to SAH patients.

Another common misconception is that reduction of
pain with analgesics excludes severe intracranial pathology.
Pathophysiologically, a limited number of pathways mediate head
pain. Since medications of any class (ie, non-steroidals, opiate
analgesics) may blunt or eradicate headache, no diagnostic
information should be ascribed to this response. Adding further to
the challenge, the pain from a small SAH can resolve
spontaneously.

With regard to history, there are two other
important and related factors, at least one of which may have
played a role in this case. The first is that patients will often
use the words "migraine" and "sinus-headache" imprecisely. Some use
"migraine" to mean any severe headache, whereas in fact, it has
particular characteristics that are well-defined by the
International Headache Society.(6) Therefore,
if a patient says "I had two migraines last week," the clinician
should proceed as if the patient used the word "headache" until
more questions confirm the headaches are indeed migraines.

The second phenomenon is that of "anchoring." The
patient in this case is diagnosed (incorrectly) with migraine,
which then becomes part of her (recent) past history.
Psychologically, this limits the open-mindedness of subsequent
clinicians evaluating the same problem. Remember that definitive
diagnosis of either tension or migraine headache requires multiple
episodes of typical symptoms (5 for migraine, 10 for tension
headache). Therefore, one should be very cautious of making these
diagnoses in patients presenting with their first or worst
headache.

Physical examination in patients with SAH is
often normal. Only 10%-15% of patients exhibit a third-nerve
palsy—85% of aneurysms are located in the anterior
circulation and are therefore unlikely to produce any cranial nerve
findings.(2) Meningismus
and ocular hemorrhages also occur only in a minority of
patients.

For all these reasons, not considering SAH in the
differential diagnosis remains the most common reason for
misdiagnosis.(1,3) Failure to
consider the diagnosis commonly results in failure to obtain
relevant investigations—specifically, computed tomography and
lumbar puncture. Even when these tests are performed, however,
clinicians sometimes fail to interpret the results correctly,
prematurely terminating the work-up in the face of an initial
negative result.

The Limitations of CT Scanning
CT is a powerful diagnostic tool in SAH, but has important
limitations. Putting aside misinterpretation, the two most serious
issues are spectrum bias and timing from onset of
headache.(1,2) In
spectrum bias, less severely affected patients (on the left side of
the bell-shaped curve of severity) have smaller bleeds and
therefore are more likely to have a negative CT scan.(7,8) Timing is
also crucial. During the first 12 hours after onset of the
headache, CT sensitivity approaches 98%. However, the 95%
confidence intervals around this number are wide, and therefore
most still recommend a negative CT be followed by a lumbar puncture
(LP).(8,9) Three days
after onset of the headache, the CT is only 85% sensitive, and at 7
days, it is only 50% sensitive.(10)

In this case, the patient's CT was on the fourth
day after onset of headache. The negative study at this stage
(which would have a sensitivity of about 80%) should not have
reassured the clinician and the correct next step would have been
to perform an LP. Because this is often viewed as overly aggressive
in these well-appearing patients, clinicians often forego this
step.(11)

Interpreting the LP Results
The LP in patients with SAH may show blood, xanthochromia, or
elevated opening pressure. Blood can be from a traumatic tap or
from true SAH; there are many methods of distinguishing between the
two, although none is entirely foolproof.(12)
Xanthochromia is probably the best method (Figure 2). Many
believe that xanthochromia must be measured by spectrophotometry;
however this technique is not used in 99% of hospital laboratories
in North America.(13) In
addition, it may be overly sensitive, with many false
positives.(11)
Experimentally, CSF with red blood cell counts above 10,000
RBCs/µL or samples that have sat for a period of time prior to
analysis may show xanthochromia in the absence of SAH.(14) An elevated
opening pressure is found in roughly two thirds of patients with
SAH and will occasionally suggest the alternative diagnoses of
idiopathic intracranial hypertension and cerebral venous
thrombosis.(1)

The best way to avoid misdiagnosis of patients
with SAH is to take a very detailed history of the current
headache, and to compare it with prior headaches. In patients with
abnormal physical examinations, the decision to further evaluate
the patient with CT, followed by LP if the CT is negative,
equivocal or technically inadequate, is clear-cut. In patients with
normal exams, clinicians should stay open to the possibility of SAH
and have a very low threshold for pursuing the same evaluation (CT
followed by LP) if this life-threatening disorder remains in the
differential diagnosis based on the history.

Jonathan A. Edlow,
MD
Associate Chief, Department of Emergency Medicine, Beth Israel
Deaconess Medical Center
Assistant Professor of Medicine, Harvard Medical School

References

1. Edlow JA, Caplan LR. Avoiding pitfalls in the
diagnosis of subarachnoid hemorrhage. N Engl J Med.
2000;342:29-36.[ go to PubMed ]

2. Edlow JA. Diagnosis of subarachnoid hemorrhage
in the emergency department. Emerg Med Clin North Am.
2003;21:73-87.[ go to PubMed ]

3. Kowalski RG, Claassen J, Kreiter KT, et al.
Initial misdiagnosis and outcome after subarachnoid hemorrhage.
JAMA. 2004;291:866-9.[ go to PubMed ]

4. Karcz A, Holbrook J, Burke M, et al.
Massachusetts emergency medicine closed malpractice claims:
1988-1990. Ann Emerg Med. 1993;22:553-9.[ go to PubMed ]

5. Schievink WI, Karemaker JM, Hageman LM, van
der Werf DJ. Circumstances surrounding aneurysmal subarachnoid
hemorrhage. Surg Neurol. 1989;32:266-72.[ go to PubMed ]

6. Classification and diagnostic criteria for
headache disorders, cranial neuralgias and facial pain. Headache
Classification Committee of the International Headache Society.
Cephalalgia. 1988;8 Suppl 7:1-96.[ go to PubMed ]

7. Kassell NF, Torner JC, Haley EC Jr, Jane JA,
Adams HP, Kongable GL. The international cooperative study on the
timing of aneurysm surgery. Part 1: Overall management results. J
Neurosurg. 1990;73:18-36.[ go to PubMed ]

8. van der Wee N, Rinkel GJ, Hasan D, van Gijn J.
Detection of subarachnoid haemorrhage on early CT: is lumbar
puncture still needed after a negative scan? J Neurol Neurosurg
Psychiatry. 1995;58:357-9.[ go to PubMed ]

9. Edlow JA, Wyer PC. Evidence-based emergency
medicine/clinical question. How good is a negative cranial computed
tomographic scan result in excluding subarachnoid hemorrhage? Ann
Emerg Med. 2000;36:507-16.[ go to PubMed ]

10. van Gijn J, van Dongen K. The time course of
aneurysmal haemorrhage on computed tomograms. Neuroradiology.
1982;23:153-6.[ go to PubMed ]

11. Morgenstern LB, Luna-Gonzales H, Huber JC Jr,
et al. Worst headache and subarachnoid hemorrhage: prospective,
modern computed tomography and spinal fluid analysis. Ann Emerg
Med. 1998;32:297-304.[ go to PubMed ]

12. Shah KH, Edlow JA. Distinguishing traumatic
lumbar puncture from true subarachnoid hemorrhage. J Emerg Med.
2002;23:67-74.[ go to PubMed ]

13. Edlow JA, Bruner KS, Horowitz GL.
Xanthochromia. Arch Pathol Lab Med. 2002;126:413-15.[ go to PubMed ]

14. Graves P, Sidman R. Xanthochromia is not
pathognomonic for subarachnoid hemorrhage. Acad Emerg Med.
2004;11:131-5.[ go to PubMed ]

Tables

Table 1. "Cannot Miss" Causes of Headache.
[Diseases or conditions that are both treatable and, if untreated,
are life, limb, brain, or vision threatening.]

Subarachnoid hemorrhage

Meningitis and encephalitis

Cervico-cranial artery dissections

Temporal arteritis

Acute narrow angle closure glaucoma

Hypertensive emergencies

Carbon monoxide poisoning

Pseudotumor cerebri

Cerebral venous and dural sinus
thrombosis

Acute strokes: hemorrhagic or
ischemic

Pituitary apoplexy

Mass lesions

    Tumor

    Abscess

    Intracranial
hematomas (parenchymal, subdural, epidural)

    Parameningeal
infections

    Colloid cyst of
3rd ventricle

Table 2. Incorrect Diagnoses Assigned to
Patients with SAH

No diagnosis made, or headache of unknown
etiology

Primary headache disorders: migraine,
tension, or cluster headaches

Meningitis and encephalitis

Systemic infection: flu, gastroenteritis,
viral syndrome

Stroke or cerebral ischemia

Hypertensive crisis

Cardiovascular diagnosis: rule out MI,
arrhythmia, or syncope

Sinus-related headache

Neck problems: cervical disc disease or
arthritis

Psychiatric diagnosis: including
malingering and alcohol intoxication

Trauma-related

Back pain

Figures

Figure 1. Regular Angiography of Posterior
Communicating Artery Aneurysm (arrow).


Figure 2. One Tube of Xanthochromic Fluid
(left) Compared to Normal CSF.