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The British Journal of Radiology, 76 (2003), 532–535 E 2003 The British Institute of Radiology

DOI: 10.1259/bjr/89012738

Red flags in patients presenting with headache: clinical


indications for neuroimaging
1
SOBRI M, MRad(USM), 2A C LAMONT, FRCR, 1N A ALIAS, MRad(UKM) and 3M N WIN, FRCP
1
Department of Radiology, University Putra Malaysia-Hospital Kuala Lumpur, 2Department of Radiology, Mater Childrens
Hospital, Brisbane, Australia and 3Department of Medicine, International Medical University, Malaysia

Abstract. Headache is a very common patient complaint but secondary causes for headache are unusual.
Neuroimaging is both expensive and has a low yield in this group. Most patients with intracranial pathology
have clinical features that would raise a ‘‘red flag’’. Appropriate selection of patients with headache for
neuroimaging to look for secondary causes is very important. Red flags act as screening tools to help in
identifying those patients presenting with headache who would benefit from prompt neuroimaging, and may
increase the yield. The aim of this study is to evaluate clinical features in patients with headache using
neuroimaging as a screening tool for intracranial pathology. 20 red flags were defined. A retrospective study of
111 patients was performed and the outcomes were divided into positive and negative. Abnormal neuroimaging
was present in 39 patients. Results were analysed using the Logistic Regression model. Sensitivity and specificity
of red flags were analysed to establish the cut-off point to predict abnormal neuroimaging and a receiver
operating characteristic (ROC) curve plotted to show the sensitivity of the diagnostic test. Three red flag
features proved to be statistically significant with the p-value of less than 0.05 on both univariate and
multivariate analysis. These were: paralysis; papilloedema; and ‘‘drowsiness, confusion, memory impairment
and loss of consciousness’’. In addition, if three or more red flags from the list were present, this showed strong
indication of abnormal neuroimaging, from cut-off point of ROC curve (area under the curve 50.76).

Headache is one of the most common medical features would identify patients with headache who would
complaints. Perkins noted that about 10% of patients benefit from neuroimaging.
with headaches seen in the emergency departments were This study aims to establish a clinical screening tool for
due to secondary causes, which may sometimes be over- patients who present with headache. We hope to show that
looked [1]. While primary headache is more common, identification of red flags can help select patients for
there is a high level of anxiety amongst both patients and neuroimaging, improve positive pick-up rates, avoid delay
physicians that a particular headache may be due to a in diagnosis and treatment, and in the long run may help
secondary cause. The incidental discovery of a significant conserve scarce health funds.
lesion associated with symptoms thought to be a primary
headache is not uncommon; aneurysm occurs in approxi-
mately 2–5%, brain tumour 1% and arteriovenous malfor- Methods and materials
mation 0.8% [2].
A retrospective study of all patients identified on the
Neuroimaging with CT and MRI are the most important
Department of Radiology computerized database who
investigations for headache. However, these investigations
presented at Hospital Universiti Sains Malaysia, Kelantan
are expensive, are not without risk to the patient and
with headache and who underwent neuroimaging during
medicolegal concerns also influence decision-making
the 12-month period from January to December 1999 was
in some communities. We believe it to be important to
undertaken. We identified patients by choosing those with
establish a set of appropriate selection criteria for con-
‘‘headache’’ as the main indication on the neuroimaging
sideration as part of the investigation work-up before request. Patients with known underlying central nervous
neuroimaging is performed. system disorder were excluded. Medical records were
‘‘Red flag’’ features are those signs or symptoms that reviewed to identify patients with one or more of 20
may indicate headache with a serious cause [3]. In the baseline variables called ‘‘red flags’’. The list of red flags in
diagnosis of headache most patients with organic or diagnosis of headache used in this study is adapted from
vascular disease that benefit from neuroimaging have been Cleveland Clinic Headache Centre (1998) (Table 1).
shown to demonstrate clinical features that would raise a All patients received one or more investigation with either
red flag [4–6]. CT, MRI or cerebral angiography. Axial 5 mm/10 mm
Although there have been some studies to identify section CT Scan was performed using Siemens. Somatom
criteria that increase the yield of neuroimaging, no specific HiQ-s (Erlangen, Germany). MRI was performed using 1.0
studies have been carried out to discover which red flag Tesla Signa Horizon Lx General Electronic (Milwaukee,
WI). Axial and sagittal T1 weighted spin-echo, axial T2
Received 5 August 2002 and in revised form 28 April 2003, accepted 9 weighted fast spin-echo, axial fluid attenuated inversion
May 2003. recovery (FLAIR) and MR angiography (MRA) were
Current address for Sobri M, Department of Radiology, UPM-HKL, routine and gadolinium given when indicated. Catheter
Jalan Masjid, 50586 Kuala Lumpur, Malaysia. angiography was performed using Sigma 16 inch General

532 The British Journal of Radiology, August 2003


Red flags in patients with headache

Table 1. List of red flags and their frequencies

Red flag Frequency Percentage


Onset of new or different headache 64 57.7
Nausea or vomiting 33 29.7
Worst headache ever experience 32 28.8
Progressive visual or neurological changes 20 18.0
Paralysis 15 13.5
Weakness, ataxia or loss of co-ordination 14 12.6
Drowsiness, confusion, memory impairment or loss of consciousness 13 11.7
Onset of headache after age of 50 years 12 10.8
Papilloedema 10 9.0
Stiff neck 6 5.4
Onset of headache with exertion, sexual activity or coughing 6 5.4
Systemic illness 5 4.5
Numbness 4 3.6
Asymmetry of pupillary response 2 1.8
Sensory loss 1 0.9
Signs of meningeal irritation 1 0.9

Electric Digital Subtraction Angiography using either 5 after multivariate regression analysis was seen in only three
French Head-Hunter or MANI catheter. out of the five patients with red flag features (Table 2).
Results were analysed using SPSS version 9.0 (Chicago,
(1) Papilloedema
IL). Confidence intervals of 95% and p-value of ,0.05
(2) Drowsiness, confusion, memory impairment or LOC
were considered statistically significant. Logistic regression
and
analysis was used to determine the association between
(3) Paralysis.
each red flag feature and outcome.
Sensitivity and specificity 262 table was used to identify Of the 20 red flag features used, 4 features were not seen
the cut-off number of red flags. Receiver operating in any patient in this study population: weight loss; tender
characteristic (ROC) curve (a plot of sensitivity versus poorly pulsatile temporal arteries; recurrent lymphadeno-
one minus specificity, where the area under the curve pathy; and persistent tinnitus.
determines the sensitivity of the diagnostic test) was then From the ROC curve, the cut-off point that is optimally
used to show the sensitivity of the diagnostic test. The derived from the sensitivity and specificity 262 table is red
point where both sensitivity and specificity are optimum flags of 3 (Figure 1).
was taken as the cut-off point.

Discussion
Results
We selected a broad set of 20 different red flags for this
111 patients who complained of headache and complied study and three were found to have a strong positive
with the selection criteria were identified from the predictive value. They were onset of paralysis, presence of
computerized radiology database between January 1999 papilloedema and ‘‘onset of a combination of confusion,
and December 1999. drowsiness, memory loss and LOC’’. Any one of these is
The age ranged from 7 years to 73 years and the mean sufficient indication for performing advanced imaging
age was 31.42¡17.77 years. Males represented 44.14% of investigations.
the group (n549) with mean age of 29.41¡2.36 years, and Paralysis is an important sign of intracranial disease
females represented 55.86% (n562) with mean age of [1, 7, 8]. A wide range of causes for paralysis was seen,
33.02¡2.37 years. Patients presented either with single or including primary brain tumours, tuberculosis meningitis,
multiple red flags with a maximum of five. infarction, carotico-cavernous fistula and bleeding aneurysm.
There were 39 patients with abnormal radiological Most had paralysis of the upper or lower limbs while
findings, while the rest were interpreted as normal. The some presented with diplopia. 10 out of 15 patients presented
onset of new or different headache was the most common with paralysis and a headache had been shown to have
red flag feature, presenting in 57.7% (n564). Nausea or abnormal neuroimaging.
vomiting occurred in 29.7% (n533) and ‘‘worst headache Papilloedema indicates increased intracranial pressure and
ever experienced’’ in 28.8% (n532) (Table 1). its importance in pointing to the presence of an intracranial
Significant linear correlation was seen with five red flag
features, these were: Table 2. Red flags with p-value less than 0.05 on multivariate
regression analysis
(1) Papilloedema
(2) Drowsiness, confusion, memory impairment or loss of Variable p-value
consciousness (LOC)
(3) Paralysis Papilloedema 0.0124
(4) Asymmetrical pupillary response Drowsiness, confusion, memory 0.0069
impairment or loss of consciousness
(5) Progressive visual or neurological changes.
Paralysis 0.0190
A positive correlation, with p-value of less than 0.05,

The British Journal of Radiology, August 2003 533


Sobri M, A C Lamont, N A Alias and M N Win

Both patients with pupil asymmetry showed intracranial


abnormalities on neuroimaging, the number of patients
(n52) was too low for statistical evaluation.
Four red flag features that we looked for did not occur
in this series; weight loss, tinnitus, tender temporal arteries
and recurrent lymphadenopathy. Weight loss associated
with headache has previously been noted as a feature in
brain tumour patients [7]. Although not a single patient
in this study had persistent tinnitus, it is nevertheless
considered an important sign as it can be due to vesti-
bulocochlear disease and associated with headache. Tender
poorly pulsatile temporal arteries are seen in temporal
arteritis, which is more common among females after
the 5th decade [15]. The headache is characteristic with
unilateral tenderness over the temporal artery region.
Neuroimaging is negative in this condition and we feel that
because the signs are characteristic, and as the pathology is
Figure 1. Receiver operating characteristic (ROC) curve. This extracranial, this feature could possibly be excluded from
graph plots sensitivity vs 12specificity giving rise to ROC the list of red flags.
curve. The graph shows area under the curve50.76. Red It was interesting to note that a change in the type or
flag53 (point50.62) represents the cut-off point (both sensis- pattern of headaches was considered important by the
tivity and specificity are optimum derived from specificity and requesting clinicians, and was the most common reason
sensitivity 262 table). for requesting neuroimaging [16, 17]. Similar findings are
noted in this study. There were three red flag features
within this group. They were onset of new or different
lesion has previously been proven [9]. Up to 38% of patients headache, a worst headache ever experienced and onset of
with a primary brain tumour may show this sign [7]. headache with exertion, sexual activity or coughing. We
However, we were unable to find a study that demonstrates found however, that this group of red flags individually
the relationship between headache and papilloedema as an did not show any statistical significance.
indicator of intracranial neuropathology. Nausea and/or vomiting is a recognized feature of raised
The group of symptoms; drowsiness, confusion, memory intracranial pressure and has been reported in up to 68%
impairment or loss of consciousness was the third signi- of patients [7, 8]. In our study, 45% of patients that
ficant red flag in this study and were considered together presented with nausea and vomiting associated with
as they signify reduction in conscious level [10, 11]. Of 13 headache were positive on neuroimaging. However, this
patients with this feature in our study, 9 were noted to did not reach statistical significance as an isolated sign.
have abnormal neuroimaging findings. From the ROC curve and 262 sensitivity and specificity
Other red flags when individually analysed did not reach table, the cut-off point at red flags of three represents the
statistical significance. We found that neither age nor sex highest value for both sensitivity and specificity of the
of the patients was statistically significant, and this was diagnostic test. The area below the curve is equal to 0.76
taken into account during analysis. calculated using trapezoidal rules [18]. Therefore, the curve
The percentage of positive neuroimaging outcomes was is sensitive and the red flag number of three should be
higher among males (41%), than females (31%), and this considered as strong indicator for predicting positive
finding was similar to a study by Ramirez-Lassepas et al neuroimaging. We concluded from this study that the
[12]. However, it was not statistically significant. Primary presence of at least any of three red flag features is the
headache has previously been shown to be more common optimum to predict positive neuroimaging in headache
in females and some studies show up to 3:1 female to male patients. Those who have three or more red flag features
ratio for migraine [13, 14]. In our study, only a small should undergo prompt neuroimaging to look for secondary
difference (44%:56%) in the incidence of headache between causes of headache.
males and females was shown. This difference is likely to A review of the literature failed to provide well-studied
be due to our sample population, which was not random- list of red flags in patients with headache, in which
ized, and therefore not representative of headache in the neuroradiological testing would have high diagnostic yield.
general population. To our knowledge, this study is a pioneer in trying to use
Headache at the extremes of age are usually significant red flag features as a screening tool for neuroimaging in
[14] and patients older than 55 have been shown to have a identifying patients with headache due to serious under-
higher incidence of neuropathology [12]. Our sample lying pathology.
however, contained a high proportion of young patients
with only 10% greater than 50 years.
The importance of progression of symptoms was
Conclusion
examined, but this can be difficult to elicit in some cases, This study reveals three statistically significant red flag
as they can sometimes be insidious. Progressive refractive features in predicting abnormal neuroimaging in patients
changes can cause vision deterioration and it can be asso- with headache. They were paralysis, reduced conscious
ciated with headache. Therefore this sign can be misleading. level and papilloedema. Patients with headache who have
However, 55% of our patients with history of progressive three or more red flag features should have a prompt
deterioration of vision had positive neuroimaging. neuroimaging study.

534 The British Journal of Radiology, August 2003


Red flags in patients with headache

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Ann Emerg Med 1989;18:1199–205.
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