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Red flags in patients presenting with headache: clinical indications for neuroimaging

¹ Department of Radiology, University Putra Malaysia-Hospital Kuala Lumpur, ² Department of Radiology, Mater Childrens Hospital, Brisbane, Australia and ³ Department of Medicine, International Medical University, Malaysia

	Abstract

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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 =0.76).

	Introduction

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Headache is one of the most common medical complaints. Perkins noted that about 10% of patients with headaches seen in the emergency departments were due to secondary causes, which may sometimes be overlooked [1]. While primary headache is more common, there is a high level of anxiety amongst both patients and physicians that a particular headache may be due to a secondary cause. The incidental discovery of a significant lesion associated with symptoms thought to be a primary headache is not uncommon; aneurysm occurs in approximately 2–5%, brain tumour 1% and arteriovenous malformation 0.8% [2].

Neuroimaging with CT and MRI are the most important investigations for headache. However, these investigations are expensive, are not without risk to the patient and medicolegal concerns also influence decision-making in some communities. We believe it to be important to establish a set of appropriate selection criteria for consideration as part of the investigation work-up before neuroimaging is performed.

"Red flag" features are those signs or symptoms that may indicate headache with a serious cause [3]. In the diagnosis of headache most patients with organic or vascular disease that benefit from neuroimaging have been shown to demonstrate clinical features that would raise a red flag [4–6].

Although there have been some studies to identify criteria that increase the yield of neuroimaging, no specific studies have been carried out to discover which red flag features would identify patients with headache who would benefit from neuroimaging.

This study aims to establish a clinical screening tool for patients who present with headache. We hope to show that identification of red flags can help select patients for neuroimaging, improve positive pick-up rates, avoid delay in diagnosis and treatment, and in the long run may help conserve scarce health funds.

	Methods and materials

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A retrospective study of all patients identified on the Department of Radiology computerized database who presented at Hospital Universiti Sains Malaysia, Kelantan with headache and who underwent neuroimaging during the 12-month period from January to December 1999 was undertaken. We identified patients by choosing those with "headache" as the main indication on the neuroimaging request. Patients with known underlying central nervous system disorder were excluded. Medical records were reviewed to identify patients with one or more of 20 baseline variables called "red flags". The list of red flags in diagnosis of headache used in this study is adapted from Cleveland Clinic Headache Centre (1998) (Table 1).

Results were analysed using SPSS version 9.0 (Chicago, IL). Confidence intervals of 95% and p-value of <0.05 were considered statistically significant. Logistic regression analysis was used to determine the association between each red flag feature and outcome.

Sensitivity and specificity 2 x 2 table was used to identify the cut-off number of red flags. Receiver operating characteristic (ROC) curve (a plot of sensitivity versus one minus specificity, where the area under the curve determines the sensitivity of the diagnostic test) was then used to show the sensitivity of the diagnostic test. The point where both sensitivity and specificity are optimum was taken as the cut-off point.

	Results

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111 patients who complained of headache and complied with the selection criteria were identified from the computerized radiology database between January 1999 and December 1999.

The age ranged from 7 years to 73 years and the mean age was 31.42±17.77 years. Males represented 44.14% of the group (n=49) with mean age of 29.41±2.36 years, and females represented 55.86% (n=62) with mean age of 33.02±2.37 years. Patients presented either with single or multiple red flags with a maximum of five.

There were 39 patients with abnormal radiological findings, while the rest were interpreted as normal. The onset of new or different headache was the most common red flag feature, presenting in 57.7% (n=64). Nausea or vomiting occurred in 29.7% (n=33) and "worst headache ever experienced" in 28.8% (n=32) (Table 1).

Significant linear correlation was seen with five red flag features, these were:

1. Papilloedema
   
2. Drowsiness, confusion, memory impairment or loss of consciousness (LOC)
   
3. Paralysis
   
4. Asymmetrical pupillary response
   
5. Progressive visual or neurological changes.
   

A positive correlation, with p-value of less than 0.05, after multivariate regression analysis was seen in only three out of the five patients with red flag features (Table 2).

1. Papilloedema
   
2. Drowsiness, confusion, memory impairment or LOC and
   
3. Paralysis.
   

From the ROC curve, the cut-off point that is optimally derived from the sensitivity and specificity 2 x 2 table is red flags of 3 (Figure 1).

View larger version (14K): [in this window] [in a new window]   Figure 1. Receiver operating characteristic (ROC) curve. This graph plots sensitivity vs 1-specificity giving rise to ROC curve. The graph shows area under the curve=0.76. Red flag=3 (point=0.62) represents the cut-off point (both sensistivity and specificity are optimum derived from specificity and sensitivity 2 x 2 table).

	Discussion

Top Abstract Introduction Methods and materials Results Discussion Conclusion References

Paralysis is an important sign of intracranial disease [1, 7, 8]. A wide range of causes for paralysis was seen, including primary brain tumours, tuberculosis meningitis, infarction, carotico-cavernous fistula and bleeding aneurysm. Most had paralysis of the upper or lower limbs while some presented with diplopia. 10 out of 15 patients presented with paralysis and a headache had been shown to have abnormal neuroimaging.

Papilloedema indicates increased intracranial pressure and its importance in pointing to the presence of an intracranial lesion has previously been proven [9]. Up to 38% of patients with a primary brain tumour may show this sign [7]. However, we were unable to find a study that demonstrates the relationship between headache and papilloedema as an indicator of intracranial neuropathology.

The group of symptoms; drowsiness, confusion, memory impairment or loss of consciousness was the third significant red flag in this study and were considered together as they signify reduction in conscious level [10, 11]. Of 13 patients with this feature in our study, 9 were noted to have abnormal neuroimaging findings.

Other red flags when individually analysed did not reach statistical significance. We found that neither age nor sex of the patients was statistically significant, and this was taken into account during analysis.

The percentage of positive neuroimaging outcomes was higher among males (41%), than females (31%), and this finding was similar to a study by Ramirez-Lassepas et al [12]. However, it was not statistically significant. Primary headache has previously been shown to be more common in females and some studies show up to 3:1 female to male ratio for migraine [13, 14]. In our study, only a small difference (44%:56%) in the incidence of headache between males and females was shown. This difference is likely to be due to our sample population, which was not randomized, and therefore not representative of headache in the general population.

Headache at the extremes of age are usually significant [14] and patients older than 55 have been shown to have a higher incidence of neuropathology [12]. Our sample however, contained a high proportion of young patients with only 10% greater than 50 years.

The importance of progression of symptoms was examined, but this can be difficult to elicit in some cases, as they can sometimes be insidious. Progressive refractive changes can cause vision deterioration and it can be associated with headache. Therefore this sign can be misleading. However, 55% of our patients with history of progressive deterioration of vision had positive neuroimaging.

Both patients with pupil asymmetry showed intracranial abnormalities on neuroimaging, the number of patients (n=2) 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 vestibulocochlear 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 extracranial, this feature could possibly be excluded from the list of red flags.

It was interesting to note that a change in the type or pattern of headaches was considered important by the requesting clinicians, and was the most common reason 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 headache, a worst headache ever experienced and onset of headache with exertion, sexual activity or coughing. We found however, that this group of red flags individually did not show any statistical significance.

Nausea and/or vomiting is a recognized feature of raised intracranial pressure and has been reported in up to 68% of patients [7, 8]. In our study, 45% of patients that presented with nausea and vomiting associated with headache were positive on neuroimaging. However, this did not reach statistical significance as an isolated sign.

From the ROC curve and 2 x 2 sensitivity and specificity table, the cut-off point at red flags of three represents the highest value for both sensitivity and specificity of the diagnostic test. The area below the curve is equal to 0.76 calculated using trapezoidal rules [18]. Therefore, the curve is sensitive and the red flag number of three should be considered as strong indicator for predicting positive neuroimaging. We concluded from this study that the presence of at least any of three red flag features is the optimum to predict positive neuroimaging in headache patients. Those who have three or more red flag features should undergo prompt neuroimaging to look for secondary causes of headache.

A review of the literature failed to provide well-studied list of red flags in patients with headache, in which neuroradiological testing would have high diagnostic yield. To our knowledge, this study is a pioneer in trying to use red flag features as a screening tool for neuroimaging in identifying patients with headache due to serious underlying pathology.

	Conclusion

Top Abstract Introduction Methods and materials Results Discussion Conclusion References

 
This study reveals three statistically significant red flag features in predicting abnormal neuroimaging in patients with headache. They were paralysis, reduced conscious level and papilloedema. Patients with headache who have three or more red flag features should have a prompt neuroimaging study.

A large multicentre prospective study would be helpful to identify the significant red flag features. Scoring according to the weighting of its significance would pave the way to a more detailed and reliable scoring system.

	Footnotes

 
Current address for Sobri M, Department of Radiology, UPM-HKL, Jalan Masjid, 50586 Kuala Lumpur, Malaysia.

Received for publication August 5, 2002. Revision received April 28, 2003. Accepted for publication May 9, 2003.

	References

Top Abstract Introduction Methods and materials Results Discussion Conclusion References

 

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