10
Adults and Children with Headache: Evidence-Based Role of Neuroimaging
L. Santiago Medina, Amisha Shah, and Elza Vasconcellos
I. Which adults with new-onset headache should undergo neuroimaging?
II. What neuroimaging approach is most appropriate in adults with new-onset headache?
III. What is the role of neuroimaging in adults with migraine or chronic headache?
IV. What is the role of imaging in patients with headache and subarachnoid hemorrhage suspected of having an intracranial aneurysm?
V. What is the recommended neuroimaging examination in adults with headache and known primary neoplasm suspected of having brain metastases?
VI. When is neuroimaging appropriate in children with headache?
VII. What is the sensitivity and specificity of computed tomography and magnetic resonance imaging?
VIII. What is the cost-effectiveness of neuroimaging in patients with headache?
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Issues
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In adults, benign headache disorders usually start before the age of 65 years. Therefore, in patients older than 65 years, secondary causes should be suspected.
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Although most headaches in children are benign in nature, a small percentage is caused by serious diseases, such as brain neoplasm.
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Computed tomography (CT) imaging remains the initial test of choice for (1) new-onset headache in adults and (2) headache suggestive of subarachnoid hemorrhage (limited evidence).
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Neuroimaging is recommended in adults with nonacute headache and unexplained abnormal neurologic examination (moderate evidence).
Key Points
Definition and Pathophysiology
Headaches can be divided into primary and secondary (Table 10.1).
Primary causes include migraine, cluster, and tension-type headache dis- orders, and secondary etiologies include neoplasms, arteriovenous mal- formations, aneurysm, infection and hydrocephalus. Diagnosis of primary headache disorders is based on clinical criteria as set forth by the Interna- tional headache Society (1). Neuroimaging should aid in the diagnosis of secondary headache disorders.
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Computed tomography angiography and magnetic resonance (MR) angiography have sensitivities greater than 85% for aneurysms greater than 5 mm. The sensitivity of these two examinations drops signifi- cantly for aneurysms less than 5 mm (moderate evidence).
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In adults with headache and known primary neoplasm suspected of having brain metastatic disease, MR imaging with contrast is the neuroimaging study of choice (moderate evidence).
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Neuroimaging is recommended in children with headache and an abnormal neurologic examination or seizures (moderate evidence).
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Sensitivity and specificity of MR imaging is greater than CT for intracranial lesions. For intracranial surgical space-occupying lesions, however, there is no difference in diagnostic performance between MR imaging and a CT (limited evidence).
Table 10.1. Common causes of primary and secondary headache
Primary headaches Migraine Cluster Tension-type Secondary headaches
Intracranial space occupying lesions Neoplasm
Arteriovenous malformation Abscess
Hematoma
Cerebrovascular disease Intracranial aneurysms Occlusive vascular disease Infection
Sinusitis Meningitis Encephalitis Inflammation
Vasculitis
Acute disseminated encephalomyelitis Increased intracranial pressure
Hydrocephalus Pseudotumor cerebri
Epidemiology
Adults
Headache is a very common symptom among adults, accounting for 18 million (4%) of the total outpatient visits in the United States each year (2).
In any given year, more than 70% of the U.S. population has a headache (3). An estimated 23.6 million people in the U.S. have migraine headaches (4,5).
In the elderly population, 15% of patients 65 years or older, versus 1%
to 2% of patients younger than 65 years, presented with secondary headache disorders such as neoplasms, strokes, and temporal arteritis (4,6).
Brain metastases are the most common intracranial tumors, far outnum- bering primary brain neoplasms (7). Approximately 58% of primary brain neoplasms in adults are malignant (7). Common primary malignant neo- plasms include astrocytomas and glioblastomas (7). Benign brain tumors account for 38% of primary brain neoplasms (7). Despite being benign, they may have aggressive characteristics causing significant morbidity and mortality (7). Meningioma is the most common type (7).
Children
In approximately 50% of patients with migraines, the headache disorder starts before the age of 20 years (4). In the U.S., adolescent boys and girls have a headache prevalence of 56% and 74%, and a migraine prevalence of 3.8% and 6.6%, respectively (2). A small percentage of headaches in chil- dren are secondary in nature.
A primary concern in children with headache is the possibility of a brain tumor (8,9). Although brain tumors constitute the largest group of solid neoplasms in children and are second only to leukemia in overall fre- quency of childhood cancers, the annual incidence is low at 3 in 100,000 (9). Primary brain neoplasms are far more prevalent in children than they are in adults (10). They account for almost 20% of all cancers in children but only 1% of cancers in adults (4). Central nervous system (CNS) tumors are the second cause of cancer-related deaths in patients younger than 15 years (11).
Overall Cost to Society
The prevalence of migraine is highest in the peak productive years of life between the ages of 25 and 55 years (12,13). The direct and indirect annual cost of migraine has been estimated at more than $5.6 billion (14).
Goals of Neuroimaging
• Diagnose the secondary causes of headache (Table 10.1) so that appro- priate treatment can be instituted.
• Exclude secondary etiologies of headache in patients with atypical primary headache disorders.
• Decrease the risk of brain herniation prior to lumbar puncture by exclud-
ing intracranial space occupying lesions.
Methodology
A Medline search was conducted using Ovid (Wolters Kluwer, New York, New York) and PubMed (National Library of Medicine, Bethesda, Mary- land). A systematic literature review was performed from 1966 through August 2003. Keywords included (1) headache, (2) cephalgia, (3) diagnostic imaging, (4) clinical examination, (5) practice guidelines, and (6) surgery.
I. Which Adults with New-Onset Headache Should Undergo Neuroimaging?
Summary of Evidence: The most common causes of secondary headache in adults are brain neoplasms, aneurysms, arteriovenous malformations, intracranial infections, and sinus disease. Several history and physical examination findings may increase the yield of the diagnostic study dis- covering an intracranial space-occupying lesion in adults. Table 10.2 shows the scenarios that should warrant further diagnostic testing (limited evi- dence) (3,4,15). The factors outlined in Table 10.2 increase the pretest prob- ability of finding a secondary headache disorder.
II. What Neuroimaging Approach Is Most Appropriate in Adults with New-Onset Headache?
Summary of Evidence: The data reviewed demonstrate that 11% to 21% of patients presenting with new-onset headache have serious intracranial pathology (moderate and limited evidence) (4,16,17). Computed tomogra- phy (CT) examination has been the standard of care for the initial evalua- tion of new-onset headache because CT is faster, more readily available, less costly than magnetic resonance imaging (MRI), and less invasive than lumber puncture (4). In addition, CT has a higher sensitivity than MRI for subarachnoid hemorrhage (SAH) (18,19). Unless further data become available that demonstrate higher sensitivity of MRI, CT is recommended in the assessment of all patients who present with new-onset headache (limited evidence) (4). Lumbar puncture is recommended in those patients in which the CT scan is nondiagnostic and the clinical evaluation reveals abnormal neurologic findings, or in those patients in whom SAH is strongly suspected (limited evidence) (4). Figure 10.1 is a suggested deci- sion tree to evaluate adult patients with new-onset headache.
Supporting Evidence for Clinical Guidelines and Neuroimaging in New-Onset Headache: Duarte and colleagues (16) studied 100 consecutive patients over Table 10.2. Suggested guidelines for neuroimaging in adult patients with new-onset headache
First or worst headache
Increased frequency and increased severity of headache New-onset headache after age 50
New-onset headache with history of cancer or immunodeficiency Headache with fever, neck stiffness, and meningeal signs Headache with abnormal neurologic examination
a 1-year period (moderate evidence). Inclusion criteria included patients admitted to the neurology unit with recent onset of headache. Recent onset of headache was defined by the authors as persistent headache of less than 1 year’s duration. All the patients studied had an unenhanced and enhanced CT. Lumbar puncture, MRI, and MR angiogram were performed in selected cases. Tumors were identified in 21% of the patients, which com- prised 16% of the patients with a negative neurologic examination.
A smaller-scale prospective study examined the association of acute headache and SAH (limited evidence) (20). All patients were examined using state-of-the art CT. Patients had a mean headache duration of approximately 72 hours (20). Of the 27 patients studied, 20 had a negative CT and four were diagnosed with SAH. Among the remaining three patients, one had a frontal meningioma, another had a hematoma associ- ated with SAH, and the other had diffuse meningeal enhancement caused by bacterial meningitis. Lumbar puncture was performed in 19 of the patients with negative CT, yielding five additional cases of SAH. Hence, CT did not demonstrate SAH in five of nine patients.
A retrospective study of 1111 patients with acute headache who had CT
evaluation found 120 (10.8%) abnormalities, including hemorrhage, infarct,
and neoplasm (limited evidence) (17). All imaging studies were done at
two teaching institutions over a 3-year period. There were statistical dif-
ferences in the percentage of intracranial lesions based on the setting in
which the CT was ordered. The inpatient rate (21.2%) was twice that of
Figure 10.1. Decision tree for use in adults with new-onset headache. For those patients who meet any of the guidelines in Table 10.2, computed tomography (CT) is suggested. For patients who do not meet these criteria or those with negative diagnostic workup, clinical observation with periodic reassessment is recom- mended. If CT is positive, further workup with CT angiography or magnetic reso- nance imaging (MRI) plus MR angiography is recommended. In selected case, conventional angiography and endovascular treatment may be warranted. If CT is negative, lumbar puncture is advised. In patients with suspected metastatic brain disease, contrast-enhanced MRI is recommended. In patients with suspected intracranial aneurysm, further assessment with CT angiography or MR angiogra- phy is warranted. CTA, CT angiography; LP, lumbar puncture; MRA, MR angiog- raphy. [Source: Medina et al. (29), with permission from Elsevier.]emergency patients (11.7%) and three times more than outpatients (6.9%;
p < .005). Of 155 CT studies performed for headache as the sole presenting symptom (14.0%), nine (5.8%) patients had acute intracranial abnormali- ties. One study in the outpatient setting that studied 726 patients with new headaches found no serious intracranial disease (limited evidence) (6). The difference in prevalence of disease among emergency patients, inpatients, and outpatients is probably related to patient selection bias.
III. What Is the Role of Neuroimaging in Adults with Migraine or Chronic Headache?
Summary of Evidence: Most of the available literature (moderate and limited evidence) suggests that there is no need for neuroimaging in patients with migraine and normal neurologic examination. Neuroimag- ing is indicated in patients with nonacute headache and unexplained abnormal neurologic examination, or in patients with atypical features or headache that does not fulfill the definition of migraine.
Supporting Evidence: Evidence-based guidelines on the use of diagnostic imaging in patients presenting with migraine have been developed by a multispecialty group called the U.S. Headache Consortium (21). Data were examined from 28 studies (moderate and limited evidence), six not blinded prospective and 22 retrospective studies. The specific recommendations from the U.S. Headache Consortium were (1) neuroimaging should be con- sidered in patients with nonacute headache and unexplained abnormal findings on the neurologic examination, (2) neuroimaging is not usually warranted in patients with migraine and normal findings on neurologic examination, and (3) a lower threshold for CT or MRI may be applicable in patients with atypical features or with headache that do not fulfill the definition of migraine.
The study by Joseph and colleagues (22) (limited evidence) in 48 headache patients found five patients with neoplasms and one with an arteriovenous malformation. Of these patients, five had physical signs and one had headache on exertion. Weingarten and colleagues (23) (limited evi- dence) extrapolated data from 100,800 adult patients enrolled in a health maintenance organization and estimated that, in patients with chronic headache and a normal neurologic examination, the chance of finding abnormalities on CT requiring neurosurgical intervention were as low as 0.01% (1 in 10,000).
In 1994, the American Academy of Neurology provided a summary
statement on the use of neuroimaging in patients with headache and a
normal neurologic examination based on a review of the literature (mod-
erate and limited evidence) (24). It concluded that routine imaging “in
adult patients with recurrent headaches that have been defined as
migraine—including those with visual aura—with no recent change in
pattern, no history of seizures, and no other focal neurologic signs of symp-
toms . . . is not warranted (4)”. This statement was based on a 1994 litera-
ture review by Frishberg (25) of 17 articles published between 1974 and
1991 that were limited to studies with more than 17 subjects per study
(moderate evidence). All patients had normal neurologic examinations. Of
897 CT or MRI studies performed in patients with migraine, only three
tumors and one arteriovenous malformation were noted, resulting in a yield of 0.4% (4 in 1000). The summary statement mentions, however, that
“patients with atypical headache patterns, a history of seizure, or focal neu- rological signs or symptoms, CT or MRI may be indicated” (4,24).
IV. What Is the Role of Imaging in Patients with Headache and Subarachnoid Hemorrhage Suspected of Having an Intracranial Aneurysm?
Summary of Evidence: In North America, 80% to 90% of nontraumatic SAH is caused by the rupture of nontraumatic cerebral aneurysms (26). Com- puted tomography angiography and MR angiography have sensitivities greater than 85% for aneurysms greater than 5 mm. The sensitivity of these two examinations drops significantly for aneurysms less than 5 mm.
Supporting Evidence: White et al. (27) searched the literature from 1988 through 1998 to find studies with 10 or more subjects in which the con- ventional angiography results were compared with noninvasive imaging.
They included 38 studies that scored more than 50% on evaluation criteria by using intrinsically weighted standardized assessment to determine suit- ability for inclusion (moderate evidence). The rates of aneurysm accuracy for CT angiography and MR angiography were 89% and 90%, respectively.
The study showed greater sensitivity for aneurysms larger than 3 mm than for aneurysms 3 mm or smaller for CT angiography (96% verses 61%) and for MR angiography (94% versus 38%).
White et al. (28) also performed a prospective blinded study in 142 patients who underwent intraarterial digital subtraction angiography to detect aneurysms (moderate evidence). Results were compared with CT angiography and MR angiography. The accuracy rates per patient for the best observer were 87% and 85% for CT angiography and MR angiogra- phy, respectively. The accuracy rates for brain aneurysm for the best observer were 73% and 67% for CT angiography and MR angiography, respectively. The sensitivity for the detection of aneurysms 5 mm or larger was 94% for CT angiography and 86% for MR angiography. For aneurysms smaller than 5 mm, sensitivities for CT angiography and MR angiography were 57% and 35%, respectively.
V. What Is the Recommended Neuroimaging Examination in Adults with Headache and Known Primary Neoplasm Suspected of Having Brain Metastases?
Summary of Evidence: In patients older than 40 years, with known primary neoplasm, brain metastasis is a common cause of headache (29). Most studies described in the literature suggest that contrast-enhanced MRI is superior to contrast-enhanced CT in the detection of brain metastatic disease, especially if the lesions are less than 2 cm (moderate evidence).
In patients with suspected metastases to the central nervous system, enhanced brain MRI is recommended.
Supporting Evidence: Davis and colleagues (30) (moderate evidence)
studied imaging studies in 23 patients that compared contrast-enhanced
MRI with double dose-contrast enhanced CT. Contrast-enhanced MRI demonstrated more than 67 definite or typical brain metastases. The double dose-delayed CT revealed only 37 metastatic lesions. The authors concluded that MRI with enhancement is superior to double dose-contrast enhanced CT scan for detecting brain metastasis, anatomic localization, and number of lesions.
Golfieri and colleagues (31) reported similar findings (moderate evidence). They studied 44 patients with small cell carcinoma to detect cerebral metastases. All patients were studied with contrast-enhanced CT scan and gadolinium-enhanced MRI. Of all patients, 43% had cerebral metastases. Both contrast-enhanced CT and gadolinium-enhanced MRI detected lesions greater than 2 cm. For lesions less than 2 cm, 9% were detected only by gadolinium-enhanced T1-weighted images. The authors concluded that gadolinium-enhanced T1-weighted images remain the most accurate technique in the assessment of cerebral metastases.
Sze and colleagues (32) performed prospective and retrospective studies in 75 patients (moderate evidence). In 49 patients, MRI and contrast- enhanced CT were equivalent. In 26 patients, however, results were dis- cordant, with neither CT nor MRI being consistently superior; MRI demonstrated more metastases in nine of these 26 patients, but contrast- enhanced CT better depicted lesions in eight of 26 patients.
VI. When Is Neuroimaging Appropriate in Children with Headache?
Summary of Evidence: Table 10.3 summarizes the neuroimaging guidelines in children with headaches. Theses guidelines reinforce the primary impor- tance of careful acquisition of the medical history and performance of a thorough examination, including a detailed neurologic examination (33).
Among children at risk for brain lesions based on these criteria, neuro- imaging with either MRI or CT is valuable in combination with close clinical follow-up (Fig. 10.2).
Supporting Evidence: In 2002 the American Academy of Neurology and Child Neurology Society published evidence-based neuroimaging recom- mendations for children (34). Six studies (one prospective and five retro- spective) met inclusion criteria (moderate evidence). Data on 605 of 1275 children with recurrent headache who underwent neuroimaging found only 14 (2.3%) with nervous system lesions that required surgical treat- ment. All 14 children had definite abnormalities on neurologic examina- tion. The recommendations from this study were as follows: (1)
Table 10.3. Suggested guidelines for neuroimaging in pediatric patients with headache
Persistent headaches of less than 1 month’s duration Headache associated with abnormal neurologic examination Headache associated with seizures
Headache with new onset of severe episodes or change in the type of headache Persistent headache without family history of migraine
Family or medical history of disorders that may predispose one to CNS lesions, and clinical or laboratory findings that suggest CNS involvement
Neuroimaging should be considered in children with an abnormal neuro- logic examination or other physical findings that suggest CNS disease.
Variables that predicted the presence of a space-occupying lesion included (a) headache of less than 1 month’s duration, (b) absence of family history of migraine, (c) gait abnormalities, and (d) occurrence of seizures. (2) Neu- roimaging is not indicated in children with recurrent headaches and a normal neurologic examination. (3) Neuroimaging should be considered in children with recent onset of severe headache, change in the type of headache, or if there are associated features suggestive of neurologic dysfunction.
Medina and colleagues (33) performed a 4-year retrospective study of 315 children with no known underlying CNS disease who underwent brain imaging for a chief complaint of headache (moderate evidence). All patients underwent brain MRI. Sixty-nine patients also underwent brain CT. Clinical data were correlated with findings from MRI and CT, and the final diagnosis, by means of logistic regression. Thirteen (4%) of patients had surgical space-occupying lesions—nine malignant neoplasms, three hemorrhagic vascular malformations, and one arachnoid cyst. Medina and colleagues identified seven independent multivariate predictors of a sur- gical lesion, the strongest of which were sleep-related headache [odds ratio 5.4, 95% confidence interval (CI): 1.7–17.5] and no family history of migraine (odds ratio 15.4, 95% CI: 5.8–41.0). Other predictors included vomiting, absence of visual symptoms, headache of less than 6 months’
duration, confusion, and abnormal neurologic examination findings. A positive correlation between the number of predictors and the risk of sur- gical lesion was noted (p < .0001). No difference between MRI and CT was noted in detection of surgical space-occupying lesions, and there were no false-positive or false-negative surgical lesions detected with either modal- ity on clinical follow-up.
Figure 10.2. Decision tree for use in children with headache. Neuroimaging is sug- gested for patients who meet any of the guidelines in Table 10.3. For patients who do not meet these criteria or those with negative findings from imaging studies, clinical observation with periodic reassessment is recommended. [Source: Medina et al. (33), with permission from the Radiological Society of North America.]
VII. What Is the Sensitivity and Specificity of Computed Tomography and Magnetic Resonance Imaging?
Summary of Evidence: The sensitivity and specificity of MRI are greater than those of CT for intracranial lesions. For surgical intracranial space- occupying lesions, however, there is no difference between MRI and CT in diagnostic performance.
Supporting Evidence: The sensitivity and specificity of CT and MRI for intracranial lesions are shown in Table 10.4. Medina and colleagues (33) (moderate evidence) showed that the overall sensitivity and specificity with MRI (92% and 99%, respectively) were higher than with CT (81% and 92%, respectively). Comparison of patients who underwent MRI and CT revealed no statistical significant disagreement between the tests for sur- gical space-occupying lesions (McNemar test, p = 0.75). The U.S. Headache Consortium evidence-based guidelines from systematic review of the lit- erature concluded that MRI may be more sensitive than CT in identifying clinically insignificant abnormalities, but MRI may be no more sensitive than CT in identifying clinically significant pathology (21).
VIII. What Is the Cost-Effectiveness of Neuroimaging in Patients with Headache?
Summary of Evidence: No well-designed cost-effectiveness analysis (CEA) in adults could be found in the literature, but CEA in children with headache suggests that MRI maximizes the quality-adjusted life years (QALY) gained at a reasonable cost-effectiveness ratio in patients at high risk of having a brain tumor. Conversely, the strategy of no imaging with close clinical follow-up is cost saving in low-risk children. Although the CT-MRI strategy maximizes QALY gained in the intermediate-risk patients, its additional cost per QALY gained is high. In children with headache, appropriate selection of patients and diagnostic imaging strat- egy may maximize quality-adjusted life expectancy and decrease costs of medical workup.
Supporting Evidence: Medina and colleagues (35) reported a CEA in chil- dren with headaches. This study assessed the clinical and economic con- sequences of three diagnostic strategies in the evaluation of children with headache suspected of having a brain tumor: MRI, CT followed by MRI for positive results (CT-MRI), and no neuroimaging with close clinical Table 10.4. Diagnostic performance of imaging
Variable Baseline (%) Range (%) Reference
Diagnostic tests MR imaging
Sensitivity 92 82–100 33, 39, 40
Specificity 99 81–100 33, 40
CT
Sensitivity 81 65–100 33, 39, 40
Specificity 92 72–100 33, 39, 40
follow-up. A decision-analysis Markov model and CEA were performed incorporating the risk group pretest or prior probability, MRI and CT sensitivity and specificity, tumor survival, progression rates, and cost per strategy. Outcomes were based on QALY gained and incremental cost per QALY gained.
The results were as follows: For low-risk children with chronic non- migraine headaches of more than 6 months’ duration as the sole symptom [pretests probability of brain tumor, 0.01% (1 in 10,000)], close clinical observation without neuroimaging was less costly and more effective than the two neuroimaging strategies. For the intermediate-risk children with migraine headache and normal neurologic examination [pretest probabil- ity of brain tumor, 0.4% (4 in 1000)], CT-MRI was the most effective strat- egy but cost more than $1 million per QALY gained compared with no neuroimaging. For high-risk children with headache of less than 6 months’
duration and other clinical predictors of a brain tumor, such as an abnor- mal neurologic examination (pretest probability of brain tumor, 4%), the most effective strategy was MRI, with a cost-effectiveness ratio of 113,800 per QALY gained compared with no imaging.
The cost-effectiveness ratio in the high-risk children with headache is in the comparable range of annual mammography for women aged 55 to 64 years at $110,000 per life-year saved (36), of colonoscopy for colorectal cancer screening for persons older than 40 years at $90,000 per life-year saved (37,38), and of annual cervical cancer screening for women begin- ning at age 20 years at $220,000 per life-year saved (36,38).
Imaging Case Studies
Case 1: Colloid Cyst
The patient presented with headache and vomiting (Fig. 10.3).
Figure 10.3. A: Unenhanced CT shows a small focal lesion with increased density at the level of the foramen of Monro (arrow). B: Axial FLAIR sequence shows increased T2-weighted signal in the lesion (arrow). No hydrocephalus noted.
Neuroimaging findings consistent with colloid cyst.
A B
Case 2: Chiari I
The patient presented with persistent headaches (Fig. 10.4).
Case 3: Brainstem Infiltrative Glial Neoplasm
The patient presented with ataxia and headaches (Fig. 10.5).
Figure 10.4. A: Unenhanced CT at craniocervical junction was interpreted as unremarkable. B: Sagittal MRI T1-weighted image shows pointed cerebellar tonsils extending more than 5 mm below the foramen magnum (arrow) consistent with Chiari I. No cervical cord hydrosyrinx noted.
Figure 10.5.A: Unenhanced CT through posterior fossa is limited by beam hardening artifact. A hypodense lesion is seen in the pons (arrows). B: Axial proton density MR image better depicts the anatomy and extent of the lesion without artifact effects (arrows).
B A
A B
Suggested Protocols
CT Imaging
CT without contrast: axial 5- to 10-mm nonspiral images should be used to assess for subarachnoid hemorrhage, tumor hemorrhage, or calcifications.
CT with contrast: axial 5- to 10-mm nonspiral enhanced images should be used in patients with suspected neoplasm, infection, or other focal intracranial lesion. If indicated, CT angiography can be performed as part of the enhanced CT.
MR Imaging
Basic brain MR protocol sequences include sagittal T1-weighted conven- tional spin-echo (repetition time, 600 ms; echo time 11 ms [600/11]), axial proton density-weighted conventional or fast spin echo (2000/15), axial T2-weighted conventional or fast spin-echo (3200/85), axial FLAIR (fluid- attenuated inversion recovery) spin-echo (8800/152, inversion time [TI]
2200 ms), and coronal T2-weighted fast spin-echo (3200/85) images (33). In patient with suspected neoplasm, infection or focal intracranial lesions gadolinium enhanced T1-weighted conventional spin-echo (600/11) images should be acquired in at least two planes (16,20).
Future Research
• Large-scale prospective studies to validate risk factors and prediction rules of significant intracranial lesions in children and adults with headache.
• Large diagnostic performance studies comparing the sensitivity, speci- ficity and receiver operating characteristic (ROC) curves of neuroimag- ing in adults and children with headache.
• Cost-effectiveness analysis of neuroimaging in adults with headaches.
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