THE PREVALENCE AND ASSOCIATED FACTORS

OF INTRACRANIAL LESIONS ON MRI AND THE

ACCURAC Y OF FLAIR SEQUENCE IN PATIENTS

WITH H EADACHE BUT NO NEUROLOGICAL

DEFICIT.

By

DR WAN DAIZYREENA BINTI WAN J AAFAR

MBBS (UNI.OF WESTERN AUSTRALIA)

Dissertation Submitted In

Partial Fulfillment of the Requirements

For Masters of Medicine

(Radiology)

UNIVERsm SAINS MALAYSIA

UNIVERSITI SAINS MALAYSIA

2007

To,

My beloved husband Ustaz Zolkijli bin Ibrahim and my delightful sons, Amir Abdul Raof

and Ahmad Naim Hafizi.

Also to my father, Haji Wan Jaafar Wan Hussein and my late mother, Allahyarhamah

Hajah Nik Suhaibah Yusoff

Thank you for your loves, support, patience, sacrifices and understanding.

This is for all of you.

ACKNOWLEGEMENTS

I would like to express my heartfelt gratitude and love to my family, for all their

sacrifices, love and support.

Special thanks for Dr Win Mar@Salmah lalaludin, my supervisor and lecturer for her

tireless support, patience, help and advices all these time and her involvement and

commitment in helping me to finish this study.

Thank you to Dr Mohd Ezane Aziz, the head of department of Radiology who had spent

countless time to help me produce a good quality dissertation.

I also would like to thank Dr Mohd Shafie Abdullah, radiologist and lecturer for willingly

involved in this study and for his time spent during and after office hours to ensure this

study is completed: Gratitudes to Dr Nik Munirah Nik Mahdi for her help in this study.

Moreover, I would like to thank Dr Noreen Norfaraheen Lee Abdullah for giving me the

idea to start this study in the fust place.

In addition, to all the lecturers of Radiology department, thank you for your advices,

assistance and support during the four years of the Masters of Medicine program.

I would also like to thank Dr Nor Azwany Yaacob, Dr Zaharah Sulaiman and Dr

Kamarul Imran, lecturers from Department of Community Medicine for their help and

support to make this study a success.

Finally yet importantly, I would like to thank all my friends and colleagues for their love

and support during these four years of joy, hard work and emotional distress.

May Allah bless all of you.

1

Table of Content Page

Acknowledgement ................................................................................. i

Table of contents ................................................................................... ii

List of tables .......................................................................................... v

List of figures ...................................................................................... vi

Abbreviations .................................................................................... vii

Abstract (Malay) .................................................................................. viii

Abstract (English) ................................................................................... X

Introduction ................................................................................................................. 1

1.1 Introduction ......................................................................................................... 1

2 Literature review ......................................................................................................... 7

2.1 Headache ............................................................................................................. 7

2.1.1 Definition and Classification ...................................................................... 7

2.1.2 Prevalence and Incidence .......................................................................... 11

2.2 Neuroimaging for headache .............................................................................. 11

2.2.1

2.2.2

Computed tomography (CT)............................................... ...................... 12

Magnetic resonance imaging (MRJ) ....................................... ..... .... ......... 13

2.2.3 Clinical application ofMRI in patients with headache ............................. 14

2.2.4 Basic concept of FLAIR ........................................................................... 15

3 Objective ................................................................................................................... 19

3.1 General objective .............................................................................................. 19

3.2 Specific Objectives ........................................................................................... 19

11

3.3 Research Questions ........................................................................................... 20

3.4 Research Hypothesis ................................•........................................................ 20

4 Methodology ............................................................................................................. 21

4.1 Study DesigIl ..................................................................................................... 21

4.2 Sample size ....................................................................................................... 21

4.3 Criteria for patients ........................................................................................... 23

4.3.1 Inclusion criteria ....................................................................................... 23

4.3.2 Exclusion criteria ...................................................................................... 24

4.4 Material and Methods ....................................................................................... 24

4.4.1 Information ............................................................................................... 24

4.4.2 MRI Protocol ............................................................................................ 25

4.4.3 Interpretation of MRI ................................................................................ 25

4.5 Statistical Analysis ............................................................................................ 26

4.6 Deflllitions ......................................................................................................... 28

5 Result ........................................................................................................................ 29

General result ................................................................................................................ 29

5.1 Prevalence of intracranial lesions in complete sequence of MRI ..................... 36

5.2 Accuracy of FLAIR sequence in detecting intracranial lesions ........................ 37

5.3 Association between intracranial lesions and clinical parameters on complete

MRI sequence ............................................................................................................... 39

6 Section Six: Discussion ............................................................................................. 43

6.1 Prevalence of abnonnal findings ...................................................................... 44

6.2 Accuracy of FLAIR sequence in detecting brain lesion ................................... 46

iii

6.2.1 False positive findings .............................................................................. 48

6.2.2 False negative findings ............................................................................. 49

6.3 Associated factors of intracranial lesions on :MRI .............................. : ............. 54

6.3.1 Age ............................................................................................................ 54

6.3.2 Gender ....................................................................................................... 55

6.3.3 Duration of headache ................................................................................ 55

6.3.4 Side of headache ....................................................................................... 57

6.3.5 Symptoms ................................................................................................. 57

6.3.6 Health status .............................................................................................. 58

6.3.7 Cost-effectiveness of FLAIR .................................................................... 63

7 Conclusion ................................................................................................................ 64

8 Limitations and Recommendation ............................................................................ 65

8.1 Limitations ........................................................................................................ 65

8.2 Recommendations ............................................................................................. 66

9 References and appendices ....................................................................................... 67

IV

List of tables

Table 1.1: MRI protocol for brain imaging in HUSM ........................................................ 3

Table 1.2: MRI cases in HUSM from 1st June 2003 until 31st May 2004 ......................... 4

Table 1.3: Number of cases of MRI brain for headache with normal neurological

examination ................................................................................................................. 5

Table 1.4 : Cost for MRI brain in HUSM ........................................................................... 6

Table 2.1: Common causes of primary and secondary headache ....................................... 8

Table 2.2: Features warranting for investigation of secondary headache ......................... 10

Table 2.3: Diagnostic yield of neuroimaging for headache with normal neurological exam

................................................................................................................................... 12

Table 5.1: Demographic characteristics of study sample ................................................. 31

Table 5.2: Association between findings of complete sequence of MRI and side of

headache .................................................................................................................... 33

Table 5.3: Frequency of side of headache with MRI diagnosis ........................................ 34

Table 5.4 : Prevalence of intracranial lesions in MRI ...................................................... 36

Table 5.5: Result regarding accuracy of FLAIR in comparison with complete MRI

sequences .................................................................................................................. 3 8

Table 5.6: Association between intracranial lesions and clinical parameters by observer A

40 ...................................................................................................................................

Table 5.7: Furthe subdivision r analysis ........................................................................... 42

Table 6.1: Cases, which were abnormal on FLAIR but normal on complete sequence ... 48

v

List of figures

Figure 5.1: Bar chart for patients' age ............................................................................... 32

Figure 6.1: Subependymal nodule of the right lateral ventricle (black arrows) - a) Tl W,

b) T2 W , c) FLA~ d) post-gadolinium .................................................................... 50

Figure 6.2: Arachnoid cyst anterior to the right cerebellum (black arrows) - a) T1 W, .... 52

Figure 6.3: Lacunar infarcts in hypertensive patient, a) T1-weighted, b) T2-weighted, c)

FLAIR ....................................................................................................................... 60

Figure 6.4: 29-year-old man with acute-on-chronic pan-sinusitis: FLAIR images on

acute-on-chronic sinusitis ......................................................................................... 62

vi

ABBREVIATIONS

CSF

CT

FLAIR

ffiJSM

IRS

MRI

NPV

PACS

PPV

SAH

SOL

SPSS

USA

Cerebral spinal fluid

Computed tomography

Fluid-attenuated inversion recovery

Hospital University Sains Malaysia

International Headache Society

Magnetic resonance imaging

Negative predictive value

Picture Archiving and Communication System

Positive predictive value

Subarachnoid haemorrhage

Space occupying lesion

Statistical Package for Social Sciences

United States of America

Vll

ABSTRAK: BAHASA MALAYSIA

T AJUK: Bilangan peratusan (prevalen) dan faktor-faktor yang berkaitan dengan

ketidaknonnalan di dalam kepala dan otak yang dikesan melalui MRI serta ketepatan

FLAIR di kalangan pesakit yang mengalami sakit kepala dan tidak mempunyai

kelemahan neurologi.

OBJEKTIF: Tujuan kajian ini adalah untuk menentukan bilangan peratusan dan faktor­

faktor yang berkaitan dengan ketidaknonnalan di dalam kepala dan otak yang dikesan

melalui MRI serta ketepatan FLAIR di kalangan pesakit yang mengalami sakit kepala

dan tidak mempunyai kelemahan neurologi.

METODOLOGI: Ini adalah kajian retrospektif dan prospektif selama 51 bulan dari 1 hb

Jun 2002 sehingga 30hb September 2006. Seramai 143 orang pesakit yang menghidap

sakit kepala dan tidak ada kelemahan neurologi serta benunur 13 tabun ke atas yang

menjalani pemeriksaan MRI otak untuk menyiasat penyebab sakit kepala mereka. Bagi

setiap kes, sirl FLAIR dan sirl lengkap MRI otak di lapurkan secara berasingan pada

masa yang berlainan oleh dua orang pakar radiologi.

KEPUTUSAN: Bilangan peratusan ketidaknormalan yang ditemui di dalam otak yang

dikesan oleh pemeriksaan MRI adalah 18.9% (95% CI: 0.06, 0.32). Sensitiviti bagi

FLAIR adalah 92.6% dan specificiti adalah 92.2%. Umur melebihi 40 tahun dan

viii

menghidap sakit kepala diantara 3 - 6 bulan didapati mempunyai hubungan dengan

ketidaknormalan yang ditemui dengan risiko sebanyak 0.191 (0.07, 0.51) dan 4.86 (1.37,

17.26) setiap satu. FLAIR dapat mengesan ketidaknormalan pada di kawasan laluan fiber,

ketumbuhan otak, jangkitan kuman pada otak dan pendarahan di dalam otak. FLAIR

tidak dapat mengesan ketumbuhan keeil di dalam otak yang menyerupai eeeair dan yang

terletak. berhampiran kawasan eeeair otak.

KESIMPULAN: Dari kajian ini, FLAIR didapati eukup sensitif untuk menges an

ketidaknormalan di dalam kepala dan otak. Oleh itu, sirl FLAIR boleh digunakan sebagai

ujian saringan di kalangan pesakit yang mengalami sakit kepala dan pemeriksaan

neurologi mereka adalah normal. Dengan itu, masa untuk pemerlksaan MR boleh

dipendekkan dan lebih rarnai pesakit boleh menjalani pemeriksaan MRI setiap hari.

Kata kUDCi: MRI, sakit kepala

IX

ABSTRACT: ENGLISH

TITLE: The prevalence and associated factors of intracranial lesions on MRI and the

accuracy of FLAIR sequence in patients with headache but no neurological deficit.

OBJECTIVES: The objectives of this study were to detennine prevalence and

associated factors of intracranial lesions on :MRI examination and the accuracy of FLAIR

in detecting intracranial lesions in patients with headache but no neurological deficit.

METHOD: A retrospective and prospective cross-sectional study was perfonned over 51

months from 1 st June 2002 until 30th September 2006. One hundred and forty-three

patients with headache but no neurological deficit aged 13 years old and above who had

underwent routine :MRI examination of brain in Hospital University Sains Malaysia were

included into this study. For each case, FLAIR sequence and complete brain series were

reviewed separately at different times by two radiologists.

RESULTS: Prevalence of intracranial lesions on complete MRI sequence was 18.9%

(95% CI: 0.06, 0.32). The sensitivity for FLAIR was 92.6% and the specificity of 92.2%.

Age more than 40 years and experiencing headache between 3 - 6 months were found to

have association with abnonnalities detected with adjusted OR 0.191 (0.07, 0.51) and

4.86 (1.37, 17.26) respectively. Intracranial abnormalities detected by FLAIR sequence

were white matter lesions, meningioma, teratoma, meningo-encephalitis and intracranial

x

haemorrhages. On the other hand, FLAIR missed to detect a small sub-ependymal nodule

and arachnoid cyst in CSF spaces.

CONCLUSION: Since FLAIR sequence is sensitive in detecting intracranial lesions, it

can be used as a screening sequence in patients with headache but no neurological deficit.

The MR examination time can be shortened and the number of patients for MR

examination per day can be increased.

Keywords: MRI, intracranial lesions, headache

XI

SECTION ONE

INTRODUCTION

Introduction

1.1 Introduction

Headache is a very common presenting symptom in clinics. Many patients complained of

headache. It represents 1% of physician's office visits and emergency departments in the

United State of America and accounting for more than 18 million outpatient visits per

year (piovesan and Kowacs, 2003).

Most patients with headache are afraid that they may have a serious illness and therefore

seek medical attention. Often they request a radiological investigation. There are more

than 300 causes of headache. Clinicians also would like to exclude the worst possible

cause for the headache, such as possibility of intracranial tumours, aneurysm or vascular

malformation before offering usual treatment for the headache. If these are detected early,

the physicians can offer the appropriate management and treatment that can be lifesaving

as well. As radiological investigations are not invasive or uncomfortable, and they can

detect presence of intracranial pathology, the threshold for requesting these investigations

is low.

On the other hand, not all headaches need radiological investigations. Therefore, clinical

assessment is very important. Presence of any neurological deficit or headache with so­

called "red flags" symptoms and signs warrant neuroimaging study (Sobri et aI., 2003).

There are likely to have positive fmdings on neuroimaging with these signs.

1

The yield of magnetic resonance imaging (MRI) in the evaluation of patients with

chronic headache and normal neurological examination is quite low, only 3.7% (Wang et

al., 2001). Therefore, it is not economical to do neuroimaging in all cases of headache, as

there will be many with negative finding. A study had found that plain computed

tomography (CT) of brain in patients presented with headache without focal neurological

deficit is enough (Jalaludin, 2001). The positive findings were only 12 cases (6.7%) out

of 180 cases.

MRI is the "gold standard" for neuroimaging. It is able to demonstrate 95% of

abnonnalities in patients with Multiple Sclerosis when compared with CT scan (paty et

al., 2000). It is also a better imaging modality because it does not involve radiation and

gives better soft tissue resolution. However, it has a long waiting list and a long imaging

time in comparison with CT scan. Usual MRI brain series contains Tl-weighted, 1'2-

weighted, fluid-attenuated inversion recovery (FLAIR) sequences in axial plane and Tl­

weighted in sagittal plane and MR angiogram. The total time of the series is 19.03

minutes (Table 1.1) and including preparation time for the patients, the time allotted is 45

minutes per patient. The time to do FLAIR only is 5.24 minutes (Table 1.1) and including

patient's preparation time, it will take only 15 minutes. Thus, if only FLAIR sequence of

MRI done for patients with headache but no focal neurological deficit, the imaging time

can be reduced and more patients can be examined.

2

The time to perform MR.I of brain is longer than that of CT scan. The protocol for MR.I of

brain in HUSM is as shown in Table 1.1. This does not include the time needed for

patient's preparation. In HUSM, time allocated for :MRI of brain is 45 minutes inclusive

of patient's preparation. There are 5 - 6 cases of MRI of brain per day. Waiting list for

the MR.I appointment takes about one to one and half months.

Table 1.1: MR.I protocol for brain imaging in HUSM

Sequences

Localizer Sagittal T1 W Axial T1W Axial T2W Axial FLAIR 3D*TOFCOW

Total

• Time of flight circle of Willis

3

Time (minutes)

1:08 3:38 2:44 2:37 5:24 4:52

19:03

A study by Herskovits et al (2001) had found that the FLAIR sensitivity is 89% in

detecting brain parenchymal abnormalities. With this high sensitivity, FLAIR can be used

as the only series to examine this type of patients. Time spent to examine one patient is

less, so three patients can be examined by FLAIR alone instead of one patient by the

whole brain series in the same period.

During one year observation by the author, there were only 11 (17.2%) cases out of 107

cases of MRI brain requested for patients with headache (Table 1.2) were found to have

brain pathology.

Table 1.2: MRI cases in HUSM from 1st June 2003 until 31st May 2004

Examinations No. of cases

All MRI examinations 1243

All brain MRI 506

Brain study of patients with headache 107

Brain study of patients with headache without neurological deficit 64

Positive intracranial pathological findings 11

4

In Hospital University Sains Malaysia (HUSM), the number of MRI requested for

headache has increased. Table 1.3 shows the number of MRI done for headache from 1 st

June 2003 until 31 st May 2004. MRI of brain comprised of 506 cases (40%) of all MRI

examinations done during the 12 months period (Table 1.2). Table 1.3 represents the

number of MRI brain study for patients with headache and normal neurological

examination divided in quarterly of a year from 1 st June 2003 until 31 st May 2004.

Table 1.3: Number of cases of MRI brain for headache with normal neurological

examination

Duration

June - August 2003 Sept - November 2003 Dec 2003 - February 2004 March - May 2004

5

No of cases

17 14 18 15

MRI examination is also expensive. The cost for MRI brain in HUSM is as shown in

Table 1.4. By cutting the time for each patient, the cost per examination can be reduced

and becomes affordable. Therefore, more patients can undergo the examination.

Table 1.4: Cost for MRI brain in HUSM

MRI

Brain without contrast Brain with contrast Brain with MRA

Patients from HUSM

RM550.00 RM 850.00 RM650.00

Patients from private clinics or hospitals

RM 850.00 RM 1350.00 RM 950.00

Therefore, the accuracy of FLAIR sequence in detecting pathology in patients with

headache and no neurological deficit need to be determined because it will reduce the

time for MRI brain in this group of patients. Furthermore, the slot for MRI can be utilised

for those patients who are really has clinical benefits.

6

SECTION TWO

LITERATURE REVIEW

Literature review

2.1 Headache

2.1.1 Dermition and Classification

Merck's Manual of Diagnosis and Therapy 17th edition (1999) gives the defInition of

headache as pain in the head or cephalagia. International Headache Society (lHS) has

divided headache into primary and secondary headache. Primary headaches are migraine,

clusters headache, tension-type headache and trigeminal autonomic cephalagia.

Secondary causes for headache can be due to intracranial pathology (infections, tumours),

head injury or referred pain from eyes, nose, paranasal sinuses, throats, ears and cervical

vertebrae (Piovesan and Kowacs, 2003). More than 90% of headache patients suffer from

primary headache (Dodick, 2003). The remaining patients will have secondary headache

caused by tumours, meningitis, giant cell arteritis, sinusitis or other medical disorders

(Table 2.1).

Intracranial pathology is extremely uncommon among patients with primary headache. A

meta-analysis study revealed only 0.18% of patients diagnosed with migraine with

normal neurological examination, will be diagnosed with signifIcant intracranial

abnormality (Dodick, 2003). The most common cause of secondary headache is sinusitis,

followed by post-traumatic headache, CSF leak and vascular disorders.

7

Table 2.1: Common causes of primary and secondary headache

Primary headaches Migraine Cluster Tension-type

Secondary headaches Intracranial space occupying lesions

Neoplasm Arteriovenous malfonnation Abscess Hematoma

Cerebrovascular disease Intracranial aneurysm Occlusive vascular disease

Infection Sinusitis Meningitis Encephalitis

Inflammation Vasculitis Acute disseminated encephalomyelitis

Increased intracranial pressure Hydrocephalus Pseudotumour cerebri

Adapted from Medina et al (2003)

8

Patients with headache nlay present to their doctors with associated symptoms, such as

nausea, vomiting, visual problems, aura, transient or pennanent paralysis/numbness, with

seizure or loss of consciousness. Clinical examination may reveal presence of

papilloedema, focal weakness or reduced sensation. A consultation for headache should

include a history, physical examination, assessment of clinical clues and a detennination

of whether features are present that suggest an investigation of secondary headache.

Dodick (2003) had given a list of features (as listed in Table 2.2) that can help in deciding

for investigation of secondary headache. Sobri et al (2003) had identified three clinical

features that have statistical significance in identifying intracranial pathology. They are

paralysis of limbs, papilloedema and altered mental states such as drowsiness, confusion,

memory impainnent and unconsciousness. Presence of focal neurological symptoms or

fmdings has 100% sensitivity for intracranial pathology with 76% specificity (Grayson et

al., 2005). Alteration of characteristics of headache with increased intensity and

frequency have 67% and 39% sensitivity and 67% and 73% specificity respectively

(Grayson et al., 2005). Data reviewed demonstrate that 11 % to 21 % of patients

presenting with new-onset headache have serious intracranial pathology (Miller, 2006).

9