the prevalence and associated factors of …
TRANSCRIPT
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