incidental findings in magnetic resonance imaging of the brains of healthy young men
TRANSCRIPT
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Journal of the Neurological Sc
Incidental findings in magnetic resonance imaging of the brains of
healthy young menB,BB
Frank Weber a,*, Heinz Knopf b
a Department of Neurology of the German Air Force Institute of Aviation Medicine, PO Box 1264 KFL, D-82242 Fuerstenfeldbruck, Germanyb Department of Radiology of the German Air Force Institute of Aviation Medicine, Division of Clinical Medicine, Fuerstenfeldbruck, Germany
Received 2 December 2004; received in revised form 12 September 2005; accepted 13 September 2005
Available online 26 October 2005
Abstract
Background and purpose: To determine the frequency of serious intracranial abnormalities in a healthy young male population.
Methods: Cranial MRI of 2 536 healthy young males, mean age 20.5 years, all applicants for military flying duties in the German Air Force.
Results: The authors report a variety of morphological abnormalities in the brains of a large population of healthy young males, providing
data on disease prevalence. Arachnoid cysts were found in 1.7% (95% CI 1.2 to 2.3%), vascular abnormalities in 0.51% (95% CI 0.29 to
0.9%), and intracranial tumors in 0.47% (95% CI 0.26 to 0.85%) of the applicants. No cerebral aneurysms were found.
Conclusion: The prevalence of primary brain tumors seems to be higher, whereas the prevalence of intracranial aneurysms is lower than
expected. Only a small percentage of the detected abnormalities require urgent medical attention.
D 2005 Elsevier B.V. All rights reserved.
Keywords: MRI; Epidemiology; Brain tumor; Aneurysm
1. Introduction
Magnetic resonance imaging (MRI) occasionally dis-
closes unexpected abnormalities, usually in the setting of an
investigation for some other reason. In such cases, the
relevance of the abnormal finding must be determined,
considering the impact on the patient. It must be decided if
the abnormality is a simple variation of the norm or whether
it is clinically serious. Most of the studies reporting on the
prevalence of such incidental findings use MRI studies that
have been performed to examine patients for any kind of
disorder [1]. Studies were rarely performed on healthy
0022-510X/$ - see front matter D 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jns.2005.09.008
i Disclaimer: The opinions in this study represent the opinions of the
authors and are not necessarily those of the German Air Force Surgeon
General or those of the Federal Ministry of Defense.ii Disclosure: The authors have no financial or competing interests to
disclose.
* Corresponding author. Tel.: +49 8141 5630 2020; fax: 49 8141 5630
2989.
E-mail address: [email protected] (F. Weber).
subjects [2–4]. However, studies on healthy subjects could
provide unbiased data to estimate the prevalence of certain
conditions, thus serving as a baseline and as a reference for
further epidemiological studies.
The present study was carried out to determine the
frequency of serious intracranial abnormalities in a healthy
young male population.
2. Methods
2.1. Study population
Participants of this study are all applicants for military
flying duties who were examined in the division of
clinical aviation medicine of the German Air Force
Institute of Aviation Medicine in the time between 01/
01/2000 and 06/30/2004. In principle, every applicant for
military flying duties undergoes cranial MRI screening in
order to rule out intracranial abnormalities that may be
hazardous for aviation safety. In their initial flight
iences 240 (2006) 81 – 84
Table 1
Normal findings and variations of the norm
Radiological result Number Percentage 95% CI
Strictly normal 1921 75.75 74.0 to 77.4
Variations of the norm
Cavum vergae 121 4.77 4.0 to 5.7
Large basal cisterns 44 1.74 1.3 to 2.3
Cysts of the pineal gland 87 3.43 2.8 to 4.2
Enlarged perivascular spaces 65 2.56 2.0 to 3.3
Asymmetry of the lateral ventricles 68 2.68 2.1 to 3.4
Occasional white matter lesions 66 2.60 2.0 to 3.3
Ossification of the cerebral falx 8 0.32 0.15 to 0.65
Empty sella 9 0.35 0.17 to 0.7
Total 2389 94.20 93 to 95
F. Weber, H. Knopf / Journal of the Neurological Sciences 240 (2006) 81–8482
physical which is supposed to determine the ‘‘medical
fitness for flying duties’’, the candidates undergo a general
medical examination including neurological, ophthalmo-
logical, orthopedical, ENT, and dental tests. The neuro-
logical examination includes EEG, visual evoked
potentials, and cranial and cervical MRI. The clinical
neurological findings of all the participants in the present
study proved to be normal.
This study was approved by the institutional review
board.
Table 2
Abnormal findings
Radiological result
Arachnoid cysts*
Intracerebral cysts/cystic posttraumatic defects
Colloid cyst of the 3rd ventricle
Chiari I-malformation and dystop cerebellar tonsils.
Cervical hydromyelia
Cervical disc prolapse
Cortical atrophy
Atrophy of the hippocampal region
Cerebellar dysplasia
Internal hydrocephalus
Vascular abnormalities
Missing anterior communicating artery
Kinking of the carotid artery
Arteriovenous malformations
Cavernomas
Venous angiomas
Hygroma
Osseous abnormalities of the skull, including fibrous dysplasia
Tumors
Hypophyseal adenomas
Epidermoid cyst
Tumor of the cerebellopontine angle
Cerebellar tumors (pilocytic astrocytoma)
Low-grade glioma
Lipoma
Tumor dorsal of the 4th ventricle, unclassifiable
Demyelinating disease
Total
Please note: In a few cases, there was more than one finding in one person. *Distrib
both sides 4; posterior fossa 5; anterior fossa 5; other 3. .Chiari I-malformation:
abnormal extension of the cerebellar tonsils through the foramen magnum � 1
classified as Chiari I. 18 cases of accompanying cervical hydromyelia, no other s
2.2. MRI
MRI is performed by one of the authors (HK) in the
following manner: Standard procedure is a transversal T2
spinecho (TSE) sequence (5.0 mm), a sagittal T2 TSE
sequence (3.0 mm), a transversal T1 true inversion recovery,
2.0 mm and a coronary fluid attenuated inversion recovery
(FLAIR), 6.0 mm. If any findings are considered suspicious,
he proceeds to a three-dimensional (3D) MR-angiography
(TOF-MRA) with secondary reconstructions (MIP) and
further T1 post-Gadolinium (Gd) series. The following
equipment was used: Magnetom Harmony 1.0 T device
manufactured by Siemens, Erlangen, Germany. 8% of MRI
investigations were followed by MRA and/or Gd series,
each. In 95% of the cases where Gd-applications were used,
the contrast enhancement was diagnostic, i.e. suspicious
findings could be confirmed or excluded.
This MRI regime provides sufficient accuracy to detect
even smaller mass effects. This is achieved by the
combination of sequences of very fine slices (2 mm) of
the inversion recovery sequence which shows distinctly
anatomic details and is reliable in detecting mass effects.
Moreover, MR-angiography and Gadolinium are applied in
doubtful cases. All MRI scans are read by the same
Number Percentage 95% CI
43 1.70 1.2 to 2.3
13 0.51 0.3 to 0.9
1 0.04 0.0 to 0.26
43 1.70 1.2 to 2.3
19 0.75 0.46 to 1.19
1 0.04 0.0 to 0.26
10 0.39 0.2 to 0.75
1 0.04 0.0 to 0.26
1 0.04 0.0 to 0.26
1 0.04 0.0 to 0.26
1 0.04 0.0 to 0.26
1 0.04 0.0 to 0.26
5 0.20 0.07 to 0.49
3 0.12 0.03 to 0.38
3 0.12 0.0 to 0.3
1 0.04 0.0 to 0.26
6 0.24 0.1 to 0.5
4 0.16 0.05 to 0.43
1 0.04 0.0 to 0.26
1 0.04 0.0 to 0.26
2 0.08 0.014 to 0.32
1 0.04 0.0 to 0.26
2 0.08 0.014 to 0.32
1 0.04 0.0 to 0.26
1 0.04 0.0 to 0.26
166 6.55 5.6 to 7.6
ution of the arachnoid cysts: left temporal 19; right temporal 7; temporal on
classification as dystop cerebellar tonsils was made in case of an isolated
cm (n =37). In 6 cases, abnormal extension was >1 cm; such cases were
econdary abnormalities in any of these cases.
F. Weber, H. Knopf / Journal of the Neurological Sciences 240 (2006) 81–84 83
radiologist (HK) who was unaware of the medical history
and the physical findings of the candidates at the time of the
MRI reading. Thus, observer variability and observer bias
are ruled out.
2.3. Statistical analysis
Confidence intervals were calculated with R, version
2.01 [5].
3. Results
2536 subjects were screened for the purpose of this study.
All subjects were males in a mean age of 20.5 years
(ranging between 17 and 35 years). The results of the MRI
screening are presented in Table 1 (normal findings and
variations of the norm) and in Table 2 (abnormal findings).
The normal or abnormal classification is arbitrary in some
categories, since it is up to the investigator’s discretion, if
very few white matter lesions in a healthy person or falx
ossifications or intracranial lipomas are considered to be
normal or abnormal findings. All abnormal findings were
clinically silent. We found 43 cases of arachnoid cysts
(1.7%; 95% CI 1.2 to 2.3%), 13 cases of vascular
abnormalities (0.51%; 95% CI 0.29 to 0.9%), and 12 cases
of intracranial tumors (0.47%; 95% CI 0.26 to 0.85%). No
cases of cerebral aneurysm were found. Tumors were
classified exclusively according to radiological criteria
without any histological confirmation. A neurosurgeon
was consulted in every tumor case. Since all candidates
were clinically healthy, a ‘‘wait and see’’ approach was
decided with additional studies depending on the further
course of the disease. Classification as ‘‘occasional white
matter lesions’’ refers to few—usually one or two, most of
them solitary—non-specific T2 hyperintensities without
Gadolinium enhancement. In one candidate we proved the
existence of many white matter hyperintensities, some of
them with circular Gadolinium enhancement. Further
workup showed MS-typical CSF abnormalities (positive
oligoclonal IgG-bands); this person’s disease was classified
as demyelinating disease.
4. Discussion
The present study describes the prevalence of incidental
findings in MRIs of the brain in a large cohort of males who
were specifically chosen for healthiness. It may thus serve
as a reference or as a baseline for further epidemiological
studies. Our population is selected under the following
conditions: young men who voluntarily apply for military
flying service, with normal general medical and neurolog-
ical findings, and who have passed a psychological
examination, when their occupational aptitude for military
flying is tested. We do not consider this an invalidation of
our results, because it is improbable that the presence of a
hitherto unknown asymptomatic intracranial abnormality
can prevent a candidate from applying for military flying
services.
4.1. Ethical considerations
We reported each and every incidental finding to our
subjects. Abnormal findings limiting medical fitness (for
military flying services) are described elsewhere [3]. All
subjects with abnormal findings were individually briefed
by one of the authors (FW) and they received detailed
information on the nature of the apparent abnormality and
medical advice for further management. In none of the
members of the study, immediate referral was necessary.
Urgent referral, however, was required in 14 cases (0.55%;
95% CI 0.31 to 0.95%). Findings such as arteriovenous
malformations, cavernomas, primary brain tumors and
demyelinating disease were classified as category justifying
urgent referral. The proportion of 0.55% is lower than
reported previously and this is due to the specific nature of
the study population [4].
4.2. Arachnoid cysts
They were detected in 43 candidates (1.7%). This
number is higher than reported previously (0.3% or
approximately 1% of all intracranial masses) [2]. Since
most of the previous data are collected from patients who
undergo cerebral MRI for some other reason, our results
seem to prove the benign and clinically silent nature of
arachnoid cysts.
4.3. Primary neoplasms
Five candidates were found to have suspicious primary
neoplasms (one brainstem tumor, two cerebellar tumors, one
low-grade glioma, one cerebellopontine angle tumor),
corresponding to a prevalence of 0.2% (95% CI 0.1 to
0.5%). Such findings correspond to Katzman’s data who
also examined asymptomatic volunteers and found 0.2% for
primary neoplasms in 1000 persons [2]. The Central Brain
Tumor Register of the United States calculated an annual
incidence of 10.4 per 100,000 person-years of primary brain
tumors from 1990 to 1994, and an incidence rate of 10 per
100,000/year has been described in the UK [6,7]. A
prevalence estimate of 0.13% for primary brain tumors
has been calculated from the first-mentioned data, which
corresponds to our findings [8].
4.4. Vascular abnormalities
We detected five arteriovenous malformations (0.2%).
This percentage is in the range of prevalences reported in
hospital-based post-mortem series (up to 0.6%), but it is
considerably higher than estimated according to a popula-
F. Weber, H. Knopf / Journal of the Neurological Sciences 240 (2006) 81–8484
tion-based study (18 per 100,000) [9]. We found three
cavernomas (0.12%) which is in the range of prevalence
data which are reported from autopsy series (0.02 to 0.53%),
although former studies based on MRI have reported a
higher prevalence of 0.4 to 0.9% [10]. We did not find a
single intracranial aneurysm although we carefully looked
for it. This is highly significant compared to an expected
prevalence of 2% (95% CI 0.0% to 0.2%). Since we did not
perform a conventional angiography and MRA unless in
selected cases, we possibly overlooked some aneurysms.
Aneurysms must exceed a critical size of 3 to 5 mm to be
discovered by MRI or MRA. However, we think that our
MRI regime provides enough accuracy to detect even
smaller aneurysms due to the combination of the sequences,
the fine slices (2 mm) of the inversion recovery sequence
which gives exact anatomic details and reliably detects mass
effects, and the MR-angiography and Gadolinium which we
would apply in doubtful cases. Our data suggest a low
prevalence in young adults and an age-related development
of aneurysms [11–13].
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