incidental findings in magnetic resonance imaging of the brains of healthy young men

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Incidental findings in magnetic resonance imaging of the brains of healthy young men B,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, Germany b 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 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 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). Journal of the Neurological Sciences 240 (2006) 81 – 84 www.elsevier.com/locate/jns

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Page 1: Incidental findings in magnetic resonance imaging of the brains of healthy young men

www.elsevier.com/locate/jns

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

Page 2: Incidental findings in magnetic resonance imaging of the brains of healthy young men

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.

Page 3: Incidental findings in magnetic resonance imaging of the brains of healthy young men

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-

Page 4: Incidental findings in magnetic resonance imaging of the brains of healthy young men

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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