Cerebellar Cortical Infarct Cavities
Correlation With Risk Factors and MRI Markers
of Cerebrovascular Disease
Laurens J.L. De Cocker, MD; Raoul P. Kloppenborg, MD, PhD;
Yolanda van der Graaf, MD, PhD; Peter R. Luijten, PhD; Jeroen Hendrikse, MD, PhD;
Mirjam I. Geerlings, PhD; for the SMART Study Group*
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Background and Purpose—Small cerebellar infarct cavities have been recently found on magnetic resonance imaging
(MRI) to preferentially involve the cerebellar cortex, but epidemiological studies are lacking. We aimed to determine the
prevalence and risk factor profiles of cerebellar cortical infarct cavities (≤1.5 cm) as well as their association with MRI
markers of cerebrovascular disease and functioning.
Methods—We analyzed the 1.5 Tesla MRI of 636 patients (mean age, 62±9 years; 81% men) from the Second Manifestations
of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study. Logistic regression analyses were performed
to estimate the associations of age, sex, vascular risk factors, MRI markers of cerebrovascular disease, and functioning
with cerebellar cortical cavities, adjusted for age and sex.
Results—Cerebellar cortical infarct cavities occurred on MRI in 10% of patients and were significantly associated with age,
intima-media thickness (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1–3.7), high levels of homocysteinemia
(OR, 1.8; 95% CI, 1.0–3.3), cortical infarcts (OR, 2.9; 95% CI, 1.6–5.4), gray matter lacunes of presumed vascular
origin (OR, 3.0; 95% CI, 1.6–5.8), brain stem infarcts (OR, 5.1; 95% CI, 1.9–13.6), and decreased brain parenchymal
fraction (OR, 0.84; 95% CI, 0.74–0.94), but not with white matter hyperintensities (OR, 1.2; 95% CI, 0.8–1.8) or white
matter lacunes of presumed vascular origin (OR, 1.1; 95% CI, 0.5–2.5). They were also associated with worse physical
functioning (OR 0.96; 95% CI, 0.94 to 0.99) but not with mental functioning.
Conclusions—Cerebellar cortical infarct cavities are far more common than previously assumed based on symptomatic case
series and are associated with markers of atherothromboembolic cerebrovascular disease. (Stroke. 2015;46:3154-3160.
DOI: 10.1161/STROKEAHA.115.010093.)
Key Words: atherosclerosis ◼ brain stem ◼ cerebrovascular disorders
◼ magnetic resonance imaging ◼ white matter
W
ith the aging population and high availability of imaging studies, it is estimated that most persons now at
least have 1 computed tomography or magnetic resonance
imaging (MRI) study of the brain during life. Knowledge
about commonly observed incidental imaging findings is
therefore mandatory. In the cerebrum, incidental infarcts are
commonly seen on MRI, with a prevalence ranging from 20%
in healthy elderly to over 50% in patients with vascular or
ischemic cerebrovascular disease.1–3 They have considerable
impact as they are associated with increased risks of stroke,
cognitive dysfunction, and dementia.4,5
Cerebellar infarcts have been well studied before in
patients presenting with clinical symptoms.6–9 Large and
small cerebellar infarcts have been found to be essentially
of atherothromboembolic origin, with the site and size of the
infarct depending on the responsible blood clot.10 Although
small cerebellar infarcts <2 cm are seen in >90% of symptomatic patients presenting with multiple cerebellar infarcts
on MRI,11,12 many small cerebellar infarcts may remain clinically occult, especially if occurring in isolation.11,13,14 Still, the
same infarcts may be detected later on as an incidental infarct
cavity on imaging studies.13–15 Recent studies have shown that
the overwhelming majority of such cerebellar infarct cavities
involve the cortex, as opposed to the much rarer lacunes (of
presumed vascular origin) affecting the deep cerebellum.13,15
In addition, cerebellar cortical cavities have recently been
confirmed to be of ischemic origin and to be easily identified
and characterized on MRI scans.13,15 Nevertheless, epidemiological studies investigating these cerebellar cortical infarct
cavities are lacking.
Received May 17, 2015; final revision received August 2, 2015; accepted August 18, 2015.
From the Department of Radiology(L.J.L.D.C., P.R.L., J.H.) and Julius Center for Health Sciences and Primary Care (R.P.K., Y.v.d.G., M.I.G.), University
Medical Center Utrecht, Utrecht, The Netherlands; and Department of Neurology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands (R.P.K.).
*A list of SMART study group members is given in the Appendix.
Correspondence to Laurens J.L. De Cocker, MD, Radiologie, Kliniek Sint-Jan/Clinique Saint-Jean, Kruidtuinlaan 32, 1000 Brussels, Belgium. E-mail
[email protected]
© 2015 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.115.010093
3154
De Cocker et al Cerebellar Cortical Infarct Cavities 3155
The aim of this study was to investigate the occurrence
and determinants of cerebellar cortical infarct cavities on brain
MRI in a cohort of patients with proven vascular disease. In
addition, we aimed to correlate the presence of these cavities
with MRI markers of cerebrovascular disease and with physical and mental functioning.
Materials and Methods
Subjects
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Data were used from the Second Manifestations of Arterial DiseaseMemory, Depression and Aging (SMART-Medea) study, a cohort
study in patients with a history of arterial disease.16,17 The SMARTMedea study is an ancillary study to the SMART-MR study, which
has been described in more detail elsewhere.18,19 In brief, between
May 2001 and December 2005, 1309 patients newly referred to the
University Medical Center Utrecht for treatment of symptomatic atherosclerotic disease (manifest coronary artery disease, cerebrovascular disease, peripheral arterial disease, or abdominal aortic aneurysm)
without MRI contraindications were enrolled in the SMART-MR
study. Exclusion criteria were age ≥80 years, diagnosis of a terminal
malignancy, lack of independence in daily activities (Rankin scale
>3), and lack of fluency in Dutch or referral back to the referring
specialist. Between April 2006 and May 2009, 710 participants had
follow-up measurements, including 3-dimensional (3D) T1-weighted
MR images to assess hippocampal volumes as part of the SMARTMedea study.
During a 1 day visit to the University Medical Center Utrecht, a
physical examination, ultrasonography of the carotid arteries, blood
and urine samplings, neuropsychological and depression assessment,
and a 1.5-Tesla brain MRI scan were performed. Questionnaires were
used for assessing demographics, risk factors and medical history,
medication use, functioning, psychosocial vulnerability and stress
factors, and depressive symptoms.
The SMART-MR and SMART-Medea studies were approved by
the ethics committee, and written informed consent was obtained
from all participants.
Study Sample
Of the 710 patients included, 44 did not have an MRI scan and 30 did
not have adequate data for segmentation. Thus, for this study, we included the 636 patients in whom an adequate 3D T1 Fast Field Echo
sequence was performed,20 which is used for optimal characterization
of cerebellar cavities, as discussed elsewhere.13,15
Magnetic Resonance Protocol
The MR investigations were performed on a 1.5-Tesla whole body
system (Gyroscan ACS-NT, Philips Medical Systems, Best, The
Netherlands). The protocol consisted of a transversal T1-weighted
gradient-echo sequence (repetition time (TR)/echo time (TE): 235/2
ms; flip angle, 80°), a transversal proton density- and T2-weighted
turbo spin echo sequence (TR/TE: 2200/11 ms and 2200/100 ms;
turbo factor 12), a transversal T2-weighted fluid attenuating inverse
recovery (FLAIR) sequence (TR/TE/inversion time: 6000/100/2000
ms), and a transversal inversion recovery sequence (TR/TE/ inversion time: 2900/22/410 ms). All former sequences were acquired with
the following MRI sequence parameters: field of view, 230 mm×230
mm; matrix size, 180×256; slice thickness, 4.0 mm; slice gap, 0.0
mm; 38 slices. In addition, a 3D T1-weighted Fast Field Echo was acquired with the following MRI sequence parameters: TR/ TE: 7.0/3.2
ms; flip angle 8°, field of view, 240 mm; matrix size, 240×256; slice
thickness, 1.0 mm; no gap; 170 slices.
Brain Segmentation
We used the T1-weighted gradient-echo, inversion recovery sequence and FLAIR sequence for brain segmentation. The probabilistic segmentation technique has been described elsewhere.21 The
segmentation program distinguishes cortical gray matter, white matter, sulcal and ventricular cerebrospinal fluid, and WMH. The results
of the segmentation analysis were checked visually for the presence
of infarcts and adapted if necessary to make a distinction between
WMH and infarct volumes. Total brain volume was calculated by
summing the volumes of gray and white matter and existing volumes
of WMHs and infarcts. All volumes cranial to the foramen magnum
were included. Thus, the total brain volume includes the cerebrum,
brain stem, and cerebellum. Total intracranial volume was calculated
by summing total brain volume, sulcal volume, and ventricular cerebrospinal fluid volume.
Measurement of Cerebral Blood Flow
Postprocessing of flow measurements was performed blinded to the
clinical or brain characteristics of the patient. For each vessel, the spatial and time-averaged flow velocity was calculated from the phasedifference images by manually drawing a region of interest around
the vessel.22 The average flow velocity in each vessel was multiplied
by the cross-sectional area of the pixels in the region of interest to
obtain the volume of flow rate. Good agreement between the repeated
volume flow rate measurements was shown in our group, with a 5%
coefficient of variation.23 The flow through the left and right internal
carotid arteries and basilar artery were assessed and summed up to
calculate the total cerebral blood flow (tCBF expressed in mL/min).
Because interindividual differences in tCBF can be partly attributed
to differences in brain volume, we expressed tCBF per 100 mL brain
tissue by dividing the tCBF by the total brain volume (mL) and multiplying this by 100 to obtain parenchymal CBF.24
Image Analysis
Cerebrum and Brain Stem
The cerebrum was visually searched for infarcts by 2 trained investigators and a neuroradiologist to make a distinction between WMH
and brain infarcts. Raters were blinded for the history and diagnosis
of the patient. Discrepancies in rating were reevaluated in a consensus meeting. Lacunes of presumed vascular origin and infarcts were
defined as focal hyperintensities on T2-weighted images (T2WI) of at
least 3 mm in diameter, whereas dilated perivascular spaces were distinguished from infarcts and lacunes of presumed vascular origin on
the basis of their location, form, and the absence of gliosis. Lacunes
of presumed vascular origin and infarcts located in the white matter
also needed to be hypointense on T1- and FLAIR-weighted images to
distinguish them from WMH. Lacunes of presumed vascular origin
were 3 to 15 mm in diameter and located in the subcortical white matter or deep gray matter (thalamus or basal ganglia). Large subcortical
infarcts were sized >15 mm and were not confluent with cortical infarcts. Supratentorial infarcts included any cortical or large subcortical infarct, as well as all lacunes of presumed ischemic origin in deep
gray or white matter. WMH volumes were expressed as percentage of
intracranial volume. Large WMH volume was defined as the highest
quintile of WMH volume.
Cerebellum
The cerebellum was visually searched for infarcts including cortical cavities by a neuroradiologist (L.J.L.D.C.) blinded for the history and diagnosis of the patient. In case of doubt, cerebellar signal
abnormalities were reevaluated in a consensus meeting with another
neuroradiologist (J.H.). For the analysis of number and location of
cerebellar infarcts, transverse T2WI were used as a screening modality25 because these are known to be more sensitive than FLAIR
for the evaluation of the posterior fossa.26 Infarcts detected on T2WI
were correlated with FLAIR- and 3D T1-weighted images to assess
the presence of cavitation (Figures 1 and 2). Cavitation was present if intralesional fluid intensity on T2WI could be confirmed on
FLAIR- or 3D T1-weighted images. The longest and shortest diameter of each infarct were measured on axial T2WI, and the mean
axial diameter was calculated as the mean of both values. For each
infarct encountered, the involvement of cortex and white matter was
3156 Stroke November 2015
Figure 1. A, Axial T2-weighted image and (B) axial fluid attenuating inverse recovery show a cerebellar cortical infarct cavity (cross
mark) in the right cerebellar hemisphere, whereas its cortical location is best seen on the sagittal reconstruction of the 3-dimensional
T1-weighted images (C). The cavity shows signal intensities equal to cerebrospinal fluid on all magnetic resonance imaging sequences
(A–C). Notice the associated large subcortical infarct at the parieto-occipital junction (C).
evaluated on 3D T1-weighted images (Figures 1 and 2). Cerebellar
cortical ­(infarct) cavities were defined as cavities ≤1.5 cm involving
the cerebellar cortex.13,15
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Vascular Risk Factors
During the patient’s baseline visit to the medical center, an overnight
fasting venous blood sample was taken to determine glucose and lipid
levels. Height and weight were measured without shoes and heavy
clothing, and the body mass index was calculated (kg/m2). Systolic
and diastolic blood pressures (mm Hg) were measured twice with a
sphygmomanometer, and the average of the two measures was calculated. Hypertension was defined as mean systolic blood pressure
≥160 mm Hg or mean diastolic blood pressure ≥ 95 mm Hg or selfreported use of antihypertensive drugs. Diabetes mellitus was defined
as glucose ≥7.0 mmol/L or self-reported use of oral antidiabetic drugs
or insulin. Total cholesterol was defined as a continuous variable expressed in mmol/L. Smoking habits and alcohol intake were assessed
with questionnaires. Pack years of smoking were calculated, and alcohol intake was categorized as never, former, or current. Patients
who had quit drinking during the past year were assigned to the category current alcohol intake. Hyperhomocysteinemia was defined as
the highest quintile of homocysteine level versus the 4 lower quintiles. Ultrasonography was performed to measure the intima-media
thickness (IMT, mm) in the left and right common carotid arteries,
represented by the mean value of 6 measurements. The highest quintile versus lower 4 quintiles of IMT were defined for data analysis.
Physical and Mental Functioning
Global cognitive functioning was measured with the Mini-Mental
State Examination.27 Patients completed the Short Form-12 (SF-12),28
a shortened version of the SF-36 Medical Outcomes Study Health
Survey,29 to measure health-related quality of life. The SF-12 questionnaire includes 1 or 2 items from each of the 8 health summary
scales of the SF-3630 and enables calculation of the Physical and
Mental Component Summary scales. The SF-12 summary scales are
positively scored and normalized to a general population mean of 50
with SD of 10. Higher SF-12 scores indicate better health-related
quality of life; a positive change in SF-12 scores indicates an improvement and a negative change indicates a deterioration in healthrelated quality of life. Because of its brevity, the SF-12 is considered
advantageous over the SF-36 for large studies focusing on overall
physical and mental functioning.30
Data Analysis
Baseline characteristics were calculated for the study sample (n=636).
Next, logistic regression analysis was performed to estimate the associations of age, sex, and vascular risk factors (history of hypertension,
systolic and diastolic blood pressure, cholesterol level, homocysteine
level, diabetes mellitus, smoking, and alcohol intake) with presence
or absence of cerebellar cortical cavities, adjusted for age and sex.
Second, logistic regression analysis was performed to estimate the association between MRI markers of cerebrovascular disease (cortical
infarcts, large subcortical infarcts, lacunes of presumed vascular origin in deep gray and white matter, and cerebral blood flow) with presence or absence of cerebellar cortical cavities, adjusted for age and
sex. In addition, the latter analyses were repeated for patients with
multiple cerebellar cortical infarct cavities. Third, linear regression
analysis was used to investigate whether presence of cerebellar cortical infarct cavities (dependent variable) was associated with changes
in physical and mental functioning (independent variable), corrected
for age and sex. Statistical analyses were performed with SPSS 20.0
(IBM Corp, Armonk, NY).
Results
Baseline characteristics of the study are presented in Table 1.
The mean age of the population was 62±9 years (range, 33–83
Figure 2. A, Axial T2-weighted image and (B) axial fluid attenuating inverse recovery (FLAIR) show a cerebellar cortical infarct cavity
(arrow) in the right cerebellar hemisphere of a 60-year-old man, occurring in combination with an excavated pontine infarction (dashed
arrows). The hyperintense borders of both cavities on FLAIR are indicative of gliosis (B). Notice the cortical location of the lesion on the
sagittal reconstruction of the 3-dimensional T1-weighted images (C).
De Cocker et al Cerebellar Cortical Infarct Cavities 3157
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years) and 80.8% were men. The majority of the population
had coronary artery disease, which was present in 64.2%
at baseline. One or more cerebellar cortical cavities were
observed in 61 (9.6%) of patients, whereas cerebellar infarcts
all together, including cerebellar cortical infarct cavities, were
observed in 11% of patients.
Age (odds ratio [OR], 1.04 per year increase; 95% confidence interval [CI], 1.01–1.07) was associated with cerebellar cortical cavities, whereas sex was not. Table 2 shows the
results of the logistic regression analyses for the associations
of vascular risk factors and MRI markers with cerebellar cortical cavities after adjustment for age and sex. A positive history of cerebrovascular disease was significantly associated
with presence of cerebellar cortical cavities (OR, 3.1; 95%
CI, 1.8–5.4). Hyperhomocysteinemia was also significantly
associated with cerebellar cortical cavities (OR, 1.8; 95% CI,
1.0–3.3) as was with a high IMT (OR, 2.0; 95% CI, 1.1–3.7).
Other vascular risk factors were not significantly associated
with cerebellar cortical cavities.
Cortical infarcts in the cerebrum (OR, 2.9; 95% CI, 1.6–
5.4), supratentorial infarcts in general (OR, 2.9; 95% CI, 1.6–
5.3), and brain stem infarcts (OR, 5.1; 95% CI, 1.9–13.6) were
significantly associated with cerebellar cortical cavities after
correction for age and sex. Cerebral lacunes of presumed vascular origin were also significantly associated with cerebellar
cortical cavities (OR, 2.4; 95% CI, 1.3–4.2) after correction
for age and sex. After subdividing cerebral lacunes according to location, lacunes in the deep gray matter were more
strongly and significantly associated with cerebellar cortical
cavities (OR, 3.0; 95% CI, 1.6–5.8), whereas lacunes of presumed vascular origin in white matter were not (OR, 1.1; 95%
CI, 0.5–2.5).
Brain parenchymal fraction was significantly associated
with the presence of cerebellar cortical cavities (OR, 0.84;
95% CI, 0.74–0.94), which persisted after additional adjustments for IMT (OR, 0.85; 95% CI, 0.75–0.95) or supratentorial infarcts (OR, 0.87; 95% CI, 0.77–0.98), but lost statistical
significance after additional adjustments for both IMT and
supratentorial infarcts (OR, 0.89; 95% CI, 0.79–1.01). No
significant associations were found between cerebellar cortical cavities and large volume of WMH (OR, 1.2; 95% CI,
0.8–1.8) or parenchymal total cerebral blood flow (OR, 1.0;
95% CI, 1.0–1.0).
Presence of cerebellar cortical infarct cavities was significantly associated with worse physical functioning (OR 0.96;
95% CI, 0.94 to 0.99), whereas it was not associated with
mental functioning (OR 0.98; 95% CI, 0.94 to 1.02) or MiniMental State Examination (OR 0.97; 95% CI, 0.8 to 1.1).
Twenty-four patients (3.8%) showed multiple cerebellar
cortical infarct cavities, with a maximum of 10 in 1 patient.
Table 1. Baseline Characteristics of the Study Sample
Age, y
Study Sample
No CCC
CCC
n=636
n=575 (90.4%)
n=61 (9.6%)
61.2±9.5
64.6±9.5
80.8
80.2
86.9
Pack years of smoking, n=633
19.6
19.5
20.3
Present alcohol consumption, %
79.0
79.0
78.3
History of arterial hypertension, %, n=631
48.3
47.2
59.0
4.8
4.8
4.7
High homocysteine level, % (highest quintile,
>15.9 µmol), n=631
20.0
18.6
32.8
High IMT, % (highest quintile, >1.11 mm), n=631
18.9
17.3
33.9
History of diabetes mellitus, %
15.7
15.0
22.0
25.3
22.8
49.2
Supratentorial infarct, %
14.0
12.2
31.1
Cerebral cortical infarct, %
13.2
11.5
29.5
0.9
0.7
3.3
20.8
18.8
39.3
White matter lacunes, %
9.9
9.6
13.1
Gray matter lacunes, %
11.5
9.7
27.9
Brain stem infarcts, %
3.3
2.4
11.5
Total WMH, % ICV, n=609
0.26
0.25
Men, %
62±9
Vascular risk factors
Cholesterol, mmol/L, n=628
Vascular disease
History of cerebrovascular disease at follow-up, %
Cerebrovascular markers and measures on MRI
Large subcortical cerebral infarct, %
Lacune of presumed vascular origin, %
0.37
Brain parenchymal fraction, % of ICV, n=609
78.4
78.5
76.8
Parenchymal total CBF, mL/min/100 mL, n=587
50.9
51.0
49.3
Basilar artery flow, mL/min/100 mL, n=618
10.3
10.3
10.1
CBF indicates cerebral blood flow; CCC, cerebellar cortical (infarct) cavity; ICV, intracranial volume; IMT, intima-media thickness;
MRI, magnetic resonance imaging; and WMH, white matter hyperintensities.
3158 Stroke November 2015
Table 2. Results of Logistic Regression Analyses With
Vascular Risk Factors and Cerebrovascular Markers and
Measures on MRI as Determinants of Cerebellar Cortical
Cavities, Corrected for Age and Sex
Odds Ratio
95% CI
Age, per year increase
1.04
1.01–1.07
Sex, men
0.6
0.3–1.3
Pack years of smoking, per year increase
1.0
1.0–1.0
Present alcohol consumption, yes/no
1.0
0.7–1.5
Vascular risk factors
History of arterial hypertension, yes/no
1.6
0.9–2.8
Diabetes mellitus, yes/no
1.4
0.7–2.8
Cholesterol level, per mmol/L increase
0.8
0.6–1.1
High homocysteine level, highest quintile vs rest
1.8
1.0–3.3
IMT, highest quintile vs rest
2.0
1.1–3.7
3.1
1.8–5.4
Cortical infarcts, yes/no
2.9
1.6–5.4
Large subcortical infarcts, yes/no
4.3
0.7–24.7
Lacunes of presumed vascular origin, yes/no
2.4
1.3–4.2
Gray matter lacunes, yes/no
3.0
1.6–5.8
White matter lacunes, yes/no
1.1
0.5–2.5
Supratentorial infarct, yes/no
2.9
1.6–5.3
Brain stem infarct, yes/no
5.1
1.9–13.6
White matter hyperintensities, highest quintile
1.2
0.8–1.8
Brain parenchymal fraction, % of ICV
0.8
0.7–0.9
Peak blood flow total, mL/min
1.0
1.0–1.0
Peak blood flow in basilar artery, mL/min/100 mL
1.0
0.9–1.1
Vascular disease
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History of cerebrovascular disease
Cerebrovascular markers and measures on MRI
CI indicates confidence interval; ICV, intracranial volume; IMT, intima-media
thickness; and MRI, magnetic resonance imaging.
In the 24 patients with at least 2 cavities, 84 cavities were
observed in total, 65 of which occurred together with at
least one more cerebellar cortical infarct cavity within the
same lobe on the ipsilateral side, whereas only 19 of these
cavities occurred without a second cerebellar cortical cavity
within the same lobe on the same side. Although patients with
multiple cerebellar cortical infarct cavities showed a slightly
higher incidence of lacunes of presumed vascular origin and a
slightly lower incidence of brain stem infarcts, no significant
differences were found.
Discussion
This study shows cerebellar cortical infarct cavities on MRI in
10% of patients with history of arterial disease. The cavities
were significantly associated with age, IMT, hyperhomocysteinemia, cerebral infarcts, and intracranial atrophy, but not with
WMH or white matter lacunes of presumed vascular origin.
Also, they were associated with worse physical but not mental
functioning.
The association with age is unsurprising as cerebellar cortical cavities are an acquired phenomenon. A previous study
has shown that these cavities are surrounded by gliosis and
correspond to the remnants of infarction.13
Cerebellar cortical infarct cavities were associated with
markers of atherosclerosis, including high IMT and hyperhomocysteinemia.31 This suggests a large vessel origin of
cerebellar cortical cavities similar to symptomatic cerebellar
infarcts.7 As such, cerebellar cortical cavities may correspond
to the chronic counterpart of small cerebellar infarctions,
which have been well studied in the acute symptomatic stage
of infarction. In these studies, small cerebellar infarcts were
found to have the same origin as large cerebellar infarcts, most
frequently being artery-to-artery and cardiogenic emboli and
rarely cryptogenic.10,32 Nevertheless, small cerebellar infarcts
are only rarely detected in the acute stage, except when occurring in combination with other symptomatic infarcts.11 This
study now suggests that most cerebellar infarcts could be
small and escape clinical attention during the acute stage of
infarction.
A significant association was found between cerebellar
cortical (infarct) cavities and imaging markers of cerebrovascular disease, including cortical infarcts and lacunes of
ischemic origin in deep gray matter. In addition, the strong
association of cerebellar cortical cavities with brain stem
infarcts suggests that both may result from large vessel disease involving the same vertebrobasilar circulation territory
(Figure 2). Also, the high frequency of multiple cerebellar
cortical infarct cavities within the same anatomic area probably results from thromboemboli within the same perfusion
territories. Although cerebellar cortical cavities were significantly associated with lacunes of presumed vascular origin
in deep gray matter, this association did not hold true for
lacunes in white matter. Indeed, lacunes in gray matter have
been found to be merely related to atherothromboembolic
closure of proximal perforating arteries, whereas lacunes in
white matter more often represent small vessel disease.5,33,34
Likewise, no association was found between cerebellar cortical cavities and WMH in the cerebrum, another MRI marker
of small vessel disease.35,36
Although we anticipated a relationship between cerebellar
cortical (infarct) cavities and a diminished blood flow related
to, for example, atherosclerotic plaques and stenosis, no association was found between cerebellar cortical cavities and
total cerebral blood flow or basilar artery flow. Nevertheless,
most cerebellar cortical cavities occur in the posterior lobe of
the cerebellum,15 which is largely perfused by the posterior
inferior cerebellar arteries arising from the vertebral arteries,
the flow of which was not assessed in this study.37,38
A final interesting observation of this study was the significant association between cerebellar cortical cavities and brain
atrophy, which persisted after correction for supratentorial
infarcts. We hypothesize that this association could be mediated by concomitant supratentorial cerebrovascular lesions
below the detection limit of 1.5-Tesla MRI, such as cerebral
microinfarcts.39 Cerebral cortical microinfarcts are associated
with brain atrophy in addition to cortical and subcortical macroinfarcts.40 Thus, cerebral cortical microinfarcts have shown
similar associations with cerebrovascular markers on MRI as
we find with cerebellar cortical cavities, which might suggest
common risk factors or a shared pathophysiology of macroinfarcts, cerebral cortical microinfarcts, and cerebellar cortical
infarct cavities.
De Cocker et al Cerebellar Cortical Infarct Cavities 3159
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Observation of cerebellar cortical infarct cavities may
have the following implications. First, our study shows a significant reduction in physical functioning in patients with cerebellar cortical infarct cavities. In addition, identification of
these cavities increases the visible burden of brain infarcts on
MRI, and recent studies indicate that the total burden of (larger
and smaller) infarcts may explain patients’ (functional) status,
including cognitive performance and prognosis.1,41 Second, in
daily clinical practice, cerebellar cortical infarct cavities add
insights to the temporal and spatial (territorial) distribution of
brain infarcts and contribute to the risk evaluation of the individual patient. In case of cerebellar cortical infarct cavities,
patient’s cerebrovascular risk factors should be evaluated and
optimization of preventive therapy be considered.
Strengths of our study include the large cohort of patients
in which cerebellar cortical infarct cavities were meticulously studied. In addition, our cohort of patients with arterial disease presumably increased the yield of patients with
cerebellar cortical infarct cavities and other manifestations
of cerebrovascular diseases. Then again, most patients were
included because of large vessel disease, and this could have
weakened the association between cerebellar cortical infarct
cavities and individual risk factors for especially large vessel
disease. Another limitation is that we could not correlate cerebellar cortical infarct cavities with atrial fibrillation because
of lacking data. From a technical point of view, the detection
of the smallest cerebellar cortical infarct cavities (microcavities) may have been limited by the use of 1.5-Tesla MRI imaging and could have been potentially increased with the use
of higher MRI field strengths instead, as has recently been
demonstrated for cortical microinfarcts in the cerebrum at
3-Tesla and 7-Tesla.39,41,42 Nevertheless, because the cerebellar cortical infarct cavities are filled with cerebrospinal fluid,
there is often a relatively large intrinsic MRI contrast between
cerebrospinal fluid within the cavity and the surrounding brain
tissue, which render these cavities relatively easy to detect in
comparison with small infarcts with only gliosis.
In conclusion, small cerebellar cortical infarct cavities on
MRI appear to be far more common than previously assumed
based on symptomatic case series, and can be considered as a
marker for atherothromboembolic disease of the brain.
Appendix
Members of the SMART study group are A. Algra, MD, PhD,
Y. van der Graaf, MD, PhD, D.E. Grobbee, MD, PhD, and
G.E.H.M. Rutten, MD, PhD, Julius Center for Health Sciences
and Primary Care; F.L.J. Visseren, MD, PhD, Department of
Vascular Medicine; F.L. Moll, MD, PhD, Department of Vascular
Surgery; L.J. Kappelle, MD, PhD, Department of Neurology;
W.P.T.M. Mali, MD, PhD, Department of Radiology; and P.A.
Doevendans, MD, PhD, Department of Cardiology.
Sources of Funding
Prof Hendrikse was supported by European Research Council (ERC)
grant number: ERC-2014-StG - 637024_HEARTOFSTROKE.
Disclosures
None.
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Cerebellar Cortical Infarct Cavities: Correlation With Risk Factors and MRI Markers of
Cerebrovascular Disease
Laurens J.L. De Cocker, Raoul P. Kloppenborg, Yolanda van der Graaf, Peter R. Luijten, Jeroen
Hendrikse, Mirjam I. Geerlings and for the SMART Study Group
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
Stroke. 2015;46:3154-3160; originally published online September 17, 2015;
doi: 10.1161/STROKEAHA.115.010093
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2015 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/46/11/3154
An erratum has been published regarding this article. Please see the attached page for:
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Correction
In the article by De Cocker et al (De Cocker LJL, Kloppenborg RP, van der Graaf Y, Luijten PR,
Hendrikse J, Geerlings MI; SMART Study Group. Cerebellar cortical infarct cavities: correlation
with risk factors and MRI markers of cerebrovascular disease. Stroke. 2015:46: 3154–3160. DOI:
10.1161/STROKEAHA.115.010093.), which published online ahead of print on September 17,
2015, and appeared in the November 2015 issue of the journal, a correction was needed. The final
version of the article presented regression coefficients rather than odds ratios for the functioning
scales.
On page 3154, Abstract section Results, line 7, “(OR, −2.6; 95% CI, −5.7 to −0.9),” has been
changed to read “(OR 0.96; 95% CI, 0.94 to 0.99).”
On page 3156, Materials and Methods Data Analysis section, second to last sentence, “Third,
linear regression analysis was used to investigate whether presence of cerebellar cortical infarct
cavities (independent variable) was associated with changes in physical and mental functioning
(dependent variable), corrected for age and sex,” has been changed to read “Third, linear regression
analysis was used to investigate whether presence of cerebellar cortical infarct cavities (dependent
variable) was associated with changes in physical and mental functioning (independent variable),
corrected for age and sex.”
On page 3157, fifth paragraph of the Results, “Presence of cerebellar cortical infarct cavities was significantly associated with worse physical functioning (OR, −2.6; 95% CI, −5.7 to
−0.9), whereas it was not associated with mental functioning (OR, −1.1; 95% CI, −2.7 to 0.8)
or MiniMental State Examination (OR, −0.4; 95% CI, −0.5 to 0.4),” has been changed to read
“Presence of cerebellar cortical infarct cavities was significantly associated with worse physical
functioning (OR 0.96; 95% CI, 0.94 to 0.99), whereas it was not significantly associated with
mental functioning (OR 0.98; 95% CI, 0.94 to 1.02) or Mini-Mental State Examination (OR 0.97;
95% CI, 0.8 to 1.1).”
The significance of the results does not differ from the original results.
The authors regret the error.
This correction has been made to the online version of the article, which is available at http://
stroke.ahajournals.org/content/46/11/3154.
(Stroke. 2016;47:e38. DOI: 10.1161/STR.0000000000000094.)
© 2016 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STR.0000000000000094
e38