JOURNAL READING

Relation of infarction location and volume to vertigo in

vertebrobasilar stroke

Dipresentasikan oleh:
dr. Ghea Sugiharti

Pembimbing: 1
dr. Arinta Puspitawati Sp. S
Relation of infarction location and
volume to vertigo in
vertebrobasilar stroke
ORIGINAL RESEARCH
Introduction

Dizziness  major public health problem and an independent

predictor of increased mortality

Dizziness and vertigo  more common among women and

elderly population

Stroke  underlying etiology in 17%–25%

4% of patients presented acute onset isolated vertigo
Introduction
Lesions affecting the following structures related to vascular vertigo
• vestibular nuclei
• nucleus prepositus hypoglossi in the dorsal brainstem,
• dorsal insular cortex: cerebellar tonsil, flocculus, nodulus, and inferior
cerebellar peduncles

Vertigo  common presentation of vertebrobasilar stroke.

Anecdotal reports  vertigo occurs more often in multiple than in single

brainstem or cerebellar infarctions

to examine the relationship of infarction volume and

Aim location to vertigo in patients diagnosed with a
vertebrobasilar stroke.
Methods

Subjects • Consecutive patients admitted to the Department of

Neurology (University Hospital of Würzburg)
• Diagnosis of vertebrobasilar stroke

Study Period • February to October 2018.

Inclusion • The patient could communicate the presence or absence of

vertigo
• Magnetic resonance imaging (MRI) could be done within 4
days of admission  showed brain infarction
 Methods

Group 1
Vertigo (+)
Vertigo definition (Bárány Society)
Patient Stratification “the feeling of self-motion, when no self
motion is occurring”
Group 2
Vertigo (-)

National Institute of Health Stroke Scale Modified Rankin Scale (mRS) and Barthel
(NIHSS)  admission index  discharge
 MRI imaging

MRI Evaluation
• Field strength of 3-Tesla • Infarction location and volume  assessed in the strong (b =
 based on standardized 1,000) diffusion-weighted images (DWI)
stroke acquisition • Single investigator (AME)  nonblinded
protocols
• Infarction  manually delineated to obtain the infarction
•
area in each slice separately
• Slice thickness of 5 mm
and an interslice gap of • The sum of all slices  to obtain the infarction volume
0.5 mm.
 01. Qualitative data
Expressed in absolute values and percentages

02. Quantitative data

Expressed using median and range

Statistic 03. Normality

Q–Q plot, histogram, and the Shapiro–Wilk test
Analysis
04. Univariate statistical tests
Categorical data  chi-squared test
if n < 5  fisher's exact test
Continuous data  mann–whitney U test
Spearman coefficient  analyze correlations

Receiver operating curve (ROC ) to calculate the

cutoff infarction volume value for the occurrence of
vertigo
An area under the curve (AUC) > 0.5 indicates Statistic
better prediction, and values closer to 1 indicate more
accurate prediction. Analysis
Univariate binary logistic regression analysis 
to measure the strength of association measured as
OR (95% CI)
Statistic Analysis
• Multivariate logistic regression with inclusion
method  to adjust for age and sex

• Fitness of this model  using a Hosmer–Lemeshow

“goodness-of-fit” test Method
• Data analyzed in SPSS ver 25

• P-values < .05  statistically significant.

 TA B L E 1 Baseline characteristics

Results
 Results

BASELINE
CHARACTERISTICS
95patients were included (Table 1)

Among vertigo (+)

• Significantly less proportion of men (53.1% vs. 77.8%, respectively,p=
.049)

Median infarction volume

• Women = 3.99 (0.92–26.86) cm3
• Men 2.32 (0.21–12.35) cm3
• (p= .11, Figure 1a)
 Results

Figure 1. (a) Total infarction volume among men and women (p = .11). (b) Total infarction volume among
vertigo (+) patients versus vertigo (−) patients (p = .008)
Results

RELATION BETWEEN INFARCT LOCATION &

VOLUME AND THE PRESENCE/ABSENCE OF
VERTIGO
Infarction location

• Cerebellum or dorsal brainstem = significantly more common among vertigo (+)

• (90.6% vs. 40.7%, p < .001)

Total infarction volume

• Larger among vertigo (+)

• 5.6 cm3 vs 0.42 cm3 (p = .008, Figure 1b)
• Difference more evident for infarctions in cerebellum (median 9.09 vs 0.26 cm 3)
Results

Figures 2 and 3  different examples for patients with vertigo (+) and vertigo (-)
patients with vertebrobasilar stroke.
 Results
a. ROC showing the relation between the total infarction volumes and vertigo
b. ROC showing the relation between the volume of infarctions located in the cerebellum and vertigo

ROC curve, a cutoff volume of >0.48 cm3 for Cutoff volume of >0.36 cm3 for cerebellum
all infarctions associated with vertigo infarctions associated with vertigo,
(sensitivity 84%; specificity 56%) sensitivity 96% & specificity 78%;
AUC (95% CI) = 0.7 (0.57–0.84), p = .008 AUC (95% CI) = 0.86 (0.69–1.0), p = .002
 Table 2. Predictors of vertigo in the binary logistic
regression models
Results

Infarction location in
cerebellum or dorsal
brainstem
and volume of >0.48 cm3
have OR (95% CI) of 16.97
(3.1–92.95), p = .001 and 4.4
(1.05–18.58),p = .043,
respectively to be associated
with vertigo
Table 3. Factors associated with a total infarction volume >0.48 cm3
in the binary logistic regression models

Results

The Hosmer–Lemeshow = nonsignificant

difference between observed & expected results
(p = .88)

In another multivariate logistic regression

adjusted  vertigo independently predicted a
total infarction volume >0.48 cm3 (OR 5.75,
95% CI 1.43–23.08, p = .01

Hosmer–Lemeshow “goodness-of-fit” = p-value

of .2
Results

Vertigo & focal neurological deficits

• Fewer patients with neurological deficits in vertigo group

• (65.6% vs. 96.3%, p = .004).
• Tendency for vertigo (+) have delayed presentation;
• Median (IQR) was 7.5 (4–46) hours compared to 4 (2–12) hours (p = .052)
• IV thrombolysis
• 15.6% in vertigo (+) group vs 37% of vertigo (-) group (p = .06)

Relation between clinical scales & infarction volume

• Infarction volume did not correlate with NIHSS score on admission (ρ = .077, p = .56)
• Correlated with mRS (ρ = .37, p = .004) & Barthel index (ρ = .33, p = .011)
Discussion

Vertigo (+) group  fewer patients with focal neurological

deficits  the patients tended to present later than the
vertigo (−) group.

Fewer patients in the vertigo (+) group received IV

thrombolysis in comparison with the vertigo (−) group

It might be speculated that women were more prone to

develop vascular vertigo ~ the infarction volume was
insignificantly larger in women

Other studies
VBS stroke more often compared to anterior circulation due to
lack of obvious neurological sign
 Discussion
• Less men
Vertigo (+) group • Fewer focal neurological deficits
• Larger total volume

• Cerebellum or dorsal brainstem significantly related

Location
to vertigo

Larger infarcts • Affect brain structures & interconnections causing

especially in
vertigo
cerebellum

Focal • From small strategically located infarctions

neurological • Comparable to moderate-severe hemiparesis in
signs small capsular infarctions
RELATION OF LOCATION & VOLUME TO
VERTIGO
Axial diameter ≤10 mm

• 14% patients with vascular vertigo

Neurological signs

• Among 27% of their patients with small lesions

• Mostly involving inferior cerebellar peduncle & lateral medulla

Vertigo

• Also found among multiple unilateral pontine lesions & single lesion in <50%
cases
CLINICAL SCALES & INFARCTION VOLUME

NIHHS score are lower among VB NIHHS not consider clinical manifestations
stroke compared to anterior circulation related to posterior circulation (vertigo,
stroke nystagmus, nausea, or vomiting)

Severe vertigo may have 0 NIHSS In our cohort, infarction volume not
mRS or Barthel index score but with mRS score of 3 if correlate with NIHSS score on admission
may show worse score he requires some help of ADL but correlated with mRS and Barthel
index on discharge
SEX, VERTIGO AND BRAIN INFARCTION

• Men ~32% higher than women in anterior or posterior circulation

Sex • VB stroke’s odd ratio higher in men

Contrarily • Men = 1/3 vertigo population

• Less men in vertigo (+)

Our cohort • Speculated that women more prone to develop vascular vertigo  diluting
proportion

Previous studies • Also found 55%–57% male among acute vascular vertigo

Volume • Insignificantly larger in women (similar to other study)

PATIENT WITH TIA (WHO) ALSO STROKE
(AHA/ASA)
WHO (Historically)

• TIA = transient focal neurological deficit lasting <24 hr

AHA/ASA revision

• TIA = transient neurological dysfunction caused by focal brain, spinal cord, or retinal
ischemia, without acute infarction

In current work

• 12/59 (20.3%) patients had no focal neurological deficits, yet had brain infarction on MRI
• Therefore met TIA old definition & modern AHA/ASA stroke definition
CLINICAL IMPORTANCE

• Negative focal deficits in vertigo can’t differ central & peripheral

vertigo
Clinical implication • May cause delay in IV thrombolysis
• infarction volume was larger in patients with vertigo

• Atrial fibrillation on anticoagulation presents with acute vertigo

Common scenario • Before anticoagulant  exclude possibly underlying large infarction
(hemorrhagic transformation may ensue)
CLINICAL IMPORTANCE
• Missed on DWI MRI
MRI (-) stroke • In ~1/3 nondisabling stroke, especially small infarctions

Vertigo absence in • May be warning sign MRI negative stroke

suspected VB stroke

Benefit of IV • Remain unclear for VB stroke with and without vertigo

thrombolysis • Large or small infarction may play role

• Infarction volume may affect clinician's decision to give or refrain IV

Wake-up VB stroke
thrombolysis.
Limitation

Nonrandomized single-center cohort  need

larger randomized multicenter studies

This study infarctions volume and location were

assessed by a single nonblinded investigator
(AME).
CONCLUSION
• Cerebellar or dorsal brainstem infarctions = strong
predictors of vertigo in vertebrobasilar stroke.
• Larger infarction volume in these structures related
to vascular vertigo.
• Vertigo without focal neurological deficit common
among vertebrobasilar stroke
• NIHSS scale has limited in assessing vertebrobasilar
stroke compared with anterior circulation stroke
 CRITICAL
APPRAISAL
 PICO

P • 59 patient with vertebrobasilar stroke

I • MRI imaging

C • Infarct location and volume between vertigo (+) and vertigo (-) group

O • Infarction location and volume as an predictor of vertigo

VALIDITY

Yes, this study aim to examine the relationship of infarction volume & location
to vertigo in patients diagnosed with a vertebrobasilar stroke
VALIDITY

Consecutive patients admitted to the Department of Neurology

(University Hospital of Würzburg) with the diagnosis of vertebrobasilar
stroke were prospectively recruited between February and October 2018
VALIDITY

● Patients were included only if they could communicate the presence or absence of vertigo, and a
magnetic resonance imaging (MRI) could be done within 4 days of admission and showed brain
infarction
● National Institute of Health Stroke Scale (NIHSS) on admission and modified Rankin Scale
(mRS) and Barthel index on discharge were used as clinical scales
● Magnetic resonance imaging scanners with a field strength of 3-Tesla were used according to our
standardized stroke acquisition protocols with a slice thickness of 5 mm and an interslice gap of
0.5 mm.
VALIDITY

The infarction location and volume were assessed in the

strong (b = 1,000) diffusion-weighted images (DWI) in our picture
archiving and communication system (PACS) by a single investigator (AME),
who was nonblinded to the clinical data
IMPORTANCE

In another multivariate logistic regression,

after adjusting for age, sex, intravenous thrombolysis,
serum level of white blood cells, and atrial fibrillation,
vertigo independently predicted a total infarction volume
>0.48 cm3 (OR 5.75, 95% CI 1.43–23.08, p = .01) as
shown in Table 3 (Hosmer–Lemeshow “goodness-of-fit”
test showed a p-value of .2)
IMPORTANCE

● No reports regarding exclusion or

drop out
● Follow up is long enough between
Feb and October 2018
WHAT ARE THE RESULT?
The infarction volume did not correlate with National Institute of Health Stroke Scale (NIHSS) score on
admission
• (Spearmanρ= .077,p= .56)

But correlated with modified Rankin Scale on discharge

• (ρ= .37,p= .004)

In the vertigo group, the proportion of men was lower

• (53.1% vs. 77.8%,p= .049)

Fewer patients had focal neurological deficits

• (65.6% vs. 96.3%,p= .004)

Patients tended to present later

• (median [IQR] was 7.5 [4–46] vs. 4 [2–12] hours,p= .052),
WHAT ARE THE RESULT?

Fewer patients received IV thrombolysis

• (15.6% vs. 37%,p= .06)

Total infarction volume was larger

• (5.6 vs. 0.42 cm3,p= .008)

In multivariate logistic regression

• Infarction location either in cerebellum or the dorsal brainstem (odds ratio [OR] 16.97, 95% CI 3.1–92.95,p= .001)
and a total infarction volume of &gt;0.48 cm3 (OR 4.4, 95% CI 1.05–18.58,p= .043) were related to vertigo.

After adjusting age, sex, IV thrombolysis, serum WBC, and AF,

• Vertigo independently predicted a total infarction volume of &gt;0.48 cm3 (OR 5.75, 95% CI 1.43–23.08,p= .01)
HOW PRECISE ARE THE RESULTS?

● To calculate the cutoff infarction volume value for the occurrence of

vertigo, a receiver operating curve (ROC) was used. We chose the
points closest possible to the upper left corner to get cutoff values
with high sensitivity. An area under the curve (AUC) > 0.5 indicates
better prediction, and values closer to 1 indicate more accurate
prediction.
● To adjust for age and sex, we conducted a multivariate logistic regression with
inclusion method. In this model, we included variables found in the univariate
model with p < .1. We tested the fitness of this model using a Hosmer–Lemeshow
goodness-of-fit” test.
● p-values < .05 were considered statistically significant.
APPLICABILITY

The nonrandomized nature of this single-

center cohort should be kept in mind before a
conclusion can be drawn from our results.
APPLICABILITY

In discussion there are plenty of

evidences regarding previous results
showing similar findings with ours.
APPLICABILITY

● The absence of focal neurological deficits in patients with vertigo should never serve as a
differentiating criterion between central and peripheral vertigo
● The clinician is ought to carefully exclude vascular vertigo with possibly underlying large
infarction, before continuing the anticoagulation in the acute phase.
● ~1/3 of nondisabling stroke, especially small brain infarctions, posterior circulation infarctions
causing mild perfusion deficits not amounting to induce DWI lesion are missed on initial brain
MRI (“MRI negative stroke”)
● Benefit from IV thrombolysis remains a matter of future research.
Journal Gerading
and Level Of
Evidence
Journal Gerading and
Level Of Evidence
Thank you doctor