LETTER TO THE EDITORS

Judgment of FLAIR signal change in DWI–FLAIR mismatchdetermination is a challenge to clinicians

Annerose Ziegler • Martin Ebinger •

Jochen B. Fiebach • Heinrich J. Audebert •

Stefanie Leistner

Received: 20 July 2011 / Revised: 4 October 2011 / Accepted: 7 October 2011 / Published online: 27 October 2011

� Springer-Verlag 2011

Dear Sirs,

Preliminary data suggest that the diffusion-weighted imag-

ing (DWI)–fluid-attenuated inversion recovery (FLAIR)

mismatch (where a new hyperintense lesion is not seen on

FLAIR but is apparent on DWI) can be used for allocation

to the most likely time window for intravenous thrombol-

ysis therapy in stroke patients [1–5, 9]. However, the cri-

teria for determination of DWI–FLAIR mismatch are

difficult to standardize, and a challenge to clinicians. In the

case described herein intravenous thrombolysis was with-

held from a patient with an unknown time of onset due to a

subtle increase of signal intensity on FLAIR, only recog-

nizable with knowledge of the DWI lesion.

The 63-year-old patient woke up with a left sensomotoric

hemiparesis, moderate dysarthria, multimodal neglect, and

anosognosia [National Institutes of Health Stroke Scale

(NIHSS) 6]. Magnetic resonance imaging (MRI) examina-

tion performed 2.5 h after first found abnormal time (FAT)

and 8.5 h after last normal time (LNT) revealed a DWI

lesion in the right middle cerebral artery (MCA) territory

with a corresponding M3 occlusion. Using visual analysis

of signal intensity changes on FLAIR and DWI, within the

area of the DWI lesion a subtle FLAIR hyperintensity was

noted (Fig. 1). Neither acute intracranial hemorrhage nor

microbleeds were visible on T2*, but white matter disease

was visible (Wahlund score 17). It was unclear whether the

subtle hyperintensity on the FLAIR lesion should be clas-

sified as DWI–FLAIR match or mismatch. After some

discussion, according to Aoki et al. [1], we deemed this as a

pattern of DWI–FLAIR match. We therefore did not give

tissue plasminogen activator (tPA). Based on the diagnosis

of atrial fibrillation, infarct etiology was classified as car-

dioembolic. The patient received aspirin only.

Unfortunately, 9 h after first found abnormal time (FAT)

the patient developed reduced consciousness, left bra-

chiofacial sensorimotor hemiplegia, severe dysarthria, and

dysphagia (NIHSS 16). Computed tomography (CT)

showed symptomatic intracranial hemorrhage (sICH) in the

posterior territory of the right MCA with 5 mm midline

shift (Fig. 2a–c). Follow-up MRI with MR angiography

showed recanalization of the right middle cerebral artery

branch (M3) and a progressive midline shift (Fig. 2d–e).

Three weeks after the acute stroke event the patient was

still severely affected with fluctuating vigilance, severe

dysphagia, and hemipareses (NIHSS 15).

Up to 25% of stroke patients awake with their symptoms

with unknown onset. DWI–FLAIR mismatch thrombolysis

may provide clinicians a practical tool for an intervention.

Recently, Aoki and colleagues described intravenous

thrombolysis based on DWI–FLAIR mismatch in stroke

with unknown onset time [1]. They observed no symp-

tomatic intracerebral hemorrhage (sICH) after DWI–

FLAIR mismatch-based thrombolysis in 10 patients with

median interval between LNT and intravenous thrombol-

ysis of 5.6 h. However, absence of sICH did not prove

increased safety in a population of 10 patients.

Our case is a good example that the definition and

clinical application of DWI–FLAIR mismatch is still an

arbitrary call, especially the judgment of FLAIR hyperin-

tensities within the DWI lesion. Focal FLAIR hyperinten-

sities within the acute DWI lesion are predictors of sICH

[2]. Patients with large signal changes on DWI are more

likely to develop early FLAIR positivities [3, 4, 6]. It is

A. Ziegler (&) � M. Ebinger � J. B. Fiebach �H. J. Audebert � S. Leistner

Department of Neurology, Charite, Universitatsmedizin Berlin,

Campus Benjamin Franklin, Hindenburgdamm 30,

12203 Berlin, Germany

e-mail: annerose.ziegler@charite.de

123

J Neurol (2012) 259:971–973

DOI 10.1007/s00415-011-6284-6

questionable whether patients with large DWI lesions and

subtle FLAIR hyperintensities should be excluded from

thrombolysis [2]. Aoki and colleagues showed in MRI

studies acquired within 24 h from stroke onset that DWI-

positive, FLAIR-negative scans were 83% sensitive and

71% specific for identifying stroke onset within 3 h [1].

Petkova and colleagues’ results improved to 94% sensitivity

when taking into consideration large DWI abnormalities

with subtle FLAIR abnormalities limited to the cortex [4].

The criteria for evaluation of a FLAIR hyperintensity

within the DWI lesion are difficult to standardize. The

generalizability of MR-based studies has been questioned,

since differences in study population, interrater agreement

(level of training and instructions to readers), and imaging

techniques used (degree of contrast used, visually versus

automatically calculated DWI–FLAIR signal changes)

influence study results [8]. The MR Witness trial applied

extensive training requirements to ensure that investigators

Fig. 1 3-T MRI DWI lesion in the posterior territory of the right middle cerebral artery and corresponding FLAIR sequences on admission

(2.5 h after FAT). Images a and c show the DWI lesion with beginning cortical demarcation on FLAIR images (b and d)

Fig. 2 a–c CT scan of the brain

with symptomatic intracerebral

hemorrhage in the territory of

the right middle cerebral artery

9 h after first found abnormal

time (9 h after FAT). d–f 3-T

MRI images show the progress

of symptomatic intracerebral

hemorrhage (26 h after FAT)

972 J Neurol (2012) 259:971–973

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agreed on the same definition, including measurements of

signal intensity [7].

In conclusion, our case illustrates that judgment of

FLAIR signal changes within DWI lesions is not yet well

defined, and in its current definition often remains difficult

to use for treatment decisions.

Conflicts of interest The authors declare no conflicts of interest.

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