Kevin King MD UT Southwestern Medical Center Division of ...

Kevin King MD
UT Southwestern Medical Center
Division of Neuroradiology
NIH CTSA Clinical Scholar

Normal Impairment
WMH

White Matter Hyperintensities are biomarkers of
preventable cerebral microvascular disease & predict risk
for cognitive and motor impairment, stroke and death
Debette S, Markus HS. The clinical importance of white matter hyperintensities on brain magnetic resonance
imaging: Systematic review and meta-analysis. BMJ. 2010.341:c3666

Vascular pathology is likely involved in a majority of
clinically significant cases of dementia, lowering the
threshold for development of Alzheimers Dementia
Black, S., F. Gao, and J. Bilbao, Understanding white matter disease: imaging-pathological correlations in vascular
cognitive impairment. Stroke, 2009. 40(3 Suppl): p. S48-52.

Normal Impairment

Without an accepted grading system, the near ubiquity of
WMH in older populations causes the finding to be
ignored by most clinicians and is a source of unnecessary
concern for many patients.

Fazekas
An Ideal Clinical Screening Scale:
Benefits:
Simple: Easy to incorporate into practise
Predictive of clinical outcomes
Areas of concern:
Rating of Deep vs. Periventricular
Reproducibility

Original Fazekas WMH Scale
Grade Descriptor Deep WMH Periventricular WMH
0 Absent None None
1 Mild Punctate Pencil Thin Lining
2 Moderate Near Confluent Smooth Halo
3 Severe Confluent Irregular band extending
into the deep white matter
Fazekas F, et al. MR signal abnormalities at 1.5 t in alzheimer's dementia and normal aging. Am. J. Roentgenol.
1987;149:351-356

Fazekas outcome correlations
equivalento to volumetry and
more complex scales
Scale Gait (SPPB) Cognition (MMSE)
Fazekas- Gouw* -0.19 -0.13
Scheltens -0.21 -0.13
Volumetry -0.22 -0.10
* included objective measurement criteria:
mild 2cm.
Gouw AA, et al. LADIS Study Group. Simple versus complex assessment of white matter hyperintensities in relation
to physical performance and cognition: the LADIS study. J Neurol. 2006 Sep;253(9):1189-96. Sep 22.

Research insights on rating
Periventricular Vs. Deep

Irregular Periventricular WMH
demonstrated = pathologic changes
as Severe Deep WMH
Fazekas, et al. revision
Grade Descriptor Deep WMH Periventricular WMH
0 Absent Absent Absent
1 Mild Punctate Pencil Thin Lining
2 Moderate Near Confluent Smooth Halo
3 Severe Confluent DWMH equivalent to Irregular PVWMH
Fazekas F, et al. Pathologic correlates of incidental mri white matter signal hyperintensities. Neurology. 1993;43:1683-
1689.

Periventricular & Deep WMH
3D analysis by De Carli et al suggested identification of
periventricular vs. deep in 2D axial images is arbitrary-
on sagittal and coronal ‘deep’ lesions often contact the
ventricle
C. DeCarli, et al. Anatomical Mapping of White Matter Hyperintensities (WMH): Exploring the Relationships
Between Periventricular WMH, Deep WMH, and Total WMH Burden. Stroke, January 1, 2005; 36(1): 50 - 55.

Periventricular & Deep WMH
Spatial analysis failed to identify distinct
populations with Deep versus Periventricular
disease.
PVWMH and DWMH correlate highly with each
other and with total WMH burden
C. DeCarli, et al. Anatomical Mapping of White Matter Hyperintensities (WMH): Exploring the Relationships
Between Periventricular WMH, Deep WMH, and Total WMH Burden. Stroke, January 1, 2005; 36(1): 50 - 55.

Questioned Reproducibility
Inter-rater reliability for Fazekas
Variable among studies ranging from poor to excellent,
kappa of .43 to .78
May be higher in studies with more advanced WMH due
to a ceiling effect
? Increased by objective criteria such as in Gouw: not
assessed for inter-rater reliability
Scheltens, P., et al., White matter changes on CT and MRI: an overview of visual rating scales. European
Task Force on Age-Related White Matter Changes. Eur Neurol, 1998. 39(2): p. 80-9.

Gouw Modification of Fazekas
Gouw et al. revision
Grade Descriptor Deep WMH Periventricular WMH
0 Absent Absent Not explicitly described.
1 Mild Single lesions < 10mm
Grouped ≤ 20mm
2 Moderate Single lesions 10-20mm
Grouped >20mm
3 Severe Single/ Confluent lesions
>20mm
Gouw AA, et al. Simple versus complex assessment of white matter hyperintensities in relation to physical
performance and cognition: The ladis study. J Neurol. 2006;253:1189-1196

Proposed Clinical Scale
Grade Descriptor Deep WMH Periventricular WMH*
0 Absent All foci

Evaluation of New Method
Subset of the Dallas Heart Study,
a multi-ethnic community based study
Age 50.7+9.7
Hispanic 15%
NonHisp Black 44%
NonHisp
White 38%
Other Race 2%
Female 52%

3T Images,
Achieva Philips Medical Systems
FLAIR
3D MP RAGE

Initial Evaluation
Test set of 52 studies demonstrating a range of WMH
volumes independently read by two reviewers
Evaluation of discordant reads demonstrated poor
agreement in categorization of small hyperintense foci

Revision
Established 3mm size threshold, reviewed 40 random
studies
Agreement for grading of no versus mild disease was
72.4% (kappa 0.44 SE 0.17) without the threshold
compared with 89.2% with the rule (kappa 0.76 SE 0.11)
with p= 0.055.

Overall Reproducibility
For initial test group enriched for large WMH volumes
Agreement of 67% (kappa=0.71) n=52
For random community sample with overall small
WMH volumes (with 3mm threshold)
Agreement of 87.5% (kappa = 0.76) n=40

Comparison with WMH Volumes
WMH scores from 559 participants showed
significant correlation with automated
volumes (spearman rho 0.57, p

Conclusion
We report the development of a visual WMH scoring
system suited for use in clinical practice.
Grade
0
Descriptor
Absent
Deep WMH
All foci

DHS Brain Study Group
Ronald M. Peshock MD 1,2
Keith M. Hulsey MS 1
Lea Alhilali MD 3
Roderick W. McColl PhD 1
Myron Weiner 4
Anthony R. Whittemore MD PhD 1
Departments of 1 Radiology, 2 Internal Medicine, and 4 Neurology
The University of Texas Southwestern Medical Center
Department of 3 Radiology
University of Pittsburgh Medical Center

Regular progression of WMH
Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study.
Manolio TA, Bryan RN, et al. Stroke. 1994 Feb;25(2):318-27.

Age Related White Matter Changes
Score: A variant of Fazekas
Grade Descriptor
0 No lesions (including symmetrical, well-defined caps or bands)
1 Focal lesions, ≥5 mm
2 Beginning confluence of lesions
3 Diffuse involvement of the entire region
• Frontal, Parieto-Occipital, Temporal, Infratentorial & Basal Ganglia scored
separately for each hemisphere
• Periventricular and Deep scored Jointly
ARWMC Scale: A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke
2001;32:1318–1322. Wahlund LO, Barkhof F, Fazekas F, Scheltens P. et al on behalf of the European Task Force on Age-
Related White Matter Changes

Fazekas has good correlation with
WMH volumetry
Scale
Agreement with
Volumetry
(Kendall W)
Fazekas- Schmidt* 0.57
Scheltens 0.48
Manolio 0.37
* included category for number of lesions with 0 for no lesions, 1 for 1 to 4
lesions, 2 for 5 to 9 lesions, and 3 for >9 lesions.
Kapeller Pet al. Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison,
interrater agreement, and correlations with quantitative measurements. Stroke. 2003 Feb;34(2):441-5.

Among the Many Systems developed:
Which to choose?
Mäntylä R, et al.Variable agreement between visual rating scales for white matter hyperintensities on MRI. Stroke.
1997 Aug;28(8):1614-23.