Letters to the Editor
Stroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. They should not exceed 750 words (including references)
and may be subject to editing or abridgment. Please submit letters in duplicate, typed double-spaced. Include a fax number for the corresponding author and
a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org).
ment are confusing values: for example, risk of atrial fibrillation/
embolization inevitably trumps competitive infarction ideas.
Regardless of putative etiology, the logical expectation in any
population of surviving stroke patients is that most prevalent
brain lesions are, indeed, small. An extensive stroke literature
review11 found no significant differences among risk factor
profiles between lacunar and nonlacunar infarcts. Hence the
heuristic power of the lacunar label in stroke now matches the
lost cause value of miasma vapors in the history of malaria
infection.
Absent the lacunar prejudice regarding pathology or pathogenesis, every brain lesion may/must be identified independently by
site, volume, temporal course, clinical correlation, if any, and
even histopathology.
Leukoaraiosis is the scholarly Greek title invented long ago
by Drs Hachinski, Potter, and Merskey12 in order to deal critically
with the new pathological entity, uniquely brought to discovery
by clinical CT and MRI. [Wardlaw’s generic label, WML, is not
a proper synonym.] They noted that the condition is “associated
with cognitive impairment and to some extent, with vascular
disease. Possible causes of white-matter changes and their
relationships to Alzheimer disease are examined, and it is argued
that a neutral term, exact enough to define white-matter changes,
sufficient as a description or label, and demanding enough to
require precise clinical and imaging descriptions is needed.” I
believe that their invitation for proof of pathogenesis is still
open,13 although popular repetition seems to justify the factoid
presumption of obscure vasculopathy.14,15,16
Wardlaw’s devastating critique of the presumptions, methodology, and conclusions of the LADIS study merits acceptance,
with the footnote that none of the LADIS patients suffered the
necessity of pathological evaluation.17,18
What Is a Lacune? Dogged déjà vu doggerel
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
To the Editor:
“Then you should say what you mean,” the March Hare went on.
“I do,” Alice hastily replied; “at least–at least I mean what I
say–that’s the same thing, you know.”
“Not the same thing a bit!” said the Hatter.
“Why, you might just as well say that ‘I see what I eat’ is the
same thing as ‘I eat what I see’!”
Alice in Wonderland
—Lewis Carroll
Dr Wardlaw’s plaintive query1 documents 21st century survival of clinical science confusion driven by hopelessly specious
terminology: “lacune,” “lacunar infarct,” “lacunar stroke,” “clinical stroke syndrome with typical symptoms and signs referable
to a small subcortical or brain stem lesion,” “clinically evident
lacunar infarct,” “clinical stroke syndrome of lacunar type where
the underlying lesion is an infarct on brain-imaging,” “3 to
15 mm cerebrospinal fluid (CSF)-filled cavities in the basal
ganglia or white matter, frequently observed coincidentally on
imaging in older people, often not clearly associated with
discrete neurological symptoms.” The sexy French L-word never
did specify etiology or pathogenesis.2,3 Neither the arbitrary
2-dimensional size range nor the requisite transformation to clear
fluid content have ever been editorially enforced.
The ancient term “stroke” specified sudden negative symptoms, often catastrophic; clinicopathologic correlation most often
identified an anatomically pertinent brain hemorrhage or infarction. Before the advent of CT and MRI, Miller Fisher invented
the lacunar concept to deal with his ultimate 65 to 70 stroke
syndromes.4 Early on he further specified that the infarctions
were the result of “lipohyalinosis”, arterial lesions caused by
vascular hypertension.5 Thence his power “proposition that small
artery disease tends to occur where it gives rise to symptoms [his
descriptive variations] rather than being distributed by chance.”
Most significant were his later pathological observations that 22
new “lacunar infarcts” included only 4 with lipohyalinosis.6 Four
empty-vessel cases were presumed to represent lysed emboli,
rather than spasm or other mechanism. The other fourteen cases
included “stenosing atheroma with superimposed thrombus (5);
stenosing atheroma (5); mural atheroma of the basilar artery (2);
microaneurysm (1); and inconclusive (1).” By Authority of
Inventor, Lacunar pathology is not consistent. It is certain that
many “lacunes” are not associated with standardized syndromes
or any symptoms at all.
In 1993 a group of investigators (TOAST) set forth a protocol
for stroke therapy with the worthy premise that “determining the
cause of stroke does influence choices for management” because
“the etiology of ischemic stroke affects prognosis, outcome, and
management.”7 Their only tested drug, danaparoid, had no
clinical value,8 but their stroke classification system survived to
become the standard research protocol.
Unfortunately, TOAST specification of cause lacks both
replicable objective justification and pathological confirmation.
Cause for each case is only the online majority vote of the
clinician investigators.9,10 Statistical guess and attractive treat-
William M. Landau, MD
Department of Neurology
Washington University School of Medicine
Saint Louis, Mo
1. Wardlaw JM. What is a lacune? Stroke. 2009;2921–2922.
2. Landau WM. Clinical Neuromythology VI: Au clair de lacune: holy,
wholly, holey logic. Neurology. 1989;39:725–730.
3. Millikan C, Futrell N. The fallacy of the lacune hypothesis. Stroke.
1990;21:1251–1257.
4. Fisher CM. Lacunes: small, deep cerebral infarcts. Neurology. 1965;15:
774 –784.
5. Fisher CM. The arterial lesions underlying lacunes. Acta Neuropathol.
1969;12:1–15.
6. Fisher CM. Lacunar infarcts: a review. Cerebrovasc Dis. 1991;1:
311–320.
7. Adams, HP Jr, Bendixen BH, Kapelle IJ, Biller J, Love BB, Gordon DL,
Marshee EE III. Classification of subtype of acute ischemic stroke:
definitions for use in a multicenter clinical trial. Stroke. 1993;24:35– 41.
8. The Publications Committee for the Trial of ORG 10172 in Acute Stroke
Treatment (TOAST) Investigators. Low molecular weight heparinoid
ORG 10172 (danaparoid), and outcome after acute ischemic stroke: a
randomized controlled trial. JAMA. 1998;279:1265–1271.
9. Landau WM. Causes of stroke. Ann Neurol. 1992;32:596.
(Stroke. 2009;40:e498-e499.)
© 2009 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.109.553065
e498
Letters to the Editor
10. Landau W, Nassief A. Time to burn the TOAST. Stroke. 2005:4;902–904.
11. Jackson C, Sudlow C. Are lacunar strokes really different? A systematic
review of differences in risk factor profiles between lacunar and nonlacunar infarcts. Stroke. 2005;36:891–901.
12. Hachinski VC, Potter P, Merskey H. Leuko-araiosis. Arch Neurol. 1984;
44:21–23.
13. Landau W. Leukoaraiosis (LA): blotchy old white matter: say no more.
J Watch Neurol. 2004;6:2–3.
14. Pantoni L, Garcia JH. Pathogenesis of leukoaraiosis. Stroke. 1997;28:
652– 659.
15. Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K,
Roman GC, Chui H, Desmond DW. Research criteria for subcortical vascular
dementia in clinical trials. J Neural Transm. 2000;59(Suppl 1):23–30.
e499
16. Chui HC. Subcortical ischemic vascular dementia. Neurol Clin. 2007;25:
717–740.
17. Gouw AA, van der Flier WM, Fazekas F, van Straaten ECW, Pantoni L,
Poggesi A, Inzitari D, Erkinjuntti T, Wahlund LO, Waldemar G, Schmidt R,
Scheltens P, Barkhof F; on behalf of the LADIS Study Group. Progression of white matter hyperintensities and incidence of new lacunes
over a 3-year period: The Leukoaraiosis and Disability Study. Stroke.
2008;39:1414 –1420.
18. Gouw AA, van der Flier WM, Pantoni L, Inzitari D, Erkinjuntti T,
Wahlund LO, Waldemar G, Schmidt R, Fazekas F, Scheltens P,
Barkhof F; on behalf of the LADIS Study Group. On the etiology of
incident brain lacunes: longitudinal observations from the LADIS
study. Stroke. 2208;39:3083–3085.
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
What Is a Lacune? Dogged déjà vu doggerel
William M. Landau
Downloaded from http://stroke.ahajournals.org/ by guest on June 18, 2017
Stroke. 2009;40:e498-e499; originally published online May 28, 2009;
doi: 10.1161/STROKEAHA.109.553065
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2009 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/40/7/e498
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Stroke is online at:
http://stroke.ahajournals.org//subscriptions/