Do white matter hyperintensities on MRI matter clinically?
BMJ 2010; 341 doi: https://doi.org/10.1136/bmj.c3400 (Published 26 July 2010) Cite this as: BMJ 2010;341:c3400
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It has been clearly demonstrated that subcortical white matter
changes of the brain in functionally unimpaired individuals may lead to
disability after 3 years [1]. It has also been found that white matter
changes are related to a fairly specific cognitive syndrome [2] and
depression [3,4], and increase the risk of stroke [5]. Yet Dr Mamun states
that dealing with the white matter disorder is "medicalisation of graceful
ageing".
In the Western world 20 to 30 thirty years ago a passive attitude
also characterized the approach to Alzheimer's disease. First when it was
abandoned the progress of dealing with the disorder started. The stroke
field has undergone a similar development. However, the handling of white
matter changes, a marker of small vessel disease, which is the most common
neurological disorder ever described, is still undermedicalised. Now time
has come for research to determine what mechanisms are responsible for the
vessel wall damage and tissue lesions but also to agree upon what actions
that should be taken in practical medicine to diminish the effect of this
slowly developing, devastating disorder. We need to decide more
specifically what vascular factors and cognitive deficits that should be
examined at different levels of white matter involvement, in different
groups of patients and at various ages. This work should be performed
within the context of cognitive medicine, a rapidly developing field of
medicine.
1. Inzitari D, Pracucci G, Poggesi A et al.; LADIS Study Group.
Changes in white matter as determinant of global functional decline in
older independent outpatients: three year follow-up of LADIS
(leukoaraiosis and disability) study cohort. BMJ. 2009 Jul 6;339:b2477.
2. Roman G, Erkinjuntti T, Wallin A et al. Subcortical Ischemic
Vascular dementia. Lancet Neurology 2002;1:426-36.
3. Alexopoulos GS, Meyers BS, Young RC et al. Clinically defined
vascular depression. Am J Psychiatry. 1997 Apr;154(4):562-5.
4. Teodorczuk A, Firbank MJ, Pantoni L et al; LADIS Group.
Relationship between baseline white-matter changes and development of late
-life depressive symptoms: 3-year results from the LADIS study. Psychol
Med. 2010 Apr;40(4):603-10. Epub 2009 Aug 12.
5. Debette S, Markus HS. The clinical importance of white matter
hyperintensities on brain magnetic resonance imaging: systematic review
and meta-analysis. BMJ. 2010 Jul 26;341:c3666. doi: 10.1136/bmj.c3666.
Competing interests: AW has received payment from Pfizer and Novartis for educational presentations
WHITE MATTER HYPERINTENSITIES IN THE YOUNG
The editorial by Wallin highlights the clinical importance of white
matter hyperintensities on MRI as a marker of small vessel disease in the
elderly.1 This is char?acterised by insidious onset and gradual
progression of executive dysfunction, loss of initiative, mental slowness,
slight gait deficits, and mild impairment of memory--symptoms that are not
always easy to identify.(1)
The prevalence of white matter hyperintensities ranges from 11-21% in
adults aged around 64 to 94% at age 82.(2) In the young, the prevalence is
around 0.5%.(3) We have recently reported the presence of white matter
hyperintensities in a prospectively identified cohort of young people
(mean age 27 years) attending our emergency department with an amphetamine
related presentation (including methamphetamine, amphetamine and
ecstasy).(4) Four of 23 (17%, 95%CI 5.7-39.5%) serious amphetamine users
had these lesions on MRI, most commonly in the frontal lobes.
This is consistent with previous reports of these lesions in
abstinent amphetamine users, as well as a range of neuroimaging
abnormalities.(5) Similar lesions have also been reported in cocaine
users.(6) These findings are consistent with the known effects of these
stimulant drugs to cause vasospasm, possibly causing a similar pattern of
MRI changes consistent with small vessel disease in a cohort of young
stimulant drug users.
Whilst the long term effects of these white matter hyperintensities
in these young drug users is yet to be observed, the reported cognitive
effects in amphetamine users could be related to small vessel disease.
Longitudinal studies are required to test this hypothesis.
REFERENCES
1. Wallin A, Fladby T. Do white matter hyperintensities on MRI matter
clinically? BMJ 2010;341:c3400.
2. 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.
3. Katzman GL, Dagher AP, Patronas NJ. Incidental findings on brain
magnetic resonance imaging from 1000 asymptomatic volunteers. JAMA
1999;282(1):36-9.
4. Fatovich DM, McCoubrie DL, Song SJ, Rosen DM, Lawn ND, Daly FF.
Brain abnormalities detected on magnetic resonance imaging of amphetamine
users presenting to an emergency department: a pilot study. Med J Aust
2010;193(5):266-8.
5. Berman S, O'Neill J, Fears S, Bartzokis G, London ED. Abuse of
amphetamines and structural abnormalities in the brain. Ann N Y Acad Sci
2008;1141:195-220.
6. Lyoo IK, Streeter CC, Ahn KH, Lee HK, Pollack MH, Silveri MM, et
al. White matter hyperintensities in subjects with cocaine and opiate
dependence and healthy comparison subjects. Psychiatry Res 2004;131(2):135
-45.
Competing interests: No competing interests
We read the article by Wallin and Fladby (2010) and systematic review
by
Debette and Marcus (2010) with much interest. They have suggested a link
between white matter hyperintensities on MRI and stroke, dementia and
death. However, they have failed to mention the relationship between white
matter changes and late onset depression also called ‘vascular
depression’
(Alexopoulos et al, 1997). Depression may present as a prodromal syndrome
of dementia and it is hypothesized that the affective and cognitive
changes
may be parts of a continuum seen in cerebrovascular disease (Lavretsky,
2004). It is important that future studies investigating the risk of white
matter
changes should also investigate effects of these changes on mood and
depressive symptoms.
Debette, S and Markus, HS (2010). The clinical importance of white
matter
hyperintensities on brain magnetic resonance imaging: systematic review
and
meta-analysis. BMJ 2010 341: c3666.
Wallin, A., Fladby, T. (2010). Do white matter hyperintensities on
MRI matter
clinically?. BMJ 341: c3400-c3400.
Alexopoulos GS, Meyers BS, Young RC et al (1997). Clinically defined
vascular
depression. American Journal of Psychiatry; 154:562-565.
Lavretsky H (2004). Vascular Depression: Recent Advances.
Current Psychosis and Therapeutics Reports. 2,1:27-32.
Competing interests:
None declared
Competing interests: No competing interests
Wallin & Fladby in their editorial1 linked to Debette &
Markus’s Systematic review and meta-analysis2 imply that all cases of
white matter hyperintensity should be thoroughly assessed and investigated
perhaps with further imaging and cerebrospinal fluid (CSF) analysis, the
latter for research studies. White matter lesions (sub-cortical
hyperintensity on T2 imaging) are extremely common incidental finding in
people in their eighties and nineties particularly amongst hospitalised
elderly where an imaging is done for unrelated indications i.e.,
unexplained headache, drowsiness, acute confusion, falls and head injury,
space occupying lesion etc. Clinical assessment of vascular risk factors
is understandable in this group (oldest old), but one would be distinctly
uncomfortable to take matter further in the absence of relevant clinical
scenario. Clinical practice needs to be contextual, and not an all-
encompassing search for everything particularly given the prevailing
credit crunch and guarded medium term economic outlook, and extra
financial burden it would impose on the society as a result for doubtful
positive outcome, if any, and potential detrimental effect it may have on
other spheres of health service delivery due to lack of funding.
1. Wallin A, Fladby T. Do white matter hyperintensities on MRI matter
clinically? BMJ 2010;341:c3400.
2. 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.
Competing interests:
Practising Stroke and General Physician
Competing interests: No competing interests
Re:White matter changes and late onset depression
Thank you for your valuable comments Dr Vattakatuchery! One reason
for not mentioning depression was that cognition in the broad sense with
executive function being one of the crucial components also includes
various aspects of mood and mood-related changes such as reduced power of
initiative and blunt perception of own and others activities.
Consequently, there is no clear-cut difference between mood and cognition.
However, we realize that it would have been better to explicitly mention
depression as a manifestation of white matter disease not the least as
there are studies supporting the notion of a white matter induced
depressive disorder [1, 2]. Thus, depression may be part of the
symptomatic manifestations of small vessel disease, and features of
depression may add to the resulting cognitive impairment. Taking into
account this both mood and in the delimited sense cognition are equally
dependant on brain white matter structure. This knowledge is important,
not the least because it has implications for treatment both of mood
disorders and of cognitive impairment in large groups of the population.
1. Alexopoulos GS, Meyers BS, Young RC et al. Clinically defined
vascular depression. Am J Psychiatry. 1997 Apr;154(4):562-5.
2. Teodorczuk A, Firbank MJ, Pantoni L et al; LADIS Group.
Relationship between baseline white-matter changes and development of late
-life depressive symptoms: 3-year results from the LADIS study. Psychol
Med. 2010 Apr;40(4):603-10. Epub 2009 Aug 12.
Competing interests: AW has received payment from Pfizer and Novartis for educational presentations