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PERIVENTRICULAR WHITE MATTER LESIONS (PWM)

Timothy C. Hain, MD. Page last modified: October 5, 2014

periventricular white matter lesions pvn
MRI (Magnetic resonance image) of the brain. This is section is in the horizontal plane, just above the ears. Periventricular white matter lesions can be seen (the white spots towards the bottom). This is a moderate case. MRI showing moderate PVM. Moderate PVM corresponds to roughly a 15% burden of Leukoariaiosis.

Between a third and 80% of MRI scans done in persons over the age of 65 have changes in their cerebral white matter (Wong et al, 2002). MRI studies of older persons with disequilibrium and gait disturbances of unknown cause often show frontal atrophy and subcortical white matter T2 hyperintense foci. (Kerber et al, 1998). Pathological studies, though scanty, suggest frontal atrophy, ventriculomegaly, reactive astrocytes in the frontal periventricular white matter, and increased arteriolar wall thickness (Whitman et al, 1999).

Causes of periventricular white matter lesions:

Casues of periventricular white matter (PWM) lesions include normal senescent changes (then they are called UBO's, for "unidentified bright objects), small strokes, and disorders related to multiple sclerosis (MS). PWM are correlated with vitamen B6 (pyridoxine) deficiency.

Getting older: Age is certainly the single most common cause of PWM. This is presumably a "wear and tear" phenomenon.

Small strokes:

A period of hypertension is a common cause. In the authors experience, just a few days of extreme hypertension may be enough. This might suggest that small bleeds are the cause in some. Clinical studies also show association with diabetes, but not consistently with atherosclerosis. PWM are often an accompaniment of migraine, and occur in roughly 20% of persons with migraine. As about 10% of the population has migraine, this means that about 2% of the population has white matter lesions due to migraine. PWM are also more common in persons with frequent syncope and orthostatic intolerance (Kruit et al, 2013)

WM lesions are associated with retinal microvascular abnormalities. Persons with both WM lesions and retinopathy have a much higher risk of clinical stroke (20% vs 1.4%), (Wong et al, 2002).

MS and related conditions:

Demyelinating disorders such as multiple sclerosis and relatives can cause PWM.

Genetic --

These numerous, interesting and largely untreatable conditions are fortunately very rare. Although experts on these conditions suggest that genetic testing should be obtained in patients with unexplained white matter lesions, it seems to us that this is debatable, as the cost of doing this testing is substantial, and the benefit in terms of changing treatment is very small, as most of these conditions have no treatment. A review of these disorders was written in 2014 by Labauge et al.

There are 3 rare familial white matter disorders, designated as "vascular disorders", with long acronyms. CADASIL, COL4A1, CRMCC

CADASIL. This is the most common one, and it is autosomal dominant. Symptoms include migraine with aura before the 4th decade, lacunar infarcts and mood disturbances before the 5th decade, and cognitive decline in the 6th decade. Testing for the notch-3 mutation that causes CADASIL is done by Athena, among other laboratories. This variant could easily be mistaken for someone with migraine having white matter lesions. MRI findings suggestive of a vascular mechanism are basically just multiple lesions on Flair. There is a rarer autosomal recessive variant.

COLA4A1. This condition was initially described in children as familial porencephaly. These children had cerebral palsy with cavities and recurrent brain hemmorages. Porencephaly is a fluid-filled cavity communicating with the lateral ventricle. The temporal lobes are typically not involved.

CRMCC is the association of white matter changes with calficiations and intracranial cysts -- a rare recessive multisystem disorder.

Other familial white disorders include familial cerebral amyloid angiopathy, Fabry disease, and others. One of these, Fabry disease, has a treatment.

In addition to the MRI's that have the "vascular pattern", another and rarer group of disorders are called "cavitary leukoencephalopathies". On MRI, these disorders have hypointensity (black spots) within large areas of demyelination (white spots) on Flair MRI. Different from the "porencephaly" cases above, the black spots (holes) do not communicate with the ventricles (i.e. do not go all the way to the big fluid filled cavities in the middle of the brain). There are several extremely rare genetic variants.

 

Serious consequences of periventricular white matter lesions

White matter lesions strongly correlate with reduced gait speed as well as reduced mental ability (Starr et al, 2003; Guttman et al, 2000; Whitman et al, 2001; Bazner et al, 2008). In other words, they slow you down and make you dumber ! Periventricular location of white matter lesions seem to cause the most serious consequences. Individuals with PVM lesions perform nearly 1 standard deviation below average on tasks involving psychomotor speed.

Acceleration in white matter hyperintensity burden, is a pathologic change that occurs early in the presymptomatic phase leading to mild cognitive impairment. In fact, on average, acceleration occurs 10 years prior to onset of mild cognitive impairment. (Silbert et al, 2012). Only a 3% burden of leukoaraiosis (white matter lesion percent of brain) is enough to reduce working memory scores 2 standard deviations (Price et al, 2012). A 3% burden on MRI, is the amount of PVM usually called "mild" on MRI reports.

If we consider gait and balance, according to a recent study of Bazner, the slow-down in walking is not extreme -- older people are about 20% slower with a large # of PVM than a small #. It would seem to us that people may simply be more cautious and walk more slowly when they are more prone to fall.

Pathologically, PWM correspond to areas of myelin thinning and gliosis, and are often accompanied by lacunar (small holes) infarctions and small vessel atherosclerotic disease. Lacunes are also associated with cognitive disturbances (Jokinen et al, 2011).

Treatment:

Practically, PVM seem to be associated with severe consequences. As once you have them, they are there for life, prevention is the main goal of treatment.

We advocate attention to reducing vascular risk factors, and especially controlling labile hypertension. Reducing elevated cholesteral, and strict control diabetes is probably helpful too. Small amounts of vitamin b6 (pyridoxine) supplementation also seem reasonable (i.e. 2 mg/day). It is not clear if daily aspirin intake is useful or harmful in persons with PVM, and in our opinion, the decision should be made on an individual basis. Beta blockers such as propranolol and related medications may be especially suitable to prevention of spikes in blood pressure. These drugs are also cardioprotective.

In persons with migraine, we generally suggest a prophylactic regimen such as a combination of low-dose aspirin and a migraine prevention agent such as verapamil. It is not known whether this treatment regimen is effective. Beta blockers would also seem very reasonable.

Treatment of the demyelinating diseases may be possible, but is outside the scope of this brief review.

With respect to the common symptom of unsteadiness, empirical treatment including physical therapy. While generally medications are not helpful in situations where fiber tracts or neurons have died, in some occasional cases, trials of medications such as antidepressants or anti-parkinsonian drugs are helpful.

We think it is unlikely that any treatment will be successful in reversing the mental slowing associated with PVM. However, there may be some room to readjust medications that are slowing down thinking independently -- such as antivertigo medications (e.g. meclizine or clonazepam), and replacing them with medications that do not impair thinking (such as betahistine).

References:

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Copyright October 5, 2014 , Timothy C. Hain, M.D. All rights reserved. Last saved on October 5, 2014