Inflammation and white matter damage in vascular cognitive impairment - PubMed (original) (raw)

Inflammation and white matter damage in vascular cognitive impairment

Gary A Rosenberg. Stroke. 2009 Mar.

Abstract

Vascular cognitive impairment is a term used to describe a heterogeneous group of diseases, including large vessel disease with strategic single and multiple strokes and small vessel disease with progressive damage to the deep white matter. Identification of patients with the progressive form of vascular cognitive impairment, referred to by some investigators as Binswanger disease, is important for treatment trials. Pathologically, Binswanger disease is associated with small vessel disease, extensive regions of demyelination, inflammatory cells around damaged blood vessels, and lacunar infarcts. Clinically, patients with Binswanger disease have impairments of gait and balance, focal neurological findings, and executive dysfunction on neuropsychological tests. White matter changes on MRI are thought to be due to hypoxic episodes related to hypoperfusion of the vulnerable deep white matter secondary to hypertension, diabetes, and other vessel diseases. Disruption of the blood-brain barrier suggests an inflammatory response. Matrix metalloproteinases are present in the brain of patients with vascular cognitive impairment and can be measured in the cerebrospinal fluid of some patients. Preliminary studies with quantification of the blood-brain barrier, using the multiple time graphical method (Patlak plots), supports disruption of the blood-brain barrier. Because no single clinical feature or diagnostic test is sufficient to identify patients with the small vessel form of vascular cognitive impairment, we propose that a multimodal approach will be needed to select patients for treatment trials.

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Figures

Figure 1

Figure 1

The relationship between the values for MMP-9 and MMP-2 in the patients with small vessel VCI or Binswanger disease (closed dots) and large vessel multi-infarct dementia (MID; open dots). Values have been normalized to control samples that were run on each gel so that samples collected at different times could be compared. Patients with VCI showed a significant correlation between the MMP-2 and the MMP-9 values. The patients with Binswanger disease tended to have higher values of both MMP-2 and MMP-9 placing them in the upper outer quadrant of the graph, whereas those with multiple infarcts tended to be in the lower inner quadrant. There was a significant positive correlation of MMP-9 and MMP-2 in the patients with VCI (r• 0.74; P• 0.001; N• 16). (Data extracted from reference .)

Figure 2

Figure 2

Multiple time graphical plots (Patlak plots) of BBB permeability with gadolinium DTPA-enhancing lesions in 2 patients with VCI. A, Fluid-attenuated inversion recovery (FLAIR) image from one patient with early changes in the white matter. B, White matter permeability maps with gray matter removed. The red regions represent increased BBB permeability in a region of white matter hyperintensity on the MRI (arrows). C, FLAIR image from a patient with advanced Binswanger disease and extensive changes in the white matter with relative sparing of the gray matter. D, Corresponding permeability map showing several smaller regions of enhanced permeability despite the extensive white matter changes (arrows). E, FLAIR image from a normal elderly control subject without white matter hyperintensities. F, Permeability map showing absence of increased permeability. Note that the color coding is not comparable in the patients and control subjects because the permeability scale is • 10• 3 in (mmol/kg• min) in the patients and • 10• 4 (mmol/kg• min) in control subjects, indicating the lack of enhancement in the control subjects. (Courtesy of Saeid Taheri, PhD.)

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