Smoking causes white matter scarring in the brain

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It’s quite possible that you are one of those people with white spots on the brain.

Healthy people aren’t spared them, but sick individuals may be more vulnerable. If you smoke, the risk increases even more..

You probably don’t notice them too much unless your doctor has you get into an MRI machine.

Then you can see them. White spots on the brain. These are the scars in your white matter.

A bit unpleasant to think about, but is there really a problem if they’re so common?

“Both yes and no,” says Asta Håberg, a neuroscience professor at NTNU.

“White spots are the most common age-related finding, but they’re not good for the brain, because it makes it more vulnerable,” says Håberg.

She has just discovered something new.

If you have scarring in the white matter in the brain, it not surprisingly affects the area where the scar is.

What Håberg and her colleagues found was that completely different parts of the brain are also affected by the scarring.

Including areas far removed from the scarred tissue.

As with many other things in life, the scars start deep and spread out.

“The effects of the white spots spread across the surface of the brain and increase in volume,” says Håberg.

This finding makes things a little more worrisome. It doesn’t help that scientists don’t really know why the white spots appear at all. Ever since they were discovered, they have been a mystery.

But a few pieces of the puzzle are in place.

Smoking and high blood pressure increase the risk,” says Håberg.

Fortunately, there’s been a shift in this habit.

Fewer young people now take up smoking. Among individuals who started when they were young, some are obviously still caught in tobacco’s grip

Statistics Norway data shows that twelve percent of Norway’s population smoked in 2018.

This shows a brain scan from the study

The effects of the white spots increase in volume as they spread across the surface of the brain. Here marked in blue. The image is credited to NTNU.

Smoking is more prevalent among people in the 65-74 age group than among those who are 49 years old or younger.

The risk of numerous different brain diseases — such as dementia or stroke — increases with age.

“Keeping your brain as healthy as possible can reduce the negative effects of other brain diseases.

Regular health advice regarding high blood pressure and not smoking are both good for the body and the brain,” says Håberg.


Systemic sclerosis (SSc) is a connective tissue disorder with widespread vascular lesions, possibly explained by immune reactions to viral or environmental factors, reperfusion injury, or anti-endothelial antibodies [12] accompanied by angiogenesis which is insufficient or defective [34]. Most studies have been directed to microvascular disease in SSc, but some studies have suggested an increased prevalence of macrovascular disease as well [56]. The development of accelerated atherosclerosis in SSc is less clear, although, an increase in carotid intima-media thickness (IMT) in SSc patients has been reported [78]. Clinically there is little evidence for increased macrovascular complications such as stroke or myocardial infarction [5].

High-resolution ultrasound is a non-invasive and practical method to examine peripheral arteries and carotid lesions, including increased intima-media thickness and atherosclerotic plaques [9]. The studies of the IMT in Egyptian patients with other rheumatic diseases documented subclinical atherosclerosis in rheumatoid arthritis [10], systemic lupus erythematosus [11], and primary osteoarthritis [12].

Some studies have concluded that ultrasound-detected carotid atherosclerotic lesions are associated with ischemic stroke [1314] and can help estimate the risk of ischemic stroke [1517] Accordingly, both the Japanese Society of Hypertension Guidelines for the Management of Hypertension and the European Society of Hypertension/European Society of Cardiology 2003 Guidelines for the Management of arterial hypertension have added increased CAA-IMT and common carotid artery plaques (CCA) as risk factors for stroke [1819].Per the Japanese Society for the Detection of Asymptomatic Brain Diseases, a silent cerebral infarct (SCI) must be ≤ 3 mm in greatest diameter [18]. The SCI can be detected by magnetic resonance imaging (MRI) and is considered an important risk factor for stroke [2021] and is associated with both psychiatric and neurologic disorders [2223].

Diffusion-weighted MRI (DWI) provides in vivo pathological information and allows the differentiation of acute stroke from chronic stroke or from non-specific white matter lesions [24]. Fluid-attenuated inversion recovery (FLAIR)-MRI demonstrated that it can detect brain abnormalities in many neurological diseases with particularly high sensitivity to detect lesions in the periventricular and subcortical regions [25].

Based on these data, we wished to examine the thickness of the carotid artery intima-media and the brain MRI-detected lesions in systemic sclerosis patients to compare them to age- and sex-matched normal controls. Secondary analyses examined large vessel disease in the SSc patients and sought to find any relationships of the carotid and CNS MRI findings with SSc clinical disease and selected laboratory parameters.

Systemic sclerosis (SSc) is a connective tissue disorder with widespread vascular lesions, possibly explained by immune reactions to viral or environmental factors, reperfusion injury, or anti-endothelial antibodies [12] accompanied by angiogenesis which is insufficient or defective [34]. Most studies have been directed to microvascular disease in SSc, but some studies have suggested an increased prevalence of macrovascular disease as well [56]. The development of accelerated atherosclerosis in SSc is less clear, although, an increase in carotid intima-media thickness (IMT) in SSc patients has been reported [78]. Clinically there is little evidence for increased macrovascular complications such as stroke or myocardial infarction [5].

High-resolution ultrasound is a non-invasive and practical method to examine peripheral arteries and carotid lesions, including increased intima-media thickness and atherosclerotic plaques [9]. The studies of the IMT in Egyptian patients with other rheumatic diseases documented subclinical atherosclerosis in rheumatoid arthritis [10], systemic lupus erythematosus [11], and primary osteoarthritis [12].

Some studies have concluded that ultrasound-detected carotid atherosclerotic lesions are associated with ischemic stroke [1314] and can help estimate the risk of ischemic stroke [1517] Accordingly, both the Japanese Society of Hypertension Guidelines for the Management of Hypertension and the European Society of Hypertension/European Society of Cardiology 2003 Guidelines for the Management of arterial hypertension have added increased CAA-IMT and common carotid artery plaques (CCA) as risk factors for stroke [1819].Per the Japanese Society for the Detection of Asymptomatic Brain Diseases, a silent cerebral infarct (SCI) must be ≤ 3 mm in greatest diameter [18]. The SCI can be detected by magnetic resonance imaging (MRI) and is considered an important risk factor for stroke [2021] and is associated with both psychiatric and neurologic disorders [2223].

Diffusion-weighted MRI (DWI) provides in vivo pathological information and allows the differentiation of acute stroke from chronic stroke or from non-specific white matter lesions [24]. Fluid-attenuated inversion recovery (FLAIR)-MRI demonstrated that it can detect brain abnormalities in many neurological diseases with particularly high sensitivity to detect lesions in the periventricular and subcortical regions [25].

Based on these data, we wished to examine the thickness of the carotid artery intima-media and the brain MRI-detected lesions in systemic sclerosis patients to compare them to age- and sex-matched normal controls. Secondary analyses examined large vessel disease in the SSc patients and sought to find any relationships of the carotid and CNS MRI findings with SSc clinical disease and selected laboratory parameters.

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Object name is 13075_2019_1877_Fig1_HTML.jpg
Fig. 1
Brain MRI for a female patient aged 42 years who suffered from SSc, disease duration: 5 years. a FLAIR-MRI shows multiple rather well-defined hyperintense. signal foci seen in the deep periventricular white matter of both parietal regions with no comparable signal abnormality on DWI (b) suggesting late subacute to chronic ischemic lesions

Lesion numbers in the brain FLAIR-MRI ranged from 0 to 34 in the patients vs 0 to 7 in the controls (P = 0.02), and the lesions were larger among patients when the lesions were classified into 3 groups (< 2 mm, ≥ 2 mm and ≥ 5 mm) (P = 0.05).In univariable correlations, there were significant positive correlations of the MRI lesion numbers with the Medsger vascular scale (r = 0.7, P = 0.02), CCA-IMT (r = 0.6, P = 0.042), and LDL (r = 0.5, P = 0.03).

Among the SSc patients, there were significant positive correlations of MRI lesion size with age (r = 0.7, P = 0.01), disease duration (r = 0.6, P = 0.03), and MRSS (r = 0.63, P = 0.01) but no other variables.

Compared to MRI-negative SSc patients, those with positive MRI findings had longer disease duration (P = 0.001), longer Raynaud’s attacks (P = 0.02), more atheromatous disease (P = 0.001–0.013), and thicker CCA-IMT (P = 0.01) (Table 5).

Table 5

The only variables which had a significant difference in a comparison between patients with positive FLAIR-MRI findings and negative FLAIR-MRI

Variables+ve MRI findings−ve MRI findingsP value
Disease duration11.75 ± 7.23.13 ± 1.60.001
Raynaud’s duration (minutes)18.13 ± 9.98.13 ± 4.40.02
Rt CAA atheroma0.25 ± 0.150.0 ± 0.00.013
Lt CAA atheroma0.38 ± 0.180.0 ± 0.00.001
CAA-IMT1.25 ± − .650.87 ± 0.180.01

Patients with thicker CCA-IMT (≥ 0.9 vs < 0.9 mm), thus examining large vessel disease, had higher mean Medsger kidney severity score (1.0 vs 0.0, P = 0.001), more MRI lesions (5.4 vs 0.9, P = 0.001), and larger MRI lesions (0.5–1.0 with P = 0.01).

There were no statistically significant differences in the frequency of MRI hyperintense lesions between limited and diffuse scleroderma patients (Fig. 2), and there were numerical but non-significant correlations between a generalized inflammatory marker (CRP), MRI lesions numbers, and atheromata in the CCA.

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Object name is 13075_2019_1877_Fig2_HTML.jpg
Fig. 2
A graph compares diffuse and limited SSc patients in regard to +ve MRI brain findings. There is no significant difference between the MRI +ve results with the type of Scleroderma

In multiple regression analysis, CCA-IMT (r = 0.8, P = 0.006), more severe Medsger kidney (r = 0.5, P = 0.05) and Medsger vascular scores (r = 0.8, P = 0.01), higher cholesterol (r = 0.7, P = 0.02), and higher LDL (r = 0.5, P = 0.02) were independent contributors to the presence of more MRI lesions.


Source:
NTNU
Media Contacts:
Asta Håberg – NTNU
Image Source:
The image is credited to NTNU.

Original Research: Open access
“The effect of white matter hyperintensities on regional brain volumes and white matter microstructure, a population-based study in HUNT”. Torgil Riise Vangberg, Live Eikenes, Asta K. Håberg.
NeuroImage doi:10.1016/j.neuroimage.2019.116158.

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