From the Guidelines
The management of hypodensities in the subcortical deep white matter should focus on addressing vascular risk factors, with aggressive control of hypertension, statin therapy for hyperlipidemia, and tight glycemic control for diabetic patients, as these measures can help prevent progression and reduce the risk of stroke and cognitive decline. When considering the management of these lesions, it's crucial to understand that their appearance on an initial assessment can vary significantly, especially when taking into account the individual's diagnostic category, genetic risk factors, and co-morbidities 1. The variability in the anatomic location and severity of white matter hyperintensities (WMHs) seen on neuroimaging must be considered, as this can alter the specific white matter tracts, gray matter regions, and cognitive function affected by the tissue rarefaction.
Some key points to consider in management include:
- Aggressive control of hypertension (target <130/80 mmHg) using appropriate antihypertensives such as ACE inhibitors (e.g., lisinopril 10-40 mg daily) or ARBs, as chronic hypertension is associated with narrowing and sclerosis of small penetrating arteries in the subcortical regions of the brain, contributing to hypoperfusion, loss of autoregulation, and ultimately to subcortical white matter demyelination, microinfarction, and cognitive decline 1.
- Statin therapy (e.g., atorvastatin 20-80 mg daily) should be initiated for hyperlipidemia, as hypercholesterolemia is a risk factor for mild cognitive impairment (MCI) and other signs of cognitive decline.
- Tight glycemic control is essential for diabetic patients (target HbA1c <7%), as diabetes is a risk factor for cognitive decline and vascular disease.
- Daily antiplatelet therapy with aspirin (75-100 mg) or clopidogrel (75 mg) may be indicated for patients with established cerebrovascular disease.
- Lifestyle modifications are crucial, including smoking cessation, moderate exercise (150 minutes weekly), Mediterranean diet, and limiting alcohol consumption.
- Regular cognitive assessment is important, as these lesions may progress to vascular cognitive impairment.
The rationale for this approach is that subcortical white matter hypodensities often represent chronic small vessel ischemic changes, and managing vascular risk factors can help prevent progression and reduce the risk of stroke and cognitive decline, as supported by the most recent and highest quality study on the topic 1. In cases where the hypodensities have a different etiology, such as multiple sclerosis or infection, disease-specific treatments would be required instead.
From the Research
Management of Hypodensities in Subcortical Deep White Matter
The management of hypodensities in the subcortical deep white matter is crucial to prevent further cognitive decline and associated risks.
- Hypertension has been associated with the presence of white matter lesions, and effective treatment may reduce the rates of both types of white matter lesions 2.
- Diabetes mellitus has also been linked to the progression of white matter hyperintensity, and insulin resistance is considered an exacerbating factor 3.
- The spatial distribution of white matter hyperintensities is key to deciphering the underlying mechanisms, and accounting for this distribution is essential for personalized therapeutic approaches 4.
- In some cases, white matter lesions may represent a secondary cause for headaches, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which should be suspected in patients with migraine, especially with aura, and bilateral, multifocal, T2/FLAIR hyperintensities in the deep white matter and periventricular white matter 5.
- Diffuse subcortical white matter hypointensity on T2/FLAIR, also known as "Dark White Matter," is a frequently underrecognized sign that can be associated with various medical conditions, including Non-Ketotic Hyperglycaemic hyperosmolar state (NKH), Encephalitis, and Moyamoya disease 6.
Risk Factors and Clinical Correlates
Several risk factors and clinical correlates have been identified for hypodensities in the subcortical deep white matter, including:
- Hypertension 2
- Diabetes mellitus 3
- Insulin resistance 3
- Vascular risk factors 4
- Genetic risk score (GRS) 4
- Migraine, especially with aura 5
- Bilateral, multifocal, T2/FLAIR hyperintensities in the deep white matter and periventricular white matter 5
- Seizures 6
- Non-Ketotic Hyperglycaemic hyperosmolar state (NKH) 6
- Encephalitis 6
- Moyamoya disease 6