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Advanced Neurology Covert cerebral small vessel disease

Figure 1. Studies associating cerebral small vessel disease burden with circulating brain-specific protein levels in neurologically asymptomatic cohorts.
Abbreviations: NFLC: Neurofilament light chain; NR2ab: Autoantibodies against the NR2 peptide of the NMDA receptor; NSE: Neuron-specific enolase,
S100B: S100B protein, UCHL1: ubiquitin C-terminal hydrolase-L1.

these patients. There is uncertainty about the necessity risk factors through pharmacological treatments and
and benefits of treatment, even among neurologists. In lifestyle modifications. However, management of
addition, inconsistencies exist in clinical definitions that covert CSVD primarily focuses on risk factor control.
distinguish truly silent covert CSVD from symptomatic Evidence regarding the impact of lifestyle modifications
covert CSVD. The European Stroke Organization (ESO) on clinical outcomes in covert CSVD remains scarce
guidelines define covert CSVD as occurring in patients and controversial. Specifically, studies have shown that
without a formal diagnosis of transient ischemic attack/ managing arterial hypertension, the primary risk factor
stroke, cognitive impairment or dementia, mobility, or in CSVD pathogenesis, by lowering blood pressure
mood disorders. 12 can reduce WMH progression. Conversely, few studies
The consequences of incidental CSVD are often have explored the association between diabetes mellitus
underestimated, leading to a concern where these and CSVD, yielding inconclusive results; no studies,
individuals are frequently overlooked in clinical settings. have evaluated the effect of glycemic control on WMH
For instance, while covert lacunar infarcts could seem reduction. The association of exercise, hyperlipidemia,
inconsistent, similar-sized infarcts in more critical regions smoking cessation, and healthy lifestyles with the
progression of CSVD also showed divergent results,
of the brain – accompanied by clinically evident stroke highlighting the need to clarify their contributions to
– prompt thorough diagnostic evaluations, treatment disease progression and the overall effectiveness of risk
with statins and antiplatelet medications, and periodic factor control in CSVD management. 12
monitoring.
Clinicians are more reticent when considering
Given the controversies surrounding the management
of covert CSVD, various guidelines have been developed. pharmacological interventions for individuals with covert
CSVD, especially regarding conventional antiplatelet
In 2017, the AHA/ASA released a statement that focused drugs such as aspirin and clopidogrel, due to the risk of
mainly on stroke prevention but not exclusively on covert hemorrhagic events. Existing guidelines advise against
CSVD. The first guidelines dedicated to this condition the use of antiplatelet drugs to prevent clinical outcomes
13
were the ESO guidelines published in 2021. More recently, in the absence of other indications for this treatment,
12
a consensus statement was developed by a group at the especially in older patients. Although some studies have
2021 Australasian Stroke Academy Conference specifically examined the administration of statin for this condition,
for managing incidentally found brain WMH. 44 very few population-based studies have demonstrated
For patients with overt CSVD, current prevention a clear association of hyperlipidemia with CSVD. There
and therapy strategies involve controlling traditional is divided opinion on whether lipid-lowering therapy

Volume 4 Issue 4 (2025) 52 doi: 10.36922/an.4841