The term cerebral small vessel disease (CSVD) or microangiopathy includes
several pathological processes of different aetiologies which cause an increase of wall
thickness (basically the basement membrane), a narrowing of the lumen, and a
weakening of walls in arterioles, capillaries and venules. These vascular modifications
cause a loss of proteins towards the interstice and a slowness of blood flow, increasing
the risk of ischemia and tissue bleeding.
The CSVD may be aetiopathogenically classified in 6 types. The CSVD type 1, called
arteriolosclerosis, is the most prevalent form and has a 6 to 10 times higher prevalence
than stroke. It is related to aging and classical vascular risk factors, like arterial
hypertension and diabetes mellitus. This review will focus on type 1 CSVD.
In the brain, the main pathological findings are loss of smooth muscle cells in the
media, accumulation of fibrohyaline material, fibrinoid necrosis, and development of
microatheromas and Charcot-Bouchard microaneurysms. The parenchymatous
consequences of these vessel modifications are both ischemic (white matter lesions,
lacunes) and haemorrhagic (microhaemorrhages, intracerebral haemorrhages). The
clinical manifestations of arteriolosclerosis include cognitive deterioration, dementia,
mood disorders, gait and motor disturbances, lacunar strokes, and disability. In vivo,
the diagnosis of CSVD is supported by neuroimaging findings (lacunes, leukoaraiosis,
white matter lesions, microhaemorrhages), especially by use of magnetic resonance
techniques. The role of other biomarkers (plasma and cerebrospinal fluid biochemical
parameters, resistance indexes in transcranial Doppler study) is not completely defined.
In patients with diagnosis of microangiopathy there are three main therapeutic
considerations. First, there are specific risks in these patients during standard clinical
management of acute ischemic stroke. Several studies showed an increased risk of
intracranial bleeding related to thrombolytic therapy for acute stroke and anticoagulant
treatment for secondary prevention. Indeed, the presence of leukoaraiosis raised the
probability of peri-operative stroke or death in patients who underwent carotid
endarterectomy. Second, the symptomatic management of patients with cognitive
impairment related to CSVD, which is currently based on memantine and
acetylcholinesterase inhibitors used in Alzheimer's disease. Third, the specific therapy
directed to vessel pathology and parenchymatous consequences (secondary
prevention). Available data support the use of antiaggregant drugs to reduce the risk of
recurrence of lacunar strokes. Aspirin, ticlopidine, aspirin plus clopidogrel, dipiridamol
plus aspirin, and cilostazol showed efficacy in this subtype of stroke. The optimal
control of arterial pressure and cholesterol level also reduces the risk of stroke,
independently if mechanism of disease was macro or microvascular. However, the
specific drugs and the optimal goals are not defined and ongoing trials are trying to
evaluate different drugs and preventive strategies (cilostazol plus aspirin, aggressive
versus standard blood pressure control). Considering the specific treatment of vascular
pathology, there are few available data. Experimental studies showed that relaxin may
increase the arterial distensibility. In humans, one ongoing trial is investigating the
efficacy and safety of an anti-amyloid beta monoclonal antibody in patients with
probable cerebral amyloid angiopathy (CSVD type 2).
Keywords: Acetylcholinesterase Inhibitors, Antiaggregants, Cerebral Amyloid
Angiopathy, Cerebral Microangiopathy, Cerebral Microhaemorrhages, Cerebral
Small Vessel Disease, Deep Brain Infarcts, Deep Intracerebral Haemorrhages,
Enlarged Perivascular Spaces, Lacunar Stroke, Memantine, Vascular Dementia,
White Matter Lesions.
