Clinical management of cerebral small vessel disease: a call for a holistic approach

Abstract

Cerebral small vessel disease (SVD) is a common global brain disease that causes cognitive impairment, ischemic or hemorrhagic stroke, problems with mobility, and neuropsychiatric symptoms. The brain damage, seen as focal white and deep grey matter lesions on brain magnetic resonance imaging (MRI) or computed tomography (CT), typically accumulates "covertly" and may reach an advanced state before being detected incidentally on brain scanning or causing symptoms. Patients have typically presented to different clinical services or been recruited into research focused on one clinical manifestation, perhaps explaining a lack of awareness, until recently, of the full range and complexity of SVD.In this review, we discuss the varied clinical presentations, established and emerging risk factors, relationship to SVD features on MRI or CT, and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle interventions. The core message is that effective assessment and clinical management of patients with SVD, as well as future advances in diagnosis, care, and treatment, will require a more "joined-up"' approach. This approach should integrate clinical expertise in stroke neurology, cognitive, and physical dysfunctions. It requires more clinical trials in order to improve pharmacological interventions, lifestyle and dietary modifications. A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel interventions. An essential prerequisite to accelerating clinical trials is to improve the consistency, and standardization of clinical, cognitive and neuroimaging endpoints.

Figure 1

Case vignette. A 75-year-old female presents to the acute medical assessment unit with recurrent falls. She has a past medical history of hypertension, hypercholesterolaemia and recent lacunar stroke 3 months ago. She is an ex-smoker of 40 pack-years. On examination her blood pressure is 169/85 mmHg, without postural hypotension, and pulse is regular. She is objectively apathetic and mildly bradyphrenic. She has a slow, shuffling gait, with preserved arm swing, and is unsteady on initiation and turning. She has mild dysarthria and a left pronator drift. She scores 22/30 on MoCA, with deficits in executive function, attention and abstraction. Her daughter reports progressive cognitive and functional decline over the past 2 years and subtle behavioural changes developing over the past month: she has become apathetic, finds it increasingly difficult to manage her finances, and is easily fatigued performing minor household tasks. Full blood count, urea and electrolytes, and C-reactive protein are normal, serum cholesterol is 5 mmol/L, HbA1c is 40 mmol/mol and electrocardiogram shows sinus rhythm, normal conduction intervals, and mild left ventricular hypertrophy. Brain MRI shows a subacute right thalamic small subcortical infarct, periventricular and deep white matter hyperintensities, enlarged perivascular spaces, and a chronic lacune: (A) Subacute small subcortical infarct in the right thalamus (yellow arrow, on FLAIR) relating to clinical lacunar stroke three months ago and white matter hyperintensities (hyperintense on FLAIR); (B) Lacunes and enlarged perivascular spaces (blue and red circles respectively, hyperintense on T2-weighted imaging. MoCA: Montreal cognitive assessment scale; MRI: Magnetic resonance imaging; FLAIR: Fluid-attenuated inversion recovery.

Figure 2

Clinical features of small vessel disease.

Figure 3

Defining the trajectory of small vessel disease. MCI: Mild cognitive impairment.

Figure 4

Factors influencing reporting of symptoms related to disease accumulation.