Introduction

Binswanger's Disease (BD), also known as subcortical arteriosclerotic encephalopathy, is a progressive form of cerebral small vessel disease (CSVD), that affects brain function by disrupting the blood supply to the brain's white matter. This condition leads to tissue degeneration, cognitive decline, urinary incontinence, and motor deficits, that gradually worsen over a decade.^1,2,3 

Aetiology

The condition can arise from numerous causes, including sporadic and genetic factors. Sporadic causes can include traumatic injury to the white matter of the brain, hypertension, smoking, and high cholesterol levels. At the same time, clinicians argue that BD can also be the result of certain hereditary conditions, such as CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy).^1,2,4 

Pathophysiology

In small vessel diseases, the arterial walls are dysfunctional, which leads to inefficient blood and oxygen supply due to chronic ischemia. The depleted blood supply often induces localised infarctions, leading to endothelial dysfunction and the breakdown of neurovasculature.² 

In BD, inadequate blood and oxygen flow mostly affects the area around the ventricles in the brain, also known as the periventricular area. This leads to ischemic periventricular leukoencephalopathy (IPVL), where the lack of blood supply causes the patient's brain tissue to soften and the white matter to degenerate.^2,3

The lack of white matter can be visualised with magnetic resonance imaging (MRI), usually showing extensive white matter loss around the ventricles, particularly in the frontal and parietal lobes.^1,2,5 The pathophysiology will eventually lead to vascular cognitive impairment, with hypertension being a key risk factor.^2,3 Ultimately, the disease process involves a complex interplay of vascular, inflammatory, and neurodegenerative mechanisms, contributing to the progressive nature of the condition.²

Symptoms associated with Binswanger disease 

Cognitive abnormalities

During BD, there is a cognitive decline induced by the lack of oxygen-associated white matter loss, which disrupts neuronal signalling in the brain. The onset of the disease usually occurs between 50-70 years of life, and the cognitive decline gradually worsens over a decade. It can be exacerbated by the so-called “mini-strokes” happening in different parts of the brain, inducing further brain damage. The most affected cognitive functions are executive function, motor deficits, and mental processing speed. Interestingly, although memory dysfunction can be present in some Binswanger cases, it is less common than in other degenerative diseases.^2,6

As the disease is hard to differentiate from other forms of dementia, care must be taken to choose the correct tools for cognitive assessment. Given the condition often doesn’t lead to memory loss, the tools screening for Alzheimer’s disease, such as the Mini Mental Status Examination (MMSE) may not show any abnormalities for patients with Binswanger disease. Therefore, the go-to routine testing used is the Montreal Cognitive Assessment (MoCA), which also tests executive function, thus making it a better tool for evaluating Binswanger cases.^2,3,5

To summarise, symptoms directly associated with cognition in BD involve:^2,3
Depressed or apathetic mood

• Inability to make decisions
• Delay in task completion
• Bad planning and organisation skills

Further behavioural manifestation of the cognitive symptoms

Unfortunately, cognitive deficits experienced by the patients often lead to other symptoms in these patients as well, making them unable to perform basic daily tasks. Therefore, individuals with BD, especially in the later stages of disease development, require constant care. Other symptoms associated with the disorder include:^2,5,6

• Difficulty speaking and swallowing, also known as pseudobulbar palsy, is caused by damage to corticobulbar white matter tracts in the brain
• Lack of facial expressions
• Changes in reflexes, often presenting as hyperreflexia (overactive reflexes), which indicate damage to the pyramidal tracts of the brain
• Slowness, rigidity, tremors, and balance problems - similar to patients with Parkinson’s disease
• Marche à petits pas, a so-called small step gait, also similar to Parkinson’s patients
• Urinary incontinence, which only occurs in later stages

Physiological symptoms

Although the aforementioned behavioural correlates are important for the recognition of the disease, other physiological markers must also be taken into consideration when making a differential diagnosis compared to other conditions, such as Alzheimer’s Disease. These symptoms include:^1,2,3,5

• Hypertension or high blood pressure: It is a crucial characteristic of BD, and its absence typically rules out the diagnosis. Chronic hypertension damages the small blood vessels in the brain, leading to the characteristic white matter changes
• Increased risk of stroke: Both ischemic and hemorrhagic strokes are more common in Binswanger's disease patients
• Increased risk of Type II Diabetes
• Other vascular risk factors: Often coexist with hyperlipidemia and smoking, which contribute to the progression of the disease

Neuroimaging correlates

The pathophysiological process of BD can be visualised using neuroimaging techniques, which visualise the brain tissue and vasculature. Image features associated with BD include:^3,5,7

• White matter hyperintensities, which are visible on T2-weighted (T2WI, a basic pulse sequence used for imaging) MRI as areas of increased signal intensity in the white matter, particularly in periventricular regions. These represent areas of chronic ischemia and demyelination
• Lacunar infarcts: Small, deep brain infarcts often seen on MRI, resulting from the blockage of small penetrating arteries
• A loss of neurons or neuronal connections is also known as brain atrophy. Particularly noticeable in subcortical regions, contributing to cognitive decline. This can be quantified using volumetric MRI techniques
• Enlarged perivascular spaces: Often visible on MRI, indicating damage to the blood-brain barrier
• Small haemorrhages in the brain tissue, also known as microbleeds, are best visualised on susceptibility-weighted MRI sequences
• Cerebral microinfarcts: Tiny areas of dead tissue due to lack of blood supply, can be visualised by high-resolution MRI
• Ventricular enlargement: Secondary to white matter loss and brain atrophy
• Reduced cerebral blood flow, which can be assessed using perfusion imaging
• Diffusion tensor imaging (DTI) abnormalities: Showing disruption of white matter tracts

MRI scan of a 72-year-old woman presenting hypertension, diabetes, impaired memory, and left-sided weakness. Numerous infarcts are present in the deep white matter in both hemispheres, indicated by the brighter areas on the scan. Credit: David C Preston.⁷

Summary

Binswanger's Disease (BD) is a progressive cerebral small vessel disease characterised by disrupted blood supply to the brain's white matter. Typically onset between ages 50-70, BD stems from factors like hypertension and genetic predispositions, causing chronic ischemia and neurovasculature breakdown.

Symptoms include cognitive decline (particularly in executive function), behavioural changes, and physical manifestations resembling Parkinson's disease. Diagnosis relies on cognitive assessments like the Montreal Cognitive Assessment (MoCA) and crucial neuroimaging techniques. MRI scans reveal white matter hyperintensities, lacunar infarcts, and brain atrophy, especially in periventricular regions.

Hypertension is a key risk factor and diagnostic marker for BD. The disease's progressive nature often leads to a need for constant care in later stages. Ongoing research aims to improve early detection and management strategies for this complex condition, potentially leading to better patient outcomes.