Introduction

Binswanger’s Disease is a form of subcortical vascular dementia, characterised by white matter hyperintensities in the brain. Its progressive nature results in difficulties in motor movements such as tremors, rigidity, gait disturbance, fine motor deficits, bradykinesia and balance, as well as accompanying cognitive and behavioural deficits. Named after the Swiss Psychiatrist Otto Binswanger, the clinician identified this unique presentation of neurodegeneration back in 1894. Over the next two centuries, advancements in technologies and diagnostics uncovered a deeper understanding of the pathophysiology of the disease to formulate effective treatments. This article seeks to explore in detail the deficits in motor abilities resulting from the disease.

Understanding motor symptoms is extremely crucial in improving a comprehensive scientific and clinical understanding of the disease manifestation, to perceive nuances in symptom presentation, in order to curate treatments that improve both medical outcomes and quality of life. 

Pathophysiology of Binswanger's disease 

Identification of pathology through imaging 

Magnetic Resonance Imaging is highly sensitive to detecting abnormalities in white matter structures.¹ Due to the relatively high spatial resolution, an MRI can allow the visualisation of small lesions to define their full extent of involvement with white matter structures. Moreover, the presence of lesions in this area, extended to structures such as the corpus callosum and the corona radiata, has been correlated to deficits in cognitive and behavioural outcomes. Perfusion MRIs that use a paramagnetic contrast agent to measure regional cerebral blood flow and blood volume reveal key biomarkers to help diagnose and visualise Binswanger’s disease – such as reduced blood flow to white matter areas in the periventricular regions, useful to identify at-risk white matter regions for early intervention.

Brain regions affected

Subcortical structures

Some of the subcortical structures affected through Binswanger’s disease include the Basal Ganglia, deep white matter, and thalamic regions. As these structures are involved in motor control and coordination, damage to specific neuronal pathways or sub-structures reveal differences in the type and intensity of motor symptoms experienced. The resulting loss of neuron populations, demyelination, as well as chronic ischemia, may explain the resulting cognitive impairment.

Periventricular areas 

The areas surrounding the lateral ventricles, known as periventricular regions, are also impacted as a result of Binswanger’s disease. Situated near major cerebral arteries, these regions are susceptible to massive reductions in cerebral perfusion occurring due to ischemic stroke. Such regions may be exposed to gliosis, a process of proliferation of glial cells such as astrocytes in response to chronic ischemia. Here, the astrocyte cells multiply to form scar-like tissue, disrupting the neural architecture and process of regeneration.²

Mechanisms leading to motor symptoms

Demyelination

Demyelination refers to the progressive loss of the myelin sheath surrounding the nerve fibres, which plays a crucial role in the efficient transmission of nerve signals. Demyelination is prevalent in Vascular Dementias, where chronic hypertension results in the narrowing of blood vessels, reducing cerebral blood flow, thereby causing hypoxia. This results in a cascade of events, where microglial cells release substances that further break down the blood-brain barrier, resulting in myelination. The resulting impairment in nerve signal transmission is one of the key causes of motor deficits in Binswanger’s. ³

Neuronal loss

Another critical factor is the loss of neurons, which further intensifies motor symptoms. Apart from demyelination, inflammation also causes axonal injury, which leads to neuronal death and further impairment of motor symptoms and cognitive health. Proton MRS (1H-MRS) and Diffusion Tensor Imaging reveal albumin and matrix metalloproteinases (MMPs), which are inflammatory markers indicating disruption of the blood-brain barrier. By monitoring the progression of white matter lesions and correlations with motor symptoms, diagnostic clarity is achieved in the integration of multimodal data.⁴

Motor symptoms in Binswanger’s disease

Motor symptoms 

Binswanger’s disease is characterised by abnormalities in gait and motor symptoms arising due to damage in white matter structures, reduced blood flow and impaired signal transmission. 

Gait abnormalities

• Gait apraxia – the inability to plan and execute motor functions required to walk – where patients struggle in maintaining a proper walking rhythm or taking initial steps despite no prior motor weaknesses
• Magnetic gait – a type of gait disturbance where their feet seem “glued” to the surface. Patients often have difficulties lifting up their feet, and may take short, shuffling steps⁵

Parkinsonism

• Bradykinesia – slowness of movement, reduced spontaneity and slower motor task execution
• Rigidity – increased muscle tone, especially in limbs, impairing a patient’s dexterity, mobility, leading to stiffness in movement and posture
• Tremor – Some patients may also experience tremors, albeit less commonly reported. These tremors cause involuntary hand movements which affect a patient’s ability to perform activities

Dysarthria

A resulting cognitive and speech deficit arising from motor control impairments, where patients face challenges in communication due to slowed speech and slurring. 

Coordination and balance issues

Motor difficulties resulting in difficulties in coordination, maintaining balance, and increasing risks of falls.⁶

Onset and progression

Early-stage motor symptoms

During the initial stages of degeneration, patients may experience mild abnormalities in gait, with an increased tendency for unsteadiness and mild shuffling. Bradykinesia may start to develop, but is often misattributed to the natural progression of ageing.

Advanced-stage motor symptoms

Certain symptoms observable to individuals indicate a further deterioration, where motor symptoms become more pronounced and debilitating. These include more prominent presentations of gait abnormalities, evident Parkinsonism features and immobility

Management and treatment

Binswanger’s disease is a challenging condition to treat due to the lack of clinical trials and research targeting the pathophysiology and treatment of this disease. Current standards of treatment involve treating Binswanger’s akin to Vascular conditions, following the standards of the American Heart Association.

Pharmacological interventions

• Antihypertensives – As hypertension is one of the most common causes and comorbidities of the pathogenic development of Binswanger’s, medications that target the reduction of blood pressure are recommended. Studies such as the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) have shown promising results on the impact of BP Reduction correlated with the reduction of white matter hyperintensities for individuals with stroke. It is also important to consult your physician on the dosage to avoid unexpected side effects⁷
• Antiplatelet agents – The effectiveness of antiplatelet therapy to reduce thrombotic events is currently being debated. While some results from trials discourage the use of antiplatelet agents (such as aspirin)⁸ to avoid risks of intracranial haemorrhage, radiological evidence shows it to be reasonable in patients with Binswanger’s. However, risks of comorbid conditions such as amyloid angiopathy must be taken into consideration
• Medications for motor symptoms (e.g., levodopa, dopamine agonists) are also cautiously recommended to help manage motor difficulties

Non-pharmacological & lifestyle modifications

Lifestyle modifications go a long way in improving adjustment to the medical condition as well as improving psychological and physical health. Physicians recommend a low-salt diet to help manage blood pressure and reduce the risk of stroke. Exercise interventions have also shown positive results in preventing cognitive decline and reducing white matter hyperintensities within the brain. It is important to maintain good cardiovascular health to reduce disease progression, and thus, it is suggested that steps must be taken to manage common conditions such as diabetes and cholesterol. The role of physical and occupational therapy is extremely useful in this regard to help improve mobility and comfort. ⁹

Genetic studies

Uncovering potential links between genetic variants and Binswanger’s disease has the potential to spearhead research in diagnostics and pathology. Identifying specific genes related to hypertension and endothelial function unique to small vessel disease and cerebral amyloid can help in formulating targeted genetic screening and form personalised prevention and treatment strategies. There is also great scope for gene therapies for the same.

Biomarkers

Identifying inflammatory, fluid-based based and radiological biomarkers helps diagnose and monitor disease progression. Utilising quantitative measurements of endothelial growth factors and inflammatory cytokines, which are commonly associated with Binswanger’s disease, are also useful to classify symptom presentations in dementia to avoid misdiagnosis. They also help formulate new medications aimed at improving endothelial function and protecting white matter integrity. Identifying biomarkers thus paves the way to model and develop specific drugs to slow disease progression.

Gaps in research and future challenges

At present, the protocols for management and treatment of symptoms do not address specific pathological and clinical presentations of Binswanger’s disease. While existing treatment strategies used are informed based on studies on Vascular conditions and cognitive impairment, it is important for future research to explore curating specific diagnostic and care standards for Binswanger’s disease. 

Summary 

• Binswanger’s disease is a type of subcortical vascular dementia characterised by white matter hyperintensities and leads to significant motor and cognitive deficits
• It affects regions of the brain such as the Basal Ganglia and Periventricular areas, causing inflammation and demyelination driven by chronic ischemia
• Degeneration in these brain regions causes Parkinsonism-like symptoms such as bradykinesia, tremors, gait abnormalities and issues with balance
• Current treatments focus on existing standards of care for vascular and stroke conditions, to control for hypertension and alleviate motor symptoms through medications
• Future research must focus on uncovering the unique pathological features of Binswanger’s, to further develop medications and interventions to improve medical outcomes and quality of life