Binswanger’s disease: toward a diagnosis agreement and therapeutic approach

Abstract

Binswanger’s disease (BD) is a progressive form of cerebral small vessel disease affecting the white matter and other subcortical structures. Clinical and imaging characteristics, neuropsychological profile and cerebrospinal fluid analysis aid in making the diagnosis. BD shares features of other small vessel diseases and degenerative neurological conditions, which makes diagnosis difficult. However, with recent developments in MRI methods and serum/cerebrospinal fluid biomarkers, we have gained a greater understanding of the complex pathophysiology of the disease that will guide us to a more certain diagnosis. There is growing evidence that the white matter injury in BD is related to endothelial dysfunction with a secondary inflammatory response leading to breakdown of the neurovascular unit. This review summarizes current and future research directions, including pathophysiological mechanisms and potential therapeutic approaches.

Keywords::

• Binswanger’s disease
• dynamic contrast enhanced MRI
• leukoaraiosis
• matrix metalloproteinases
• neuroinflammation
• neurovascular unit
• small vessel disease
• subcortical ischemic vascular disease
• vascular cognitive impairment

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Binswanger’s disease (BD) is a form of cerebral small vessel disease characterized by cognitive impairment, gait disturbances with small subcortical ischemic strokes and ischemic white matter hyperintensities. It is strongly associated with long-standing hypertension and symptoms that progress over time.

• Advanced imaging, neuropsychological testing and cerebrospinal fluid evaluation are aids to support the diagnosis of BD.

• Blood pressure control is the main therapy that most likely delays progression of the disease.

• Antiplatelet therapy, statins, diet and exercise also play an important role in the medical management of this condition.

• Avoid dual antiplatelet therapy or anticoagulation for secondary stroke prevention unless benefits are clearly more than risks (e.g., afib, cardiac stent).

• Converging evidence suggests that endothelial dysfunction and neuroinflammation leads to blood–brain barrier disruption in BD patients. These changes can be measured by new MRI methods.

• New clinical scales and outcome biomarkers will facilitate the selection and execution of clinical trials with BD patients.

• As new pathophysiology is revealed, novel therapeutics will target other mechanisms such as inflammation, arterial stiffness and clearance of cerebral waste material in the coming years.

Notes

^†WMHs are seen in T2 and Fluid Attenuating Recovery (FLAIR) MRI sequences. Large WMHs are always present in BD patients, although specific threshold size has not been yet established.

^‡WM atrophy is typically larger than gray matter atrophy.

^§If present, should be mostly subcortical.

CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; TCD: Transcranial Doppler; WMHs: White matter hyperintensities.