Introduction

The term “leukoencephalopathy” refers to a heterogeneous group of disorders characterized by the degeneration of the white matter of several etiologies: vascular, toxic, infectious and genetic. The last group includes the so called leukodystrophies 1.
The term Binswanger’s disease was given by Elois Alzheimer in 1902 in honour of his professor, Otto Binswanger, who first described the clinical and pathological aspects of the disease in 18842. Binswanger’s disease, or “subcortical arteriosclerotic encephalopathy”, as Olszewski called it 60 years after its first discovery 3, refers to a type of leukoencephalopathy linked to circulatory and vascular factors with significant clinical consequences frequently associated with arterial hypertension, arteriosclerosis and strokes 4.
Binswanger’s disease represents one of the causes which lead to vascular cognitive impairment alongside cerebral lacunes, amyloid angiopathy and some forms of Alzheimer diseases, and it may coexist with any of these disorders 5. Louis Caplan established in 1995 the first criteria for that are required for diagnosis and they are sub-divided into three categories which we will enunciate briefly in the following paragraphs 2. These criteria still hold to the present day and have been adapted through the course of time along with a better understanding of the physiopathological and morphopathological characteristics.

I. The presence of known or hypothesized risk factors

The most important and frequently described risk factor associated with Binswanger disease is chronic, uncontrolled, arterial hypertension, therefore its absence in a patient with cognitive impairment and neurological signs should lead to questioning the diagnosis5. The explanation most often proposed is that chronic arterial hypertension is responsible for the narrowing of the small blood vessels due to lipohyalinosis and fibrosis with subsequent blood flow reduction and hypoxia. These phenomena lead to a local neuroinflammatory response which in turn result in myelin sheath degeneration 6. Other risk factors such as diabetes mellitus, smoking, dyslipidemia, sleep apnoea, atrial fibrillation, although frequently present in these patients, have a smaller role in establishing the diagnosis of the disease 5. Exclusion of other diseases which lead to white mater degeneration, such as multiple sclerosis, AIDS or radiation toxicity is crucial2.

II. Clinical features

An essential element lies in the way the clinical aspects of the disease evolve, with stepwise or gradual progression of the cognitive impairment and other neurological signs and symptoms 2,5,7. First symptoms usually appear between the fifth and the seventh age decade7. The clinical course of the illness is variable and evolves over a 5- to 10-year period. There doesn’t seem to be any gender bias. Cognitive and behavioural changes are characterized by dementia and a dysexecutive syndrome (changes in attentional control, working memory, and short-term memory, impulse control and abulia in the final stages) 2,5. Computations and mathematical functions are usually deficient 2. Abnormalities of long-term memory, language and visual-spatial functions are not as prominent as in patients with Alzheimer’s or Pick’s disease and therefore the MMSE (Mini Mental State Examination) can often be within normal range, while the MOCA score (Montreal Cognitive Assessment) may evidence cognitive impairment 5. History often reveals past strokes which can be sometimes typical to one of the multiple lacunar syndromes, pure motor hemiparesis being the most frequent of them 7. In other patients, the focal neurologic deficits can have a subacute onset with progressions during days or weeks and are sometimes associated with strokes. Cognitive and behavioural impairment, motor and gait disturbances, falls, incontinence evolve with periods of stabilization, plateaus and periods of improvement. A mixture of pyramidal tract signs, extrapyramidal signs and pseudobulbar signs can often be seen 2,5,7.

III. Imaging

The first imaging descriptions of the lesions were given using Computer Tomography (CT). The ubiquitous characteristic of the illness is represented by the changes to the subcortical white matter which has a bilateral presentation, described as low dense lesions without contrast enhancement. These lesions are most often present in the periventricular regions, especially adjacent to the frontal horns. These changes were named leukoaraiosis by Hachinski and they denote the rarefaction of the subcortical white matter. Juxtacortical white matter (“U”-association fibers) is often spared. It is important to mention that these changes can be present without any neurological signs and can be also associated with aging 7. White matter disorders are better characterized on MRI which has a greater sensitivity than CT. The areas of demyelination are described on MRI as large, confluent, white mater hyperintensities (on T2WI and FLAIR sequences), with ill-defined borders. The lesions are discretely hypointense on T1WI sequences. Lesions are usually bilateral, symmetric and grouped around the frontal horns, but can have variable degrees of extension, and both the periventricular and deep white matter can be affected, but the juxtacortical white matter is always spared, as mentioned before. Subcortical lacunes and “mini-strokes” are often found and the Virchow-Robin perivascular spaces are frequently enlarged4,5, 8. Lesions can also be present in the white matter of the brain-stem, especially the central pons (the medulla oblongata and the midbrain are also more often than not spared)9. Mild to moderate white matter atrophy is also a common finding 5. Diffusion weighted imaging (DWI) can detect acute ischemic lesions. Subcortical microbleeds can be seen in Binswanger’s disease and can be detected on SWI sequences, but their presence in large numbers or if they are located in the cortical regions should raise the suspicion of amyloid angiopathy 5.