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.