Binswanger's disease: a review.

V Babikian and A H Ropper

Stroke. 1987;18:2-12
doi: 10.1161/01.STR.18.1.2
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Progress Review
Binswanger's Disease: A Review
Viken Babikian and Allan H. Ropper

INSWANGER'S disease (BD) is characterized

by cerebrovascular lesions in the hemispheral
white matter. Interest in BD has been stimulated recently by reports of low density in the periventricular white matter on computerized tomography
(CT) and magnetic resonance imaging (MRI) in elderly patients with dementia. This radiographic appearance also is common in asymptomatic patients. To
better define the clinical features associated with the
characteristic white matter lesions of BD, we reviewed
the international literature from 1912 to the present for
pathologically verified cases accompanied by relatively complete clinical descriptions. Twenty-one reports
with 46 patients were found and, with a case of our
own, are summarized in Table 1. The initial symptoms, rate of progression, presence of dementia, and
other clinical features were variable. The pathologic
features of these 47 cases were, by contrast, uniform
and constitute the best basis for defining BD as a disease. The precise cause of the characteristic, presumably ischemic, white matter changes is unknown.

the title "Subcortical Arteriosclerotic Encephalopathy." In the next decade, several well-documented
cases 36 were published, and the pathophysiology of
periventricular white matter degeneration was studied. 78 More recently emphasis has been on premortem
recognition of the disease. Caplan and Schoene in
1978 presented 11 cases, stressed the clinical features
and course of the illness, and emphasized hypertension.9 Rosenberg et al correlated the clinical, CT, and
pathological findings in a case, raising interest in the
radiological appearance of BD. 10 Large series of patients have been reported with CT findings compatible
with BD. 1112 MRI is probably even more sensitive than
CT for the detection of the typical white matter lesions
of BD.13-16

History
In three articles on the differential diagnosis of general paralysis of the insane, Binswanger in 1894 described 8 patients with a subtype of cerebral arteriosclerosis.1 Their clinical courses were characterized by
slowly progressive intellectual deterioration starting in
the sixth decade, punctuated by seizures and strokelike events. Extensive white matter atrophy, predominantly in a periventricular and temporal-occipital distribution, spared the basal ganglia and the cortical
mantle. Binswanger suggested that white matter atrophy resulted from deficient blood supply caused by
arteriosclerosis. In 1902 Alzheimer added microscopic
observations emphasizing that the cortex was relatively unaffected, while the white matter had focal degeneration and glial proliferation.2 He also considered a
causal relation to arteriosclerosis, noting severe
atherosclerosis of the deep white matter long penetrating vessels. Famell and Globus in 19323 reported a
patient with clinical and pathological findings similar
to those described by Binswanger.
In a major review in 1962, Olszewski translated the
articles by Binswanger, Alzheimer, and Nissl and presented two new cases. 4 He emphasized the presence of
associated lacunes and cortical infarcts, and suggested

Incidence of Presumed BD
The incidence of BD is uncertain because there is no
consensus about the specific clinical features of the
disease and no diagnostic test. In a study of 1,000
brains at the Tokyo Metropolitan Geriatric Hospital,
Tomonaga et al identified 45 with pathological
changes of "Progressive Subcortical Vascular Encephalopathy."17 The incidence was 3.8% in the elderly,
highest in those with cerebrovascular disease (6.7%).
However, clinical features or selection criteria for autopsy examination were not specified. The incidence
in Japan might be higher than expected for the U.S.
since hypertension is more prevalent in Japan.18
The incidence of CT findings suggesting BD was
1.6 % among the CT scans of 1,700 patients with cerebral atrophy in one study.19 This is comparable to
Zeumer's 0.5% obtained from 13,000 CT scans at a
neurology clinic" and Kinkel's 1.7% of 1,633 CT
scans.20 In contrast, Goto et al found 5% of 4,742 scans
with diffuse white matter disease, increasing with
age,12 and Pullicino et al found 8% of 65 unselected
consecutive CT scans of patients above age 60. 2I Goto's series12 included patients from two hospitals, one
group with mental deterioration and the other selected
because of cerebrovascular disease, perhaps favoring
more positive scans. Similarly, in Pullicino's series,21
half of the patients had mental impairment. The incidence of radiological features consistent with BD is
therefore likely to be 1-5% in the elderly, increasing
with age, hypertension, and severity of cerebrovascular disease.

From the Cerebral Blood Flow Laboratory and the Neurological/

Neurosurgical Intensive Care Unit, Massachusetts General Hospital, Boston, Massachusetts.
Address for reprints: Dr. Ropper, Department of Neurology,
Massachusetts General Hospital, Boston, MA 02114.
Received April 3, 1986; accepted August 21, 1986.

Epidemiology
The average age at onset of symptoms in the 47
tabulated cases was 57 years (range 40-78) (Table 1);
83% were in their sixth or seventh decade.3-*91022-36
Men and women were equally affected. The average

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Babikian and Ropper

Binswanger's Disease

duration of disease from the earliest symptoms to death

was 5 years (range, 2 months-22 years). Hypertension
(systolic blood pressure [BP] documented above 140
mm Hg or diastolic above 90 mm Hg, or a heart weight
over 350 g) was present in 36 patients; 4 were reported
(but not documented) to be hypertensive, and 1 patient
was reportedly normotensive. In 6 there was inadequate information about BP. Therefore, 40 of 41
(98%) with information available were hypertensive.
Other frequently associated medical problems, inconsistently reported and therefore making their incidence
unclear, included diabetes mellitus, coronary artery
disease, infection preceding onset of symptoms, and
prior malignancy.
Clinical Features of the 47 Patients
ONSET AND COURSE. The onset of symptoms began
with an acute, focal neurological deficit, consistent
with a stroke, in 14 cases (33% with information available). A slower, less abrupt onset was reported in 28
(66%), 6 with focal symptoms; 2 lacked information
about onset, and in another 3 the history was inadequate (Table 1). The subsequent course of the illness
followed one of three patterns: In 19 (43% with information available), gradual progression without acute
deficits; in 6 (14%), strokes alone without progression;
in 19 (43%), gradual progression of symptoms exacerbated by acute focal deficits. Periods of relative improvement or stability were unusual but were reported
in a few. In 3 cases, the clinical details were insufficient to establish the rate of progression.
SYMPTOMS AND SIGNS. Except for 1 or 2 patients,
changes in mental status occurred in all (Table 1).
Changes were present at the onset as the main or only
feature in 14, and in at least 30 (65%) they occurred
early in the illness. An insidious progression of memory deficit was most common, but mental changes
were sometimes described after an ictus, giving the
appearance of sudden onset. Intellectual deterioration
was often vaguely described; slight confusion, a
change in character, apathy and loss of interest in usual
activities, paranoia, or a mild memory deficit were
frequent descriptive terms. Marked difficulties in judgment and orientation and dependence on others for
daily activities were present later. An amnestic syndrome dominated the early illness in at least 26 cases.
Alterations of mood and behavior were prominent;
patients were described as "euphoric," "elated," or
"aggressive." Overt depression was reported in 10 patients (21%), with suicide attempts in 3. Aphasia,36
hemianopia,31 anosognosia, or apraxia353* were uncommon.
In 42 cases (89%), a complex clinical picture of
mild asymmetric pyramidal (reflex asymmetries,
hemiparesis), extrapyramidal (rigidity), or cerebellar
signs (limb or gait ataxia) were present, at times concomitantly in the same patient. Lateralizing motor
signs were absent at the onset in a few patients. Frequent falls were among the initial symptoms in 3 cases,
and a gait disorder appeared in at least 25 patients.
Dysarthria with or without pseudobulbar features, and

in the more advanced cases urinary incontinence, were

frequent. Seizures were reported in 8 patients (17%),
and myoclonic jerks in 1. Lateralizing or focal signs
seemed less prominent early in the course, when mental status changes dominated the clinical picture.
Pathology
The pathological findings were the most consistent
features in the cases tabulated (Table 1). Autopsy findings, when information was available, showed evidence of prolonged hypertension. The meninges were
usually normal. Gyral atrophy and sulcal enlargement
of varying degrees, usually not severe, were frequent.
Discrete lacunar infarctions were present in 39 of 42
cases (93%) adequately studied, involving the white
matter of the internal capsule, centrum semiovale, basal ganglia, and occasionally, cerebellum. Cerebral infarction was noted in at least 15 cases. Coronal sections of typical cases had several confluent areas of
white matter discoloration, separate from lacunes, described as soft, puckered, and granular. The areas
affected, usually patchy and relatively symmetric, involved more commonly the occipital and periventricular white matter.5'2527 However, asymmetric,31 focal,24
and mainly frontal10 distributions of white matter abnormalities were described in a few cases. The cerebellum was occasionally affected.31 The corpus callosum
was often secondarily thinned, but primary white matter lesions were not reported there.
Lateral ventricular enlargement was present in 38 of
40 cases (95%) with information available, though
measurements were infrequently given. It was often
suggested that the occipital horns were enlarged earlier
or to a greater extent than the anterior horns. Ventricular enlargement was judged consistent with the degree
of periventricular white matter tissue loss and generally reflected its distribution.
The large vessels at the base of the brain showed
atheromatous changes of various degrees in 40 of 43
cases (93%). Severe stenosis was occasionally described.410 Although it is not possible to assess the
hemodynamic significance of these atheromatous lesions, most were unlikely to cause significant distal
hemodynamic effects.
The microscopic distribution and severity of the
white matter Changes were inhomogeneous. In mildly
affected areas, the findings sometimes consisted only
of swollen myelin sheaths. In advanced lesions, loss of
myelin and oligodendrocytes was more prominent than
fragmented axis cylinders. At their extreme, these
changes became zones of white matter rarefaction or
cavitation with scattered microcystic areas of infarction. Astrocytic gliosis, almost invariably present, was
at times prominent. The subcortical association fibers
were, as a rule, spared. Islands of myelin loss and
destruction had irregular edges, especially as one approached the cortex, with normal-looking areas adjacent to fragments of affected tissue.
Microscopic vascular changes were invariably present, most prominent in the white matter arterioles.
Cortical vessels were usually, but not always, better

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Stroke

Vol 18, No 1, January-February 1987

Table 1. Clinical Course and Pathology

Author (ref)
Ladame (22)
FameU (3)
Davison (23)
Neumann (24)
Garcin (25)

Jelgersma (26)
Olszewski (4)
Mikol (5)

Yvonneau (27)
Biemond (28)
Ishino (29)
Aronson (6)
Burger (30)
Caplan (9)

Cherif (31)
Rosenberg (10)
White (32)
Zeumer (33)
Janota (34)

Dupuis (35)
Dubas(36)

Patient 1

Age at
onset/sex
47/F
40/F
65/M
47/F
567M
53/M
63/F
61/F
51/F
63/M
58/M
63/M
58/F
74/M
48/F
63/F
59/F
6(VF
58/M
52/M
50/M
44/F
57/M
54/M
78/M
58/F
65/F
63/M
69/F
50/M
57/M
55/F
56/M
55/M
54/F
46/F
52/F
50/F
50/F
61/M
55/M
52/F
64/F
65/M
58/M
64/M
76/F

BP
NS
NS
210/120
Elevated
250/120
Elevated
NS
220/120
180/120
NS
160/100
150/60
150/80
NS
220/210/110
220/130
Normal
170/110
240/140
-/150
228/110
Heart 450 g
200/110
190/100
220/120
220/120
Elevated
210/110
NS
230/160
190/120
190/110
160/80-100
210/120
190/110
165/105
200/140
Elevated
250/130
230/120
210/140
230/140
200/110
230/120
230/120
170/90

Sx at onset
MS
Falls
Focal Sx
MS
Gait, focal Sx
Focal Sx
MS
MS
Focal Sx
NS
Focal Sx
Focal Sx
Gait
Focal, consc.
Focal Sx
MS/seizure
MS
Focal Sx
MS
MS, gait
MS
Ataxia, seizure
MS, focal Sx
Focal Sx
MS, falls
Focal Sx
MS
Gait, focal Sx
Focal Sx
NS
Gait, MS
MS
Focal Sx
Focal Sx
MS
MS, gait
Focal Sx
MS
Gait, speech
MS, gait
Focal Sx
Focal Sx
Focal Sx
MS
MS, gait
MS
MS

Acute
deficit

Subacute
progress

+
-

+
+
+
-

NS
+
+
+
+

NS
+
+

NS
+

+
+

+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+

+
+
+
+
+
+
+
+
+
+
NS
+
+
+
+
+
+
+
+

+
+
+
+
+
+
+
+
+
+
+
+

Seizures
+
NS
NS
+
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS

+
+
NS
NS
+
Myocl. jerks
+
+
NS
+
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
-

NS = information not available; MS = change of mental status; + = present; = absent; Consc. = "troubles de la conscience.

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Babikian and Ropper

Binswanger's Disease

Table 1. (continued)
Mental status exam
Irritability, euphoria, anxiety, memory
"Nervousness," confusion, disorientation
Confusion, restlessness, euphoria
"Senile dementia," depression
Memory, attention, hemianopsia, "decheance intellectuelle"
Patient unable to give history
Irritability, confusion
Labile affect, mania, confusion
NS
Memory
Euphoria, indifference
Episodes of confusion, "atteinte psychique"
Disorientation, memory
No history, "coma vigil"
Memory, judgment, attention
Memory, euphoria, depression, alexia, apraxia
Memory, sensory aphasia
Global dementia, agarphia, apraxia
Attention, memory, disorientation, akinetic mute
Confusion, irritability, paranoia, depression, memory
Judgment, confusion, depression, memory, mutism
Confusion, memory, intellect
Confusion, memory
Withdrawn, attention
Confusion, mutism, aphasia, hemianopsia
Memory, intellect
Aphasia, echolalia, anosognosia
Disorientation, intellect, memory, dysarthria
Memory, attention, "irascible," depression
Progressive dementia
Memory, elation, intellect, dressing apraxia
'Temper," hallucinations, paranoia
Memory, confusion, paranoia
"Violent," "slow," "lazy," depression
Memory, insight, confabulation, dysphasia
Depression
Depression
Disorientation, apraxia, depression, irritability
Memory
Memory, indifference, character
Behavior, dysarthria, memory, acalculia
Aphemia
Agitation, intellect, memory
Memory, intellect, character
Intellect, character
Memory, character, depression
Memory, confusion

Large
vents
NS
NS

+
NS
-

+
+
+
+
+
+
+
+
+
+
+
+
NS
+
+
+
+
+
+
+
+
+
+
+
NS
+
+
+
+
+
+
+
+
+
NS
NS

+
+
+
+
+

White matter

Large
vessel athero

Small
vessel disease

Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present

NS
Present
Moderate
Mild
Present
Severe
Present
Present
Moderate
Severe
Absent
Present
Absent
NS
Severe
Present
Moderate
NS
Severe
Severe
Present
Present
Severe
Severe
Mild
Severe
Present
Severe
Severe
NS
Moderate
Moderate
Severe
Present
Mild
Moderate
Present
Moderate
Severe
Present
Severe
Moderate
Moderate
Present
Present
Absent
Severe

Present
Present
Present
Mild
Present
Severe
Severe
Present
Severe
Present
Present
Severe
Present
Present
Present
Present
Present
Severe
Present
Present
Present
Present
Severe
Severe
Severe
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Present
Severe
Present
Present
Present
Present
Present
Present
Present
Severe
Severe

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Stroke

preserved (Garcin's third case23). The walls of small

vessels were thickened, with lipohyalinosis of the media and fibrosis of the adventitia; lumens were seldom
totally occluded. Perivascular infiltration with inflammatory lymphocytes and histiocytes was noted in at
least 7 patients. Staining for vascular amyloid deposition was only rarely performed. 5 "
Microscopic examination of the cortex was specifically noted to be normal in at least 15 cases
(32%).26MM In 13, limited, nonspecific findings (e.g.,
"few small streaks"34) were found in the cortex. Cortical infarction was described in only 15 patients
(32%).4'9'30 In Mikol's second case5 abnormalities in
the cortex were thought to represent an extension of
contiguous white matter pathology. Cortical changes,
inconsistent from one case to another, were less prominent than white matter changes. Findings consistent
with other pathological diagnoses (e.g., neurofibrillary tangles) were either mild or absent and not thought
to explain clinical observations.
Diagnostic Tests
CEREBROSPINAL FLUID. Findings, reported in 23

cases, were normal in 9. Mildly elevated protein (up to

90 mg/dl) was found in 8 (35%), and in a ninth the
protein was 190 mg/dl. The leukocyte count was elevated in only 2 ( < 2 0 cells/mm3). Opening pressures,
when measured, were normal.
ELECTROENCEPHALOGRAM. EEG, reported in 27 pa-

tients, was characterized by diffuse background theta

or delta slowing in 14 (52%). Predominantly focal or
asymmetric slowing, especially over the temporal or
frontal areas, was also frequent.10'28 In the few patients
with serial EEG's, focal changes were obscured by
generalized background slowing as the disease advanced.30 Periodic activity with sharp and slow wave
complexes were reported in 1 case.32 However, normal
EEG's were reported in at least 3 longstanding
cases.9'23
RADIOLOGY. Information concerning CT changes in
clinically and pathologically verified cases of BD remains limited.1012'3335 Only 4 of the patients listed in
the table had CT scans. In patients clinically presumed
to have BD, CT has shown diminished white matter
density and enlarged ventricles, frequently with mild
cortical atrophy and lacunar infarctions. White matter
hypodensity has been mainly periventricular, extending into the centrum semiovale, with the region just
anterior to the frontal horns of the lateral ventricles
frequently abnormal.10'19 Posterior white matter has occasionally been the initial site of involvement radiographically." The temporal lobes have infrequently
been described specifically, possibly because of sparing of that area or difficulty in accurately imaging them
by conventional CT.' 9 In severely affected patients,
areas of low density have usually involved extensive
frontal, parietal, and occipital regions. Contrast infusion has enhanced the gray-white density difference,33
but not the white matter lesions themselves.10 The diminished white matter density has been quantified by
comparing gray-white attenuation differences of spe-

Vol 18, No 1, January-February 1987

cific brain areas in patients with BD to controls. Goto

et al found a significant difference of 11-15 Hounsfield units by comparing the centrum semiovale to
parietal gray matter in 40 presumed BD patients.12
The clinical significance of periventricular white
matter low absorption (WMLA) on CT is unclear at
present. The pathology of the white matter hypodense
areas in our tabulated cases consisted of loss of myelinated fibers with relative preservation of axons, gliosis,
and multiple small cystic infarcts of variable sizes.
Some evidence supports a relation between the severity of clinical manifestations, particularly dementia,
and the extent of CT change. 1219 In Rosenberg's case,
progression of WMLA corresponded to clinical deterioration.10 In Zeumer's series," even patients without
initial dementia but with severe morphological CT
changes deteriorated clinically when reappraised. In
contrast, almost all large pertinent series have reported
a proportion of patients with typical CT findings of
WMLA lacking mental changes. 1213 This dissociation
was supported by DeReuck et al in their pathological
observations in a patient with a normal neurological
examination.37 WMLA may be present in otherwise
asymptomatic, hypertensive elderly patients.
These contradictory conclusions may in part be related to inconsistent definitions such as dementia,
"mental deterioration,"12 and "psycho-organic impairment,"" or inaccurate diagnoses. Quantification of CT
findings has also usually been omitted. Technical differences in imaging have not been assessed. Both clinical and CT long term follow-up are needed to determine the significance of WMLA in asymptomatic
patients. White matter hypodensity may be a nonspecific observation consistent with a variety of pathological states.
Etiology
The likely ischemic nature of the characteristic
white matter lesions was initially noted by Binswanger. The width of the media of arterioles in BD
was found to be greater than in comparable cases with
intracerebral hemorrhage or hypertensive encephalopathy.38 The incidence of arteriolar changes increased
with the severity of white matter pathology.17 These
observations support a relation between the white matter arteriolar and pathologic findings similar to lipohyalinosis of penetrating arterioles and lacunar infarction. DeReuck suggested that the periventricular area
is an "end zone" for ventriculopetal perforating vessels
arising from the surface cerebral arteries.7 Chronically
decreased perfusion of these zones, without occlusion,
could cause a unique type of ischemic demyelination
and tissue infarction. A similar mechanism has been
proposed by Dubas et al36 in patients with amyloid
angiopathy associated with leukoencephalopathy,
which has many similarities to BD. Amyloid deposition in the long medullary arteries could produce distal
tissue ischemia and vessel wall hypoxia with consequent transudation of plasma. Tissue edema (whether
secondary to hypertension, trauma, or acidosis) in conjunction with hypoxemia, has been suggested by Fei-

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Babikian and Ropper

Binswanger's Disease

gin and Popoff8 as the cause of degeneration of myelin

sheaths. These authors propose that the vascular
changes may be paradoxically the result rather than the
cause of hypertension and tissue degeneration.
Treatment
The treatment of BD has mainly been preventive,
with early detection and judicious control of hypertension. It has been suggested but not substantiated that
aggressive treatment of high blood pressure could reduce brain perfusion and cause further progression of
the disease. A therapeutic trial with a vasodilating
agent to improve cerebral blood flow has been helpful
in one patient.28 Whether antiedema or antiplatelet
agents or anticoagulants are valuable is unknown.
Some complications of the disease are also amenable
to therapy. For example, seizures or depression, the
latter a feature not often appreciated, could result in
symptomatic improvement if treated. Experience with
the second case presented below suggested that aggressive control of blood pressure to close to normal levels
was associated with clinical improvement for over a
year, followed by relative stability.
Illustrative Cases
PATIENT 1. This woman presented at age 70 for
treatment of hypertension (170/90 mm Hg) and syncope. Neurological examination at age 76 was normal
except for an equivocal right Babinski sign. EEG revealed mild slowing, more prominent on the left. A
memory deficit was noted when she forgot to take her
medications. She was lost on her way to the hospital

and called on several consecutive days to ask about her

next appointment. She was confused, insisted on seeing the doctor minutes after being in the office, then
discussed her deceased husband as if he were alive.
There were bilateral Babinski signs. At 77 she could
not recognize her doctor of more than fifteen years. At
age 80, she was alert but unsure of the time and location. She thought she was 90, gave the date as 1943,
smiled inappropriately, and was easily distracted. She
performed simple tasks such as writing her name, subtracted but multiplied when asked to add, and repeated
only 4 digits forward. She was unable to recall any of 3
objects at 5 minutes. Speech was fluent with occasional misnaming, and there were bilateral grasp responses. After a syncopal episode, she developed a
mild right hemiparesis that resolved in 48 hours. EEG
showed continuous generalized 24 Hz slowing, often
sharp and rhythmic, more pronounced than 4 years
previously, with frontal predominance. CT revealed
diffuse atrophy and periventricular low attenuation
(Figure 1). She died of an acute myocardial infarction.
The brain weighed 1,380 g with minimal cortical
atrophy. The hemispheral white matter was slightly
discolored, especially centrally, with an abnormal rubbery texture, but the ventricles were not enlarged. The
vessels of the circle of Willis and the vertebral and
basilar arteries had severe but nonocclusive atherosclerosis. The right anterior cerebral artery was occluded 2
cm distal to its origin. Small focal softenings were
found in the left hippocampus, left frontal corona radiata, and splenium of the right corpus callosum adjacent to the occluded anterior cerebral artery (Figure 2).

FIGURE 1. Patient 1: CT scan shows periventricular and centrum semiovale low density with enlarged
ventricles and widened sulci.

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Stroke

Vol 18, No 1, January-February 1987

with the head and neck extended. His steps shortened

and then became shuffling. Several months later he sat
in a chair most of the day and lost interest in food,
losing about 30 pounds. Blood pressure was 170/120
mm Hg. He walked with a 3-in. heel base and 1-ft
steps, turning very slowly, taking 8-10 small steps and
shuffling, without festination. At the end of extension
there was slight cogwheeling, particularly on the right.
The toes were flexed, and he had Myerson's sign and
an oral sucking response. His face lacked emotional
expression. The CT scan showed small areas of decreased attenuation in the thalamic and basal ganglionic regions with mild cortical atrophy (Figure 4). The
following year, on antihypertensive medications
bringing blood pressure to 130/80-85 mm Hg, his
walking improved remarkably, and he became more
spontaneous. Carbidopa-levodopa (Sinemet) administration was associated with slight further improvement
in his gait. After a year of relative clinical stability, his
gait again deteriorated, though not to its previous state,
and he began having episodes of uncontrollable crying
and urinary incontinence. MRI showed widespread
periventricular white matter changes and multiple
small lacunar infarctions (Figure 5).

FIGURE 2. Patient 1: A transverse section reveals discolored

frontal white matter and areas of focal softening in splenium of
corpus callosum and white matter adjacent to anterior horn of
lateral ventricle.

Microscopic examination showed pale staining of

deep and periventricular white matter in almost all
hemispheral sections (Figure 3), with gliosis particularly prominent around some small vessels. Subcortical U-fiber tracts were spared. Infarcts in the left frontal corona radiata and splenium of the corpus callosum
appeared several weeks and several months old, respectively. The left hippocampus infarct was gliotic;
smaller thalamic infarcts, asymmetric but bilateral,
were probably 1-2 weeks old. Many cortical sections
had senile plaques, but these were not prominent in the
hippocampi, and neurofibrillary tangles were sparse.
The brainstem and cerebellum were normal. Mediumsized arterioles on the surface of the cortex had marked
intimal hyperplasia and penetrating vessels showed
lipohyalinosis. Vessels within hemispheral white matter were surrounded by pronounced itat cribtt, many
showing lipohyalinosis, some totally occluded. These
changes were more severe in deeper white matter regions than subcortically. Some cortical vessels were
surrounded by a small number of lymphocytes and
perivascular gliosis, and birefringence was seen in occasional cortical and deeper vessels with Congo Red
staining and polarized light.
PATIENT 2. A 64-year-old hypertensive man was
first seen at age 61 for the abrupt onset of gait difficulty
beginning with momentary episodes of body freezing

Discussion
BD is an illness of elderly hypertensive patients
characterized clinically by disorders of memory,
mood, and cognition; focal motor signs; and less often,
a pseudobulbar syndrome with deterioration of gait
and sphincter control. The illness is usually slowly
progressive, often interrupted by strokes and partial
recovery. Seizures occasionally occur. There are often
abrupt clinical changes without typical strokes. The
diagnosis currently rests on the clinical features supported by diffuse white matter changes on CT or MRI.
Currently available data does not permit an unequivocal diagnosis from radiologic features alone.
The most consistent feature of BD is the characteristic pathological white matter change. It seems prudent
to define the disease by the presence of this change
because it distinguishes BD from other cerebrovascular diseases and other processes. The CT and MRI
changes reflecting white matter infarction are less specific, but are probably diagnostic when associated with
the clinical features and course outlined above.
The high incidence of CT abnormalities, similar to
those seen in cases with BD, in asymptomatic elderly
patients may reflect improved ability to detect preclinical cases that were unnoticed in the past. The incidence
of BD may be underestimated since patients likely to
develop the disease are subject to other more common
lethal complications of hypertension, such as myocardial infarction or other forms of cerebrovascular disease. Alternatively, the white matter changes may not
be primarily responsible for clinical abnormalities.
The leukoencephalopathy characteristic of BD is
thought to be ischemic. Hachinski et al, in describing
"multi-infarct dementia"39 were not referring to a specific pathologic entity; over the past six decades clinicopathologic correlations have established several

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Binswanger's Disease

FIGURE 3. Patient 1: Whole

mounts (H-E stain) revealing palor of subcortical white matter
(top) and area of focal infarction
in splenium of corpus callosum
(bottom).

types of dementia related to vascular disease. 4 0 ^ The

"hat lacunaire" of Marie,40 dementia resulting from
multiple cortical ischemic lesions, 4142 and a mental
deterioration associated with "border-zone" infarctions4143 have been described. Some demented patients
do not have a single form of cerebrovascular disease,
but are affected by a mixture of lacunar, embolic, and
watershed infarctions. To use Fisher's words: "cerebrovascular dementia is a matter of strokes large and
small."43 BD is therefore a form of vascular dementia
with a clinical picture and pathology distinguishable
from other types, therefore meriting separate consideration. We disagree with those classifying BD as simply
a multiinfarct dementia37 because of the characteristic
white matter changes and the irregularity and inconsistency of focal stroke syndromes. BD resembles "itat
lacunaire," differing by earlier and more pronounced
mental changes. Multiple lacunes are present in both
entities, but they do not cause the typical BD white
matter changes, and clinical accompaniments of lacunes seem less frequent in BD.

The clinical differentiation between Alzheimer's

disease and BD is often difficult. Impaired memory
and cognitive functions occur in both, but hypertension, strokes, and asymmetric motor and sensory deficits, especially early in the illness, suggest BD. Predominant memory difficulty without accompanying
confusion, apathy, or change in character was uncommon in our review of reported cases. The presence of
white matter hypodensity with cortical and lacunar
infarcts on CT scan also help distinguish Alzheimer's
disease from BD. The impaired mental function associated with normal pressure hydrocephalus (NPH),
when unaccompanied by incontinence and gait disorder, simulates BD. Mild white matter low density,
sometimes seen surrounding the enlarged frontal horns
in NPH,46 simulates the white matter hypodensity of
BD. However, ventricular enlargement is generally
less prominent and white matter hypodensity more extensive in BD. The pathology of the two diseases is
different in spite of several cases of "idiopathic NPH"
with multiple basal ganglionic and periventricular

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Vol 18, No 1, January-February 1987

FIGURE 4. Patient 2. Scan demonstrating

focal areas of decreased attenuation consistent with lacunar infarcts in the basal
ganglionic regions bilaterally.

FIGURE 5. Patient 2 :T2-weighted images show prominent ventricles and prolonged signal from the areas surrounding the lateral ventricles. In addition, several discrete areas of prolonged signal consistent with lacunes
can be identified deep in the white matter.

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Binswanger's Disease

white matter lacunar infarcts47 probably consistent

with BD.
Hypertension, the rule in patients with BD, is absent
in exceptional cases with typical pathological changes;
blood pressure measurements over the years preceding
and during clinical deterioration were documented to
be normal in these cases. In our review there was at
least one such patient,28 and we are familiar with another such case autopsied at our hospital; however, that
patient had no certain symptoms of BD.
Whether BD is a syndrome caused by different pathophysiologic mechanisms or, more likely, a distinct
disease remains uncertain. It does seem that clinical
and radiographic features in pathologically proven
cases of BD, summarized above, are characteristic
enough to allow diagnosis and distinction from other
dementias in most cases. Although the patients we
selected for analysis are relatively homogeneous
pathologically, similar pathologic findings have been
reported in other conditions. 3748 Damage to white matter or its response to a variety of ischemic conditions
may be similar. Patients with typical radiologic abnormalities but no dementia may develop signs of BD
later. A clearer idea of the precise cause of the characteristic white matter lesions requires more detailed
clinicopathologic correlation, with serial sectioning of
small vessels supplying the gliotic areas, experimental
investigation of chronically hypertensive animals, and
perhaps positron emission tomography of patients with
presumed BD.
Acknowledgments
The authors thank Drs. E.P. Richardson and Walter
Koroshetz, C.S. Kubik Laboratory for Neuropathology of the Department of Pathology, Massachusetts
General Hospital, for the pathological description of
Case 1, and Dr. C M . Fisher, Department of Neurology, Massachusetts General Hospital, for helpful discussion.
References
1. Binswanger O: Die Abgrcnzung dcr allgcmeincn progressive!!
Paralyse. Berliner Klin wochenschr 1894;31:1103-1105,
1137-1139, 1180-1186
2. Alzheimer A: Die Seelenstorungen auf arteriosclerotischer
Grundlage. Allgemeine Z Psychiatrie psychischger Med 1902;
59:695-711
3. Famell FJ, Globus JH: Chronic progressive vascular subcortical encephalopathy. Arch Neurol Psych 1932;27:593-604
4. Olszewski J: Subcortical arteriosclerotic encephalopathy.
World Neurol 1965;3:359-374
5. Mikol J: Maladie de Binswanger et formes apparcntees. Rev
Neurol (Paris) 1968;118:111-132
6. Aronson SM, Perl DP (eds): Clinical neuropathological conference. Dis Nerv Syst 1974;35:286-291
7. DeReuck J: The human peri ventricular arterial blood supply
and the anatomy of cerebral infarctions. Eur Neurol 1971 ;5:
321-334
8. Feigin I, Popoff N: Neuropathological changes late in cerebral
edema: The relationship of trauma, hypertensive disease and
Binswanger's encephalopathy. J Neuropathol Exp Neurol
1963,22:500-511
9. Caplan LR, Schoene WC: Clinical features of subcortical arteriosclerotic encephalopathy (Binswanger disease). Neurology
1978;28:1206-1215

11
10. Rosenberg GA, Kornfeld M, Stovring J, Bicknell JM: Subcortical arteriosclerotic encephalopathy (Binswanger): Computerized tomography. Neurology 1979;29:1102-1106
11. Zeumer H, Hacke W, Kolmann HL, Ringelstein EB: Subcortical arteriosclerotic encephalopathy (Binswanger's disease).
Exp Brain Res 1982;5(suppl):272-276
12. Goto K, Ishii N, Fukasawa H: Diffuse white matter disease in
the geriatric population. Radiology 1981;141:687-695
13. Naheedy MH, Gupta SR, Young JC, Ghobrial M, Rubino FA,
Ross ER, Hindo W: Periventricular white matter changes and
subcortical dementia. Clinical, neuropsychological, radiological and pathological correlation (abstract). AJNR 1985;6:468
14. Young IR, Randell CP, Kaplan PW, James A, Bydder GM,
Steiner RE: NMR imaging in white matter disease of the brain
using spin-echo sequences. J Comput Assist Tomogr 1983;
7:290-294
15. Brant-Zawadzki M, Fein G, Van Dyke C, Kieman R, Davenport L, deGrootJ: MR imaging of the aging brain: Patchy white
matter lesions and dementia. AJNR 1985;6:675-682
16. Erkinjuntii T, Sipponen JT, Iivanainen M, Ketonen L, Sulkava
R, Sebbonen RE: Cerebral NMR and CT imaging in dementia.
J Comput Assist Tomogr 1984;8: 614-618
17. Tomonaga M, Yamanoushi H, Tohgi H, Kameyama M:
Clinicopathologic study of progressive subcortical vascular encephalopathy (Binswanger type) in the elderly. J Am Geriatr
Soc 1982;30: 524-529
18. Caplan LR: Binswanger's disease, in Vinken PJ, Bruyn GW,
Klawans HL (eds): Handbook of Clinical Neurology, vol 46,
NeurobehavioralDisorders. New York, Elsevier Science Publishers, 1985, pp 317-321
19. Valentine AR, Moseley IF, Kendall BE: White matter abnormality in cerebral atrophy: Clinicoradiological correlations. J
Neurol Neurosurg Psychiatry 198O;43:139-142
20. Kinkel WR, Jacobs L, Polachini I, Bates V, Heffner RR:
Subcortical arteriosclerotic encephalopathy (Binswanger's disease). Arch Neurol 1985;42:951-959
21. Pullicino P, Eskin T, Ketonen L: Prevalence of Binswanger's
disease. Lancet 1983;1:939
22. Ladame C: Encephalite sous-corticale chronique. Encephale
1912;7:13-39
23. Davison C: Progressive subcortical encephalopathy. J Neuropathol Exp Neurol 1942;l:42-48
24. Neumann MA: Chronic progressive subcortical encephalopathy. Report of a case. / Gerontol 1947;2:57-64
25. Garcin R, Lapresle J, Lyon G: Encephalopathie sous-corticale
chronique de Binswanger. Rev Neurol (Paris) 1960;102:
423-440
26. Jelgersma HC: A case of encephalopathia subcorticalis chronica (Binswanger's disease). Psychiatr Neurol 1964;147:81-89
27. Yvonneau M, Vital CL, Lafforgue J, Kinsala MS: L'encephalopathie sous-corticale chronique de Binswanger. Bordeaux
Med 1969; 2:1135-1141
28. Biemond A: On Binswanger's subcortical arteriosclerotic encephalopathy and the possibility of its clinical recognition.
Psychiatr Neurol Neurochir 1970;73:413-417
29. Ishino H, Higashi H, HayaharaT, JJceda H, Otsuki S: A case of
subcortical arteriosclerotic encephalopathy (Binswanger's disease). Folia Psychiatr Neurol Jpn 1972;26:39-44
30. Burger PC, Burch JG, Kunze U: Subcortical arteriosclerotic
encephalopathy (Binswanger's disease). Stroke 1976;7:
626-631
31. Ali Cherif A, Labrecque R, Pellissicr JF, Ponset M, Boudouresques J: Encephalopathie sous-corticale de Binswanger.
Rev Neurol (Paris) 1979; 135:665-678
32. White JC: Periodic EEG activity in subcortical arteriosclerotic
encephalopathy (Binswanger's type). Arch Neurol 1979;36:
485-489
33. Zeumer H, Schonsky B, Sturm KW: Predominent white matter
involvement in subcortical arteriosclerotic encephalopathy
(Binswanger disease). J Comput Assist Tomogr 1980;4:14-19
34. Janota I: Dementia, deep white matter damage and hypertension: "Binswanger disease." Psychol Med 1981 ;11:39-48
35. Dupuis M, Brucher JM, Gonsette RE: Observation anatomoclinique d'une encephalopathie sous-corticale arteriosclereuse

Downloaded from http://stroke.ahajournals.org/ by guest on September 23, 2014

Stroke

12

36.
37.
38.

39.
40.
41.
42.
43.

avec hypodensite de la substance blanche au scanner cerebral.

Ada Neurol Belg 1984;84:131-140
Dubas F, Gray F, Roullet E, Escourolle R: Leucoencephalopathies arteriopathiques. Rev Neurol (Paris) 1985;141:93108
DeReuck J, Crevits L, DeCoster W et al: Pathogenesis of
Binswanger chronic progressive subcortical encephalopathy.
Neurology 1980;30:920-928
Okeda R: Morphometrische Vergleichsuntersuchungen an
Hirnarterien bei Binswangerscher Encephalopathie und Hochdruckencephalopathie. Ada Neuropathol (Berl) 1973;26:
23-43
Hachinski VC, Lassen NA, Marshall J: Multi-infarct dementia. A cause of mental deterioration in the elderly. Lancet
1974;2:207-210
Marie P: Des foyers lacunaires de desintegration et des differents autres etats cavitaires du cerveau. Rev Med 1901;31:
281-298
Bousser MG: Les conceptions actuelles des demences arteriopatiqes. Encephale 1977; 111:357-372
Jellinger K: Neuropathological aspects of dementias resulting
from abnormal blood and cerebrospinal fluid dynamics. Ada
Neurol Belg 1976;76:83-102
Romanul FCA, Abramovicz A: Changes in brain and pial ves-

44.
45.

46.
47.
48.

Vol 18, No 1, January-February 1987

sels in arterial border zones. A study of 13 cases. Arch Neurol

1964; 11:40-65
Kaplan JG, Katzman R, Horoupian DS, Fuld PA, Mayeux R,
Hays A: Progressive dementia, visual deficits, amyotrophy and
microinfarcts. Neurology 1985;35:789-796
Fisher CM: Dementia in cerebral vascular disease, in Toole JF,
Siekert R, Whisnant J (eds): Cerebral Vascular Diseases, 6th
Princeton Conference. New York, Grune & Stratton, 1968, pp
232-236
Jacobs L, Kinkel W: Computarized axial transverse tomography in normal pressure hydrocephalus. Neurology 1976;26:
501-507
Earnest MP, Fahn S, Karp JH: Normal pressure hydrocephalus
and hypertensive cerebrovascular disease. Arch Neurol
1974;31:262-266
Huang K, Wu L, Luo Y: Binswanger's disease: Progressive
subcortical encephalopathy or multi-infarct dementia? Can J
Neurol Sci 1985;12:88-94

KEY WORDS Binswanger's disease dementia vascular

subcortical arteriodementia lacunes white matter
sclerotic encephalopathy

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