Journal of Neurology, Neurosurgery, and Psychiatry 1990;53:961-965

Clinical diagnosis of Binswanger's disease

David A Bennett, Robert S Wilson, DavidW Gilley, Jacob H Fox

AbstractTo aid in the prospective study of Bins-wanger's disease, a poorly understoodform of vascular dementia, a standar-dised criteria for its antemortem diag-nosis was proposed. These criteriainclude dementia, bilateral radiologicalabnormalities on computed tomography(CT) or magnetic resonance imaging(MRI), and at least two of the followingthree clinical findings: A) a vascular riskfactor or evidence of systemic vasculardisease; B) evidence of focal cerebro-vascular disease; and C) evidence of"subcortical" cerebral dysfunction.These criteria were validated in twoways. First, by retrospectively applyingthem to a series of 30 demented patientswith various pathological diagnoses.Second, by prospectively applying themto a series of 184 patients with clinicallytypical Alzheimer's disease. The sen-sitivity and specificity of the criteriaappear adequate for use in clinicalresearch.

Rush Presbyterian-StLukes Medical Center,Chicago, Illinois,United StatesRush Alzheimer'sDisease CenterD A BennettR S WilsonD W GilleyJ H FoxDepartment ofNeurologyD A BennettJ H FoxDepartment ofPsychology and SocialSciencesR S WilsonCorrespondence to:Dr Bennett, RushAlzheimer's Disease Center,710 S Paulina Street,8 North JRB, Chicago,Illinois 60612-3864, UnitedStates.Received I I October 1989and in revised form 5 March1990.Accepted 14 March 1990

Vascular disease is consistently reported as thesecond leading cause of dementia.'2 Nonethe-less, neither its prevalence nor defining clin-ical, radiological or histopathological featuresare settled.34 Much of the controversy stemsfrom the heterogeneity of the vascular demen-tias.34 Therefore, recent reviews of vasculardementia stress the need to dinstinguish be-tween the various vascular dementias and todevelop specific clinical, radiological andpathological criteria for each type."'

Binswanger's disease (BD), a forrn of vas-cular dementia, was for years considered arelatively rare disorder diagnosed only Lttnecropsy.' The sensitivity of magneticresonance imaging (MRI) to subcortical whitematter pathology, however, has rekindledinterest in the disorder and raised the pos-sibility of its antemortem diagnosis. Unfor-tunately, the typical radiological lesions ofBDare routinely seen in both elderly dementedand non-demented patients.67 Furthermore,not all of the lesions visualised by MRI have avascular basis."2 In fact, about 30% ofpatients with clinically typical Alzheimer'sdisease (AD) have similar lesions.'3For physicians evaluating demented

patients, the controversy surrounding theradiological abnormalities poses the clinicaldilemma of how to diagnose dementedpatients who have white matter lesions(WMLs) on computed tomography (CT) or

MRI. Clearly, many of these patients do nothave BD. Resolution of this dilemma requiresstandardised criteria for the clinical diagnosisof Binswanger's disease. The purpose of thispaper is to propose such criteria.Although there is undoubtedly a prodromal

phase of BD when dementia is not evident,Binswanger considered this illness a dement-ing disorder and a recent review by Babikianand Ropper concluded that the illness is"characterized clinically by disorders ofmemory, mood, and cognition".6 Therefore,we propose that the diagnosis be reserved forpatients who are demented. The identical res-triction is placed on the diagnosis of AD. Forresearch purposes, the presence of dementiashould be confirmed by neuropsychologicaltesting.

Radiological criteria for BD are complicatedby the fact that several types of lesions areidentifiable on MRI. Periventricular caps andrims are nearly ubiquitous findings on MRI.Pathologically, they represent areas ofsubependymal gliosis, and probably do nothave a vascular aetiology. Subcortical WMLsmay be either small infarcts, focal areas ofdemyelination, or dilated perivascularspaces."'" It is difficult to distinguish betweenthese lesions. However, a recent MRI-path-ological study found that the majority of MRIlesions corresponding to dilated perivascularspaces were round or linear, isointense relativeto cerebrospinal fluid, and less than 2 x 2mm." Therefore, the radiological criteria forthe diagnosis of BD requires bilateral leuk-oaraiosis on CT, or bilateral, multiple ordiffuse, subcortical high signal T2 weighted

Table I Criteria for the clinical diagnosis ofpossibleBinswanger's Disease

1 Dementia must be established by clinical examination andconfirmed by neuropsychological tests.

2 One finding from two of the following three groups must bepresent:A) the presence of a vascular risk factor or evidence of

systemic vascular disease (for example, hypertension,diabetes, a history of myocardial infarction, cardiacarrhythmia, or congestive heart failure);

B) evidence of focal cerebrovascular disease (for example, ahistory of stroke, or demonstration of a focal pyramidal orsensory sign);

C) evidence of "subcortical" cerebral dysfunction (forexample, a Parkinsonian, magnetic, or "senile" gait,Parkinsonian or gegenhalten rigidity, or a history ofincontinence secondary to a spastic bladder).

3 The radiological criteria requires bilateral leukoaraiosis oncomputed tomography (CT), or bilateral and, multiple ordiffuse, subcortical high signal T2 weighted lesions greaterthan 2 x 2 mm on magnetic resonance (MR) scan.

The proposed criteria lose their validity in the presence of:1 multiple or bilateral cortical lesions on CT or MR; or2 severe dementia (for example, MMS < 10)

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lesions greater than 2 x 2 mm on MRI. Toseparate BD from other types of vasculardementia, the radiological diagnosis ofBD alsorequires the absence of either large or multiplecortical lesions which may contribute to thepatient's dementia.The proposed clinical and historical features

of BD which should accompany dementia andthe appropriate MRI or CT examination arebased on a review of pathologically verifiedcases ofBD in the English and French languageliterature. The criteria are outlined in table 1.Three classes of findings define BD. Theseinclude: A) a vascular risk factor or evidence ofsystemic vascular disease; B) evidence of focalcerebrovascular disease; and C) evidence of"subcortical" cerebral dysfunction. Weexcluded reports of mixed AD/BD, mixedvascular dementia, and non-vasculardemyelinating syndromes, as well as cases withvery atypical histories, unilateral involvement,lack of clinical data, or lack of clinical evidenceof dementia. Of the 62 remaining path-ologically verified cases of BD,8 1-38 41 (66%)met all three clinical criteria presented in table1, and 59 (95%) had at least two of three clinicalfindings. We therefore propose that two of thethree clinical findings outlined above are neces-sary for the diagnosis of BD.

In this paper we report the results of twoevaluations of the validity of these diagnosticcriteria. In the first study, the sensitivity of thecriteria was assessed by retrospectively apply-ing them to a series of 30 pathologically diag-nosed cases ofdementia ofvarying aetiology. Inthe second study, the specificity of the criteriawas evaluated by applying them prospectivelyto a series of 184 patients with clinically typicalAD.

MethodPart I Pathological seriesOne neurologist (DAB), blind to the path-ological diagnosis, reviewed the medicalrecords of 45 patients who had a clinicaldiagnosis of dementia and a brain necropsyperformed at Rush Presbyterian-St Luke'sMedical Center (RPSLMC) between 1975-88.Patients without clinical evidence of dementia,a complete neurological examination, and a CTor MRI scan were excluded, leaving 30 cases.The clinical, radiological and pathological datawere recorded on a standardised form. Onlyvariables explicitly mentioned in the chart werescored as present. The diagnostic criteriaoutlined in table 1 were then applied to theclinical and radiological data on the 30 cases.The pathological criteria for the diagnosis of

BD were those outlined by Olszewski.2' Therehad to be diffuse areas of demyelination sparingthe subcortical U-fibres, arteriosclerosis of thepenetrating blood vessels, and small infarcts inthe subcortical white or grey matter. Althoughcontroversial, additional subcortical gliosis wassupportive, but not necessary for the diagnosis.If other abnormalities were present, cases wereclassified as mixed (for example, mixed BD/AD).A diagnosis ofAD was made when numerous

neuritic plaques (NP) were present throughoutthe hippocampus and neocortex. After 1985,NP were quantified and the diagnosis ofAD followed the recommendations ofKhachaturian et al.' A diagnosis of Multi-infarct dementia (MID) required large multi-ple cortical strokes. No attempt was made toquantify the amount of infarcted tissue. Otherdiagnoses were made by contemporarystandards.

Part II Clinical seriesThe sample consisted of 795 consecutivepatients referred to the Rush Alzheimer's Dis-ease Center (RADC) between 1985-88 forevaluation of possible dementia. Evaluationsincluded a standard medical history,neurological examination, neuropsychologicaltesting, and standard laboratory procedures.Selection from this series required a diagnosisof typical AD,39 a technically satisfactory MRIscan, and a modified ischaemic score less thanthree;40 184 patients met these criteria. TheMR scans were performed on a Technicare 0-5Tesla superconductive scanner at theRPSLMC. Examinations included TI weigh-ted saggital and axial acquisitions and T2weighted multislice multiecho saggital andaxial acquisitions. All MRIs were rated for thenumber and location of abnormalities." Theproposed diagnostic criteria were then appliedto these 184 patients. To assess the incrementalvalidity of the MRI, the cases were classifiedboth with and without the MRI criterion.

ResultsPart I Pathological series Table 2 depicts thepathological diagnoses of the retrospectivelyreviewed cases of dementia. Four patients had apathological diagnosis of BD and all four metBD criteria. One of two patients with mixedBD and AD met criteria. Two patients hadMID, one of whom also had concomitant AD.Both met the clinical criteria for BD, but notthe radiological criterion because of multiplecortical lesions on their brain scans. Twelvepatients had AD, only one of whom fulfilledthe criteria. Of five cases of Creutzfeld-Jakobdisease, one met the criteria. None of theremaining cases, including patients with Pick'sdisease, thalamic gliosis, Parkinson's diseasewith dementia, and two with no pathologicaldiagnosis met the criteria. The agreement be-tween the clinical and pathological diagnoseswas significant (Fisher's Exact Test, p =0 0008, two-tailed).

Part II Clinical series Of the 184 patients witha diagnosis of AD, 32 (17A4%) met at least twoof the three clinical criteria. However, onlythree of these patients also met the radiologicalcriteria. Therefore, only 1 6% (3/184) of thesepatients with clinically typical AD met theproposed criteria. In four of these 184 patients,AD was confirmed pathologically.

Gait disorders and incontinence are commonfindings in severely demented patients. Wetherefore compared dementia severity in thosewho did and did not meet clinical criteria. The

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Table 2 Criteria for the clinical diagnosis of Binswanger's disease in a retrospective pathologic series of 30 cases ofdementia

Clinical Criteria

Case Path Diagnosis Risk' Focal2 Subcor' Rad' Met Crit

1 BD + + + + Yes2 BD + - + + Yes3 BD + + + + Yes4 BD + + + + Yes5 BD/AD + - + + Yes6 BD/AD - - - + No7 MID + + + - No8 MID/AD + + + - No9 AD - - - - No10 AD - - - - No11 AD - - - - No12 AD + - - - No13 AD - - + - No14 AD + + + - No15 AD - - + + No16 AD - - - + No17 AD - - + - No18 AD + + + - No19 AD - - + - No20 AD + - + + Yes21 CJD - - - - No22 CJD + + + - No23 CJD - - + - No24 CJD - + + + Yes25 CJD - + + - No26 Pick's + - - + No27 Th + + + - No28 PD - - + - No29 No Diagnosis + - - - No30 NoDiagnosis + - - - No

'Risk factor or evidence of atherosclerosis.'History of stroke or evidence of focal cerebral disease.3Evidence of "subcortical" cerebral dysfunction.'CT or MRI.BD = Binswanger's disease; AD = Alzheimer's disease; BD/AD = BD with AD; MID = Multiple infarcts; MID/AD = MIDwith AD; CJD = Creutzfeldt-Jakob disease; Pick's = Pick's disease; Th = Thalamic gliosis; PD = Parkinson's disease.

former had an average Mini-Mental State(MMS) examination4' of 11-5 (5 9); the latterhad a mean(SD) MMS of 14-2 (8 3). Althoughthis trend is not statistically significant (t(1,182) = 1-57, p = 0 057), it suggests cautionwhen applying these criteria to severelydemented patients.

DiscussionGuided by reports of pathologically verifiedcases, we developed an explicit diagnosticscheme for the antemortem diagnosis of BDbased on historical, clinical, and radiologicalinformation. Diagnoses based on these criteriawere in close agreement with pathologicaldiagnoses in a retrospective series of 30patients. Application ofthe criteria to a series of184 patients with clinically typical AD resultedin few diagnostic misclassifications (1 6%). Wepropose that these criteria may be useful inclinical dementia research. Indeed, differencesin memory and affective disturbances can bedemonstrated between patients with AD andthose meeting our criteria.4243 We recognise,however, that prospective clinicopathologicalstudies are needed for both verification andrefinement of this scheme.

Until 1978, the diagnosis of BD was madeonly at necropsy. Caplan and Schoene were thefirst to attempt an antemortum diagnosis ofBD.8 They reviewed five cases ofpathologicallyconfirmed BD (one of whom had concomitantAD) and made clinical diagnoses in six otherpatients. They emphasised many of the same

historical and clinical findings that we advance.Babikian and Ropper also stressed similar datain a 1987 review of BD.6 However, both papers

stopped short of advocating a specific diagnos-tic scheme.For the specific clinical criteria, vascular risk

factors and focal cerebral dysfunction are

widely recognised features of the syndrome.68However, other features of the syndromeremain controversial.Although both Binswanger and Alzheimer

regardedBD as a dementing illness, Olszewski,in his trenchant 1962 review, advocated thatthe diagnosis be made strictly on pathologicalgrounds.25 Recent reviews, however, havereverted to the earlier position, thereby re-

introducing the clinical requisite that dementiabe documented to make the diagnosis.467 Werecognise that this represents a somewhatarbitrary limitation to the syndrome. However,we were guided by the precedent set withAlzheimer's disease and by the belief that a

more uniform definition of BD will ultimatelylead to a better understanding of the disease.Our criteria include neurological signs of

"subcortical" cerebral dysfunction such as a

gait disorder, Parkinsonism or incontinence.Although these findings are common in BD,they are not widely appreciated. However, gait

disorders and Parkinsonism resulting fromsubcortical vascular disease are well describedin the neurological literature. 45 In 1929 Crit-chley described several types of arterioscleroticParkinsonism occurring either alone, or incombination with pseudobulbar, pyramidal or

cerebellar signs.' All ofthem could merge withtype 3, which was Parkinsonism with dementiaand incontinence. Although the pathology ofthese cases was heterogeneous, some includedchanges consistent with BD. Subsequentstudies support Critchley's contention that

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vascular disease can result in pseudobulbarsigns, Parkinsonian features and an akinetic-rigid syndrome with dementia.' Although theterm "arteriosclerotic Parkinsonism" iscurrently out of vogue, in a recent survey of 33leading authorities in movement disordersfrom ten countries, 16 agreed that the designa-tion is acceptable, while only six disagreed and11 were uncertain.47In a recent clinical series, Parkinsonism was

a common finding in vascular dementia ingeneral,48 and BD in particular.48 Thesepatients had multiple strokes prohibiting pre-cise clinico-anatomical correlations. However,focal subcortical vascular lesions implicate thethalamus and putamen in disorders of stance,gait and incontinence. Thus there is ampleevidence to support the criteria of gait disor-ders, Parkinsonism and incontinence.

It is the role of neuroradiology in the diag-nosis of BD which is perhaps the most con-troversial. Rosenberg et al first reportedbilateral white matter hypodensities on CT in aman with dementia, hypertension and spas-ticity, with pathologically proven BD.49 Loizouet al followed this report by using similar CTfindings to confirm the clinical diagnosis ofBDin 15 patients.50 Their patients were clinicallysimilar to Caplan's and one case of BD wasverified at necropsy. In 1985, Kinkel et alcompared the sensitivity of MR in 23 patients(eight of whom were asymptomatic) with CTdocumented "leukoencephalopathy of un-known origin".'5 MRI was unquestionablymore sensitive in delineating WMLs, and theyconcluded that "the lack of neurological find-ings in this group is not necessarily inconsistentwith the diagnosis of subcortical arterio-sclerotic encephalopathy [BD].'5A number of other investigators now

advocate that WMLs on MRI are sufficientevidence for a diagnosis of BD .7 Yet, severalstudies have shown that not all white matterabnormalities onMR or CT are vascular."'2 Infact, such lesions are seen in many individualswithout neurological deficits and in about 30%of patients with typical AD.'3 They are highlyage-related among healthy elderly individualsand also correlate with the presence ofcerebrovascular risk factors, though not neces-sarily symptomatic cerebrovascular disease.9 0Despite this apparent lack of specificity, it doesappear that MRI scanning is exceptionallysensitive to vascular lesions. Furthermore,well-designed clinical studies have consistentlydemonstrated increased CT and MRI abnor-malities in vascular dementia, compared withAD.5 Of the 62 pathologically verified reportsof BD, 18 had a brain scan. Of those, 83-3%(15/18) showed leukoaraiosis on CT and 100%(3/18) showed multiple bilateral white matterabnormalities on MRI. Finally, within our ownclinical series, the addition of the MRIcriterion to the diagnostic system significantlyreduced apparent misdiagnoses of patientswith AD from 17-4% to. 1-6%. We submittherefore that these radiological findings beconsidered a necessary, but not sufficient, com-ponent of the clinical diagnosis of BD.Our criteria offer several advantages over

Hachinski's ischaemic score (IS)."52 First, theIS was not designed for BD though it has beenused.53 In fact, less than half of the 62 patho-logically verified cases ofBD in the English andFrench literature met IS criteria for multi-infarct dementia. Second, we emphasise clini-cal evidence of "subcortical" cerebral dys-function. Third, we incorporate radiologicalconfirmation of bilateral white matter path-ology. Fourth, we eliminate items which arecommon in other dementias, for example, noc-turnal confusion, personality changes anddepression.54 And fifth, items which aredifficult to assess and have poor interraterreliability are excluded.55Although the diagnostic system presented

here holds promise, it is not without its limita-tions. Most importantly, it cannot distinguishBD from mixed AD/BD. The same criticism islevied against the IS. Unfortunately, untilthere is a diagnostic marker for AD, thislimitation seems inevitable. Mixed AD/vas-cular dementia probably represents the chanceoccurrence of two common diseases in theelderly. However, the combination ofAD andBD may not always be fortuitous. Brun andEngland56 suggest that loss of myelin with"incomplete" white matter infarction and reac-tive gliosis are common histopathological find-ings in AD. These lesions are difficult todistinguish from BD on MR scan and mayresult from hypoperfusion.56 In addition, thereis some evidence implicating AD in thedevelopment of a neurogenic vasculopathy.57Finally, the histopathological findings of BDmay also be seen in patients with cerebralamyloid angiopathy with and without con-comitant AD.5859A second problem is how to classify cases of

mixed vascular dementia, that is mixed BD andcortical strokes. In an effort to define a morehomogeneous sample of BD patients forresearch purposes, we chose to exclude patientswith more than one cortical stroke evident onbrain scan. Although Tomlinson et al recom-mend that a diagnosis ofMID requires at least50 ml, and preferably 100 ml, of infarcted braintissue,1 this suggestion does not take intoaccount lesion location, which studies demon-strate is important in the pathophysiology ofvascular dementia.' In fact, in a recent clin-icopathological study of MID, only five of 23patients with a pathological diagnosis of vas-cular dementia had more than 50 ml of infarc-ted tissue, and seven had less than 10 ml.6'The status of BD resembles that of AD

before the seminal work of Tomlinson and hiscolleagues 20 years ago. At that time, AD wasan underrecognised cause of mental deteriora-tion with poorly defined clinical features. Sincethen the introduction of standardised criteriafor the clinical diagnosis of AD has greatlyincreased diagnostic accuracy.396263 Standardised criteria for BD are likely to have a similarimpact on the study of this illness. Since CTand MRI abnormalities are common in theelderly, clinical criteria must accompnayradiological findings when making theantemortum diagnosis of BD. Such criteriashould be specific enough to exclude patients

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with AD from the sample. Our criteria meetthese objectives and should therefore proveuseful in the prospective study of this puzzlingdisease.We are especially indebted to Dr Christopher Goetz, fortranslating the French cases in addition to his perceptivecriticism. We also thank Dr Raymond Clasen, for performingthe pathology, Dr Michael Huckman, for reading our MRI scansand Cathy Mills for preparing the tables and references. Thisstudy was supported in part by a grant from the ChicagoCommunity Trust, Searle Fund.

1 Tomlinson BE, Blessed G, Roth M. Observations on thebrains of demented old people. J Neurol Sci 1970;11:205-42.

2 Schoenberg BS, Kokmen E, Okazaki H. Alzheimer's diseaseand other dementing illnesses in a defined United Statespopulation: incidence rates and clinical features. AnnNeurol 1987;22:724-9.

3 Brust JCM. Vascular dementia is overdiagnosed. ArchNeurol 1988;45:799-801.

4 Scheinberg P. Dementia due to vascular disease-a multifac-torial disorder. Stroke 1988;19:1291-9.

5 Meyer JS, McClintic KL, Rogers RL, Simms P, Mortel KF.Etiological considerations and risk factors for multi-infarct dementia. J Neurol Neurosurg Psychiatry 1988;51:1489-97.

6 Babikian V, Ropper AH. Binswanger's disease: a review.Stroke 1987;18(1):2-12.

7 Roman GC. Senile dementia of the Binswanger type. Avascular form of dementia in the elderly. JAMA1987;258(13): 1782-8.

8 Caplan LR, Schoene WC. Clinical features of subcorticalarteriosclerotic encephalopathy (Binswanger's disease).Neurology 1978;28:1206-15.

9 Awad IA, Spetzler RF, Hodak JA, Awad CA, Carey R.Incidental subcortical lesions identified on magneticresonance imaging in the elderly. I Correlation with ageand cerebrovascular risk factors. Stroke 1986;17:1084-9.

10 Awad IA, Johnson PC, Spetzler RF, Hodak JA. Incidentalsubcortical lesions identifiedon magnetic resonance imag-ing in the elderly. II Postmortem pathological correla-tions. Stroke 1986;17:1090-7.

11 Braffman BH, Zimmerman RA, Trojanowski JQ, et al.Brain MR: pathological correlation with gross and his-topathology. 1 Lacunar infarction and Virchow-Robinspaces. Am JNeuro Radiol 1988;9:621-8.

12 Braffman BH, Zimmerman RA, Trojanowski JQ, et al.Brain MR: pathological correlation with gross and his-topathology. 2 Hyperintense white-matter foci in theelderly. Am J Neuro Radiol 1988;9:629-36.

13 Wilson RS, Bennett DA, Fox JH, et al. Alzheimer's disease:prevalence and clinical significance of white-matterlesions on magnetic resonance imaging. Ann Neurol1988;24(1):160-1.

14 Ladame C. Encephalite sous-corticale chronique.L'Encephale 1912;7:13-39.

15 Kinkel WR, Jacobs L, Polachini I, Bates V, Heffner RR Jr.Subcortical arteriosclerotic encephalopathy (Binswan-ger's disease). Computed tomographic, nuclear magneticresonance, and clinical correlations. Arch Neurol 1985;42(10):951-9.

16 Aronson SM, Perl DP, eds. Clinical neuropathologicalconference. Dis Nerv Syst 1974;35:286-91.

17 Biemond A. On Binswanger's subcortical arterioscleroticencephalopathy and the possibility of its clinical recogni-tion. Psychiatr Neurol Neurochir 1970;73:413-7.

18 Dubas F, Gray F, Roullet E, Escourolle R. Leucoence-phalopathies arteriopathiques. Rev Neurol (Paris)1985;141 :93-108.

19 Dupuis M, Brucher JM, Gonsette RE. Anatomo-clinicalobservation of atherosclerotic subcortical encephalopathy("Binswanger's disease") with hypodensity of the whitematter on brain scan. Acta Neurol Belg 1984;84(3):131-40.

20 Garcin R, Lapresle J, Lyon G. Encephalopathie sous-corticale chronique de Binswanger. rev Neurol (Paris)1960;102:423-40.

21 Hurwitz BJ, Heyman A, Burger PC, Drayer BP. Subcorticalarteriosclerotic encephalopathy (Binswanger's disease).Report of a case simulating psychiatric disease and normalpressure hydrocephalus. NC Med J 1987;48(4):182-6.

22 Ishino H, Higashi H, Hayahara T, Ikeda H, Otsuki S. A caseof subcortical arteriosclerotic encephalopathy (Binswan-ger's disease). Folia Psychiatr Neurol Jpn 1972;26(1):39-44.

23 Jelgersma HC. A case of encephalopathia subcorticalischronica (Binswanger's disease). Psychiatr Neurol 1964;147:81-9.

24 Rousseau P. Binswanger's disease: a cause of dementia in theelderly. South Med J 1988;81(10): 1329-30.

25 Olszewski J. Subcortical arteriosclerotic encephalopathy.World Neurol 1965j3:359-74.

26 Earnest MP, Fahn S, Karp JH. Normal pressure hydro-cephalus and hypertensive cerebrovascular disease. ArchNeurol 1974;31:262-6.

27 Burger PC, Burch JG, Kunze U. Subcortical arterioscleroticencephalopathy (Binswanger's disease). A vascularetiology of dementia. Stroke 1976;7(6):626-31.

28 Koto A, Rosenberg G, Zingesser LH, Horoupian D, Katz-man R. Syndrome of normal pressure hydrocephalus:possible relation to hypertensive and arteriosclerotic vas-culopathy.J Neurol Neurosurg Psychiatry 1977;40:73-9.

29 Zeumer H, Schonsky B, Sturm KW. Predominant white

matter involvement in subcortical arteriosclerotic ence-phalopathy (Binswanger disease). J Comput Assist Tomogr1980;4:14-9.

30 Goto K, Ishii N, Fukasawa H. Diffuse white matter diseasein the geriatric population. Radiology 1981;141:687-95.

31 Janota I. Dementia, deep white matter damage and hyper-tension: 'Binswanger's disease'. Psychol Med 1981;11(1):39-48.

32 DeWitt LD, Kistler JP, Miller DC, Richardson EP Jr,Buonanno FS. NMR-neuropathologic correlation instroke. Stroke 1987;18(2):342-51.

33 Garcia-Albea E, Cabello A, Franch 0. Subcortical arterio-sclerotic encephalopathy (Binswanger's disease): a reportof five patients. Acta Neurol Scand 1987;75(5):295-303.

34 Mahler ME, Cumming JL, Tomiyasu U. Atypical dementiasyndrome in an elderly man. J Am Geriat Soc 1987;35:1116-26.

35 Gupta SR, Naheedy MH, Young JC, Ghobrial M, RubinoFA, Hindo W. Periventricular white matter changes anddementia. Clinical, neuropsychological, radiological, andpathological correlation. Arch Neurol 1988;45:637-41.

36 Yvonneau M, Vital CL, Lafforgue J, Kinsala MS. L'en-cephalopathie sous-corticale chronique de Binswanger.Bordeaux Med 1969;2:1135-41.

37 Huang K, Wu L, Luo Y. Binswanger's disease: progressivesubcortical encephalopathy or multi-infarct dementia?Can J Neurol Sci 1985;12(2):88-94.

38 Mikol J. Maladie de Binswanger et formes apparentees. RevNeurol (Paris) 1968;118:111-32.

39 McKhann G, Drachman D, Folstein M, Katzman R, PriceD, Stadlan EM. Clinical diagnosis ofAlzheimer's disease:report of the NINCDS-ADRDA Work Group under theauspices of Department of Health and Human ServicesTask Force on Alzheimer's disease. Neurol 1984;34:939-44.

40 Rosen WG, Terry RD, Fuld PA, Katzman R, Peck A.Pathological verification of ischemic score in differentia-tion of dementias. Ann Neurol 1980;7:486-8.

41 Folstein MF, Folstein SE, McHugh PR. "Mini-MentalState": a practical method for grading the cognitive stateof patients for the clinician. J Psychiat Res 1975;12:189-98.

42 Gilley DW, Wilson RS, Bennett DA, Fox JH. Depression inputative Binswanger's disease. Ann Neurol 1989;26:154.

43 Bernard BA, Wilson RS, Gilley DW, Waters WF, Fox JH.Semantic encoding and episodic memory in Alzheimer'sdisease and multi-infarct dementia. J Clin Exp Neuro-psychol 1989;11:52-3.

44 Mancardi GL, Romangnoli P, Tassinari T, Gandolfo C,Primavera A, Loeb C. Lacunae and cribiform cavities ofthe brain. Eur Neurol 1988;28:11-7.

45 Thompson PD, Marsden CD. Gait disorder of subcorticalarteriosclerotic encephalopathy: Binswanger's disease.Mov Disord 1987;2(1):1-8.

46 Critchley M. Arteriosclerotic Parkinsonism. Brain 1929;52:23-83.

47 Duvoisin RC, Golbe LI. Towards a definition ofParkinson'sdisease. Neurology 1989;39:746.

48 Kotsoris H, Barclay LL, Kheyfets S, Hulyalkar A, Dough-erty J. Urinry and gait disturbance as markers for earlymulti-infarct dementia. Stroke 1987;18:138-41.

49 Rosenberg GA, Kornfeld M, Stovring J, Bicknell JM.Subcortical arteriosclerotic encephalopathy (Binswan-ger): computerized tomography. Neurology 1979;29:1102-6.

50 Loizou LA, Kendall BE, Marshall J. Subcortical arterios-clerotic encephalopathy: a clinical and radiological inves-tigation. JNeurol Neurosurg Psychiatry 1981;44:294-304.

51 Erkinjuntti T, Ketonen L, Sulkava R, Vuorialho M, Palo J.Do white matter changes on MRI and CT differentiatevascular dementia from Alzheimer's disease? J NeurolNeurosurg Psychiatry 1987;50:37-42.

52 Hachinski VC, IliffLD, Zilhka E, et al. Cerebral blood flowin dementia. Arch Neurol 1975;32:632-7.

53 Hershey LA, Modic MT, Jaffe DF, Greenough PG. Natualhistory of the vascular dementias: a prospective study ofseven cases. Can JNeurol Sci 1986;13:559-65.

54 Gilley DW, Wilson RS, Bennett DA, Bernard BA, Fox JH.Predictions of behavioural disturbance in Alzheimer'sdisease. JGerontol (in press).

55 Gustafson L, Nilsson L. Differential diagnosis of preseniledementia on clinical grounds. Acta Psychiatr Scand1982;65:194-209.

56 Brun A, Englund E. A white matter disorder in dementia ofthe Alzheimer type: a pathoanatomical study. Ann Neurol1986;19:253-62.

57 Scheibel AB, Duong T, Tomiyasu U. Denervation micro-angiopathy in senile dementia, Alzheimer type. AlzheimerDisease Assoc Dis 1987;1:19-37.

58 Gray F, Dubas F, Roullet E. Escourolle R. Leukoen-cephalopathy in diffuse hemorrhagic cerebral amyloidangiography. Ann Neurol 1985;18:54-9.

59 Bird TD, Sumi SM, Nemens EJ, et al. Phenotypicheterogeneity in familial Alzheimer's disease: a study of24kindreds. Ann Neurol 1989;25:12-25.

60 Loeb C, Gandolfo C, Bino G. Intellectual impairment andcerebral lesions in multiple cerebral infarcts. A clinical-computed tomography study. Stroke 1988;19:560-5.

61 Erkinjuntti T, Haltia M, Palo J, Sulkava R, Paetau A.Accuracy of the clinical diagnosis of vascular dementia: aprospective clinical and post-mortem neuropathologicalstudy. JNeurol Neurosurg Psychiatry 1988;51:1037-44.

62 Khachaturian ZS. Diagnosis of Alzheimer's disease. ArchNeurol 1985;42:1097-105.

63 Fox JH, Penn R, Clasen R, et al. Pathological diagnosis inclinically typical Alzheimer's disease. New Engl J Med1985;313:1419-20.

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