|Year : 2016 | Volume
| Issue : 4 | Page : 478-481
Clinical correlates of leukoaraiosis: A study of 175 patients
Rustom S Wadia1, Sandesh K Ghiya2, Joshita Singh3, Santosh M Sontakke1, Vishwas Bharadwaj4, Rahul V Sonawane4, Yogesh P Bade4, K Shrikanth4, Nikhil Goli4, Rohit Singh Chauhan4, Nilesh A Nadkarni5
1 Consultant Neurologist, Pune, Maharashtra, India
2 Consultant Radiologist, Pune, Maharashtra, India
3 Resident at Ruby Hall Clinic, Pune, Maharashtra, India
4 Assistant Professor, Bharati Medical College, Pune, Maharashtra, India
5 Consultant Neurologist, Columbia Asia Hospital, Pune, Maharashtra, India
|Date of Submission||13-Apr-2016|
|Date of Decision||10-May-2016|
|Date of Acceptance||16-Jun-2016|
|Date of Web Publication||21-Nov-2016|
Rustom S Wadia
Director Neurological Services, Ruby Hall Clinic, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: In India, the correlates of leukoaraiosis (LA) have not been widely reported. This study was designed to investigate the factors which correlate with LA. Materials and Methods: We included patients with LA who consented for the study and graded their severity on the basis of Fazekas scale. We excluded patients with LA who did not consent/cooperate for the study as also patients with other white matter changes which mimic LA. Results: LA is a common and under-rated cause of disability. Presentations include cognitive decline, gait disturbance, dysarthria, bladder/bowel sphincter disturbances, and increased risk of stroke. The comorbidities include hyperhomocysteinemia, hypertension, dyslipidemia, tobacco use, ischemic heart disease, previous stroke, atrial fibrillation, chronic renal failure, and bariatric surgery.
Keywords: Cognitive decline, gait and sphincter disturbances, leukoaraiosis
|How to cite this article:|
Wadia RS, Ghiya SK, Singh J, Sontakke SM, Bharadwaj V, Sonawane RV, Bade YP, Shrikanth K, Goli N, Chauhan RS, Nadkarni NA. Clinical correlates of leukoaraiosis: A study of 175 patients. Ann Indian Acad Neurol 2016;19:478-81
|How to cite this URL:|
Wadia RS, Ghiya SK, Singh J, Sontakke SM, Bharadwaj V, Sonawane RV, Bade YP, Shrikanth K, Goli N, Chauhan RS, Nadkarni NA. Clinical correlates of leukoaraiosis: A study of 175 patients. Ann Indian Acad Neurol [serial online] 2016 [cited 2021 Sep 18];19:478-81. Available from: https://www.annalsofian.org/text.asp?2016/19/4/478/194425
| Introduction|| |
The story of ischemic small vessel disease of brain dates 50 years back when Fisher described lacunar infarcts in 1965.  This was in the days before computed tomography (CT) scan when the diagnosis was done by clinical examination during life and careful postmortem examination after death. As neuroimaging became widely available, Hachinski et al.  coined the term leukoaraiosis (LA) to denote "white matter like air" (leuko = white, araiosis = rarefaction) in 1987. LA appears as low-density lesions around ventricles on CT scan, and magnetic resonance imaging (MRI) demonstrates them more clearly as hyperintensities on fluid-attenuated inversion recovery imaging. During 1987-1994, several "normal people" were observed to have LA on CT scan which made physicians wonder if it was an incidental finding in old age. The Rotterdam Scan Study was a community-based study of apparently normal 1077 persons in the age group 65-84 years, of which 10% had periventricular and deep white matter hyperintensities increasing in incidence with age.  Those with LA were found to have a significantly increased risk of subsequent new stroke, dementia, and mortality.
There are many studies about LA from the Western parts of the world. , In India, the correlates of LA have not been widely reported. This study was designed to investigate the factors which correlate with LA.
| Materials and Methods|| |
The study was a prospective observational study carried out at a single tertiary care referral center between November 2011 and October 2014.
Patients with LA were analyzed. The severity of LA on MRI was graded on Fazekas scale. 
Clinical examination of patients included the following:
- Mini-Mental Status Examination (MMSE)
- Frontal lobe functions: trail making test A, trail making test B, and digit symbol test
- Three-minute walk test.
The executive functions and walking speed were compared with age- and sex-matched controls.
- Patients with LA who were asymptomatic
- Conditions such as Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL), cerebral amyloid angiopathy, exposure to cranial radiation, multiple sclerosis, HIV, and Hashimoto's encephalitis which may mimic LA on neuroimaging
- Patients with LA who in addition had infarcts more than 2 cm suggesting large vessel disease
- Patients who did not cooperate for examination.
All patients underwent stroke workup including fasting and postprandial blood sugar, serum lipid profile, homocysteine level, electrocardiogram (ECG), echocardiography, and MRI brain.
| Results|| |
A total 175 patients were studied. Males comprised 68% of cases. The number of patients in age groups <50, 50-60, 60-70, 70-80, and >80 years were 7, 29, 69, 55, and 15, respectively. When all outdoor and indoor patients in our tertiary care center were considered, patients with LA were found to comprise 26.98% of all cases with cerebral vascular diseases.
Comorbid conditions associated with LA are listed in [Table 1].
Clinical features of patients are tabulated in [Table 2]. When executive function was being checked, it was found that trail making test A could be completed in 25 s only by 6% patients with LA, whereas all controls could complete in 25 s. Trail making test B was completed by all controls in 30 s, whereas only 4% patients with LA could complete in that period. Digit symbol test involving 9 digits could be completed by all controls in 80 s. However, 78%, 14%, and 8% patients with LA could, respectively, solve <5, 6-8, and all 9 digit symbols correctly in 80 s.
Radiologic features of the study group are shown in [Table 3].
| Discussion|| |
In our study, it was noted that LA comprised 26.98% of all indoor and outdoor patients with cerebral vascular diseases presenting to our center. Even in studies done in France,  UK,  and Germany,  the prevalence of LA was nearly 25% of the cases of cerebral vascular diseases.
Pantoni and Garcia  summarized different risk factors for LA. They included older age, male gender, hypertension, history of transient ischemic attack/stroke/myocardial infarction/heart failure, left ventricular hypertrophy on ECG, elevated fibrinogen, and factor VII activity. Additional risk factors such as smoking and raised homocysteine were noted in the Rotterdam Scan Study. , Radiologically, periventricular LA is found to correlate more with aging and hypertension rather than deep white matter hyperintensities alone.  Comorbidities associated with LA as noted in our study are mentioned in [Table 1]. Identification of modifiable risk factors for LA is important as their prevention can potentially reduce morbidity and mortality.
In the present study, clinical features encountered in patients with LA include cognitive decline, dysarthria, gait impairment, sphincter disturbance, and increased risk of stroke. They compare well with the available literature.
Tarvonen-Schröder et al.  noted that dementia, dependence for basic and instrumental activities of daily living, gait impairment, urinary incontinence, mental change, and night time confusion were more common in patients with LA than those without. Lawrence et al.  observed that patients with LA had significant executive dysfunction. In a Korean study, Kim et al. observed lower MMSE and verbal learning test scores in patients with LA than those without.  In our study, 20.6% had mild cognitive impairment, whereas 39.4% had dementia.
Briley et al. noted increase in gait disturbances with an increase in the severity of LA.  Baezner et al. noted that walking speed and balance were inversely related to the severity of LA.  LA increased the risk of falls in elderly,  especially if it involved periventricular and frontal deep white matter.  Patients with LA who had gait disturbance have higher morbidity and mortality compared to those without gait disturbance.  In our study, patients with LA covered lesser distances than those without LA on 3-min walk test.
Poggesi et al. noted that urinary urgency (but not nocturia, urinary frequency, and urinary incontinence) was associated with severity of LA irrespective of their cognitive decline, gait disturbance, or depression.  In our study, 28% patients had bladder/bowel sphincter disturbances.
Henninger et al. observed that presence of severe subcortical LA contributes to larger cortical infarct volumes and worse functional outcomes.  Patients with more severe LA are more prone for stroke recurrence within 90 days,  as also on 5 years follow-up.  Thus, LA is a marker of increased cerebral susceptibility to ischemia. In our study, 42% of patients with LA had stroke. We will like to highlight two interesting features of the strokes in LA: (1) Three of our cases had multiple new lacunar infarcts at presentation raising the possibility of embolic stroke, but no source of embolism was found. We feel that multiple infarcts in these cases occur due to hemodynamic factors resulting from low flow in the brain with widespread small vessel disease. (2) Three of our cases presenting with stroke were found to have a small hemorrhage mostly due to a small vessel rupture. Several studies have shown that these patients should be restarted on the single antiplatelet agent after the bleed subsides as the subsequent risk of ischemic stroke is actually significantly more than recurrent hemorrhage. ,
| Conclusion|| |
LA is a common and under-rated cause of disability. Presentations include cognitive decline, gait disturbance, dysarthria, bladder/bowel sphincter disturbances, and increased risk of stroke. The comorbidities tend to be similar to those of ischemic strokes.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Fisher CM. Lacunar strokes and infarcts: A review. Neurology 1982;32:871-6.
Hachinski VC, Potter P, Merskey H. Leuko-araiosis. Arch Neurol 1987;44:21-3.
Breteler MM, van Swieten JC, Bots ML, Grobbee DE, Claus JJ, van den Hout JH, et al.
Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: The Rotterdam Study. Neurology 1994;44:1246-52.
Steingart A, Hachinski VC, Lau C, Fox AJ, Diaz F, Cape R, et al.
Cognitive and neurologic findings in subjects with diffuse white matter lucencies on computed tomographic scan (leuko-araiosis). Arch Neurol 1987;44:32-5.
Tarvonen-Schröder S, Röyttä M, Räihä I, Kurki T, Rajala T, Sourander L. Clinical features of leuko-araiosis. J Neurol Neurosurg Psychiatry 1996;60:431-6.
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol 1987;149:351-6.
Bogousslavsky J, Van Melle G, Regli F. The Lausanne Stroke Registry: Analysis of 1,000 consecutive patients with first stroke. Stroke 1988;19:1083-92.
Wolfe CD, Rudd AG, Howard R, Coshall C, Stewart J, Lawrence E, et al.
Incidence and case fatality rates of stroke subtypes in a multiethnic population: The South London Stroke Register. J Neurol Neurosurg Psychiatry 2002;72:211-6.
Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: Incidence, recurrence, and long-term survival in ischemic stroke subtypes: A population-based study. Stroke 2001;32:2735-40.
Pantoni L, Garcia JH. The significance of cerebral white matter abnormalities 100 years after Binswanger's report. A review. Stroke 1995;26:1293-301.
Vermeer SE, van Dijk EJ, Koudstaal PJ, Oudkerk M, Hofman A, Clarke R, et al.
Homocysteine, silent brain infarcts, and white matter lesions: The Rotterdam Scan Study. Ann Neurol 2002;51:285-9.
Gebeily S, Fares Y, Kordahi M, Khodeir P, Labaki G, Fazekas F. Cerebral white matter hyperintensities (WMH): An analysis of cerebrovascular risk factors in Lebanon. Int J Neurosci 2014;124:799-805.
Lawrence AJ, Brookes RL, Zeestraten EA, Barrick TR, Morris RG, Markus HS. Pattern and rate of cognitive decline in cerebral small vessel disease: A prospective study. PLoS One 2015;10:e0135523.
Kim TW, Kim YH, Kim KH, Chang WH. White matter hyperintensities and cognitive dysfunction in patients with infratentorial stroke. Ann Rehabil Med 2014;38:620-7.
Briley DP, Wasay M, Sergent S, Thomas S. Cerebral white matter changes (leukoaraiosis), stroke, and gait disturbance. J Am Geriatr Soc 1997;45:1434-8.
Baezner H, Blahak C, Poggesi A, Pantoni L, Inzitari D, Chabriat H, et al.
Association of gait and balance disorders with age-related white matter changes: The LADIS study. Neurology 2008;70:935-42.
Srikanth V, Beare R, Blizzard L, Phan T, Stapleton J, Chen J, et al.
Cerebral white matter lesions, gait, and the risk of incident falls: A prospective population-based study. Stroke 2009;40:175-80.
Blahak C, Baezner H, Pantoni L, Poggesi A, Chabriat H, Erkinjuntti T, et al.
Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: Cross sectional results from the LADIS study. J Neurol Neurosurg Psychiatry 2009;80:608-13.
Briley DP, Haroon S, Sergent SM, Thomas S. Does leukoaraiosis predict morbidity and mortality? Neurology 2000;54:90-4.
Poggesi A, Pracucci G, Chabriat H, Erkinjuntti T, Fazekas F, Verdelho A, et al.
Urinary complaints in nondisabled elderly people with age-related white matter changes: The Leukoaraiosis and DISability (LADIS) Study. J Am Geriatr Soc 2008;56:1638-43.
Henninger N, Khan MA, Zhang J, Moonis M, Goddeau RP Jr. Leukoaraiosis predicts cortical infarct volume after distal middle cerebral artery occlusion. Stroke 2014;45:689-95.
Kim GM, Park KY, Avery R, Helenius J, Rost N, Rosand J, et al.
Extensive leukoaraiosis is associated with high early risk of recurrence after ischemic stroke. Stroke 2014;45:479-85.
Kumral E, Güllüoglu H, Alakbarova N, Karaman B, Deveci EE, Bayramov A, et al.
Association of leukoaraiosis with stroke recurrence within 5 years after initial stroke. J Stroke Cerebrovasc Dis 2015;24:573-82.
Thijs V, Lemmens R, Schoofs C, Görner A, Van Damme P, Schrooten M, et al.
Microbleeds and the risk of recurrent stroke. Stroke 2010;41:2005-9.
Soo YO, Yang SR, Lam WW, Wong A, Fan YH, Leung HH, et al.
Risk vs benefit of anti-thrombotic therapy in ischaemic stroke patients with cerebral microbleeds. J Neurol 2008;255:1679-86.
[Table 1], [Table 2], [Table 3]