Multiple Subcortical Infarcts Research Articles

Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism.

To determine if synucleinopathy pathology is related to REM sleep behavior disorder (RBD) plus dementia or parkinsonism. The clinical and neuropathologic findings were analyzed on all autopsied cases evaluated at Mayo Clinic Rochester from January 1990 to April 2002 who were diagnosed with RBD and a neurodegenerative disorder. Ubiquitin and/or alpha-synuclein immunocytochemistry was used in all cases. The clinical and neuropathologic diagnoses were based on published criteria. Fifteen cases were identified (14 men). All had clear histories of dream enactment behavior, and 10 had RBD confirmed by polysomnography. RBD preceded dementia or parkinsonism in 10 (66.7%) patients by a median of 10 (range 2 to 29) years. The clinical diagnoses included dementia with Lewy bodies (DLB) (n = 6); multiple-system atrophy (MSA) (n = 2); combined DLB, AD, and vascular dementia (n = 1); dementia (n = 1); dementia with parkinsonism (n = 1); PD (n = 1); PD with dementia (n = 1); dementia/parkinsonism/motor neuron disease (n = 1); and AD/Binswanger's disease (n = 1). The neuropathologic diagnoses were Lewy body disease (LBD) in 12 (neocortical in 11 and limbic in 1) and MSA in 3. Three also had argyrophilic grain pathology. In the LBD cases, concomitant AD pathology was present in six (one also with Binswanger's pathology, and one also with multiple subcortical infarcts). In the setting of degenerative dementia or parkinsonism, RBD often reflects an underlying synucleinopathy.

CADASIL, artériopathie cérébrale et systémique autosomale dominante associée à des accidents ischémiques sous-corticaux et à une leucoencéphalopathie: une revue

CADASIL is an increasingly recognised inherited arterial disease involving brain vessels and, to a lesser degree, systemic vessels, with an autosomal dominant pattern of transmission. Affected individuals have migraine, mood disturbances, cognitive changes and recurrent strokes often progressing to subcortical dementia associated with pseudobulbar palsy, gait disturbances, and loss of sphincter control. The disease begins at the age of 40 to 50 and death eventually occurs usually 20 years after the first manifestation of the disease. Magnetic resonance imaging and pathological examination show multiple subcortical lacunar infarcts and diffuse leukoencephalopathy. Brain and leptomeningeal vessels and, to a lesser degree, systemic arterial vessels show nonamyloid, nonarteriosclerotic changes characterised by a hyaline thickening and deposition of a granular eosinophilic material in the media. Cardiovascular risk factors, particularly hypertension, are usually missing. At the ultrastructural level, the most consistent finding consists of a deposition of a granulated osmiophilic material in the extracellular matrix and a destruction of vascular smooth muscle cells. The presence of this material in small arteries of a skin biopsy allows to confirm the suspicion of CADASIL in presence of suggestive clinical and brain imaging features and of similar clinical symptoms in first relatives. The disease has been reported in several families and shown to be caused by strongly stereotyped mutations of the Notch3 gene on chromosome 19q12. However, occurrence of CADASIL due to de novo noninherited mutation of Notch3 gene has also been reported. Recent investigations have shown that the expression of the nonmutated Notch3 is restricted to vascular smooth muscle cells in adult human tissues. In CADASIL, a cleavage product of mutated Notch3 dramatically accumulates at the cytoplasmic membrane of smooth muscle cells near the granular osmiophilic deposits.

Cerebrovascular reactivity and subcortical infarctions.

To investigate the association between different kinds of ischemic lesions and cerebrovascular reactivity (CR) and to evaluate their relationships with the major risk factors for stroke. We evaluated CR using the breath-holding index technique during bilateral transcranial Doppler monitoring of flow velocity in the middle cerebral arteries of 41 consecutive patients attending our clinic for a recent, first-ever, ischemic stroke and in 15 control subjects. Based on the location of the lesion determined by computed tomography, the following 3 types of infarctions were identified: cortical (or territorial), single subcortical, and subcortical with multiple silent subcortical infarctions. Patients with a condition of severe carotid artery stenosis or occlusion, which in itself could account for altered CR, were excluded from this study. All physiological and pathologic conditions that could possibly cause an impairment in CR were recorded. The breath-holding index was significantly lower in the multiple subcortical infarctions group than in the control subjects (P < .001), single subcortical infarctions group (P < .01), and cortical infarctions group (P < .01). In all of the groups male sex (P < .05) and a history of hypertension (P < .05), regardless of whether hypertension was treated, correlated with low CR. The multiple regression analysis indicated that the only significant factor able to influence the breath-holding index was the type of lesion. Nonstenotic patients with first-ever stroke who had a recent symptomatic subcortical infarction associated with multiple silent infarctions seem to have an impaired cerebrovascular reserve capacity. The strong association of subcortical infarctions with multiple silent infarctions with low CR indicates the role of small vessel vasculopathy and hypoperfusion as possible pathogenetic mechanisms of subcortical infarctions with multiple silent infarctions.

Screening of vascular cognitive impairment on a Hungarian cohort

Cerebrovascular disease is a major public health problem in Eastern European countries. A Hungarian post-stroke population was examined to estimate the rate of dementia, the risk factors for cognitive impairment, and the applicability of a recently established Canadian diagnostic checklist in this cohort. Chronic cerebrovascular outpatients were screened for cognitive impairment with a combined checklist: the Diagnostic Checklist for Vascular Dementia established by the Consortium of Canadian Centres for Clinical Cognitive Research using the Mini Mental State Examination instead of the detailed neuropsychological part of the Checklist. Of the 247 consecutive patients at a cerebrovascular outpatient unit, 176 had cerebrovascular disorder diagnosed either by computed tomography (CT; n=126) or by the clinical signs. Of these, 15% were cognitively impaired and 5% fulfilled the criteria of dementia. The mean age of the patients with cognitive impairment was significantly higher than that of patients with normal cognition (68.2+/-10.2 and 60.5+/-10.5 years, P<0.001). The Barthel index was significantly lower in the cognitively affected group than in non-affected patients (92.4+/-16.0 and 97.1+/-8.7, P=0.027). Diabetes and more than two subcortical infarcts on CT or magnetic resonance imaging were more frequent in patients with cognitive loss (P=0.043 and P=0.013, respectively). Cognitive performance was also influenced by the level of education. Higher age, diabetes, motor deficits, and multiple subcortical infarcts are risk factors for cognitive impairment after stroke. The combined checklist appears to be a practical screening test for cognitive impairment in patients with chronic cerebrovascular diseases.

Increased apolipoprotein E4 allele frequency is associated with vascular dementia in the Hungarian population.

The regulatory role of apolipoprotein E in lipid transport and metabolism was utilized to investigate the allelic association between the apolipoprotein E4 (apoE4) allele and vascular dementia (VD) in a selected sample of Hungarian patients with multiple deep subcortical infarcts and leukoaraiosis. Thirty-four Caucasian VD cases and 79 healthy control probands were involved in this study according to the criteria of ICD-10 and NINDS-AIREN International Workshop Diagnostic Criteria. The genomic DNA was isolated from whole blood and the apoE alleles were determined by polymerase chain reaction. The E2, E3 and E4 allele frequencies in the VD group were 5%, 76%, and 19%, respectively; and significant (P<0.03) differences were found in comparison with the data on the healthy controls (E2, 6%; E3, 87%; E4, 8%). The apoE4 allele frequency was intermediate between HC and Alzheimer's dementia group (28%). These results indicate that the apoE4 allele could be a risk factor not only for certain primary degenerative, but also for vascular dementias.

CADASIL in a North American family: clinical, pathologic, and radiologic findings.

To expand the reported phenotypic range of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Despite numerous patient reports, our knowledge of the phenotypic range of CADASIL remains incomplete. We performed clinical, pathologic, and radiologic examinations on members of a family with CADASIL. The proband is a 61-year-old man with a history of migraine and depression who has experienced multiple subcortical infarctions resulting in a stepwise decline. Neuropsychological testing documented a dementia syndrome with frontal lobe features and neurologic examination noted a left hemiparesis and a right-sided palmomental reflex. Brain biopsy with light microscopy revealed a nonatherosclerotic small-vessel angiopathy with periodic acid-Schiff positive granular changes in the media and white matter gliosis, with unremarkable cortex. Genetic testing confirmed a Notch3 mutation. The proband's first cousin has a history of depression, one seizure possibly resulting from an acute stroke, and a learning disorder. Neuropsychological testing demonstrated deficits in executive function and neurologic examination noted persistent extraneous adventitial movements, poor coordination, and primitive reflexes. Skin biopsy with electron microscopy demonstrated granular osmiophilic material within the basement membrane of vascular smooth muscle cells, which is considered to be pathognomonic of CADASIL. The proband's older son and younger son have histories of migraine and depression, respectively, and both also had learning disorders. MRI revealed diffuse white matter disease extending into the temporal lobes, and lacunar infarctions in these four nonhypertensive patients. Other family members have experienced migraine, recurrent stroke, dementia, and depression. CADASIL is a genetic basis for vascular dementia that may be manifest earlier in life than previously reported.

Cognitive deficits of mild dementia: A comparison between dementia of the Alzheimer's type and vascular dementia.

This study was designed to examine the profiles of cognitive deficits in 11 mildly demented patients with dementia of Alzheimer's type (DAT), five with vascular dementia with multiple subcortical lacunar infarcts (VDS), and seven with vascular dementia with extensive white matter lesions (VDW) in comparison with 23 aged individuals without dementia. Memory, attention, abstract thinking, and visuospatial function were assessed using the Japanese translation of the Wechsler Memory Scale-Revised (WMS-R) and the Japanese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Compared with normal aged individuals, three dementia groups were significantly impaired in the memory and abstract thinking. However, the performances on several tests on attention (i.e. Mental Control and Visual Memory Span Backward from WMS-R) and visuospatial function (i.e. Object Assembly from WAIS-R) differed significantly between the DAT and VDS groups, with VDS being the worst in terms of performance than was DAT. This study suggests that, in the mildly demented stage, the patients with DAT have few problems in the attention and visuospatial function, but those with VDS have impairments in these cognitive abilities.

Coronary artery bypass grafting-associated ischemic stroke. A clinical and neuroradiological study.

Ischemic stroke occurring after coronary artery bypass grafting (CABG) has been attributed to various factors. Little is known about the perioperative course and radiological topography of CABG-associated strokes. In this study the clinical and computed tomography features of 25 patients with ischemic stroke following coronary artery bypass grafting were evaluated. Four patients awakened with focal signs, and 21 developed an ischemic stroke 1 to 22 days after surgery. All 4 patients with early stroke had prolonged episodes of operative hypotension. Three of these patients had multiple subcortical and cortical infarcts. Of the 21 patients with late-onset ischemic stroke, 19 had single-territory infarcts (middle cerebral artery territory, N = 12; posterior cerebral artery territory, N = 4; anterior cerebral artery territory, N = 3). Two patients had multiple territory infarcts in the anterior and posterior circulation. No watershed infarcts were found in any of the 25 patients. New-onset atrial fibrillation and location of ischemic stroke in a single vascular territory were more common in patients who had an ischemic stroke after an asymptomatic interval. Duplex sonographic findings of the carotid arteries and oculoplethysmography (OPG) were available for 13 patients. Only 1 patient had an ipsilateral carotid stenosis. Of 21 patients who underwent postoperative two-dimensional echocardiography (with additional transesophageal echocardiography in 4), 2 had a left ventricular thrombus. These findings support the concept that post-CABG stroke is likely embolic.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a clinicopathological and genetic study of a Swiss family.

This paper reports a Swiss family affected by a cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) linked to chromosome 19q12. In three generations several members of this family had recurrent stroke-like episodes and, some developed subcortical dementia, migraine-like headaches, and depression. The clinically affected family members had multiple subcortical infarcts and diffuse leukoencephalopathy on MRI. Necropsy of one patient showed a distinctive non-amyloid and non-atherosclerotic angiopathy of small cerebral and leptomeningeal arteries with concentric depositions of a basophilic granular material replacing the smooth muscle cells of the media. Linkage analysis with five chromosome 19 markers spanning the estimated CADASIL interval showed the absence of any recombinant and positive Lod scores, highly suggestive of linkage of this condition to the CADASIL locus. CADASIL might be an underestimated cause of familial stroke and should be considered in the differential diagnosis of hereditary stroke.

Cognitive dysfunction following subcortical infarction.

To determine the association between computed tomographic scan findings of subcortical infarction, periventricular lucency, and ventricular enlargement and a patient's performance on a range of neuropsychological tests. Prospective study of patients in whom computed tomographic scanning identified discrete areas of subcortical lucency that were consistent with multiple subcortical infarcts and in whom there was no evidence for additional cerebral computer tomographic pathology. Hospital practice that included both inpatients and ambulatory patients. One hundred forty-seven consecutive appropriate computed tomographic scans were identified. Sixty-two patients were excluded because of concomitant medical disorders, and eight refused participation. We describe 77 patients. Performance on a battery of neuropsychological tests. The number of infarcts but not the volume of infarction, periventricular lucency, and cerebral ventricular enlargement but not cortical atrophy were significantly associated with impaired performance on neuropsychological tests. The number of infarcts correlated with impaired performance on tests, and this impaired performance was thought to be dependent on the function of frontal systems, while periventricular lucency and ventricular enlargement correlated with impaired performance on a wider range of tests, including tests that depended on memory and language. The number of infarcts, periventricular lucency, and ventricular enlargement are the computed tomographic head scan parameters that correlated with severity of impaired performance on neuropsychological tests in patients with subcortical infarction. Cognitive impairment is presumed to be the result of cortical disconnection following disruption of the connections between the subcortical regions and the frontal cortex.

Frontal Systems Impairment Following Multiple Lacunar Infarcts

To characterize cognitive impairments following multiple subcortical lacunar infarcts (lacunes), we prospectively compared the neuropsychological performance of 11 subjects with multiple lacunes with 11 medical control subjects matched for age and education who had no clinical or computed tomographic evidence of central nervous system disease. Subjects with multiple subcortical lacunes displayed neuropsychological signs of frontal system dysfunction, even though only 27% met the criteria for clinical diagnosis of dementia. They exhibited significant deficits in shifting mental set, response inhibition, and executive function. In addition, they were more often rated apathetic on a behavior-rating scale. We propose a continuum of cognitive impairments in lacunar states, ranging from frontal systems impairment to dementia.