Subcortical Ischemic Lesions Research Articles

The Relationship between 24-Hour Blood Pressure Readings, Subcortical Ischemic Lesions and Vascular Dementia

Background: Twenty-four-hour blood pressure (BP) readings have been found to correlate with hypertensive target organ damage. Lacunar infarcts (LI) and white matter lesions (WML) probably represent manifestations of cerebral hypertensive target organ damage. This study was conducted to better delineate the relationships between 24-hour BP measurements, LI/WML and small vessel disease cognitive impairment/vascular dementia (CI/VD). Methods: Two hundred patients with first-time symptomatic LI were examined with 24-hour BP monitoring. The degree of nocturnal BP dip, (daytime BP – nighttime BP)/daytime BP, was categorized into three groups: dippers (>0.1), nondippers (0–0.1) and reverse dippers (<0). WML were subdivided into periventricular hyperintensities (PVH) and subcortical hyperintensities. Results: The breakdown of patients was: 50% nondippers, 27.5% reverse dippers and 22.5% dippers. Forty-one patients (20.5%) were found to have CI and dementia. Male sex (OR 3.35; 95% CI 1.20–9.34), advanced PVH (OR 14.42; 95% CI 5.62–36.98) and absence of a dipping status (nondipper: OR 12.62; 95% CI 1.37–115.95; reverse dipper: OR 11.95; 95% CI 1.27–112.11) were independently associated with CIVD after multivariate analysis. High nighttime systolic BP (OR 3.93; 95% CI 1.38–11.17), high daytime (OR 2.06; 95% CI 1.03–4.04) and nighttime diastolic BP (OR 2.48; 95% CI 1.13–5.45) and absence of a dipping status (nondipper: OR 2.7; 95% CI 1.03–7.05; reverse dipper: OR 3.78; 95% CI 1.38–10.34) were significantly associated with PVH. Conclusions: High prevalence of a nondipping status was found in the LI cohort. A nondipping status appears to be directly associated with CIVD independent of PVH. This study indicates the need for further studies to investigate whether or not controlling nighttime BP will help reduce the risk for CI/VD development.

Subcortical lesions after transient thread occlusion in the rat: T2‐weighted magnetic resonance imaging findings without corresponding sensorimotor deficits

To investigate infarct evolution and functional consequences of exclusive subcortical or cortico-subcortical strokes, transient middle cerebral artery occlusion (MCAO) was conducted in Wistar rats. MCAO was induced in male Wistar rats (260-300 g) for 60 minutes. Lesion volumes and absolute T2 times on magnetic resonance imaging (MRI) were assessed 1 and 14 days after MCAO using a 4.7-T MRI animal scanner in conjunction with functional testing (adhesive tape removal, cylinder test, and ledged beam walking). Functional test scores were not distinguishable between sham-operated animals (N = 5) and those with exclusive caudoputaminal infarct (N = 8; group cp), but showed significant deficits in animals with cortico-subcortical infarction (N = 10; group cp+). The cp group had lower absolute T2 times and a more pronounced reduction in T2 lesion volume over time than the subcortical component in the cp+ group. There was no correlation of T2 lesion size or absolute T2 times and functional impairment in either group. When judged from functional tests alone, subcortical ischemic lesions may not be diagnosed reliably. Furthermore, T2-weighted (T2-w) MRI does not well anticipate functional deficits in primarily striatal lesions.

Early cerebral hemodynamic changes during passive movements and motor recovery after stroke.

Recovery from hemiplegia is a complex phenomenon that depends on various adaptive processes involving both the affected and the unaffected hemisphere. Our aim in this study was to investigate changes in cerebral perfusion in hemiplegic stroke patients during passive movements and their correlation with the subsequent motor recovery. The study included 30 patients with single, subcortical ischemic cerebral lesions. Within 14 days (range 8 to 14 days) from stroke onset, all patients were examined for the effects of passive elbow movements on cerebral blood flow in the middle cerebral arteries (MCAs) by means of bilateral transcranial Doppler (TCD) ultrasonography. On the same day as TCD assessment, they were also evaluated clinically with the Canadian Neurological Scale (CNS) and with Medical Research Council (MRC) scale for motor deficit of the affected arm. A clinical evaluation using the same scales was repeated after two months of motor rehabilitation therapy. We investigated the relationship between changes of Mean Flow Velocity (MFV) during passive movements and degree of recovery after stroke. The logistic regression procedure indicated that out of all factors considered as possibly related to a good clinical motor deficit recovery of the affected arm, evaluated by means of MRC, only the MFV percentage increase played a predictive role. In particular, for each additional point of contralateral MFV percentage increase during passive movement of the affected arm, the relative probability of good clinical recovery increased 5.68 times (95% CI=1.76-18.40; p=0.004). Similar results were found when the clinical recovery was measured by means of the CNS (slope=0.40, p<0.001). Passive movements in hemiplegic stroke patients before clinical recovery elicit activation patterns that may be critical for the restoration of motor function.I n particular, early and consistent activation of the affected hemisphere, as detected with TCD, seems to predict the positive evolution of a motor deficit.

A new reproducible model of an epidural mass lesion in rodents. Part I: Characterization by neurophysiological monitoring, magnetic resonance imaging, and histopathological analysis.

The goal of this study was to characterize a new model of an epidural mass lesion in rodents by means of neurophysiological monitoring, magnetic resonance imaging, and histopathological analysis. Changes in intracranial pressure (ICP), cerebral perfusion pressure (CPP), and laser Doppler flowmetry (LDF) values, intraparenchymal tissue partial oxygen pressure (PtiO2), and electroencephalography (EEG) activity were evaluated in the rat during controlled, epidural expansion of a latex balloon up to a maximum ICP of 60 mm Hg. The initial balloon inflation was followed by periods of sustained inflation (30 +/- 1 minute) and reperfusion (180 +/- 5 minutes). Histopathological analysis and magnetic resonance (MR) imaging were performed to characterize the lesion. The time to maximum balloon expansion and the average balloon volume were highly reproducible. Alterations in EEG activity during inflation first appeared when the CPP decreased to 57 mm Hg, the LDF value to 66% of baseline values. and the PtiO2 to 12 mm Hg. During maximum compression, the CPP was reduced to 34 mm Hg, the LDF value to 40% of baseline, and the PtiO2 to 4 to 5 mm Hg. The EEG tracing was isoelectric during prolonged inflation and the values of LDF and PtiO2 decreased due to accompanying hypotonia. After reperfusion, the CPP was significantly decreased (p < 0.05) due to the elevation of ICP. Both the LDF value and EEG activity displayed incomplete restoration, whereas the value of PtiO2 returned to normal. Histological analysis and MR imaging revealed brain swelling with a midline shift and a combined cortical-subcortical ischemic lesion beyond the site of balloon compression. This novel model of an epidural mass lesion in rodents closely resembles the process observed in humans. Evaluation of pathophysiological and morphological changes was feasible by using neurophysiological monitoring and MR imaging.

Impact of subcortical ischemic lesions on behavior and cognition.

Both cerebrovascular disease and AD are common in the elderly. There are various types of underlying damage to tissue and vessels in vascular cognitive impairment, and the neural mechanisms producing cognitive impairment and the clinical picture are different among the subtypes. Among them, small subcortical infarcts disrupting cortico-subcortical circuits and white matter lesions are the commonest types, and the combination of these two types of lesions might be more realistic than each pure form. Moreover, cognitive impairment of vascular origin may be superimposed on AD. Both vascular and degenerative mechanisms contribute to the development of cognitive impairment, especially in old age, whether they are two independent parallel processes or interacting pathologies. Subcortical small lesions involving the thalamus, caudate, and globus pallidus disrupt cortico-subcortical circuits, resulting in cognitive dysfunction. Disruption of the frontal-subcortical circuits leads to cognitive impairment with striking frontal lobe features, and disruption of the memory-related circuits leads to amnesia. White matter changes, which are certainly related to chronic cerebral ischemia in some patients, are another issue. Patients with dementia and white matter changes may have either AD with cerebrovascular changes or a form of VaD, or a combination of these two etiologies. However, our series of studies have suggested that white matter changes in AD patients are superimposed phenomena of vascular origin and that white matter changes contribute to specific neurological and neuropsychiatric manifestations, but not to global cognitive impairment, which is more closely associated with the degenerative process.

Vascular Cognitive Impairment

Abstract: The term vascular cognitive impairment (VCI) is now employed to capture the spectrum of illness and disability arising from impaired cognitive function of vascular origin. As such, it supplants the more narrowly focussed terms “Vascular dementia (VaD)” and “multi‐infarct dementia”. It is meant to include both those whose cognitive impairment is different from that assumed by the usual criteria for dementia. Traditionally, dementia criteria have been modelled on AD, a disorder with more characteristic neuropathological and clinical disease expression than is seen in VaD, which can occur in many forms. VCI is common, and is associated with many adverse outcomes, including worse cognition, institutionalization, and death.One form of VCI is coincident AD and VaD, a category which, although it has been comparatively neglected, may be amongst the most common forms of dementia. Another common form of VCI has a predilection for subcortical ischemic lesions, and for a clinical presentation which reflects frontal and subcortical involvement.At present, there is no specific treatment for VCI, although several agents appear to offer the hope of both treatment and prevention. Further research on the clinical, pathological and mechanistic underpinnings of this important syndrome is needed. For a long time, VaD has been recognized as the second most common cause of dementia.1,2) More recently, however, the concept of cognitive impairment in relation to cerebrovascular disease has been expanded. This paper will review the notion of “vascular cognitive impairment” (VCI) as it relates to clinical practice, and to our understanding of disease mechanisms in dementia and related disorders. It will propose that while the expanded concept has merit, within it are to be found distinct subgroups, including some of particular importance as targets for clinical trials of therapeutic and even preventive interventions.

Cerebrovascular Pathology Contributes to the Heterogeneity of Alzheimer's Disease.

Heterogeneous pathology in Alzheimer's Disease (AD) is due to variability in the nature and severity of lesions, overlap with other neurodegenerative diseases such as Parkinson's disease, or the co-existence of cerebrovascular disease. In the MGH-ADRC autopsy archives, remote cerebral infarcts (CVA) were reported in 30% of the otherwise uncomplicated AD cases. To determine the potential significance of cerebrovascular lesions in relation to AD, the relative densities (CERAD grading criteria) of Bielschowsky-stained AD lesions and Ab-amyloid immunoreactive plaques were compared among cases of AD+CVA (N=52), AD (N=48), aged controls (NC; N=9), and aged controls with AD lesions (ADC; N=8). The prevalence of the ApoE varepsilon 4 allele was also determined for each group. This study demonstrated: 1) higher densities of Bielschowsky-stained plaques in AD, AD+CVA, and ADC than in NC (P<0.0001); 2) more abundant neurofibrillary tangles in AD relative to all other groups (P<0.0005), and in AD+CVA and ADC relative to NC (P<0.05); and 3) increased densities of Ab-amyloid-immunoreactive plaques in AD relative to AD+CVA (P=0.0003). In AD+CVA, cerebral vascular lesions consisting of remote microscopic cortical and subcortical white matter infarcts, ischemic lesions, and leukoaraiosis were consistently distributed in structures typically damaged by AD neurodegeneration, as well as in the basal ganglia. The ApoE varepsilon 4 allele was more prevalent in the AD+CVA (70%) than in the AD (58%) group (P=0.05). Since the AD and AD+CVA groups had similar degrees of dementia, the results suggest that cerebral vascular lesions in regions typically destroyed by AD may contribute to the clinical manifestations of AD.

Altered brain energy metabolism in demented patients with multiple subcortical ischemic lesions. Working hypotheses.

We report the results of brain metabolic studies (using magnetic resonance spectroscopy) in three groups of individuals: (1) demented patients with multiple subcortical ischemic lesions (n = 18); (2) nondemented, age-matched controls (n = 21); and (3) demented patients with neurodegenerative disease, probably of the Alzheimer type (n = 19). Patients with dementia with subcortical vascular lesions, as demonstrated by appropriate imaging studies, had an increase of phosphate energy charge in areas of the cerebral cortex (especially prominent in the frontal regions) superficial to and excluded from the subcortical lesions. We hypothesize that this increased energy charge might be caused by reduced metabolic activity of disconnected brain tissue or by astrocytic hypertrophy and hyperplasia that accompanies subtle ischemic, cortical alterations.

Bestimmung der regionalen, zerebrovaskulären Perfusionsreserve (rCPR) mit der quantitativen Fluß/Volumen (F/V)-SPECT

NPS (aphasia or neglect) are a regular concomitant symptom of cortical, and, occasionally, subcortical ischemic lesions. In 19 patients with subcortical lesions (eight with NPS, 11 without NPS), F/V-SPECT was employed to search for changes in rCPR in both, lesions and ipsilateral cortex. Results were correlated with NPS and MRI findings. Compared to the unaffected hemisphere, all subcortical lesions showed reduced regional cerebral blood flow (rCBF) (-16 to -23%), increased regional cerebral blood volume (rCBV) (+34 to +62%), and decreased or missing rCPR (-27 to -28%). Compared to MRI, there was no difference in lesion size in the thromboembolic lesions. Hemodynamic low-flow infarcts, however, were greater with SPECT than in MRI. In patients without NPS, the adjacent cortex was normal in SPECT and MRI. In addition, patients with NPS revealed reduced rCBF (-18%), increased rCBV (+19%), and decreased rCPR (-22%) in the adjacent cortex. MRI was normal in the same cortical area. These results indicate that NPS in subcortical lesions may be caused by a hemodynamic mechanism causing reduction of rCPR in the adjacent cortex.