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H S Markus

Publications and source records attributed to H S Markus.

At least 19 recordsLinked to original sources
PubMed2006

The use of intraoperative monitoring and treatment of symptomatic microemboli in carotid artery stenting: case report and discussion.

Carotid artery stenting is a recently introduced treatment in symptomatic atherosclerotic carotid artery disease with acceptable complication rates. The major risk is perioperative embolic stroke. Transcranial Doppler ultrasonography (TCD) can be used to identify embolic signals and guide therapy. We present a case of symptomatic embolization in a 72-year-old female following carotid stent deployment complicated by haemodynamic changes. Despite concurrent dual antiplatelet medication significant symptomatic embolization occurred even after restoration of the blood pressure, and modulation of the rate of embolization was achieved using dextran-40 guided by TCD monitoring. The patient recovered from an initially profound hemiparesis and dysphasia to minor sensory changes. Microemboli are common following carotid artery stenting and there appears to be a threshold phenomenon associated with prolonged embolization and progression to cerebral infarction. TCD can be used to detect particulate microemboli and therefore may be useful in guiding antithrombotic therapy in this setting. Dextran-40 has been shown to reduce the embolic load following carotid endarterectomy and was used to good effect in this patient in terms of both embolic load and clinical outcome. This is the first case of embolization following carotid stenting successfully treated with dextran-40, and offers a further option for therapeutic intervention in microembolism detected by TCD and stresses the importance of perioperative monitoring of embolic load for postoperative stroke risk.

Aged↗
PubMed2006

Polymorphisms in genes of the renin-angiotensin system and cerebral small vessel disease.

BACKGROUND: Genetic variation in the renin-angiotensin system (RAS) has been implicated in stroke, particularly the small vessel disease (SVD) subtype. Furthermore, there may be two distinct subtypes of cerebral SVD, isolated lacunar infarction (ILI) and ischaemic leukoaraiosis (ILA). METHODS: 300 patients with well-phenotyped SVD and 600 controls were genotyped for five polymorphisms in the angiotensinogen (AGT) gene and eight polymorphisms within the angiotensin-converting enzyme (ACE) gene. RESULTS: AGT and ACE polymorphisms and haplotypes were no more common in SVD cases as a whole or the two subtypes. Amongst hypertensives only, an AGT promoter polymorphism (-20A-->C), was associated with the ILA subtype (multivariate odds ratio 1.716, 95% confidence interval 1.073-2.746, p = 0.024). CONCLUSIONS: RAS genetic variants are not strong risk factors for cerebral SVD. The AGT -20C allele may be a risk factor for the leukoaraiosis subtype amongst hypertensives.

Angiotensinogen↗
PubMed2006

The cognitive profiles of CADASIL and sporadic small vessel disease.

BACKGROUND: Interpretation of treatment trials in vascular dementia is confounded by the presence of coexistent Alzheimer disease (AD) pathology. The younger onset genetic disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) offers a model of pure vascular dementia, in which such confounding is unlikely. To validate CADASIL's use as a model it is important to show it results in a similar cognitive impairment. METHODS: The same neuropsychological assessment was administered to patients with CADASIL (n = 34, 14 of whom had had stroke), sporadic small vessel disease (SVD) presenting with lacunar stroke and having confluent leukoaraiosis (n = 54), and healthy controls (n = 25). RESULTS: A similar pattern of neuropsychological impairment was seen in the two diseases, with prominent early executive dysfunction. Patients with CADASIL and SVD performed worse than controls on Trails switching test (CADASIL p = 0.006; SVD p < 0.001), and on verbal fluency test (CADASIL p = 0.015; SVD p = 0.004). The SVD group also performed worse on immediate (p = 0.050) and delayed (p = 0.049) memory. When only patients with CADASIL with stroke were included in analysis with SVD subjects, all of whom had had stroke, a very similar cognitive profile was seen. The only difference was on verbal fluency, where CADASIL subjects performed worse (p = 0.044). CONCLUSION: Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and small vessel disease show a similar pattern of cognitive deficits. This suggests that CADASIL provides a model of pure vascular dementia relevant for sporadic small vessel disease vascular dementia.

Age Factors↗
PubMed2006

White matter damage on diffusion tensor imaging correlates with age-related cognitive decline.

BACKGROUND: Damage to white matter tracts, resulting in "cerebral disconnection," may underlie age-related cognitive decline. METHODS: Using diffusion tensor MRI (DTI) to investigate white matter damage, and magnetic resonance spectroscopy (MRS) to look at its underlying pathologic basis, the authors investigated the relationship between white matter structure and cognition in 106 healthy middle-aged and elderly adults. Fractional anisotropy (FA) and mean diffusivity (MD) values, whole brain white matter histograms, and regions of interest placed in the white matter of the centrum semiovale were analyzed. Correlations with executive function, working memory, and information-processing speed were performed. RESULTS: There was a progressive reduction in FA and increase in diffusivity with age in both region of interest (r = 0.551, p < 0.001), and whole brain histograms (r = 0.625, p < 0.001). DTI values correlated with performance in all three cognitive domains. After controlling for age, DTI parameters correlated with working memory but not with the other two cognitive domains. MRS studies found a correlation of N-acetyl aspartate, a neuronal marker, with DTI parameters (r = 0.253, p < 0.05). CONCLUSION: The results are consistent with white matter damage due to axonal loss, causing age- related cognitive decline. Working memory may be particularly dependent on complex networks dependent on white matter connections.

Aged↗
PubMed2006

EFNS guideline on neuroimaging in acute stroke. Report of an EFNS task force.

Neuroimaging techniques are necessary for the evaluation of stroke, one of the leading causes of death and neurological impairment in developed countries. The multiplicity of techniques available has increased the complexity of decision making for physicians. We performed a comprehensive review of the literature in English for the period 1965-2005 and critically assessed the relevant publications. The members of the panel reviewed and corrected an initial draft, until a consensus was reached on recommendations stratified according to the European Federation of Neurological Societies (EFNS) criteria. Non-contrast computed tomography (CT) scan is the established imaging procedure for the initial evaluation of stroke patients. However, magnetic resonance imaging (MRI) has a higher sensitivity than CT for the demonstration of infarcted or ischemic areas and depicts well acute and chronic intracerebral hemorrhage. Perfusion and diffusion MRI together with MR angiography (MRA) are very helpful for the acute evaluation of patients with ischemic stroke. MRI and MRA are the recommended techniques for screening cerebral aneurysms and for the diagnosis of cerebral venous thrombosis and arterial dissection. For the non-invasive study of extracranial vessels, MRA is less portable and more expensive than ultrasonography but it has higher sensitivity and specificity for carotid stenosis. Transcranial Doppler is very useful for monitoring arterial reperfusion after thrombolysis, for the diagnosis of intracranial stenosis and of right-to-left shunts, and for monitoring vasospasm after subarachnoid hemorrhage. Currently, single photon emission computed tomography and positron emission tomography have a more limited role in the evaluation of the acute stroke patient.

Humans↗
PubMed2005

Damage within a network of white matter regions underlies executive dysfunction in CADASIL.

OBJECTIVE: To identify the important sites of white matter disruption that underpin executive dysfunction in CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a genetic model of pure subcortical vascular disease. METHODS: The anatomic pattern of correlation between tissue integrity and executive function was explored with diffusion tensor imaging (DTI), which provides quantitative measures of tissue integrity. Eighteen nondemented patients with CADASIL underwent DTI and cognitive assessment. DTI was normalized to a standard template and correlations assessed at every voxel across the brain with Statistical Parametric Mapping with cluster-level correction for multiple comparisons. RESULTS: For executive tasks, correlations were found in a number of discrete regions in the white matter of the frontal lobes. A distinct, nonoverlapping pattern of correlation was seen for verbal memory. Significant independent correlations remained in some regions after co-varying for age and IQ. CONCLUSIONS: Different cognitive functions correlate with structural integrity at different sites in the white and subcortical gray matter. The distribution of regions correlating specifically with executive function provides clues to the organization of the relevant cognitive networks and their important white matter projections. The cingulum bundle is one candidate tract that may carry anteroposterior connections important for executive processes.

Adult↗
PubMed2005

Phosphodiesterase 4D gene, ischemic stroke, and asymptomatic carotid atherosclerosis.

BACKGROUND AND PURPOSE: Phosphodiesterase 4D (PDE4D) was identified recently as the first novel stroke gene to predispose to ischemic stroke independently of conventional risk factors. An association was only found with large vessel and cardioembolic stroke, suggesting a mechanism of accelerated atherosclerosis. We sought to replicate this association in ischemic stroke as a whole, and individual stroke subtypes, in a non-Icelandic European population. To assess a role in early atherosclerosis, we also sought associations with underlying asymptomatic atherosclerosis itself, assessed by carotid ultrasound in a community population. METHODS: A total of 737 consecutive white patients with stroke and 933 white community controls free of symptomatic cerebrovascular disease were examined using a case control methodology. For association with atherosclerosis, intima-media thickness (IMT) in a community population (n=1000) was assessed using carotid ultrasound. Nineteen single nucleotide polymorphisms (SNPs) and 1 minisatellite in the PDE4D gene were determined, with haplotyping undertaken using Phase 2.0. RESULTS: No association with ischemic stroke overall was identified. Six of the 19 SNPs were associated with cardioembolic stroke and 2 different SNPs with large vessel disease. There was no association with carotid artery IMT or carotid plaque in the asymptomatic community subjects. CONCLUSIONS: The PDE4D gene is not a major risk factor for ischemic stroke, or early atherosclerosis, within the 2 European population samples studied. On analysis of individual stroke subtypes, there is a possible association with cardioembolic stroke, but the lack of association with carotid IMT and plaque would suggest that this is via a mechanism other than accelerated atherosclerosis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2005

Brief cognitive assessment for patients with cerebral small vessel disease.

BACKGROUND: Cerebral small vessel disease is a common cause of cognitive impairment and vascular dementia. The cognitive deficit differs from that in Alzheimer's disease, with greater executive/attentional dysfunction and relatively intact episodic memory. OBJECTIVE: To develop brief assessment tools that are better adapted to the neuropsychological profile of cerebral small vessel disease. METHODS: 32 subjects with ischaemic leukoaraiosis (history of lacunar stroke and leukoaraiosis on MRI), aged 50 to 84 years, and 17 age and education matched controls had a brief executive assessment, which took 20 minutes to administer, and a wide range of additional tests. The ability of the brief executive assessment to discriminate between groups-both individually and in combination-was evaluated and compared with that of the whole battery. RESULTS: The brief executive assessment provided good sensitivity and specificity for identifying subjects with ischaemic leukoaraiosis (sensitivity 88%, specificity 88%, using the optimal combination of scores). The best individual tests were trail making and digit symbol, which were both far more sensitive than the mini-mental state examination (MMSE). The ability to discriminate between groups was maintained in subjects with MMSE > 27 and across the whole age range. The brief executive assessment performed well compared with the whole battery, with additional tests accounting for only a further 12% of between-group variance. CONCLUSIONS: The brief executive assessment was sensitive to deficits found in ischaemic leukoaraiosis and discriminated them from the cognitive effects of healthy aging. The assessment has potential for bedside use and as a cognitive end point for clinical trials.

Aged↗
PubMed2004

White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease.

There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3) after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.

Arterioles↗
PubMed2004

Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis.

BACKGROUND: Cerebral small vessel disease is a common cause of vascular dementia. Both discrete lacunar infarcts and more diffuse ischaemic changes, seen as confluent high signal (leukoaraiosis) on T2 weighted magnetic resonance imaging (MRI), occur. However, there is a weak correlation between T2 lesion load and cognitive impairment. Diffusion tensor MRI (DTI) is a new technique that may provide a better index of white matter damage. OBJECTIVES: To determine whether DTI measures are correlated more strongly with cognitive performance than lesion load on T2 weighted images, and whether these correlations are independent of conventional MRI parameters. METHODS: 36 patients with ischaemic leukoaraiosis (leukoaraiosis plus a previous lacunar stroke) and 19 healthy volunteers underwent DTI, conventional MRI, and neuropsychological assessment. RESULTS: On DTI, diffusivity was increased both within lesions and in normal appearing white matter. Mean diffusivity of normal appearing white matter correlated with full scale IQ (r = -0.46, p = 0.009) and tests of executive function. These correlations remained significant after controlling for age, sex, brain volume, and T1/T2 lesion volumes. No significant correlation was identified between T2 lesion load and IQ or neuropsychological scores. Of conventional measures, brain volume correlated best with cognitive function. CONCLUSIONS: Diffusion tensor measurements correlate better with cognition than conventional MRI measures. They may be useful in monitoring disease progression and as a surrogate marker for treatment trials. The findings support the role of white matter damage and disruption of white matter connections in the pathogenesis of cognitive impairment in cerebral small vessel disease.

Aged↗
PubMed2004

Cerebral perfusion and stroke.

Stroke is a heterogeneous syndrome caused by multiple disease mechanisms, but all result in a disruption of cerebral blood flow with subsequent tissue damage. This review covers the mechanisms responsible for regulation of the normal cerebral circulation, and how they are disrupted in disease states. A central concept in treating patients with acute ischaemic stroke is the existence of an ischaemic penumbra of potentially salvageable tissue, and the evidence for its existence in humans is reviewed.

Acute Disease↗
PubMed2003

Serial MRI of a mycotic aneurysm of the cavernous carotid artery.

Cerebral mycotic or infective aneurysms are a rare complication of infectious illness, and such aneurysms of the intracavernous portion of the internal carotid artery are rare. They have been described as a consequence of cavernous sinus infection in an immunocompromised host, but not previously in a renal transplant recipient. We present such a case with serial MRI showing progression from arterial narrowing to aneurysm formation. Transcranial Doppler sonography of the middle cerebral artery showed distal asymptomatic embolisation from the aneurysm.

Aneurysm, Infected↗
PubMed2003

"CADASIL coma": an underdiagnosed acute encephalopathy.

The main clinical features of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy) are stroke, dementia, and migraine. A reversible acute encephalopathy was the principal presentation in six of 70 patients in a British prevalence study. The episodes lasted seven to 14 days, presenting with fever, acute confusion, coma, and fits; there was full recovery but in two cases identical episodes recurred some years later. All patients had a previous history of migraine with aura and were originally misdiagnosed as viral encephalitis. CADASIL should be considered in acute unexplained encephalopathies. MRI white matter changes, previous migraine with aura, and a family history of stroke and dementia may be useful pointers to the diagnosis.

Acute Disease↗
PubMed2003

Vertebral artery origin angioplasty and primary stenting: safety and restenosis rates in a prospective series.

OBJECTIVES: To report a single centre ongoing experience of endovascular treatment for atherosclerotic vertebral artery origin stenosis in a series of symptomatic patients, with follow up imaging to determine the incidence of restenosis. METHODS: 14 patients with vertebral artery origin stenosis on catheter angiography were treated. Angioplasty without stenting was undertaken in the first four patients, all of whom had follow up catheter angiography at one year. Subsequently, patients were treated by primary stenting and followed up with colour Doppler ultrasound examination. RESULTS: The procedure was technically successful in all treated arteries, with no immediate complications. The degree of stenosis was reduced from (mean (SD)) 73 (18)% before treatment to 21 (26)% immediately after treatment in the angioplasty alone group (p = 0.059). In the primary stenting patients, the severity of stenosis was reduced from 82 (8)% to 13 (13)% immediately after treatment (p < 0.001). Restenosis to 70% or greater occurred at one year in all four patients initially treated by angioplasty without stenting. One patient subsequently developed further symptoms and was retreated by stenting. One of the 10 patients treated by primary stenting developed restenosis. None of the remaining patients had further posterior circulation ischaemic symptoms during a mean follow up period of 33.6 months (range 1 to 72 months). CONCLUSIONS: Restenosis occurs often after vertebral artery origin balloon angioplasty without stenting but is uncommon after stenting. Primary stenting is therefore recommended to maintain patency at this site, and had a low complication rate in this series.

Adult↗
PubMed2002

Diagnostic strategies in CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited autosomal dominant condition characterized by migraine, recurrent stroke, and dementia. It results from mutations in the notch3 gene but mutations may occur at multiple sites making molecular diagnosis time consuming. It has been suggested that the presence of granular osmiophilic material (GOM) on skin biopsy and involvement of the anterior temporal lobe and external capsule on MRI may help in diagnosis. METHODS: The authors identified 83 potential index cases from the British population and screened exons 2 to 23 of notch3. MRI scans were scored using a modified Scheltens scale. Skin biopsy was performed in a subgroup. RESULTS: Fifteen different point mutations were identified in 48 families, 73% of which were in exon 4, 8% in exon 3, and 6% in each of exons 5 and 6. Moderate or severe involvement of the anterior temporal pole on MRI had a sensitivity of 89% and specificity of 86% for diagnosis of CADASIL, whereas external capsule involvement had a high sensitivity of 93% but a low specificity of 45%. Skin biopsy, performed in 18 cases, had a sensitivity of 45% and specificity of 100%. CONCLUSIONS: The spectrum of mutations in this study can be used to plan appropriate screening protocols; a suggested protocol is to screen exon 4, and proceed to exons 3, 5, and 6 where indicated. GOM on skin biopsy is diagnostic but can be negative. Anterior temporal pole involvement on MRI is a useful diagnostic marker.

Adult↗
PubMed2002

Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis.

BACKGROUND: Ischemic leukoaraiosis (ILA) refers to diffuse T2-weighted white matter hyperintensity in the context of a previous clinical lacunar stroke. Reduced cerebral blood flow (CBF) in white matter has been demonstrated, but it is not known whether hypoperfusion is confined to lesions or extends into normal-appearing white matter. Demonstrating changes in normal-appearing white matter would provide clues to the importance of hypoperfusion in pathogenesis and would be an obvious target for therapies aimed at restoring white matter blood flow. METHODS: Twenty-one patients with ILA, and 16 age-matched control subjects, underwent exogenous contrast-based quantitative perfusion MRI. CBF was determined both within and outside areas of T2-weighted hyperintensity in both periventricular white matter and the centrum semiovale. RESULTS: CBF of normal-appearing white matter was reduced in periventricular regions (for patients with ILA, 17.9 +/- 5.6 mL/100 g/min; for controls, 21.6 +/- 5.1 mL/100 g/min; p = 0.046). CBF in gray matter and normal-appearing white matter of the centrum semiovale did not differ significantly between groups. In normal-appearing white matter in patients, CBF was higher in the centrum semiovale than periventricular white matter, with a similar trend in control subjects. CONCLUSIONS: Hypoperfusion may be an early feature in the development of periventricular lesions in ILA and may play a direct pathogenic role. Serial studies are now needed to determine whether these changes herald the appearance of new lesions and represent "at risk" white matter, and to determine whether pharmacological agents can restore perfusion of normal-appearing white matter.

Aged↗
PubMed2001

Normal-appearing white matter in ischemic leukoaraiosis: a diffusion tensor MRI study.

Ischemic leukoaraiosis is a consistent concomitant of vascular dementia. Conventional MRI provides little information about underlying white matter tract disruption and correlates poorly with cognitive dysfunction. Diffusion tensor MRI may provide better markers of tract integrity. Changes in the normal-appearing white matter were demonstrated in 30 patients with ischemic leukoaraiosis compared with 17 age-matched control subjects. These changes correlated with executive dysfunction assessed by the Wisconsin Card Sorting Test.

Aged↗