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Biomedical subjects

Michael Hennerici

Publications and source records attributed to Michael Hennerici.

At least 19 recordsLinked to original sources

Risk of rapid global functional decline in elderly patients with severe cerebral age-related white matter changes: the LADIS study.

BACKGROUND: Age-related white matter changes (ARWMCs), frequently detected on neuroimaging, are associated with motor, cognitive, urinary, and mood disorders. The LADIS (LeukoAraiosis and DISability) Study primarily aims to assess ARWMCs as a determinant of global functional decline in the elderly population. METHODS: We enrolled 639 patients (mean age, 74.1 +/- 5.0 years; 45.1% male) referred for nondisabling complaints, who had ARWMCs detected on brain magnetic resonance imaging (MRI) of mild, moderate, or severe grade according to the Fazekas scale. At the 1-year follow-up, 619 were reassessed using the Instrumental Activities of Daily Living (IADL) scale. Of these, 506 were totally independent at baseline, and 113 were impaired in only 1 item of the IADL scale. We studied the 1-year transition to 2 or more activities limited and selective functional impairments as cofactors of functional decline. RESULTS: The rate of transition was 9%, 15%, and 26%, in the mild, moderate, and severe ARWMC group, respectively. Comparing the severe with the mild ARWMC groups and adjusting for age and for other predictors of decline, the risk was more than 2-fold higher (odds ratio; 2.38; 95% confidence interval, 1.29-4.38) in patients with 0 or 1 activity limited, and 3-fold higher (odds ratio, 3.02; 95% confidence interval, 1.34-6.78) among patients fully independent at baseline. Both motor and cognitive deterioration predominantly explained the effect of ARWMCs on global functional decline. CONCLUSION: Elderly patients who are functionally independent and who have severe ARWMCs are at considerable risk of becoming more dependent in a short period, mostly owing to motor and cognitive deterioration.

Aged↗

Costs of acute stroke care on regular neurological wards: a comparison with stroke unit setting.

OBJECTIVES: Stroke unit care has been shown to be beneficial but costly. In an own previous study, the resource utilization of stroke unit care has been evaluated. Since the resource utilization on regular neurological wards is widely unknown, we determined the costs for acute stroke care on regular neurological wards to compare both treatment settings. METHODS AND PATIENTS: We included 253 consecutive in-patients with the diagnosis of ischemic stroke (IS), intracerebral hemorrhage (ICH) or transient ischemic attack (TIA) treated on regular wards at a German University Department of Neurology, between 1 January and 30 June 1998. The modified Rankin scale (mRS) was used to assess outcome. Costs of stroke care were calculated from the perspective of the healthcare provider (hospital) by using a bottom-up approach. Resource utilization was compared to stroke unit care as determined in a previous study. Prices of 2002 were used (in Euros). RESULTS: IS was present in 78% (n=196), TIA in 13% (n=34), and ICH in 9% (n=23) of patients. Length of stay was 11.1+/-8.9 (mean+/-S.D., IS), 11.1+/-6.5 (TIA), and 16.9+/-15.5 (ICH) days (p>0.05). Mean costs of stroke care were euro 3060 (US$ 3180) for TIA, euro 3070 (US$ 3200) for IS and euro 5210 (US$ 5430) for ICH (p<0.05, ICH versus IS and TIA). The highest costs were due to non-medical care (46%) and personnel (25%). The mRS improved during hospitalization from 3.0+/-1.6 to 2.2+/-1.8 (p<0.01). Compared to care on regular neurological wards, mean costs per admission with treatment on stroke units increased by 7.0%, mean costs per day by 15.6%. CONCLUSION: The comparison - considering a potential bias of patient selection - shows that acute stroke unit care is approximately 16% more costly than treatment on regular neurological wards due to higher resource use of personnel and diagnostic procedures. Stroke unit treatment tends to decrease post-acute in-patient care costs.

Acute Disease↗

High-dose atorvastatin after stroke or transient ischemic attack.

BACKGROUND: Statins reduce the incidence of strokes among patients at increased risk for cardiovascular disease; whether they reduce the risk of stroke after a recent stroke or transient ischemic attack (TIA) remains to be established. METHODS: We randomly assigned 4731 patients who had had a stroke or TIA within one to six months before study entry, had low-density lipoprotein (LDL) cholesterol levels of 100 to 190 mg per deciliter (2.6 to 4.9 mmol per liter), and had no known coronary heart disease to double-blind treatment with 80 mg of atorvastatin per day or placebo. The primary end point was a first nonfatal or fatal stroke. RESULTS: The mean LDL cholesterol level during the trial was 73 mg per deciliter (1.9 mmol per liter) among patients receiving atorvastatin and 129 mg per deciliter (3.3 mmol per liter) among patients receiving placebo. During a median follow-up of 4.9 years, 265 patients (11.2 percent) receiving atorvastatin and 311 patients (13.1 percent) receiving placebo had a fatal or nonfatal stroke (5-year absolute reduction in risk, 2.2 percent; adjusted hazard ratio, 0.84; 95 percent confidence interval, 0.71 to 0.99; P=0.03; unadjusted P=0.05). The atorvastatin group had 218 ischemic strokes and 55 hemorrhagic strokes, whereas the placebo group had 274 ischemic strokes and 33 hemorrhagic strokes. The five-year absolute reduction in the risk of major cardiovascular events was 3.5 percent (hazard ratio, 0.80; 95 percent confidence interval, 0.69 to 0.92; P=0.002). The overall mortality rate was similar, with 216 deaths in the atorvastatin group and 211 deaths in the placebo group (P=0.98), as were the rates of serious adverse events. Elevated liver enzyme values were more common in patients taking atorvastatin. CONCLUSIONS: In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events, despite a small increase in the incidence of hemorrhagic stroke. (ClinicalTrials.gov number, NCT00147602 [ClinicalTrials.gov].).

Adult↗

Age, hypertension, and lacunar stroke are the major determinants of the severity of age-related white matter changes. The LADIS (Leukoaraiosis and Disability in the Elderly) Study.

BACKGROUND: Age-related white matter changes (ARWMC), seen on neuroimaging with high frequency in older people, are thought to be consequent to the effect of vascular risk factors and vascular diseases including hypertension and stroke. Among the proofs conventionally required for a factor to be considered a risk factor for a definite pathology, there is the demonstration of a trend in risk exposure related to disease severity. We sought whether such a trend existed in the association of vascular risk factors or comorbidities with the severity of ARWMC aiming particularly at further elucidating the relative roles of hypertension and stroke in this regard. METHODS: The LADIS (Leukoaraiosis and Disability) Study is evaluating the role of ARWMC as an independent determinant of the transition to disability in the elderly. Six hundred and thirty-nine nondisabled subjects (mean age 74.1+/-5.0, M/F: 288/351) with ARWMC of different severity grades on MRI (mild, moderate, or severe according to the Fazekas scale) were assessed at baseline for demographics, vascular risk factors, and comorbidities, and are being followed up for 3 years. RESULTS: Age, frequency of hypertension and history of stroke increased along with increasing ARWMC severity independently of other factors. For hypertension, however, this occurred only in subjects without a stroke history, while for stroke history, it mainly depended on lacunar stroke. The amount of cigarettes smoked and the interaction between hypercholesterolemia and smoking predicted only the most severe ARWMC grade. CONCLUSIONS: The LADIS Study confirms that age, hypertension and lacunar strokes are the major determinants of ARWMC. Smoking and hypercholesterolemia provide additional risk.

Age Factors↗

Effects of simultaneous application of ultrasound and microbubbles on intracerebral hemorrhage in an animal model.

Microbubble-enhanced sonothrombolysis (MEST) may be an alternative therapeutic option in ischemic stroke. Clinical study of the efficacy of MEST as an adjunct stroke therapy, before imaging with CT or MRI, requires experimental data on the safety of this approach in the presence of hemorrhagic stroke. We, therefore, investigated the effect of diagnostic transcranial ultrasound combined with microbubbles (US + MB) in an experimental animal model of intracerebral hemorrhage (ICH). ICH was induced in anesthetized rats by intracerebral collagenase injection. Transcranial ultrasound (2 MHz, mechanical index 1.3, 1051 kPa) was applied 3 h after ICH induction to rat brains for 30 min during a continuous IV infusion of sulfur hexafluoride microbubbles (SonoVue). The size of cerebral hemorrhage, the extent of brain edema, and the amount of apoptosis were compared with those from control rats with ICH but without US + MB. Results showed no significant effect of US + MB on hemorrhage size (control 23.3 +/- 10.7 mm(3), US + MB 20.3 +/- 5.8 mm(3)), on the extent of brain edema (control 3.3 +/- 2.0%, US +MB 3.5 +/- 1.9%), or on the rate of apoptosis (control 5.2 +/- 1.5%, US + MB 5.2 +/- 1.0%). We conclude that diagnostic ultrasound in combination with microbubbles does not cause additional damage to the rat brain during ICH in our experimental set-up. This finding provides support for the use of MEST as an early stroke therapy.

Animals↗

Leukoaraiosis predicts hidden global functioning impairment in nondisabled older people: the LADIS (Leukoaraiosis and Disability in the Elderly) Study.

OBJECTIVES: To determine whether leukoaraiosis severity is independently associated with differences in global functioning in nondisabled elderly patients. DESIGN: Cross-sectional data analysis from an ongoing longitudinal multicenter and multinational study. SETTING: The Leukoaraiosis and Disability Study, a collaboration aimed at assessing leukoaraiosis as an independent predictor of the transition to disability in older people. PARTICIPANTS: Six hundred thirty-nine nondisabled subjects (288 men, 351 women, mean age+/-standard deviation 74.1+/-5.0) with magnetic resonance imaging-detected leukoaraiosis of different severity and presenting with one of the following: mild cognitive or motor disturbances, minor cerebrovascular events, or mood alterations or in whom leukoaraiosis was incidentally identified. MEASUREMENTS: Centralized assessment of leukoaraiosis severity according to the three severity degrees of the Fazekas scale; Disability Assessment for Dementia (DAD) Scale for measurement of global functioning. RESULTS: At baseline, 44% of participants had a mild, 31% a moderate, and 25% a severe degree of leukoaraiosis. A significant trend toward declining performance on the DAD Scale was apparent with increasing leukoaraiosis score severity (total score=98.8, 98.6, 97.5, respectively, in the three leukoaraiosis categories, analysis of variance P=.002). Similar trends were obtained for basic (P=.01) and instrumental (P<.001) function items. The statistical significance of these differences was confirmed in a multiple linear regression analysis correcting for numerous factors known to influence disability in older people. Executive function test performance declined along with increasing leukoaraiosis severity and was significantly related to DAD total score. CONCLUSION: Even in nondisabled elderly patients, levels of functional ability are related to white matter lesion severity. Executive dysfunction may mediate this relationship.

Activities of Daily Living↗

Neurodegeneration with features of NIFID and ALS--extended clinical and neuropathological spectrum.

Heterogeneous clinical and neuropathological features have been observed in the recently described neuronal intermediate filament inclusion disease (NIFID). The immunohistological findings common to all cases are alpha-internexin and neurofilament-positive neuronal cytoplasmic inclusions, which have not been found in comparable density in other neurodegenerative disorders. Notwithstanding these common features, the cases reported so far have shown differences concerning age at onset, constellation and dominance of symptoms as well as type and distribution of additional neuropathological findings. Here we present the first NIFID case that exhibits severe involvement of lower motor neurons. Also, this patient may have had a clinical onset of disease in early childhood, as she was diagnosed as having dysarthria, which could not be attributed to any other cause at the age of 3 years. This case is a further contribution to the spectrum of this novel neurodegenerative disease.

Adolescent↗

Development of a neuropsychological battery for the Leukoaraiosis and Disability in the Elderly Study (LADIS): experience and baseline data.

The relationship between age-related white matter changes and cognitive performance in independent elderly people is still not clear. The Leukoaraiosis and Disability in the Elderly study (LADIS) involves 11 European centers. It aims to assess the role of the age-related white matter changes as an independent factor in the transition to disability, and in cognitive performance of an independent elderly population. A comprehensive neuropsychological battery was constructed in order to harmonize the cognitive assessment across countries. Patients were evaluated at baseline and during the 3-year follow-up with the Mini-Mental State Examination, a modified version of the VADAS-Cog (Alzheimer's Dementia Assessment Scale plus tests of Delayed recall, Symbol digit, Digit span, Maze, Digit cancellation and Verbal fluency), Trail making and Stroop test. Six hundred thirty-eight patients (mean age 74 +/- 5 years; mean educational level 10 +/- 4, F/M: 351/287) were included in this study. Neuropsychological data were analyzed test by test and also grouped in three compound measures (executive, memory and speed/motor control domains). Older subjects (>74 years) performed significantly worse than younger subjects on the ADAS-Mod and on the tests of memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Participants with higher educational level (>8 years of school) showed better performances on the compound measures for memory (t(631) = 3.25; p = 0.001), executive functions (t(581) = 4.68; p = 0.001) and speed/motor control (t(587) = 4.01; p = 0.001). Using multiple regression analysis models to study the influence of demographic variables on cognitive performance, age and education remained important variables influencing test performance. In the LADIS population baseline data, older age and lower educational levels negatively influence neuropsychological performance.

Aged↗

Multiparametric MRI and ultrasound findings in patients with internal carotid artery dissection.

In this study, clinical, MRI, and ultrasound findings in 33 patients with 37 MRI-confirmed internal carotid artery dissections (ICADs) were investigated. In 24 of 37 (64.9%) diffusion-weighted MRI (DWI) revealed acute ischemic brain lesions. ICADs with subsequent DWI lesions usually had a concentric position of the mural hematoma (14 of 24; 58.3%). In contrast, ICADs without DWI lesions (13 of 37; 35.1%) demonstrated an eccentric position of the mural hematoma (10 of 13; 76.9%), sometimes without ultrasound abnormality (5 of 13; 38.5%), while nonischemic clinical signs were frequent (11 of 13; 84.6%). A hemodynamic stroke pattern with comparatively large ischemic lesions along the hemodynamic risk zones was noted in 7 of 24 patients (29.2%).

Brain↗

Supratentorial age-related white matter changes predict outcome in cerebellar stroke.

BACKGROUND AND PURPOSE: Little is known about the relevance of age related white matter lesions (WMLs) concerning outcome after first-ever territorial stroke. Based on an index patient, we hypothesized that age and pre-existent WMLs rather than infarct volume and topography determine outcome. PATIENTS AND METHODS: Thirty-four consecutive patients with magnetic resonance diffusion-weighted imaging-proven isolated acute cerebellar infarction were prospectively entered on our stroke data registry. Patients with pre-existent neurological deficits, hemorrhagic, or malignant cerebellar infarction were excluded. Patients were stratified using Rankin and Barthel disability scales into groups: I complete recovery, II moderate, and III significant disability 14 days after stroke onset. RESULTS: Initial neurological and functional scores were similar among all the groups with vertigo, nausea, unsteadiness, and limb ataxia being the most common. Infarct volume, vascular territories, and comorbidity did not predict clinical outcome. In contrast, presence and severity of supratentorial WMLs and age significantly determined outcome by functional tests. CONCLUSIONS: In patients with isolated cerebellar infarction functional outcome correlated with the coexistence of age-related WMLs rather than stroke volume and topography. This reflects the loss of compensatory network integrity as the equivalent of functional incapacity beyond local lesion disturbances.

Adult↗

Matrix metalloproteinases in cerebrovascular diseases.

Matrix metalloproteinases are important factors for tissue remodelling and are activated during several physiological and pathological conditions, including cerebrovascular diseases. We give an overview of the structure, production and physiological effects of these widely distributed proteases and describe the genetic background and regulation pathways. In particular, we discuss the role of matrix metalloproteinases in vascular remodelling concerning ischaemic stroke, brain haemorrhage, vascular dementia, carotid artery plaques and cerebral aneurysms.

Cerebrovascular Disorders↗

Diffusion-weighted and perfusion MRI demonstrates parenchymal changes in complex partial status epilepticus.

Diffusion-weighted MRI (DWI) and perfusion MRI (PI) have been mainly applied in acute stroke, but may provide information in the peri-ictal phase in epilepsy patients. Both transient reductions of brain water diffusion, namely a low apparent diffusion coefficient (ADC), and signs of hyperperfusion have been reported in experimental and human epilepsy case studies. We studied 10 patients with complex partial status epilepticus (CPSE) with serial MRI including DWI and PI. All patients showed regional hyperintensity on DWI, and a reduction of the ADC in (i) the hippocampal formation and the pulvinar region of the thalamus (six out of 10 patients), (ii) the pulvinar and cortical regions (two out of 10), (iii) the hippocampal formation only (one out of 10), and (iv) the hippocampal formation, the pulvinar and the cortex (one out of 10). In all patients a close spatial correlation of focal hyperperfusion with areas of ADC/DWI change was present. In two patients hyperperfusion was confirmed in additional SPECT (single photon emission computed tomography) studies. All patients received follow-up MRI examinations showing partial or complete resolution of diffusion and perfusion abnormalities depending on the length of the follow-up interval. The clinical course, EEG and SPECT results all indicate that MRI detected changes related to prolonged epileptic activity. Combined PI and DWI can visualize haemodynamic and tissue changes after CPSE in the hippocampus, thalamus and affected cortical regions.

Adult↗

Hemodynamic reserve and high-intensity transient signals in moyamoya disease.

BACKGROUND: Moyamoya disease (MMD) as a rare obstructive cerebrovascular disease is assumed to present with ischemic symptoms due to hemodynamic compromise. However, alternative mechanisms, such as cerebral embolism in low-flow territories, may also contribute to clinical symptoms. The incidence of high-intensity transient signals (HITS) and the degree of hemodynamic compromise were studied in symptomatic patients with MMD. METHODS: Twenty-four patients (17 female, 7 male; mean age 33 +/- 13 years) with clinical symptoms attributable to cerebral ischemia and the angiographic features of MMD (21 definite form, 3 probable MMD; 22 patients 'late stage' MMD, 2 patients 'early stage' MMD) in 45 affected hemispheres were enrolled in the present study. Patients underwent parallel estimation of hemodynamic compromise by means of functional blood flow (rCBF) studies using SPECT, PET or xenon-CT and HITS detection by TCD. RESULTS: Hemodynamic compromise was observed in 37/40 (92%) hemispheres studied. During TCD monitoring, HITS were detected in 3 patients (12.5%), with a total frequency of 3 (6.6%) in the 45 hemispheres investigated. All patients with HITS showed hemodynamic compromise in functional rCBF studies. In these patients, HITS were recorded ipsilateral to the symptomatic hemisphere. HITS occurred in late stage MMD patients only once, while both cases with early stage MMD demonstrated multiple HITS. CONCLUSIONS: The incidence of HITS in patients with MMD appears to be lower compared to patients with atherosclerotic or atherothrombotic arterial obstructions. In addition, ischemia-related symptoms in 'late stage' MMD seem to be caused by hemodynamic compromise in the majority of these patients.

Adult↗

Differential pattern of hand-tapping compromise in vascular versus idiopathic parkinsonism: a study based on computerized movement analysis.

We tested the characteristics and the differential pattern of upper extremity motor compromise, comparing hand tapping in patients with subcortical vascular encephalopathy (SVE; n = 18), idiopathic Parkinson's disease (PD; n = 18), and in healthy controls (n = 18). Both patient groups showed significant compromise in hand tapping compared with that in controls, with higher coefficients of variability (CV) regarding tapping amplitude and angular velocity, determined using a computerized movement analysis system. A differential tapping pattern in both patient groups could be demonstrated in that patients with PD showed lower tapping amplitudes than patients with SVE. Both patient groups displayed abnormalities in tapping rhythmicity compared with that in the control group.

Brain Ischemia↗

Multiplanar transcranial ultrasound imaging: standards, landmarks and correlation with magnetic resonance imaging.

The purpose of this study was to define a standardized multiplanar approach for transcranial ultrasound (US) imaging of brain parenchyma based on matched data from 3-D US and 3-D magnetic resonance imaging (MRI). The potential and limitations of multiple insonation planes in transverse and coronal orientation were evaluated for the visualization of intracranial landmarks in 60 healthy individuals (18 to 83 years old, mean 41.4 years) with sufficient temporal bone windows. Landmarks regularly visualized even in moderate sonographic conditions with identification rates of >75% were mesencephalon, pons, third ventricle, lateral ventricles, falx, thalamus, basal ganglia, pineal gland and temporal lobe. Identification of medulla oblongata, fourth ventricle, cerebellar structures, hippocampus, insula, frontal, parietal and occipital lobes was more difficult (<75%). We hypothesize that multiplanar transcranial US images, with standardized specification of tilt angles and orientation, not only allow comparison with other neuroimaging modalities, but may also provide a more objective framework for US monitoring of cerebral disease than freehand scanning.

Adolescent↗