Klaus Gröschel

Early Outcome of Carotid Angioplasty and Stenting With and Without Cerebral Protection Devices. A Systematic Review of the Literature

Background— Carotid angioplasty and stenting (CAS) is increasingly being used for treatment of symptomatic and asymptomatic carotid artery disease (CAD). To evaluate the efficacy of cerebral protection devices in preventing thromboembolic complications during CAS, we conducted a systematic review of studies reporting on the incidence of minor stroke, major stroke, or death within 30 days after CAS. Summary of Review— We searched for studies published between January 1990 and June 2002 by means of a PubMed search and a cumulative review of reference lists of all relevant publications. In 2357 patients a total of 2537 CAS procedures had been performed without protection devices, and in 839 patients 896 CAS procedures had been performed with protection devices. Both groups were similar with respect to age, sex distribution, cerebrovascular risk factors, and indications for CAS. In many studies the periprocedural complication rates had not been presented separately for patients with symptomatic and asymptomatic CAD. The combined stroke and death rate within 30 days in both symptomatic and asymptomatic patients was 1.8% in patients treated with cerebral protection devices compared with 5.5% in patients treated without cerebral protection devices (&khgr;2=19.7, P <0.001). This effect was mainly due to a decrease in the occurrence of minor strokes (3.7% without cerebral protection versus 0.5% with cerebral protection; &khgr;2=22.4, P <0.001) and major strokes (1.1% without cerebral protection versus 0.3% with cerebral protection; &khgr;2=4.3, P <0.05), whereas death rates were almost identical (≈0.8%; &khgr;2=0.3, P =0.6). Conclusions— On the basis of this early analysis of single-center studies, the use of cerebral protection devices appears to reduce thromboembolic complications during CAS. These technical aspects should be taken into account before the initiation of further randomized trials comparing CAS with carotid endarterectomy.

New Brain Lesions After Carotid Stenting Versus Carotid Endarterectomy A Systematic Review of the Literature

Background and Purpose— Against the background of a relatively low rate of clinical events during carotid angioplasty and stenting (CAS) or carotid endarterectomy (CEA), diffusion-weighted imaging (DWI) is increasingly being used to compare the incidence of new ischemic lesions after both procedures. In addition, DWI may also provide a means of defining the role of different CAS techniques on this adverse outcome. Therefore, we performed a PubMed search and systematically analyzed all peer-reviewed studies published between January 1990 and June 2007 reporting on the occurrence of new DWI lesions after CAS or CEA. Summary of Review— In 32 studies comprising 1363 CAS and 754 CEA procedures, the incidence of any new DWI lesion was significantly higher after CAS (37%) than after CEA (10%) (P<0.01). Similar results were obtained in a meta-analysis focusing on those studies directly comparing the incidence of new DWI lesions after either CEA or CAS (OR, 6.1; 95% CI, 4.19 to 8.87; P<0.01). The use of cerebral protection devices (33% vs 45% without; P<0.01) and closed-cell designed stents during CAS (31% vs 51% with open-cell stents; P<0.01), as well as selective versus routine shunt usage during CEA (6% vs 16%; P<0.01) significantly reduced the incidence of new ipsilateral DWI lesions. Conclusions— New DWI lesions occur more frequently after CAS than after CEA. However, technical advances mainly in the field of endovascular therapy potentially reduce the incidence of these adverse ischemic events. In this scenario, DWI appears to be an ideal tool to compare and further improve both techniques.

Enhanced Detection of Paroxysmal Atrial Fibrillation by Early and Prolonged Continuous Holter Monitoring in Patients With Cerebral Ischemia Presenting in Sinus Rhythm

Background and Purpose Diagnosis of paroxysmal atrial fibrillation is difficult but highly relevant in patients presenting with cerebral ischemia yet free from atrial fibrillation on admission. Early initiation and prolongation of continuous Holter monitoring may improve diagnostic yield compared with the standard of care including a 24-hour Holter recording. Methods— In the observational Find-AF trial (ISRCTN 46104198), consecutive patients presenting with symptoms of cerebral ischemia were included. Patients free from atrial fibrillation at presentation received 7-day Holter monitoring. Results— Two hundred eighty-one patients were prospectively included. Forty-four (15.7%) had atrial fibrillation documented by routine electrocardiogram on admission. All remaining patients received Holter monitors at a median of 5.5 hours after presentation. In those 224 patients who received Holter monitors but had no previously known paroxysmal atrial fibrillation, the detection rate with early and prolonged (7 days) Holter monitoring (12.5%) was significantly higher than for any 24-hour (mean of 7 intervals: 4.8%, P=0.015) or any 48-hour monitoring interval (mean of 6 intervals: 6.4%, P=0.023). Of those 28 patients with new atrial fibrillation on Holter monitoring, 15 (6.7%) had been discharged without therapeutic anticoagulation after routine clinical care (ie, with data from 24-hour Holter monitoring only). Detection rates were 43.8% or 6.3% for short supraventricular runs of ≥10 beats or prolonged episodes (<5 hours) of atrial fibrillation, respectively. Diagnostic yield appeared to be only slightly and not significantly increased during the first 3 days after the index event. Conclusions— Prolongation of Holter monitoring in patients with symptoms of cerebral ischemic events increases the rate of detection of paroxysmal atrial fibrillation up to Day 7, leading to a relevant change in therapy in a substantial number of patients. Early initiation of monitoring does not appear to be crucial. Hence, prolonged Holter monitoring (≥7 days) should be considered for all patients with unexplained cerebral ischemia.

Systematic Review of Early Recurrent Stenosis After Carotid Angioplasty and Stenting

Background and Purpose— Carotid angioplasty and stenting (CAS) has emerged as a potential alternative to endarterectomy (CEA) for the treatment of carotid artery disease. Aside from the periprocedural complication rates, the benefits of CAS will be affected by the incidence of recurrent carotid stenosis. Methods— We conducted a systematic analysis of all peer-reviewed studies reporting on the rate of restenosis (≥50%) after CAS based on duplex ultrasound or angiography that were published between January 1990 and July 2004. We identified 34 studies that reported on a total of 4185 patients with a follow-up of 3814 arteries over a median of 13 months (range, 6 to 31 months). The ultrasound criteria and the lower thresholds for defining a recurrent stenosis were very heterogeneous. Results— The cumulative restenosis rates after 1 and 2 years were ≈6% and 7.5% in those studies, which used a lower restenosis threshold ≥50% to 70% and ≈4% in the first 2 years after CAS in those studies, which used a lower restenosis threshold >70% to 80%. Conclusions— In reviewing the current literature, the early restenosis rates after CAS compare well with those reported for CEA. However, this analysis of the peer-reviewed literature also indicates that the early restenosis rates after CAS might be higher than previously suggested in observational surveys. Therefore, an active follow-up of all stented arteries seems to be warranted. Moreover, the bulk of endovascular data are derived from small studies with short follow-up periods so that the long-term durability of CAS still needs to be established in large trials. Ideally, these studies should use a clear and uniform definition of restenosis and identical follow-up schedules.

A Systematic Review on Outcome After Stenting for Intracranial Atherosclerosis

BACKGROUND AND PURPOSE Angioplasty and stenting is increasingly being used for the treatment of intracranial stenoses. Based on a literature search (01/1998 to 04/2008) we sought to determine the immediate and long-term outcomes, as well as the durability of this procedure. SUMMARY OF REVIEW We identified 31 studies dealing with 1177 procedures, which had mainly been performed in patients with a symptomatic (98%) intracranial high-grade stenosis (mean: 78+/-7%) at high technical success rates (median: 96%; interquartile range [IQR]: 90% to 100%). The periprocedural minor or major stroke and death rates ranged from 0% to 50% with a median of 7.7% (IQR: 4.4% to 14.3%). Periprocedural complications were significantly higher in the posterior versus the anterior circulation (12.1%, versus 6.6%, P<0.01, odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.21 to 3.10), but did not differ between patients treated with a balloon-mounted (n=906) versus those who had been treated with a self-expandable stent (n=271; 9.5% versus 7.7%, P=0.47, OR: 1.15, CI:0.76 to 2.05). Restenosis >50% occurred more frequently after the use of a self-expandable stent (16/92; 17.4%, mean follow-up time: 5.4 months) than a balloon-mounted stent (61/443; 13.8%, mean follow-up time: 8.7 months; P<0.001, log-rank test). CONCLUSIONS Although intracranial stenting appears to be feasible, adverse events vary widely. Against the background of the results of this review yielding a high rate of restenoses and no clear impact of new stent devices on outcome, the widespread application of intracranial stenting outside the setting of randomized trials and in inexperienced centers currently does not seem to be justified.

Incidence of New Brain Lesions After Carotid Stenting With and Without Cerebral Protection

Background and Purpose— Diffusion-weighted imaging (DWI) may be a useful tool to evaluate the efficacy of cerebral protection devices in preventing thromboembolic complications during carotid angioplasty and stenting (CAS). The goals of this study were (1) to compare the frequency, number, and size of new DWI lesions after unprotected and protected CAS; and (2) to determine the clinical significance of these lesions. Methods— DWI was performed immediately before and within 48 hours after unprotected or protected CAS. Clinical outcome measures were stroke and death within 30 days. Results— The proportion of patients with any new ipsilateral DWI lesion (49% versus 67%; P<0.05) as well as the number of new ipsilateral DWI lesions (median=0; interquartile range [IQR]=0 to 3 versus median=1; IQR=0 to 4; P<0.05) were significantly lower after protected (n=139) than unprotected (n=67) CAS. The great majority of these lesions were asymptomatic and less than 10 mm in diameter. Although there were no significant differences in clinical outcome between patients treated and not treated with protection devices (7.5% versus 4.3%, not significant), the number of new DWI lesions was significantly higher in patients who developed a stroke (median=7.5; IQR=1.5 to 17) than in patients who did not (median=0; IQR=1 to 3.25; P<0.01). Conclusions— The use of cerebral protection devices significantly reduces the incidence of new DWI lesions after CAS of which the majority are asymptomatic and less than 10 mm in diameter. The frequent occurrence of these lesions and their close correlation with the clinical outcome indicates that DWI could become a sensitive surrogate end point in future randomized trials of unprotected versus protected CAS.

Functional significance of age-related differences in motor activation patterns

Recent functional MRI (fMRI) studies have revealed an increased task-related activation in older subjects during a variety of cognitive or perceptual tasks, which may signal beneficial compensatory activity to counteract structural and neurochemical changes associated with aging. Under the assumption that incremental movement rates are associated with an increased functional demand on the motor system, we used fMRI and acoustically paced movements of the right index finger at six different frequencies (2.0, 2.5, 3.0, 4.0, 5.0 and 6.0 Hz) to investigate the behavioral significance of additionally recruited brain regions in a group of healthy, older subjects (mean age 66 +/- 8 years) compared with a group of young (mean age 23 +/- 7 years) subjects. The actual tapping frequency (F(1,14) = 0.049, P = 0.829), the tapping interval (F(1,14) = 0.043, P = 0.847), and the error rates (F(1,14) = 0.058, P = 0.743) did not differ significantly between both groups, whereas there was a significant increase in reaction time in the older subjects (F(1,14) = 281.786, P < or = 0.001). At all frequencies, the older subjects demonstrated significant overactivation within the ipsilateral sensorimotor and premotor cortex. However, we did not observe an increased age-related overactivation during higher movements rates in these or other motor regions. Moreover, the magnitude of the hemodynamic response in overactivated regions remained constant across all frequencies. In contrast to cognitive tasks, these findings indicate that an age-related overactivation within the motor system is not related to the functional demand and does not necessarily reflect reorganization to compensate for the neurobiological changes of aging.

Magnetic resonance imaging-based volumetry differentiates progressive supranuclear palsy from corticobasal degeneration

Because there are no biological markers for the clinical diagnosis of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), we established a mathematical model based on three-dimensional magnetic resonance (MR) imaging to differentiate between these parkinsonian disorders. Using MR imaging-based volumetry we studied the pattern of atrophic changes in patients with probable, possible or definite PSP (n = 33) or CBD (n = 18). Patients were compared with 22 controls with similar age. To establish a mathematical model that would allow for differentiation of PSP, CBD and controls we performed a discriminant analysis. We found a significant reduction in average brain, brainstem, midbrain and frontal gray matter volumes in patients with PSP, whereas patients with CBD showed atrophy of parietal cortex and corpus callosum. With the exception of reduced midbrain volumes in PSP, the measured volumes of anatomical structures showed an extensive overlap with the normal range on an individual basis. Using only post mortem confirmed cases of PSP (n = 8) and CBD (n = 7) as well as all controls, the volumes of midbrain, parietal white matter, temporal gray matter, brainstem, frontal white matter and pons were identified to separate best between groups and were used to construct a model with two canonical variables. This model allowed to correctly predict the diagnosis in 95% of controls as well as in 76% of all PSP and 83% of all CBD patients. Similar results were obtained only when patients with a possible and probable diagnosis of PSP and CBD, who were not involved in the development of the discriminant analysis, were classified. 3D-MR imaging-based volumetry may help to differentiate PSP from CBD ante mortem.

Mechanical recanalization in basilar artery occlusion: The ENDOSTROKE study

A study was undertaken to evaluate clinical and procedural factors associated with outcome and recanalization in endovascular stroke treatment (EVT) of basilar artery (BA) occlusion.

The cerebral control of speech tempo: opposite relationship between speaking rate and BOLD signal changes at striatal and cerebellar structures.

So far, only sparse data on the cerebral organization of speech motor control are available. In order to further delineate the neural basis of articulatory functions, fMRI measurements were performed during self-paced syllable repetitions at six different frequencies (2-6 Hz). Bilateral hemodynamic main effects, calculated across all syllable rates considered, emerged within sensorimotor cortex, putamen, thalamus and cerebellum. At the level of the caudatum and the anterior insula, activation was found restricted to the left side. The computation of rate-to-response functions of the BOLD signal revealed a negative linear relationship between syllable frequency and response magnitude within the striatum whereas cortical areas and cerebellar hemispheres exhibited an opposite activation pattern. Dysarthric patients with basal ganglia disorders show unimpaired or even accelerated speaking rate whereas, in contrast, cerebellar dysfunctions give rise to slowed speech tempo which does not fall below a rate of about 3 Hz. The observed rate-to-response profiles of the BOLD signal thus might help to elucidate the pathophysiological mechanisms of dysarthric deficits in central motor disorders.