How to deal with incompletely treated AVMs: experience of 67 cases and review of the literature.

INTRODUCTION: Despite the availability of multimodal treatment options, some arteriovenous malformations remain difficult to treat, either for intrinsic reasons at initial presentation or for reasons evolving during the course of treatment. Frequently, such cases can be easily resolved with further therapy, but some become a continuously growing treatment dilemma while exhausting dwindling therapeutic options. PATIENTS AND METHODS: A retrospective analysis was performed to identify patients with cerebral AVM who were treated unsuccessfully. Treatment was termed "not successful" if (1) postoperative angiography showed a residual AVM or missing flow reduction after palliative embolization, (2) therapy was associated with a substantial deterioration of existing neurological deficits or death, or (3) rebleeding from residual AVM occurred after therapy. Special interest was focused on the angiographic appearance of residual AVMs, their characteristic features, and their follow-up regarding second and third therapies. RESULTS: According to these criteria we identified 46 internal patients from our own series of 474 patients and 21 external patients who were referred from other institutions or sought a second opinion after incomplete treatment elsewhere. Out of those 67 cases, 50 patients (74.6%) were diagnosed with a residual AVM. Eleven patients (16.4%) experienced a deterioration of their clinical condition under therapy. Six patients did not show a flow reduction after palliative embolization. Twenty-five of the 67 patients were readmitted because of an ICH, either originating from an AVM residual or under palliative embolization. Thus, an increased risk of re-hemorrhage was found for palliative embolization (n = 16) in partially treated lesions (n = 10) and in patients with AVM grade IV and V located in eloquent regions (n = 22). In dealing with residual AVMs, microsurgical resection alone or in combination was found to be the most efficient therapeutic option, being successful in 58.9% of cases. CONCLUSION: An estimated 10% of AVM treatments may fail because of inadequate selection of either patients or management. Besides, for thorough decision-making, angiographic follow-up in all AVM patients is mandatory to allow an early identification of patients with an incompletely treated AVM requiring a second attempt. Major attention should be focused especially on high-risk subgroups with complex AVMs, partially treated AVMs, or those treated by only a palliative regimen.

Clinical and angiographic risk factors for stroke and death within 30 days after carotid endarterectomy and stent-protected angioplasty: a subanalysis of the SPACE study.

BACKGROUND: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are used to prevent ischaemic stroke in patients with stenosis of the internal carotid artery. Better knowledge of risk factors could improve assignment of patients to these procedures and reduce overall risk. We aimed to assess the risk of stroke or death associated with CEA and CAS in patients with different risk factors. METHODS: We analysed data from 1196 patients randomised to CAS or CEA in the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE) trial. The primary outcome event was death or ipsilateral stroke (ischaemic or haemorrhagic) with symptoms that lasted more than 24 h between randomisation and 30 days after therapy. Six predefined variables were assessed as potential risk factors for this outcome: age, sex, type of qualifying event, side of intervention, degree of stenosis, and presence of high-grade contralateral stenosis or occlusion. The SPACE trial is registered at Current Controlled Trials, with the international standard randomised controlled trial number ISRCTN57874028. FINDINGS: Risk of ipsilateral stroke or death increased significantly with age in the CAS group (p=0.001) but not in the CEA group (p=0.534). Classification and regression tree analysis showed that the age that gave the greatest separation between high-risk and low-risk populations who had CAS was 68 years: the rate of primary outcome events was 2.7% (8/293) in patients who were 68 years old or younger and 10.8% (34/314) in older patients. Other variables did not differ between the CEA and CAS groups. INTERPRETATION: Of the predefined covariates, only age was significantly associated with the risk of stroke and death. The lower risk after CAS versus CEA in patients up to 68 years of age was not detectable in older patients. This finding should be interpreted with caution because of the drawbacks of post-hoc analyses.

30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority trial.

BACKGROUND: Carotid endarterectomy is effective in stroke prevention for patients with severe symptomatic carotid-artery stenosis, and carotid-artery stenting has been widely used as alternative treatment. Since equivalence or superiority has not been convincingly shown for either treatment, we aimed to compare the two. METHODS: 1200 patients with symptomatic carotid-artery stenosis were randomly assigned within 180 days of transient ischaemic attack or moderate stroke (modified Rankin scale score of < or =3) carotid-artery stenting (n=605) or carotid endarterectomy (n=595). The primary endpoint of this hospital-based study was ipsilateral ischaemic stroke or death from time of randomisation to 30 days after the procedure. The non-inferiority margin was defined as less than 2.5% on the basis of an expected event rate of 5%. Analyses were on an intention-to-treat basis. This trial is registered at Current Controlled Trials with the international standard randomised controlled trial number ISRCTN57874028. FINDINGS: 1183 patients were included in the analysis. The rate of death or ipsilateral ischaemic stroke from randomisation to 30 days after the procedure was 6.84% with carotid-artery stenting and 6.34% with carotid endarterectomy (absolute difference 0.51%, 90% CI -1.89% to 2.91%). The one-sided p value for non-inferiority is 0.09. INTERPRETATION: SPACE failed to prove non-inferiority of carotid-artery stenting compared with carotid endarterectomy for the periprocedural complication rate. The results of this trial do not justify the widespread use in the short-term of carotid-artery stenting for treatment of carotid-artery stenoses. Results at 6-24 months are awaited.

Long-term follow-up of cerebral aneurysms after endovascular therapy prediction and outcome of retreatment.

BACKGROUND AND PURPOSE: The purpose of this study was to analyze angiographic and clinical results before and after additional endovascular therapy in patients with previously coiled but reopened cerebral aneurysms and to identify possible risk factors for retreatment of an aneurysm. MATERIALS AND METHODS: Follow-up with selective digital subtraction angiography was performed in 323/596 (54.2%) patients harboring 342 aneurysms with a mean follow-up time of 28.6 months. The patients were divided into 3 groups: group A, who remained stable after initial treatment; group B, who showed minor morphologic changes; and group C, who underwent repeat treatment. Univariate and multivariate regression analyses were performed to determine possible risk factors for aneurysmal retreatment. RESULTS: Single or multiple retreatment was performed in 33 of 323 (10.2%) patients. Retreatment of small aneurysms (< or =10 mm) with small necks (< or =4 mm) was performed in 6 of 214 aneurysms. When summarizing all other aneurysms as a "risk group" (n = 128), the odds ratio (OR) for retreatment in the "risk group" was 3.11 (95% CI: 1.43-6.75; P = .004). In patients with residual aneurysm after the first treatment, OR for retreatment was 3.96 (95% CI: 1.48-10.65; P = .006), whereas a neck remnant, clinical presentation, and aneurysmal localization were not predictive. We observed no resulting morbidity and mortality from the 33 retreatment procedures. CONCLUSION: In our series, the retreatment of aneurysmal recurrences was a safe procedure. The best single predictors of aneurysmal recurrence were aneurysmal anatomy (neck width >4 mm and diameter >10 mm) and the presence of a residual aneurysm after initial treatment. A limitation in our study was the significant number of patients lost to follow-up (22.7%).

The amount of solid cerebral microemboli during carotid stenting does not relate to the frequency of silent ischemic lesions.

BACKGROUND AND PURPOSE: Carotid artery stent placement (CAS) may be associated with clinically silent cerebral lesions. We prospectively evaluated the association of the number of solid cerebral microemboli during unprotected CAS with the frequency of silent cerebral lesions as detected by diffusion-weighted MR imaging (DWI). METHODS: We performed multifrequency transcranial Doppler detection of solid microemboli in the ipsilateral middle cerebral artery (MCA) during CAS in 27 consecutive patients with symptomatic high-grade carotid stenoses. No embolus protection was used in any of the cases. DWI before and 24 +/- 2 hours after CAS was used to detect new ischemic lesions. RESULTS: We detected 484 solid microemboli in 17 patients (63%). On MR imaging 24 +/- 2 hours after CAS, 6 patients (22%) had developed 13 new clinically silent DWI lesions within the ipsilateral MCA territory. In patients with Doppler evidence of solid emboli during CAS, the incidence of new DWI lesions was higher (29%) than in patients without Doppler evidence of solid emboli during the procedure (10%); this difference was not statistically significant (P = .25). The number of solid microemboli during CAS in patients with new ipsilateral DWI lesions was not significantly different from that in patients without new ipsilateral DWI lesions. CONCLUSIONS: Solid microembolism is a common event during unprotected CAS; however, the frequency of procedure-related silent cerebral lesions appears to be independent of the number of solid cerebral microemboli during the procedure.

Disarrangement of fiber tracts and decline of neuronal density correlate in glioma patients--a combined diffusion tensor imaging and 1H-MR spectroscopy study.

BACKGROUND AND PURPOSE: Diffusion tensor imaging (DTI) and MR spectroscopy are noninvasive, quantitative tools for the preoperative assessment of gliomas with which the quantitative parameter fractional anisotropy (FA) and the concentration of neurometabolites N-acetylaspartate (NAA), choline (Cho), creatine (Cr) of the brain can be determined. Measurements of FA and NAA reflect the integrity of fiber tracts and the presence of neurons, respectively. This investigation examines changes of FA and NAA and compares these different aspects in architecture of gliomas after spatial coregistration. METHODS: DTI and chemical shift (1)H-MR spectroscopy was performed in 34 healthy volunteers and 69 patients with histologically confirmed (n = 48) or morphologically suspected (n = 21) non-necrotic brain glioma. Volumes of interest (VOIs) were placed in the tumor center (TC), the tumor border (TB), the normal-appearing white matter adjacent to the tumors (TNWM), and in the white matter of the contralateral hemisphere (NWMC). Median FA values and NAA/Cr and NAA/Cho ratios were calculated in the patients' VOIs and the gray and white matter of the volunteers. Correlations of FA values and NAA ratios were calculated. RESULTS: Continuous changes of FA and NAA from the tumor center to the periphery (the adjacent white matter and the contra-lateral hemisphere, respectively) were observed, where median values were: TC: 0.73 +/- 0.45, 0.47 +/- 0.58, 0.17 +/- 0.15 (NAA/Cr, NAA/Cho, FA); TB: 1.06 +/- 0.53, 1.00 +/- 0.15, 0.23 +/- 0.08; TNWM: 1.42 +/- 2.48, 1.21 +/- 0.95, 0.34 +/- 0.09; and NWMC: 1.63 +/- 0.72, 1.56 +/- 1.34, 0.38 +/- 0.08. Correlation of median FA values and NAA ratios in the cumulative group of patients was high (r = 0.99 [NAA/Cr], 0.95 [NAA/ Cho] at P < .01). Correlation between the individual NAA ratios and the FA values was moderate (r = 0.53 [NAA/Cr], 0.51 [NAA/Cho] at P < .01). CONCLUSION: In gliomas, the degree of tissue organization decreases continuously from the surrounding tissue toward the center of the tumor accompanied by a concordant decrease of NAA. This uniform behavior of FA and NAA reflects a decreasing integrity of both neuronal structures and fibers.

Effect of intravenous thrombolysis on MRI parameters and functional outcome in acute stroke <6 hours.

BACKGROUND AND PURPOSE: The goals of this study were to examine MRI baseline characteristics of patients with acute ischemic stroke (AIS) and to study the influence of intravenous tissue plasminogen activator (tPA) on MR parameters and functional outcome using a multicenter approach. METHODS: In this open-label, nonrandomized study of AIS patients with suspected anterior circulation stroke, subjects received a multiparametric stroke MRI protocol (diffusion- and perfusion-weighted imaging and MR angiography) within 6 hours after symptom onset and on follow-up. Patients were treated either with tPA (thrombolysis group) or conservatively (no thrombolysis group). Functional outcome was assessed on day 90 (modified Rankin Score; mRS). RESULTS: We enrolled 139 AIS patients (no thrombolysis group, n=63; thrombolysis group, n=76). Patients treated with tPA were more severely affected (National Institutes of Health Stroke Scale score, 10 versus 13; P=0.002). Recanalization rates were higher in the thrombolysis group (Thrombolysis in Myocardial Infarction criteria 1 through 3 on day 1; 66.2% versus 32.7%; P<0.001). Proximal vessel occlusions resulted in larger infarct volumes and worse outcome (P=0.02). Thrombolysis was associated with a better outcome regardless of the time point of tPA treatment (< or =3 hours or 3 to 6 hours) (univariate analysis: mRS < or =2, P=0.017; mRS < or =1, P=0.023). Age (P=0.003), thrombolytic therapy at 0 to 6 hours (P=0.01), recanalization (P=0.016), lesion volume on day 7 (P=0.001), and initial National Institutes of Health Stroke Scale score (P=0.001) affected functional outcome (mRS on day 90) positively (multivariate analysis). The time point of tPA therapy affected the recanalization rate (P=0.024) but not final infarct volume. CONCLUSIONS: In this pilot study, tPA therapy had a beneficial effect on vessel recanalization and functional outcome. Multiparametric MRI delineates tissue at risk of infarction in AIS patients, which may be helpful for the selection of patients for tPA therapy. tPA therapy appeared safe and effective beyond a 3-hour time window. This study delivers the rationale for a randomized, MR-based tPA trial.

Three-dimensional pulsatile flow simulation before and after endovascular coil embolization of a terminal cerebral aneurysm.

The effect of different percentages of coil mesh in a cerebral aneurysm on the pulsatile flow and pressure in the parent vessel and aneurysm lumen was evaluated. Geometric data on a basilar tip aneurysm and vertebrobasilar arteries after subarachnoid hemorrhage was obtained by computer tomographic angiography. Intraarterial pressure was measured at four vertebrobasilar points before and after treatment with detachable coils. Pulsatile flow was documented by transcranial ultrasonography. A three-dimensional computer simulation was created using a commercial fluid dynamics solver for four aneurysm conditions: (1) before intervention; (2) with a 20% filling showing a complete cessation of the inflow through the aneurysm neck; (3) with a 12% filling showing an incomplete deceleration of inflow through the aneurysm neck, with a remaining flow around the embedded platinum coils; and (4) with a 12% filling and simulation of clotted aneurysm dome, which did not inhibit persisting flow phenomena. The relative pressure amplitudes neither increased nor decreased under the different simulated aneurysm filling conditions. Inserted platinum coils can immediately and decisively relieve the influx of pulsating blood and allow for initial clotting. To reach this effect, a volume density of 20% platinum coil mesh in the aneurysm neck is needed.

Vascular recanalizing techniques in interventional neuroradiology.

Vascular recanalizing techniques only recently became methods of some clinical importance. Angioplasty of the subclavian artery in cases with subclavian steal syndrome has now been performed in so many instances that it can be judged safe. Angioplasty at the origin of the vertebral artery has not yet been performed in as many cases. However, even there this method is obviously less hazardous than surgery. Local intraarterial fibrinolytic therapy is the only therapy providing some success in progressive stroke from vertebrobasilar thrombosis. In contrast to the vertebrobasilar territory local fibrinolytic therapy within the carotid territory has to be strictly limited to some special indications.

Cerebellar ataxia. Clinical and CT findings in two cases of rare etiology.

Two low density lesions of the cerebellum which did not occupy space are reported. The neuropathological diagnosis of one case was subacute leucencephalitis. In the other case, the diagnosis of a Pelizaeus-Merzbacher's disease is discussed, taking into consideration the clinical observation, development and the CT findings.

[Nonaneurysmal vascular pressure lesions of the cranial nerves (author's transl)]. / Nichtaneurysmatische gefässbedingte Druckläsionen von Hirnnerven

Four cases of facial spasm and 1 case of oculomotor paresis are described. The source of the disorder in all 5 cases is mostlikely not an aneurysm of the vessels of the base of the brain. The literature is discussed and thereby it is shown that mechanical disturbances of other cranial nerves (II, V, VI, IX, XII) can be caused by similar vascular (nonaneurysmal) abnormalities.

The role of continuous-wave Doppler sonography in the diagnosis and management of basilar and vertebral artery occlusions, with special reference to its application during local fibrinolysis ("Vertebrobasilar disease. Time for a new strategy." Louis R. Caplan, 1981).

In general, the prognosis of bilateral vertebral or basilar artery occlusions is very poor. No satisfactory management of this condition is known; in addition, the early diagnosis of severe lesions of the "intradural vertebrobasilar artery" on the basis of clinical signs and symptoms alone is difficult and regularly requires invasive procedures. Continuous-wave Doppler sonography has proved to be of great value in the primary diagnosis of vertebrobasilar thrombosis. In two cases, in whom bilateral intracranial vertebral artery lesions and basilar thrombosis were successfully treated with the help of local intraarterial fibrinolysis, Doppler sonography proved to be a reliable diagnostic tool for the evaluation and the non-invasive follow-up of thrombolysis. Clinical, Doppler sonographic and angiographic findings are presented and correlated.

The role of plasma hyperviscosity in subcortical arteriosclerotic encephalopathy (Binswanger's disease).

Five haemorheological variables (haematocrit, plasma viscosity, red cell aggregation, red cell deformability and yield shear stress) and the plasma fibrinogen concentration were determined in blood samples from 21 untreated patients with subcortical arteriosclerotic encephalopathy (SAE, Binswanger's disease). The results were compared with those obtained in blood samples from 40 untreated patients with lacunar infarcts and from 275 healthy control subjects without vascular risk factors. Pathological ("solid body") flow behaviour was detected in the blood of both groups of patients (SAE and lacunar infarcts). However, highly elevated plasma viscosity was a consistent feature only of SAE. The authors present the hypothesis that the high plasma viscosity in patients with SAE may account for the progressive degeneration of cerebral white matter. It is postulated that microcirculatory abnormalities due to microrheological changes may be one of the many missing links in the pathophysiology of SAE.

Percutaneous transluminal angioplasty of the vertebral artery. A therapeutic alternative to operative reconstruction of proximal vertebral artery stenoses.

Percutaneous transluminal angioplasty (PTA) of the proximal vertebral artery was performed in 13 patients with stenosis of the proximal vertebral arteries. All of these patients had symptoms indicating vertebrobasilar insufficiency. PTA was performed only if an extreme reduction of the total diameter of both vertebral arteries was present. Only 13 patients have fulfilled the strict selection criteria in the last 3 years. All patients were monitored during the procedure by means of continuous-wave Doppler ultrasound and electrophysiological techniques. After PTA their neurological and vascular conditions were serially examined. Of the 13 patients, 8 showed marked improvement of both subjective and objective clinical symptoms. During an observation period of 2-25 months (average: 15 months) reocclusion of the angioplasty was observed in only 2 cases, without any additional neurological sequelae. Electrophysiological and Doppler sonographic monitoring during PTA helped to minimize the risk of angioplasty.

Combined neuroradiological and neurosurgical treatment of intracerebral arteriovenous malformations.

Four patients with intracerebral vascular malformations underwent preoperative butylcyanoacrylate embolization via a calibrated leak catheter, in order to reduce the risks of surgery alone. In three cases the malformation was removed without causing neurological deficits. One patient died later from recurrent bleeding.

Carotid endarterectomy: factors influencing perioperative complications.

Early carotid surgery has been suggested to be an important cause of perioperative deterioration due to secondary haemorrhage into a recent brain infarction. It has also been suggested that the existence of preoperative neurological deficits may worsen the prognosis of surgical treatment in carotid disease. Neither of these observations could be confirmed; severe perioperative complications (5%) in this study of carotid endarterectomy were strongly related to the degree of carotid stenosis. This aspect of carotid surgery has not been previously studied. Even though technical difficulties may play an exaggerated role in a training hospital system, it is nevertheless necessary to assess the impact of surgical procedures of different extent when the "acceptable risk" for carotid surgery is calculated.

The haemorheological features of lacunar strokes.

Clinical and haemorheological data were recorded in 40 patients with lacunar strokes confirmed clinically and by computed tomography. The following haemorheological variables were monitored: haematocrit, erythrocyte aggregation, erythrocyte deformability, plasma viscosity, fibrinogen concentration and yield shear stress. Clinically, most patients had case histories and features according to the description of Fisher. All haemorheological parameters with the exception of the haematocrit were pathological when compared with values obtained from a normal control group. In descending order of frequency the pathological changes were in erythrocyte aggregation, plasma viscosity and erythrocyte deformability.

Monitoring of hemispheric or brainstem functions with neurophysiologic methods during interventional neuroradiology.

Interventional neuroradiology, sometimes requiring full anesthesia, is now performed in high-risk patients. The neurologic state of an anesthetized patient cannot always be sufficiently evaluated during the neuroradiologic examination. In such cases neurophysiological methods provide information about some aspects of the patient's cerebral condition. Three useful neurophysiological methods for monitoring hemispheric or brainstem functions during the neuroradiologic procedure are on-line or Fourier-transformed electroencephalographic (EEG) analysis; the monitoring of somatosensory-evoked potentials; and the monitoring of brainstem acoustic-evoked potentials. All methods can be done in the operating room with small, mobile equipment.

Local intraarterial thrombolysis in vertebrobasilar thromboembolic disease.

The poor prognosis of basilar artery occlusion is well known. Systemic anticoagulation rarely prevents a lethal outcome. A new therapeutic approach involves selective perfusion of streptokinase through the vertebrobasilar artery via a coaxial catheter system. Three of five reported cases demonstrated successful vascular recanalization with clinical improvement.

Predicting hemodynamic ischemia by transcranial Doppler monitoring during therapeutic balloon occlusion of the internal carotid artery.

PURPOSE: Our objective was to evaluate the sensitivity of transcranial Doppler (TCD) sonographic monitoring during permanent balloon occlusion of the internal carotid artery (ICA) in predicting hemodynamic ischemia. METHODS: Thirty-two consecutive patients underwent controlled therapeutic balloon occlusion of the ICA. Selection criteria included assessment of the circle of Willis by compression angiography, clinical tolerance during a 20-minute test occlusion, and TCD monitoring of the ipsilateral middle cerebral artery. The mean blood flow velocity (MBFV) (n = 32) and pulsatility index (PI) (n = 28) were recorded. In 25 patients, MBFV changes upon motor stimulation were recorded before and after ICA occlusion. RESULTS: Twenty-eight (88%) of the patients had no complications. Three patients suffered delayed symptoms 30 minutes to 20 hours after balloon detachment. Two of these patients recovered spontaneously within 1 day, the other improved after extracranial/intracranial (EC/IC) bypass surgery. One patient, who did not tolerate the test occlusion, suffered a hemodynamic stroke despite EC/IC bypass before permanent balloon occlusion. No embolic complications occurred. The mean MBFV reduction was 20% (range, 0% to 55%); the mean PI reduction was 20% (range, 0% to 56%). No complications occurred in patients who had mild MBFV and PI reduction (30% or less, n = 21). All three patients with severe MBFV or PI reduction (> 50%) had neurologic symptoms. Among those with moderate MBFV or PI reduction (30% to 50%, n = 8), symptoms developed in only one patient who had moderate reduction of both MBFV (33%) and PI (38%). Motor vasoreactivity showed wide variation and was markedly reduced in two symptomatic patients. CONCLUSION: TCD monitoring reflects changes in cerebral hemodynamics after therapeutic balloon occlusion of the ICA. MBFV and PI reductions under 30% are highly predictive of clinical tolerance. A reduction of more than 50% may be a critical threshold for the occurrence of symptoms; in such cases, EC/IC bypass should be considered before proceeding with permanent balloon occlusion.