Endovascular stroke therapy in Austria: a nationwide 1-year experience.

BACKGROUND AND PURPOSE: Based on a tight network of stroke units (SUs) and interventional centres, endovascular treatment of acute major intracranial vessel occlusion has been widely implemented in Austria. Documentation of all patients in the nationwide SU registry has thereby become mandatory. METHODS: Demographic, clinical and interventional characteristics of patients who underwent endovascular treatment for acute ischaemic stroke in 11 Austrian interventional centres between 1 October 2013 and 30 September 2014 were analysed. RESULTS: In total, 301 patients (50.5% women; median age 70.5 years; median National Institutes of Health Stroke Scale score 17) were identified.193 patients (64.1%) additionally received intravenous thrombolysis. The most frequent vessel occlusion sites were the M1 segment of the middle cerebral artery (n = 161, 53.5%), the intracranial internal carotid artery (n = 60, 19.9%) and the basilar artery (n = 40, 13.3%). Stent retrievers were used in 235 patients (78.1%) and adequate reperfusion (modified Thrombolysis in Cerebral Infarction scores 2b and 3, median onset to reperfusion time 254 min) was achieved in 242 patients (81.4%). Symptomatic intracranial haemorrhage occurred in 7%. 43.8% of patients (n = 132) had good functional outcome (modified Rankin Scale score 0-2) and the mortality rate was 20.9% (n = 63) after 3 months. Compared to the anterior circulation, vertebrobasilar stroke patients had higher mortality. Patients with secondary hospital transportation had better outcomes after 3 months than in-house treated patients. CONCLUSION: Our results document nationwide favourable outcome and safety rates of endovascular stroke treatment comparable to recent randomized trials. The ability to provide such data and the need to further optimize such an approach also underscore the contribution of respective registries.

High cardiovascular event rates in patients with asymptomatic carotid stenosis: the REACH Registry.

BACKGROUND AND PURPOSE: Data on current cardiovascular event rates in patients with asymptomatic carotid artery stenosis (ACAS) are sparse. We compared the 1-year outcomes of patients with ACAS > or =70% versus patients without ACAS in an international, prospective cohort of outpatients with or at risk of atherothrombosis. METHODS: The Reduction of Atherothrombosis for Continued Health Registry enrolled patients with either > or =3 atherothrombotic risk factors or established atherothrombotic disease. We investigated the 1-year follow-up data of patients for whom physicians reported presence/absence of ACAS at the time of inclusion. RESULTS: Compared with patients without ACAS (n = 30 329), patients with ACAS (n = 3164) had higher age- and sex-adjusted 1-year rates of transient ischaemic attack (3.51% vs. 1.61%, P < 0.0001), non-fatal stroke (2.65% vs. 1.75%, P = 0.0009), fatal stroke (0.49% vs. 0.26%, P = 0.04), cardiovascular death (2.29% vs. 1.52%, P = 0.002), the composite end-point cardiovascular death/myocardial infarction/stroke (6.03% vs. 4.29%, P < 0.0001) and bleeding events (1.41% vs. 0.81%, P = 0.002). In patients with ACAS, Cox regression analyses identified history of cerebrovascular ischaemic events as most important predictor of future stroke (HR 3.21, 95% CI 1.82-5.65, P < 0.0001). CONCLUSION: Asymptomatic carotid artery stenosis was associated with high 1-year rates of cardiovascular and cerebrovascular ischaemic events. Stroke was powerfully predicted by prior cerebrovascular ischaemic events.

Postprocedural high-density lipoprotein cholesterol predicts carotid stent patency at 1 year.

The durability of carotid artery stenting (CAS) is affected by the occurrence of myointimal proliferation and in-stent restenosis (ISR). We aimed to identify clinical, angiographic, and laboratory predictors of ISR, paying special attention to postprocedural metabolic factors. A total of 102 consecutive patients with successful CAS for > or =70% atherosclerotic internal carotid artery stenosis were followed up with neurological assessment and duplex sonography 1 day, 1 month, and 1 year after CAS. Lipid profile and hemoglobin A(1c) were tested at the 1-month follow-up visit. Ten (10%) patients had ISR > or =50% after 1 year. Compared with patients without ISR (n = 92), patients with ISR were more often current smokers (33% vs. 70%, P = 0.034) and had significantly lower 1-month high-density lipoprotein (HDL) cholesterol: median (range) 47 (24-95) mg/dl vs. 39.5 (25-50) mg/dl, P = 0.031. Multivariate logistic regression analyses identified 1-month HDL cholesterol >45 mg/dl as the only independent predictor of carotid stent patency at 1 year (P = 0.033, OR = 0.09, 95% CI 0.01-0.83). Postprocedural HDL cholesterol levels predict carotid stent patency at 1 year. With the possibility of elevation of HDL cholesterol by lifestyle changes and medication, this finding may have implications for the future management of patients undergoing CAS.

Timing of stenting of symptomatic carotid stenosis is predictive of 30-day outcome.

For patients with symptomatic carotid stenosis, benefit from carotid artery stenting (CAS) highly depends on the 30-day stroke and death rates. Identification of predictors of unfavourable outcome would help guide the patient selection. We analysed the influence of clinical and angiographic factors on the 30-day outcomes of 77 consecutive patients who underwent CAS for > or = 60% symptomatic carotid stenosis within 180 days of transient ischaemic attack or moderate stroke (modified Rankin Scale score < or = 3). The 30-day composite end-point for stroke (7.8%) and death of any cause (1.3%) was 9.1%. Patients with complicated CAS were older than patients with uncomplicated CAS (mean age 75.1 +/- 8.2 vs. 65.9 +/- 9.5 years, P = 0.015) and underwent stenting significantly earlier after the qualifying event: median delay 1.5 weeks (range: 0.2-3.0) vs. 3.2 weeks (range: 0.5-26), P = 0.004. In multivariate logistic regression analyses, age [odds ratio (OR) = 1.148; 95% confidence interval (CI): 1.011-1.304 and P = 0.033] and delay of treatment < 2 weeks (OR = 22.399; 95% CI: 2.245-223.445 and P = 0.008) remained the only variables significantly associated with 30-day outcome. CAS carries a considerable risk in old patients and when performed early (< 2 weeks) after the qualifying event. Future reports should address the timing of CAS.

Rapid loss of microvascular integrin expression during focal brain ischemia reflects neuron injury.

The integrity of cerebral microvessels requires the close apposition of the endothelium to the astrocyte endfeet. Integrins alpha1beta1 and alpha6beta4 are cellular matrix receptors that may contribute to cerebral microvascular integrity. It has been hypothesized that focal ischemia alters integrin expression in a characteristic time-dependent manner consistent with neuron injury. The effects of middle cerebral artery occlusion (MCAO) and various periods of reperfusion on microvasclar integrin alpha1beta1 and alpha6beta4 expression were examined in the basal ganglia of 17 primates. Integrin subunits alpha1 and beta1 colocalized with the endothelial cell antigen CD31 in nonischemic microvessels and with glial fibrillary acidic protein on astrocyte fibers. Rapid, simultaneous, and significant disappearance of both integrin alpha1 and beta1 subunits and integrin alpha6beta4 occurred by 2 hours MCAO, which was greatest in the region of neuron injury (ischemic core, Ic), and progressively less in the peripheral (Ip) and nonischemic regions (N). Transcription of subunit beta1 mRNA on microvessels increased significantly in the Ic/Ip border and in multiple circular subregions within Ic. Microvascular integrin alpha1beta1 and integrin alpha6beta4 expression are rapidly and coordinately lost in Ic after MCAO. With loss of integrin alpha1beta1, multiple regions of microvascular beta1 mRNA up-regulation within Ic suggest that microvessel responses to focal ischemia are dynamic, and that multiple cores, not a single core, are generated. These changes imply that microvascular integrity is modified in a heterogeneous, but ordered pattern.

Time course of cerebral blood flow velocity in central nervous system infections. A transcranial Doppler sonography study.

In a 3-year period, 110 patients with central nervous system infections of various causes were examined serially by means of transcranial Doppler sonography. In viral-induced infections, no changes of flow velocity in basal cerebral arteries were seen, whereas in bacterial meningitis, a significant increase of blood flow velocity in the middle cerebral artery was recorded. Its extent was mainly associated with the type of the infectious agent, most frequently observed in pneumococcal meningitis (77%). The increase was up to 100% of the baseline values and was reversible in all cases. All patients were offered full-scale neurointensive care, and all subjects with bacterial meningitis were fully heparinized.

Isolated pontine lesion in algid cerebral malaria: clinical features, management, and magnetic resonance imaging findings.

Malaria, the most important of all tropical diseases, causes approximately one million deaths per year. In Plasmodium falciparum malaria, the organs most affected are the brain, kidneys, lungs, and liver. Cerebral involvement is the most important lethal complication with a mortality rate of up to 50%. We report a patient with malignant, tertian falciparum malaria with an initial parasitemia rate of 60% and severe cerebral, hepatorenal, and pulmonary involvement. In addition to the severe diffuse encephalopathy, an initial neurologic examination showed signs of a pontine lesion that was confirmed by cerebral magnetic resonance imaging. We therefore conclude that cerebral malaria may be responsible for focal neurologic lesions that can be demonstrated by this procedure.

Impaired microcirculation and tissue oxygenation in human cerebral malaria: a single photon emission computed tomography and near-infrared spectroscopy study.

Serial single photon emission computed tomography (SPECT), near-infrared spectroscopy (NIRS), and transcranial doppler (TCD) sonography examinations were performed to investigate changes of cerebral perfusion and tissue oxygenation in a patient with complicated cerebral malaria that have been acquired in Nigeria. On admission to the Neurologic Intensive Care Unit in Innsbruck, Austria, SPECT and NIRS revealed focal right hemispheric hypoperfusion and decreased oxygen saturation, respectively, correlating exactly to the patient's right hemispheric localizing signs. In contrast, TCD examinations of the basal cerebral vessels revealed normal flow patterns. The patient showed an initial Plasmodium falciparum parasitemia rate of 30% and was cured by intravenous quinine and oral mefloquine therapy. He was discharged without neurologic symptoms. Follow-up SPECT and NIRS examinations revealed regular cerebral perfusion and oxygenation patterns in both cortical hemispheres. In summary, the presented findings provide first evidence that noninvasive SPECT and NIRS may be important diagnostic tools in the evaluation of impaired cerebral microcirculation in patients with P. falciparum malaria.

Rehabilitation approaches to stroke.

This article describes the state of the science in stroke rehabilitation dealing with three main topics: (1) General approach to stroke rehabilitation (stroke services and stroke units), (2) Neurophysiological and pharmacological interventions (facilitation of brain repair mechanisms) and (3) Experimental approaches (neuronal transplantation). Stroke rehabilitation is an active process beginning during acute hospitalisation, progressing to a systematic program of rehabilitation services and continuing after the individual returns to the community. There is world-wide consensus that stroke patients should be treated at specialised stroke unit with specially trained medical and nursing staff, co-ordinated multidisciplinary rehabilitation and education programs for patients and their families. Stroke Unit has been shown to be associated with a long-term reduction of death and of the combined poor outcomes of death and dependency, independent of patients age, sex, or variations in stroke unit organisations. No study has clearly shown to what extent the beneficial effect is due to specific rehabilitation strategies. New imaging studies in stroke patients indicate altered post stroke activation patterns, which suggest some functional reorganisation. Reorganisation may be the principle process responsible for recovery after stroke. It is assumed that different post ischaemic interventions like physiotherapy, occupational therapy, speech therapy, electrical stimulation, etc. facilitates such changes. Scientific evidence demonstrating the values of specific rehabilitation interventions after stroke is limited. Comparisons between different methods in current use have so far mostly failed to show that any particular physiotherapy, occupational therapy, speech therapy or stroke rehabilitation strategy is superior to another. Clinical data are strongly in favour of early mobilisation and training. Pharmacological interventions in animals revealed that norepinephrine, amphetamine and other alpha-adrenergic stimulating drugs can enhance motor performance after unilateral ablation of the sensory motor cortex. The clinical data in humans are rather contradictory. Neural grafting and neurogenesis are new potential modes of stroke therapy. Neural grafting enhanced functional outcome and reduced thalamic atrophy in rats only when combined with housing in enriched environments. Recent studies have shown that stem cells can differentiate to neurons in the adult human dentate gyrus in vivo.

The persistent vegetative state after closed head injury: clinical and magnetic resonance imaging findings in 42 patients.

OBJECT: In this retrospective study, the authors analyzed the frequency, anatomical distribution, and appearance of traumatic brain lesions in 42 patients in a posttraumatic persistent vegetative state. METHODS: Cerebral magnetic resonance (MR) imaging was used to detect the number of lesions, which ranged from as few as five to as many as 19, with a mean of 11 lesions. In all 42 cases there was evidence on MR imaging of diffuse axonal injury, and injury to the corpus callosum was detected in all patients. The second most common area of diffuse axonal injury involved the dorsolateral aspect of the rostral brainstem (74% of patients). In addition, 65% of these patients exhibited white matter injury in the corona radiata and the frontal and temporal lobes. Lesions to the basal ganglia or thalamus were seen in 52% and 40% of patients, respectively. Magnetic resonance imaging showed some evidence of cortical contusion in 48% of patients in this study; the frontal and temporal lobes were most frequently involved. Injury to the parahippocampal gyrus was detected in 45% of patients; in this subgroup there was an 80% incidence of contralateral peduncular lesions in the midbrain. The most common pattern of injury (74% in this series) was the combination of focal lesions of the corpus callosum and the dorsolateral brainstem. In patients with no evidence of diffuse axonal injury in the upper brainstem (26% in this series), callosal lesions were most often associated with basal ganglia lesions. Lesions of the corona radiata and lobar white matter were equally distributed in patients with or without dorsolateral brainstem injury. Moreover, cortical contusions and thalamic, parahippocampal, and cerebral peduncular lesions were also similarly distributed in both groups. CONCLUSIONS: The data indicate that diffuse axonal injury may be the major form of primary brain damage in the posttraumatic persistent vegetative state. In addition, the authors demonstrated in this study that MR imaging, in conjunction with a precise clinical correlation, may provide useful supportive information for the accurate diagnosis of a persistent vegetative state after traumatic brain injury.

Hemodynamic findings in migraine patients on transcranial Doppler sonography.

Forty migraine patients were examined by means of 3D-transcranial Doppler scanning (TCD). The complete circle of Willis was investigated in all patients during headache-free intervals. TCD investigations were repeated in 10 patients during a migraine attack, in one patient twice. Based on the diagnostic criteria of the "headache classification committee of the international headache society" 23 patients were assigned to a "migraine without aura" group and 17 to a "migraine with aura" group. Twenty age-matched volunteers, not suffering from headache or any vascular disease, served as a control group. No significant differences were detected between the hemodynamic data of the control group and the migraine groups both with respect to the headache-free interval and the attack. No hemodynamic changes in keeping with the pathophysiologic hypothesis of vasospasm were found in the proximal segments of the basal cerebral arteries.

[Course and management of tetanus]. / Verlauf und Management des Tetanus.

Within a span of 18 months 4 patients (2 men, 2 women) were admitted with generalized tetanus to our neurological intensive care unit. The "period of onset" ranged from 2 to 14 days. All patients needed artificial ventilation over 17 to 38 days. The clinical course was complicated by gram-negative pneumonia in 3 of the 4 patients. Time of hospitalization ranged between 35 and 60 days. One patient had never been immunized against tetanus. The other 3 had not received a booster dose for over 10 years. All 4 patients survived, 3 of them without sequelae.

[Cerebral and spinal nocardia infection. A case report]. / Zerebrale und spinale Nokardieninfektion. Ein Fallbericht.

We report a case of multiple cerebral and spinal abscesses due to Nocardia asteroides in a non-immunocompromised patient. The initial central nervous system manifestation was a sterile meningitis, with secondary development of multiple cerebral and spinal abscesses. Since the location of the abscesses did not allow neurosurgical exploration and the cultures remained negative, the diagnosis was finally established by raised antibody titres to Nocardia asteroides. After specific antibiotic therapy, resolution of the spinal and cerebral abscesses was documented on the basis of serial magnetic resonance tomography and computed tomography controls.

Continuous positive airway pressure breathing increases cerebral blood flow velocity in humans.

The effect of a continuous positive airway pressure (CPAP) of 12 cm H2O on mean middle cerebral artery flow velocity (CBFV) was studied in nine human volunteers by means of transcranial Doppler sonography (TCD). During CPAP breathing, CBFV increased (45 +/- 9 vs 59 +/- 11 cm/s; P < 0.001; mean +/- SD), and pulsatility index (PI) decreased (0.87 +/- 0.1 vs 0.74 +/- 0.2; P < 0.05), indicating an increase in cerebral blood flow due to cerebral vasodilation. This phenomenon should be taken into account when CPAP is applied to patients with intracranial disease or when assessing CBFV patterns of patients during CPAP respiration.

E-selectin appears in nonischemic tissue during experimental focal cerebral ischemia.

BACKGROUND AND PURPOSE: E-selectin participates in leukocyte-endothelial adhesion and the inflammatory processes that follow focal cerebral ischemia and reperfusion. The temporal and topographical patterns of microvascular E-selectin presentation after experimental focal cerebral ischemia are relevant to microvascular reactivity to ischemia. METHODS: The upregulation and fate of E-selectin antigen during 2 hours of middle cerebral artery occlusion (n = 4) and 3 hours of occlusion with reperfusion (1 hour, n = 4; 4 hours, n = 6; 24 hours, n = 6) were evaluated in the nonhuman primate. E-selectin and E:P-selectin immunoreactivities were semiquantitated with the use of computerized light microscopy video imaging and laser confocal microscopy. RESULTS: Three patterns of microvascular E-selectin expression, defined by the antibody E-1E4, were confirmed by complete elimination of E-1E4 binding after incubation with soluble recombinant human E-selectin: (1) Low immunoperoxidase intensity was observed in ischemic microvessels at 2 hours of occlusion extending to 4 hours of reperfusion (E-selectin/laminin = 0.32 +/- 0.10). (2) A significant fraction of ischemic microvessels displayed high-intensity E-selectin signal by 24 hours of reperfusion (0.61 +/- 0.17) compared with control and nonischemic tissues (2P < .003). (3) In the contralateral nonischemic basal ganglia and other nonischemic tissues, low but significant E-selectin levels appeared by 24 hours of reperfusion (2P = .0005). The latter were further confirmed by an E:P-selectin immunoprobe. CONCLUSIONS: E-selectin antigen is distinctively and significantly upregulated in nonhuman primate brain after focal ischemia and reperfusion. The late appearance of E-selectin in nonischemic cerebral tissues suggests stimulation by transferable factors generated during brain injury.

Cerebrospinal fluid (CSF) pharmacokinetics of intraventricular vancomycin in patients with staphylococcal ventriculitis associated with external CSF drainage.

We studied the efficacy and pharmacokinetics of intraventricularly administered vancomycin in three patients with shunt-associated staphylococcal ventriculitis. We instilled 10 mg of the drug intraventricularly every 24 hours. Cerebrospinal fluid (CSF) levels were measured 1 hour after instillation and then every 2 hours. Peak vancomycin levels reached a mean of 292.9 microg/mL. The mean trough levels, measured immediately before readministration of vancomycin, were 7.6 microg/mL; this level has proved to be sufficient for maintaining the necessary steady-state serum concentration of vancomycin. All three patients were cured clinically and bacteriologically, and CSF parameters returned to normal within 5-13 days. No side effects were observed. Our results suggest that intraventricularly administered vancomycin is a valuable therapeutic strategy for treating shunt-associated staphylococcal ventriculitis. In addition, we provide evidence that 10 mg of vancomycin, administered intraventricularly every 24 hours, allows maintenance of therapeutic drug levels in the CSF for at least 24 hours.