The ARUBA trial: current status, future hopes.

BACKGROUND AND PURPOSE: Report on the status of an on-going National Institutes of Neurological Disorders and Stroke (NINDS)-supported clinical trial of management of unbled brain arteriovenous malformations. SUMMARY OF REVIEW: Begun in April 2007 with 3 centers, the trial has grown to 65 centers, and has randomized 124 patients through mid-June 2010 en route to the planned 400. The current literature continues to support the rationale for the trial. CONCLUSIONS: ARUBA is steadily approaching its monthly randomization goals and has already reached the number needed to test the maximum published interventional complication rates against the minimum hemorrhage rates for natural history.

Multimodal early rehabilitation and predictors of outcome in survivors of severe traumatic brain injury.

BACKGROUND: To determine the effect of brain lesion pattern on early recovery after severe traumatic brain injury (TBI). METHODS: In a setting of a multimodal early rehabilitation unit at a level I trauma center, 135 consecutive survivors of severe TBI (mean age, 40 years, 25% women) were studied prospectively. Assessment of disability was performed weekly using an extended Barthel Index (eBI) ranging from -325 to +100 points. Clinical and brain morphologic variables were tested in multivariate logistic regression models to determine predictors of outcome. RESULTS: Imaging revealed cerebral contusion in 115 patients (85%) affecting the frontal (n = 80), temporal (n = 62), parieto-occipital (n = 17), brain stem (n = 13), and cerebellar (n = 5) regions. In addition, 80 patients (59%) showed diffuse brain edema, 75 (55%) subarachnoid, 37 (28%) subdural, and 18 (13%) epidural hemorrhage. After a mean stay of 72 +/- 51 days in the early rehabilitation unit, one patient died, 40 (30%) revealed good outcome (median eBI, +55), and a further 43 patients (32%) showed excellent outcomes (eBI, 90-100). Temporal (odds ratio 2.6; 95% confidence interval 1.1-6.5) and brain stem contusions (odds ratio 13.8; 95% confidence interval 3.0-64.1) were independent predictors of poor outcome. CONCLUSIONS: Temporal and brain stem contusions constitute independent risk factors for poor outcome in survivors of severe TBI. The results further suggest a high potential for multimodal early rehabilitation after severe TBI.

Recovery of visual field defects: a large clinical observational study using vision restoration therapy.

PURPOSE: In small experimental trials, vision restoration therapy (VRT), a home-based rehabilitation method, has shown to enlarge the visual field and improve reaction times in patients with lesion involving the CNS. We now evaluated the outcome of VRT in a large sample of clinical patients and studied factors contributing to subjective and objective measures of visual field alterations. METHODS: Clinical observational analysis of visual fields of 302 patients before and after being treated with computer-based vision restoration therapy for a period of 6 months at eight clinical centers in central Europe. The visual field defects were due to ischemia, hemorrhage, head trauma, tumor removal or anterior ischemic optic neuropathy. Primary outcome measure was a visual field assessment with super-threshold perimetry. Additionally, conventional near-threshold perimetry, eye movements and subjective reports of daily life activities were assessed in a subset of the patients. RESULTS: VRT improved patients' ability to detect super-threshold stimuli in the previously deficient area of the visual field by 17.2% and these detection gains were not significantly correlated with eye movements. Notable improvements were seen in 70.9% of the patients. Efficacy was independent of lesion age and etiology, but patients with larger areas of residual vision at baseline and patients>65 years old benefited most. Conventional perimetry validated visual field enlargements and patient testimonials confirmed the improvement in every day visual functions. CONCLUSIONS: VRT improves visual functions in a large clinical sample of patients with visual field defects involving the CNS, confirming former experimental studies.

Clinical outcome after first and recurrent hemorrhage in patients with untreated brain arteriovenous malformation.

BACKGROUND AND PURPOSE: The morbidity from spontaneous hemorrhage of untreated brain arteriovenous malformations (AVM) is not well described. METHODS: The 241 consecutive AVM patients (mean age 37+/-16 years, 52% women) from the prospective Columbia AVM Databank initially presenting with hemorrhage were evaluated using the Rankin Scale (RS) and the National Institute of Health Stroke Scale (NIHSS). From the 241 AVM patients, 29 (12%) had subsequent intracranial hemorrhage during follow-up. For further comparisons, 84 non-AVM patients with intracerebral hemorrhage from the Northern Manhattan Study (NOMAS) served as a control group. RESULTS: In 241 AVM patients presenting with hemorrhage the median RS was 2 and the median NIHSS was 1 (49% RS 0 to 1, 61% NIHSS <2). The median time between hemorrhage and clinical evaluation was 11 days (mean 219 days). Recurrent AVM hemorrhage during follow-up resulted in no significant increase in morbidity (median RS 2, P=0.004; median NIHSS 3, P=0.322; time between hemorrhage and study evaluation: median 55 days, mean 657 days). Among AVM-hemorrhage subtypes, parenchymatous AVM hemorrhage was associated with higher stroke morbidity (odds ratio, 2.9; 95% CI, 1.5 to 5.8 for NIHSS > or =2) than nonparenchymatous hemorrhages. Parenchymatous AVM hemorrhage had a significantly better outcome (median NIHSS 1) than non-AVM related hemorrhage (median NIHSS 12; P<0.0001). CONCLUSIONS: Hemorrhage, either at initial presentation or during follow-up of untreated AVM patients appears to carry a lower morbidity than intracranial hemorrhage from other causes. These findings support a careful weighing of risks from interventional treatment and natural history.

Endovascular recanalization therapy in acute ischemic stroke.

BACKGROUND AND PURPOSE: To assess the outcome in acute ischemic stroke patients not eligible for systemic thrombolysis (outside the 3-hour time window, after surgery, or on anticoagulant) undergoing endovascular recanalization therapy (ERT) at the Columbia University Medical Center (CUMC) and to determine US nationwide usage and outcome of ERT in acute ischemic stroke. METHODS: Patients treated at CUMC from 2001 to 2004 and the Nationwide Inpatient Sample (NIS) comprising 20% of all admissions in the United States from 1999 to 2002 were analyzed retrospectively. RESULTS: Thirty-one patients underwent ERT. Mean age was 68+/-14 years, 68% were female, and 45% nonwhite (occlusion sites: internal carotid artery 29%; middle cerebral artery 39%; posterior circulation 32%). Pharmacological or mechanical ERT was initiated beyond 3 hours after symptom onset (median time 4.4 hours) in 61%, 29% had surgery, and 39% were on anticoagulant medication. At discharge, 32% had modified Rankin Scale scores of 0 to 2 (52% discharged home or to rehabilitation facilities); overall mortality was 29%, of which 19% were fatal intracerebral hemorrhages. From the NIS cohort, 477 patients (0.17% of all strokes and 14% of all thrombolysis cases) underwent ERT. Fifteen percent died, and approximately 50% were discharged home or to rehabilitation facilities. Intracerebral hemorrhage occurred in 6%. Fewer good outcomes of the CUMC cohort may be explained by more unfavorable premorbid patient characteristics compared with the NIS cohort. CONCLUSIONS: Despite significant variability in patient characteristics and treatment methods among 2 sources of data analyzed, ERT in stroke patients not eligible for intravenous thrombolysis appears to be a relatively safe and effective treatment alternative that is being used increasingly nationwide.

Determinants of staged endovascular and surgical treatment outcome of brain arteriovenous malformations.

BACKGROUND AND PURPOSE: Therapy of brain arteriovenous malformations (AVMs) often requires the combination of different treatment modalities. Independently assessed data on neurologic outcome after multidisciplinary AVM therapy are scarce. METHODS: The 119 consecutive patients (49% women, mean age 34+/-13 years) with brain AVMs receiving endovascular embolization followed by surgical treatment were analyzed. Neurologic impairment was assessed prospectively by a neurologist using the modified Rankin Scale (mRS) before, during, and after completed AVM therapy. The association of demographic, clinical, and morphologic characteristics with new treatment-related neurologic deficits was calculated. RESULTS: The 119 patients were treated with 240 superselective embolizations (median, 2; range, 1 to 8) using n-butyl cyanoacrylate. Mean follow-up time after surgery was 9.6+/-13.2 months. On the Spetzler-Martin scale, 8% of the AVMs were grade 1, 27% grade 2, 40% grade 3, 22% grade 4, and 3% grade 5. Disabling treatment-related complications (mRS> or =3) occurred in 5% (95% confidence interval [CI], 1% to 9%) of the patients. Nondisabling new deficits were observed in another 42% (95% CI, 33% to 51%). No patient died. Nonhemorrhagic AVM presentation (odds ratio [OR], 5.00; 95% CI, 1.75 to 14.29), deep venous drainage (OR, 3.09; 95% CI, 1.43 to 6.64), AVM location in an eloquent brain region (OR, 2.42; 95% CI, 1.10 to 5.33), and large AVM size (OR, 1.05; 95% CI, 1.01 to 1.09) were independently associated with new treatment-related deficits. CONCLUSIONS: Our results suggest an increased treatment risk for patients with previously unbled AVMs from combined endovascular and surgical AVM therapy. Additional risk factors for treatment-related neurologic deficits may be large AVM size, deep venous drainage, and AVM location in eloquent brain regions.

Olive oil based nutrition in multiple trauma patients: a pilot study.

OBJECTIVE: A negative effect of hyperglycemia on clinical outcome has been proposed for patients treated under intensive care conditions. So far, however, the safety and effect of fat based nutrition regimen, especially of olive oil based emulsions, have not been systematically studied. DESIGN AND SETTING: Prospective, open-labeled, randomized, pilot study in a 14-bed surgical intensive care unit. PATIENTS AND INTERVENTIONS: Thirty-three consecutive, severe multiple trauma patients (injury severity score 31.6+/-11.5) were included; 18 (L group) received a parenteral lipid-based nutrition; 15 (G group) were given a standard parenteral glucose-based nutrition. MEASUREMENTS AND RESULTS: The energy expenditure (EE) showed no difference between groups and no significant difference between the energy intake/EE ratio. The daily mean energy intake was lower in the L group (17.9+/-6.3 kcal/kg) than in the G group (22.3+/-4.2 kcal/kg). Triglycerides and nitrogen balance showed no significant differences between groups. The L group had significantly lower blood glucose (L 7.4+/-1.6, G 8.7+/-1.6 mmol/l), carbon dioxide production, and minute volume and shorter duration of mechanical ventilation (L 13.0+/-8.9, G 20.4+/-7.0 days), and stay in the ICU (L 17.9+/-11.2, G 25.1+/-7.0 days). CONCLUSIONS: Our findings suggest a good tolerance, a decrease in blood glucose, clinically relevant shortening of ICU stay, and shorter time on mechanical ventilation for patients treated with olive oil based than with conventional glucose-heavy nutrition.

Does brain temperature correlate with intracranial pressure?

OBJECTIVE: A positive correlation between brain temperature and intracranial pressure (ICP) has been proposed for patients under intensive care conditions. DESIGN AND METHODS: Data were recorded at 5-minute intervals in patients under ICP monitoring conditions. Brain temperature: combined ICP/temperature probe (Raumedic), core temperature: indwelling urinary catheter with temperature probe (Rüsch). The correlation between brain temperature and ICP was assessed by computing an estimated mean correlation coefficient (re) and by a time series analysis. PATIENTS: Forty consecutive neurosurgical patients receiving intensive care therapy for trauma, cerebrovascular malformation, and spontaneous hemorrhage were studied. A total of 48,892 measurements (9778 h) were analyzed. No additional interventions were performed. RESULTS: The median ICP was 14 mm Hg (range: -13 to 167). The brain temperature (median 38 degrees C; range 23.2 to 42.1) was 0.3 degrees C (range: -3.6 to 2.6) higher than the core temperature (median 37.7 degrees C; range 16.6 to 42.0), P<0.001. The mean Pearson correlation between ICP and brain temperature in all patients was re=0.13 (P<0.05); the time series analysis (assuming a possible lagged correlation between ICP and brain temperature) revealed a mean correlation of 0.05+/-0.25 (P<0.05). Both correlation coefficients indicate that any relationship between brain temperature and ICP accounts for less than 2% of the variability [coefficient of determination (r)<0.02]. CONCLUSIONS: These data do not support the notion of a clinically useful correlation between brain temperature and ICP.

Treatment of arteriovenous malformations of the brain.

The treatment of ruptured and unruptured brain arteriovenous malformations (AVMs) is driven by the need to prevent incident or recurrent intracranial hemorrhages. Improving feasibility of the rapidly developing endovascular, neurosurgical, and radiotherapeutic procedures leads to invasive treatment of an increasing number of neurologically intact patients with accidentally diagnosed AVMs. Recent data confirm that the natural history risk of unruptured AVMs is significantly lower than the risk of those presenting with rupture, and the treatment risk of invasive management of unruptured AVMs seems higher than their natural history risk. The treatment decision algorithm for these patients remains unsettled, as no randomized clinical trial data exist on the benefit of invasive AVM treatment for patients with bled or with unbled AVMs. The recently launched study A Randomized Trial of Unruptured Brain AVMs (ARUBA) will be the first trial randomizing patients with nonhemorrhaged AVMs to invasive versus conservative management.

Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy.

PURPOSE OF REVIEW: Brain arteriovenous malformations (AVMs) are currently being treated in a variety of ways, including medical management, endovascular procedures, neurosurgery and radiotherapy. The widespread diffusion of these various treatment approaches is partially driven by the existence of variations in the perception about the risks of rupture, and how devastating such events would be. RECENT FINDINGS: Data from the most recent studies suggest the majority of AVM patients are diagnosed without signs of hemorrhage, further, that the natural history risk for the unruptured cohort is far more benign than for those presenting with rupture. In cases where hemorrhage occurs, the clinical syndrome is significantly less disabling than in patients with non-AVM related hemorrhage. For unruptured AVMs, current morbidity data suggest a higher risk for invasive management than for the natural history of untreated patients. SUMMARY: No randomized clinical trial data exist on the benefit of invasive AVM treatment, and the most contentious issue at present is whether intervention should be considered for AVMs that have not bled. In a scientific sense, invasive treatment for unruptured brain AVMs may be considered experimental therapy awaiting the results from 'A Randomized Trial of Unruptured Brain AVMs' (ARUBA), which is currently underway.

Incidence of adult brain arteriovenous malformation hemorrhage in a prospective population-based stroke survey.

BACKGROUND: Brain arteriovenous malformations (AVMs) represent a potential source of intracranial hemorrhage, especially in young adults, but prospective population-based incidence data on AVM hemorrhage are lacking. We investigated the incidence of first-ever AVM hemorrhage in adults based on population data from the Northern Manhattan Stroke Study (NOMASS). METHODS: NOMASS is a prospective, population-based, stroke incidence survey collecting all hospitalized and nonhospitalized cases with first-ever (incident) stroke over the age of 20 in a ZIP code-defined area. All patients undergo CT and/or MR brain imaging and clinical data are systematically collected from the medical records. For this study, data on all cases with incident intracranial hemorrhage, i.e. any intracerebral, intraventricular and/or subarachnoid hemorrhage, occurring between July 1, 1993 and June 30, 1997 were used. Patients with intracranial hemorrhage due to trauma, tumor or intracranial vascular malformations other than a previously unknown AVM were excluded from the study. RESULTS: Of the 207 patients diagnosed with a first-ever intracranial hemorrhage, 3 cases (1.4%) with an underlying brain AVM were identified. The crude incidence rate for first-ever AVM hemorrhage in our adult population was 0.55 per 100,000 person-years (95% confidence interval 0.11-1.61). CONCLUSIONS: Our results support prior findings from retrospective surveys. Population-based studies providing a prospective design for AVM detection and diagnosis are needed to confirm the data.