Jae H. Choi

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 ≥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.

Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy

Purpose of reviewBrain 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 findingsData 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. SummaryNo 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.

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.

Selective Brain Cooling with Endovascular Intracarotid Infusion of Cold Saline: A Pilot Feasibility Study

BACKGROUND AND PURPOSE: Endovascular brain cooling as a method for rapid and selective induction of hypothermic neuroprotection has not been systematically studied in humans. In this clinical pilot study we investigated the feasibility, safety, and physiologic responses of short-term brain cooling with IC-CSI. MATERIALS AND METHODS: We studied 18 patients (50 ± 10 years old, 9 women) undergoing follow-up cerebral angiography after previous treatment of vascular malformations. Isotonic saline (4–17°C) was infused into 1 internal carotid artery at 33 mL/min for 10 minutes. Brain (JVB) and bladder/esophageal temperature measurements (n = 9) were performed. Both MCAs were monitored with transcranial Doppler sonography (n = 13). Arterial and JV blood were sampled to estimate hemodilution and brain oxygen extraction. RESULTS: JVB temperature dropped ∼0.84 ± 0.13°C and systemic temperature by 0.15 ± 0.08°C from baseline (JVB versus systemic temperature: P = .0006). Systolic MCA-flow velocities decreased from 101 ± 27 to 73 ± 18 cm/s on the infused side and from 83 ± 24 to 78 ± 21 cm/s on the contralateral side (relative changes, −26 ± 8% versus −4 ± 27%; P = .009). Changes in hematocrit (−1.2 ± 1.1%) and cerebral arteriovenous oxygen difference (0.2 ± 1.0 mL O2/100 mL) were not significant. Doppler data showed no signs of vascular spasm or microemboli. No focal neurologic deficits occurred. Pain was not reported. CONCLUSIONS: The results of this pilot study suggest that brain cooling can be achieved safely, rapidly, and selectively by means of IC-CSI, opening a new potential avenue for acute neuroprotection. Clinical investigations with control of infusion parameters and measurements of CBF, oxygen consumption, and brain temperature are warranted.

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.

Neuroprotection for ischemic stroke using hypothermia

The development of animal models of acute stroke has allowed the evaluation of mild and moderate hypothermia as a therapeutic modality in this clinical setting. Studies have demonstrated that animals subjected to hypothermia up to 3 hours after the primary central nervous system insult have reduced mortality and neuronal injury, and improved neurological outcome. These results warranted the evaluation of hypothermia in clinical trials.Even though hypothermia has potent neuroprotective effects in animal models of ischemic stroke, there are only a few clinical studies of therapeutic hypothermia in humans. Because of the small number of patients in the studies and the absence of matched controls, clinical studies are considered pilot studies for feasibility and safety. Thus, therapeutic hypothermia for ischemic stroke remains a promising but fiercely debated therapeutic modality.This review summarizes the animal model studies that have led to clinical trials in acute ischemic stroke. The existing techniques for inducing brain cooling, the mechanisms of neuroprotection, the complications of therapeutic hypothermia, and the future perspective of the field are also discussed.

Brain cooling maintenance with cooling cap following induction with intracarotid cold saline infusion: A quantitative model

Intracarotid cold saline infusion (ICSI) is potentially much faster than whole-body cooling and more effective than cooling caps in inducing therapeutic brain cooling. One drawback of ICSI is hemodilution and volume loading. We hypothesized that cooling caps could enhance brain cooling with ICSI and minimize hemodilution and volume loading. Six-hour-long simulations were performed in a 3D mathematical brain model. The Pennes bioheat equation was used to propagate brain temperature. Convective heat transfer through jugular venous return and the circle of Willis was simulated. Hemodilution and volume loading were modeled using a two-compartment saline infusion model. A feedback method of local brain temperature control was developed where ICSI flow rate was varied based on the rate of temperature change and the deviation of temperature to a target (32 degrees C) within a voxel in the treated region of brain. The simulations confirmed the inability of cooling caps alone to induce hypothermia. In the ICSI and the combination models (ICSI and cap), the control algorithm guided ICSI to quickly achieve and maintain the target temperature. The combination model had lower ICSI flow rates than the ICSI model resulting in a 55% reduction of infusion volume over a 6h period and higher hematocrit values compared to the ICSI model. Moreover, in the combination model, the ICSI flow rate decreased to zero after 4h, and hypothermia was subsequently maintained solely by the cooling cap. This is the first study supporting a role of cooling caps in therapeutic hypothermia in adults.

Major Neurologic Improvement following Endovascular Recanalization Therapy for Acute Ischemic Stroke

Background: We aimed to identify the rate of major neurologic improvement (MNI) at 24 h following endovascular recanalization therapy (ERT) for acute ischemic stroke and its association with short-term outcome. Methods: We retrospectively reviewed consecutive acute ischemic stroke patients presenting to our institution over 4 years and undergoing ERT. Angiograms were independently reviewed. Data on demographics, medical history, initial NIHSS score, 24-hour NIHSS score, site of acute vascular lesion, pre- and posttreatment Thrombolysis in Myocardial Infarction scores, symptomatic intracerebral hemorrhage (within 36 h of intervention that was associated with a 4-point decline in NIHSS score) and discharge disposition were collected. We used logistic regression analysis to identify predictors of MNI (defined as ≥8-point improvement in NIHSS or a score of 0–1 at 24 h) and favorable discharge status (defined as home or acute rehabilitation). Results: Sixty-eight patients were included (median age = 71 years, 60% women, median NIHSS score = 19.5, anterior circulation = 75%). The modes of ERT were pharmacologic only (28%), mechanical only (35%) and multimodal therapy (37%). Thrombolysis in Myocardial Infarction 2 or 3 recanalization was achieved in 64.7% (mechanical only 46%, pharmacologic only 63% and multimodal 84%). The outcomes were: symptomatic intracerebral hemorrhage (11.8%), MNI (26.5%) and favorable discharge (41.2%). Age (OR = 0.93, p = 0.003) and cardioembolic stroke subtype (OR = 6.0, p = 0.018) were independent predictors of MNI. MNI was a strong predictor of favorable discharge status (OR = 46.4, p < 0.001). Conclusions: Despite initial stroke severity, MNI occurred in over one fourth of the patients and independently and strongly predicted favorable discharge outcome.

Reliability, Asymmetry, and Age Influence on Dynamic Cerebral Autoregulation Measured by Spontaneous Fluctuations of Blood Pressure and Cerebral Blood Flow Velocities in Healthy Individuals

Cerebral autoregulation (CA) enables the brain to maintain stable cerebral blood flow (CBF). CA can be assessed noninvasively by determining correlations between CBF velocity (CBFV) and spontaneous changes in blood pressure. Postrecording signal analysis methods have included both frequency‐ and time‐domain methods. However, the test‐retest reliability, cross‐validation, and determination of normal values have not been adequately established.

The Role of Intracarotid Cold Saline Infusion on a Theoretical Brain Model Incorporating the Circle of Willis and Cerebral Venous Return

This study describes a theoretical model of brain cooling by intracarotid cold saline infusion which takes into account redistribution of cold perfusate through the circle of Willis (CoW) and cold venous return (VR) from the head. This model is developed in spherical coordinates on a four tissue layer hemispherical geometrical configuration. Temperature evolution is modeled according to the Pennes bioheat transfer equation. Simulations were run over a 1 hour period and 30 ml/min of freezing cold saline with the baseline model (no VR, no CoW), VR model (without CoW), and CoW model (with VR). The VR model demonstrates continuing temperature drop in the treatment region of the brain not observed in the baseline model and its final mean ipsilateral anterior temperature was approximately 31 degC. The temperature effect in the CoW model was present but less robust in the ipsilateral anterior region, as final temperature was 32 degC. However, cooling was also achieved in contralateral and posterior brain regions. This model continues to demonstrate the feasibility of intracarotid cold saline infusion for ischemic stroke therapy.