Joao Gomes

Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) Final Results

Background and Purpose— Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke. Methods— Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not. Results– In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (P=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (P=0.32). Conclusion— This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.

Glucocorticoid therapy in neurologic critical care

Background:The pivotal role of inflammation and edema across the spectrum of central nervous system injury has driven extensive investigation into the therapeutic potential of glucocorticoids. Objective:To review the experimental and clinical data relating to the efficacy and adverse effects of glucocorticoids in conditions encountered in critical neurologic and neurosurgical illness. Data Source:Search of MEDLINE and Cochrane databases, manual review of article bibliographies. Data Synthesis and Conclusions:The efficacy of glucocorticoids is well established in ameliorating edema associated with brain tumors and in improving outcome in subsets of patients with bacterial meningitis. Despite frequently encouraging experimental results, clinical trials of glucocorticoids in ischemic stroke, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, and traumatic brain injury have not shown a definite therapeutic effect. The evidence supporting glucocorticoid therapy for spinal cord injury is controversial; however methylprednisolone continues to be widely employed in this setting.

Safety and Tolerability of Deferoxamine Mesylate in Patients With Acute Intracerebral Hemorrhage

Background and Purpose— Treatment with the iron chelator, deferoxamine mesylate (DFO), improves neurological recovery in animal models of intracerebral hemorrhage (ICH). We aimed to evaluate the feasibility, safety, and tolerability of varying dose-tiers of DFO in patients with spontaneous ICH, and to determine the maximum tolerated dose to be adopted in future efficacy studies. Methods— This was a multicenter, phase-I, dose-finding study using the Continual Reassessment Method. DFO was administered by intravenous infusion for 3 consecutive days, starting within 18 hours of ICH onset. Subjects underwent repeated clinical assessments through 90 days, and computed tomography neuroimaging pre- and post-drug-administration. Results— Twenty subjects were enrolled onto 5 dose tiers, starting with 7 mg/kg per day and ending with 62 mg/kg per day as the maximum tolerated dose. Median age was 68 years (range, 50–90); 60% were men; and median Glasgow Coma Scale and National Institutes of Health Stroke Scale scores on admission were 15 (5–15) and 9 (0–39), respectively. ICH location was lobar in 40%, deep in 50%, and brain stem in 10%; intraventricular hemorrhage was present in 15%. DFO was discontinued because of adverse events in 2 subjects (10%). Six subjects (30%) experienced 12 serious adverse events, none of which were drug-related. DFO infusions were associated with mild blood-pressure-lowering effects. Fifty percent of patients had modified Rankin scale scores ⩽2, and 39% had modified Rankin scale scores of 4 to 6 on day 90; 15% died. Conclusions— Consecutive daily infusions of DFO after ICH are feasible, well-tolerated, and not associated with excessive serious adverse events or mortality. Our findings lay the groundwork for future studies to evaluate the efficacy of DFO in ICH.

Intra-Arterial Therapy for Acute Ischemic Stroke Under General Anesthesia versus Monitored Anesthesia Care

Background: Recent studies have shown that intra-arterial recanalization therapy (IAT) for acute ischemic stroke (AIS) is associated with worse clinical outcomes when performed under general anesthesia (GA) compared to local anesthesia, with or without conscious sedation. The reasons for this association have not been systematically studied. Methods: We retrospectively reviewed 190 patients who underwent IAT for anterior circulation AIS from January 2008 to December 2012 at our institution. Baseline demographics, vessels involved, acute stroke treatment including intravenous tissue type plasminogen activator (tPA) use, use of GA vs. monitored anesthesia care (MAC), location of thrombus, recanalization grade, radiologic post-procedural intracerebral hemorrhage, and 30-day outcomes were collected. Relevant clinical time points were recorded. Detailed intra-procedural hemodynamics including maximum/minimum heart rate, systolic blood pressure (BP), diastolic BP, mean BP, use of pressors and episodes of hypotension were collected. Our studys outcomes were as follows: in-hospital mortality, 30-day good outcome (mRS ≤2), successful recanalization and radiologic post-procedural intracerebral hemorrhage. Results: Ninety-one patients received GA and 99 patients received MAC. There was no significant difference in the NIHSS score between the two groups but the GA group had a higher number of ICA occlusions (31.9 vs. 18.2%, p = 0.043). The time from the start of anesthesia to incision (23.0 ± 12.5 min vs. 18.7 ± 11.3 min, p = 0.020) and the time from the start of anesthesia to recanalization (110 ± 57.2 vs. 92.3 ± 43.0, p = 0.045) was longer in the GA group. The time from incision to recanalization was not significantly different between the two groups. mRS 0-2 was achieved in 22.8% of patients in the MAC group compared to 14.9% in GA (p = 0.293). Higher mortality was seen in the GA group (25.8 vs. 13.3%, p = 0.040). Successful recanalization (TICI 2b-3) was similar between the GA and MAC (57.8 vs. 48.5%, p = 0.182) groups, but GA had a higher number of parenchymal hematomas (26.3 vs. 10.1%, p = 0.003). There was no difference in the intra-procedural hemodynamic variables between the GA and MAC groups. Anesthesia type was an independent predictor for mortality (along with age and initial NIHSS), and the only independent predictor for parenchymal hematomas, with MAC being protective for both. Conclusion: Our study has confirmed previous findings of GA being associated with poorer outcomes and higher mortality in patients undergoing IAT for AIS. Detailed analysis of intra-procedural hemodynamics did not reveal any significant difference between the two groups. Parenchymal hematoma was the major driver of the difference in outcomes.

Symptomatic and Asymptomatic Retinal Embolism Have Different Mechanisms

Purpose— To investigate differences between symptomatic and asymptomatic retinal embolism regarding the frequency and source of cerebral microemboli. Methods— Thirty-seven patients with transient monocular blindness or retinal infarction and 27 patients (29 eyes) with asymptomatic retinal embolism were prospectively enrolled. Patients underwent a transcranial Doppler study and noninvasive imaging of the cervical internal carotid arteries (ICA). The middle cerebral artery (MCA) ipsilateral to the affected eye was monitored for 30 minutes for microembolic signals (MES), which were saved and analyzed offline. Age-matched controls (n=15) had no history of retinal or brain ischemia, <50% ICA stenosis, and normal ophthalmologic examinations. Results— MES were detected in 0/15 (0%) controls, 11/37 (30%) MCAs in the symptomatic group (P =0.02), and 3/29 (10%) MCAs in the asymptomatic group (P =0.54). Nine of 11 (82%) symptomatic eyes with MES had ipsilateral ICA stenosis of ≥50%, as compared with 0/3 (0%) eyes in the asymptomatic group with MES (P =0.03). Both MES and ICA stenosis of >50% were present in 9/37 (24%) cases in the symptomatic and in 0/29 (0%) cases of the asymptomatic group (P =0.0036). Conclusions— The frequency and potential source of cerebral microemboli in symptomatic and asymptomatic retinal embolism are different. Cerebral microemboli are more frequent in symptomatic patients and are associated with ICA stenosis.

Binswanger disease — An update

Binswanger disease is a common cause of vascular dementia in the elderly. This report up-dates the pathological and clinical findings, imaging identification emphasizing recent advances, and diagnosis of this condition.

Residency Training: The role of neurocritical care in resident education

Neurology is traditionally recognized as primarily an outpatient or consultative specialty, usually attracting candidates whose main focus may not necessarily be the management of complex critically ill patients or the performance of invasive procedures. However, the advent of modern mechanical ventilation and, more recently, effective therapies for the treatment of acute ischemic stroke and other neurologic catastrophes is bringing about a paradigm shift, with neurologists increasingly assuming a more aggressive attitude and rapid response to frequently disabling and often fatal pathologies.

Safety and Hemodynamic Profile of Propofol and Dexmedetomidine Anesthesia during Intra-arterial Acute Stroke Therapy

BACKGROUND There is limited data on the safety, hemodynamic profile, and outcome of patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke (AIS) under sedation with dexmedetomidine (DEX) versus propofol (PROP). METHODS Retrospective study of patients with anterior circulation AIS, who underwent IAT without intubation, and received either DEX or PROP between January 2008 and December 2012, was performed. Demographics, stroke treatments, time metrics, anesthesia, intraprocedural hemodynamics, vasopressor use, infarct volumes, recanalization status, and intracerebral hemorrhage were collected. RESULTS Seventy-two patients met inclusion criteria, of which 35 received DEX and 37 PROP. There was no difference in baseline demographics, stroke treatments, successful recanalization, hemorrhages, infarct volume growth, good clinical outcome (mRS ≤ 2 [19% versus 22%, P = .742]), or in-hospital mortality (18% versus 8%, P = .225) between DEX and PROP. The DEX group had lower intraprocedural minimum systolic blood pressure (103 ± 27 versus 114 ± 18 mm Hg, P = .032) and minimum mean arterial pressure (MAP; 67 ± 17 versus 77 ± 10 mm Hg, P = .006). More patients in the DEX group experienced episodes of hypotension (MAP < 60 mm Hg; 24% versus 3%; P = .010) and had higher vasopressor requirement (phenylephrine: 1825 ± 2390 versus 491 ± 884 mcg, P = .007) compared to PROP. CONCLUSIONS There was no difference in good clinical outcome or in-hospital mortality in patients undergoing IAT for AIS using DEX versus PROP sedation. However, hemodynamic instability and vasopressor requirement were significantly higher in the DEX group. DEX should be cautiously utilized in IAT.

Intra-arterial vasodilator therapy for parainfectious cerebral vasospasm

Cerebrovascular complications of bacterial meningitis may include vasculitis, vasospasm or vasoconstriction, delayed cerebral infarction, venous and arterial thrombosis, intracranial aneurysm formation. The role of invasive endovascular therapies has not been well studied for infectious vasospasm, which can lead to dire neurologic consequences. We present 2 patients who were diagnosed with bacterial meningitis. Brain MRI showed areas of acute ischemia. Neurologic worsening was seen in both patients despite aggressive medical management. Follow-up imaging demonstrated significant narrowing of the intracranial vessels with associated new scattered infarcts. Both patients underwent targeted intra-arterial vasodilator infusion with angiographically improved vessel caliber and distal flow. The neurological exam subsequently stabilized in both cases. Follow-up radiographic images demonstrated no further ischemia in one of the 2 patients. Vasculopathy and vasospasm causing delayed ischemic neurologic deficit is a rare, but severe complication of acute meningitis. It can be a significant predictor of poor prognosis, and the disease may progress despite aggressive medical therapy. Although frequently used in subarachnoid hemorrhage-related vasospasm, to our knowledge, this is the first report of endovascular vasodilator treatment as adjunctive intervention in patients with meningitis associated vasculopathy.

Types of Strokes

There are two main types of strokes: ischemic and hemorrhagic. Ischemic strokes are far more common than hemorrhagic strokes. The brain has a blood supply which is fairly consistent between individuals. Ischemic strokes can be due to large-vessel atherosclerosis, aortocardioembolism, small-vessel occlusion, other determined causes, and undetermined causes. Hemorrhagic strokes are most often due to hypertension but may be caused by specific blood vessel abnormalities and other medical problems. The clinical impact of a stroke depends largely on the stroke’s location in the brain, whether it is ischemic or hemorrhagic, and the size/severity of the stroke itself.