Juan R. Carhuapoma

Treatment of Intraventricular Hemorrhage With Urokinase Effects on 30-Day Survival

BACKGROUND AND PURPOSE Intraventricular hemorrhage (IVH) remains associated with high morbidity and mortality. Therapy with external ventricular drainage alone has not modified outcome in these patients. METHODS Twelve pilot IVH patients who required external ventricular drainage were prospectively treated with intraventricular urokinase followed by the randomized, double-blinded allocation of 8 patients to either treatment or placebo. Observed 30-day mortality was compared with predicted 30-day mortality obtained by use of a previously validated method. RESULTS Twenty patients were enrolled; admission Glasgow Coma Scale score in 11 patients was </=8; 10 patients had pulse pressure <85 mm Hg. Mean+/-SD ICH volume in 16 patients was 6.21+/-7.53 cm(3) (range 0 to 23.88 cm(3)), and mean+/-SD intraventricular hematoma volume was 44.26+/-31.65 cm(3) (range 1.31 to 100.36 cm(3)). Four patients (20%) died within 30 days. Predicted mortality for these 20 patients was 68.42% (range 3% to 100%). Probability of observing </=4 deaths among 20 patients under a 68.42% expected mortality is 0.000012. CONCLUSIONS Intraventricular urokinase may significantly improve 30-day survival in IVH patients. On the basis of current evidence, a double-blinded, placebo-controlled, multicenter study that uses thrombolysis to treat IVH has received funding and began January 1, 2000.

Diffusion-Weighted MRI and Proton MR Spectroscopic Imaging in the Study of Secondary Neuronal Injury After Intracerebral Hemorrhage

BACKGROUND AND PURPOSE Cerebral ischemia has been proposed as contributing mechanism to secondary neuronal injury after intracerebral hemorrhage (ICH). Possible tools for investigating this hypothesis are diffusion-weighted (DWI) and proton magnetic resonance spectroscopic imaging ((1)H-MRSI). However, magnetic field inhomogeneity induced by paramagnetic blood products may prohibit the application of such techniques on perihematoma tissue. We report on the feasibility of DWI and (1)H-MRSI in the study of human ICH and present preliminary data on their contribution to understanding perihematoma tissue functional and metabolic profiles. METHODS Patients with acute supratentorial ICH were prospectively evaluated using DWI and (1)H-MRSI. Obscuration of perihematoma tissue with both sequences was assessed. Obtainable apparent diffusion coefficient (Dav) and lactate spectra in perihematoma brain tissue were recorded and analyzed. RESULTS Nine patients with mean age of 63.4 (36 to 87) years were enrolled. Mean time from symptom onset to initial MRI was 3.4 (1 to 9) days; mean hematoma volume was 35.4 (5 to 80) cm(3). Perihematoma diffusion values were attainable in 9 of 9 patients, and (1)H-MRSI measures were obtainable in 5 of 9 cases. Dav in perihematoma regions was 172.5 (120.0 to 302.5)x10(-5) mm(2)/s and 87.6 (76.5 to 102.1)x10(-5) mm(2)/s in contralateral corresponding regions of interest (P=0.002). One patient showed an additional area of reduced Dav with normal T(2) intensity, which suggests ischemia. (1)H-MRSI revealed lactate surrounding the hematoma in 2 patients. CONCLUSIONS DWI and (1)H-MRSI can be used in the study of ICH patients. Our preliminary data are inconsistent with ischemia as the primary mechanism for perihematoma tissue injury. Further investigation with advanced MRI techniques will give a clearer understanding of the role that ischemia plays in tissue injury after ICH.

Intra-arterial papaverine-induced seizures: case report and review of the literature.

BACKGROUND Microcatheter-guided intra-arterial (IA) papaverine infusion in conjunction with balloon angioplasty is an available therapy for patients with symptomatic vasospasm after subarachnoid hemorrhage (SAH) that is refractory to hypertensive, hypervolemic therapy. However, side effects and complications have been reported in association with its use. CASE DESCRIPTION We report on a patient who developed symptomatic vasospasm after subarachnoid hemorrhage due to rupture of a left terminal internal carotid artery (ICA) saccular aneurysm. Seven days after the hemorrhage and 4 days after surgical clipping, the patient developed aphasia and right hemiparesis due to vasospasm, which was refractory to maximal medical treatment with volume and blood pressure elevation. Cerebral angiography identified severe narrowing of distal ICA and proximal middle cerebral artery segments bilaterally. These findings partially resolved after balloon angioplasty. However, after 300 mg of IA papaverine, the patient developed generalized convulsions. This occurred despite therapeutic serum levels of phenytoin. Twenty-four hours later, after brief neurologic improvement, recurrent neurologic deficits prompted repeat papaverine administration. Seizures again occurred after the administration of 240 mg of IA papaverine and prevented administration of the full dose. The patient did not develop further seizures and her neurologic deficits continue to resolve. CONCLUSIONS IA papaverine-induced seizures are infrequently reported. This potential complication should be considered when papaverine administration is entertained in the treatment of anterior circulation refractory symptomatic vasospasm after SAH.

Brain edema after human cerebral hemorrhage: A magnetic resonance imaging volumetric analysis

&NA; Although perihematoma brain edema can significantly modify neurologic outcome after intracerebral hemorrhage (ICH), our knowledge of its natural history is incomplete. We report on the correlation between hematoma (HV) and edema volumes (EV) in 14 patients with ICH during the first week after the ictus using MRI volumetric analysis. We conducted a retrospective MRI volumetric analysis of intraparenchymal hematomas and surrounding perihematoma brain edema in 14 patients with ICH. The mean age was 54.4 years (range 32–71 years). The time from symptom onset to MRI was 3.5 days (range 1–6) days, and the etiology of ICH was as follows: hypertension (70%), arteriovenous malformation rupture (19%), and postpallidotomy (11%). The mean HV was 15 mL (range 0.9–67.4 mL), and the mean EV was 17.3 mL (range 2.8–50.6 mL). Using linear regression analysis, we demonstrated EV to be significantly and directly related to HV: (EV) = 7.68 + 0.64(HV); r = 0.8; P = 0.001. In conclusion, we report significant and direct correlation between the HV and EV within the first week after ICH. The clinical implications of this observation, if confirmed, will help to better design clinical trials in ICH research as well as to better allocate adequate clinical resources in high‐risk subgroups of patients with ICH.

Minimally invasive surgery for intracerebral haemorrhage

Purpose of reviewSpontaneous intracerebral haemorrhage (ICH) imposes a significant health and economic burden on society. Despite this, ICH remains the only stroke subtype without a definitive treatment. Without a clearly identified and effective treatment for spontaneous ICH, clinical practice varies greatly from aggressive surgery to supportive care alone. This review will discuss the current modalities of treatments for ICH including preliminary experience and investigative efforts to advance the care of these patients. Recent findingsOpen surgery (craniotomy), prothrombotic agents and other therapeutic interventions have failed to significantly improve the outcome of these stroke victims. Recently, the Surgical Trial in Intracerebral Haemorrhage (STICH) II assessed the surgical management of patients with superficial intraparenchymal haematomas with negative results. MISTIE II and other trials of minimally invasive surgery (MIS) have shown promise for improving patient outcomes and a phase III trial started in late 2013. SummaryICH lacks a definitive primary treatment as well as a therapy targeting surrounding perihematomal oedema and associated secondary damage. An ongoing phase III trial using MIS techniques shows promise for providing treatment for these patients.

Regulation of the cerebral circulation by cytochrome P450 epoxygenase activity

Abstract Cytochrome P450 epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which can dilate cerebral vessels. In glial cell cultures, glutamate stimulates the release of EETs. Thus, an astrocyte-based epoxygenase pathway could form a link in the coupling of blood flow to neuronal activity. To test this hypothesis, neuronal activation was produced by mechanical displacement of the whiskers of anesthetized rats while monitoring red cell flux by laser-Doppler flowmetry over whisker barrel sensory cortex. N-methylsulfonyl-6-(2-propargyloxyphenol) hexanamide (MS-PPOH) or miconazole, two different types of P450 epoxygenase inhibitors, were superfused over the cortical surface in different groups of rats. Both inhibitors markedly reduced the increase in cortical perfusion during whisker stimulation. To test the effect of these inhibitors on the increase in blood flow evoked by N-methyl- d -aspartate (NMDA), drugs were delivered via microdialysis probes in the striatum, while local blood flow was measured by the hydrogen clearance technique. Both MS-PPOH and miconazole blocked the increase in striatal blood flow during microdialysis perfusion of NMDA. These results support a role for P450 epoxygenase activity in the coupling of cortical blood flow to whisker stimulation and to pharmacological activation of NMDA receptors in striatum.