Early Quantification of Hematoma Hounsfield Units on Noncontrast CT in Acute Intraventricular Hemorrhage Predicts Ventricular Clearance after Intraventricular Thrombolysis.

BACKGROUND AND PURPOSE: Thrombolytic efficacy of intraventricular rtPA for acute intraventricular hemorrhage may depend on hematoma composition. We assessed whether hematoma Hounsfield unit quantification informs intraventricular hemorrhage clearance after intraventricular rtPA. MATERIALS AND METHODS: Serial NCCT was performed on 52 patients who received intraventricular rtPA as part of the Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage trial and 12 controls with intraventricular hemorrhage, but no rtPA treatment. A blinded investigator calculated Hounsfield unit values for intraventricular hemorrhage volumes on admission (t0), days 3-4 (t1), and days 6-9 (t2). Controls were matched uniquely to 12 rtPA-treated patients for comparison. RESULTS: Median intraventricular hemorrhage volume on admission for patients treated with intraventricular rtPA was 31.9 mL (interquartile range, 34.1 mL), and it decreased to 4.9 mL (interquartile range, 14.5 mL) (t2). Mean (±standard error of the mean) Hounsfield unit for intraventricular hemorrhage was 52.1 (0.59) at t0 and decreased significantly to 50.1 (0.63) (t1), and to 45.1 (0.71) (t2). Total intraventricular hemorrhage Hounsfield unit count was significantly correlated with intraventricular hemorrhage volume at all time points (t0: P = .002; t1: P < .001; t2: P < .001). On serologic and CSF analysis at t0, only higher CSF protein was positively correlated with intraventricular hemorrhage Hounsfield units (P = .03). In 24 matched patients treated with rtPA and controls, total intraventricular hemorrhage Hounsfield units were significantly lower in patients treated with rtPA at t2 (P = .02). Higher Hounsfield unit quantification of fourth ventricle hematomas independently predicted slower clearance of this ventricle (95% CI, 0.02-0.14; P = .02), along with higher intraventricular hemorrhage volume (95% CI, 0.02-0.41; P = .03) and lower CSF protein levels (95% CI, -0.003 to -0.002; P < .001). CONCLUSIONS: Intraventricular hemorrhage Hounsfield unit counts decrease significantly in the acute phase and to a greater extent with intraventricular rtPA treatment. Intraventricular hemorrhage Hounsfield units are correlated significantly with CSF protein and not with serum erythrocyte or platelet concentrations. Hounsfield unit counts may reflect intraventricular hemorrhage clot composition and rtPA sensitivity.

Compressed EEG pattern analysis for critically ill neurological-neurosurgical patients.

Recent advances in continuous electroencephalogram (EEG) monitoring with digital EEG acquisition, storage, and quantitative analysis allow uninterrupted assessment of cerebral cortical activity in critically ill neurological-neurosurgical patients. Early recognition of worsening brain function can prove of vital importance as one can initiate measures aimed to prevent further brain damage. Although continuous EEG monitoring provides adequate spatial and temporal resolution and is able to continuously assess brain function in these critically ill patients, it requires a trained electroencephalographer to interpret the massive amounts of data generated. This limitation impedes the widespread use of EEG in assessing real-time brain function in critically ill patients. Here, we demonstrate the utility of a novel method of automated EEG analysis that segments and extracts EEG features, classifies and groups them according to various patterns, and then presents them in a compressed fashion. This permits real-time viewing of several hours of EEG on a single page. Examples are presented from three patients, two with recurrent seizures and one with diagnosis of subarachnoid hemorrhage. These patients illustrate the ability of this novel method to detect important real-time physiological changes in brain function that could enable early interventions aimed to prevent irreversible brain damage.

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.

P-450 epoxygenase and NO synthase inhibitors reduce cerebral blood flow response to N-methyl-D-aspartate.

Epoxyeicosatrienoic acids are cerebral vasodilators produced in astrocytes by cytochrome P-450 epoxygenase activity. The P-450 inhibitor miconazole attenuates the increase in cerebral blood flow (CBF) elicited by glutamate. We evaluated whether epoxygenase activity is involved in the CBF response to activation of the N-methyl-D-aspartate (NMDA) receptor subtype by using two structurally distinct inhibitors, miconazole and N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH), a selective epoxygenase substrate inhibitor. Drugs were delivered locally through microdialysis probes in striata of anesthetized rats. Local CBF was measured by hydrogen clearance and compared with CBF in contralateral striatum receiving vehicle. Microdialysis perfusion of NMDA doubled CBF and increased nitric oxide (NO) production estimated by recovery of labeled citrulline in the dialysate during labeled arginine infusion. Perfusion of miconazole or MS-PPOH blocked the increase in CBF without decreasing citrulline recovery. Perfusion of N(omega)-nitro-L-arginine decreased baseline CBF and inhibited the CBF response to NMDA. Perfusion of MS-PPOH did not inhibit the CBF response to sodium nitroprusside. We conclude that both the P-450 epoxygenase and NO synthase pathways are involved in the local CBF response to NMDA receptor activation, and that the signaling pathway may be more complex than simply NO diffusion from neurons to vascular smooth muscle.

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.

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

Moyamoya syndrome associated with Sneddon's syndrome and antiphospholipid-protein antibodies.

BACKGROUND: There are anecdotal reports of the rare combination of Sneddon's syndrome, lupus anticoagulant, and Moyamoya. To our knowledge, we now report the first case of anticardiolipin antibodies, Sneddon's syndrome, and Moyamoya. METHODS: Case-report and systematic literature review. RESULTS: A 37-year-old woman had 31/2 years of recurrent left-sided sensory-motor symptoms. More recently, she had experienced vertigo, diplopia, and imbalance. Medical history included headaches, labile hypertension, left arm venous thrombosis requiring anticoagulation, and cigarette smoking. On examination she had livedo reticularis, limited left eye abduction, and left hemiparesis. Magnetic resonance imaging (MRI) showed right frontal, left parieto-occipital and pontine high intensity lesions on T(2)-weighted images consistent with ischemia and abnormally increased flow-void in the basal ganglionic regions. Conventional cerebral angiography showed a Moyamoya pattern. Transesophageal echocardiography and electroencephalogram were normal. Serologic studies were remarkable for anticardiolipin antibodies immunoglobulin G isotype only. She responded favorably to carbamazepine as treatment of presumptive focal seizures, and long-term anticoagulation. Seven other cases reported in the literature were found and reviewed, with different combinations of Moyamoya, Sneddon's syndrome, and antiphospholipid-protein antibodies. The mean age was 37 (range 18-59, SD+/-16) years, male/female ratio 3/5; clinical features included cognitive changes (4 pts), ischemic stroke (6pts), seizures (1pt), and intracranial hemorrhage (2pts). Anticoagulation/steroids/anti-platelet agents were empirically associated with a favorable survival and functional outcome in 6 cases. CONCLUSION: This case expands the spectrum of associations with Moyamoya, and in conjunction with a review of the literature, suggests that evaluation for antiphospholipid-protein antibodies is recommended in cases of Moyamoya syndrome.

Cerebral venous thrombosis and anticardiolipin antibodies.

BACKGROUND AND PURPOSE: The association of cerebral venous thrombosis (CVT) with a variety of pathological states is well established. However, there are only rare isolated reports of CVT associated with anticardiolipin antibodies (aCL). METHODS: To clarify the clinical and neuradiological features as well as outcome of patients with CVT associated with aCL, we reviewed the records of all patients with CVT evaluated at our institution between 1989 and 1996 (retrospective and prospective) and systematically reviewed the pertinent literature. RESULTS: We identified 8 aCL+ and 7 aCL- patients with CVT. No patients with lupus anticoagulant (LA) were identified. The mean age was 23 +/- 11.01 (range, < 1 to 36) years in the aCL+ and 38 +/- 9.30 (range, 25 to 54) years in the aCL- patients (P = .016). Six of 8 aCL+ and 5 of 7 aCL- patients were women. The dural sinuses were involved in all aCL+ and in 6 of 7 aCL- patients, while deep venous system thrombosis occurred in 5 of 8 (63%) aCL+ and 1 of 7 (14%) aCL- patients. In the aCL+ patients CVT was associated with puerperium or oral contraceptive use (n = 6), and sickle cell trait (n = 1), and in the aCL- patients CVT was associated with systemic lupus erythromatosus (n = 1), myelodysplasti syndrome (n = 1), colonic cancer (n = 1), oral contraceptive use or puerperium (n = 3), and dehydration (n = 1). Seven aCL+ patients received either intrasinus urokinase or intravenous heparin sulfate, and 1 received aspirin. Four aCL+ patients developed new onset or worsening of preexisting migraine, 2 developed recurrent peripheral venous thrombosis, and 1 went on to have intracranial hypertension. Twenty additional patients with CVT associated with antiphospholipid antibodies (aPL) were found reported in the literature. The overall mean age was 36 +/- 11.6 (range, 21 to 62) years, and 14 (70%) were women. LA was present in 11 of 18 tested, aCL in 7 (35%), LA and aCL in 1, and the type of aPL was not reported in 3. The mean age for the aCL+ only group was 28 years and for the LA+ (with or without aCL+) was 34 years. Only 1 patient, whose aPL type was not specified, had thrombosis of the deep venous system in addition to involvement of the dural sinuses. CONCLUSIONS: Our series and review suggest that aCL may be an important factor contributing to development of CVT even in the presence of other potential etiologies or risk factors. Onset of aCL+ CVT occurs at a relative young age and with relatively more extensive superficial and deep cerebral venous system involvement than aCL- CVT.