[Usefulness of Edoxaban for Deep Cerebral Venous Sinus Thrombosis with Hemorrhagic Infarction:A Case Report].

We describe a case of deep cerebral venous sinus thrombosis(DCVST)that was successfully treated by oral administration of the Xa inhibitor edoxaban. A 53-year-old man was admitted to our hospital because of a headache and undifferentiated dizziness. Computed tomography(CT)demonstrated a low-density area in the bilateral thalamus and high-density lesions in the internal cerebral veins(ICVs)and vein of Galen. Magnetic resonance imaging with diffusion-weighted images detected areas of hyperintensity in the bilateral thalamus. Additionally, the inferior sagittal sinus, ICV, and vein of Galen were not detected by CT venography or cerebral angiography. We therefore diagnosed DCVST and started anticoagulation therapy with heparin(IV)and warfarin. A week after admission, lesions that showed hypointensity on T2* images and high density on CT scans were detected in the bilateral thalamus. We thought that hemorrhagic infarction had occurred in association with DCVST, and changed the anticoagulation therapy to oral administration of edoxaban on day 9. The patient's symptoms gradually diminished, and CT venography indicated partial recanalization of the DCV from the ICV to the vein of Galen on day 72. We report our experience, and discuss the safety and usefulness of the Xa inhibitor for treating DCVST with hemorrhagic infarction.

Sildenafil-related cerebral venous sinus thrombosis and papilledema: a case report of a rare entity.

We present a rare case of cerebral venous sinus thrombosis associated with long-term and high-dose use of sildenafil. A 29-year-old man was referred to our neuroophthalmology clinic for bilateral visual deterioration and severe headache. He had stage 2 papilledema and other clinical and neurological examinations were normal. He had used the drug for nearly 2 years, two to three times a day. All laboratory parameters including blood count cell, coagulation panels, and genetic tests including methylene-tetrahydrofolate reductase and factor V Leiden mutation were unremarkable. The brain magnetic resonance imaging result confirmed transverse cerebral venous sinus thrombosis (CVST). The opening pressure of cerebrospinal fluid (CSF) was 43 cm H2O with normal biochemistry and no cells. Clinicians must be aware of the possibility of CVST when the patient uses sildenafil.

Idiopathic intracranial hypertension in a paediatric population: a retrospective observational study on epidemiology, symptoms and treatment.

Idiopathic intracranial hypertension (IIH) is a disorder of unknown origin, which is characterized by elevated intracranial pressure (ICP) without underlying etiological evidence of neurological disease. The purpose of the current study was to evaluate epidemiological features, clinical presentation, diagnostic findings and treatment of sixteen children (7 males and 9 females) with IIH. Medical records of the patients were obtained from the University Paediatric Hospital of Catania, Italy. Clinical features, investigations and treatment approaches were retrieved. The mean age of the sixteen children at onset of symptoms was 9 years (range: 4 to 16 years). Most of the patients were classified as pre-pubertal. Mean BMI was 28.9 kg/m2. In 93.75% of patients headache was the presenting clinical symptom; and in the same percentage papilledema was detected as the accompanied sign during diagnostic flow-chart. The mean lumbar puncture opening pressure (LPOP) was 350 mm H2O. Fifty percent of the cases had normal brain imaging, while 12.5% showed enlarged optic nerve diameter and one patient had an intraocular protrusion of the optic nerve on MRI. Two patients (12.5%) had venous sinus stenosis, and one case showed an abnormal spinal MRI. With regard to therapeutic approaches, 93.75% of the cases were successfully treated with Acetazolamide. None of the patients required surgical procedures, and all neuroimaging findings disappeared after receiving treatment. In the present study we investigated the association of IIH with venous sinus stenosis. We also found ocular ultrasound to be a useful non-invasive alternative method for determining papilledema in paediatric IIH, specifically in an emergency.

[Thrombosis of the sinus durae matris as a complication of therapy in patients with Hodgkin lymphoma].

AIM: To describe thrombosis of the sinus durae matris (TSDM) in lymphomas. SUBJECTS AND METHODS: 402 patients with Hodgkin lymphoma were treated using the BEACOPP-14 protocol in 2006 to 2013. Thrombotic events occurred in 6% of the patients, including 3 (0.8%) who developed brain magnetic resonance imaging-verified TSDM. RESULTS: TSDM developed in 3 women aged 17, 18, and 25 years during 3-6 chemotherapy cycles involving glucocorticosteroids in a dose of 80 mg/m2 on days 1-7 and an oral contraceptive used continuously for 1.5-3 months. The symptoms of thrombosis were severe headache; 2 patients had convulsive syndrome with short-term loss of consciousness. Anticoagulant therapy with intravenous heparin 20,000--24,000 U/day led to thrombus recanalization within 4-10 days. No rethromoboses were observed during a subsequent follow-up. CONCLUSION: The BEACOPP-14 treatment in young women with Hodgkin lymphoma who continuously take oral contraceptives should be combined with anticoagulant therapy, by monitoring their coagulogram.

Endovascular management of cerebral venous sinus thrombosis.

Cerebral venous sinus thrombosis (CVST) is characterized by formation of widespread thrombus within the cerebral venous sinus system. CVST can cause venous hypertension, venous infarcts, hemorrhage and seizures. It is managed in most cases with systemic anticoagulation through the use of heparin to resolve the thrombus. Patients that demonstrate clinical deterioration while on heparin are often treated with endovascular strategies to recanalize the sinuses. We present the case of a patient with widespread CVST, involving his superior sagittal sinuses and bilateral transverse sigmoid sinuses, who was treated with a combination of endovascular therapies. The video can be found here: http://youtu.be/w3wAGlT7h8c .

Impact of anticoagulation on the short-term outcome in a population of neonates with cerebral sinovenous thrombosis: a retrospective study.

To investigate the impact of anticoagulation on short-term outcome (1 month) in neonates with cerebral sinovenous thrombosis, the authors conducted a retrospective chart review of neonates admitted to 2 tertiary hospitals over a 5- and 8-year period, respectively. Neonates with confirmed radiographic evidence of cerebral sinovenous thrombosis were included. Eighteen total patients treated with hydration only were identified. Approximately 50% of these neonates showed clot extension or other complications on follow-up imaging that were obtained within 72 hours with either magnetic resonance imaging or computed topography. Five neonates were treated with anticoagulation, and none of these patients developed new infarcts or hemorrhages. The results of this retrospective study suggest that anticoagulation is safe in neonates with cerebral sinovenous thrombosis. Early follow-up scans can help treatment decision. Larger studies are needed to develop standardized guidelines for the evaluation and treatment of neonatal cerebral sinovenous thrombosis.

Role of coagulation factors in cerebral venous sinus and cerebral microvascular thrombosis.

OBJECTIVE: The objective of this study was to define the relative contributions of three major pro- and anti-coagulation pathways (heparin-antithrombin, protein C, and tissue factor (TF)) in the thrombogenic responses that occur in large and small vessels of the brain. METHODS: Cerebral venous sinus thrombosis was induced by topical application of FeCl3 on the superior sagittal sinus, while photoactivation of fluorescein was used to induce thrombus formation in cerebral microvessels. Heparin, activated protein C (APC), and antibodies to either APC or TF were used to assess thrombogenesis in wild-type mice. Mutant mice that overexpress the endothelial protein C receptor (EPCR-tg) or with TF deficiency in Tie2-expressing endothelial cells (LTFE) were also used. RESULTS: Thrombus formation in the superior sagittal sinus of wild-type mice was attenuated by heparin and in EPCR-tg mice, while treatment with the APC antibodies enhanced thrombogenesis. Arteriolar thrombosis was largely unresponsive to the interventions studied. However, in cerebral venules, thrombosis was inhibited by heparin and in EPCR-tg mice. TF antibody treatment also inhibited venular thrombosis, with a similar attenuation noted in LTFE mice. CONCLUSION: Thrombin promotes while the APC pathway blunts thrombus formation in an experimental model of cerebral venous sinus thrombosis. TF involvement is more evident in cerebral microvascular thrombogenesis, with endothelial cell-associated TF mediating this response in venules, but not arterioles.

Continuous thrombolysis and repeated thrombectomy with the Penumbra System in a child with hemorrhagic sinus thrombosis: technical note.

UNLABELLED: Cerebral venous sinus thrombosis (CVST) is an uncommon but potentially lethal event. When showing a malignant clinical course despite anticoagulant therapy, new endovascular techniques and technology allow the possibility of more aggressive thrombolysis and thrombectomy. The authors present a case of recanalization of an extensive cerebral thrombosis using a new endovascular thromboaspiration device, the Penumbra System. BACKGROUND AND PURPOSE: CVST in children is a rare but potentially lethal disorder. When showing a malignant progression despite anticoagulant therapy, the use of local thrombolytics and thrombectomy procedures might provide therapeutic solution. METHODS: A 16-year-old girl presented with signs and symptoms of a hemorrhagic cerebral sinus thrombosis and showed progression despite full dose anticoagulant therapy. The evolution being attributed to increasing mass effect, decompressive surgery was performed without clinical improvement. Further brain imaging demonstrated progression of the sinus thrombosis. Repeated local thrombectomy with the Penumbra thrombectomy system and continuous, relatively low dose local thrombolysis was performed during a period of 60 h, resulting in recanalization and clinical improvement. The methodology of combined thromboaspiration and thrombolysis is described. CONCLUSIONS: We present a novel method for revascularization using the Penumbra System in combination with long-term, relatively low dose thrombolysis, in the setting of both clinically and morphologically progressive, hemorrhagic sinus thrombosis. The procedure proved to be both safe and effective and may be considered in the future for patients with progressive sinovenous thrombosis despite adequate medical therapy.

Endovascular thrombectomy and thrombolysis for severe cerebral sinus thrombosis: a prospective study.

BACKGROUND AND PURPOSE: Most patients with cerebral sinus thrombosis (CST) recover after treatment with heparin, but a subgroup has a poor prognosis. Those patients may benefit from endovascular thrombolysis. METHODS: Prospective case series. Patients with sinus thrombosis were selected for thrombolysis if they had an altered mental status, coma, straight sinus thrombosis, or large space-occupying lesions. Urokinase was infused into the sinuses (bolus 120 to 600 x 10(3) U; then 100 x 10(3) U/h) via a jugular catheter, in 15 cases combined with mechanical thrombus disruption or removal. RESULTS: We treated 20 patients (16 women), mean age 32 years. Twelve patients were comatose and 14 had hemorrhagic infarcts before thrombolysis. Twelve patients recovered (Rankin score 0 to 2), 2 survived with handicaps, and 6 died. Factors associated with a fatal outcome were leukemia (3/6 versus 0/14, P=0.02) and large hemorrhagic infarcts (4/6 versus 2/14, P=0.04). Seizures were less frequent in the fatal cases (P=0.05). Patients who died had a larger mean lesion surface than survivors (30.5 versus 13.6 cm(2); P=0.03), larger midline shift (5.2 versus 1.7 mm; P=0.02), and a more rapid course (2.7 versus 8.2 days; P=0.01). Five patients who died had large hemispheric infarcts and edema before thrombolysis, causing herniation. Five patients had increased cerebral hemorrhage (3 minor, 2 major) after thrombolysis. CONCLUSIONS: Thrombolysis can be effective for severe sinus thrombosis, but patients may deteriorate because of increased cerebral hemorrhage. Patients with large infarcts and impending herniation did not benefit.

Recurrent venous thrombosis including cerebral venous sinus thrombosis in a patient taking sildenafil for erectile dysfunction.

Acquired or hereditary prothrombotic risk factors may lead to cerebral venous sinus thrombosis (CVST), particularly when other predisposing factors coexist. A 57-year-old man experienced right leg deep venous thrombosis, severe thrombosis of the haemorrhoid plexus and CVST over a 12-month period during which he was taking sildenafil regularly twice a week. Sildenafil is a phosphodiesterase 5 (PDE5)-inhibitor used for erectile dysfunction (ED). A slight reduction in antithrombin III and free protein S levels was demonstrated. After suspension of sildenafil and six months on oral anticoagulants, clinical improvement was obtained. Recurrent venous thrombosis, including CVST, may complicate prolonged treatment with PDE5-inhibitors in subjects at risk. Periodic monitoring of clotting factors is recommended in these subjects.

Endovascular embolization of the swine rete mirabile with Eudragit-E 100 polymer.

BACKGROUND AND PURPOSE: Both adhesive and nonabrasive embolic agents are available for arteriovenous malformation (AVM) embolization. The purpose of this study was to evaluate a novel ethanol-based nonadhesive liquid embolic material in a swine AVM model. MATERIALS AND METHODS: Eudragit (copolymer of methyl and butyl methacrylate and dimethylaminoethyl methacrylate) was dissolved in 50% ethanol and 50% iopamidol. Eudragit was injected into 9 retia mirabilia (RMs). Ethanol and iopamidol mixture were injected into 4 RMs for comparison. Three RMs embolized with Eudragit mixture were evaluated both angiographically and histopathologically acutely (3-24 hours) and at 30 days and 90 days after embolization. RESULTS: No procedural complications from Eudragrit embolization were noted, including retention or adhesion of the microcatheter. Various degrees of inflammation were observed in the acute and 30-day specimens. Two RMs showed partial recanalization on both histopathology and follow-up angiography in the 30-day group. Arterial fibrosis and calcification were observed in the 30- and 90-day specimens. The internal elastic lamina was disrupted in the 30- and 90-day specimens, but there was no evidence of Eudragit extravasation or hemorrhage. Endothelial damage was seen in all specimens and was particularly severe in the 30- and 90-day specimens. CONCLUSION: Eudragit polymer induced inflammation in thrombosis similar to n-butyl 2-cyanoacrylate, but without the disadvantages of perivascular hemorrhage and extravasation of embolization material. Although recanalization of some embolized RMs was noted, further investigation into Eudragit as a potentially useful embolic material for brain AVMs is warranted.

Intra-arterial administration of fasudil hydrochloride for vasospasm following subarachnoid hemorrhage - analysis of time-density curve with digital subtraction angiography.

The cerebral circulatory dynamics were evaluated before and after intra-arterial administration of fasudil hydrochloride in 20 patients with angiographic vasospasm after subarachnoid hemorrhage (SAH). The region of interest time-density curves obtained before and after intra-arterial administration of fasudil hydrochloride were compared in the proximal portion of the middle cerebral artery in the early arterial phase, the distal portion of the middle cerebral artery in the late arterial phase, and the transverse sinus in the venous phase. In the early arterial phase, the time to peak and the time to half-peak were significantly reduced. In the late arterial phase and venous phase, the time to peak was significantly reduced. These results suggest that intra-arterial administration of fasudil hydrochloride induced dilation of the proximal arteries, and improved cerebral microcirculation. The present study suggests that intra-arterial administration of fasudil hydrochloride is effective as a treatment for vasospasm following SAH.

4991W93 inhibits release of calcitonin gene-related peptide in the cat but only at doses with 5HT(1B/1D) receptor agonist activity?

Calcitonin gene-related peptide (CGRP) is a marker for trigeminovascular activation and is released during the headache phase of migraine and cluster headache. CGRP may have a role in migraine through its potent cranial vasodilator effects, or by an action on trigeminal nerve activity, both of which are targeted by 5HT(1B/1D) agonist drugs. CP122,288, a conformationally restricted analogue of sumatriptan that is a potent inhibitor of neurogenic plasma protein extravasation (PPE), was ineffective at inhibiting CGRP release at a single low dose; and is also ineffective as an acute anti-migraine compound. However, it remained unclear as to whether, as a class, the conformationally-restricted triptan analogues could have inhibitory effects on CGRP in higher doses. 4991W93, a conformationally restricted analogue of zolmitriptan, is also a potent inhibitor of PPE at doses without 5HT(1B/1D)-mediated effects, that was developed as an anti-migraine drug, and thus was suitable to test whether higher doses of such conformationally restricted triptan analogues could inhibit trigeminal-evoked CGRP release. The superior sagittal sinus (SSS) was stimulated in 14 anaesthetised cats and external jugular vein blood samples were analysed by radioimmunoassay for CGRP levels before, 1 min after SSS stimulation, and 1 min after SSS stimulation in the presence of 4991W93. Stimulation of the SSS resulted in release of CGRP from the external jugular vein. 4991W93 at a dose of 0.1 and 10 microg/kg, selected for maximal PPE blocking effects in rodents, was ineffective at inhibiting CGRP release, with an SSS stimulation level of 78+/-4 pmol/l compared to a post-4991W93 level of 79+/-3 pmol/l (n=4). In comparison CGRP release was inhibited after a dose of 100 microg/kg 4991W93 from 64+/-6 to 36+/-3 pmol/l (n=5). Given that 4991W93 is inactive clinically at non-vascular doses, it seems clear that the 5HT(1B/1D) agonist effects of the compound are necessary for blockade of CGRP release and thus any anti-migraine action. Taken with the clinical results, these data emphasise the importance of CGRP release in migraine, and suggest that other non-5HT-based pharmacological targets may account for PPE blockade in animal studies.

Fos expression in the trigeminocervical complex of the cat after stimulation of the superior sagittal sinus is reduced by L-NAME.

Primary neurovascular headaches, such as migraine and cluster headache probably involve activation of trigeminovascular pain structures projecting to the trigeminocervical complex of neurons in the caudal brain stem and upper cervical spinal cord. It has recently been demonstrated that blockade of the synthesis of nitric oxide (NO) by an NO synthesis inhibitor can abort acute migraine attacks and thus it is of interest to determine whether there is an influence of NO generation on trigeminocervical neurons. Cats were anaesthetised with alpha-chloralose (60 mg/kg, i.t.). supplemental 20 mg/kg, intravenously (i.v.)) and halothane for surgery (0.5-3% by inhalation). A circular midline craniotomy was performed to isolate the superior sagittal sinus (SSS) for electrical stimulation (0.3 Hz, 150 V, 250 micros duration for 2 h). Two groups were compared, one stimulated after administration of vehicle and the other stimulated after administration of N(G)-nitro-L-arginine methylester (L-NAME: 100 mg/kg, i.v.). After stimulation of the SSS Fos immunoreactivity was observed in lamina I/IIo of the trigeminal nucleus caudalis and dorsal horns of C1 and C2 to a median total of 136 cells (range 122-146). After L-NAME treatment Fos expression was significantly reduced to 40 cells (24-54; P < 0.02). In conclusion, inhibition of NO synthesis L-NAME markedly reduces Fos expression in the trigeminocervical complex of the cat. These data taken together with the clinical observations of the effect of NO synthesis blockade in migraine suggest a role for NO generation in mediating nociceptive transmission in acute migraine.

Differential effects of low dose CP122,288 and eletriptan on fos expression due to stimulation of the superior sagittal sinus in cat.

CP122,288, a conformationally restricted analogue of sumatriptan, is a highly potent inhibitor of neurogenic plasma protein extravasation (PPE) in rat and guinea pig at low doses where it has no 5HT1B-mediated vascular actions. We have examined its effect on a model of trigeminovascular nociception to assess the relative importance of vasoconstrictor and serotonin (5HT)(1B/1D) agonist activity to the modulation trigeminal neuronal activation. For comparison to activate relevant 5HT receptors, the clinically effective relatively lipophilic 5HT(1B/1D) agonist eletriptan was studied in parallel. The superior sagittal sinus was isolated in the alpha-chloralose (60 mg/kg, i.p. and 15-20 mg/kg i.v. supplement every 2 h) anaesthetized cat. Animals were prepared for stimulation and then maintained for 24 h before stimulation and perfusion for Fos immunohistochemistry. Stimulation of the superior sagittal sinus (250 micros, 100 V, 0.3 Hz) resulted in Fos expression in cells in the trigeminal nucleus caudalis and superficial laminae of the dorsal horns of C(1-2). Administration of low dose CP122,288 (100 ng/kg) had no effect on Fos expression after sinus stimulation either when administered alone or in combination with mannitol; the latter to ensure access to the trigeminocervical complex. The number of cells in the superficial laminae of the trigeminal nucleus caudalis with stimulation being a median of 50 (quartile range: 47-53) and 48 (35-48) after CP122,288, and after CP122,288 and mannitol 45 (41-53). In comparison, the clinically effective 5HT(1B/1D) agonist, eletriptan, reduced Fos expression in the trigeminocervical complex to a median of 24 (21-33). These data demonstrate that the potent inhibitor of neurogenic plasma protein extravasation (PPE) CP122,288 has no effect on Fos expression in central trigeminal neurons when administered at a dose which blocks PPE in rat and guinea pig, but has no vasoconstrictor 5HT(1B/1D) activity, and while ensuring its access to central trigeminal neurons. The data suggest that activation of the 5HT(1B/1D) receptor is important for the clinical action of this class of compounds and is consistent with the fact the CP122,288 is ineffective in the treatment of the acute attack of migraine.

Substance P blockade with the potent and centrally acting antagonist GR205171 does not effect central trigeminal activity with superior sagittal sinus stimulation.

The development and use of serotonin-1B/1D agonists to treat the acute attack of migraine has been a significant advance, but their vasoconstrictor effects have lead to a search for non-vasoconstrictor approaches to the management of the acute attack of migraine. One such suggested approach has been substance P (neurokinin-1) antagonists, since substance P is involved in mediating neurogenic plasma protein extravasation and has long been held to have a role in pain transmission. In this study, one such candidate compound, GR205171, a highly lipophilic potent neurokinin-1 antagonist, has been tested in a model of trigeminovascular nociception with considerable predictive value for anti-migraine activity. The superior sagittal sinus was isolated in the alpha-chloralose (60 mg/kg, i.p., and 20 mg/kg, i.v., supplemented every 2 h)-anaesthetized cat. The sinus was stimulated electrically (100 V, 250 micros duration, 0.3 Hz) and neurons in the dorsal C2 spinal cord monitored using electrophysiological methods. In separate experiments, the animals were prepared for stimulation and then maintained for 24 h before stimulation and perfusion for Fos immunohistochemistry. Stimulation of the superior sagittal sinus resulted in activation of cells in the dorsal horn of C2. Cells fired with a probability of 0.7 +/- 0.1 at a latency of 10.7 +/- 0.2 ms. Administration of GR205171 (100 microg/kg, i.v.) had no effect on probability of firing or latency. Stimulation of the sinus in separate cats resulted in increased expression over control levels in the superficial laminae of the trigeminal nucleus caudalis and C1/2 dorsal horns. GR205171 in the same dose had no effect upon Fos expression. Inhibition of substance P by the potent, selective and brain penetrant neurokinin-1 antagonist GR205171 had no effect upon either cell firing or Fos expression in the central trigeminal cells activated by stimulation of the superior sagittal sinus. These data and the published clinical data for other compounds suggest that neurokinin-1 blockade alone will not be an effective anti-migraine strategy. Further data will be required to assess whether neurokinin-1 antagonists will have any more general value in pain.

Zolmitriptan (311C90) does not interact with fluoxetine in healthy volunteers.

Zolmitriptan (Zomig, formerly 311C90) is a selective 5-hydroxytryptamine (5-HT)1B/1D-receptor agonist with central and peripheral activity for the acute treatment of migraine. This randomized, placebo-controlled, crossover study investigated the effects of fluoxetine administration on the pharmacokinetics and pharmacodynamics of zolmitriptan. Twenty volunteers were given single doses of fluoxetine 20 mg or an identical placebo daily for 28 days prior to receiving a single 10 mg oral dose of zolmitriptan. Sixteen volunteers completed the two treatment phases. The pharmacokinetic parameters of zolmitriptan and its metabolites were not significantly affected by fluoxetine pretreatment. The pharmacodynamic effects of zolmitriptan were also unaffected by fluoxetine pretreatment. There were small, clinically insignificant increases in blood pressure following zolmitriptan which were unaltered by fluoxetine. Zolmitriptan was well tolerated when given alone or concomitantly with fluoxetine. These results indicate that there is no contraindication to the use of zolmitriptan in patients treated concurrently with selective serotonin reuptake inhibitors and that no adjustment of the zolmitriptan dose is required in these circumstances.

Effects of indomethacin on brain blood flow, cerebral metabolism, and sagittal sinus prostanoids after hypoxia.

We tested the hypotheses that during recovery from hypoxia, newborn piglets exhibit a posthypoxic cerebral hyperemia, indomethacin-pretreated piglets exhibit a posthypoxic cerebral hypoperfusion, and that the changes caused by indomethacin are dose dependent and related to the loss of prostanoids. We studied piglets exposed to 40 min of hypoxia after pretreatment with high (5 mg/kg, n = 9) or low (0.3 mg/kg, n = 8) doses of indomethacin or placebo (n = 9) and allowed to recover for 120 min. In the placebo and low-dose pretreatment groups, total and regional brain blood flow increased during hypoxia but returned to baseline 10 min after hypoxia. High-dose indomethacin pretreatment was associated with a posthypoxic hypoperfusion to certain brain regions at 10 min of recovery to values similar to those after indomethacin treatment before the onset of hypoxia. During and after hypoxia, the cerebral metabolic rate of oxygen was preserved in both the placebo and low-dose groups and decreased significantly during hypoxia in the high-dose group. Sagittal sinus prostacyclin was reduced significantly in both indomethacin-treated groups throughout the study. We conclude that a posthypoxic hyperemia is not observed in newborn piglets. This finding was not altered by pretreatment with a therapeutic dose of indomethacin, whereas a pharmacological dose was associated with selective hypoperfusion to certain brain regions both before hypoxia and during recovery from hypoxia.

CSF, sagittal sinus, and jugular venous pressures during desflurane or isoflurane anesthesia in dogs.

Previous studies to determine whether desflurane increases cerebrospinal fluid (CSF) pressure are inconclusive because none have included all of the following: multiple doses of desflurane, administration for at least several hours, examination at normo- and hypocapnia, a concurrent comparison group, direct measurement of both intra- and extracranial CSF pressures, and measurement of venous pressures that influence CSF pressure. The present study was designed to determine whether CSF pressure increases during 4.0 h desflurane anesthesia using a study design that included the above elements. Catheters were placed in the lateral cerebral ventricle, cisterna magna, sagittal sinus, and jugular vein of 12 dogs anesthetized with thiopental 12 mg.kg-1.h-1 and halothane 0.5 to 0.8%. Catheter pressures were measured, and the CSF-sagittal sinus pressure gradient and slope of the gradient to CSF pressure relationship were determined during control conditions. Then, 6 dogs were anesthetized with desflurane and 6 dogs were anesthetized with isoflurane, and the same values were determined for 1.0 h at each of four experimental conditions: 0.5 and 1.0 minimum alveolar concentration (MAC) during normocapnia (PaCO2 35-39 mm Hg) and 0.5 and 1.0 MAC during hypocapnia (PaCO2 20-24 mm Hg). CSF and sagittal sinus pressures, but not jugular venous pressure, increased with both desflurane and isoflurane. The greater increase of CSF pressure with 4.0 h desflurane (to 40.2 +/- 12.7 cm H2O) than with 4.0 h isoflurane (to 26.2 +/- 11.5 cm H2O) was attributable to an increase of CSF pressure that was greater during 2.0 h desflurane and normocapnia than during 2.0 h isoflurane and normocapnia, and to an increase of CSF pressure during 2.0 h desflurane and hypocapnia that was similar to that during 2.0 h isoflurane and hypocapnia. The greater increase of CSF pressure during desflurane may have resulted, in part, from increased CSF volume as indicated by a positive CSF-sagittal sinus pressure gradient (in contrast, there was little or no CSF-sagittal sinus pressure gradient during isoflurane) and a steeper slope of the gradient to CSF pressure relationship.