Tetsuro Sayama

Role of inducible nitric oxide synthase in the cerebral vasospasm after subarachnoid hemorrhage in rats

The involvement of de novo nitric oxide synthase (NOS) induction in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH) was examined using a rat model of SAH. SAH was induced by endovascular perforation with Nylon thread. The rats were killed at different time intervals, from one day to seven days after endovascular perforation. Inducible NOS messenger RNA (mRNA) expression was determined by reverse-transcription polymerase chain reaction (RT-PCR) and the distribution of iNOS positive cells was immunohistochemically examined. In the vascular tissue with a subarachnoid membrane, iNOS mRNA was expressed from one day to seven days after SAH. Inducible NOS positive cells were mainly recognized in the vascular tissue, but not in the brain parenchyma. The distribution of nitrotyrosine, an indicator of peroxynitrite production was also examined immunohistochemically and nitrotyrosine-positive cells were observed almost at the same sites of iNOS induction. To determine the role of iNOS in the development of cerebral vasospasm, we measured the diameter of the middle cerebral artery in animals either treated or not treated with aminoguanidine (AG), a selective inhibitor of iNOS. AG ameliorated the vasoconstrictive change after SAH. These results are thus considered to provide molecular and immunohistochemical evidence showing that iNOS expression following SAH and NO produced by iNOS can develop cerebral vasospasm after SAH.

High incidence of hyponatremia in patients with ruptured anterior communicating artery aneurysms.

Abstract We studied the incidence and timing of hyponatremia (Na < 135 mEq l~1) after subarachnoid hemorrhage (SAH) with special reference to ruptured anterior communicating artery (A-com) aneurysms. Hunt and Kosnik (HK) grading, symptomatic vasospasm in A-com aneurysm, and hydrocephalus were analyzed for connections to hyponatremia in 55 patients with ruptured A-com aneurysms, 65 with ruptured internal cerebral artery (ICA) aneurysms, and 49 with ruptured middle cerebral artery (MCA) aneurysms. Hyponatremia occurred in 28 (51%) of 55 patients with A-com aneurysms and in nine (18%) of 49 patients with MCA aneurysms. Severe hyponatremia (Na < 130 mEq-1) occurred in 16 patients (29%) in the A-com group, four patients (6%) in the ICA group, and three patients (6%) in the MCA group. The A-com aneurysm group had a significantly higher incidence of mild hyponatremia (p < 0.01) and severe hyponatremia (p< 0.001) than other groups. Among A-com cases, hyponatremia occurred significantly more often in HK grade III and IV cases (p < 0.05), in cases with vasospasm (p < 0.001), and in cases with hydrocephalus (p < 0.01). Respective days of onset for symptomatic vasospasm and for hyponatremia were day 7.6 ±4.4 and day 10.6± 5.8 following SAH, representing a 3-day delay for hyponatremia (p<0.05). In most patients hyponatremia resolved within 28 days following SAH. Hyponatremia occurred more often with A-com aneurysms, possibly because of vasospasm around the A-com or hydrocephalus causing hypothalamic dysfunction. Since hypervolemic therapy can cause hyponatremia, particularly careful observation is required during such therapy in patients with A-com aneurysm. [Neurol Res 2000; 22: 151-155

EXPRESSION OF INDUCIBLE NITRIC OXIDE SYNTHASE IN RATS FOLLOWING SUBARACHNOID HEMORRHAGE

The possible expression of the inducible isoform of nitric oxide synthase (iNOS) was examined in a rat model of subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage was induced by the injection of autologous blood into the cisterna magna using stereotactic technique under general anesthesia. The rats were then killed at specific time intervals between 4 hours to 7 days after SAH. Reverse-transcriptional polymerase chain reaction (RT-PCR) revealed the expression of iNOS mRNA in the homogenate obtained from the tissue around the circle of Willis one day after SAH (Day 1). No iNOS mRNA was detected either in the sham-operated animals, or at any of the other time intervals after SAH. An immunohistochemical study was performed to examine the localization of iNOS-positive cells in the central nervous system. Inducible NOS immunoreactivity was thus observed in the mononuclear cells and polymorphonuclear cells infiltrating into the subarachnoid space of the basal cistern on Day 1. This immunoreactivity persisted faintly on Day 2, but had completely disappeared on Day 7. A vascular diameter study disclosed a vasoconstrictive change in the middle cerebral artery after SAH. Taken together, these results are thus considered to confirm the expression of iNOS in the infiltrated inflammatory cells after the insult of SAH, which may therefore play an introductory role in the development of the pathological series of events after SAH, including vasospasm.

Cilostazol Improves Outcome after Subarachnoid Hemorrhage: A Preliminary Report

Background: Cerebral vasospasm (VS) is the most common cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Reversal of VS by intra-arterial infusion of cyclic adenosine monophosphate (cAMP)-elevating agents has been reported; however, the preventive role in the development of VS is not fully understood. This study is designed to evaluate the possible efficacy of using cilostazol, a selective inhibitor of phosphodiesterase type 3 and a cAMP-elevating agent, in patients with SAH. Methods: In this prospective randomized study, we enrolled 100 SAH patients who met the following criteria: neck clipping within 72 h after onset, Hunt and Hess (HH) score ≤4, modified Rankin scale (mRS) score ≤2 prior to ictus, and no serious cardiovascular complications. Patients were divided into control and cilostazol groups; we focused on the effects of cilostazol on the decrease in the incidence of symptomatic VS, cerebral infarction, and the mRS score at discharge. Result: Patients’ age, male/female ratio, mRS score prior to ictus, HH grade, Fisher group, site of the aneurysm, drugs prescribed during the observation period, and length of hospital stay were not different between the groups. Cilostazol did not significantly decrease the incidence of symptomatic VS (37.3% in the control vs. 22.4% in the cilostazol group, p = 0.183) and cerebral infarction (27.5% in control vs. 10.2% in the cilostazol, p = 0.091). However, mRS score was significantly improved at discharge (2.6 in controls vs. 1.5 in the cilostazol group, p = 0.041). Patients’ age being ≤65 years (OR = 8.47, 95% CI = 2.45–29.32, p = 0.0007), Fisher group ≤3 (OR = 4.64, 95% CI = 1.00–21.45, p = 0.049), HH grade ≤2 (OR = 4.31, 95% CI = 1.27–14.59, p = 0.019), no hydrocephalus (OR = 8.55, 95% CI = 1.72–19.23, p = 0.0046), and cilostazol use (OR = 5.52, 95% CI = 1.61–18.90, p = 0.0065) were independent predictors of good outcomes (mRS score ≤2). Conclusion: Cilostazol may improve outcomes after SAH, but further double-blind, placebo-controlled studies are required for a definitive conclusion.

Normal diffusion-weighted imaging in cerebral air embolism complicating angiography

Abstract We report a case of cerebral air embolism resulting from accidental air infection during cerebral angiography. A 60-year-old man was accidentally injected with air via the left subclavian artery. Angiography demonstrated air within the basilar artery. The patient showed signs of posterior circulation ischaemia (confusion, blindness, gaze palsy and hemiparesis). However, MRI, including diffusion-weighted imaging, showed no abnormality 4 h later. The patient was treated with hyperbaric oxygen within 5 h of the embolism. All symptoms and signs resolved completely within a week.

Cranial fasciitis with massive intracranial extension

The case of a 10-monthold boy with cranial fasciitis is described. The patient had a rapidly growing subcutaneous mass in the left frontotemporal region. Computed tomography and magnetic resonance imaging clearly demonstrated a mass in the left temporoparietal bone extending both intra-and extracranially. The tumor seemed to originate from the calvarium, being located between the periosteum and the dura mater. Total resection of the tumor was performed, and the tumor was histologically identified as cranial fasciitis. A brief review of the literature is included that emphasizes the need for further investigation of this benign lesion that is frequently confused with a malignant neoplasm.

Three-dimensional CT angiography for the surgical management of the vertebral artery-posterior inferior cerebellar artery aneurysms

SummaryBackground. Surgery of vertebral artery-posterior inferior cerebellar artery (VA-PICA) aneurysms is not easy because there is a close anatomical relationship between aneurysms and the surrounding neurovascular structures, and bony structures in the lateral foramen magnum. The preoperative evaluation for a circumstantial comprehension of anatomical relationships is very important for the surgical treatment of the VA-PICA aneurysms. Our experience in using three-dimensional CT angiography (3D-CTA) for the surgical management of VA-PICA aneurysms is herein reported. Methods and findings. We successfully performed neck clipping in 5 cases of VA-PICA aneurysm using 3D-CTA. On 3D reconstructed images, we could see the characteristics of the aneurysms such as their relationships to the jugular tubercle and hypoglossal canal, the projecting direction of the dome, and the configuration of the neck in each case. 3D-CTA also provided a clear surgical view as well as the relationships of the aneurysms to the VA and origin of the PICA. Based on such information, we selected the most appropriate surgical approach among the transcondylar fossa approach, the transcondylar approach, or the far lateral approach with a C1 laminectomy. Conclusions. Since 3D-CTA demonstrates the surgical anatomy of VA-PICA aneurysms in detail, it is very useful for helping surgeons to select the optimal approach.

Intraarterial injection of colforsin daropate hydrochloride for the treatment of vasospasm after aneurysmal subarachnoid hemorrhage: preliminary report of two cases

We describe two patients with symptomatic vasospasms after aneurysmal subarachnoid hemorrhage who were successfully treated with intraarterial injection of colforsin daropate hydrochloride (HCl). Colforsin daropate HCl is capable of directly stimulating adenylate cyclase, which in turn causes vasorelaxation via elevated intracellular concentrations of cyclic adenosine monophosphate. We suggest that colforsin daropate HCl might be a useful therapeutic tool in treating cerebral vasospasm.

Arterial Spin Labeling Perfusion Magnetic Resonance Image with Dual Postlabeling Delay: A Correlative Study with Acetazolamide Loading 123I-Iodoamphetamine Single-Photon Emission Computed Tomography

BACKGROUND Perfusion magnetic resonance image with arterial spin labeling (ASL) provides a completely noninvasive measurement of cerebral blood flow (CBF). However, arterial transient times can have a marked effect on the ASL signal. For example, a single postlabeling delay (PLD) of 1.5 seconds underestimates the slowly streaming collateral pathways that maintain the cerebrovascular reserve (CVR). To overcome this limitation, we developed a dual PLD method. SUBJECTS AND METHODS A dual PLD method of 1.5  and 2.5 seconds was compared with (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading to assess CVR in 10 patients with steno-occlusive cerebrovascular disease. RESULTS In 5 cases (Group A), dual PLD-ASL demonstrated low CBF with 1.5-second PLD in the target area, whereas CBF was improved with 2.5-second PLD. In the other 5 cases (Group B), dual PLD-ASL depicted low CBF with 1.5-second PLD, and no improvement in CBF with 2.5-second PLD in the target area was observed. On single-photon emission computed tomography, CVR was maintained in Group A but decreased in Group B. CONCLUSIONS Although dual PLD methods may not be a completely alternative test for (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading, it is a feasible, simple, noninvasive, and repeatable technique for assessing CVR, even when employed in a routine clinical setting.

Arterial Spin-Labeling Magnetic Resonance Perfusion Imaging with Dual Postlabeling Delay in Internal Carotid Artery Steno-occlusion: Validation with Digital Subtraction Angiography

BACKGROUND Arterial spin-labeling magnetic resonance perfusion imaging (ASL-MRI) allows noninvasive measurement of cerebral blood flow (CBF) but depends on the arterial transit time (ATT). With the commonly used single postlabeling delay (PLD) of 1.5 seconds, slow flow through collateral vessels may be underestimated. We used both 1.5 and 2.5 seconds to overcome this problem. We validated these PLD settings by measuring the ATT and identifying the angiographic circulation using digital subtraction angiography (DSA). METHODS We retrospectively selected 5 patients with unilateral occlusion or stenosis of the internal carotid artery (ICA) in whom ASL-MRI showed low CBF with 1.5-second PLD in the target area and improved CBF with 2.5-second PLD. We then compared the ASL-MRI findings visually with DSA findings at 1.5 and 2.5 seconds after injection of the contrast. When arterial transit artifacts (ATAs), attributed to stagnant intravascular spin-labeled blood, were observed, DSA findings were analyzed visually at 4.5 seconds. RESULTS DSA revealed that the hypovascular area seen at 1.5 seconds was improved via the primary and secondary collaterals and delayed anterograde flow at 2.5 seconds. Serpiginous or round-shaped ATAs, which appeared in nearly the same configuration on dual PLD ASL-MRI, were attributed to stagnant collaterals and flow in the M2 portion of the middle cerebral artery and ICA during the late venous phase. CONCLUSIONS Use of dual PLD times was validated by the DSA findings. ATA detection using the dual PLDs also differentiated well-developed and stagnant collateral vessels from focal hyperperfusion.