Does Gross Total Resection Improve Progression-Free and Overall Survival in Pediatric Intracranial Ependymomas? Single-Center Clinical Experience Of 61 Cases.

OBJECTIVE: To share our clinical experience of 25 years and identify prognostic factors for progression-free and overall survival in pediatric intracranial ependymomas. METHODS: In total, 61 children who were treated between 1995 and 2020 in a single institution were included in the study. Medical records of the patients were retrospectively reviewed to obtain and analyze the following data: patient age at first surgery, sex, presenting symptoms, hydrocephalus and any invasive treatment, anatomic site, extent of resection, pathologic grade, time to progression, and time to death. Progression-free and overall survival rates and affecting factors were analyzed by Kaplan-Meier method. RESULTS: Dysphagia, number of surgeries, and spinal seeding were associated with progression free and overall survival in univariate analysis. The extent of resection, World Health Organization grade, and visual problems were also associated with progression whereas sex was associated with overall survival. Cox regression identified the extent of resection and single surgery as an independent prognostic factor for progression-free survival. No independent factor was found for overall survival. CONCLUSIONS: This single center experience of 25 years confirms the beneficial effect of gross total resection on disease progression. Although spinal seeding seems to affect survival rates, greater number of cases are needed to reveal its full effect.

The effect of pentoxifylline on cerebral vasospasm following experimental subarachnoid hemorrhage.

OBJECTS: Cerebral vasospasm is an important event that occurs following subarachnoid hemorage which has significant mortality and morbidity. The goal in this study was to investigate the effect of pentoxifylline on vasospasm in an experimental subarachnoid hemorrhage model. METHODS: In this study, 20 male New Zeland White rabbits weighing 3000-3500 g were assigned randomly to four groups. Animals in group 1 served as controls. Animals in group two received only intravenous pentoxifylline injection 3 times in 12 h intervals. In group 3, SAH was induced and no injection was given. Animals in group 4 received intravenous pentoxifylline (6 mg/kg) injections 3 times at 12th, 24th and 36th hours after subarachnoid hemorrhage induction. All animals were sacrificed and basilar arteries were removed at 48th hour. Basilar artery vessel diameters, wall thicknesses and luminal section areas were measured with Spot for Windows version 4.1. Statistical analysis was performed using ANOVA and Kruskall-Wallis tests. RESULTS: Mean basilar artery luminal section areas and luminal diameters in group 4 were significantly higher compared to group 3 (p < 0.05). Basilar artery wall thicknesses and were found to be higher in group 3 than in other groups and this was also statistically significant (p < 0.05). CONCLUSION: Our study demonstrated that intravenous administration of pentoxifylline significantly decreases vasospasm after subarachnoid hemorrhage.

Azathioprine as a Neuroprotective Agent in Experimental Traumatic Spinal Cord Injury.

AIM: To evaluate the protective effects of azathioprine, a macrophage-inhibiting agent, on secondary injury in spinal cord trauma. MATERIAL AND METHODS: A total of 40 Wistar rats were randomly divided into 4 groups. All the animals had undergone T8-10 laminectomy. Except in group I (control), all the animals were exposed to spinal cord trauma at the T9 level. Animals in group II (trauma) received no treatment following trauma. Animals in group 3 (treatment) and group IV (vehicle) were given intraperitoneal azathioprine 4 mg/kg and saline 2 ml, respectively, 30 minutes after the trauma. Half of the animals in each group were sacrificed 24 hours after injury and specimens were used for biochemical and immunohistochemical evaluations. The rest of the animals were followed-up for 4 weeks in terms of neurological functions and were also sacrificed to perform the histopathological analysis. RESULTS: Significant decrease in apoptotic cells and improved neurological function were observed in the animals treated with azathioprine. Biological and immunohistochemical analysis also showed less oxidative stress in this group compared to those without treatment. CONCLUSION: Azathioprine, a potent macrophage-inhibiting agent, has been shown to decrease the extent of secondary injury following spinal cord trauma.

Investigation of the Possible Protective Effects of Ketamine and Dantrolene on the Hippocampal Apoptosis and Spatial Learning in Rats Exposed to Repeated Electroconvulsive Seizures as a Model of Status Epilepticus.

AIM: To evaluate the possible neuroprotective effects of ketamine and dantrolene on the hippocampal apoptosis and spatial learning in rats exposed to repeated electroconvulsive seizures (ECS) as a model of status epilepticus (SE). MATERIAL AND METHODS: Twenty-four rats were assigned to 4 groups. 1st Group was Sham. 2nd Group was ECS: ECS was induced by ear electrodes via electrical stimulation. The same ECS protocol was applied to the 3th and 4th Groups which received ketamine (40 mg/kg s.c.) or dantrolene (5 mg/kg i.p.) 1 h before each ECS, respectively. Following 30 days of recovery, the cognitive status of the animals was evaluated via Morris Water Maze (MWM). The same experimental protocol was repeated 14 days afterward to evaluate the retention of the memory. Hippocampal apoptosis was examined in corresponding experimental groups. RESULTS: All the animals in four groups learned the task with no significant difference between groups in MWM. The ECS+ketamine group showed memory impairment 14 days afterward. ECS+dantrolene group was not different from controls. ECS caused long term apoptotic processes in dentate gyrus (DG) and non-apoptotic neuronal injury in CA1 and CA2. CONCLUSION: Dantrolene and ketamine inhibited apoptosis and showed neuroprotective effects. Although ketamine and dantrolene inhibited ECS-induced apoptosis and non-apoptotic injury, they did not produce similar effects on memory retention. It will be warranted to evaluate cognitive dysfunction by taking into consideration the other factors in addition to apoptosis and neurodegenerative changes.

Long-Term Outcomes of Pediatric Meningioma Surgery: Single Center Experience with 23 Patients.

AIM: To evaluate the long-term outcomes and prognostic variables in a surgical cohort of pediatric meningiomas treated in a single institution. MATERIAL AND METHODS: Medical records and follow-up notes of 23 pediatric patients aged < 18 years (12 male and 11 female; mean age on presentation, 13.1 ± 4.4 years) harboring 27 meningiomas operated between 1994 and 01/2019 at Hacettepe University Ihsan Dogramaci Children’s Hospital were evaluated. RESULTS: One patient had neurofibromatosis (NF) type 1, and five patients had NF2. Tumors were most commonly located in the convexity (n=6) and parasagittal or falcine (n=6). Gross total resection was performed in 70.4% of cases. WHO grade I tumors accounted for 56% of all cases, whereas high-grade meningiomas accounted for 44% (33% grade II, 11% grade III). The mean follow-up duration was 10.3 ± 7.7 years. Three patients (13%) died during follow-up, and 76.2% of the patients had favorable outcome (Glasgow Outcome Scale > 3) during the last follow-up assessment. Ten patients (43.5%) had relapse. In univariate analysis, low histological grade (p=0.030) and gross total resection (p=0.024) were associated with favorable outcome. The 10-year overall survival rate was 86%. CONCLUSION: Meningiomas in the pediatric age group are surgically treatable tumors with fairly good outcomes. However, relapses are common even for low-grade tumors; therefore, long-term surveillance and aggressive treatment are needed.

Survival Benefit with Gross Total Resection and Adjuvant Radiotherapy in Childhood Atypical Teratoid/Rhabdoid Tumors: Results of a Single-Center Cohort of 27 Cases.

AIM: To share a single center experience with 27 atypical teratoid/rhabdoid tumor (AT/RT) cases, and to determine the effect of gross total tumor resection and other clinical characteristics on the overall survival rate of AT/RT. MATERIAL AND METHODS: We included 27 patients-with a histopathologically confirmed primary intracranial childhood AT/ RT-who were operated in our clinic between January 2000 and December 2017. Age, sex, tumor location, disseminated disease, the presence of hydrocephalus, symptom duration till diagnosis, the extent of resection, and adjuvant radiotherapy were evaluated for their influence on overall survival. RESULTS: Median age at diagnosis for 27 patients was 19.1 months (7.2 months-5 years). Gross total resection was possible in 13 (48.72%) patients. Except for three patients who died of perioperative complications, all patients received chemotherapy and 11 received radiotherapy. In univariate analysis, male sex, older age at diagnosis (≥24 months), gross total resection, and radiotherapy were associated with overall longer survival; however, radiotherapy remained the only significant parameter in multivariate analysis. CONCLUSION: AT/RT is a rare and dreadful brain tumor that has low survival rates despite contemporary treatment. Radiotherapy seems to prolong survival; however, large-scale studies are needed to establish prognostic factors.

Is the Knowledge Pertaining to Adult Glioblastomas Enough for Pediatric Cases? Prognostic Factors in Childhood.

AIM: Pediatric glioblastoma (GBM) is still a topic obscurity. The aim of this study was to explore clinical, radiological and pathological features, and prognostic factors affecting the outcomes. MATERIAL AND METHODS: We retrospectively reviewed our database for prognostic factors for 42 consecutive pediatric patients with histologically proven GBM treated in our hospital. RESULTS: The study reached at 20 boys and 22 girls, with a mean age of 10.2 years. Almost all patients (97.6%) had supratentorial tumors; lobar/hemispheric (68.3%), thalamic (26.8%) and suprasellar-hypothalamic region (4.8%). Total of 11/42 children had seeding metastases (mean 11.5 months) either preoperatively or postoperatively. Gross total resection (GTR) was achieved in 13 patients (30.9%) in the first surgery. Perioperative mortality and morbidity rates were 4.7% and 19%, respectively. Patients were followed for an average of 18.1 months. The median progression-free and overall survivals were 7.0 (95% CI: 5.9-8.0) and 11.0 (95% CI: 8.9-13.1) months, respectively. 1-year, 2-year and 5-year progression-free survival and overall survivals were 30.9% vs. 50.0%, 11.9% vs. 19.0%, 4.8% vs. 9.5%; respectively. CONCLUSION: Gross total resection should be safely attempted in pediatric GBM. In addition, a thorough and frequent radiological evaluation of the entire neuraxis for seeding metastases is recommended both at diagnosis and follow-ups.

Traumatic Acute Subdural Hematomas: Analysis of Outcomes and Predictive Factors at a Single Center.

AIM: In the present study, we evaluated the association of the Glasgow Coma Scale (GCS) score and amount of blood loss with mortality in patients presenting with traumatic acute subdural hematoma (ASDH). MATERIAL AND METHODS: This retrospective study was performed on 99 patients who were operated for traumatic acute subdural hematoma (ASDH) without any systemic association at a single center. Epidural hematoma was reported to be the most common additional pathology. Age, sex, mechanism of trauma, time interval between onset of trauma and admission to the emergency ward, associated problems, thickness of hematoma and Glasgow Coma Scale (GCS) score at the time of admission and on discharge were all studied. RESULTS: The GCS score was inversely proportional to the thickness of hematoma and interval between onset of trauma and surgery (p < 0.05). Although the mortality rate was reported to be high in traffic accidents, the rate was low in patients with head trauma only (p < 0.05). The mortality rate was high in patients with associated pathologies (p < 0.05). Lost patients were reported to be older patients with more extensive ASDH or those who presented earlier with a low GCS (p < 0.05). CONCLUSION: ASDH is associated with high mortality. GCS score and the thickness of the ASDH are important predictors of mortality. Age, additional trauma, and interval between trauma and hospital admission are major predictive factors for mortality.

Topiramate as a neuroprotective agent in a rat model of spinal cord injury.

Topiramate (TPM) is a widely used antiepileptic and antimigraine agent which has been shown to exert neuroprotective effects in various experimental traumatic brain injury and stroke models. However, its utility in spinal cord injury has not been studied extensively. Thus, we evaluated effects of TPM on secondary cellular injury mechanisms in an experimental rat model of traumatic spinal cord injury (SCI). After rat models of thoracic contusive SCI were established by free weight-drop method, TPM (40 mg/kg) was given at 12-hour intervals for four times orally. Post TPM treatment, malondialdehyde and protein carbonyl levels were significantly reduced and reduced glutathione levels were increased, while immunoreactivity for endothelial nitric oxide synthase, inducible nitric oxide synthase, and apoptotic peptidase activating factor 1 was diminished in SCI rats. In addition, TPM treatment improved the functional recovery of SCI rats. This study suggests that administration of TPM exerts neuroprotective effects on SCI.

Outcomes and demostration of cranial firearm injuries: A multicenter retrospective study.

BACKGROUND: Cranial firearm injuries (CFAI) are associated with significant morbidity and mortality.This study was aimed to determine the factors affecting mortality of CFAI cases managed in our institution by a retrospective analysis of CT scans and clinical data. METHODS: This multicenter retrospective study examined two hundred and nineteen patients presenting to neurosurgery clinics after CFAI between January 2012 and November 2014. Age, sex, Glasgow Coma Score (GCS), CT findings, and mortality and morbidity rates of the patients were analyzed to determine the factors affecting mortality. RESULTS: Mean age of the study population was 24.19±12.25 years, 85.8% of them were male. The most common CT findings were fracture (100%), intracranial hemorrhage (61.2%), and an intracranially located foreign body (44.3%). A cranial operation was performed in 64.8% of the victims. Mean GCS on admission was 8±3.9, which increased in survivors (p<0.05). CONCLUSION: CFAIs are associated with increased mortality and morbidity. We determined that many factors affected morbidity and mortality rates, and patient age, presence of intracranial hemorrhage, GCS, and treatment protocols were significantly associated with mortality.

Enigmatic entity in childhood: clival chordoma from a tertiary center's perspective.

PURPOSE: Chordoma is a rare neoplasm that arises from embryonic notochordal remnants along the axial skeleton (i.e., clivus, sacrum) and the vertebral bodies. They comprise less than 1 % of CNS tumors and 1-4 % of all bone malignancies. It rarely affects children and adolescents (<5 %). Chordomas are locally aggressive and highly recurrent. Their management is challenging for clinicians. METHODS: This retrospective study includes six pediatric patients with pathological evidence of clival chordoma. These cases were identified over a period of 15 years in a tertiary care institute. RESULTS: There were two boy and four girls with a mean age of 10.6 years (range, 4-16 years). The chief complaint was due to cranial nerve palsy (or dysfunction), mostly affecting lower cranial nerves (66.6 %), followed by diplopia and headache. One patient had obstructive sleep apnea. All patients were operated and a total of 15 surgeries were performed (mean, 2.5). Tumor recurrence was observed in four patients (67 %). Two-year and 5-year progression-free survivals (PFS) were 67 and 33 %, respectively. None of the patients were lost either during the surgery or the follow-up period (6.9 years: 1-14 years). CONCLUSIONS: Clival chordomas are challenging tumors in neurosurgical practice. A multidisciplinary approach is warranted in each patient. Today, the best management strategy seems to be surgical resection followed by radiotherapy. Chemotherapy should be considered in selective and preference basis. Sharing institutional experiences will provide future insights in prognosis of these rare tumors. Implementing newer surgical instruments, endoscope in particular, is encouraged in management of the clival chordomas.

De novo formation of brain tumors in pediatric population following therapeutic cranial irradiation.

PURPOSE: Tumors of central nervous system (CNS) are accounted as the second most common tumors in childhood (21% of all cancers) following hematologic malignancies. The patients can suffer more than one cancer in their lifetime, and radiotherapy is claimed for de novo formation of a new tumor in years after treatment of an initial tumor. METHODS: We have retrospectively analyzed our database for defining radiotherapy-related de novo brain tumors operated in between January, 2000 and August, 2012. New tumors in the field of radiotherapy were included into the study. RESULTS: The retrospective analysis revealed six patients (two girls and four boys) eligible for further evaluation. The children were irradiated at an age in the range of 5 and 12 years (mean, 7.8). The primary diagnoses were hematological malignancies in two (acute lymphocytic leukemia and non-Hodgkin lymphoma (NHL)) and solid tumors in other four (two pilocytic astrocytoma, one craniopharyngioma, and one grade 3 astrocytoma). All patients received cranial radiotherapy. The mean latency period for the "second tumor" was 9.5 years. The pathological diagnoses for de novo new tumors were as follows: glial tumor (two cases), medulloblastoma (two cases), mesenchymal tumor (one case), and meningeal sarcoma (one case). All de novo tumors were high graded. Mean survival was 14.6 months. CONCLUSIONS: de novo brain tumors after irradiation has poor prognosis in neurosurgical practice. Vigilance and awareness for possibility of de novo new tumor are warranted for both families and physicians at follow-ups even years after the treatment of initial tumors.

Cavernous malformations of the central nervous system (CNS) in children: clinico-radiological features and management outcomes of 36 cases.

BACKGROUND: Cavernous malformations (CMs) of the central nervous system (CNS) are angiographically occult vascular lesions that affect approximately 0.5 % of the general population, and one quarter of all CMs occurs in children. METHODS: We retrospectively analyzed demographic, clinical, radiological, management, and follow-up data of 36 pediatric patients with CMs from a single institution. RESULTS: The mean age of the children at first presentation and at operation was 8.7 and 9.6 years, respectively. However, a bimodal age distribution was found with peak under 4 years and above 12 years. Seizure was the most common single presenting symptom (38.9 %), and 61.1 % of patients had at least one seizure before the admission. Focal neurological deficits (410.7 %), intracranial hypertension (27.8 %), and headache (2.8 %) were the other manifestations. Acute/subacute hemorrhage was evident at presentation in 63.9 %. The patients under 6 years of age were found to have significantly more giant cavernomas (69 vs 20 %; p = 0.011), and more overt hemorrhages (81 vs 47 %; p = 0.065) at diagnosis than those patients above 12 years. Surgery was performed in 31 patients (32 CMs), with 26 total and 6 incomplete resections. Mean follow-up duration was 6.9 ± 4.1 years. Of all patients, 63.8 % had excellent and 30.5 % had good clinical outcomes, and also 90.9 % of the epileptic patients were seizure-free (Engel Class I) at the last follow-up. CONCLUSIONS: Younger children tend to harbor larger CMs and present with hemorrhage more frequently than older ones. Microsurgical resection should be the treatment of choice in symptomatic and accessible CMs.

Thalamic tumors in children.

INTRODUCTION: Thalamic tumors are rare tumors which are usually diagnosed in the pediatric age group. Although recent developments in neurosurgical practice allow more radical treatments, information about outcome is scarce for these deep-seated challenging tumors. METHODS: Medical records of 45 pediatric patients who presented with thalamic tumors between 1999 and 2012 were reviewed. DISCUSSION: Prognostic implication of tumor characteristics and patient variables are discussed. Although challenging, recent innovations in the field of neurosurgery and refinements in technique may prolong survival in some cases.

Benign cerebellar pilocytic astrocytomas in children.

AIM: Cerebellar astrocytomas are benign tumors of the central nervous system. They represent 10% of all pediatric intracranial brain tumors and 30% of all pediatric posterior fossa tumors especially in the first two decades of life. MATERIAL AND METHODS: We reviewed the medical records of patients; age at the time of surgery, pre- and post operative magnetic resonance imaging (MRI), localisation of the tumor, hydrocephalus, surgical approach, pre- and post operative neurological status, post operative adjuvant therapy and outcome were documented. RESULTS: The male to female ratio was 20/11. Age at the time of evaluation ranged from 3 to 23 years. Age at the time of surgery ranged from 1 to 18 years. Follow-up duration after surgery was 1-12 years. 55% of these tumors were located at the cerebellar vermis and 45% were at the cerebellar hemispheres. Complete surgical resection was done in 74% of these patients. 5 patients had a second operation because of residual tumor. Ventriculoperitoneal shunt insertion was performed in 3 of 31 patients because of symptomatic hydrocephalus and 1 patient had an endoscopic third ventriculostomy pre-operatively. 90% of these patients had no neurological sequelae at follow-up evaluation. CONCLUSION: Cerebellar astrocytomas are benign tumors where total resection is possible in the majority of cases with an excellent outcome.

The effect of phosphodiesterase inhibitor tadalafil on vasospasm following subarachnoid hemorrhage in an experimental rabbit model.

BACKGROUND: despite the years of study on it, cerebral vasospasm following subarachnoid hemorrhage is still an important cause of mortality and morbidity. The presented study was undertaken to show whether phosphodiesterase inhibitor tadalafil can attenuate the vasospasm process following subarachnoid bleeding. METHOD: in this study, 20 male New Zealand White rabbits weighing 2,500-3,000 g were randomly assigned to four groups. Animals in group 1 were controls. In group 2, animals were given oral tadalafil at 12, 24 and 36 h and SAH was not induced. SAH induced animals in group 3 did not receive any medication. In group 4, animals received tadalafil at 12, 24 and 36 h after SAH induction. All animals were sacrificed via exsanguination at 48 h after induction of SAH. Brains and brainstems with overlying basilar arteries were removed and stored in fixative at +4°C overnight. Basilar arteries were sectioned from four separate zones, and four sections were obtained from each rabbit. Basilar artery luminal section areas were measured by using SPOT for Windows version 4.1. Statistical comparisons were performed using Kruskal Wallis and ANOVA tests. FINDINGS: the SAH induced group which had been treated with tadalafil had significantly greater basilar artery luminal area than the untreated group (p < 0.05). There was no significant difference between control group and non-SAH induced group in terms of luminal areas. CONCLUSION: tadalafil has a potentially preventive effect in treatment of cerebral vasospasm following subarachnoid bleeding.

Comparison of nimodipine delivery routes in cerebral vasospasm after subarachnoid hemorrhage: an experimental study in rabbits.

BACKGROUND: nimodipine is the most widely preferred and administered calcium channel blocker in cerebral vasospasm prevention and treatment. There is no experimental or clinical study investigating the comparative effects of routine treatment modalities. METHOD: 35 male New Zealand White rabbits were assigned randomly to one of seven groups: Control, only SAH, SAH/oral nimodipine, SAH/IV nimodipine, SAH/IT nimodipine, SAH/IA nimodipine, SAH/angiography. FINDINGS: basilar artery vessel diameters are measured by angiography. Basilar artery vessel diameters and luminal sectional areas are measured in pathology slides. Basilar artery thicknesses were significantly higher in group 2 and 7 than the others (p < 0.05). Luminal sectional areas in group 5 and 6 were significantly higher than other groups (p < 0.05). We found no significant difference in group 1, 5 and 6 (p > 0.05). Basilar section areas in group 3 and 4 were significantly higher than group 2 but lower than group 1. CONCLUSION: this is the first study to show the most effective drug delivery route in CVS after SAH. Nimodipine treatment in cerebral vasospasm is useful. This study showed that selective IA nimodipine treatment and IT nimodipine treatment must be preferred to IV and oral treatments of chronic vasospasm following SAH.

The effect of intracisternal Zn (II) protoporphyrin IX on vasospasm process in the experimental subarachnoid hemorrhage model.

BACKGROUND: although there has been much work on it for years, cerebral vasospasm as a complication of subarachnoid bleeding is still an important cause of mortality and morbidity. The presented study was designed to examine the effects of heme oxygenase inhibitor, Zn (II) protoporphyrin IX, on vasospasm process. METHOD: in this study 20 male New Zealand White rabbits weighing 2,500 to 3,000 g were randomly assigned to four groups. Animals in group 1 were controls. In group 2, animals were SAH induced only and no treatment given. SAH induced animals in group 3 received intracisternal Zn (II) protoporphyrin IX 0.5 mg/kg in DMSO solution, at 0 and 24 h of SAH induction. In group 4, animals received only intracisternal DMSO at 0 and 24 h after SAH induction. All animals were sacrificed via exsanguination at 72 h after induction of SAH. Brains and brainstems with overlying basilar arteries were removed and stored in fixative at +4°C overnight. Basilar arteries were sectioned from four seperate zones, and four sections were obtained from each rabbit. Basilar artery luminal section areas and vessel wall thicknesses were measured by using SPOT for Windows version 4.1. Statistical comparisons were performed using Mann-Whitney and ANOVA tests. FINDINGS: basilar arterial wall thicknesses in group 3 were smaller than that of group 2 (p < 0.05). Luminal section areas in group 3 were significantly greater than luminal section areas of group 2 (p < 0.05). CONCLUSION: ZnPP has a potentially beneficial effect on cerebral vasospasm after subarachnoid bleeding.

Comparison of intrathecal cilostazol and nimodipine treatments in subarachnoid hemorrhage: an experimental study in rabbits.

OBJECTIVE: intrathecal administration of calcium channel antagonists has been proposed to reduce cerebral vasospasm (CVS) in animal subarachnoid hemorrhage (SAH) models. Also, delayed CVS treatment model with oral administration of cilostazol can be seen in the literature. METHODS: in this study, 25 male New Zealand white rabbits were randomly assigned to five groups: control, SAH only, SAH/nimodipine, SAH/cilostazol, SAH/vehicle. The animals' basilar arteries were sectioned from four separate zones and four sections were obtained from each rabbit. Basilar artery luminal section areas were measured by using SPOT for windows Version 4.1 computer program. RESULTS: basilar artery luminal section areas in SAH/ nimodipine and SAH/ cilostazol groups were significantly higher than SAH only group (P < 0.05). CONCLUSION: phosphodiesterase 3 inhibitor cilostazol has vasodilatory effects without affecting cerebral blood flow. Nimodipine is a calcium channel blocker and is still used in vasospasm therapy either oral or intravenously. This study demonstrates that prophylactic bolus intrathecal administration of either cilostazol or nimodipine equally prevents SAH-associated CVS in an animal model. We therefore propose that cilostazol is a candidate for clinical trials in the treatment of delayed vasospasm.