Novel Insights from Clinical Practice Pediatr Neurosurg DOI: 10.1159/000511879 Received: May 5, 2020 Accepted: September 19, 2020 Published online: December 10, 2020 Cerebral Vasospasm after Posterior Fossa Tumor Surgery: A Case Report and Literature Review Selcuk Gocmen a Gokhan Acka a Kutlay Karaman b Serdar Kahraman a aDepartment of Neurosurgery, Anadolu Medical Center, Kocaeli, Turkey; bDepartment of Radiology, Anadolu Medical Center, Kocaeli, Turkey Established Facts • Cerebral vasospasms are a possible complication of cerebral tumor surgery. • Only 6 pediatric cases of cerebral vasospasm following tumor resection have been reported in the literature till date. Novel Insights • Delayed neurological deterioration may be seen after pediatric posterior fossa tumor surgery. • Symptomatic vasospasms following posterior fossa tumor resection should be included in the differential diagnoses for delayed and unexpected neurological decline in patient status. • This is the first reported case of cerebral vasospasm following resection of a medulloblastoma located in the vermis of the cerebellum and fourth ventricle. Abstract Introduction: This report presents an unusual case of symptomatic vasospasm following resection of posterior fossa tumor in a 9-year-old female patient. To the best of our knowledge, only 6 pediatric cases of vasospasms as a complication of brain tumor surgery have been reported in the literature previously. Case Presentation: After an uneventful 12 days karger@karger.com www.karger.com/pne © 2020 S. Karger AG, Basel postoperatively, the patient suddenly presented with acute neurological deterioration on the 13th day and MR angiography showed bilateral narrowing of the supraclinoid segments of the internal carotid artery and the proximal parts of the A1 and M1 segments. Hypervolemia and vasospasm treatments were administered, and the patient exhibited no neurological deficit at the time of discharge, confirmed via normal MRI. Conclusion: Early diagnosis and intervention in case of suspected symptomatic cerebral vasospasm after pediatric posterior fossa tumor surgery are essential in order to achieve favorable outcomes. © 2020 S. Karger AG, Basel Selcuk Gocmen Department of Neurosurgery, Anadolu Medical Center Cumhuriyet Mah. 2255. Street Gebze 41400 (Turkey) s_gocmen @ yahoo.com Downloaded by: Karolinska Institutet, University Library 130.237.122.245 - 12/19/2020 6:04:31 PM Keywords Cerebral vasospasm · Brain tumor · Posterior fossa · Medulloblastoma · Pediatric age Symptomatic cerebral vasospasms, although fairly well documented in patients with aneurysmal subarachnoid hemorrhage (SAH) and traumatic brain injuries [1– 4], are relatively uncommon in individuals undergoing brain tumor resection. They contribute significantly to morbidity and mortality in patients of all ages and may easily be confused with cerebral edema and surgical injury, leading to misdiagnosis and incorrect treatment [4]. They are most commonly associated with pituitary tumors and sellar meningiomas and are rarely observed in relation to posterior fossa tumors [1, 3]. Resection of posterior fossa tumors, which are frequently detected in childhood, may be associated with an unexpected and rare complication, cerebral vasospasm. Therefore, neurological deterioration and suspected vasospasms in the delayed postoperative period should be immediately treated using relevant anti-vasospasm therapy, including medical management and/or endovascular interventions (e.g., angioplasty, intra-arterial vasodilators) in order to ensure favorable outcomes. Furthermore, daily transcranial Doppler examinations may be used for follow-up of pediatric patients. This case report summarizes the mechanisms, diagnostic evaluations, and prompt treatment measures used to achieve a favorable outcome following occurrence of symptomatic vasospasm after surgical removal of a posterior fossa tumor. Case Report A female patient, aged 9 years, was admitted to our department with a complaint of headache, vomiting, double vision, and ataxia for a period of 3 months. Neurological examination showed cerebellar ataxia, impaired tandem gait, Romberg sign (+), horizontal nystagmus, and diplopia without cranial nerve palsy. Gadoliniumenhanced MRI showed the presence of a tumor that originated from the vermis of the cerebellum and extended into the fourth ventricle. Additionally, supratentorial hydrocephalic changes and transependymal permeation of cerebrospinal fluid (CSF) were also observed. The medulloblastoma often presents as a heterogeneous mass on T2-weighted images, with hypo- and hyperintense regions representing cysts, necrosis, and calcifications (shown in Fig. 1a). Contrast enhancement may also be observed in a significant majority (shown in Fig. 1b). High cellularity and nuclear-cytoplasmic ratios of the medulloblastoma can lead to restricted diffusion of water particles in the tumor and low apparent diffusion coefficient values, resulting in the tumor exhibiting a characteristically high signal in diffusion-weighted MR images (shown in Fig. 1c) and low signals on apparent diffusion coefficient maps. In the current case, the tumor was completely removed by carrying out median suboccipital craniotomy in the concorde posi- 2 Pediatr Neurosurg DOI: 10.1159/000511879 tion using neuro-navigation, intraoperative neuro-monitoring, and fluorescent microscopy. External ventricular drainage was not inserted after tumor resection as normal CSF circulation was observed during surgery. The surgical duration was 5 h, including 2 h for tumor resection, and total intraoperative bleeding was 300 mL. Blood loss due to tumor resection per se was approximately 100 mL, and histopathological examination showed a diagnosis of classical medulloblastoma. Since she was an abroad patient, her prolonged hospitalization period was selected as the patient was from overseas, and she was fully conscious and exhibited no further neurological deficits during the first 12 days after surgery. However, neurological examination on the 13th day showed lethargy, increase of cerebellar ataxia, and impaired tandem gait. Her metabolic and infectious parameters were within the normal range, and bright intravascular signal intensity consistent with slow flow in both middle cerebral artery (MCA) branches was observed in the FLAIR sequence (shown in Fig. 2a). Diffusion-weighted-MRI, T2-weighted, and FLAIR series showed no acute ischemic changes in the brain, while 3D time-offlight MR angiographic (MRA) examinations (performed secondary to these findings and on both sides) showed findings consistent with bilateral narrowing of the ICA supraclinoid segments and proximal parts of A1 and M1 segments (shown in Fig. 2b). Coronal MR angiogram may exhibit the all part of ICA better than axial images in these cases. The vertebrobasilar system was normal, no evidence of intra- or extra-axial hemorrhage was detected, and the supratentorial ventricular enlargement was seen to be diminished in comparison with the preoperative MR images. The patient was moved to the pediatric critical care unit for 4 days, and nimodipine (15 mcg/kg/h, 2 mL/h IV infusion for 5 days), steroids (dexamethasone 0.6 mg/kg/day, 4 × 4 mg IV for 1 week), intravenous piracetam (Nootropil 800 mg, 4 × 1 IV for 1 week), and hyperdynamic therapy (H therapy) were started to reduce the severity of cerebral vasospasm and improve long-term outcomes. The aim was to achieve 95 percentile (113/75 mm/Hg) or higher blood pressure, as appropriate for the patient age (9-year old), sex (female), height (130 cm), and weight (26 kg). Additionally, 1,500 cc/day fluid therapy was administered for 4 days to achieve euvolemia. The efficacy of treatment was monitored using periodic neurological examination, and the patient’s condition was seen to improve gradually within 4 days. Her symptoms and MRI findings improved drastically within 10 days, and no neurological deficits were observed at the time of discharge. The patient completed chemotherapy and radiotherapy treatment, and MRI investigation at the 2-year postsurgical follow-up showed that the patient was still stable (shown in Fig. 3). Discussion Previous evidence suggests that delayed cerebral ischemia caused by vasospasms after intracranial tumor resection are rare in adult and pediatric patients, and even more so following posterior fossa tumor resection (incidence rate: 1.9%) [5, 6]. In their systematic review, Alotaibi et al. [1] identified 40 reported cases of cerebral vasospasms following tumor resection, and the mean age of Gocmen/Acka/Karaman/Kahraman Downloaded by: Karolinska Institutet, University Library 130.237.122.245 - 12/19/2020 6:04:31 PM Introduction a c b Fig. 1. T2-weighted image showing a hyperintense mass located in the midline of the posterior fossa (a); Gado- a Color version available online linium-enhanced axial T1-weighted image showing presence of a tumor with well-defined margins and solid enhancement originating from the vermis of the cerebellum and extending into the fourth ventricle (b); Medulloblastomas are characterized by high signal in DWI and low ADC values (c). DWI, diffusion-weighted; ADC, apparent diffusion coefficient. b Fig. 2. FLAIR sequence showing bright in- travascular signal intensity consistent with slow flow in both MCA branches (Red arrows) (a); 3D TOF MRA images showing bilateral narrowing of the ICA supraclinoid segments and proximal parts of A1 and M1 segments (Red arrows) (b). MCA, middle cerebral artery; TOF, time-of-flight; MRA, MR angiographic. a b Cerebral Vasospasm following Tumor Surgery Pediatr Neurosurg DOI: 10.1159/000511879 3 Downloaded by: Karolinska Institutet, University Library 130.237.122.245 - 12/19/2020 6:04:31 PM Fig. 3. Gadolinium-enhanced axial (a)/sagittal (b) T1-weighted images of the patient after completion of radiotherapy and chemotherapy showing stable condition 2 years after surgery. Gocmen/Acka/Karaman/Kahraman Downloaded by: Karolinska Institutet, University Library 130.237.122.245 - 12/19/2020 6:04:31 PM Full recovery 3H therapy, nimodipine, steroids, piracetam Bilateral ICA, A1 and M1 H therapy, hyperdynamic therapy; MCA, middle cerebral artery. Lethargy, cerebellar ataxia 13 days 9/F Vermis of cerebellum and fourth ventricle medulloblastoma Vegetative state Nimodipine, 3H therapy, decompressive craniectomy after 7 days Bilateral ICA, basilar arteries Changed of mental status Gocmen et al. [current report] Pediatr Neurosurg DOI: 10.1159/000511879 Left ventral medulla oblongata schwannoma 16/M Qi et al. [4] 3 days Full recovery (after 6 weeks prolonged course) EVD steroids, 3H therapy, intratechal nicardipine Left ICA, basilar artery, progress circle of Willis territories bilaterally Focal weakness, aphasia, lethargy, bradycardia, brainstem reflexes ↓ Left cerebellar, medulloblastoma 17/M Dalvi et al. [9] 14 days Full recovery EVD, 3H therapy, nimodipine (1 week) Bilateral ICA, MCA and ACA Left hemiparesis, facial weakness 8 days Left hypoglossal schwannoma Afshari et al. [8] 9/F Full recovery (mild facial paralysis due to surgery) V/P shunt, 3H therapy, nimodipine (10 days) Right PCA, M1, left PCA, A2, M1, carotid terminus Headache, N/V, ataxia, bilaterally legs weakness, dysphasia 10 days 10/F Rao et al. [3] Right CPA, anaplastic medulloblastoma Bihemispheric and brainstem infarcts, exitus 3H therapy, nimodipine, anti-coagulation Bilateral ICA and vertebral arteries Left hemiparesis and right partial ptosis 16 days 1.3/F Lee et al. [2] Left CPA, neuroectodermal tm Full recovery 3H therapy, angioplasty Right ICA, MCA, PCA Changed of mental status 7 days 6/F Bejjani et al. [7] Third nerve schwannoma Outcome Treatment Vessels involved Symptoms Onset Pathology Age, years/sex Authors Table 1. Summary of reported cases of symptomatic vasospasm following brain tumor resection in childhood 4 the patients was only 41 years (range: 1–69 years). Additionally, the morbidity and mortality (30%) rates were high, and the onset of vasospasm symptoms peaked on the 7th–8th days and primarily involved the anterior circulation [1]. Early diagnosis and treatment of cerebral vasospasm are critical as the clinical presentation is variable and often progressive. Only 6 pediatric cases of vasospasms as a complication of brain tumor surgery have been reported so far (Table 1) [2–4, 7–9], making our patient the 7th. The mean age of these patients was 9.5 years (range 1.3–17 years), and the onset of symptoms typically occurred between days 3–16 (mean: 10 days) and peaked on the 7th–8th days. Pituitary tumors and sellar meningiomas were most commonly associated with this complication [1], while posterior fossa tumors and skull base tumor resections were very rarely associated with symptomatic vasospasms (with only 9 cases being reported so far) [1]. Interestingly, posterior fossa tumors exhibited a greater tendency to cause diffuse vasospasms [1], which have also been observed after resection of schwannomas, astrocytoma, brain metastasis, and neuroectodermal tumor [3]. To the best of our knowledge, this is the first reported case of a diffuse cerebral vasospasm following resection of a medulloblastoma located in the vermis of the cerebellum and fourth ventricle. Multiple physiopathological mechanisms, such as direct mechanical trauma, intraoperative bleeding, vascular factors (vessel encasement, displacement, and narrowing), release of vasoactive substances, hypothalamic dysfunction after resection of sellar or parasellar tumors, tumor location, tumor pathology, and compression may help explain vasospasms in the postoperative period [1, 2, 4, 8, 10]. Intraoperative bleeding facilitating spillage of blood into the subarachnoid space is also known to be correlated with this complication [1] and could likely explain the vasospasm observed in the current case where the occurrence of approximately 100 mL of intraoperative bleeding in the basal cistern during tumor resection could have led to SAH, even without direct contact of the supratentorial vessels. The patient exhibited complete recovery after appropriate vasospasm treatment. The trigeminal system regulates the blood flow and metabolism of the brain and could represent another possible mechanism for occurrence of vasospasm [4]. Lee et al. [2] previously reported a case of vasospasm after resection of a primitive neuroectodermal tumor at the cerebellopontine angle, and attributed this to a systemic autoimmune or paraneoplastic postsurgical response. In the cur- rent case, the patient underwent radiotherapy and chemotherapy after recovering from cerebral vasospasm and remained uneventful 2 years after surgery. Cerebral vasospasm should be considered in the differential diagnoses for neurological deterioration following brain tumor resection should include cerebral vasospasms. Despite their ability to detect vasospasms within the intracranial vasculature, MRAs are not routinely used for control MRIs after brain surgery. Instead, FLAIR sequences based on fast spin-echo sequences are available in a majority of commercial clinical MR systems and are used to improve the detectability of small lesions closer to the CSF. They can also detect occlusion by increasing the signal within arteries in patients with hyperacute ischemic stroke [11], and these are sometimes described as “hyperintense vessel signals.” Such intra-arterial hyperintense signals in FLAIR images may indicate lack of flow void, total obstruction of the artery, or slow flow. FLAIR images play a crucial role in the decision to carry out MR angiography for postoperative control MRI investigation. 3D time-of-flight MRAs are noninvasive; do not require radiation and contrast; can show cranial arterial systems with high spatial resolution; and are also capable of multiplanar reconstruction. Previous literature suggests that MRAs have an overall specificity of 97% with regard to detection of cerebral arterial vasospasms [12]. Digital subtraction angiography is the gold standard for diagnosing cerebral vasospasm; however, it is invasive, difficult to repeat, and can induce complications. Therefore, Rao et al. [3] emphasized the utility of transcranial Doppler ultrasonographies in diagnosing pediatric vasospasms following brain tumor resection, and also highlighted the successful use of hemodynamic augmentation for treatment. Early detection of arterial vasospasms is necessary for effective treatment and improvement of clinical outcomes, and the recommended treatment algorithm may be similar to that used in an SAH. In addition to triple H therapy and calcium channel blockers [13], endovascular options such as balloon angioplasty and vasodilator treatment can also be used for focal refractory vasospasms [2, 8]. Aggressive treatments may be necessary to prevent ischemia and further neurological deficits, and all cases of arterial vasospasms reported till date underwent triple H therapy. In the current case, intravenous steroids and piracetam were used in addition to hypervolemia and hypertension treatment and calcium channel blocker in order to target cerebral edema and regulate microvascular circulation. Although there is no evidence on the efficacy of piracetam in the treatment of pediatric delayed cere- bral ischemia till date, previous studies have reported its uses in the regulation of cerebral microvascular circulation [14]. Our treatment protocol aimed to achieve normal hematocrit levels as hemodilution may affect oxygen delivery to the brain, as per the latest guidelines on treatment of cerebral vasospasms [15]. In conclusion, diffuse symptomatic vasospasms following posterior fossa tumor resection are extremely rare and challenging in pediatric patients and are associated with high morbidity and mortality rates. Therefore, they should be included in the differential diagnoses of delayed and unexpected neurological decline in the patient’s status. Delayed diagnosis of cerebral vasospasms may lead to poor outcomes, and MRIs should be used for early detection if symptomatic cerebral vasospasms are suspected after posterior fossa tumor surgery, even in the late postoperative period. In this report, we summarized correct diagnosis of vasospasm in our pediatric patient and described the aggressive and timely treatment delivered, resulting in an uneventful postoperative period. Cerebral Vasospasm following Tumor Surgery Pediatr Neurosurg DOI: 10.1159/000511879 Statement of Ethics This work complies with the guidelines for human studies, and the research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The authors confirm that written informed consent was collected from the parent/legal guardian prior to treatments and for publication of data and images. Conflict of Interest Statement The authors have no conflicts of interest to declare. Funding Sources The authors did not receive any funding. Author Contributions 5 Downloaded by: Karolinska Institutet, University Library 130.237.122.245 - 12/19/2020 6:04:31 PM Selcuk Gocmen: contributed to the design of the work, revised the manuscript critically for intellectual content, is accountable for all aspects of the work and for ensuring that all questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved, approved the final version of manuscript for publication. Gokhan Acka: contributed to the design and interpretation of data, revised the manuscript critically for crucial intellectual content, is accountable for all aspects of the work and for ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved, approved the final version of manuscript for publication. Kutlay Karaman: contributed to the design of the work and interpretation of images, revised the manuscript critically for intellectual content, is accountable for all aspects of the work and for ensuring that all questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved, approved the final version of manuscript for publication. Serdar Kah- raman: contributed to the design of the work, revised the manuscript critically for intellectual content, is accountable for all aspects of the work and for ensuring that all questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved, approved the final version of manuscript, has revised for publication. References 6 Pediatr Neurosurg DOI: 10.1159/000511879 6 Bejjani GK, Sekhar LN, Yost AM, Bank WO, Wright DC. Vasospasm after cranial base tumor resection: pathogenesis, diagnosis, and therapy. 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