Original Paper Pediatr Neurosurg 1998;29:300–303 Thomas T. Lee a, c John Ragheb a, c Jocelyn C. Bruce b, d Nolan Altman b, d Glenn Morrison a, c Departments of a Neurological Surgery and Received: September 18, 1998 Accepted: October 9, 1998 Diffuse Cerebral Vasospasm with Ischemia after Resection of a Cerebellopontine Angle Primitive Neuroectodermal Tumor in a Child b Radiology, Miami Children’s Hospital, and Departments of c Neurological Surgery and d Pathology, University of Miami School of Medicine, Miami, Fla., USA OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO Key Words Primitive neuroectodermal tumor Malignant brain tumor Rhabdoid tumor Cerebral vasospasm Stroke Paraneoplastic syndrome Abstract This case report describes a 15-month-old female who developed diffuse cerebral vasospasm after resection of a cerebellopontine angle primitive neuroectodermal tumor. The patient developed an acute dense left hemiparesis 16 days postoperatively with partial right ptosis. Initial magnetic resonance imaging and diffusion study were unremarkable, though a magnetic resonance angiography 1 day later demonstrated severe intracranial vasospasm of both carotid and vertebral arteries. The vasospasm was confirmed with cerebral angiography. The patient progressed to bihemispheric infarcts with laminar necrosis despite combination therapy with anticoagulation, pharmacological hypertension, hypervolemia, and nimodipine. The clinical course, radiographic, and pathological findings are presented. OOOOOOOOOOOOOOOOOOOOOO Introduction Cerebral vasospasm is most frequently associated with subarachnoid hemorrhage after rupture of an intracranial aneurysm. Vasospasm has also been reported after penetrating intracranial trauma, closed head injuries and head and neck surgery [1]. Symptomatic vasospasm is rare after resection of brain tumors, though occasional reports of such occurrences after posterior fossa tumor resection in adults can be found in the literature [2–5]. To our knowledge, no previous case of postoperative vasospasm after pediatric brain tumor resection has been reported. The authors report a case of a young patient presenting with a cerebellopontine angle tumor. The patient developed severe vasospasm refractory to medical therapy that ultimately resulted in bilateral hemispheric and ultimate- ABC © 1999 S. Karger AG, Basel 1016–2291/98/0296–0300$17.50/0 Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Accessible online at: http://BioMedNet.com/karger ly brainstem infarction. The clinical, radiographic, and pathological findings are presented. The discussion focuses on the occurrence of vasospasm after resection of a posterior fossa malignant neoplasm. Therapeutic options and possible etiologies are explored. Case Report This previously healthy 15-month-old female, product of a fullterm pregnancy after in vitro fertilization, presented 2 months prior to surgery with a peripheral left seventh nerve palsy shortly after a febrile illness. A noncontrast computerized tomography (CT) scan was obtained and she was diagnosed at an outside institution as having Bell’s palsy. Retrospective review of the CT scan demonstrated a small, minimally hyperdense lesion near the left cerebellopontine angle. Her facial palsy improved on steroids, only to reoccur once the steroids were stopped. A magnetic resonance imaging (MRI) scan John Ragheb, MD Department of Neurological Surgery, D4–6 University of Miami School of Medicine 1501 NW 9th Avenue, Miami, FL 33136 (USA) Tel. +1 (305) 243 6536, Fax +1 (305) 243 5588, E-Mail Jragheb@newssun.med.miami.edu a b c d e Fig. 1. a, b Axial (a) and coronal (b) T1-weighted spin-echo MRI [400/15/2 (repetition time/echo time/excitations)] with gadolinium injection demonstrated a left cerebellopontine angle homogeneously enhancing mass. c Axial diffusion weighted image b value 1200 combined cardinal gradients (x,y,z) with single shot echo planar technique which shows increased signal in the right parietal and occipital region. d Lateral image of an arch injection shows severe narrowing of the supraclinoid carotid arteries and basilar artery. e Axial T1weighted MR with patchy hyperintensity along the cortical and subcortical regions of bilateral cerebral hemispheres and basal ganglia consistent with cortical laminar necrosis. showed an enhancing mass in the left cerebellopontine angle with mild mass effect (fig. 1a, b). She was referred for neurosurgical consultation. Neurological examination revealed a mildly irritable infant with a peripheral left seventh and eighth nerve palsy. The tongue also slightly deviated to the left upon protrusion. Motor strength was normal and reflexes were symmetric. The general physical exam was unremarkable. Dexamethasone was started and she was taken to surgery where a left suboccipital craniotomy with resection of tumor was performed. A soft purplish tumor was encountered. The portion adjacent to the brainstem and the dura were rather pale and tough in consistency and mildly vascular, resembling that of a meningioma. Frozen section revealed a small cell neoplasm with frequent mitoses. Small portions of residual tumor were left adherent to the anterolateral surface of the brainstem and the seventh and eighth nerve complex. Pathologic examination of the tumor with hematoxylin and eosin (HE) staining revealed a highly cellular neoplasm comprised of small undifferentiated cells with grouping and pseudolobulation (fig. 2). Small cells with small hyperchromatic nuclei were mixed with cells Diffuse Cerebral Vasospasm Pediatr Neurosurg 1998;29:300–303 301 after which she again deteriorated neurologically, ultimately becoming quadriparetic and unresponsive. Follow-up MRI showed bilateral cerebral ischemia, and subsequently, bilateral laminar necrosis (fig. 1e). Her clinical condition was further complicated by vancomycin-resistant enterococcus urosepsis. In light of her neurological condition and failure to respond to maximal medical therapy the decision was made to discontinue aggressive medical therapy after 2 weeks. Comfort measures were instituted. She expired after a cardiopulmonary arrest on the 29th day of the hospitalization. The family declined an autopsy examination. Discussion Fig. 2. The HE stain showed a highly malignant tumor made up of spindle and epithelioid cells arranged in rows and small lobules. HE. !250. containing larger, irregular vesicular nuclei and occasional nucleoli. In a few areas, the cells appeared to be epithelioid, containing moderate amounts of clear or vacuolated cytoplasm. Numerous mitotic figures and individual necrotic cells were noted throughout the specimen. Immunoperoxidase staining was positive for CD-99 [a primitive neuroectodermal tumor (PNET) marker], and focally positive for epithelial membrane antigen, keratin, NB, and synaptophysin, but negative for s-100, GFAP, and desmin. The final diagnosis was that of a PNET with epithelioid (rhabdoid) and neuronal differentiation. Her neurological condition was unchanged after surgery. A postoperative MRI revealed minimal residual tumor near the internal auditory meatus. She was discharged home on postoperative day 5 on a dexamethasone taper. A spinal MRI revealed a suspicious enhancing mass in the thoracic paraspinal muscles. Cerebrospinal fluid cytology and a nuclear medicine bone scan were normal. Sixteen days after discharge the patient returned to the hospital with irritability and a left hemiparesis. A MRI with and without contrast was unchanged from the immediate postoperative MRI and a MRI diffusion study was unremarkable. The peripheral white blood cell count was 15,000 and the erythrocyte sedimentation rate was also elevated at 40. A lumbar puncture revealed a mild pleocytosis. She was started on intravenous steroids and broad spectrum antibiotics. Antibiotics were stopped 3 days later when the cerebrospinal fluid cultures were finalized. The evening of readmission she developed a partial right ptosis without miosis. A follow-up MR diffusion study 24 h later demonstrated right hemispheric ischemia (fig. 1c). A magnetic resonance angiogram, performed to rule out cervical carotid artery dissection, demonstrated diffuse intracranial vascular tapering. The patient was anticoagulated with intravenous heparin to keep PTT between 50 and 60. Transcranial Doppler (TCD) examination revealed bilateral middle cerebral artery and anterior cerebral artery velocities of greater than 300 cm/s. A cerebral angiogram confirmed the severe tapering of both carotid and both vertebral arteries (fig. 1d). The patient was started on nimodipine, volume expansion with intravenous albumin, as well as dobutamine to artificially elevate the blood pressure. She remained neurologically stable for 48 h, 302 Pediatr Neurosurg 1998;29:300–303 Cerebral vasospasm occurs most often in the setting of aneurysmal subarachnoid hemorrhage [1, 6]. Generally, the more severe the hemorrhage in the subarachnoid space, the more likely vasospasm will occur [7]. Significant morbidity is associated with clinical vasospasm. Though less frequently observed, traumatic subarachnoid hemorrhage is also associated with vasospasm and cerebral ischemia [1]. The diagnosis of clinical vasospasm is generally made in the appropriate clinical setting by the presence of neurological deterioration with vasospasm documented by TCD and/or cerebral angiogram [6]. Vasospasm after resection of an intracranial neoplasm is rare. Few cases have been reported in the literature even in the adult population [2–5, 8, 9]. These reported cases of vasospasm were generally associated with significant intraoperative hemorrhage, and/or posterior fossa or skull base neoplasms [2, 3, 9]. The neurological deficits were generally transient. To our knowledge the present case is the first reported case of vasospasm after the resection of a pediatric intracranial neoplasm. The diagnosis was made on the basis of TCD and angiography. The patient unfortunately progressed to bilateral hemispheric ischemia and brainstem infarction. The cause of the vasospasm in this case was not clear. The patient had a malignant posterior fossa neoplasm, unlike several previous cases of adult vasospasm after skull base tumor resection for benign tumors [2–5]. Unlike the previously reported cases there was no substantial intraoperative hemorrhage. Hypothalamic dysfunction, as previously proposed to be the mechanism for vasospasm after resection of sellar or parasellar tumors [3], was unlikely the cause in this case because of location. The rhabdoid elements of the tumor suggest an autoimmune or ‘paraneoplastic’ type response as a possible etiology of the vasospasm. A host antibody response to a rhabdoid tumor antigen which also ‘recognized’ the cerebral vasculature is a plausible explanation. This theory would Lee/Ragheb/Bruce/Altman/Morrison correlate with the 2-week delay between surgery, and ‘exposure’ to the tumor antigen, and the appearance of symptoms correlating with the time course of an IgG response. The absence of an arterial biopsy or postmortem examination makes this theory impossible to prove. Her erythrocyte sedimentation rate was only 40, and a serum protein electrophoresis, ANA and LE prep were negative. The traditional treatment of vasospasm consists of induced hypervolemia, hypertension, and nimodipine [1]. Mild degree of hemodilution to a hematocrit of between 30 and 35 was also reported to be helpful [1]. Intra-arterial papaverine infusion and balloon angioplasty are also used in cases of focal vasospasm refractory to medical management. In this case, all medical therapies were attempted, in addition to systemic anticoagulation. Papaverine administration and balloon angioplasty were not attempted in this particular case because of the diffuse vasospasm and the established infarction as indicated by MRI scan. An earlier magnetic resonance angiogram (cranial) at the onset of clinical symptoms might have enabled earlier endovascular intervention prior to development of radiographic infarction. The pathological diagnosis of an intracranial rhabdoid tumor is difficult and remains controversial [10, 11]. Nearly 60% of all intracranial rhabdoid tumors are found in the posterior fossa [11]. Frequently, the majority of the tumors may be indistinguishable from a PNET. Positive staining for epithelial membrane antigen, vimentin, and smooth-muscle antigen may aid in the diagnosis. The genetic abnormality has been mapped to chromosome 22. These tumors were considered by Rorke et al. [10, 11] to be teratoid/rhabdoid tumors, despite the focal appearance of the rhabdoid features. The tumor in the present patient demonstrated positivity for CD-99, an antigen not tested for in the previous reported series, as well as synaptophysin. The final diagnosis was therefore that of a PNET with rhabdoid and neuronal features. It is still possible that this case simply represented a rhabdoid tumor, as the overall clinical course and outcome resemble that of a rhabdoid tumor [10, 11]. OOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO References 1 Doberstein C, Martin NA: Cerebral Blood Flow in Clinical Neurosurgery; in Youmans J (ed): Neurological Surgery, ed 4. Philadelphia, Saunders, 1996, pp 519–569. 2 Aoki N, Origitano TC, Al-Mefty O: Vasospasm after resection of skull base tumor. Acta Neurochir 1995;132:53–58. 3 Cervoni L, Salvati M, Santoro A: Vasospasm following tumor removal: Report of 5 cases. Ital J Neurol Sci 1996;17:291–294. 4 Kusunose M, Fukuda O, Saito T, Takaku A, Endo S: Diffuse cerebral artery vasospasm following total resection of posterior fossa meningioma: A case report. No Shinkei Geka 1997; 25:953–957. Diffuse Cerebral Vasospasm 5 Shirasaka A, Ninchoji T, Uemura K, Shinohara Y, Kuwahara T, Yamazaki K: Delayed vasospasm complicated with the postoperative stage of the meningioma: A case report. No Shinkei Geka 1993;21:745–749. 6 Mahla ME, Friedman WA: Monitoring the nervous system; in Youmans J (ed): Neurological Surgery, ed 4. Philadelphia, Saunders, 1996, pp 402–438. 7 Fisher CM, Kistler JP, Davis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computer tomographic scanning. Neurosurgery 1987;6:1–10. 8 LeRoux PD, Haglund MM, Mayberg MR, Winn HR: Symptomatic cerebral vasospasm following tumor resection: Report of two cases. Surg Neurol 1991;36:25–31. 9 Smith PG, Killeen TE: Carotid artery vasospasm complicating extensive skull base surgery: Cause, prevention, and management. Otolaryngol Head Neck Surg 1987;97:1–7. 10 Rorke LB, Packer R, Biegel J: Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood. J Neurooncol 1995;24: 18–21. 11 Rorke LB, Packer RJ, Biegel JA: Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: Definition of an entity. J Neurosurg 1996;85:56–65. Pediatr Neurosurg 1998;29:300–303 303 Copyright: S. Karger AG, Basel 1998. Reproduced with the permission of S. Karger AG, Basel. Further reproduction or distribution (electronic or otherwise) is prohibited without permission from the copyright holder.