Papillary Tumor Of The Pineal Region Research Articles

Papillary Tumor of Pineal Region: A Case Report

Pineal region tumors constitute about 0.4%-1% of intracranial tumors in adults. These tumors may arise from pineal gland itself or structures around it which are all termed as pineal region tumor. Papillary tumor of the pineal region is a non-parenchymal tumor of the pineal region. First described in 2003, it is an extremely rare tumor. We have presented a case of 27-year-old female patient presented as a pineal tumor. After successful excision, the tumor proved to be Papillary tumor of Pineal region (PTPR) both histomorphologically and immunohistochemical study.
 Pulse Volume 12-14 2020-2022 p.13-15

Papillary Tumor of the Pineal Region: A Case Report and Literature Review

Pineal tumors of the pineal region (PTPR) are rare neuroepithelial tumors of the central nervous system, and their clinical features often lack specificity, so it is always difficult to make a definite diagnosis before surgery, and the treatment is mainly based on complete surgical resection. We report the case of a 21-year-old male who presented with intermittent dizziness and headache with vomiting for more than 2 months. The imaging revealed a mass in the region of the pineal region with obstructive hydrocephalus. After the hospitalization, the patient underwent a microscopic excision of the pineal mass, and the tissue was sent for histopathological examination and available immunohistochemical tests, which resulted in a definitive diagnosis of a papillary tumor of the pineal region. He had undergone several radiation treatments during his hospitalization and remained recurrence-free until the latest follow-up visit. This article highlights the similarities between this case and the PTPR described in WHO 2021 in terms of clinical presentation, imaging, and histopathological features. Therefore, this case report completes the sample database of PTPRs. By reviewing the literature related to PTPRs, we hope that this report will be helpful to improve the understanding of clinicians and pathologists about this rare tumor. However, more relevant studies are needed to clarify the pathogenesis, prognosis, and optimal treatment options to achieve early diagnosis, early treatment, and improved prognosis.

Diagnosis and Treatment of Pineal Region Tumors in Adults: A EURACAN Overview.

Simple SummaryPineal region tumors are rare intracranial tumors. A deeper knowledge of these tumors’ molecular mechanisms has been gained in recent years, which has led to a new classification and new potential systemic treatments. Surgery remains the mainstay of treatment, while radiotherapy and systemic therapy depend on histological, molecular, and clinical characteristics. This paper highlights recent developments in the diagnosis and treatment of these tumors.Pineal region tumors are rare intracranial tumors, accounting for less than 1% of all adult intracranial tumor lesions. These lesions represent a histologically heterogeneous group of tumors. Among these tumors, pineal parenchymal tumors and germ cell tumors (GCT) represent the most frequent types of lesions. According to the new WHO 2021 classification, pineal parenchymal tumors include five distinct histotypes: pineocytoma (PC), pineal parenchymal tumors of intermediate differentiation (PPTID), papillary tumor of the pineal region (PTPR), pinealoblastoma (PB), and desmoplastic myxoid tumor of the pineal region, SMARCB1-mutant; GCTs include germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, mixed GCTs. Neuroradiological assessment has a pivotal role in the diagnostic work-up, surgical planning, and follow-up of patients with pineal masses. Surgery can represent the mainstay of treatment, ranging from biopsy to gross total resection, yet pineal region tumors associated with obstructive hydrocephalus may be surgically managed via ventricular internal shunt or endoscopic third ventriculostomy. Radiotherapy remains an essential component of the multidisciplinary treatment approach for most pineal region tumors; however, treatment volumes depend on the histological subtypes, grading, extent of disease, and the combination with chemotherapy. For localized germinoma, the current standard of care is chemotherapy followed by reduced-dose whole ventricular irradiation plus a boost to the primary tumor. For pinealoblastoma patients, postoperative radiation has been associated with higher overall survival. For the other pineal tumors, the role of radiotherapy remains poorly studied and it is usually reserved for aggressive (grade 3) or recurrent tumors. The use of systemic treatments mainly depends on histology and prognostic factors such as residual disease and metastases. For pinealoblastoma patients, chemotherapy protocols are based on various alkylating or platinum-based agents, vincristine, etoposide, cyclophosphamide and are used in association with radiotherapy. About GCTs, their chemosensitivity is well known and is based on cisplatin or carboplatin and may include etoposide, cyclophosphamide, or ifosfamide prior to irradiation. Similar regimens containing platinum derivatives are also used for non-germinomatous GCTs with very encouraging results. However, due to a greater understanding of the biology of the disease’s various molecular subtypes, new agents based on targeted therapy are expected in the future. On behalf of the EURACAN domain 10 group, we reviewed the most important and recent developments in histopathological characteristics, neuro-radiological assessments, and treatments for pineal region tumors.

OTHR-15. Papillary tumor of the pineal region: case series of this rare pediatric entity

BACKGROUND: The optimal management of pediatric papillary tumors of the pineal region (PTPR) is not yet established. We report three cases, as an addition to the existing literature. PATIENT 1: A 22-month-old female presented with progressive ataxia and incoordination, found to have an enhancing solid and cystic mass centered within the pineal region, with associated obstructive hydrocephalus. Tumor biopsy revealed PTPR, prompting a subsequent subtotal resection. No adjuvant therapy was recommended. Patient has remained without evidence of disease progression for 92 months, since resection. PATIENT 2: An 8-year-old female presented with progressive headaches and new-onset generalized seizures, found to have a heterogeneously enhancing pineal lesion, with associated obstructive hydrocephalus. Following a biopsy demonstrating PTPR, patient underwent subtotal resection of the tumor. A second resection was completed 6 months later followed by focal irradiation. Targeted next-generation sequencing (NGS) demonstrated two non-targetable genomic alterations (CREBBP and MLL2). The patient remains without tumor recurrence, now 37 months, since irradiation. PATIENT 3: A 7-year-old male with Autism spectrum disorder presented with new-onset focal complex seizures. A brain MRI showed a heterogeneously enhancing lesion in the region of the pineal gland, with associated obstructive hydrocephalus. A tumor biopsy revealed PTPR, prompting a subsequent gross total resection (GTR). NGS demonstrated no reportable genomic alterations. Methylome profiling classified the tumor as PTPR, group B. Post-operative imaging with no residual tumor and he has remained without tumor progression, now eight months, since resection. CONCLUSION: PTPR are extremely rare in the pediatric setting, and were initially introduced in the WHO 2007 classification as grade II-III pineal gland tumors with distinct morphologic and immunohistochemical features. GTR is the mainstay of treatment but post-surgical management remains controversial. The clinical course is characterized by frequent local recurrence, hence, adjuvant chemotherapy and/or irradiation may be necessary upon disease progression.

P14.89 Papillary tumor of the pineal region: three cases from a single institution

Abstract BACKGROUND Papillary tumors of the pineal region are highly unusual lesions of unknown incidence. These are neuroepithelial tumors with papillary and solid areas. There is no standardized treatment because of the difficulty to make randomized prospective trials due to its rarity. We report three patients with papillary tumor of the pineal region. MATERIAL AND METHODS Retrospective review of the clinical records of patients with papillary tumor of the pineal region at a tertiary neurological center in Buenos Aires, Argentina was done between 2/2012-04/2021. Clinical characteristics, imaging, pathology, treatment and follow-up data were obtained. RESULTS Two patients were male and one female. All three patients were adults, two in the fourth decade of life and one in the seventh. Clinical presentation included headache along with either visual symptoms, gait disturbance, or both. Imaging workup included brain and spinal magnetic resonance imaging, finding expanding lesions in the pineal region, hyperintense in FLAIR/T2 sequences, with gadolinium enhancement in T1 with contrast sequence and variable degrees of hydrocephalus. Spinal lesions were not found in these patients. Cerebrospinal fluid cytology was negative in all cases. Tumor biopsy was the initial approach in all cases. Two patients underwent an initial third ventriculostomy procedure but all were submitted to a supracerebellar infratentorial approach for major resection. Posterior treatment included chemoradiotherapy with temozolomide. One patient had a distant recurrence after seven years with and remained with stable disease for two more years, and the other two patients are under control with no recurrence after 2 and 2.5 years respectively. CONCLUSION Papillary tumors in the pineal regions are aggressively treated as recurrence is very frequent regarding previous reports (> 70%). Total resection is the only predictive factor associated to better outcome, however, more information is needed in order to achieve treatment consensus.

Retractorless interforniceal approach for microsurgical resection of a papillary tumor of the pineal region: operative video and technical nuances.

In this illustrative video, the authors demonstrate microsurgical resection of a papillary tumor of the pineal region using a retractorless interforniceal approach via the anterior interhemispheric transcallosal route. The tumor presented to the posterior third ventricle occluding the cerebral aqueduct, resulting in obstructive hydrocephalus. The retractorless interforniceal approach is performed in the lateral position with BICOL collagen spacers to keep the corridor open. Gross-total resection was achieved, and the patient was neurologically intact without needing a permanent shunt. The operative nuances and pearls of technique for safe microdissection and gentle handling of the retractorless interforniceal approach are demonstrated.The video can be found here: https://stream.cadmore.media/r10.3171/2021.4.FOCVID2139.

Pineal Parenchymal Tumor of Intermediate Differentiation (PPTID) and Papillary Tumor of Pineal Region (PTPR): A Review.

Pineal parenchymal tumors account for less than 0.3% of all CNS tumors and "Pineal parenchymal tumor of intermediate differentiation" (PPTID; World Health Organization (WHO) grades II and III) exhibit intermediary differentiation and prognosis. However "Papillary tumor of the pineal region" (PTPR; WHO grades II and III) is a distinct entity. This combination of rarity and apparent similarity often leads to perplexity regarding the treatment and prognosis among neurosurgeons. In this review, we have tried to elucidate the differences in clinical as well as treatment modalities and outcomes of these two entities. We used the PubMed Database to search for all relevant articles using the keywords "pineal parenchymal tumor of intermediate differentiation" and "Papillary tumor of the pineal region." Articles having details regarding demographic and clinical variables along with treatment and outcomes were chosen for this study. Full text of these articles was analyzed, and data tabulated. A total of 25 articles for PPTID and 45 for PTPR were found suitable for inclusion in this study. The studies were either case reports or small retrospective series with only one systemic review for each pathology. Despite the poor quality of data, some trends were apparent. Surgical resection offered a survival benefit in both pathologies. Radiotherapy was effective in increasing the survival in PPTID, while there was little to no effect in PPTR. Chemotherapy was not found to be beneficial in either. Both of these tumors have moderate growth rate and potential for malignant behavior. This continuum of characteristics makes their optimal treatment strategy difficult and confusing. The discussion on comprehensive literature review should give information for neurosurgeons to decide on optimal treatment strategies.

Papillary tumour of the pineal region: a case report

BackgroundPapillary tumor of the pineal region is an unusual, recently described entity with potential for misinterpretation as either an ependymoma or choroid plexus papilloma. With few reported cases, there is little data regarding the biologic behavior, natural course and optimal treatment for these patients. Further accumulation of reports will assist with defining this entity and may provide further insight into management of such patients.Case presentationThis patient was a 24-year-old male with new onset seizures and a decreased level of consciousness. MRI scan showed a large heterogeneously enhancing solid-cystic mass in the pineal region extending to the third ventricle.DiscussionPapillary tumor of the pineal region is a neuroepithelial tumor with distinct morphological and immunohistochemical features that can be utilized to help differentiate it from other primary and metastatic tumors occurring within this region. Although there is currently no clear consensus, the potential for disease progression and CSF dissemination supports early aggressive therapy in these patients.

Molecular subgrouping of primary pineal parenchymal tumors reveals distinct subtypes correlated with clinical parameters and genetic alterations.

Tumors of the pineal region comprise several different entities with distinct clinical and histopathological features. Whereas some entities predominantly affect adults, pineoblastoma (PB) constitutes a highly aggressive malignancy of childhood with a poor outcome. PBs mainly arise sporadically, but may also occur in the context of cancer predisposition syndromes including DICER1 and RB1 germline mutation. With this study, we investigate clinico-pathological subgroups of pineal tumors and further characterize their biological features. We performed genome-wide DNA methylation analysis in 195 tumors of the pineal region and 20 normal pineal gland controls. Copy-number profiles were obtained from DNA methylation data; gene panel sequencing was added for 93 tumors and analysis was further complemented by miRNA sequencing for 22 tumor samples. Unsupervised clustering based on DNA methylation profiling separated known subgroups, like pineocytoma, pineal parenchymal tumor of intermediate differentiation, papillary tumor of the pineal region and PB, and further distinct subtypes within these groups, including three subtypes within the core PB subgroup. The novel molecular subgroup Pin-RB includes cases of trilateral retinoblastoma as well as sporadic pineal tumors with RB1 alterations, and displays similarities with retinoblastoma. Distinct clinical associations discriminate the second novel molecular subgroup PB-MYC from other PB cases. Alterations within the miRNA processing pathway (affecting DROSHA, DGCR8 or DICER1) are found in about two thirds of cases in the three core PB subtypes. Methylation profiling revealed biologically distinct groups of pineal tumors with specific clinical and molecular features. Our findings provide a foundation for further clinical as well as molecular and functional characterization of PB and other pineal tumors, including the role of miRNA processing defects in oncogenesis.

Molecular characterization of histopathological ependymoma variants.

According to the WHO classification, ependymal tumors are classified as subependymomas, myxopapillary ependymomas, classic ependymomas, anaplastic ependymomas, and RELA-fusion-positive ependymomas (RELA-EPN). Among classic ependymomas, the WHO defines rare histological variants, i.e., the clear cell, papillary, and tanycytic ependymoma. In parallel, global DNA methylation patterns distinguish nine molecular groups, some of which tightly overlap with histopathological subgroups. However, the match of the aforementioned histological variants to DNA methylation classes remains unclear. We analyzed histomorphology, clinical parameters, and global DNA methylation of tumors with the initial histological diagnoses of tanycytic (n = 12), clear cell (n = 14), or papillary ependymoma (n = 19). Forty percent of these tumors did not match to the epigenetic profile of ependymomas, using a previously published DNA methylation-based classifier for brain tumors. Instead, they were classified as low-grade glioma (n = 3), plexus tumor (n = 2), CNS high-grade neuroepithelial tumor with MN1 alteration (n = 2), papillary tumor of the pineal region (n = 2), neurocytoma (n = 1), or did not match to any known brain tumor methylation class (n = 8). Overall, integrated diagnosis had to be changed in 35.6% of cases as compared to the initial diagnosis. Among the tumors molecularly classified as ependymoma (27/45 cases), tanycytic ependymomas were mostly located in the spine (5/7 cases) and matched to spinal or myxopapillary ependymoma. 6/8 clear cell ependymomas were found supratentorially and fell into the methylation class of RELA-EPN. Papillary ependymomas with a positive ependymoma match (12/19 cases) showed either a "papillary" (n = 5), a "trabecular" (n = 1), or a "pseudo-papillary" (n = 6) growth pattern. The papillary growth pattern was strongly associated with the methylation class B of posterior fossa ependymoma (PFB, 5/5 cases) and tumors displayed DNA methylation sites that were significantly different when compared to PFB ependymomas without papillary growth. Tumors with pseudo-papillary histology matched to the methylation class of myxopapillary ependymoma (4/6 cases), whereas the trabecular case was anatomically and molecularly a spinal ependymoma. Our results show that the diagnosis of histological ependymoma variants is challenging and epigenetic profiles may improve diagnostic accuracy of these cases. Whereas clear cell and papillary ependymomas display correlations between localization, histology, and methylation, tanycytic ependymoma does not represent a molecularly distinct subgroup.

Papillary Tumor of the Pineal Region: Systematic Review and Analysis of Prognostic Factors.

Clinical outcomes and biological behavior of papillary tumors of the pineal region (PTPR) are still under investigation. The best therapeutic strategy has not been defined. To perform a comprehensive patient-level analysis of all PTPR cases and identify their clinical features, treatment options, and prognostic factors. A search of the medical databases for case series and reports on PTPRs from January 2003 to June 2017 was performed. Data addressing PTPR's clinical presentation, imaging, treatment, and histological features were. Variables associated with the primary outcome of 36-mo survival were identified through Cox regression models. The initial search yielded 1164 studies, of which 71 were included (60 case reports and 11 case series), containing 177 patients (mean age 33.0±15.3 yr and 53.2% male). Intracranial hypertension and hydrocephalus prevailed as the clinical picture. Surgery was performed on 82.0% and gross total resection (GTR) was achieved on 71.4%. A total of 56.8% recurred after a median 29 mo (quartiles 10.5-45.5). The 36-mo survival rate was 83.5% (95% confidence interval [CI] 76.2-89.2%). Good functional outcomes (Glasgow Outcome Scale 4/5) were observed in 60.0%. The variables of interest were inconsistently reported and the multivariable analysis final sample was 133 patients. After adjustment for age, tumor size (each additional centimeter, hazard ratio [HR] 1.99, 95% CI 1.12-3.53, P=.019) and surgical treatment (HR 0.16, 95% CI 0.05-0.45, P=.001) were associated with 36-mo survival. Tumor size and surgery are associated with improvement in 36-mo survival. We did not observe any significant benefits from GTR or adjuvant treatments.

Papillary Tumor of the Pineal Region in an Adolescent

Papillary Tumor of the Pineal Region in an Adolescent

Primary pineal tumors - Unraveling histological challenges and certain clinical myths.

Pineal gland tumors range from the well-differentiated "pineocytoma" [World Health Organization (WHO) grade I], which have a very good prognosis, to the aggressive and poorly differentiated "pineoblastoma" (WHO grade IV) with "pineal parenchymal tumor of intermediate differentiation" (PPTID; WHO grades II and III) occupying intermediary differentiation and prognosis. Papillary tumor of the pineal region (PTPR; WHO grades II and III) is a distinct entity with propensity for recurrence and spinal dissemination. However, the diagnostic criteria to differentiate these entities, especially between WHO grades II and III of both PPTID and PTPR, remain nebulous. To evaluate the relative frequency of the individual entities and histomorphological (including the proliferation indices) features across the spectrum of pineal parenchymal tumors (PPTs) [including PTPRs] along their course. All cases of PPTs were retrieved, reviewed, and graded based on the histological criteria defined in the literature. PPTID, more commonly seen in young adults, was the most common subtype of PPT. This was followed by pineoblastoma which was more commonly seen in children. Clinical progression was seen in both grades II and III of PPTID; however, it was more commonly seen in cases with a MIB1 labeling index of >10%. PTPRs (both grades II and III) showed an aggressive histological transformation and also intraparenchymal metastasis. PPTIDs are the most common adult primary PPTs and have the potential to progress and disseminate in both grades II and III. Both grades of PTPRs have a metastatic potential. These findings suggest the need for postoperative adjuvant therapy in both grades of PPTID and PTPR.

Stereotactic Radiosurgery for Pineal Region Tumors.

Pineal region tumors represent a heterogeneous group of different histologic entities, for which the management can be a significant challenge, due to their critical location and frequent aggressive behavior. Traditional management includes surgical resection, fractionated radiation therapy, and chemotherapy. Stereotactic radiosurgery (SRS) is being increasingly used in the treatment of these tumors. It is used as primary therapy for pineocytomas and papillary tumors of the pineal region, as an adjuvant radiation boost in combination with radiation or chemotherapy for pineoblastomas and germ cell tumors, or in the context of tumor recurrence. The reported morbidity is low, consisting in transient oculomotor disturbance in most cases. As a non-invasive alternative to microsurgical resection, SRS should always be considered when discussing these challenging cases.

Microsurgical Resection of Posterior Third Ventricular/Pineal Region Papillary Tumor Via Supracerebellar Infratentorial Approach: 3-Dimensional Operative Video

The posterior third ventricle and pineal region can harbor different pathologies. The supracerebellar infratentorial approach allows a direct access to the pineal region and posterior third ventricle and provides wide exposure of the arachnoid planes and deep venous system. In this 3-dimensional video, we present a patient with posterior third ventricular/pineal region tumor who underwent microsurgical resection via supracerebellar infratentorial approach. The patient is a 28-year-old woman with history of hydrocephalus who underwent endoscopic third ventriculostomy and biopsy at an outside hospital. The histopatology of the tumor was papillary tumor of the pineal region. The patient was referred for further surgical resection due to enlargement of her tumor on follow-up radiological imaging. The surgery and the patient's postoperative course were uneventful and the patient remained unchanged in the postoperative period. The important steps of the surgical approach and microsurgical resection are demonstrated in this 3-dimensional surgical video. The patient consented to publication of her images.

Papillary Tumor of the Pineal Region: Case Report and Literature Review

AbstractPapillary tumor of the pineal region (PTPR) is a neuroectodermal tumor thought to originate from cells of the subcommissural organ. Its oncologic properties are still under investigation, as well as the most suitable therapeutic measures for this type of neoplasm. We report the case of a 36-year-old woman with a 1-year history of headache and intermittent diplopia. The magnetic resonance imaging (MRI) scan showed a heterogeneously enhancing mass in the pineal region that caused an acute hydrocephalus, and an emergency shunt derivation was necessary. One week later, the patient was submitted to subtotal tumor resection, and remained asymptomatic in the post-operative period. In the follow-up, the patient remained asymptomatic; in the imaging control 3.5 years after the surgical resection, local recurrence was identified, and the patient was submitted to a local radiation protocol. Our literature review showed an early clinical onset due to intracranial hypertension signs. Definitive clinical onset might be reached only through a histopathological examination. Gross total resection followed by radiotherapy is the current standard of care. Local recurrence is often observed, with rare dissemination to the cerebral spinal fluid. The natural history of the PTPR remains unknown, as well as the best treatment strategy. Large case series with longer follow-ups are necessary for further conclusions.

A case of rare Papillary Tumor of the Pineal Region (PTPR) with leptomeningeal metastases treated with Bevacizumab and Chemotherapy (P6.135)

A case of rare Papillary Tumor of the Pineal Region (PTPR) with leptomeningeal metastases treated with Bevacizumab and Chemotherapy (P6.135)

Papillary Tumor of the Pineal Region: A Case Report

Pineal region tumors are uncommon lesions in the central nervous system. Papillary tumor of the pineal region is recently recognized as a separate disease. Its incidence, treatment, and outcome are not well-defined. We have reported the case of a 6 yearold- boy with papillary tumor of the pineal region. He presented with headaches, nausea and vomiting and, after a biopsy, was referred for radiotherapy. The patient received 54 Gy irradiation to the pineal region followed by a chemotherapy regimen of cisplatin, vincristine, and lomostine. His tumor decreased slightly. After 4 years, the patient has remained well and attends school. He is under routine follow-up. We suggest radical radiotherapy as the main treatment for papillary tumors of the pineal region.

Unedited microneurosurgery of a large recurrent papillary tumor of the pineal region.

Background:Papillary tumor of the pineal region (PTPR) is a new entity introduced in the 2007 World Health Organization (WHO) nomenclature to describe a rare grade II–III pineal lesion with epithelial-like papillary architecture and particular immunohistochemical features. PTPR is extremely rare in children. Herein, we present an unedited gross total microsurgical resection of a histologically confirmed WHO grade III PTPR. Our aim is to demonstrate the efficiency and safety of our microsurgical technique into deep brain territories under the principle “simple, clean, and preserving the normal anatomy.” For this, a posterior occipital interhemispheric approach and a proper praying sitting position were essential.Case Description:A patient with recurrent PTPR after a subtotal resection abroad underwent sitting praying position and left occipital craniotomy. The opened dura based on the superior sagittal sinus was strongly retracted providing hemostasis of the epidural space. The pericallosal cistern was reached by an interhemispheric approach with cerebrospinal fluid release. Under careful navigation, the tumor was recognized. Following high microscopic magnification, tissue samples were obtained for immediate histological studies and internal debulking of the tumor was performed with ring forceps and long bipolar forceps as well. After a careful dissection and devascularization of the lesion, the tumor was softly but constantly pulled out with long ring microforceps in the right hand, whereas a thumb-regulated suction tube in the left hand acted oppositely, detaching the lesion from surrounding structures. Bipolar coagulation forceps were used to shrink the tumor and to remove it by piecemeal reduction. Water irrigation provided a clean surgical field and helped us to separate deep borders of the lesion by water dissection technique. Finally, careful tumor detachment from the deep venous system and meticulous hemostasis of the surgical site ensured a safe surgery. The postoperative course was uneventful. The patient underwent radiohemotherapy as an adjuvant treatment and is alive and free of recurrence almost 4 years after surgery.Conclusion:This unedited video offers all detailed aspects that are, as the senior author JH considers, essential for a neurosurgeon when performing an efficient and safe surgery into the pineal region for this very rarely documented papillary tumor.Videolink:http://surgicalneurologyint.com/videogallery/pineal-region-tumor

Papillary tumor of the pineal region accompanied by Parinaud's syndrome: magnetic resonance imaging findings.

Papillary tumor of the pineal region accompanied by Parinaud's syndrome: magnetic resonance imaging findings.