From the Department of Ophthalmology (NG-C, YR, MS), Rabin Medical Center, Beilinson Campus, Petach Tikva; the Pediatric Ophthalmology Unit (NG-C, YR, MS) and the Departments of Pediatric Radiology (LK), Oncology (HT, IJC), and Neurosurgery (SM), Schneider Children’s Medical Center of Israel, Petach Tikva; and the Sackler Faculty of Medicine (NG-C, JH, LK, HT, MS, IJC, SM), Tel Aviv University, Tel Aviv, Israel.
The authors have no financial or proprietary interest in the materials presented herein.
The authors thank Gloria Ginzach for her editorial assistance.
Address correspondence to Nitza Goldenberg-Cohen, MD, Pediatric Ophthalmology Unit, Schneider Children’s Medical Center of Israel, Petach Tikva 49202, Israel.
Parinaud syndrome, also known as dorsal mid-brain syndrome or pretectal syndrome, is characterized by abnormalities often associated with eyelid retraction, pupil dysfunction, or both due to intrinsic or extrinsic damage to the dorsal mid-brain.1 In children, it often occurs as a complication of hydrocephalus and increased intracranial pressure induced by pineal region tumors.2,3 Ophthalmological examination reveals paralysis of up gaze movements, dissociation of pupillary response to light and accommodation, and failure of convergence.4–6 Some patients show immediate improvement after placement of a ventriculoperitoneal shunt,7,8 or slower improvement after treatment of the causative factor.9 Although resolution is considered unlikely, historically, patients with Parinaud syndrome have not been observed over an extended period and the long-term prognosis is unknown.
Our review of the literature yielded one report of spontaneous improvement in upward gaze 4.5 years after treatment of traumatic hydrocephalus in an adult.10 However, this report involved trauma-related and not tumor-related Parinaud syndrome. Furthermore, the outcome in children may differ. Although Cho et al.11 conducted a 10-year follow-up study of patients with pineal region tumors, wherein 17 of the 35 children had varying degrees of Parinaud syndrome, they focused on the oncological findings, with no mention of the ophthalmological outcome. Therefore, a more thorough analysis of the ophthalmological sequelae of Parinaud syndrome is warranted.
The current study examined the long-term pathological and ophthalmological findings in children with tumor-related Parinaud syndrome who were diagnosed and treated at our center during the past 7 years.
Patients and Methods
The study was approved by the local and national Human Research Ethics Committees and was conducted in accordance with the tenets of the Declaration of Helsinki.
The computerized files of the Neuro-Ophthalmology Clinic of Schneider Children’s Medical Center of Israel, a major tertiary facility, from 2000 to 2007 were searched for children with Parinaud syndrome who were younger than 17 years at diagnosis. Children with pineal region tumors but no evidence of Parinaud syndrome were excluded from the study. Of the 7 children identified, one was not included in the current analysis because she had already been diagnosed and treated for another malignancy (thyroid carcinoma) as part of Turcot syndrome. She acquired Parinaud syndrome 2 years after detection of the pineal region tumor, but immediately following biopsy.
Of the 6 children eligible for the study, 4 had been referred from other hospitals. The medical records were analyzed for patient age and sex, initial presentation and symptoms, date of diagnosis, cause of the syndrome, ophthalmological findings at diagnosis and follow-up, treatment, and neuroimaging findings at diagnosis and follow-up. The magnetic resonance imaging (MRI) scans made at diagnosis and follow-up were revised. In cases due to tumor, the tumor classification and maximal diameter of the mass were documented and the postoperative focal parenchymal defects were evaluated.
The study group included 5 boys and 1 girl with a mean age of 8.8 years at diagnosis (range: 4 to 16.6 years; median: 8 years). The mean duration of follow-up was 4.2 years (range: 1.4 to 10 years). Symptoms at presentation (Table 1) included headache or vomiting in 5 patients, blurred vision or “bumping into objects” in 2 patients, and hearing loss with vertigo in 1 patient. All had papilledema, indicating increased cranial pressure, at diagnosis; in 1 patient, the papilledema was detected incidentally on work-up for febrile gastroenteritis. The average duration between presentation and diagnosis/therapy was 3.6 weeks. Cranial imaging at diagnosis revealed hydrocephalus in all patients. The clinical diagnosis of Parinaud syndrome was made at the initial eye examination and evaluation at our referral center.
Table 1: Symptoms and Signs at Diagnosis in 6 Children with Parinaud Syndrome
Ophthalmological evaluation at presentation showed normal visual acuity in 4 patients (Table 1). Bilateral visual acuity measured 20/100 in 1 patient, although she did not complain of blurred vision. In another patient, visual acuity was 20/30 in the right eye and 20/200 in the left eye, indicating left optic neuropathy. The child who “bumped into objects” had visual acuity of 20/20 in both eyes. None of the children had eyelid retraction. All had limitation of up gaze—supranuclear in 4 patients and infranuclear in 2 patients. All had convergence insufficiency, convergence retraction nystagmus, and light-near dissociation, which is typical of Parinaud syndrome. One patient had new-onset esotropia secondary to the increased intracranial pressure and abducens palsy, in addition to vertical diplopia due to trochlear nerve palsy. None had complaints or vertical diplopia caused by the up gaze paresis. The acute abducens paresis resolved after the intracranial pressure decreased, revealing convergence insufficiency.
In all 6 cases, the cause of the Parinaud syndrome was traced to an underlying tumor (Table 2): pineal germinoma in 4 patients, mature pineal teratoma in 1 patient, and pineal astrocytoma in 1 patient. Treatment consisted of surgical shunting procedures for the hydrocephalus in addition to complete or partial removal of the tumor mass (Table 2). Four patients received adjuvant chemotherapy, in addition to total brain irradiation in 3 of them (Table 2). The most improvement was achieved during the first 4 months after treatment.
Table 2: Diagnosis, Treatment, and Neuroimaging Follow-Up in 6 Children with Parinaud Syndrome
Imaging follow-up, performed in 5 patients (Table 2), showed complete excision of the tumor (no residual mass) in 3 patients, all of whom had a focal parenchymal defect in the mid brain. In the other 2 patients, a residual mass in the pineal region was present, causing compression of the tectum in one. One patient had leukomalacia.
Ophthalmological examination at the last follow-up visit (Table 3) revealed normal visual function (visual acuity, visual fields, color vision) in 5 of the 6 children. The remaining child, who had bilateral optic neuropathy, had reduced visual acuity (worst eye: hand motions), color vision, and visual fields in addition to bilateral optic atrophy, probably following long-standing papilledema. All children showed significant improvement in ocular up gaze, but with varying residual limitation in up gaze (minimal in 2 patients) and convergence insufficiency.
Table 3: Ophthalmological Findings at the End of Follow-Up in 6 Children with Parinaud Syndrome
Alternate esotropia with spasm (ocular neuromyotonia) developed in 1 patient after surgery and radiation therapy. Exotropia was measured in 2 patients. One showed a rapid deterioration in visual acuity with optic atrophy after the initial dose of chemotherapy, and treatment was stopped. In the other, anisocoria with a dilated left pupil due to third cranial nerve palsy was noted immediately after surgery (Table 3). The latter patient underwent strabismus surgery. Convergence retraction nystagmus, especially when attempting up gaze, was documented in 5 children.
All children (12 eyes) had persistent light-near dissociation at the end of follow-up. Only 1 child had some pupillary response to light.
The parents reported learning difficulties in 4 children, of whom 3 were treated with radiation and also had cognitive delay. Three of the children with learning difficulties had moderate to severe convergence insufficiency (Table 3).
The current study describes the long-term ophthalmological findings in 6 children with dorsal mid-brain (Parinaud) syndrome, all of whom had tumors in the region of the pineal gland: germinoma, astrocytoma, or teratoma. The incidence of the pineal region tumor subtypes was similar to that reported previously.11 By contrast, in adults with Parinaud syndrome, the hydrocephalus is usually not tumor related.5
All children tended to have subtle but significant residual ophthalmological findings years after diagnosis and definitive treatment. Although the average duration between presentation and therapy was less than a month, the outcome was still characterized by permanent damage and persistent symptoms and signs.
Two children had reduced vision already at diagnosis (one was bumping into objects), and one was incidentally diagnosed following fundus examination and findings of papilledema. All improved except one in whom visual function severely deteriorated in both eyes. The inability of the children to express themselves accurately and their possible unawareness of the visual dysfunction because of their young age may have contributed to the delay in diagnosis. Children with visual disturbances hardly ever complain, even when monocular visual loss occurs,12 as in our series.
None of the children were aware of their limitation in up gaze. When diplopia existed, it was not due to the up gaze limitation but to new-onset paretic strabismus, a common nonspecific consequence of increased intracranial pressure. Only in one case did long-standing papilledema prompt a diagnostic neuroimaging study.
One child had hearing loss, a rare finding in patients with pineal region tumors. Our search of the literature revealed only one report of a 12-year-old boy with a malignant pineal germ cell tumor and severe hearing loss.13 The authors attributed the hearing loss to direct bilateral compression of the inferior colliculi, and it resolved completely after tumor resection.
Although the ocular findings of Parinaud syndrome were also traditionally believed to partially resolve with treatment of the tumor and the hydrocephalus,11,13,14 our study shows that minor sequelae may remain. Despite the rapid improvement that occurred in all of our patients immediately after surgery, on follow-up, we found minimal changes in all parameters of the syndrome examined. All of the children had various degrees of abnormal eye movement and pupil response to light years after diagnosis. Five had convergence retraction nystagmus. The best outcome was noted in the patient with a benign teratoma that was surgically removed without adjuvant therapy, but we cannot generalize the findings from a single patient. We speculate that the signs were due to the residual pineal region mass or the focal parenchymal defect in the mid brain noted on neuroimaging after treatment.
Tumor-related Parinaud syndrome in children may cause ophthalmological complications. In this study, we described the long-term ophthalmological findings in six children with dorsal mid-brain (Parinaud) syndrome, all of whom had tumors in the region of the pineal gland. Such patients tend to have subtle but measurable residual ophthalmological findings years after diagnosis and definitive treatment. The current study indicates that the ophthalmologist plays a crucial role in detecting these complications both at diagnosis of the disease and in the long term, after treatment of the underlying cause. The residual ophthalmological impairments after tumor resection are not expected to undergo spontaneous resolution.
- Pearce JM. Parinaud’s syndrome. J Neurol Neurosurg Psychiatry. 2005;76:99. doi:10.1136/jnnp.2003.031310 [CrossRef]
- Aguilar-Rebolledo F, Zarate-Moysen A, Quintana-Roldan G. [Parinaud’s syndrome in children]. Rev Invest Clin. 1998;50:217–220.
- Donat JF, Okazaki H, Gomez MR, Reagan TJ, Baker HL Jr, Laws ER Jr, . Pineal tumors: a 53-year experience. Arch Neurol. 1978;35:736–740.
- Moffie D, Ongerboer de Visser BW, Stefanko SZ. Parinaud’s syndrome. J Neurol Sci. 1983;58:175–183. doi:10.1016/0022-510X(83)90215-0 [CrossRef]
- Pierrot-Deseilligny CH, Chain F, Gray F, Serdaru M, Escourolle R, Lhermitte F. Parinaud’s syndrome: electro-oculographic and anatomical analyses of six vascular cases with deductions about vertical gaze organization in the premotor structures. Brain. 1982;105:667–696.
- Amendola BE, McClatchey K, Amendola MA. Pineal region tumors: analysis of treatment results. Int J Radiat Oncol Biol Phys. 1984;10:991–997.
- Waga S, Okada M, Yamamoto Y. Reversibility of Parinaud syndrome in thalamic hemorrhage. Neurology. 1979;29:407–409.
- Pollack IF, Pang D, Albright AL. The long-term outcome in children with late-onset aqueductal stenosis resulting from benign intrinsic tectal tumors. J Neurosurg. 1994;80:681–688. doi:10.3171/jns.1994.80.4.0681 [CrossRef]
- Keane JR. The pretectal syndrome: 206 patients. Neurology. 1990;40:684–690.
- Miller NR. Late improvement in upward gaze in a patient with hydrocephalus related Parinaud dorsal midbrain syndrome. Br J Ophthalmol. 2006;90:123. doi:10.1136/bjo.2005.081810 [CrossRef]
- Cho BK, Wang KC, Nam DH, et al. Pineal tumors: experience with 48 cases over 10 years. Childs Nerv Syst. 1998;14:53–58. doi:10.1007/s003810050175 [CrossRef]
- Cohen BH, Garvin JH Jr, . Tumors of the central nervous system. In: Rudolph CD, Rudolph AM, Hostetter MK, Lister G, Siegel NJ. Rudolph’s Pediatrics. New York: McGraw-Hill; 2003:2220.
- Gaspar N, Verschuur A, Mercier G, Couanet D, Sainte-Rose C, Brugières L. Reversible hearing loss associated with a malignant pineal germ cell tumor: case report. J Neurosurg. 2003;99:587–590. doi:10.3171/jns.2003.99.3.0587 [CrossRef]
- Shin HJ, Cho BK, Jung HW, Wang K. Pediatric pineal tumors: need for a direct surgical approach and complications of the occipital transtentorial approach. Childs Nerv Syst. 1998;14:174–178. doi:10.1007/s003810050206 [CrossRef]
Symptoms and Signs at Diagnosis in 6 Children with Parinaud Syndrome
|Patient||Sex||Age (Y)||Presenting General Complaints||Presenting Ocular Complaints||Delay in Diagnosis (Mo)||Neuroimaging Findings||Ocular Findings||Visual Acuity|
|1||M||4||Headache, vomiting||None||1||Pineal reg. tu., hydrocephalus||Papilledema and sluggish reaction to light||20/100 OD, 20/100 OS|
|2||M||8||Headache, vomiting, vertigo, hearing loss||Blurred vision||1.5||Pineal reg. tu., hydrocephalus||Papilledema (long-standing) with left optic neuropathy||20/30 OD, 20/200 OS|
|3||M||7||Gastroenteritis, fever, stupor||None||None||Pineal reg. tu., hydrocephalus||Papilledema (incidental finding)||20/30 OD, 20/30 OS|
|4||M||9||Headache, fever||Bumping into objects, vertical diplopia||1||Pineal reg. tu., hydrocephalus||Papilledema, abducens and trochlear nerve palsy||20/20 OD, 20/20 OS|
|5||F||8||Vomiting||None||1||Pineal reg. tu., hydrocephalus||Papilledema||20/30 OD, 20/30 OS|
|6||M||16.6||Headache, vomiting||None||UK (less than 1)||Pineal reg. tu., hydrocephalus||Papilledema||20/25 OD, 20/25 OS|
Diagnosis, Treatment, and Neuroimaging Follow-Up in 6 Children with Parinaud Syndrome
|Patient||Tumor Type (Size in cm)||Shunting Procedure||Chemotherapy/Radiation||Neuroimaging Follow-up|
|1||Pineal mature teratoma (2 × 2.5 ×2.6)||VP||No adjuvant therapy||N/A|
|2||Pineal germinoma (2.3 ×3 × 3)||VP||Chemotherapy||34 months, no RM, LD 1.1 × 0.4 post PVL|
|3||Pineal germinoma (1.2 ×1.2 ×1.5)||VP||Chemotherapy, radiation||26 months, RM 1.2 ×1.2, No LD|
|4||Pineal germinoma (4 × 3.5 × 3.2)||VP||Chemotherapy, radiation||25 months, RM 2.2 ×1.0, no LD, pressure on tectum|
|5||Pineal astrocytoma (1.5 ×2.0)||VP||No adjuvant therapy||42 months, no RM, LD 0.3 ×1.5|
|6||Pineal germinoma (3 × 3 ×4)||VP||Chemotherapy, radiation||50 months, no RM, LD 1.6 ×1.2 ×1.2 tectum & mid-brain|
Ophthalmological Findings at the End of Follow-Up in 6 Children with Parinaud Syndrome
|Patient||Age at FU (Y)||Length of FU (Y)||Visual Acuity||Eyelid Retraction||Limited Up Gaze||Conv.||CRN||Pupil Response to Light||Ishihara Color Test||VF||Disc Appearance||Strabismus/LD|
|1||9.3||5.3||20/100 OD, 20/100 OS||20/25 OD, 20/25 OS||No||No||Limited IN||Min. limited||Normal||Yes||Sluggish||Residual||Full||Full||PE||Nl||None|
|2||11.3||3.3||20/30 OD, 20/200 OS||20 cm FC OD, HM OS||No||No||Limited SN||Limited||Mod-severe||Yes||NR||NR||2/10 OD, 0/10 OS||None||PE||Bil OA||Exotropia (sensory)/LD|
|3||8.4||1.4||20/30 OD, 20/30 OS||20/25 OD, 20/25 OS||No||No||Limited IN||Min. limited||Mod-severe||None||NR||NR||Full||Full||PE||Nl||None/LD+|
|4||11.2||2.2||20/20 OD, 20/20 OS||20/20 OD, 20/20 OS||No||No||Limited SN||Limited||Mod-severe||Yes||NR||NR||Full||Full||PE||Nl||None/LD+|
|5||18||10||20/30 OD, 20/30 OS||20/20 OD, 20/20 OS||No||No||Limited SN||Limited||Normal||Yes||NR||NR left dilated pupil||Full||Full||PE||Nl||Exotropia (left 3rd CN paralysis)|
|6||19.3||3||20/25 OD, 20/25 OS||20/20 OD, 20/20 OS||No||No||Limited SN||Limited||Mod-severe||Yes||NR||NR||Full||Full||PE||Nl||Esotropia (6th CN paralysis)/LD+|