Abstract
Background
Dorsal midbrain syndrome (also known as Parinaud syndrome and pretectal syndrome) is a well-known complication of tumors of the pineal region. However, there are few reports regarding outcomes, especially in children. The purpose of this study was to report the ophthalmic outcomes in a group of children with pineal tumors treated at a single institution.
Methods
The medical records of pediatric patients diagnosed with pineal region tumors and evaluated at our ophthalmology clinic were studied retrospectively. Descriptive statistics were used to assess rate of dorsal midbrain syndrome, defined as one or more of the following: limitation of upgaze, pupillary light-near dissociation, and convergence retraction nystagmus. Treatment outcomes were recorded.
Results
A total of 35 subjects (age range, 5 months to 20 years) were included, 18 (51%) of whom were found to have dorsal midbrain syndrome. Of those 18, 16 patients (89%) had limitation of upgaze, 15 (83%) had pupillary light-near dissociation, and 9 (50%) had convergence-retraction nystagmus. Convergence insufficiency was noted in 5 patients (28%); exotropia (either intermittent or constant), in 9 (50%). Improvement in dorsal midbrain syndrome findings following treatment was seen in 7 of 17 patients (41%), but only 2 (12%) experienced complete resolution. Treatment consisted of surgery, radiation, and/or chemotherapy.
Conclusions
In our study cohort of children with pineal tumors have a high incidence of dorsal midbrain syndrome. Most cases had residual findings after treatment.
Dorsal midbrain syndrome (also known as Parinaud syndrome and pretectal syndrome) is a well-known complication of tumors of the pineal region. Major components of this syndrome include supranuclear limitation of upgaze, pupillary light-near dissociation, lid retraction (Collier’s sign), and convergence-retraction nystagmus. Minor components can include horizontal eye movement disturbances such as convergence insufficiency and exotropia. Skew deviation has also been described.1
It is thought that most of the symptoms associated with this syndrome resolve following treatment of the pineal tumor. The few publications on this topic report on mixed cohorts of children and adults.2 Also, surgical outcomes in these patients have not been widely reported.3 A comprehensive, longitudinal evaluation of pediatric patients with dorsal midbrain syndrome as a result of pineal tumors has not been previously performed. Thus, the prevalence of long-term ocular problems in children with pineal tumors has not been well described. The purpose of this study was to report the ophthalmic outcomes in a group of children with pineal tumors treated at our institution.
Subjects and Methods
This study was approved by the institutional review boards of St. Jude Children’s Research Hospital and the University of Tennessee Health Science Center, Memphis, and complied with the US Health Insurance Portability and Accountability Act of 1996. The medical records of pediatric patients diagnosed with pineal region tumors at St. Jude Children’s Research Hospital from 1995 to 2012 were reviewed retrospectively. Patients who received an ophthalmological examination within 6 months of tumor diagnosis as well as at least one additional visit (with 1 exception, described below) were included. Patients were considered to have dorsal midbrain syndrome if they had one or more of the following diagnostic signs: limitation of upgaze, pupillary light-near dissociation, or convergence-retraction nystagmus. Convergence insufficiency was diagnosed if a patient had a remote near point of convergence, an exophoria at near, and asthenopia. Ophthalmic outcomes, including visual acuity, alignment, and strabismus treatments (including prisms, orthopic exercises, and strabismus surgery) were also recorded.
Results
A total of 82 patients were treated for pineal region at our institution during the study period. Of these, 23 expired before they could be evaluated by our ophthalmology clinic; 11 were never referred to the eye clinic. Forty-eight were seen in the eye clinic at some point during their treatment; of these, 35 met inclusion criteria. Only 5 patients had an eye examination prior to neurosurgical intervention. The included patients’ characteristics and clinical features are shown in Table 1. Average age at diagnosis was 10.2 years (range, 5 months to 18 years). The tumor types of the included patients are noted in Table 2.
Table 1.
Patient characteristics and clinical features of the 35 patients meeting inclusion criteria
| Characteristic | Number | Percentage |
|---|---|---|
| Sex | ||
| Male | 28 | 80.0 |
| Female | 7 | 20.0 |
| Race | ||
| White | 20 | 57.1 |
| African American | 8 | 22.9 |
| Asian | 1 | 2.9 |
| Other | 6 | 17.1 |
| Radiation therapy | ||
| Yes | 32 | 91.4 |
| No | 3 | 8.6 |
| Chemotherapy | ||
| Yes | 25 | 71.4 |
| No | 10 | 28.6 |
| Surgical intervention | ||
| Gross total resection | 13 | 37.1 |
| Partial resection | 10 | 28.6 |
| Biopsy or shunt only | 9 | 25.7 |
| No surgery | 3 | 8.6 |
Table 2.
Tumor types of 35 patients meeting inclusion criteria
| Tumor diagnosis, pineal region | Number |
|---|---|
| Astrocytoma, pilocytic | 2 |
| Atypical teratoid rhabdoid tumor | 1 |
| Germ cell tumor, mixed | 5 |
| Germinoma | 8 |
| Germinoma, suprasellar and pineal | 2 |
| Region | |
| Lesion | 1 |
| Mature teratoma | 1 |
| Pineoblastoma | 13 |
| Teratoma, malignant | 1 |
| Pineal germ cell tumor | 1 |
Of the 35 patients, 18 (51%; mean age, 9 years; range, 5 months to 18 years) were diagnosed with dorsal midbrain syndrome. Of these 18, 16 patients had undergone a neurosurgical procedure prior to the first eye clinic visit. The age, vision, tumor type, presenting signs and symptoms, and follow-up condition of each patient with dorsal midbrain syndrome are provided in Table 3. Average length of follow-up was 37 months (range, 1–132 months). Of the 18 patients with dorsal midbrain syndrome (Table 3B), 16 (89%) had limitation of upgaze; 15 (83%), pupillary light-near dissociation; and 9 (50%), convergence-retraction nystagmus.
Table 3A.
Patient age, visual acuity, and tumor types for 18 patients with dorsal midbrain syndrome
| Patient | Age at diagnosis, years | Pineal region tumor type | BCVA initial | BCVA final |
|---|---|---|---|---|
| 1 | 11 | Astrocytoma | 20/20 OU | 20/20 OD 20/25 OS |
| 2a | 0.92 | Atypical teratoid Rhabdoid tumor | Blink to light OUb | Fix and follow OUb |
| 3 | 11 | Germ cell tumor, mixed | 20/20 OU | 20/40 OU |
| 4 | 18 | Germ cell tumor, mixed | 20/25 OU | 20/30 OD 20/20 OS |
| 5 | 9 | Germ cell tumor, mixed | 20/25 OU | 20/20 OD 20/25 OS |
| 6c | 12 | Germinoma | 20/25 OU | No follow-up |
| 7 | 11 | Germinoma | 20/20 OD 20/25 OS |
20/20 OU |
| 8 | 11 | Germinoma | 20/20 OU | 20/20 OU |
| 9 | 17 | Germinoma | 20/30 OD 20/25 OS |
20/20 OU |
| 10a | 13 | Unspecified | 20/40 OD 20/25 OS |
20/25 OU |
| 11 | 6 | Mature teratoma | 20/40 OD CF at 6 feet OS |
20/20 OD CF OS |
| 12 | 13 | Pineoblastoma | 20/30 OD 20/25 OS |
20/30 OD 20/25 OS |
| 13 | 5 | Pineoblastoma | 20/40 OD 20/30 OS |
20/50 OD 20/40 OS |
| 14 | 5 | Pineoblastoma | 20/30 OD 20/40 OS |
20/50 OD 20/80 OS |
| 15a | 0.42 | Pineoblastoma | Fix and followb | Fix and followb |
| 16a | 4 | Pineoblastoma | Fix and follow OU | 20/40 OD 20/25 OS |
| 17 | 7 | Teratoma, malignant | CF at 2 feet OD HM OS |
20/40 OD 20/200 OS |
| 18 | 10 | Germ cell tumor | 20/25 OD 20/20 OS |
20/20 OD 20/40 OS |
BCVA, best-corrected visual acuity; CF, counting fingers; HM, hand motion; OD, right eye; OS, left eye; OU, both eyes; VA, visual acuity.
Patient died.
Preverbal child.
International patient, no follow-up available.
Table 3B.
Presenting symptoms in 18 patients with dorsal midbrain syndrome
| Patient | Presenting symptoms | Presenting dorsal midbrain syndrome symptoms |
|---|---|---|
| 1 | Headache, nausea, vomiting | Limitation in upgaze, pupillary light–near dissociation, convergence retraction nystagmus |
| 2a | Symptoms of obstructive hydrocephalus, pendular nystagmus, right ET, limitation in downgaze | Limitation in upgaze, pupillary light–near dissociation |
| 3 | Delayed papilledema, limitation in downgaze | Limitation in upgaze, pupillary light–near dissociation, convergence retraction nystagmus |
| 4 | Headache, diplopia, ataxia | Limitation in upgaze |
| 5 | Headache, nausea, vomiting, Diplopia, eyelid retraction | Limitation in upgaze Pupillary light–near dissociation, convergence retraction nystagmus |
| 6b | Diplopia, XT, remote near point of convergence | Pupillary light–near dissociation |
| 7 | Headache | Limitation in upgaze, pupillary light–near dissociation, convergence retraction nystagmus |
| 8 | Headache, nausea, vomiting, diplopia | Limitation in upgaze, pupillary light–near dissociation, convergence retraction nystagmus |
| 9 | Diplopia | Limitation in upgaze |
| 10a | Diplopia, blurry vision | Limitation in upgaze, pupillary light–near dissociation, convergence retraction nystagmus |
| 11 | Headache | Limitation in upgaze, pupillary light–near dissociation, convergence retraction nystagmus |
| 12 | Diplopia, headache, nausea, vomiting, photophobia | Pupillary light–near dissociation |
| 13 | Headache, tremors, discoordination, diplopia, photophobia | Limitation in upgaze, convergence retraction, nystagmus |
| 14 | Headache, nausea, vomiting | Limitation in upgaze, pupillary light–near dissociation |
| 15a | Bulging fontanelles | Limitation in upgaze, pupillary light–near dissociation |
| 16a | Neurologic decline, somnolence, nonreactive pupils, XT, right HT, limitation of downgaze, trochlear nerve palsy, limitation in downgaze | Limitation in upgaze, pupillary light–near dissociation |
| 17 | Left exotropia, headache, nausea, vomiting, limitation in downgaze | Limitation in upgaze, pupillary light–near dissociation |
| 18 | Headache, somnolence, precocious puberty, diplopia, blurry vision, photophobia, papilledema, limitation in downgaze | Limitation in upgaze, pupillary light–near dissociation, convergence retraction nystagmus |
ET, esotropia; XT, exotropia; HT, hypertropia.
Patient died.
International patient, no follow-up available.
On follow-up (Table 3C), 5 patients (28%) with dorsal midbrain tumor also had convergence insufficiency, and 9 (50%) had either intermittent or constant exotropia. One patient (patient 5) had eyelid retraction.
Table 3C.
Signs and symptoms at final follow-up in 18 patients with dorsal midbrain syndrome
| Patient | Follow-up signs or symptoms | Dorsal midbrain syndrome symptom resolution |
|---|---|---|
| 1 | Asthenopia, blurry vision, remote near point of convergence, convergence insufficiency | No improvement |
| 2a | Limitation of downgaze, left HT, X(T), cortical visual impairment | No improvement |
| 3 | XT, intermittent diplopia | No improvement |
| 4 | X(T) | Resolved |
| 5 | None | Improved |
| 6b | No follow-up | No follow-up |
| 7 | None | Improved |
| 8 | None | Resolved |
| 9 | Right HT, diplopia | Improved |
| 10a | Right HT, X(T), convergence insufficiency | Improved |
| 11 | Left XT, optic atrophy, macular RPE changes in the left eye | No improvement |
| 12 | Diplopia, exophoria, poor convergence, convergence insufficiency | No improvement |
| 13 | XT, optic atrophy, convergence insufficiency | No improvement |
| 14 | None | Improved |
| 15a | None | Improved |
| 16a | Right XT, right HT, trochlear nerve palsy | Improved |
| 17 | Left XT, limitation of downgaze | No improvement |
| 18 | XT, convergence insufficiency | No improvement |
HT, hypertropia; HoT, hypotropia; RPE, retinal pigment epithelium; XT, exotropia; (X)T, intermittent exotropia.
Patient died.
International patient, no follow-up available.
One international patient (patient 6) was only seen once, having come to our institution for radiation therapy. Follow-up care was provided in his home country. We included this patient in our tabulation for dorsal midbrain syndrome but not in our calculations for resolution or no resolution, because follow-up data is wanting.
Improvement in dorsal midbrain syndrome findings over the follow-up period was seen in 7 of 17 patients (41%). Only 2 patients (12%) experienced complete resolution (Table 3C).
Four children had impaired visual acuity (worse than 20/40; Table 3A). Patient 11 had poor vision in the left eye due to optic atrophy and macular retinal pigment epithelial changes as a result of previous nerve fiber layer edema. Patient 13 was noted to have optic atrophy in both eyes. Patient 14 developed cataracts (left greater than right) that had not been removed at final follow-up. Patient 17 developed a foveal scar in the left eye. The patient was first noted to have this on routine 6-month follow-up examination. No retinal abnormality was noted on any prior eye examination. Work-up did not reveal any evidence of active or prior infection.
Of the 5 patients noted to have convergence insufficiency, a single patient (patient 1) had resolution of symptoms during the follow-up period, and 1 (patient 12) was prescribed patching as needed for diplopia but was later lost to follow-up. Another was treated with convergence exercises but had little improvement in symptoms. This patient developed a right hypertropia from a trochlear nerve palsy due to hemorrhage into her vascular tumor. The hemorrhage was treated with a neurosurgical procedure, but the patient expired due to rebleed (patient 10). The remaining 2 patients subsequently developed a convergence insufficiency type exotropia. The first of these patients (patient 14) had a large-angle intermittent exotropia and a clinical course complicated by bilateral cataracts requiring cataract extraction with intraocular lens implantation as well as optic atrophy and amblyopia. He later underwent successful strabismus surgery. The second patient (patient 18) had diplopia and a large-angle exotropia that was greater at near than at distance. He underwent a lateral rectus recession and medial rectus resection of the right eye. He had resolution of his diplopia after strabismus repair.
In addition to the patients described above, surgery was recommended in another case. This child (patient 3) had a small-angle alternating exotropia, but his parents did not pursue surgical intervention.
One pineal tumor patient, not included in the 18 dorsal midbrain syndrome patients, developed an esotropia with mild abduction deficit. Although this could have been a pseudo-abducens nerve palsy sometimes seen with dorsal midbrain syndrome, she did not have any other signs of dorsal midbrain syndrome. Furthermore, she had a history of ventriculotomy and optic atrophy. Therefore, we were unable to definitively state whether this was a pseudo-abducens nerve palsy or a limitation of abduction resulting from hydrocephalus. She underwent a medial rectus recession and lateral rectus resection of the right eye and had an excellent outcome.
One patient (patient 9) did not require surgery but did require prism in glasses for a persistent right hypertropia with diplopia. This patient, despite improvement in upgaze limitation, still required the prismatic correction at final follow-up examination.
Discussion
There are few reports in the literature regarding the ophthalmological outcomes of children treated for pineal tumors.2,4–8 Our study provides evidence that ocular sequelae can persist in the long term in these children.2,3 Our results regarding the incidence of dorsal midbrain syndrome are similar to previously published accounts, which report both adult and pediatric patients. Suzuki and colleagues4 reported 24 cases of pineal tumors. They found upgaze limitation in 16 cases (67%), nonreactive pupils in 8 (33%), and nystagmus (of various causes) in 9 (38%). They did not report outcomes after treatment.4 Jooma and Kendall5 also did not comment on outcomes but reported an initial incidence of 40% (14/35) for limitation in upgaze, 54% (19/35) for light-near dissociation, and 22.9% (8/35) for nystagmus. Considering all 35 of our included patients, we found an incidence of about 46% for upgaze limitation, 43% for pupillary abnormalities, and 26% for convergence retraction nystagmus.
Dinc and colleagues6 reported 5 cases (only 1 pediatric patient) of pineal epidermoid tumors. They found that 3 of the 5 patients had dorsal midbrain syndrome on presentation. No further details regarding those patients with dorsal midbrain syndrome were provided and follow-up information on ophthalmic outcomes was not reported.6
A few case reports show complete improvement of motility disorders after treatment. Nagaishi and colleagues7 reported an 11-year-old boy with germinoma of the pineal region that presented with limited upgaze and convergence, mild pupillary dilation, and poor light reactivity in the right eye; after treatment the patient “regained normal eye movement.”7
Goldenberg-Cohen and colleagues2 reported residual ophthalmic findings in children with dorsal midbrain syndrome after pineal tumors. In this series of 6 children, all had limitation of upgaze and convergence retraction nystagmus; 5 had nonreactive pupils, and the remaining child exhibiting poor reactivity. On follow-up examination, upgaze improved in all and was only minimally limited in 2. Only 1 child showed some pupillary reaction to light. Convergence retraction nystagmus resolved in only 1 patient. They also reported that all 6 patients had convergence insufficiency at presentation, with only 2 returning to normal convergence after tumor treatment. One patient developed an esotropia due to trochlear nerve palsy from hydrocephalus, and 2 patients had an exotropia on final follow-up examination.2 This small case series supports our findings that the signs of dorsal midbrain syndrome often improve but do not fully resolve.
Hart and colleagues8 reported 20 patients (8 children) who underwent surgical resection of a pineal tumor. They found a preoperative rate of “visual disturbance” of 35% (90% had preoperative ophthalmic evaluation; the 2 who did not were too ill) and a postoperative rate of 55% (all but 1 had postoperative ophthalmic evaluation). Of the 11 patients who did not have ocular motility problems before neurosurgery, 9 had no visual disturbance after surgery, and the remaining 2 had resolution of their ophthalmic problems by the 1-year follow-up. Of the patients with “long-term (one-year or greater)” postoperative ophthalmic dysfunction: upgaze palsy and convergence-retraction nystagmus were seen in 55%, exotropia or esotropia in 25%, skew deviation in 15%, and disorders of vergence/accommodation in 20%.8 Although this series reports on both adults and children, it has a similar rate of dorsal midbrain syndrome to ours, at 51%, with a majority still having long-term ocular alignment and motility problems. Because most of our patients in this retrospective study did not have ophthalmic evaluation until after neurosurgical procedures, we did not divide our patients into before and after neurosurgery groups. This likely explains our rates of dorsal midbrain syndrome being similar to Hart and colleagues’ postsurgery group. A prospective study using ophthalmic examination before and after surgery may help determine what ocular problems are caused by the tumor itself as opposed to neurosurgical treatment.
Although it is a relatively small series and limited by its retrospective nature, our study is the largest series to date of children with dorsal midbrain syndrome after treatment for a pineal tumor. It reveals a similar incidence of dorsal midbrain syndrome when compared with previous studies. Our study stresses the need for long-term ophthalmic care of these children, because many will be left with residual motility deficits and strabismus.
Acknowledgments
This work was funded in part by an unrestricted grant from Research to Prevent Blindness. Support to St. Jude Children’s Research Hospital was also provided by the Cancer Center Support (CORE) grant (CA21765, C. Roberts, Principal Investigator) and the American Lebanese-Syrian Associated Charities (ALSAC). Funding for AG was provided by the Noyes Brain Tumor Foundation and Musicians Against Childhood Cancer.
The authors thank Jeannie Haman, PhD, for editorial assistance.
Footnotes
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