dominantly in males; however neonatal teratomas are more oftenseen in females.7 Our patient represents one of the few with a purefourth-ventricular immature teratoma diagnosed beyond the ageof 2 years.

Maximal surgical decompression of the tumor provides a smal-ler load for adjuvant chemotherapy and radiotherapy especially inthe setting of immature and malignant teratomas and may be cura-tive in smaller benign teratomas. The prognosis for intracranial ter-atomas remains guarded with a 1-year survival rate of 7.2% notedin a large series of infants.8 Chemotherapy, consisting of etoposide,cisplatin and bleomycin or cyclophosphamide, is advocated evenafter total removal of immature teratomas.6 A variable responseto chemotherapy has been noted in these tumors.6 Ogawa et al. re-ported a 10-year survival rate of 70% and a 5-year survival rate ofless than 50% respectively for patients with immature and malig-nant teratomas.9 Survivors exhibit developmental delay even aftersuccessful surgery.7

Though pure immature teratomas in the posterior fossa are re-ported in children aged between 20 days and 2½ years, teratomasoccurring in older children in this location are associated withmedulloblastomas.1,3–5 A search for a tumor associated with theimmature teratoma was negative in our patient. It would be reason-able to consider the possibility of the development of neuroectoder-mal tumors from primary extra-gonadal teratomas in childrenwhen the process of cerebellar differentiation within the tumor isdisrupted by the genetic makeup of the underlying germ cell tu-mor.3–5 Some authors include primitive neural tubules, rosettesand yolk sac formation and exclude disorganized but mature tissuefor accurately grading and prognosticating recurrence of immature

teratomas.5 Primitive neuronal tissue and yolk sac tissue were seenon tumor histology in our patient (Fig. 3).

In malignant teratomas, it is recommended that tumor activitybe monitored by means of alpha-feto protein and human chorionicgonadotropin levels.1,6 However, this was not performed in ourpatient. Antenatal ultrasound diagnosis of an intracranial teratomais possible, with the earliest diagnosis made at 21 weeksgestation.1,10

References

1. Bavbek M, Altinörs N, Caner H, et al. Giant posterior fossa teratoma. Childs NervSyst 1999;15:359–61.

2. Desai K, Nadkarni T, Muzumdar D, et al. Midline posterior fossa teratoma-casereport. Neurol Med Chir 2001;41:94–6.

3. Das S, Muro K, Goldman S, et al. Medulloblastoma arising from an immatureteratoma of the posterior fossa. Case report. J Neurosurg 2007;106:61–4.

4. Morelli RJ. Teratoma of the fourth ventricle. Case report. J Neurosurg 1973;38:355–7.

5. Longano A, Conyers R. Medulloblastoma arising from intracranial immatureteratoma. Pathology 2010;42:102–4.

6. Lee YH, Park EK, Park YS, et al. Treatment and outcomes of primary intracranialteratoma. Childs Nerv Syst 2009;25:1581–7.

7. Arslan E, Usul H, Baykal S, et al. Massive congenital intracranial immatureteratoma of the lateral ventricle with retro-orbital extension: a case report andreview of the literature. Pediatr Neurosurg 2007;43:338–42.

8. Wakai S, Arai T, Nagai M. Congenital brain tumors. Surg Neurol 1984;21:597–609.

9. Ogawa K, Toita T, Nakamura K, et al. Treatment and prognosis of patients withintracranial nongerminomatous malignant germ cell tumors: amultiinstitutional retrospective analysis of 41 patients. Cancer 2003;98:369–76.

10. Rickert CH, Probst-Cousin S, Louwen F, et al. Congenital immature teratoma ofthe fetal brain. Childs Nerv Syst 1997;13:556–9.

doi:10.1016/j.jocn.2010.06.009

298 Case Reports / Journal of Clinical Neuroscience 18 (2011) 298–299

Amantadine induced reversible corneal edema

Milind Deogaonkar a,⇑, Kathy Wilson a, Jerrold Vitek b

a Cleveland Clinic, Center of Neurological Restoration, S-31, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195, USAb Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA

a r t i c l e i n f o

Article history:Received 1 June 2010Accepted 13 June 2010

Keywords:AmantadineCorneal edemaDrug-induced dyskinesiaParkinson’s disease

a b s t r a c t

Amantadine is becoming more commonly used for Parkinson’s disease (PD), particularly for its efficacy intreating the drug-induced dyskinesias. Corneal edema is a known but unusual side effect of amantadinetherapy, rarely reported in the neurological literature. We report amantadine-induced reversible cornealedema in a patient with advanced PD.

� 2010 Elsevier Ltd. All rights reserved.

1. Introduction

Amantadine is an antiviral drug used in the treatment of Par-kinson’s disease1 (PD) and, in more recent years, for the treat-ment of drug-induced dyskinesia associated with PD. Whileunusual, toxic, reversible corneal edema can be associated withamantadine therapy; there are only a few reports.2–8 We report

⇑ Corresponding author. Tel.: +1 216 444 5188; fax: +1 216 445 9999.E-mail address: deoganm@ccf.org (M. Deogaonkar).

a patient with advanced PD with amantadine-induced reversiblecorneal edema.

2. Case report

A 61-year-old right-handed female patient presented with a7-year history of idiopathic PD. Her initial symptoms were rightupper extremity resting tremor. One year after the tremor startedshe was diagnosed with PD and was started on amantadine. Overthe next 6 years she was also treated with pramipexole, ropini-role, carbidopa/levodopa and entacapone. She subsequently

Fig. 1. Slit-lamp examination of right (a) and left (b) eye showing amantadine-induced severe corneal edema with (c, d) complete resolution after discontinuation ofamantadine therapy. (This figure is available in colour at www.sciencedirect.com.)

Case Reports / Journal of Clinical Neuroscience 18 (2011) 298–299 299

developed blurred vision, decreased visual acuity and dryness ofthe eyes, and was referred to ophthalmology. On slit-lamp exam-ination she was found to have profound corneal edema (Fig. 1a, b)and her visual acuity was 20/200 in both eyes. Although she hadbeen on amantadine for 6 years, it was discontinued. One monthafter discontinuation of amantadine therapy her corneal edemahad completely resolved (Fig. 1c, d) and her vision hadrecovered back to 20/20 in both eyes. Her corneal pachymetryhad improved from 0.81 mm to 0.64 mm in the right eye, andfrom 0.78 mm to 0.66 mm in the left eye. Her tear film was re-established. Her PD symptoms were well-controlled on carbidopa/levodopa and entacapone therapy.

3. Discussion

Amantadine is a commonly used medication in the treatmentof PD1 and for drug-induced dyskinesia associated with use ofanti-parkinsonian medications. Ophthalmologic adverse events ofamantadine are uncommon and hence are sometimes under-recognized.2,3,5–8 A retrospective post-marketing surveillanceVeterans Health Administration study of patients on amantadinefound that 0.27% of patients developed corneal edema over the2-year study.4 The relative risk of developing corneal edema fora person taking amantadine was 1.7.4 The mechanism ofcorneal endothelial toxicity caused by amantadine resulting in cor-neal edema is still unclear. Various hypotheses range from cornealdeposits of the drug through the tears to idiosyncratic hyper-sensitivity.2

doi:10.1016/j.jocn.2010.06.010

This report highlights an uncommon complication of a com-monly used medication in various neurological disorders. Patientswith advanced PD are elderly, have poor balance and are prone tofall. Any blurring of vision in these patients can increase the risk offall significantly. In practice, blurred vision is commonly blamed ondopamine agonists without carrying out detailed ophthalmologicexamination. This report suggests that any patient treated withamantadine who complains of increased falls or worsening visionshould undergo a slit-lamp examination to rule out this reversibleadverse effect of amantadine therapy.

References

1. Fahn S, Isgreen WP. Long-term evaluation of amantadine and levodopacombination in parkinsonism by double-blind crossover analyses. Neurology1975;25:695–700.

2. Chang KC, Kim MK, Wee WR, et al. Corneal endothelial dysfunction associatedwith amantadine toxicity. Cornea 2008;27:1182–5.

3. Dubow JS, Rezak M, Berman AA. Reversible corneal edema associated withamantadine use: an unrecognized problem. Mov Disord 2008;23:2096–7.

4. French DD, Margo CE. Postmarketing surveillance of corneal edema, Fuchsdystrophy, and amantadine use in the Veterans Health Administration. Cornea2007;26:1087–9.

5. Hughes B, Feiz V, Flynn SB, et al. Reversible amantadine-induced corneal edemain an adolescent. Cornea 2004;23:823–4.

6. Jeng BH, Galor A, Lee MS, et al. Amantadine-associated corneal edemapotentially irreversible even after cessation of the medication. Ophthalmology2008;115:1540–4.

7. Kubo S, Iwatake A, Ebihara N, et al. Visual impairment in Parkinson’s diseasetreated with amantadine: case report and review of the literature. ParkinsonismRelat Disord 2008;14:166–9.

8. Pond A, Lee MS, Hardten DR, et al. Toxic corneal oedema associated withamantadine use. Br J Ophthalmol 2009;93:281, 413.