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Parkinsonism as an unusual presenting symptom of pineal gland teratoma
Parkinsonism as an Unusual Presenting Symptom of Pineal Gland Teratoma Mae Concepcion J. Dolendo, MD*, Tan Poh Lin, MMed (Peds)*, Ong Hian Tat, MMed (Peds)*, Quah Thuan Chong, MMed (Peds)*, and Lee Kam Yiu Timothy, MD†
We report a case of a 14-year-old Chinese boy with immature teratoma of the pineal gland who manifested with parkinsonism. Diagnostic evaluation revealed hydrocephalus and an immature teratoma of the pineal gland extending to the thalamus. An urgent ventriculoperitoneal shunt was inserted, and chemotherapy was given to reduce the tumor size. The tumor was completely excised 2 months after diagnosis with improvement of clinical signs and symptoms. His symptoms recurred 3 months later with sudden onset of obtundation, tremors, cogwheel rigidity, and marked bradykinesia. Magnetic resonance imaging (MRI) revealed a small enhancing lesion in the pineal region and progressive hydrocephalus on serial studies. He was treated with carbidopa/levodopa and amantadine, but marked improvement was only observed after reprogramming his VP shunt. Features consistent with the growing teratoma syndrome were noted during this period. These were progressive pineal gland tumor enlargement documented on MRI without increase in previously elevated alpha-fetoprotein levels. The tumor continued to enlarge despite gamma knife radiosurgery. Secondary parkinsonism is a rare presentation of pineal gland tumors and has not been reported in association with the growing teratoma syndrome. © 2003 by Elsevier Inc. All rights reserved.
From the *Children’s Medical Institute and the †Department of Neurosurgery, National University Hospital, Singapore.
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PEDIATRIC NEUROLOGY
Vol. 28 No. 4
Dolendo MCJ, Lin TP, Tat QH, Chong QT, Timothy LMY. Parkinsonism as an unusual presenting symptom of pineal gland teratoma. Pediatr Neurol 2003;28:310-312.
Introduction Parkinsonism is a rare manifestation of brain tumors, and a phenomenon not often described in children. We present a case of immature pineal gland teratoma manifesting as bradykinesia with tremors and cogwheel rigidity evolving in his clinical course. Germ cell tumors comprise 4% of all primary brain tumors in Japan and Southeast Asia. This incidence is higher compared with 1% in Europe and the United States. Forty-five percent of pineal gland tumors are germinomas, 17% are astrocytomas, nongerminomatous germ cell tumors including immature/mature teratomas account for 16%, while 22% constitute pineal parenchymal tumors and other tumor types [1,2]. Because of their rarity, brain tumors in particular immature pineal gland teratomas are not often considered as a differential diagnosis for childhood parkinsonism. There are anecdotal reports of secondary parkinsonism in children but, to the author’s knowledge, there is none describing a concurrent growing teratoma syndrome, a condition associated with tumor recurrence despite gross total resection and chemotherapy. Case Report A 14-year-old Chinese boy presented with a month-long history of persistent headache, lapse in memory, poor handwriting, and deteriorating schoolwork. On admission, he had blurred vision and tinnitus. On examination, he had bradykinesia, broad-based gait, masklike facies, slow monotonous speech, and dysdiadochokinesia. He had the triad of Parinaud’s syndrome with failure of upward gaze, convergence nystagmus, and pupils that react better to accommodation. Full blood count and biochemical profiles were normal. Serum alpha-fetoprotein (AFP) level was initially normal at 5 ug/L but later rose to levels of 70 ug/L. An MRI scan of the brain demonstrated a pineal gland tumor extending to the thalamus (Fig 1), associated with obstructive hydrocephalus. An emergency ventriculoperitoneal shunt was inserted, and, subsequently, stereotactic biopsy was performed. Histology of the tumor was consistent with an immature pineal gland teratoma. He was given two courses of carboplatin, etoposide, and bleomycin without reduction in tumor size. Subsequently, total tumor resection was performed through an infratentorial supracerebellar approach. This procedure was followed by three courses of chemotherapy. His symptoms improved, his AFP normalized, and he was able to attend school. Three months later, he presented acutely with increased somnolence, tremors, and cogwheel rigidity. A
Communications should be addressed to: Dr. Dolendo; Children’s Medical Institute, National University Hospital; 5, Lower Kent Ridge Road; Singapore 119074. Received July 23, 2002; accepted October 4, 2002.
© 2003 by Elsevier Inc. All rights reserved. doi:10.1016/S0887-8994(02)00620-3 ● 0887-8994/03/$—see front matter
Figure 1. Gadolinium enhanced MRI scan at diagnosis demonstrating an inhomogeneous mass in the pineal gland.
repeat MRI scan of the brain revealed an enhancing mass in the pineal region, but this was initially attributed to postoperative MRI signal changes. AFP levels were not raised. His condition then deteriorated with increasing somnolence, tremors becoming more marked, as well as symptoms of dysphagia, dysarthria, and urinary incontinence. He was treated with carbidopa/levodopa and amantadine with mild improvement in his parkinsonian symptoms. A follow-up MRI revealed hydrocephalus and the VP shunt was reprogrammed. After changing the VP shunt pressures, he was more responsive, with disappearance of tremors, improved speech, and ability to ambulate. Two months after the onset of these symptoms, his MRI revealed definite tumor recurrence. This was managed with gamma knife radiosurgery. There was a short interval of improvement after radiosurgery. However, a month later, his symptoms of somnolence and parkinsonism returned after aggressive tumor growth. There was evidence of dissemination as shown by the leptomeningeal
involvement on MRI (Fig 2) as well as raised cerebrospinal fluid (CSF) and serum AFP levels. He died 2 weeks later.
Discussion Germ cell tumors account for 0.1-4% of primary brain neoplasms. They arise mainly in the pineal and suprasellar regions, presumably because of aberrant migration of primordial germ cells to these areas during the 6th week of gestation. Among pineal gland tumors, germinomas are the most common, accounting for 41-65% of cases [3-6]. Intracranial teratomas are fairly uncommon and are associated with a poorer therapeutic response.
Figure 2. Follow-up MRI scan at time of relapse revealing recurrent tumor in the pineal gland with leptomingeal involvement.
Dolendo et al: Pineal Teratoma Presenting as Parkinsonism 311
Because of its anatomic relationship to the third ventricle and deep venous structures, germ cell tumors in the pineal region most commonly present with hydrocephalus, visual symptoms, obtundation, ataxia, and pyramidal tract signs. In this patient the appearance of parkinsonism can be attributed to the tumor’s infiltrative involvement of the nigro-striate-pallidal system, and edema contributed by the massive tumor may have also affected the thalamus. A few reports of isolated massive hydrocephalus without direct cortical invasion causing parkinsonism may also offer another explanation [7-9]. Nevertheless, it is possible that the condition was brought forth by all these mechanisms occurring altogether. Atypical symptoms such as visual field defects, motor weakness, and pyramidal signs raise the suspicion that parkinsonism is secondary to another pathology. Various authors have cited intracranial lesions, such as tumor metastasis, meningioma, lymphoma, cavernous angioma, astrocytoma, and thalamic tumors causing parkinsonism [10-13]. Large brain tumors can damage both presynaptic dopaminergic nigrostriatal neurons and postsynaptic dopamine receptors, which can cause atrophy of the substantia nigra and a decrease in dopamine manifesting as secondary parkinsonism. Because of the rarity of this condition, reports on secondary parkinsonism in children are mainly anecdotal. Apart from intracranial lesions, this condition has been reported in association with VP shunt failure, hypoxicischemic encephalopathy, viral encephalitis, haloperidol treatment, toxicity to cytosine arabinoside, cyclophosphamide, amphotericin B, and methotrexate [14]. It is interesting that despite chemotherapy, total tumor resection, and radiosurgery, this patient’s tumor continued to recur, at times without elevated tumor markers that made early suspicion of a recurrence difficult. Such a condition has been described in two children and an adult, a phenomenon referred to as the growing teratoma syndrome [6]. In this condition, immature components of a teratoma may respond to treatment, but mature teratomas remain fairly resistant and grow despite treatment. Management of pineal gland tumors requires aggressive multimodality approaches with surgery, radiotherapy, and chemotherapy to improve outcome [15]. A histologic diagnosis is important in view of the better prognosis with treatment that is directed towards the tumor type. Stereotactic biopsy under experienced hands can be performed safely with high diagnostic yield that facilitates rational
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treatment. In pineal gland teratomas the extent of tumor removal is the single most important prognostic factor, since these tumors are fairly resistant to radiotherapy or chemotherapy. Conclusion A case of an immature pineal gland teratoma presenting with parkinsonism and features of the growing teratoma syndrome is described. Though rare, intracranial tumor should be considered when parkinsonism presents early in childhood because it is potentially treatable and mortality can be avoided with early diagnosis. The authors thank Dr. Tay Kiat Hong Stacey and Tay Siew Leng for their assistance.
References [1] Bloom HCG. Primary intracranial germ cell tumours. Clinics in Oncology: Germ Cell Tumours 1983;233–7. [2] Oi S. Controversy pertaining to therapeutic modalities for tumors of the pineal region: a worldwide survey of different patient populations. Childs Nerv Syst 1992;8:332– 6. [3] Choi JU. Treatment of germ cell tumors in the pineal region. Childs Nerv Syst 1998;14:41-8. [4] Packer RJ. Intracranial germ cell tumors. Oncologist 2000;5: 312-20. [5] Gabrovski S. Germ cell tumors of the brain: Their course and management. Khirurgiia 1997;50:8-15. [6] O’Callaghan AM. The growing teratoma syndrome in a nongerminomatous germ cell tumor of the pineal gland: A case report and review. Cancer 1997;80:942–7. [7] Cho BK. Pineal tumors: Experience with 48 cases over 10 years. Childs Nerv Syst 1998;14:53– 8. [8] Brazin ME. Reversible parkinsonism from shunt failure. Pediatr Neurol 1985;1:306 –7. [9] Krauss JK. Parkinsonism and rest tremor secondary to supratentorial tumours sparing the basal ganglia. Acta Neurochir (Wien) 1995; 133:2–9. [10] Chang DC. Parkinsonism as an initial manifestation of brain tumor. Zhonghua Yi Xue Za Zhi 2000 Aug;63:658 – 62. [11] Sanchez-Guerra M. Primary brain lymphoma presenting as Parkinson’s disease. Neuroradiology 2001;43:36 – 40. [12] Szelozynska K. Manifestations of thalamic tumors in children. Neurol Neurochir Pol 1976;10:743–7. [13] Krauss JK. Movement disorders in astrocytomas of the basal ganglia and the thalamus. J Neurol Neurosurg Psychiatry 1992;55: 1162–7. [14] Pranzatelli M. Clinical spectrum of secondary parkinsonism in childhood: A reversible disorder. Pediatr Neurol 1994;10:131-40. [15] Knappe UJ. Treatment and long term outcome of pineal nongerminomatous germ cell tumors. Pediatr Neurosurg 1998;28:214 –5.
We report a case of a 14-year-old Chinese boy with immature teratoma of the pineal gland who manifested with parkinsonism. Diagnostic evaluation revealed hydrocephalus and an immature teratoma of the pineal gland extending to the thalamus. An urgent ventriculoperitoneal shunt was inserted, and chemotherapy was given to reduce the tumor size. The tumor was completely excised 2 months after diagnosis with improvement of clinical signs and symptoms. His symptoms recurred 3 months later with sudden onset of obtundation, tremors, cogwheel rigidity, and marked bradykinesia. Magnetic resonance imaging (MRI) revealed a small enhancing lesion in the pineal region and progressive hydrocephalus on serial studies. He was treated with carbidopa/levodopa and amantadine, but marked improvement was only observed after reprogramming his VP shunt. Features consistent with the growing teratoma syndrome were noted during this period. These were progressive pineal gland tumor enlargement documented on MRI without increase in previously elevated alpha-fetoprotein levels. The tumor continued to enlarge despite gamma knife radiosurgery. Secondary parkinsonism is a rare presentation of pineal gland tumors and has not been reported in association with the growing teratoma syndrome. © 2003 by Elsevier Inc. All rights reserved.
From the *Children’s Medical Institute and the †Department of Neurosurgery, National University Hospital, Singapore.
310
PEDIATRIC NEUROLOGY
Vol. 28 No. 4
Dolendo MCJ, Lin TP, Tat QH, Chong QT, Timothy LMY. Parkinsonism as an unusual presenting symptom of pineal gland teratoma. Pediatr Neurol 2003;28:310-312.
Introduction Parkinsonism is a rare manifestation of brain tumors, and a phenomenon not often described in children. We present a case of immature pineal gland teratoma manifesting as bradykinesia with tremors and cogwheel rigidity evolving in his clinical course. Germ cell tumors comprise 4% of all primary brain tumors in Japan and Southeast Asia. This incidence is higher compared with 1% in Europe and the United States. Forty-five percent of pineal gland tumors are germinomas, 17% are astrocytomas, nongerminomatous germ cell tumors including immature/mature teratomas account for 16%, while 22% constitute pineal parenchymal tumors and other tumor types [1,2]. Because of their rarity, brain tumors in particular immature pineal gland teratomas are not often considered as a differential diagnosis for childhood parkinsonism. There are anecdotal reports of secondary parkinsonism in children but, to the author’s knowledge, there is none describing a concurrent growing teratoma syndrome, a condition associated with tumor recurrence despite gross total resection and chemotherapy. Case Report A 14-year-old Chinese boy presented with a month-long history of persistent headache, lapse in memory, poor handwriting, and deteriorating schoolwork. On admission, he had blurred vision and tinnitus. On examination, he had bradykinesia, broad-based gait, masklike facies, slow monotonous speech, and dysdiadochokinesia. He had the triad of Parinaud’s syndrome with failure of upward gaze, convergence nystagmus, and pupils that react better to accommodation. Full blood count and biochemical profiles were normal. Serum alpha-fetoprotein (AFP) level was initially normal at 5 ug/L but later rose to levels of 70 ug/L. An MRI scan of the brain demonstrated a pineal gland tumor extending to the thalamus (Fig 1), associated with obstructive hydrocephalus. An emergency ventriculoperitoneal shunt was inserted, and, subsequently, stereotactic biopsy was performed. Histology of the tumor was consistent with an immature pineal gland teratoma. He was given two courses of carboplatin, etoposide, and bleomycin without reduction in tumor size. Subsequently, total tumor resection was performed through an infratentorial supracerebellar approach. This procedure was followed by three courses of chemotherapy. His symptoms improved, his AFP normalized, and he was able to attend school. Three months later, he presented acutely with increased somnolence, tremors, and cogwheel rigidity. A
Communications should be addressed to: Dr. Dolendo; Children’s Medical Institute, National University Hospital; 5, Lower Kent Ridge Road; Singapore 119074. Received July 23, 2002; accepted October 4, 2002.
© 2003 by Elsevier Inc. All rights reserved. doi:10.1016/S0887-8994(02)00620-3 ● 0887-8994/03/$—see front matter
Figure 1. Gadolinium enhanced MRI scan at diagnosis demonstrating an inhomogeneous mass in the pineal gland.
repeat MRI scan of the brain revealed an enhancing mass in the pineal region, but this was initially attributed to postoperative MRI signal changes. AFP levels were not raised. His condition then deteriorated with increasing somnolence, tremors becoming more marked, as well as symptoms of dysphagia, dysarthria, and urinary incontinence. He was treated with carbidopa/levodopa and amantadine with mild improvement in his parkinsonian symptoms. A follow-up MRI revealed hydrocephalus and the VP shunt was reprogrammed. After changing the VP shunt pressures, he was more responsive, with disappearance of tremors, improved speech, and ability to ambulate. Two months after the onset of these symptoms, his MRI revealed definite tumor recurrence. This was managed with gamma knife radiosurgery. There was a short interval of improvement after radiosurgery. However, a month later, his symptoms of somnolence and parkinsonism returned after aggressive tumor growth. There was evidence of dissemination as shown by the leptomeningeal
involvement on MRI (Fig 2) as well as raised cerebrospinal fluid (CSF) and serum AFP levels. He died 2 weeks later.
Discussion Germ cell tumors account for 0.1-4% of primary brain neoplasms. They arise mainly in the pineal and suprasellar regions, presumably because of aberrant migration of primordial germ cells to these areas during the 6th week of gestation. Among pineal gland tumors, germinomas are the most common, accounting for 41-65% of cases [3-6]. Intracranial teratomas are fairly uncommon and are associated with a poorer therapeutic response.
Figure 2. Follow-up MRI scan at time of relapse revealing recurrent tumor in the pineal gland with leptomingeal involvement.
Dolendo et al: Pineal Teratoma Presenting as Parkinsonism 311
Because of its anatomic relationship to the third ventricle and deep venous structures, germ cell tumors in the pineal region most commonly present with hydrocephalus, visual symptoms, obtundation, ataxia, and pyramidal tract signs. In this patient the appearance of parkinsonism can be attributed to the tumor’s infiltrative involvement of the nigro-striate-pallidal system, and edema contributed by the massive tumor may have also affected the thalamus. A few reports of isolated massive hydrocephalus without direct cortical invasion causing parkinsonism may also offer another explanation [7-9]. Nevertheless, it is possible that the condition was brought forth by all these mechanisms occurring altogether. Atypical symptoms such as visual field defects, motor weakness, and pyramidal signs raise the suspicion that parkinsonism is secondary to another pathology. Various authors have cited intracranial lesions, such as tumor metastasis, meningioma, lymphoma, cavernous angioma, astrocytoma, and thalamic tumors causing parkinsonism [10-13]. Large brain tumors can damage both presynaptic dopaminergic nigrostriatal neurons and postsynaptic dopamine receptors, which can cause atrophy of the substantia nigra and a decrease in dopamine manifesting as secondary parkinsonism. Because of the rarity of this condition, reports on secondary parkinsonism in children are mainly anecdotal. Apart from intracranial lesions, this condition has been reported in association with VP shunt failure, hypoxicischemic encephalopathy, viral encephalitis, haloperidol treatment, toxicity to cytosine arabinoside, cyclophosphamide, amphotericin B, and methotrexate [14]. It is interesting that despite chemotherapy, total tumor resection, and radiosurgery, this patient’s tumor continued to recur, at times without elevated tumor markers that made early suspicion of a recurrence difficult. Such a condition has been described in two children and an adult, a phenomenon referred to as the growing teratoma syndrome [6]. In this condition, immature components of a teratoma may respond to treatment, but mature teratomas remain fairly resistant and grow despite treatment. Management of pineal gland tumors requires aggressive multimodality approaches with surgery, radiotherapy, and chemotherapy to improve outcome [15]. A histologic diagnosis is important in view of the better prognosis with treatment that is directed towards the tumor type. Stereotactic biopsy under experienced hands can be performed safely with high diagnostic yield that facilitates rational
312
PEDIATRIC NEUROLOGY
Vol. 28 No. 4
treatment. In pineal gland teratomas the extent of tumor removal is the single most important prognostic factor, since these tumors are fairly resistant to radiotherapy or chemotherapy. Conclusion A case of an immature pineal gland teratoma presenting with parkinsonism and features of the growing teratoma syndrome is described. Though rare, intracranial tumor should be considered when parkinsonism presents early in childhood because it is potentially treatable and mortality can be avoided with early diagnosis. The authors thank Dr. Tay Kiat Hong Stacey and Tay Siew Leng for their assistance.
References [1] Bloom HCG. Primary intracranial germ cell tumours. Clinics in Oncology: Germ Cell Tumours 1983;233–7. [2] Oi S. Controversy pertaining to therapeutic modalities for tumors of the pineal region: a worldwide survey of different patient populations. Childs Nerv Syst 1992;8:332– 6. [3] Choi JU. Treatment of germ cell tumors in the pineal region. Childs Nerv Syst 1998;14:41-8. [4] Packer RJ. Intracranial germ cell tumors. Oncologist 2000;5: 312-20. [5] Gabrovski S. Germ cell tumors of the brain: Their course and management. Khirurgiia 1997;50:8-15. [6] O’Callaghan AM. The growing teratoma syndrome in a nongerminomatous germ cell tumor of the pineal gland: A case report and review. Cancer 1997;80:942–7. [7] Cho BK. Pineal tumors: Experience with 48 cases over 10 years. Childs Nerv Syst 1998;14:53– 8. [8] Brazin ME. Reversible parkinsonism from shunt failure. Pediatr Neurol 1985;1:306 –7. [9] Krauss JK. Parkinsonism and rest tremor secondary to supratentorial tumours sparing the basal ganglia. Acta Neurochir (Wien) 1995; 133:2–9. [10] Chang DC. Parkinsonism as an initial manifestation of brain tumor. Zhonghua Yi Xue Za Zhi 2000 Aug;63:658 – 62. [11] Sanchez-Guerra M. Primary brain lymphoma presenting as Parkinson’s disease. Neuroradiology 2001;43:36 – 40. [12] Szelozynska K. Manifestations of thalamic tumors in children. Neurol Neurochir Pol 1976;10:743–7. [13] Krauss JK. Movement disorders in astrocytomas of the basal ganglia and the thalamus. J Neurol Neurosurg Psychiatry 1992;55: 1162–7. [14] Pranzatelli M. Clinical spectrum of secondary parkinsonism in childhood: A reversible disorder. Pediatr Neurol 1994;10:131-40. [15] Knappe UJ. Treatment and long term outcome of pineal nongerminomatous germ cell tumors. Pediatr Neurosurg 1998;28:214 –5.