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Basal ganglia germinoma with progressive cerebral hemiatrophy
Basal Ganglia Germinoma With Progressive Cerebral Hemiatrophy Edwin Liu, MD,* Richard L. Robertson, MD,† Adre du Plessis, MD,* and Scott L. Pomeroy, MD, PhD* The authors describe a 7-year-old Chinese-American female with a germinoma of the basal ganglia who presented with progressive hemiparesis and cerebral hemiatrophy. The additional finding of markedly elevated antiphospholipid antibodies suggests the possibility of an autoimmune pathogenesis for the progressive cerebral atrophy, as well as the later development of cognitive decline, tics, and obsessive-compulsive behaviors. © 1999 by Elsevier Science Inc. All rights reserved. Liu E, Robertson RL, du Plessis A, Pomeroy SL. Basal ganglia germinoma with progressive cerebral hemiatrophy. Pediatr Neurol 1999;20:312-314.
Introduction Germinomas, which are believed to arise from the primordial germ cells, are the least malignant and most common of all germ cell tumors, a category that also includes embryonal cell carcinomas, endodermal sinus tumors, choriocarcinomas, and teratomas [1]. Germinomas represent 0.5-2.1% of all intracranial tumors and have a peak incidence in the latter half of the second decade [2]. Most of these tumors are found at the midline in the pineal or suprasellar regions. The authors present a case of an off-midline germinoma with progressive cerebral hemiatrophy.
From the Departments of *Neurology; and †Radiology; Children’s Hospital; Harvard Medical School; Boston, Massachusetts.
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Case Report A 7-year-old, previously healthy and developmentally normal, righthanded Chinese-American female developed a slowly progressive rightsided hemiparesis. Two months after the onset of these symptoms, computed tomography (not shown) revealed mineralization of the left globus palidus and expansion of the frontal horn of the left lateral ventricle, indicating tissue loss. Magnetic resonance imaging (MRI) revealed volume loss of the left caudate head and abnormal T2-weighted signal within the internal capsule (Fig 1). At other levels, signal abnormalities were also present in the left frontal white matter and corona radiata. Changes indicating wallerian degeneration were evident in the left cerebral peduncle. Her mental status examination was normal except for a slight decrease in spontaneous speech. Neurologic examination revealed a hemiparesis with hyperreflexia, an extensor plantar response, and diminished vibratory sensation on the right. A stroke evaluation, including bilateral selective internal carotid cerebral angiography, transthoracic echocardiogram, and a 24-hour Holter monitor, was negative but did not include antiphospholipid antibodies. Cerebrospinal fluid (CSF) examination was unremarkable, including cytologic analysis on three separate occasions. Metabolic screening, including serum and CSF lactate and pyruvate and amino acids, were within normal limits. One month later a follow-up MRI (not shown) revealed progressive left cerebral atrophy with atrophy of the right cerebellar hemisphere consistent with crossed cerebellar diaschisis. MR spectroscopy did not reveal elevated lactate levels. Her condition remained stable until 11 months later when she developed difficulties with memory and attention, a tic of her left shoulder, and compulsions, such as repeating the phrase “nice tie” whenever anyone with a tie walked in the room. Examination revealed a slight increase in her foot drop. Neuropsychologic testing demonstrated reduced language functioning, distractibility, and difficulty with cognitive complexity. A repeated MRI (not shown) revealed a new signal abnormality involving the basal ganglia and genu of the internal capsule on the opposite side but no evidence of mass effect on either side. Repeated cerebral angiogram again revealed no abnormalities. Brain single-photon emission computed tomography (SPECT) (Fig 2) revealed markedly decreased perfusion throughout the left hemisphere, particularly in the middle cerebral artery distribution, with no improvement after administration of acetazolamide. Further evaluation revealed an elevated antiphospholipid IgG level of 72 (reference range less than 19). One month later, MRI demonstrated a heterogeneous mass in the left basal ganglia, with compression of the left frontal horn and ipsilateral foramen of Monro. Heterogeneous intense enhancement of the mass was present after intravenous gadolinium diethylenetriamine pentaacetic acid administration (Fig 3). Stereotactic biopsy of the lesion and the absence of elevated CSF tumor markers (alpha-fetoprotein was 1.6, carcino embryonic antigen was less than 0.8, and human chorionic gonadotropin was 72) were consistent with a pure germinoma. Antiphospholipid antibodies remained elevated. The patient underwent radiation therapy with 2,550 cGy to the whole brain and a 2,160 boost to the tumor, which resulted in shrinkage of the tumor, as demonstrated by serial computed tomography examinations. One year follow-up has demonstrated no further neurologic deterioration.
Communications should be addressed to: Dr. Pomeroy; Department of Neurology; Enders 260; The Children’s Hospital; 300 Longwood Avenue, Boston, MA 02115. Received July 23, 1998; accepted December 1, 1998.
© 1999 by Elsevier Science Inc. All rights reserved. PII S0887-8994(98)00161-1 ● 0887-8994/99/$20.00
Figure 1. Axial T2-weighted MRI (TR 5 3200 ms, TE 5 85 ms, 1 NEX) at presentation demonstrates tissue loss of the left caudate head with expansion of the frontal horn of the left lateral ventricle, as well as foci of increased signal in the left internal capsule (arrow).
Figure 3. Axial T1-weighted MRI (TR 5 600 ms, TE 5 14 ms, 2 NEX) after the intravenous administration of gadolinium diethylenetriamine pentaacetic acid (0.1 mmol/kg) reveals intense heterogeneous enhancement of a mass within the left basal ganglia encroaching on the frontal horn. Note the increased prominence of the subarachnoid spaces of the left cerebral hemisphere indicating atrophic changes.
Discussion Although central nervous system (CNS) germinomas usually occur at the midline, several reports from Asian countries have found that up to 14% of these tumors arise within the basal ganglia or thalamus [2,3], a geographic bias consistent with the Chinese background of the au-
thors’ patient. A recent review of 42 cases also revealed a strong sex and age bias, with a male/female ratio of 20:1, with all patients between 6 and 20 years of age [2]. As was the case with the authors’ patient, these patients often present with progressive hemiparesis, personality or men-
Figure 2. Hexamethylpropylene single-photon emission computed tomography study in axial and coronal planes before and after acetazolamide administration reveals decreased perfusion to the left cerebral hemisphere. The lack of change after acetazolamide administration indicates limited vascular reserve.
Liu et al: Germinoma With Cerebral Hemiatrophy 313
tal status changes, and cerebral hemiatrophy. Other reported findings have included dystonia, oculomotor palsy, hemianopsia, diabetes insipidus, and seizures [2]. The mechanism of cerebral hemiatrophy in these tumors is poorly understood. Although a distinctly unusual accompaniment of CNS tumors, up to 33% of basal ganglia germinomas demonstrate ipsilateral cerebral hemiatrophy [2]. Cerebral hemiatrophy has also occasionally been associated with astrocytomas, suggesting that this phenomenon is not entirely specific to germinomas [4]. It has been proposed that atrophy occurs as a result of tumor involvement of internal capsule fibers or thalamic ganglion cells with interruption of thalamocortical connections [4]. Ipsilateral hypoperfusion has also been previously described in basal ganglia germinomas [5]. Crossed cerebellar diaschisis has been described in strokes and gliomas in addition to basal ganglia germinomas [5] and has been postulated to be the result of involvement of corticopontocerebellar axons [6]. Elevated antiphospholipid antibodies have been reported in association with a number of malignancies, including ovarian tumors [7]. The presence of elevated antiphospholipid antibodies in this patient suggests an autoimmune process as an alternative explanation for the progressive cerebral atrophy. Such a process has also been proposed to underlie Rasmussen’s encephalitis in which cerebral hemiatrophy is likewise a prominent feature [8]. In addition, a precedent for an autoimmune pathogenesis for symptoms, such as tics, obsessive compulsive behaviors, and cognitive deficits, similar to those seen in this patient has been established with the recent description of the syndrome of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections [9]. Basal ganglia germinomas often are associated with progressive cognitive decline, a large contributor to the morbidity of these tumors. In a recent series of primary CNS germinal tumors, Ono et al. [10] found all nine patients with basal ganglia tumors to have moderate to
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severe mental retardation compared with 74% of patients with pineal tumors who had normal IQs. For this reason and because these tumors respond readily to radiation therapy [1,2], prompt diagnosis may significantly improve overall outcome. The authors therefore recommend that the constellation of a progressive hemiparesis with abnormalities of the basal ganglia or thalamus and cerebral hemiatrophy in patients younger than 20 years of age should prompt a thorough search for a tumor of germ cell origin, including CSF cytology, measurement of tumor markers in CSF, and serum and early biopsy of any suspicious mass, even in the absence of any overt mass effect.
References [1] Horowitz MB, Hall WA. Central nervous system germinomas. Arch Neurol 1991;48:652-7. [2] Tamaki N, Lin T, Shirataki K, et al. Germ cell tumors of the thalamus and the basal ganglia. Childs Nerv Syst 1990;6:3-7. [3] Moon WK, Chang KH, Kim IO, et al. Germinomas of the basal ganglia and thalamus: MR findings and a comparison between MR and CT. Am J Roentgenol 1994;162:1413-7. [4] Maehara T, Machida T, Tsuchiya K, Iio M. Brain tumors with ipsilateral cerebral hemiatrophy. Am J Neuroradiol 1983;4:478-80. [5] Tsuchida Y, Tsuboi K, Yanaka K, Nose T. Basal ganglia germinoma with crossed cerebellar diaschisis. Neurol Med Chir 1993; 33:779-82. [6] Fulham MJ, Brooks RA, Hallett M, DiChiro G. Cerebellar diaschisis revisited: Pontine hypometabolism and dentate sparing. Neurology 1992;42:2267-73. [7] Ruffatti A, Aveosa S, Del Ross T, Tonetto S, Fiorentino M, Todesco S. Antiphospholipid antibody syndrome associated with ovarian cancer: A new paraneoplastic syndrome? J Rheumatol 1994;21:2162-3. [8] Andrews PI, McNamara JO. Rasmussen’s encephalitis: An autoimmune disorder? Curr Opin Neurobiol 1996;6:673-8. [9] Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases. Am J Psychiatry 1998;155:264-71. [10] Ono N, Kakegawa T, Zama A, et al. Factors affecting functional prognosis in survivors of primary central nervous system germinal tumors. Surg Neurol 1994;41:9-15.
Introduction Germinomas, which are believed to arise from the primordial germ cells, are the least malignant and most common of all germ cell tumors, a category that also includes embryonal cell carcinomas, endodermal sinus tumors, choriocarcinomas, and teratomas [1]. Germinomas represent 0.5-2.1% of all intracranial tumors and have a peak incidence in the latter half of the second decade [2]. Most of these tumors are found at the midline in the pineal or suprasellar regions. The authors present a case of an off-midline germinoma with progressive cerebral hemiatrophy.
From the Departments of *Neurology; and †Radiology; Children’s Hospital; Harvard Medical School; Boston, Massachusetts.
312
PEDIATRIC NEUROLOGY
Vol. 20 No. 4
Case Report A 7-year-old, previously healthy and developmentally normal, righthanded Chinese-American female developed a slowly progressive rightsided hemiparesis. Two months after the onset of these symptoms, computed tomography (not shown) revealed mineralization of the left globus palidus and expansion of the frontal horn of the left lateral ventricle, indicating tissue loss. Magnetic resonance imaging (MRI) revealed volume loss of the left caudate head and abnormal T2-weighted signal within the internal capsule (Fig 1). At other levels, signal abnormalities were also present in the left frontal white matter and corona radiata. Changes indicating wallerian degeneration were evident in the left cerebral peduncle. Her mental status examination was normal except for a slight decrease in spontaneous speech. Neurologic examination revealed a hemiparesis with hyperreflexia, an extensor plantar response, and diminished vibratory sensation on the right. A stroke evaluation, including bilateral selective internal carotid cerebral angiography, transthoracic echocardiogram, and a 24-hour Holter monitor, was negative but did not include antiphospholipid antibodies. Cerebrospinal fluid (CSF) examination was unremarkable, including cytologic analysis on three separate occasions. Metabolic screening, including serum and CSF lactate and pyruvate and amino acids, were within normal limits. One month later a follow-up MRI (not shown) revealed progressive left cerebral atrophy with atrophy of the right cerebellar hemisphere consistent with crossed cerebellar diaschisis. MR spectroscopy did not reveal elevated lactate levels. Her condition remained stable until 11 months later when she developed difficulties with memory and attention, a tic of her left shoulder, and compulsions, such as repeating the phrase “nice tie” whenever anyone with a tie walked in the room. Examination revealed a slight increase in her foot drop. Neuropsychologic testing demonstrated reduced language functioning, distractibility, and difficulty with cognitive complexity. A repeated MRI (not shown) revealed a new signal abnormality involving the basal ganglia and genu of the internal capsule on the opposite side but no evidence of mass effect on either side. Repeated cerebral angiogram again revealed no abnormalities. Brain single-photon emission computed tomography (SPECT) (Fig 2) revealed markedly decreased perfusion throughout the left hemisphere, particularly in the middle cerebral artery distribution, with no improvement after administration of acetazolamide. Further evaluation revealed an elevated antiphospholipid IgG level of 72 (reference range less than 19). One month later, MRI demonstrated a heterogeneous mass in the left basal ganglia, with compression of the left frontal horn and ipsilateral foramen of Monro. Heterogeneous intense enhancement of the mass was present after intravenous gadolinium diethylenetriamine pentaacetic acid administration (Fig 3). Stereotactic biopsy of the lesion and the absence of elevated CSF tumor markers (alpha-fetoprotein was 1.6, carcino embryonic antigen was less than 0.8, and human chorionic gonadotropin was 72) were consistent with a pure germinoma. Antiphospholipid antibodies remained elevated. The patient underwent radiation therapy with 2,550 cGy to the whole brain and a 2,160 boost to the tumor, which resulted in shrinkage of the tumor, as demonstrated by serial computed tomography examinations. One year follow-up has demonstrated no further neurologic deterioration.
Communications should be addressed to: Dr. Pomeroy; Department of Neurology; Enders 260; The Children’s Hospital; 300 Longwood Avenue, Boston, MA 02115. Received July 23, 1998; accepted December 1, 1998.
© 1999 by Elsevier Science Inc. All rights reserved. PII S0887-8994(98)00161-1 ● 0887-8994/99/$20.00
Figure 1. Axial T2-weighted MRI (TR 5 3200 ms, TE 5 85 ms, 1 NEX) at presentation demonstrates tissue loss of the left caudate head with expansion of the frontal horn of the left lateral ventricle, as well as foci of increased signal in the left internal capsule (arrow).
Figure 3. Axial T1-weighted MRI (TR 5 600 ms, TE 5 14 ms, 2 NEX) after the intravenous administration of gadolinium diethylenetriamine pentaacetic acid (0.1 mmol/kg) reveals intense heterogeneous enhancement of a mass within the left basal ganglia encroaching on the frontal horn. Note the increased prominence of the subarachnoid spaces of the left cerebral hemisphere indicating atrophic changes.
Discussion Although central nervous system (CNS) germinomas usually occur at the midline, several reports from Asian countries have found that up to 14% of these tumors arise within the basal ganglia or thalamus [2,3], a geographic bias consistent with the Chinese background of the au-
thors’ patient. A recent review of 42 cases also revealed a strong sex and age bias, with a male/female ratio of 20:1, with all patients between 6 and 20 years of age [2]. As was the case with the authors’ patient, these patients often present with progressive hemiparesis, personality or men-
Figure 2. Hexamethylpropylene single-photon emission computed tomography study in axial and coronal planes before and after acetazolamide administration reveals decreased perfusion to the left cerebral hemisphere. The lack of change after acetazolamide administration indicates limited vascular reserve.
Liu et al: Germinoma With Cerebral Hemiatrophy 313
tal status changes, and cerebral hemiatrophy. Other reported findings have included dystonia, oculomotor palsy, hemianopsia, diabetes insipidus, and seizures [2]. The mechanism of cerebral hemiatrophy in these tumors is poorly understood. Although a distinctly unusual accompaniment of CNS tumors, up to 33% of basal ganglia germinomas demonstrate ipsilateral cerebral hemiatrophy [2]. Cerebral hemiatrophy has also occasionally been associated with astrocytomas, suggesting that this phenomenon is not entirely specific to germinomas [4]. It has been proposed that atrophy occurs as a result of tumor involvement of internal capsule fibers or thalamic ganglion cells with interruption of thalamocortical connections [4]. Ipsilateral hypoperfusion has also been previously described in basal ganglia germinomas [5]. Crossed cerebellar diaschisis has been described in strokes and gliomas in addition to basal ganglia germinomas [5] and has been postulated to be the result of involvement of corticopontocerebellar axons [6]. Elevated antiphospholipid antibodies have been reported in association with a number of malignancies, including ovarian tumors [7]. The presence of elevated antiphospholipid antibodies in this patient suggests an autoimmune process as an alternative explanation for the progressive cerebral atrophy. Such a process has also been proposed to underlie Rasmussen’s encephalitis in which cerebral hemiatrophy is likewise a prominent feature [8]. In addition, a precedent for an autoimmune pathogenesis for symptoms, such as tics, obsessive compulsive behaviors, and cognitive deficits, similar to those seen in this patient has been established with the recent description of the syndrome of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections [9]. Basal ganglia germinomas often are associated with progressive cognitive decline, a large contributor to the morbidity of these tumors. In a recent series of primary CNS germinal tumors, Ono et al. [10] found all nine patients with basal ganglia tumors to have moderate to
314
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severe mental retardation compared with 74% of patients with pineal tumors who had normal IQs. For this reason and because these tumors respond readily to radiation therapy [1,2], prompt diagnosis may significantly improve overall outcome. The authors therefore recommend that the constellation of a progressive hemiparesis with abnormalities of the basal ganglia or thalamus and cerebral hemiatrophy in patients younger than 20 years of age should prompt a thorough search for a tumor of germ cell origin, including CSF cytology, measurement of tumor markers in CSF, and serum and early biopsy of any suspicious mass, even in the absence of any overt mass effect.
References [1] Horowitz MB, Hall WA. Central nervous system germinomas. Arch Neurol 1991;48:652-7. [2] Tamaki N, Lin T, Shirataki K, et al. Germ cell tumors of the thalamus and the basal ganglia. Childs Nerv Syst 1990;6:3-7. [3] Moon WK, Chang KH, Kim IO, et al. Germinomas of the basal ganglia and thalamus: MR findings and a comparison between MR and CT. Am J Roentgenol 1994;162:1413-7. [4] Maehara T, Machida T, Tsuchiya K, Iio M. Brain tumors with ipsilateral cerebral hemiatrophy. Am J Neuroradiol 1983;4:478-80. [5] Tsuchida Y, Tsuboi K, Yanaka K, Nose T. Basal ganglia germinoma with crossed cerebellar diaschisis. Neurol Med Chir 1993; 33:779-82. [6] Fulham MJ, Brooks RA, Hallett M, DiChiro G. Cerebellar diaschisis revisited: Pontine hypometabolism and dentate sparing. Neurology 1992;42:2267-73. [7] Ruffatti A, Aveosa S, Del Ross T, Tonetto S, Fiorentino M, Todesco S. Antiphospholipid antibody syndrome associated with ovarian cancer: A new paraneoplastic syndrome? J Rheumatol 1994;21:2162-3. [8] Andrews PI, McNamara JO. Rasmussen’s encephalitis: An autoimmune disorder? Curr Opin Neurobiol 1996;6:673-8. [9] Swedo SE, Leonard HL, Garvey M, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: Clinical description of the first 50 cases. Am J Psychiatry 1998;155:264-71. [10] Ono N, Kakegawa T, Zama A, et al. Factors affecting functional prognosis in survivors of primary central nervous system germinal tumors. Surg Neurol 1994;41:9-15.