J Neurol (2013) 260:3161–3163 DOI 10.1007/s00415-013-7162-1
LETTER TO THE EDITORS
Juvenile parkinsonism as an initial manifestation of gliomatosis cerebri Wooyoung Jang • Seung Hyun Ha • Shin Kwang Khang • Juhan Kim • Seung Hyun Kim Hee-Jin Kim
•
Received: 7 August 2013 / Revised: 11 September 2013 / Accepted: 20 September 2013 / Published online: 25 October 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Dear Sirs, Some types of infiltrative tumors are not visible at an early stage by conventional structural brain imaging techniques such as magnetic resonance imaging (MRI) [5]. Vates et al. [6] described various clinical manifestations of gliomatosis cerebri, which included mental change, headache, dementia, seizure, and gait abnormalities. However, there are few reports of parkinsonism as an initial manifestation of GC [1]. A 17-year-old female presented with left hand tremor for one month. She had no history of tremor inducing medication, illicit drug or alcohol abuse. There was no remarkable hereditary disorder causing parkinsonism. On initial neurological examination, only resting and postural tremor of the left hand and mild hypomimia were observed. The tremor had a frequency of 2–3 Hz and the frequency was not changed during distraction. Brain MRI including
W. Jang and S. H. Ha contributed equally to this work.
Electronic supplementary material The online version of this article (doi:10.1007/s00415-013-7162-1) contains supplementary material, which is available to authorized users. W. Jang Department of Neurology, Gangneung Asan Hospital, College of Medicine, University of Ulsan, Gangneung, Republic of Korea S. H. Ha J. Kim S. H. Kim H.-J. Kim (&) Department of Neurology, College of Medicine, Hanyang University Hospital, 17 Haengdang-dong, Seongdong-gu, Seoul 133-792, Republic of Korea e-mail: [email protected] S. K. Khang Department of Pathology, College of Medicine, Ulsan University, Seoul, Republic of Korea
T1, T2, diffusion weighted imaging, and T1 gadolinium enhancement imaging yielded no significant findings. Serological findings for secondary parkinsonism were normal, including thyroid function test, autoimmune disease screening tests, serum ceruloplasmin, and serum pyruvate/lactate ratio. L-DOPA was challenged up to 1,200 mg but there was no improvement of symptoms. The patient presented no autonomic symptoms and positional blood pressure test revealed no orthostatic hypotension. Toxicology screening including manganese was also negative. Over the next two months the patient complained of intermittent dizziness and slowness of her left hand. Thereafter, tremor and slowness spread to the right upper extremity. Left dominant bilateral bradykinesia, resting tremor with postural component, and cogwheel rigidity were noted. She showed postural instability on the pull test (UPDRS-III score was 19). There were no significant findings on follow up T1, T2, diffusion weighted MRI and T1 gadolinium enhancement imaging (Fig. 1a) and N-(3fluoropropyl)-2-b-carbomethoxy-3-b-(4-iodophenyl) nortropane positron emission tomography (FP-CIT PET) imaging. All electrophysiologic studies including nerve conduction study, electromyography, and electroencephalography (EEG) were normal for motor neuron disease and symptomatic epileptic syndrome. Genetic tests as a panel for hereditary movement disorders (PARK2, PANK2, FXTAS, ATP7B, SCA 1, 2, 3, 6, DYT 1, DYT 5, and Huntington’s disease) were all negative. Six months later the patient began to show cognitive decline and frequent syncope. On brain MRI, a newly developed high signal intensity was observed in a T2weighted sequence in the right parietal lobe, and these lesions spread to the left parietal lobe within one month (Fig. 1b). Epileptiform discharge in the left frontal area
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3162 Fig. 1 Sequential changes of brain MRI, MRS and FDG PET images. a After three months of disease there is no significant finding. b After eight months of disease, a T2 high signal appears in the bilateral temporooccipito-parietal lobe. c FDGPET reveals diffuse hypometabolism in the whole brain d MRS shows a high peak of choline. e, f Hematoxylineosin staining of brain tissues. Some tumor cells possess elongated spindle-shaped nuclei (arrow), a common feature of gliomatosis cerebri (original magnification 91000)
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J Neurol (2013) 260:3161–3163
J Neurol (2013) 260:3161–3163
was noted on EEG, and neuropsychological test revealed decrement of overall cerebral function. 18F-fluorodeoxyglucose (FDG) PET showed diffuse reduction of glucose metabolism (Fig. 1c). Magnetic resonance spectroscopy (MRS), revealed a high choline peak in the right parietal lobe (Fig. 1d). Because an infiltrative tumor was suspected, a brain biopsy was performed. In microscopic findings, some of the tumor cells had elongated spindle-shaped nuclei, a common feature of GC (Fig. 1e, f). Some of the clinical findings and disease course in this patient are of considerable interest. Firstly, there was no structural or functional abnormality of the basal ganglia. In the majority of previous cases of tumor-induced parkinsonism, direct striatal involvement or secondary compression of the striatum by various structural lesions was observed. Plowman et al. [5] suggested on the basis of a PET study that gliomatosis cerebri caused functional disconnection of the cerebral cortex. Therefore, interruption of the striatal output to the supplementary motor area is the most likely explanation for the parkinsonism in our patient. Second, juvenile parkinsonism induced by GC has not previously been reported. In addition to the parkinsonism, there were ‘key signs’ that raised suspicion of tumor-induced parkinsonism, and these signs, such as pyramidal tract involvement, cognitive impairment, and seizure, are helpful in assigning GC etiology[3, 4]. She had been suffering from ‘‘pure parkinsonism’’ for six months without any other ‘key signs’ such as cognitive decline and seizure. Finally, a negative brain MRI cannot exclude tumorinduced parkinsonism. FDG PET scans of GC revealed markedly reduced glucose uptake in multiple brain regions with involvement of the white matter, compatible with
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biopsy findings. This finding is compatible with type I classical form of GC according to a previous report [2]. Therefore, we suggest that GC should be listed among the disorders that cause juvenile parkinsonism, and consideration given to a meticulous evaluation including conventional MRI, MRS. FDG-PET might also be considered when no definite structural abnormality revealed. Acknowledgments This study was supported by the cluster research fund of Hanyang University (HY-2009-C). Conflicts of interest conflict of interest.
The authors declare no financial or other
Ethical standard Informed consent was obtained from this patient according to the regulations of the Institutional Review Board of Hanyang University Medical Center.
References 1. Asada T, Takayama Y, Tokuriki Y, Fukuyama H (2007) Gliomatosis cerebri presenting as a parkinsonian syndrome. J Neuroimaging Off J Am Soc Neuroimaging 17:269–271 2. Desclee P, Rommel D, Hernalsteen D, Godfraind C, de Coene B, Cosnard G (2010) Gliomatosis cerebri, imaging findings of 12 cases. J Neuroradiol 37:148–158 3. Dolendo MC, Lin TP, Tat OH, Chong QT, Timothy LK (2003) Parkinsonism as an unusual presenting symptom of pineal gland teratoma. Pediatr Neurol 28:310–312 4. Ho BL, Lieu AS, Hsu CY (2008) Hemiparkinsonism secondary to an infiltrative astrocytoma. Neurologist 14:258–261 5. Plowman PN, Saunders CA, Maisey MN (1998) Gliomatosis cerebri: disconnection of the cortical grey matter, demonstrated on PET scan. Br J Neurosurg 12:240–244 6. Vates GE, Chang S, Lamborn KR, Prados M, Berger MS (2003) Gliomatosis cerebri: a review of 22 cases. Neurosurgery 53:261–271 discussion 271
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LETTER TO THE EDITORS
Juvenile parkinsonism as an initial manifestation of gliomatosis cerebri Wooyoung Jang • Seung Hyun Ha • Shin Kwang Khang • Juhan Kim • Seung Hyun Kim Hee-Jin Kim
•
Received: 7 August 2013 / Revised: 11 September 2013 / Accepted: 20 September 2013 / Published online: 25 October 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Dear Sirs, Some types of infiltrative tumors are not visible at an early stage by conventional structural brain imaging techniques such as magnetic resonance imaging (MRI) [5]. Vates et al. [6] described various clinical manifestations of gliomatosis cerebri, which included mental change, headache, dementia, seizure, and gait abnormalities. However, there are few reports of parkinsonism as an initial manifestation of GC [1]. A 17-year-old female presented with left hand tremor for one month. She had no history of tremor inducing medication, illicit drug or alcohol abuse. There was no remarkable hereditary disorder causing parkinsonism. On initial neurological examination, only resting and postural tremor of the left hand and mild hypomimia were observed. The tremor had a frequency of 2–3 Hz and the frequency was not changed during distraction. Brain MRI including
W. Jang and S. H. Ha contributed equally to this work.
Electronic supplementary material The online version of this article (doi:10.1007/s00415-013-7162-1) contains supplementary material, which is available to authorized users. W. Jang Department of Neurology, Gangneung Asan Hospital, College of Medicine, University of Ulsan, Gangneung, Republic of Korea S. H. Ha J. Kim S. H. Kim H.-J. Kim (&) Department of Neurology, College of Medicine, Hanyang University Hospital, 17 Haengdang-dong, Seongdong-gu, Seoul 133-792, Republic of Korea e-mail: [email protected] S. K. Khang Department of Pathology, College of Medicine, Ulsan University, Seoul, Republic of Korea
T1, T2, diffusion weighted imaging, and T1 gadolinium enhancement imaging yielded no significant findings. Serological findings for secondary parkinsonism were normal, including thyroid function test, autoimmune disease screening tests, serum ceruloplasmin, and serum pyruvate/lactate ratio. L-DOPA was challenged up to 1,200 mg but there was no improvement of symptoms. The patient presented no autonomic symptoms and positional blood pressure test revealed no orthostatic hypotension. Toxicology screening including manganese was also negative. Over the next two months the patient complained of intermittent dizziness and slowness of her left hand. Thereafter, tremor and slowness spread to the right upper extremity. Left dominant bilateral bradykinesia, resting tremor with postural component, and cogwheel rigidity were noted. She showed postural instability on the pull test (UPDRS-III score was 19). There were no significant findings on follow up T1, T2, diffusion weighted MRI and T1 gadolinium enhancement imaging (Fig. 1a) and N-(3fluoropropyl)-2-b-carbomethoxy-3-b-(4-iodophenyl) nortropane positron emission tomography (FP-CIT PET) imaging. All electrophysiologic studies including nerve conduction study, electromyography, and electroencephalography (EEG) were normal for motor neuron disease and symptomatic epileptic syndrome. Genetic tests as a panel for hereditary movement disorders (PARK2, PANK2, FXTAS, ATP7B, SCA 1, 2, 3, 6, DYT 1, DYT 5, and Huntington’s disease) were all negative. Six months later the patient began to show cognitive decline and frequent syncope. On brain MRI, a newly developed high signal intensity was observed in a T2weighted sequence in the right parietal lobe, and these lesions spread to the left parietal lobe within one month (Fig. 1b). Epileptiform discharge in the left frontal area
123
3162 Fig. 1 Sequential changes of brain MRI, MRS and FDG PET images. a After three months of disease there is no significant finding. b After eight months of disease, a T2 high signal appears in the bilateral temporooccipito-parietal lobe. c FDGPET reveals diffuse hypometabolism in the whole brain d MRS shows a high peak of choline. e, f Hematoxylineosin staining of brain tissues. Some tumor cells possess elongated spindle-shaped nuclei (arrow), a common feature of gliomatosis cerebri (original magnification 91000)
123
J Neurol (2013) 260:3161–3163
J Neurol (2013) 260:3161–3163
was noted on EEG, and neuropsychological test revealed decrement of overall cerebral function. 18F-fluorodeoxyglucose (FDG) PET showed diffuse reduction of glucose metabolism (Fig. 1c). Magnetic resonance spectroscopy (MRS), revealed a high choline peak in the right parietal lobe (Fig. 1d). Because an infiltrative tumor was suspected, a brain biopsy was performed. In microscopic findings, some of the tumor cells had elongated spindle-shaped nuclei, a common feature of GC (Fig. 1e, f). Some of the clinical findings and disease course in this patient are of considerable interest. Firstly, there was no structural or functional abnormality of the basal ganglia. In the majority of previous cases of tumor-induced parkinsonism, direct striatal involvement or secondary compression of the striatum by various structural lesions was observed. Plowman et al. [5] suggested on the basis of a PET study that gliomatosis cerebri caused functional disconnection of the cerebral cortex. Therefore, interruption of the striatal output to the supplementary motor area is the most likely explanation for the parkinsonism in our patient. Second, juvenile parkinsonism induced by GC has not previously been reported. In addition to the parkinsonism, there were ‘key signs’ that raised suspicion of tumor-induced parkinsonism, and these signs, such as pyramidal tract involvement, cognitive impairment, and seizure, are helpful in assigning GC etiology[3, 4]. She had been suffering from ‘‘pure parkinsonism’’ for six months without any other ‘key signs’ such as cognitive decline and seizure. Finally, a negative brain MRI cannot exclude tumorinduced parkinsonism. FDG PET scans of GC revealed markedly reduced glucose uptake in multiple brain regions with involvement of the white matter, compatible with
3163
biopsy findings. This finding is compatible with type I classical form of GC according to a previous report [2]. Therefore, we suggest that GC should be listed among the disorders that cause juvenile parkinsonism, and consideration given to a meticulous evaluation including conventional MRI, MRS. FDG-PET might also be considered when no definite structural abnormality revealed. Acknowledgments This study was supported by the cluster research fund of Hanyang University (HY-2009-C). Conflicts of interest conflict of interest.
The authors declare no financial or other
Ethical standard Informed consent was obtained from this patient according to the regulations of the Institutional Review Board of Hanyang University Medical Center.
References 1. Asada T, Takayama Y, Tokuriki Y, Fukuyama H (2007) Gliomatosis cerebri presenting as a parkinsonian syndrome. J Neuroimaging Off J Am Soc Neuroimaging 17:269–271 2. Desclee P, Rommel D, Hernalsteen D, Godfraind C, de Coene B, Cosnard G (2010) Gliomatosis cerebri, imaging findings of 12 cases. J Neuroradiol 37:148–158 3. Dolendo MC, Lin TP, Tat OH, Chong QT, Timothy LK (2003) Parkinsonism as an unusual presenting symptom of pineal gland teratoma. Pediatr Neurol 28:310–312 4. Ho BL, Lieu AS, Hsu CY (2008) Hemiparkinsonism secondary to an infiltrative astrocytoma. Neurologist 14:258–261 5. Plowman PN, Saunders CA, Maisey MN (1998) Gliomatosis cerebri: disconnection of the cortical grey matter, demonstrated on PET scan. Br J Neurosurg 12:240–244 6. Vates GE, Chang S, Lamborn KR, Prados M, Berger MS (2003) Gliomatosis cerebri: a review of 22 cases. Neurosurgery 53:261–271 discussion 271
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