CLINICAL REPORT Hemiparkinsonism Secondary to an Infiltrative Astrocytoma Bo-Lin Ho, MD,* Ann-Shung Lieu, MD,† and Chung-Yao Hsu, MD, PhD* Background: Brain tumors are uncommon etiologies of parkinsonism. The clinical manifestations of tumoral parkinsonism may sometimes resemble those of idiopathic origin. Increased awareness of this rare entity is important for an earlier prompt diagnosis and treatment. Review Summary: A previously healthy, 60-year-old man developed slowly progressive right-sided resting tremor and bradykinesia over 8 months. Although idiopathic Parkinson disease was the initial diagnosis, the parkinsonian symptoms were not responsive to medical treatment with levodopa and a dopamine agonist. Brain computed tomography failed to reveal an intracranial lesion. Brain magnetic resonance imaging demonstrated an infiltrative, slightly enhancing mass in the left mesial temporal lobe extending to the left basal ganglion and insula. Histopathologic findings confirmed the diagnosis of high-grade astrocytoma. The parkinsonian symptoms subsided after tumor removal; however, ipsilateral hemiparesis developed postoperatively. Conclusions: Neuroimaging is recommended for investigation of atypical parkinsonism. We suggest that brain magnetic resonance imaging is preferred for patients with drug-resistant parkinsonism or concurrent signs apart from extrapyramidal symptoms, because some mass lesions are not observed by computed tomography scan. Key Words: brain tumor, hemiparkinsonism, astrocytoma (The Neurologist 2008;14: 258 –261) I ntracranial neoplasm is an uncommon cause of secondary parkinsonism. Brain tumors may produce parkinsonian symptoms by compression or distortion of the basal ganglia and their circuitry, or rarely by direct infiltration and destruction.1,2 Intrinsic tumors of the basal ganglia usually do not result in parkinsonism.3 Brain computed tomography (CT) or magnetic resonance imaging (MRI) is recommended in the evaluation of movement disorders, especially if the clinical From the Departments of *Neurology and †Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. Reprints: Chung-Yao Hsu, MD, PhD, Department of Neurology, Kaohsiung Medical University Hospital, No.100, Tz-You 1st Road, 80756 Kaohsiung, Taiwan. E-mail: cyhsu@kmu.edu.tw. Copyright © 2008 by Lippincott Williams & Wilkins ISSN: 1074-7931/08/1404-0258 DOI: 10.1097/NRL.0b013e31816c43ea 258 presentation is atypical, unilateral, or accompanied by long tract signs.4 In this report, we describe a patient with progressive hemiparkinsonism secondary to an infiltrative astrocytoma in the contralateral basal ganglion. We emphasize the significance of neuroimaging studies for early detection of structural lesions as the cause of atypical parkinsonism. CASE REPORT A previously healthy, 60-year-old man was hospitalized because of right-sided resting tremor and bradykinesia with slow progression over 8 months. He had no systemic diseases, such as diabetes mellitus and hypertension, and no history of head trauma, alcoholism, or major operation. He had never been exposed to either heavy metals or chemical materials. His family history concerning movement disorders was negative. On his first admission in August 2005, general physical examination was normal. Neurologic examination revealed bradykinesia, mild cogwheel rigidity on the right side, and 4 Hz resting tremor in his right arm with “pill-rolling” feature. Masked face was present without facial asymmetry. There was no cognitive dysfunction, and no difficulty in speaking or writing. The cranial nerves were intact without vertical gaze palsy. Strength was normal. Deep tendon reflexes were slightly brisk on the right side, and plantar responses were flexor bilaterally. His walking was slow, and he had gait disturbance because of mild bradykinesia in his right leg. Decreased right arm swing was observed during walking. No axial rigidity, cerebellar dysfunction, or sensory deficit was detected. Laboratory data including complete blood count, liver and renal panels, electrolytes, and thyroid hormones were normal. Chest radiograph and brain CT were unremarkable. We had titrated antiparkinsonism drugs up to 300 mg/75 mg The Neurologist • Volume 14, Number 4, July 2008 The Neurologist • Volume 14, Number 4, July 2008 Hemiparkinsonism Secondary to an Infiltrative Astrocytoma FIGURE 2. Three months after cyberknife radiosurgery, postcontrast brain CT demonstrated minimal tumoral hemorrhage with marked perifocal edema (A); the patient underwent tumor resection by craniotomy subsequently for alleviation of mass effect. Two months after craniotomy, residual tumor progression with interval worsening of brain edema was noted (B). FIGURE 1. Brain MRI demonstrated an infiltrative mass lesion in left mesial temporal lobe extending to left basal ganglion and insula, with high signal intensity in fluid-attenuated inversion recovery images (A,B), and faint enhancement in postcontrast T1-weighted images (C,D). of levodopa-carbidopa and 1 mg of ropinirole per day, however, failed to control the parkinsonian symptoms. Despite there were neither atypical symptoms of Parkinson disease (PD) nor progression of initial presentations; subsequent brain MRI with gadolinium demonstrated a mass lesion in the left mesial temporal lobe extending to the left basal ganglion and insula, with high signal intensity in T2weighted images and minimal enhancement in postcontrast T1-weighted images (Fig. 1). There was mass effect to adjacent structures causing minimal midline shift. Magnetic resonance spectroscopy showed a dominant choline peak with decreased N-acetylaspartate. A low-grade astrocytoma was suspected. Because of the stable clinical condition of the patient, he was discharged and referred to the outpatient department for regular follow-up. The patient went to another hospital for a second opinion, and underwent a stereotactic biopsy in November 2005. Pathologic findings revealed a high-grade astrocytoma (WHO grade III). The patient then underwent cyberknife radiosurgery in December 2005. A right hemiparesis developed although the resting tremor in the right arm diminished. Three months later, the patient had progressive conscious disturbance resulting from tumoral hemorrhage in the left cerebral hemisphere with impending subfalcine herniation (Fig. 2A). He then underwent tumor removal by craniotomy, followed by being treated with thalidomide (200 mg/d) as adjuvant chemotherapy. The right hemiparesis remained stationary without recurrent tremor postoperatively. However, aspiration pneumonia developed, which was complicated by respiratory failure on subsequent days. A fol© 2008 Lippincott Williams & Wilkins low-up brain CT revealed residual tumor progression with worsening of brain edema (Fig. 2B). After a long stay in the intensive care unit for the treatment of complicated pneumonia, the patient finally died because of the septic shock in August 2006. DISCUSSION Parkinsonism is characterized by the clinical features of resting tremor, bradykinesia, cogwheel rigidity, flexed posture, loss of postural reflexes, and freezing phenomenon.5 Idiopathic PD makes up the majority of the cases with parkinsonism, whereas the secondary forms may be attributed to various etiologies such as drug-induced extrapyramidal symptoms, metabolic dysfunction, intoxication, infection, vascular events, and neurodegenerative disorders. Intracranial tumor is an uncommon cause of symptomatic parkinsonism, accounting for only 0.3% of presentations in a prospective evaluation of 907 patients with supratentorial tumors. The pathogenesis of tumor-induced parkinsonism has been proposed to involve the direct compression of structural lesion or injury of the dopaminergic nigrostriatal pathways, or disruption of striatal efferents.3,6 – 8 Patients with parkinsonism secondary to brain tumors usually exhibit characteristics of hemi- or lateralized extrapyramidal symptoms and signs, abnormalities of extraocular movements, corticospinal or cerebellar dysfunction, high intracranial pressure, and an incomplete classic triad of tremor, rigidity, and akinesia.2,9 However, certain variants of parkinsonism may present with 259 The Neurologist • Volume 14, Number 4, July 2008 Ho et al TABLE 1. Literature Review of Secondary Parkinsonism Associated With Underlying Brain Tumors Authors Patient Age, Sex Tumor Location and Type Laterality of Initial Manifestation 42 F 56 M 14 M 63 F 61 M 64 F 71 F 74 M 10 M 3.5 M 39 F 75 M 22 F 41 F Right midbrain cavernoma Right BG cavernoma Immature pineal gland teratoma Left midbrain polycystic astrocytoma Right pterional meningioma Bilateral BG and corpus callosum high-grade B cell lymphoma Left frontal (parasagittal) tumor Renal cell carcinoma with brain metastasis Right cerebral peduncle low-grade glioma Pontomesencephalic low-grade astrocytoma Left pontomesencephalic cystic astrocytoma Bilateral BG (globus pallidus) high-grade Hodgkin lymphoma Left BG cystic hemangioblastoma Bilateral BG infiltrating low-grade oligodendroglial tumor Unilateral Unilateral Bilateral Unilateral Unilateral Unilateral Bilateral Bilateral Bilateral Bilateral Bilateral Bilateral Unilateral Unilateral Li and Zhong16 Ertan et al17 Dolendo et al18 Yoshimura et al15 Salvati et al12 Sánchez-Guerra et al19 Chang et al20 Pohle and Krauss 14 Cicarelli et al13 Pramstaller et al21 Bosch et al22 de Sèze et al9 Prognosis Good Good Poor Good Good Poor Good Good Loss of follow-up Good Poor Good Good BG indicates basal ganglion. some of these clinical features as well. Therefore, neuroimaging studies are of great diagnostic value, especially in the case of unusual clinical presentations or poor medical response. Movement disorders resulting from brain tumors usually have a good prognosis, and even make a complete recovery after tumor removal.4 Compressive lesions have better reversibility of clinical symptoms than infiltrative ones.2,10 However, many factors related to surgery such as local ischemia, postoperative hemorrhage, impaired venous drainage, or diffuse hypoxia related to general anesthesia may cause impaired nigrostriatal transmission bilaterally leading to the transient resting and postural tremor.11 Tumor size and peritumoral edema may play an important role in compressing and consequently impairing perfusion of the basal ganglia region.12 In our patient, the infiltrative growth pattern of the tumor made it difficult to achieve a complete resection. Prominent perifocal edema also led to a poor prognosis. In 1985, Polyzoidis et al reviewed 49 cases of parkinsonism caused by brain tumors, and most of these cases were supratentorial, extra-axial benign lesions.2 Intra-axial or infiltrative tumors involving basal ganglia were thought to be rare. However, we found increasing prevalence of intrinsic tumors associated with tumoral parkinsonism in the past 10 years (summarized in the Table 1).9,12–22 Five patients were diagnosed with low-grade gliomas based either on histopathologic or radiologic findings.9,13–15 The disagreement between us might attribute to the development of MRI that shows higher resolution particularly in detecting infiltrative glioma in the brain. A pontomesencephalic location and bilateral basal ganglia involvement made tumor resection more difficult.9,13,14 However, a good prognosis was generally achieved by surgical resection or levodopa therapy only in patients with low-grade gliomas. Because some intracranial tumors present with the clinical picture of idiopathic PD, and the extrapyramidal disorders can precede other symptoms or remain isolated 260 until an advanced tumor stage, the definite diagnosis may sometimes be delayed. Neuroimaging studies are recommended in patients with parkinsonism disease, with atypical parkinsonism or a poor response to medications for Parkinson disease. Increased awareness of this rare tumor presentation is important for prompt diagnosis and treatment. REFERENCES 1. Krauss JK, Paduch T, Mundinger F, et al. Parkinsonism and rest tremor secondary to supratentorial tumours sparing the basal ganglia. Acta Neurochir (Wien). 1995;133:22–29. 2. Polyzoidis KS, McQueen JD, Rajput AH, et al. Parkinsonism as a manifestation of brain tumor. Surg Neurol. 1985;23:59 – 63. 3. Krauss JK, Nobbe F, Wakhloo AK, et al. Movement disorders in astrocytomas of the basal ganglia and the thalamus. J Neurol Neurosurg Psychiatry. 1992;55:1162–1167. 4. Bhatoe HS. Movement disorders caused by brain tumours. Neurol India. 1999;47:40 – 42. 5. Fahn S, Przedborski S. Parkinsonism. In: Rowland LP, ed. Merritt’s Textbook of Neurology. 11th ed. Philadelphia: Lippincott Williams & Wilkins; 2005:828 – 836. 6. Leenders KL, Findley LJ, Cleeves L. PET before and after surgery for tumor-induced parkinsonism. Neurology. 1986;36:1074 –1078. 7. Miyagi Y, Morioka T, Otsuka M, et al. Striatal glucose metabolism and 关18F兴fluorodopa uptake in a patient with tumorinduced hemiparkinsonism. Neurosurgery. 1993;5:838 – 841. 8. Straube A, Sigel K. Parkinsonian syndrome caused by a tumor of the left supplementary motor area. J Neurol Neurosurg Psychiatry. 1988;51:730–731. 9. de Seze J, Defebvre L, Ruchoux MM, et al. Hemiparkinsonism revealing an infiltrating low-grade oligodendroglial tumor. Eur Neurol. 1998;40: 234 –236. © 2008 Lippincott Williams & Wilkins The Neurologist • Volume 14, Number 4, July 2008 10. Wakai S, Nakamura K, Niizaki K, et al. Meningioma of the anterior third ventricle presenting with parkinsonism. Surg Neurol. 1984;21:88 –92. 11. Wenning GK, Luginger E, Sailer U, et al. Postoperative Parkinsonian tremor in a patient with a frontal meningioma. Mov Disord. 1999;14: 366 –388. 12. Salvati M, Frati A, Ferrari P, et al. Parkinsonian syndrome in a patient with a pterional meningioma: case report and review of the literature. Clin Neurol Neurosurg. 2000;102:243–245. 13. Cicarelli G, Pellecchia MT, Maiuri F, et al. Brain stem cystic astrocytoma presenting with “pure” parkinsonism. Mov Disord. 1999;14:364 – 366. 14. Pohle T, Krauss JK. Parkinsonism in children resulting from mesencephalic tumors. Mov Disord. 1999;14:842– 846. 15. Yoshimura M, Yamamoto T, Iso-o N, et al. Hemiparkinsonism associated with a mesencephalic tumor. J Neurol Sci. 2002;197:89 –92. 16. Li ST, Zhong J. Surgery for mesencephalic cavernoma: case report. Surg Neurol. 2007;67:413– 417. © 2008 Lippincott Williams & Wilkins Hemiparkinsonism Secondary to an Infiltrative Astrocytoma 17. Ertan S, Benbir G, Tanriverdi T, et al. Parkinsonism caused by cavernoma located in basal ganglion. Parkinsonism Relat Disord. 2005;11: 517–519. 18. Dolendo MC, Lin TP, Tat OH, et al. Parkinsonism as an unusual presenting symptom of pineal gland teratoma. Pediatr Neurol. 2003;28: 310 –312. 19. Sanchez-Guerra M, Cerezal L, Leno C, et al. Primary brain lymphoma presenting as Parkinson’s disease. Neuroradiology. 2001;43:36 – 40. 20. Chang DC, Lin JJ, Lin JC. Parkinsonism as an initial manifestation of brain tumor. Zhonghua Yi Xue Za Zhi (Taipei). 2000;63:658 – 662. 21. Pramstaller PP, Salerno A, Bhatia KP, et al. Primary central nervous system lymphoma presenting with a parkinsonian syndrome of pure akinesia. J Neurol. 1999;246:934 –938. 22. Bosch J, Vilalta J, Tintore M, et al. Parkinsonian hemi-syndrome as the initial manifestation of supratentorial cystic hemangioblastoma in a patient with Von Hippel-Lindau disease. Rev Neurol. 1998;26:221– 223. 261