ORIGINAL ARTICLE Anaplastic Astrocytoma Presenting as Reversible Posterior Leukoencephalopathy Syndrome Tomokatsu Yoshida, MD,*‡ Fumitoshi Niwa, MD,‡ Satoshi Kimura, MD,† and Masanori Nakagawa, MD* Abstract: We report a 60-year-old man with grade III astrocytoma, who presented with status epilepticus. The initial MRI did not demonstrate typical findings of an astrocytoma but rather showed reversible posterior leukoencephalopathy syndrome (RPLS). N-Isopropil-p-关123I兴 iodoamphetamine single photon emission computed tomography (SPECT) demonstrated hyperperfusion in this area. A brain tumor should be considered and the patient carefully followed by MRI, even if the MRI white matter lesion pattern suggests RPLS. This is especially relevant in the presence of atypical findings for RPLS on SPECT. Key Words: astrocytoma, reversible posterior leukoencephalopathy syndrome, MRI, SPECT, status epileptics (The Neurologist 2006;12: 311–313) A naplastic astrocytoma is classified as grade III astrocytoma by the World Health Organization. Pathologically, anaplastic astrocytomas are composed of cells with small, dark nuclei that vary in size and shape and include cysts or necrosis, as well as abnormal tumor vessels. Compared with glioblastoma multiforme classified as grade IV astrocytoma, anaplastic astrocytomas show lower degrees of necrosis or cystic formation and increased abnormal vascularity.1,2 Anaplastic astrocytoma, which typically appears hypointense to the surrounding brain on T1-weighted imaging (T1WI) and hyperintense on T2-weighted imaging (T2WI), appears as contrast-enhancing, ring-shaped lesions on MRI. However, these findings should not appear in low-grade astrocytoma. We report a case of anaplastic astrocytoma, in which the initial symptom was status epilepticus and MRI did not demonstrate typical findings but rather suggested reversible posterior leukoencephalopathy syndrome (RPLS). From the *Research Institute for Neurological Diseases and Geriatrics, Department of Neurology and Gerontology, and †Department of Neurosurgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; and the ‡Department of Neurology, Ayabe City Hospital. Reprints: Tomokatsu Yoshida, Research Institute for Neurological Diseases and Geriatrics, Department of Neurology and Geroniology, Kyoto Prefectural University of Medicine, Kawaramachi Hirokoji 465, Kamigyoku, Kyoto 602-0841, Japan. E-mail: tomo-kayo@k8.dion.ne.jp. Copyright © 2006 by Lippincott Williams & Wilkins ISSN: 1074-7931/06/1206-0311 DOI: 10.1097/01.nrl.0000250947.19679.51 The Neurologist • Volume 12, Number 6, November 2006 CASE REPORT On July 31, 2003, a 60-year-old man was brought to our emergency room because of convulsion. He had a history of hypertension and was treated with an antihypertensive drug, but there was no history of epilepsy, renal, or other disorders. Blood pressure on arrival was 102/66 mm Hg. Neurologic examination showed confusion, but there were no other symptoms such as cortical blindness and motor palsy. The patient did not complain of headache. After arriving at our hospital, he had 2 further generalized seizures. Cranial computed tomography (CT) showed low intensity in the white matter in the right parietooccipital area. Laboratory findings, including Ca, Mg, lactic acid, and pyruvic acid, were normal. Tumor markers, including soluble interleukin 2 receptor, the high elevation of which suggests malignant lymphoma, were negative. Serologic tests for vasculitis were negative. Serologic test was negative for various viruses, including herpes simplex virus, herpes zoster, cytomegalovirus, and Japanese encephalitis virus. Initial cerebrospinal fluid pressure was 140 mm H2O, and the cerebrospinal fluid contained 1 cell/mm3. The cerebrospinal fluid protein level was 46 mg/dL, and the glucose level was 80 mg/dL. Electroencephalography showed marked epileptogenic activity consisting of spike-wave discharges at the right parietal area. The patient was treated with diazepam, flunitrazepam, and phenytoin. Twelve hours later, the neurologic symptom returned to normal. Thereafter, he was treated with phenytoin (250 mg/d, p.o.), and there have not been any further seizures to date. Blood pressure was not increased and antihypertensive drugs were not administered. MRI was performed on days 4, 18, and 40 after admission (Fig. 1A–C). On day 4 after admission, T2WI and fluid-attenuated inversion recovery (FLAIR) sequence MRI demonstrated increased signal intensity in the right parietooccipital lobe, centered mainly at the gray matter–white matter junction. On day 18, this abnormality became much clearer. Gadolinium-enhanced T1WI could not be performed, because of mild renal failure caused by rhabdomyolysis after the seizure. On follow-up examination performed on day 40, this high signal intensity was almost resolved. N-isopropil-p-关123I兴 iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) was performed on days 5 and 19 after admission (Fig. 2A, B). SPECT images were obtained 30 minutes after intravenous injection of 167 MBq 123I-IMP. Delayed images were not performed. On days 5 and 19, SPECT demonstrated hyperper- 311 The Neurologist • Volume 12, Number 6, November 2006 Yoshida et al FIGURE 1. MRI findings (A–D, FLAIR; E, gadolinium-enhanced T1WI). A, On day 4 after admission. Increased signal intensity was demonstrated in the right parietooccipital lobe, centered mainly on the gray matter–white matter junction. B, On day 18. The abnormality shown on day 4 became much clearer. C, On day 40. The high signal intensity was almost resolved. D, On day 70. The high-intensity lesion reappeared and became larger, and (E) ring-shaped lesions in the right parietooccipital lobe appeared on gadolinium-enhanced T1WI. FIGURE 2. 123I-IMP SPECT. On day 5 (A) and day 19 (B) after admission, SPECT demonstrated hyperperfusion in the right parietooccipital area where increased signal was shown on T2WI and FLAIR sequence MRI. C, On day 70, the hyperperfused area became larger. fusion in the right parietooccipital area where the increased signal was shown on T2WI and FLAIR sequence MRI. After the series of first seizures, there were no sequelae and no further seizures. However, T2WI and FLAIR sequence MRI performed 70 days after admission showed the reappearance of a high-intensity area (Fig. 1D). Furthermore, ring-shaped lesions in the right parietooccipital lobe appeared on gadolinium-enhanced T1WI (Fig. 1E). SPECT performed on day 70 demonstrated that the size of the hyperperfused area had increased. Partial right posteroparietal lobectomy was performed and a grade III astrocytoma with small, dark nuclei that varied in size and shape, including cysts or necrosis and abnormal tumor vessels, was noted. Then, the patient received postoperative radiation therapy and chemotherapy. DISCUSSION In this patient, it was difficult to establish a diagnosis of low-grade astrocytoma until the core lesion became clearer on MRI, because the patient demonstrated a course similar to RPLS. 312 RPLS is a clinical and radiologic syndrome characterized by the following features: (1) the clinical findings in these patients make up a recognizable syndrome characterized by headache, decreased alertness, altered mental functioning, seizures, and visual loss; (2) the neuroimaging findings suggest white matter edema in posterior portions of the cerebral hemispheres; (3) the clinical signs and abnormalities on imaging are always reversible.3 The causes of RPLS are hypertensive encephalopathy, eclampsia, immunosuppressive therapy, and so on.3 To our knowledge, there have only been 2 reports of brain tumor presenting as RPLS in cases of intravascular lymphomatosis4 and grade II astrocytoma,5 respectively. However, neither of these reports described SPECT findings. SPECT findings in our case showed increased perfusion in posterior regions of the cerebral hemispheres, which was more extensive than the corresponding foci of increased T2WI signal, shown during the hypertensive crisis.3 Furthermore, after normalization of blood pressure, resolution of this abnormality6 or hypoperfusion7 was shown. © 2006 Lippincott Williams & Wilkins The Neurologist • Volume 12, Number 6, November 2006 However, our patient’s blood pressure was not elevated at that time. Therefore, the mechanism of hypertensive encephalopathy might not be applicable to the patient. It is likely that single photon emission computed tomography imaging is an excellent diagnostic tool in the setting of new-onset seizures with atypical findings on magnetic resonance imaging. In the patient, partial status epilepticus involving 3 episodes of seizures occurred first. Under this condition, vasogenic edema is induced because regions of vasodilatation and vasoconstriction develop and because of breakdown of the blood-brain barrier. Such vasogenic edema appears within 5 days after status epilepticus and persists for about 4 weeks.5 High intensity in the right parietooccipital area on T2WI might have been vasogenic edema caused by partial status epilepticus and had almost disappeared within 40 days. The tumor itself could lead to status epilepticus, although the lesion was too small to be detected on plain MRI. Therefore, as the tumor grew, T2 hyperintensity might have reappeared. Hyperperfusion on 123I-IMP SPECT continued even after the high intensity on MRI disappeared, which is not typical for RPLS. Although high uptake of 123I-IMP SPECT in highgrade astrocytoma is also not common, several cases in which this tumor demonstrated hyperperfusion were reported.8 –10 Sugou et al8 reported that an increased vascular bed and blood flow with preservation of the blood-brain barrier could © 2006 Lippincott Williams & Wilkins Astrocytoma Presenting as RPLS be related to high uptake of 123I-IMP on early image in some gliomas. It is likely that SPECT imaging is an excellent diagnostic tool in the setting of new-onset seizures with atypical findings on MR imaging. We reported a case of anaplastic astrocytoma initially presenting as RPLS. We should consider brain tumor and carefully follow the patient by MRI, even if the patient seems to recover well after seizures and the white matter lesion on MRI appears to be reversible as in RPLS, especially in the presence of atypical findings for RPLS on SPECT or other imaging modality. REFERENCES 1. Burger PC, Vogel FS, Green SB, et al. 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