Korean J Urol Oncol 2008;6(2):104-106

Paraneoplastic Limbic Encephalitis Associated with Testicular Seminoma

Weol Min Kim, Jin Seon Cho1, Soo Kee Min2, Seon Hye Jung, Mi-Sun Oh, Byung-Chul Lee Departments of Neurology, 1Urology and 2Pathology, Hallym University Sacred Heart Hospital, Hallym Univeristy College of Medicine, Anyang, Korea

Although paraneoplastic limbic encephalitis (PLE) is most commonly associated with small cell lung cancer, testicular cancer has also been recognized as a rare cause of PLE. In Korea, PLE associated with testicular seminoma has not been reported. We report a patient with testicular seminoma who initially presented with acute transverse myelitis and showed a manifestation of PLE later on. A careful testicular examination is important, especially when patients present with limbic encephalitis and transverse myelitis of unknown etiology. (Korean J Urol Oncol 2008;6:104-106) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏 Key Words: Paraneoplastic syndrome, Limbic encephalitis, Testis, Seminoma

Paraneoplastic limbic encephalitis (PLE) is a rare disorder that admitted and seen by us due to bilateral lower leg weakness, affects the mesial temporal lobe and vital limbic system struc- predominantly on the left side, grade 4 according to the tures, which can be caused by various neoplasms. Recently PLE Medical Research Council, that had developed two days before. associated with testicular seminoma has been recognized in- His anal sphincteric function was intact and the perianal sensa- creasingly and well characterized onconeuronal antibody, an- tion was preserved. He had a decreased pain and temperature ti-Ma2, was detected.1 Abnormalities in eye movement, short- sensation below T10 dermatome with a preserved position and term memory loss, seizure, or personality changes are able to vibration sensation. Deep tendon reflexes were increased bi- be detected as neurological complications. In contrast to other laterally in his knees and ankles with left-sided ankle clonus. paraneoplastic syndromes, a remarkable number of patients Spinal magnetic resonance images (MRI) were non-contributory show neurological improvement after complete resection of tes- except for L4 and L5 intervertebral disc herniations. Cerebro- 2 ticular seminoma. We report a patient with neurological syn- spinal fluid (CSF) showed an opening pressure of 200mmH2O, dromes associated with antecedent testicular seminoma. protein 47.8mg/dl, glucose 62mg/dl, absence of red blood cell (RBC) and white blood cell (WBC), negative oligoclonal CASE REPORT bands, and normal immunoglobulin G levels. Posterior tibial and median nerve sensory evoked potentials disclosed no A 37-year-old man with no previous medical history was abnormalities. Under presumptive diagnosis of acute transverse hospitalized with acute progressive psychosis and paranoidic myelitis, we started steroid pulse therapy with 1g of methyl- delusion. Two months prior to the hospitalization, he had been prednisolone per day for 5 days. The patient showed complete improvement in his gait and left leg weakness, and he was Received May 30, 2008, Accepted June 27, 2008 discharged. Correspondence：Byung-Chul Lee, Department of Neurology, Hallym Six weeks after discharge, the patient was admitted again for University College of Medicine, 896, Pyeongchon-dong, Dongan- gu, Anyang 431-070, Korea. Tel: 82-31-380-3742, Fax: 82-31- an episode of complex partial seizure. Neither brain MRI nor 381-4659, E-mail: [email protected] electroencephalography showed abnormal findings. The lumbar This paper was partly supported by the Korea Health 21 & D project, Ministry of Health and Welfare (A06-0171-B51004-06N1-00060B). puncture revealed an opening pressure of 210mmH2O, RBC 104 Weol Min Kim, et al：Paraneoplastic Limbic Encephalitis Associated with Testicular Seminoma 105 with 0/mm3, and WBC 1/mm3 in the CSF. Viral and bacterial including a PCR for herpes simplex virus, were all negative. studies, including tuberculosis, were negative. During the hospi- Fortunately, no distant metastasis was detected on F-18 fluo- tal course, two seizure episodes occurred. He was treated with rodeoxyglucose PET-CT (Fig. 1). Radical orchiectomy was per- topiramate 100mg bid daily and had no more seizure attacks. formed, and pathological examination confirmed anaplastic However, he became anxious, appeared to be distressed, and seminoma (Fig. 2) which classified as T1N0M0 by TNM classi- complained of urinary difficulty. A urologic consultation re- fication. He received adjuvant radiotherapy on para-aortic area vealed a hard scrotal mass, and scrotal ultrasonography sug- for 3 weeks. After surgery, his psychiatric problems and neuro- gested intratesticular seminoma (2.72x1.65cm) in the right logical symptoms improved dramatically. At 6 months after op- testis. Serum lactate dehydrogenase, α-fetoprotein, and HCG eration, he returned to his life without any sequelae or re- levels were 717IU/l, 2.77ng/ml, and less than 1.2mIU/ml, currence of seminoma. respectively. He also began to exhibit paranoid delusions and acute psychiatric disturbances. Neuropsychiatric tests showed DISCUSSION verbal and visual memory impairments especially memory reg- istration (Korean Mini-Mental Status Examination 29/30). CSF Only about 0.01% of patients with cancer experience symp- examination showed mild pleocytosis (27 WBC/mm3) without toms or signs of paraneoplastic syndrome.3 Testicular semi- malignant cells or elevated proteins. Viral and bacterial studies, noma is the most common solid tumor among men aged 15 to 34 years. PLE associated with testicular seminoma is rare. However, it can manifest as sensorimotor peripheral neuro- pathy, parkinsonism,4 and neuropsychiatric findings5 or limbic encephalomyelitis.2 The diagnosis of PLE is difficult because neurologic symp- toms frequently precede the detection of the primary cancer.6 Once PLE is suspected, extensive clinical, laboratory, and ra- diologic evaluations are mandatory. Although not widely avail- able, the autoantibody test including anti-Ma2 is also helpful for detecting PLE. Fig. 1. Mildly increased FDG uptake(arrow) is noted in the right In this case, the patient's history and clinical findings were scrotum, suggesting malignant testicular tumor. compatible with the current diagnostic criteria of PLE.2 First,

Fig. 2. (A) Cut surface of testis shows a well-demarcated resilient nodular mass of red tan friable tissue, measuring 2.9x2.2x2.0cm. (B) Microscopic view shows frequent mitosis (0-3/HPF) consistent with anaplastic seminoma (H&E, x200). 106 대한비뇨기종양학회지：제6권 제2호 2008 the patient showed a ‘myelitis-like' history which is often asso- tis, the diagnosis of paraneoplastic syndrome associated with ciated with paraneoplastic encephalomyelitis that is caused by testicular seminoma might have been made earlier and pre- various primary cancers.3 However, we were not able to con- vented further progression of the disease in our patient. firm whether his transverse myelitis was caused by remote ef- fects of his seminoma or not. Second, his brain MRI appeared REFERENCES normal in two serial studies. According to the previous studies signal changes in various parts of brain parenchyma are fre- 1. Voltz R, Gultekin SH, Rosenfeld MR, Gerstner E, Eichen J, quently observed in brain MRI of the patients with PLE. Posner JB, et al. A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. However, brain MRI abnormalities are not essential for the di- N Engl J Med 1999;340:1788-95 agnosis of PLE.2 According to Dalmau et al.6 who studied 38 2.Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, patients with anti-Ma2 associated encephalitis, 11 of 33 patients Dalmau J. Paraneoplastic limbic encephalitis: neurological initially showed normal brain MRI findings. Thus, a normal symptoms, immunological findings and tumour association in brain MRI dose not entirely exclude PLE. The symptoms and 50 patients. Brain 2000;123:1481-94 signs of PLE can occasionally be caused by other diseases, in- 3. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med 2003;349:1543-54 cluding systemic lupus erythematosus,7 Wernicke-Korsakoff en- 4. Bosl GJ, Motzer RJ. Testicular germ-cell cancer. N Engl J 8 9 cephalopathy, and herpes virus encephalomyelitis. In our pa- Med 1997;337:242-53 tient, we were able to exclude these disorders by serologic and 5. Scheid R, Voltz R, Guthke T, Bauer J, Sammler D, von CSF examinations. Cramon DY. Neuropsychiatric findings in anti-Ma2-positive One of the characteristic features of PLE is the prompt im- paraneoplastic limbic encephalitis. Neurology 2003;61:1159-61 6. Dalmau J, Graus F, Villarejo A, Posner JB, Blumenthal D, provement of symptoms and signs when treatment is Thiessen B, et al. Clinical analysis of anti-Ma2-associated performed. The neuropsychiatric abnormalities were improved encephalitis. Brain 2004;127:1831-44 dramatically after radical orchiectomy in this case. The patient's 7. Stubgen JP. Nervous system lupus mimics limbic encephalitis. favorable clinical course after orchiectomy also supports the di- Lupus 1998;7:557-60 agnosis of PLE rather than other disorders that directly affect 8. Parkin AJ, Dunn JC, Lee C, O'Hara PF, Nussbaum L. Neuropsychological sequelae of Wernicke's encephalopathy in the central nervous system. a 20-year-old woman: selective impairment of a frontal memo- In our patient, we could not identify the cause of the pa- ry system. Brain Cogn 1993;21:1-19 tient's problems until the testicular ultrasonography was 9. Kararizou E, Markou I, Zalonis I, Gkiatas K, Triantafyllou N, performed. If we had performed a careful testicular examination Kararizos G, et al. Paraneoplastic limbic encephalitis present- when the patient was admitted with the acute transverse myeli- ing as acute viral encephalitis. J Neurooncol 2005;75:229-32