Pearls & Oy-sters: Cognitive and Affective Dysfunction Caused by a Small Cerebellar Hemangioblastoma.

The primary function of the cerebellum is the coordination and regulation of movement; therefore, cerebellar tumors usually present with ataxia, dysarthria, and vertigo. Large tumors also cause elevated intracranial pressure that may lead to a disturbance of consciousness. Furthermore, it has become increasingly evident that the cerebellum plays a substantial role in cognitive and affective processing. A 44-year-old female patient presented with a 1-month history of depression and flat affect. She had no cerebellar symptoms including no coordination dysfunction or dysarthria. Cognitive function tests revealed impairments in attention, execution, and processing speed. Hamilton Depression Scale and Hospital Anxiety Depression Scale indicated moderate-to-severe depression. Magnetic resonance (MR) imaging revealed a 7-mm enhancing lesion in the culmen of the cerebellar vermis with surrounding edema. Technetium-99m ethyl cysteinate dimer single-photon emission tomography (SPECT) showed hypoperfusion in the left frontal lobe. Although she was initially treated with corticosteroids for presumed sero-negative autoimmune encephalitis, her symptoms persisted. She then underwent cerebellar lesion resection. The histologic diagnosis was hemangioblastoma. The patient's symptoms dramatically improved within 1 week of resection, including improved batteries for cognitive function and depression. Complete regression of cerebellar edema and left frontal lobe hypoperfusion was observed on MR and SPECT images, respectively. This case reiterates the crucial influence of the cerebellum on cognitive and affective function. Moreover, cognitive dysfunction may be masked in cases with focal cerebellar symptoms or elevated intracranial pressure and, consequently, not adequately evaluated.

Impact of comorbidities on oncological outcomes of Japanese patients with high grade soft tissue sarcomas.

BACKGROUND: Considering the invasiveness of standard multidisciplinary approaches used for the treatment of soft tissue sarcoma, including surgery with wide margins, intensive chemotherapy, and radiotherapy, evaluation of comorbidities in high-grade soft tissue sarcoma patients is essential. Several previous studies have reported the impact of comorbidities on the survival of soft tissue sarcoma patients. Patient health status differs between nationalities or ethnic groups and only limited data has been reported with respect to the impact of comorbidities on Japanese soft tissue sarcoma patients. METHODS: The incidence of each comorbidity, relationship between comorbidities and underlying clinicopathological factors, relationship between treatment status and comorbidities, and impact of comorbidities on disease-specific death in 136 patients with high-grade soft tissue sarcoma at the authors' institution were analyzed. For the evaluation of comorbidities, the updated Charlson comorbidity index was applied. RESULTS: Of the patients, 25% presented with more than one comorbidity. Elderly patients showed a significantly higher incidence of comorbidities (p < 0.0001). Patients with congestive heart failure (p = 0.004), dementia (p < 0.0001), hemiplegia/paraplegia (p < 0.0001), and renal disease (p < 0.0001) showed worse prognosis. Tumor grade (p = 0.01) and updated Charlson comorbidity index (p < 0.0001) were independent risk factors for disease-specific death. CONCLUSIONS: Comorbidity status was a significant risk factor for disease-specific death in Japanese patients with high-grade soft tissue sarcoma. Innovations in comorbidity management may be a means for the improvement of oncological outcomes in soft tissue sarcoma. Given the difficulties in conducting standard randomized control studies in this field, data accumulation from real-world cases appears to be the most practical approach in establishing and applying strategies for the treatment of patients with comorbidities or elderly patients.

Association of Dermatomyositis Sine Dermatitis With Anti-Nuclear Matrix Protein 2 Autoantibodies.

Importance: Reports on dermatomyositis (DM) sine dermatitis (DMSD) are scarce, and the concept of the disease has not been widely accepted. Objective: To confirm the existence of DMSD, determine its prevalence, and characterize its serologic features. Design, Setting, and Participants: This is a cohort study that reviewed clinical information, laboratory data, and muscle pathology slides from January 2009 to August 2019. We further assessed the follow-up data of 14 patients with DMSD. The median (interquartile range) follow-up period was 34 (16-64) months. Muscle biopsy samples, along with clinical information and laboratory data, were sent to a referral center for muscle diseases in Japan for diagnosis. Of patients whose myopathologic diagnosis was made at the National Center of Neurology and Psychiatry between January 2009 and August 2019, 199 patients were eligible for inclusion. These patients underwent full investigation for DM-specific autoantibodies (against transcriptional intermediary factor γ, Mi-2, melanoma differentiation-associated gene 5, nuclear matrix protein 2 [NXP-2], and small ubiquitin-like modifier activating enzyme ); however, 17 patients were excluded because their muscle fibers did not express myxovirus resistance protein A, a sensitive and specific marker of DM muscle pathology. Main Outcomes and Measures: Diagnosis of DMSD was based on the absence of a skin rash at the time of muscle biopsy. Results: Of the 182 patients, 93 were women (51%) and 46 were children (25%) (<18 years). Fourteen patients (8%) had DMSD and none were clinically diagnosed with DM. Among the 14 patients with DMSD, 12 (86%) were positive for anti-NXP-2 autoantibodies, while the remaining 2 were positive for anti-transcriptional intermediary factor γ and anti-Mi-2 autoantibodies, respectively. Only 28% of patients (47 of 168) with a skin rash were positive for anti-NXP-2 autoantibodies, indicating a significant association between anti-NXP-2 autoantibodies and DMSD (86% [12 of 14] vs 28% [47 of 168]; P < .001). This association was also supported by multivariable models adjusted for disease duration (odds ratio, 126.47; 95% CI, 11.42-1400.64; P < .001). Conclusions and Relevance: Dermatomyositis sine dermatitis does exist and accounts for 8% of patients with DM confirmed with muscle biopsy. Dermatomyositis sine dermatitis is significantly associated with anti-NXP-2 autoantibodies, which contrasts with anti-MDA5 DM, which is typically clinically amyopathic in presentation. It is essential to distinguish DMSD from other types of myositis because DM-specific therapies that are currently under development, including Janus kinase inhibitors, may be effective for DMSD.

Calreticulin as A Novel Potential Metastasis-Associated Protein in Myxoid Liposarcoma, as Revealed by Two-Dimensional Difference Gel Electrophoresis.

Myxoid liposarcoma (MLS) is a mesenchymal malignancy. To identify innovate seeds for clinical applications, we examined the proteomes of primary tumor tissues from 10 patients with MLS with different statuses of postoperative metastasis. The protein expression profiles of tumor tissues were created, and proteins with differential expression associated with postoperative metastasis were identified by two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. The validation was performed using specific antibodies and in vitro analyses. Using 2D-DIGE, we observed 1726 protein species and identified proteins with unique expression levels in metastatic MLS. We focused on the overexpression of calreticulin in metastatic MLS. The higher expression of calreticulin was confirmed by Western blotting, and gene silencing assays demonstrated that reduced expression of calreticulin inhibited cell growth and invasion. Our findings suggested the important roles of calreticulin in MLS metastasis and supported its potential utility as a prognostic biomarker in MLS. Further investigations of the functional properties of calreticulin and other proteins identified in this study will improve our understanding of the biology of MLS and facilitate novel clinical applications.

Clinical significance of the tail-like pattern in soft-tissue sarcomas on magnetic resonance imaging.

BACKGROUND: An infiltrating abnormal signal around soft-tissue tumors along the fascial, neurovascular, or musculature plane on magnetic resonance imaging (T2-weighted, gadolinium-enhanced T1-weighted, or short-tau inversion recovery) is recognized as the "tail-like pattern". The tail-like pattern was intensively analyzed in myxofibrosarcoma, but not in other sarcomas. We aimed to answer some key questions about the tail-like pattern such as its incidence and effect on oncological outcomes. METHODS: The presence of the tail-like pattern in 114 soft-tissue sarcomas was evaluated on T2-weighted images or gadolinium-enhanced T1-weighted images, or both. We analyzed the incidence of the tail-like pattern in all cases and in specific histological subtypes. We also assessed the clinical backgrounds of the presence of the tail-like pattern and its impact on achieving adequate surgical margins and oncological outcomes, including local recurrence and overall survival. RESULTS: The tail-like pattern was detected in 50% of cases. The tail-like pattern was most common in myxofibrosarcoma and undifferentiated pleomorphic sarcoma, and less common in low-grade sarcomas. Trans-compartmental invasion of the tumor and high-grade malignancy were common clinical backgrounds for the presence of the tail-like pattern. The presence of the tail-like pattern significantly inhibits the achievement of preoperatively planned surgical margins despite planning the margins outside the tail-like pattern area. The tail-like pattern was an independent risk factor for local recurrence. The pattern was not an independent risk factor for worse overall survival, although it was a risk factor in univariate analysis. CONCLUSION: The tail-like pattern is clinically significant in myxofibrosarcomas and other sarcomas with respect to the preoperative evaluation of malignancy by magnetic resonance imaging, and negatively affects successful resection and oncological outcomes. A more sophisticated modality for the evaluation and clinical management of the tail-like pattern is needed in the future.

Preoperative Ultrasonographic Evaluation for Malignancy of Soft-Tissue Sarcoma: A Retrospective Study.

BACKGROUND: Ultrasonography is useful for distinguishing between benign and malignant soft-tissue tumors. However, no study has focused on its usefulness in the differential diagnosis between low-grade and high-grade soft-tissue sarcomas. We conducted a retrospective study to determine the usefulness of the parameters of ultrasonograph and to develop a practical scoring system for distinguishing between high-grade and low-grade sarcomas. METHODS: Twenty-two cases of low-grade and 43 cases of high-grade malignant soft-tissue sarcoma were enrolled. Ultrasonography parameters including the longest diameter, depth of the tumor, echogenicity, tumor margin, and vascularity defined according to Giovagnorio's criteria were analyzed as factors to distinguish between the two types of sarcoma. Significant factors were entered into a multivariate model to define the scores for distinction according to the odds ratio. The usefulness of the score was analyzed via receiver operating characteristic analyses. RESULTS: In univariate analysis, tumor margin, echogenicity, and vascularity were significantly different between low- and high-grade sarcomas. In the multivariate regression model, the odds ratio for high-grade vs. low-grade sarcoma was 8.8 for tumor margin, 69 for echogenicity, and 8.3 for vascularity. Scores for the risk factors were defined as follows: 1, ill-defined margin; 2, hypoechoic echogenicity; and 1, type IV in Giovagnorio's criteria. The sum of each score was confirmed by receiver operating characteristic analysis. The area under the curve was 0.95, with a cut-off score of 3, indicating that the scoring system was useful. CONCLUSION: The ultrasonography parameters of tumor margin, echogenicity, and vascularity are useful for distinguishing between low- and high-grade sarcomas.

Mean Platelet Volume Is Associated with Early Neurological Deterioration in Patients with Branch Atheromatous Disease: Involvement of Platelet Activation.

BACKGROUND: The most attentive clinical problem in patients with branch atheromatous disease (BAD) is early neurological deterioration (END). Although the platelet activation (PA) is involved in pathogenesis, the relationship between PA and END has remained unclear. We investigated clinical data including mean platelet volume (MPV, fL) as a marker for PA to identify clinically useful biomarkers for END. METHODS: A total of 64 patients with BAD were investigated retrospectively, and divided into 2 groups based on whether neurologic symptoms deteriorated or not: BAD with and without END (END and non-END). The END was defined as patients with point increase of 1 or greater in the National Institutes of Health Stroke Scale (NIHSS); non-END was defined as those without such increase. Clinical features such as NIHSS, modified Rankin scale (mRS), laboratory data including MPV, lesion size (LS, mm) on admission, and treatments were compared between the 2 groups. RESULTS: Of 64 patients, 17 cases had an END. The median values of NIHSS, mRS, MPV, and LS on admission were significantly greater in END than in non-END (P < .05, respectively). There was no correlation of MPV with NIHSS, mRS and LS, respectively. The median values of MPV were significantly higher in END than in non-END and control (P < .05, respectively). A receiver operating characteristic curve indicated a value of 10.1 as cutoff level for MPV to discriminate between END and non-END. CONCLUSIONS: High MPV values on admission may be an independent biomarker for END. Physicians should pay more careful attention to END in BAD showing MPV values higher than 10.1 on admission.

Preoperative evaluation of intraoperative blood loss during malignant soft tissue tumor resection by ultrasonography.

BACKGROUND: Preoperative evaluation of the risk of surgery-related blood loss in malignant soft tissue tumor resection is difficult because of wide variations in histological subtype, malignancy, location, and size. Ultrasonography is useful for the evaluation of blood flow around a soft tissue tumor and has the potential to preoperatively estimate intraoperative blood loss in tumor resection. To date, there has been no report regarding blood loss evaluation using ultrasonography in this field. PATIENTS AND METHODS: The usefulness of information obtained by ultrasonography, including tumor size, vessel density in the tumor, and blood flow volume in the vessels, was analyzed for the prediction of intraoperative blood loss in malignant soft tissue tumor resection. RESULTS: Vessel density in the tumor and blood flow in the vessels were identified as independent risk factors for blood loss. Using these factors, a new index for the prediction of blood loss was established. Receiver operating characteristic analyses revealed a high area under the curve value (0.80), confirming the accuracy of the index for the prediction of blood loss. CONCLUSION: Ultrasonography is a useful modality for predicting intraoperative blood loss in malignant soft tissue tumor surgery.

Vertebral Artery Stump Syndrome.

Carotid stump syndrome is a well-documented embolic source for ischemic stroke. However, few cases have been reported of a similar condition - termed vertebral artery stump syndrome - which affects the posterior circulation after vertebral artery origin occlusion. We herein report a case of infarction of the right superior cerebellar artery and left posterior inferior cerebellar artery territories due to vertebral artery stump syndrome. In this interesting case, a turbulent flow at the distal side of the vertebral artery occlusion was captured on ultrasonography, and was identified as the probable mechanism of vertebral artery stump syndrome.

Differential diagnosis between benign and malignant soft tissue tumors utilizing ultrasound parameters.

PURPOSE: Preoperative discrimination between benign and malignant soft tissue tumors is critical for the prevention of excess application of magnetic resonance imaging and biopsy as well as unplanned resection. Although ultrasound, including power Doppler imaging, is an easy, noninvasive, and cost-effective modality for screening soft tissue tumors, few studies have investigated reliable discrimination between benign and malignant soft tissue tumors. METHODS: To establish a modality for discrimination between benign and malignant soft tissue tumors using ultrasound, we extracted the significant risk factors for malignancy based on ultrasound information from 40 malignant and 56 benign pathologically diagnosed soft tissue tumors and established a scoring system based on these risk factors. RESULTS: The maximum size, tumor margin, and vascularity evaluated using ultrasound were extracted as significant risk factors. Using the odds ratio from a multivariate regression model, a scoring system was established. Receiver operating characteristic analyses revealed a high area under the curve value (0.85), confirming the accuracy of the scoring system. CONCLUSION: Ultrasound is a useful modality for establishing the differential diagnosis between benign and malignant soft tissue tumors.

Development of Stemness in Cancer Cell Lines Resistant to the Anticancer Effects of Zoledronic Acid.

BACKGROUND: Drug resistance is closely related to cancer cell stemness, that is acquired along with resistance to various anticancer agents. However, this has not been investigated as a potential mechanism underlying cancer cell resistance to zoledronate, that is used to suppress bone metastasis. MATERIALS AND METHODS: Zoledronate-resistant A549 lung cancer and MG63 osteosarcoma cell lines were established by repeated treatment with sub-lethal concentrations of zoledronate. Expression levels of the stem cell marker NANOG, cMYC, octamer-binding transcription factor 4, and sex-determining region Y-box 2 were evaluated and sphere formation was compared between parental and resistant cell lines. Tumourigenicity was assessed in vivo. RESULTS: Stem cell marker expression was up-regulated and sphere formation was enhanced in resistant compared to parental cells and showed greater tumour formation capacity in mice. CONCLUSION: Repeated treatment of malignant tumour cell lines with zoledronate, induces the development of drug resistance and stemness.

D-dimer Level Changes During Systemic Chemotherapy Can Predict Prognosis of High-grade Musculoskeletal Sarcoma Patients.

BACKGROUND/AIM: Plasma D-dimer levels have been known to be associated with tumor progression; we, therefore, investigated whether the D-dimer levels during preoperative systemic chemotherapy can be prognostic indicators in patients with high-grade musculoskeletal sarcoma. PATIENTS AND METHODS: We investigated 28 cases of high-grade sarcomas, and evaluated the utility of D-dimer levels for preoperative evaluation of the effects of systemic chemotherapy. RESULTS: Among the candidate parameters determined based on D-dimer levels at several time-points of neoadjuvant chemotherapy and several oncological outcomes, the plasma D-dimer level completion of the second course of chemotherapy and the ratio of plasma D-dimer levels at completion of preoperative chemotherapy to the level of plasma D-dimer on referral, could significantly predict patient prognosis (p=0.049 and p=0.02, respectively). CONCLUSION: D-dimer level changes could be a helpful marker for preoperative evaluation of the effect of systemic chemotherapy in terms of prognosis prediction in high-grade musculoskeletal sarcoma patients.

[A case of cerebellar brainstem form of progressive multifocal leukoencephalopathy associated with idiopathic CD4+ lymphocytopenia].

A 77-year-old woman presented with a 6-month history of slowly progressive cerebellar ataxia. T2-weighted MRI showed high signal intensity in the left upper dorsal pons and bilateral middle cerebellar peduncles. JC virus (JCV) DNA was detected in cerebrospinal fluid (CSF). The patient had no HIV infection, collagen disease, or a history of immunosuppressive treatment, but she was found to have CD4+ lymphocytopenia. We made a diagnosis of cerebellar brainstem form of progressive multifocal leukoencephalopathy (PML) presenting as cerebellar ataxia, which was presumably associated with idiopathic CD4+ lymphocytopenia. Following the treatment with mefloquine, the patient slightly improved clinically and JCV-DNA became negative in CSF.

Analysis of the risk factors for febrile neutropenia in patients with bone and soft tissue sarcoma.

BACKGROUND: Although systemic chemotherapy is inevitably selected as the modality of treatment for high-grade bone and soft tissue sarcoma (BSTS), limited information is available regarding febrile neutropenia (FN). PATIENTS AND METHODS: FN incidence, blood culture results and risk factors were analyzed in 35 patients with high-grade BSTS. RESULTS: FN occurred in 51% of the patients and 24% of the courses of systemic chemotherapy. Culture results indicated pathogen in only 33.3% of patients who had FN. Methicillin-resistant Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus were frequently observed. Body weight of less than 61.0 kg and a tumor originating from the bone in a patient-based analysis, and serum albumin <4.2 g/dl and having a source of infection in a course-based analysis were independent risk factors for FN. CONCLUSION: Considerably high risks for FN during chemotherapy for BSTS were confirmed. The risk factors presented here appeared to differ from those in previously reported guidelines.

Unplanned resection of a soft tissue sarcoma: clinical characteristics and impact on oncological and functional outcomes.

BACKGROUND: Over the past three decades, several studies have reported worse outcomes with unplanned resection for malignant soft tissue tumors. However, the impact of these studies on preventing unnecessary unplanned resection remains unknown. METHODS: In a retrospective survey on the treatment of soft tissue sarcomas, we compared cases of unplanned resection with cases of planned resection in terms of the properties of unplanned resection and the oncological and functional outcomes. For the unplanned resection cases, an additional wide resection was performed. RESULTS: Of 92 cases, unplanned resection was performed in 24 (26 %). Small or subcutaneous tumors were significantly more frequently subjected to unplanned resection. In 17 of 24 unplanned resection cases, residual tumors (70.8 %) were noted. Plastic surgery was more frequently needed for unplanned resection cases. There was no significant difference between the unplanned resection and control cases with regard to oncological outcome. However, as to local recurrence and overall survival, the events occurred only in the cases with residual tumors in the additional wide resection specimen in the unplanned resection group. There was no significant difference in functional evaluation, except for emotional acceptance, which had a better score in the unplanned resection group. CONCLUSIONS: Despite repeated cautions regarding unplanned resection in terms of its inadequate procedure which contradicts the principles of soft tissue sarcoma treatment, unplanned resections are still frequently performed. Perhaps the small size and subcutaneous location of the sarcomas in the unplanned resection group did not evoke the probability of malignancy for the surgeons who initially managed them. Even though an additional wide resection was performed, a residual tumor would lead to a worse outcome. An effective awareness program to avoid unnecessary unplanned resections for soft tissue sarcoma should be considered.

D-dimer levels in the differential diagnosis between lipoma and well-differentiated liposarcoma.

BACKGROUND: Lipoma and well-differentiated liposarcoma (WDLS) are two representative lipogenic soft tissue tumors that have similar clinical, radiological, and pathological characteristics. Accordingly, it is difficult to distinguish these tumors preoperatively. Plasma D-dimer levels are associated with the status of tumor progression, and we hypothesized that D-dimer levels could contribute to differential diagnosis. The D-dimer levels of these two entities have not yet been reported. PATIENTS AND METHODS: We investigated 43 cases of lipoma and 14 cases of WDLS. We evaluated the utility of D-dimer levels and other clinicopathological factors for preoperative differential diagnosis between the two entities. RESULTS: Receiver operating characteristic analysis revealed that the D-dimer level may contribute to differential diagnosis (area under the curve=0.73). Univariate and multivariate models demonstrated that plasma D-dimer levels (p=0.001 (univariate), and p=0.006 (multivariate)) and lower extremity location (p=0.006 (univariate), and p=0.03 (multivariate)) were independent risk factors for WDLS. CONCLUSION: The D-dimer level may be a helpful marker for preoperative differential diagnosis between lipoma and WDLS.

[Cross-reactivity of Instant-View M-1 for detection of benzodiazepine-related drugs and their metabolites in urine].

Immunoassays are useful methods for the determination of regulated drugs in clinical and forensic laboratories. Although the Instant-View M-1 (IV M-1) immunoassay kit is frequently used to screen drugs in laboratories in Japan, basic information about the IV M-1 such as its specificity and reactivity is not available. In this study, we determined the specificity and cross-reactivity of IV M-1 for the detection of benzodiazepine-related drugs and their metabolites in urine. The IV M-1 could detect triazolobenzodiazepines such as triazolam in urine at concentrations > or = 300 ng/mL. However, thienodiazepines such as etizolam could not be detected because of lack of cross reactivity. A correlation was observed between the structure of the metabolites and the reactivity of the kit; 4-hydroxy metabolites of alprazolam and triazolam were detectable, whereas a-hydroxy metabolites were not. Furthermore, 7-amino metabolites such as nitrazepam could not be detected at any concentration, including high concentrations. The specificity and reactivity of various kits used for detection of drugs in urine are different. Therefore, it is necessary to consider the basic features of the kit used while assessing the results obtained.

Lung cancer cell line sensitivity to Zoledronic acid is BAX-dependent.

BACKGROUND: Zoledronate (Zol), an anti-osteoclastic and anticancer drug, is used to control bone metastasis in several cancer types, including non-small cell lung cancer (NSCLC). However, the mechanisms behind Zol resistance in NSCLC are unclear. MATERIALS AND METHODS: Zol-resistant cell lines were developed by repeated treatment of A549 and H1650 NSCLC cell lines with Zol. We measured cell proliferation and apoptosis following Zol treatment and also examined the BCL2 superfamily expression. RNAi was used to confirm the role of key molecules in development of resistance. RESULTS: Repeated Zol treatment engendered resistance, in which apoptosis induction was attenuated. From the BCL2 superfamily, BAX was commonly down-regulated in resistant cells, and silencing of BAX in parental cell lines also induced drug resistance. CONCLUSION: Repeated treatment of NSCLC cell lines with Zol leads to drug resistance, which is in part due to BAX down-regulation.

Proteomic approach toward personalized sarcoma treatment: lessons from prognostic biomarker discovery in gastrointestinal stromal tumor.

Sarcomas range from curable tumors to those causing death via metastasis and recurrence. Thus, there is an urgent need for biomarker identification in order to assess the degree of malignancy, predict prognosis, and evaluate possible therapies. Various proteomic approaches and different clinical materials have been used to this end, and candidate biomarkers have been reported for the different types of sarcomas. However, the sample size used in these biomarker studies was generally insufficient, and thus far, no biomarker has been proved useful in clinics. Given that sarcomas are rare, biomarker validation in this setting is more challenging than in other malignancies. In gastrointestinal stromal tumor, adjuvant therapy has proven to be effective. However, only 40% patients experience metastasis after curative surgery alone, and the rest of the patients may not need adjuvant therapy. Using a proteomic approach, we identified pfetin (potassium channel tetramerization domain containing 12, KCTD 12) as a novel prognostic biomarker for sarcoma, and immunohistochemically confirmed its clinical usefulness by a multiinstitutional validation study. Here, we describe our experience and discuss the critical points in the discovery of this biomarker.

[Anti-Ma2, anti-NMDA-receptor and anti-GluRε2 limbic encephalitis with testicular seminoma: short-term memory disturbance].

A 36-year-old man presented with cognitive impairment and disturbance of short-term memory functions with character change. Cerebrospinal fluid analysis revealed no abnormalities; however, brain MRI revealed high-signal intensity from bilateral hippocampus lesions on fluid attenuated inversion recovery (FLAIR) images and T(2) weighted images. The 18F-fluorodeoxyglucose PET demonstrated high glucose uptake in the bilateral hippocampus lesions. He was diagnosed as limbic encephalitis, and was administered high-dose intravenous methylprednisolone and immune adsorption plasma therapy followed by intravenous immunoglobulin therapy. MRI abnormalities improved after treatment but recent memory disturbance remained. Ma2 antibody, NMDA-receptor antibody, and GluRε2 antibody were positive. Eleven months atter the onset of disease, the tumor was identified in left testicle by ultrasound and removed the tumor. The pathological findings were seminoma. We experienced a case of paraneoplastic limbic encephalitis associated with seminoma with short-term memory disturbance. The occurrence of paraneoplastic limbic encephalitis with antibodies against cell membrane (NMDA-receptor antibody and GluRε2 antibody) and intracellular (Ma2 antibody) is rare even in the literature.