Ken Morii

Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia

Germ-cell tumors of the central nervous system generally develop in the midline, but the tumors can also occur in the basal ganglia and/or thalamus. However, MR images have rarely been documented in the early stage of the tumor in these regions. We retrospectively reviewed MR images obtained on admission and approximately 3 years earlier in two patients with germinoma in the basal ganglia, and compared them with CT. In addition to hyperdensity on CT, both hyperintensity on T1-weighted images and a small hyperintense lesion on T2-weighted images were commonly seen in the basal ganglia. These findings may be early MRI signs of germinoma in this region, and the earliest and most characteristic diagnostic feature on MRI was atrophy of the basal ganglia, which was recognizable before development of hemiparesis.

Characteristic features of malignant lymphoma with central nervous system involvement.

BACKGROUND Cerebral lymphoma is becoming increasingly common. METHODS We reviewed the records of all our patients with non-Hodgkins lymphoma (NHL) seen from April 1987 to August 1996 in our institute. Our analysis of these patients with lymphomatous central nervous system (CNS) involvement documents the clinical features, histology, and prognostic factors in CNS lymphoma. RESULTS A total of 351 cases of NHL were treated in our institute. CNS lymphoma was found in 58 of 351 (16.5%) patients in our series. Forty-nine of 58 (84.5%) patients with CNS involvement also had systemic disease. Primary CNS lymphomas were detected in nine patients. Leptomeningeal infiltration was seen in 31 of 58 patients, whereas intracerebral infiltration was detected in 28 patients. Initial symptoms of CNS involvement included severe headache, muscle weakness, and other neurological signs. Malignant cells were detected in 32 of 132 studies in the cerebrospinal fluid examination. In the nine patients with primary CNS lymphoma, the median survival time was 16.5 months (range, 4-28 months). The overall median survival of the 58 CNS lymphoma patients was only 13.4 months (range, 1 to 32 months). CONCLUSIONS Because prophylactic treatment was only successful in systemically well-controlled patients, control of systemic lymphoma seems to be of great importance.

Cranial base chordoma – long term outcome and review of the literature

SummaryBackground. The purpose of this study is to clarify the latest long-term therapeutic result for cranial base chordomas. We are seeking an improvement of long term therapeutic outcome through a review of cranial base chordomas treated in our institute and of the published literature in the era of multimodality therapy. Materials and methods. We retrospectively reviewed 13 consecutive patients with cranial base chordoma, including ten males and three females with mean age of 39.5 years (range 5–76 years). Results. The method of initial treatment included surgery and post-operative conventional local irradiation (IR) in 9 patients, surgery and IR followed by post-operative stereotactic radiosurgery (SRS) in 2 patients, surgery as well as SRS in one patients, and surgery as well as SRS followed by IR in one patient. Subtotal removal (over 95%) was accomplished in eight patients. The mean follow-up period after completion of surgery and initial radiotherapy was 122 months (median 108 months). According to the Kaplan-Meier estimate method, the 5-year survival rate was 82.5%: 11 out of 13 patients survived longer than 5 years and five patients survived longer than 10 years. With a longer follow-up period than the previous reports, our series has provided a 5-year survival rate comparable to that of proton beam therapy. Although our series indicates a favourable outcome, surgical resection followed by IR or SRS failed to control tumour growth in five patients. Conclusions. IR and/or SRS provided results comparable with proton beam or heavy particle therapy in our series of cranial base chordomas probably because the radiation field must have covered the target of the tumour volume sufficiently, and reduction of gross tumour volume reduced the target size for radiotherapy. Pursuit of further effective combinations of IR and stereotactic radiotherapy (SRS, proton beam, heavy particle) after tangible resection, especially for residual and recurrent lesions, will be an acceptable framework to achieve a better therapeutic outcome for cranial base chordomas than at present.

The generation of anti-tumoral cells using dendritic cells from the peripheral blood of patients with malignant brain tumors

Abstract Dendritic cells (DCs) can be the principal initiators of antigen-specific immune responses. We analyzed the in vitro-responses against brain tumor cells using DCs from the peripheral blood of patients with brain tumors. Peripheral blood mononuclear cells (PBMC) were obtained from 19 patients with malignant brain tumors: 12 metastatic brain tumors of lung adenocarcinoma, 7 high-grade astrocytomas. PBMC were cultured with 100 ng/ml of GM-CSF and 10 ng/ml of IL-4 for 5–7 days in order to produce mature DCs. The autologous tumor lysate (5 mg/ml, containing 1 × 106 cells) was then added to the cultured DCs. Using the DCs generated by these treatments, we assessed the changes that occurred in their immune responses against brain tumor via 51Cr-release and lymphocyte proliferation assays. We found that the matured DCs displayed the typical surface phenotype of CD3+, CD45+, CD80+ and CD86+. After the pulsation treatment with tumor lysate, DCs were found to have strong cytotoxic T lymphocyte activity, showing 42.5 ± 12.7% killing of autologous tumor cells. We also found an enhancement of allogeneic T cell proliferation after pulsing the DC with tumor lysate. These data support the efficacy of DC-based immunotherapy for patients with malignant brain tumors.

cDNA cloning and mRNA expression analysis of the human neuronatin: High level expression in human pituitary gland and pituitary adenomas

The authors cloned the nearly complete cDNA of human neuronatin with the aid of an expressed sequence tag (EST) database, and analyzed its expression in various human tissues by Northern blot analysis. The nucleotide and deduced amino acid sequences of the human neuronatin showed a high similarity to those of rodents. The Northern blot analysis revealed that the human neuronatin message was expressed predominantly in the fetal brain in the brain-specific manner, but only faintly in the adult brain. Among the various adult human tissues examined, the anterior pituitary gland was shown to be the only place where the neuronatin mRNA was strongly expressed. Intense neuronatin expression was also observed in several human pituitary adenomas, including ACTH-producing, GH-producing, and nonfunctioning adenomas, but hardly detected in other brain tumors.

Structure and chromosome assignment of human S100 α and β subunit genes

The human S-100 α and β subunit genes were isolated from human genomic DNA library. The restriction endonuclease mapping and DNA sequencing analysis revealed that both subunit genes consisted of three exons and two introns. Two Ca 2+ -binding domains were independently encoded by exon 2 and exon 3. Spot-blot hybridization analysis with flow-sorted chromosomes showed that human α and β subunit genes were assigned to chromosome 1 and chromosome 21, respectively.

Ictal focal hyperperfusion demonstrated by arterial spin-labeling perfusion MRI in partial epilepsy status

Dear Sir, Pulsed arterial spin-labeling (PASL) perfusion magnetic resonance imaging (MRI) is a noninvasive method of measuring regional cerebral blood flow (rCBF) without contrast medium and has been routinely applied in cerebrovascular diseases as a cerebral perfusion measurement [1]. In partial epilepsy, ictal cortical hyperperfusion is believed to be a useful marker for identifying epileptogenic zone, and singlephoton emission computed tomography (SPECT) is commonly used for evaluating differences between interictal and ictal cerebral perfusions. Few reports have described hemodynamic changes detected by PASL in interictal [2–4] and peri-ictal states [5, 6]. Recently, we had a rare opportunity to conduct PASL imaging and also diffusion-weighted imaging (DWI) of a patient both in partial epilepsy status (PES) and during the interictal state. Our patient, a 25-year-old man with normal development and no neurological deficits, had sometimes experienced a short-term feeling of visual distortion in the left half of his visual field since age 20 years. He had his first generalized convulsion and was admitted to our hospital. One week later, he complained of frequent occurrences of blurred vision or elementary visual hallucinations like flickering lights in the left half of his visual field, sometimes accompanied by rotating his head to the left. An electroencephalogram (EEG) recorded three ictal events during 30 min. The ictal pattern showed rhythmic bursting epileptic activities arising from the right occipital region, gradually reaching high amplitude and spreading to surrounding areas within approximately 2 min and then finished without generalizing (Fig. 1a). He presented with seizures at a frequency of five to six times per hour in the daytime, so-called PES. After starting carbamazepine administration, the seizures gradually decreased and had disappeared 3 days later. He experienced left visual field loss for a few days even after the seizures had disappeared but ultimately recovered from this deficit. MRI scans were performed on a 3 T MRI system (MAGNETOM Verio; Siemens AG, Munich, Germany) on the first day that frequent seizures occurred (Fig. 1b–d) and 1 week after the seizures had completely disappeared (Fig. 2). Cortical evaluation by reversed Short T1 inversion recovery (STIR) imaging indicated an anomaly consistent with a cortical malformation in the right medial occipital region (Fig. 1b). PASL was performed with a pulsed sequence, using QUIPSII perfusion mode [7] and the following parameters: nine slices; FOV read, 300.0 mm; FOV phase, 206.0; slice thickness, 10.0 mm; TE/TR/ Tl1/Tl2020/3,500/800/2,200 ms. PASL results were coregistered with FLAIR images. While focal hyperintense signals on DWI were observed in the limited area of the M. Oishi :Y. Fujii Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Japan

Brain metastasis in patients with sarcoma: An analysis of histological subtypes, clinical characteristics, and outcomes

BACKGROUND The clinical characteristics of brain metastasis from sarcoma are not well known. We examined the incidence and the characteristics of brain metastasis in patients with sarcomas. METHODS All sarcoma patients treated at our institution from 1975 to 1998 were reviewed for brain metastasis. Diagnosis of the primary tumor was confirmed histologically, and brain metastasis was confirmed using computed tomographic (CT) brain scan. RESULTS Brain metastasis was found in 27 (5.6%) of 480 patients with systemic sarcoma (7.2% soft part sarcoma, 3.5% bone sarcoma, 15.1% distant metastasis). Of these 27 sarcoma patients with brain metastases, lung metastasis occurred in 16 patients (59.3%). Out of 10 patients surgically treated, 8 patients survived more than 16 months. Median survival period after craniotomy was 25.4 months. CONCLUSIONS We recommend aggressive treatment for those patients with brain metastases whose performance scores are over 70.

Results of Treatment of 112 Cases of Primary CNS Lymphoma

BACKGROUND Chemotherapy with or without radiotherapy is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, either as a single agent or in combination with other drugs. Due to the lack of well-conducted randomized trials, the optimal treatment remains controversial. Available retrospective studies are difficult to discuss, however, some common themes can be found. METHODS One hundred and twelve patients with PCNSL were treated with four different regimens over a period of 24 years. Treatment regimens were: whole-brain irradiation (WBI) alone, MVP (MTX, vincristine, and predonisolone), ProMACE-MOPP hybrid (cyclophosphamide, pirarubicin, etoposide, vincristine, procarbazine, prednisone, and MTX) and R-MTX (rituximab, MTX, pirarubicin, procarbazine, and prednisone) combined-modality therapy. RESULTS The median failure-free survival was 16 months, and the median overall survival (OS) was 24 months. The 2- and 5-year actuarial probability of survival was 52.4 +/- 4.8% [95% confidence intervals (CI)] and 30.2 +/- 4.8% (95% CI), respectively. The ProMACE-MOPP protocol, Karnofsky performance status (KPS), MTX dose and WBI were associated with good OS by univariate models. By multivariate analysis, MTX dose, WBI dose, and its square dose were significantly associated with good OS. 20-30 Gy WB, and 500 mg/m(2) of MTX dose appeared important determinants of OS. CONCLUSIONS A modest dose of MTX (500 mg/m(2)) followed by reduced-dose WBI for patients who respond appears a feasible treatment approach that minimizes serious toxicity.

Structure and expression of human and rat D2 dopamine receptor genes

D2 dopamine receptor may be related with the pathogenesis of Parkinsons disease and schizophrenia. Furthermore, the antipsychotic drugs have high affinity for D2 dopamine receptor. We carried out the cloning of the genomic DNA for human D2 dopamine receptor and clarified the structure of this gene. Our isolated gene spans about 15 kbp and consists of seven exons interrupted by six introns. However, putative first exon was not yet identified. Spot blot hybridization analysis of cell sorter fractionated human chromosomal DNA with D2 receptor genomic DNA revealed the localization of this gene in the chromosome 11 fraction. We analyzed human genomic DNA by Southern blot hybridization with D2 dopamine receptor genomic DNA as a probe, but so far we could not find RFLP. Northern blot analyses of brain RNA of several animals and rat brain RNA after various treatments were carried out. Developmental changes of D2 dopamine receptor mRNA were observed in the rat brains.