Fluctuations in Upper and Lower Body Movement during Walking in Normal Pressure Hydrocephalus and Parkinson's Disease Assessed by Motion Capture with a Smartphone Application, TDPT-GT.

We aimed to capture the fluctuations in the dynamics of body positions and find the characteristics of them in patients with idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease (PD). With the motion-capture application (TDPT-GT) generating 30 Hz coordinates at 27 points on the body, walking in a circle 1 m in diameter was recorded for 23 of iNPH, 23 of PD, and 92 controls. For 128 frames of calculated distances from the navel to the other points, after the Fourier transforms, the slopes (the representatives of fractality) were obtained from the graph plotting the power spectral density against the frequency in log-log coordinates. Differences in the average slopes were tested by one-way ANOVA and multiple comparisons between every two groups. A decrease in the absolute slope value indicates a departure from the 1/f noise characteristic observed in healthy variations. Significant differences in the patient groups and controls were found in all body positions, where patients always showed smaller absolute values. Our system could measure the whole body's movement and temporal variations during walking. The impaired fluctuations of body movement in the upper and lower body may contribute to gait and balance disorders in patients.

Artificial Intelligence Distinguishes Pathological Gait: The Analysis of Markerless Motion Capture Gait Data Acquired by an iOS Application (TDPT-GT).

Distinguishing pathological gait is challenging in neurology because of the difficulty of capturing total body movement and its analysis. We aimed to obtain a convenient recording with an iPhone and establish an algorithm based on deep learning. From May 2021 to November 2022 at Yamagata University Hospital, Shiga University, and Takahata Town, patients with idiopathic normal pressure hydrocephalus (n = 48), Parkinson's disease (n = 21), and other neuromuscular diseases (n = 45) comprised the pathological gait group (n = 114), and the control group consisted of 160 healthy volunteers. iPhone application TDPT-GT captured the subjects walking in a circular path of about 1 meter in diameter, a markerless motion capture system, with an iPhone camera, which generated the three-axis 30 frames per second (fps) relative coordinates of 27 body points. A light gradient boosting machine (Light GBM) with stratified k-fold cross-validation (k = 5) was applied for gait collection for about 1 min per person. The median ability model tested 200 frames of each person's data for its distinction capability, which resulted in the area under a curve of 0.719. The pathological gait captured by the iPhone could be distinguished by artificial intelligence.

Quantitative Gait Feature Assessment on Two-Dimensional Body Axis Projection Planes Converted from Three-Dimensional Coordinates Estimated with a Deep Learning Smartphone App.

To assess pathological gaits quantitatively, three-dimensional coordinates estimated with a deep learning model were converted into body axis plane projections. First, 15 healthy volunteers performed four gait patterns; that is, normal, shuffling, short-stepped, and wide-based gaits, with the Three-Dimensional Pose Tracker for Gait Test (TDPT-GT) application. Second, gaits of 47 patients with idiopathic normal pressure hydrocephalus (iNPH) and 92 healthy elderly individuals in the Takahata cohort were assessed with the TDPT-GT. Two-dimensional relative coordinates were calculated from the three-dimensional coordinates by projecting the sagittal, coronal, and axial planes. Indices of the two-dimensional relative coordinates associated with a pathological gait were comprehensively explored. The candidate indices for the shuffling gait were the angle range of the hip joint < 30° and relative vertical amplitude of the heel < 0.1 on the sagittal projection plane. For the short-stepped gait, the angle range of the knee joint < 45° on the sagittal projection plane was a candidate index. The candidate index for the wide-based gait was the leg outward shift > 0.1 on the axial projection plane. In conclusion, the two-dimensional coordinates on the body axis projection planes calculated from the 3D relative coordinates estimated by the TDPT-GT application enabled the quantification of pathological gait features.

Cervical ganglioneuroma arising from the dorsal root ganglion: illustrative case.

BACKGROUND: Ganglioneuroma is a benign and well-differentiated tumor derived from neural crest cells, which occurs infrequently, with most patients being female and adolescents. While predilection sites are the posterior mediastinum and retroperitoneal cavity, ganglioneuroma originating from the dorsal root ganglion is very rare. Here the authors report a case with C2 dorsal root ganglion-derived ganglioneuroma with some literature review. OBSERVATIONS: A 45-year-old male patient complained of persistent right-side throbbing occipital headache for more than a year. Magnetic resonance imaging (MRI) of the cervical spine revealed a dumbbell-shaped intradural extramedullary tumor from the C2 posterior surface of the odontoid to right C1-2 intervertebral foramen with high T2- and low T1-weighted signal intensities. The tumor displayed homogeneous contrast enhancement by MRI. The authors suspected schwannoma and performed a tumorectomy for both diagnosis and treatment purposes. Intraoperative findings showed that the tumor originated from the dorsal root ganglion, and pathological examination revealed ganglioneuroma. Immediately after the tumorectomy, the throbbing occipital headache disappeared and the patient was discharged from the hospital without major complications. LESSONS: Although ganglioneuroma derived from the dorsal root ganglion is very rare, a differential diagnosis of the ganglioneuroma should be made, when schwannoma is suspected.

Current Trends in the Surgical Management of Intramedullary Tumors: A Multicenter Study of 1,033 Patients by the Neurospinal Society of Japan.

OBJECTIVE: We performed a retrospective observational study to demonstrate the surgical risks and long-term prognoses of intramedullary tumors in Japan using a multicenter registry authorized by the Neurospinal Society of Japan. METHODS: Data from 1,033 consecutive patients with intramedullary tumors, treated between 2009 and 2020, were collected from 58 centers. Patients with spinal lipomas or myxopapillary ependymomas were excluded. Patient characteristics, clinical presentations, imaging characteristics, treatments, and outcomes were analyzed. The modified McCormick scale was used to classify functional status. Survival was described using Kaplan-Meier curves, and multivariable logistic regression analyses were performed. RESULTS: The mean age of the patients was 48.4 years. Data of 361 ependymomas, 196 hemangioblastomas, 168 astrocytic tumors, 160 cavernous malformations, and the remaining 126 cases including subependymomas, metastases, schwannomas, capillary hemangiomas, and intravascular B-cell lymphomas were analyzed. Twenty-two patients were undiagnosed. The mean follow-up duration was 46.1 ± 38.5 months. Gross total tumor removal was achieved in 672 tumors (65.1%). On the modified McCormick scale, 234 patients (22.7%) had worse postoperative grades at the time of discharge. However, neurological status gradually improved. At 6 months postoperatively, 251 (27.5%), 500 (54.9%), and 160 patients (17.6%) had improved, unchanged, and worsened grades, respectively. Preoperative functional status, gross total tumor removal, and histopathological type were significantly associated with mortality and functional outcomes. CONCLUSION: Our findings demonstrate better postoperative functional outcomes in patients with fewer preoperative neurological deficits. Degree of resection, postoperative treatments, and prognoses are closely related to the histology of intramedullary tumors.

Development of Smartphone Application for Markerless Three-Dimensional Motion Capture Based on Deep Learning Model.

To quantitatively assess pathological gait, we developed a novel smartphone application for full-body human motion tracking in real time from markerless video-based images using a smartphone monocular camera and deep learning. As training data for deep learning, the original three-dimensional (3D) dataset comprising more than 1 million captured images from the 3D motion of 90 humanoid characters and the two-dimensional dataset of COCO 2017 were prepared. The 3D heatmap offset data consisting of 28 × 28 × 28 blocks with three red-green-blue colors at the 24 key points of the entire body motion were learned using the convolutional neural network, modified ResNet34. At each key point, the hottest spot deviating from the center of the cell was learned using the tanh function. Our new iOS application could detect the relative tri-axial coordinates of the 24 whole-body key points centered on the navel in real time without any markers for motion capture. By using the relative coordinates, the 3D angles of the neck, lumbar, bilateral hip, knee, and ankle joints were estimated. Any human motion could be quantitatively and easily assessed using a new smartphone application named Three-Dimensional Pose Tracker for Gait Test (TDPT-GT) without any body markers or multipoint cameras.

Description of the Diversity in Surgical Indication and Surgical Strategies for Primary Spinal Cord Tumors: A Nationwide Survey by the Neurospinal Society of Japan.

OBJECTIVE: To assess the current management of primary spinal cord tumors (PSCTs) and determine whether and to what extent there are differences in surgical strategies for PSCTs. METHODS: The Neurospinal Society of Japan conducted a survey between April 1 and 30, 2021. Certified spine surgeons were requested for information on the frequency of surgeries in 2020 and the surgical strategies adopted for each PSCTs. The following tumor histologies were focused: schwannoma, meningioma, and cauda equina tumor as extramedullary tumors; and ependymoma, hemangioblastoma, astrocytoma, and cavernoma as intramedullary tumors. The participants were divided according to their response as follows: experts, who had experienced ≥ 100 surgeries for PSCTs, and nonexperts. RESULTS: Among 308 participants (63%), 35 (11%) were experts. The total number of PSCTs in 2020 was 802 of which 564 tumors were extramedullary and 223 were intramedullary. Schwannoma accounted for 53% of the extramedullary tumors, and ependymoma accounted for 39% of the intramedullary tumors. Surgical strategies significantly differed among both the experts and nonexperts groups. Some discrepancies in the adopted surgical strategies were observed between groups. Some of the nonexperts, and none of the experts, ruled out surgery for schwannomas (Eden type 4), astrocytomas, or cavernomas. Five nonexperts (2.2%), and none of the experts, resected the entire dura for meningiomas. CONCLUSION: A nationwide survey revealed that a sufficient consensus did not exist regarding surgical strategies for PSCTs. A disease-specific registry for PSCTs is necessary in academic societies.

[Lumbar Interbody Fusion:How to Achieve Reliable Bone Fusion?]

The goal of surgery for degenerative spine disease is to decompress nerves; however, extensive spinal decompression may compromise spinal stability. Therefore, spinal fusion surgery is performed to immediately stabilize such anatomical disruption during a short hospital stay and to allow quick recuperation. Recently, implants such as pedicle screws and intervertebral cages have been regularly used in lumbar fusion surgery. These implants are used to reconstruct the functional unit of the failed spine, correcting any deformity if necessary and maintaining its fixation until complete bone fusion. In other words, the essence of spinal fusion surgery is not the placement of implants but the induction of bone fusion. Therefore, each case requires a carefully developed surgical plan to achieve sufficient bone fusion for spinal stabilization. In this article, we describe the mechanism and the surgical technique for achieving reliable interbody fusion.

Synovial Cyst of the Atlantoaxial Joint Removed through a Posterior Intradural Approach.

Introduction. Synovial cysts rarely develop in the atlantoaxial joint. We report a case of posterior C1-2 laminectomy for a synovial cyst of the atlantoaxial joint which passed through the dorsal dura and put pressure on the cervical spinal cord. Case Presentation. A 62-year-old man with rapid progression of pain and weakness in the left upper extremity presented to our hospital. A cervical spine X-ray showed left C5-6 and C6-7 stenoses. A cervical magnetic resonance imaging showed an intradural extramedullary cystic lesion on the right side of the ventral cervical spinal cord at the C1-2 level and severe compression of the cervical spinal cord. Because a cyst was partially enhancing, a tumor lesion was not identifiable. Due to severe spinal cord compression, we performed intradural cyst removal via a posterior intradural approach with C1-2 laminectomy and left-sided C5-6 and C6-7 foraminotomies. One year after surgery, the cyst did not recur, and atlantoaxial instability did not appear. Discussion. A compressive lesion on the cervical spinal cord was not identified preoperatively as a synovial cyst. However, intraoperative and pathological findings suggested that the compressive lesion can be a synovial cyst which passed through the dorsal dura. The surgical treatment strategy for a synovial cyst of the atlantoaxial joint is controversial due to factors, such as the presence of atlantoaxial instability, level of cyst causing compression of the cervical spinal cord, severity of myelopathy, and cyst location. In the present study, the cervical spinal cord was highly compressed and the cyst was located on the right side of the cervical spinal cord; we chose cyst removal through a posterior intradural approach with C1-2 laminectomy.

A Case of Atopic Myelitis with Cervical Cavernous Angioma.

Atopic myelitis, a type of myelitis which appears in patients with elevated serum levels of immunoglobulin E (IgE), occurs more commonly in the cervical spinal cord, but this mechanism has not yet been elucidated. Herein, we experienced a case of atopic myelitis developed during the growth of cervical cavernous angioma caused by bleeding. A 37-year-old woman suffered from hand swelling caused by a house cat licking. At the same time when cavernous angioma had grown, she experienced a numbness in her four extremities, and multifocal peritumoral hyperintense spinal cord signals were seen. The diagnosis of atopic myelitis was made because we observed significantly elevated levels of specific IgE antibody to cat dander. Symptoms disappeared immediately after steroid pulse therapy. We subsequently resected a cavernous angioma, and eosinophil invasion was found inside it. This is the first case report of atopic myelitis which developed in association with spinal cord vascular lesions. A local blood-brain barrier breakdown due to hemorrhagic lesions of the spinal cord may have contributed to the onset of atopic myelitis.

Surgical Treatment for Occipital Condyle Fracture, C1 Dislocation, and Cerebellar Contusion with Hemorrhage after Blunt Head Trauma.

Occipital condyle fractures (OCFs) have been treated as rare traumatic injuries, but the number of reported OCFs has gradually increased because of the popularization of computed tomography (CT) and magnetic resonance imaging (MRI). The patient in this report presented with OCFs and C1 dislocation, along with traumatic cerebellar hemorrhage, which led to craniovertebral junction instability. This case was also an extremely rare clinical condition in which the patient presented with traumatic lower cranial nerve palsy secondary to OCFs. When the patient was transferred to our hospital, the occipital bone remained defective extensively due to surgical treatment of cerebellar hemorrhage. For this reason, concurrent cranioplasty was performed with resin in order to fix the occipital bone plate strongly. The resin-made occipital bone was used to secure a titanium plate and screws enabled us to perform posterior fusion of the craniovertebral junction. Although the patient wore a halo vest for 3 months after surgery, lower cranial nerve symptoms, including not only neck pain but also paralysis of the throat and larynx, improved postoperatively. No complications were detected during outpatient follow-up, which continued for 5 years postoperatively.

[Juxta-facet Cyst Associated with Conjoined Nerve Roots:A Case Report].

We report a case of a patient with a juxta-facet cyst and conjoined nerve roots. A 66-year-old man presented with left leg pain from the past 4 months. Neurological examinations revealed L5 and S1 radiculopathy on the left side. Magnetic resonance imaging(MRI)detected a mass lesion located near the left intervertebral joint at the level of L5/S1 and canal stenosis at the level of L3/L4. A juxta-facet cyst was diagnosed by arthrography. We performed a curettage and resection of the mass, posterior lumbar interbody fusion at the level of L5/S1, and laminectomy at the level of L3/L4. Conjoined left L5/S1 nerve roots were observed during surgery. The patient recovered from the symptoms of L5 and S1 radiculopathy immediately after surgery. Postoperative review of the preoperative computed tomography images revealed bony abnormality in the L5/S1 joint. We speculate that the bony abnormality may be associated with the development of conjoined nerve roots and the juxta-facet cyst.

Simultaneous discovery of cranial and spinal intradural chordomas: case report.

The present case illustrates the unexpected occurrence of intradural chordomas that were simultaneously discovered in cranial and spinal locations. A 63-year-old female presented with weakness in the left upper extremity. The patient visited a local doctor and underwent brain computerized tomography (CT). CT revealed a brain tumor, and she was referred to our hospital. Brain magnetic resonance imaging (MRI) demonstrated a midline intradural retroclival tumor in addition to an intradural extramedullary mass lesion at the level of C1-C2. The patient developed a spastic gait disturbance that forced her to use a cane. She underwent laminectomy at C1-C2 along with total removal of the tumor and showed no remarkable symptoms after surgery. Histopathological examination confirmed the diagnosis of chordoma. One month after the cervical surgery, the intracranial tumor was subtotally removed in intracranial surgery via the right subtemporal approach. Histopathological data were identical to that of the cervical tumor. The patient consulted another hospital and underwent gamma-knife surgery. Her neurological examination is relatively unchanged 20 months after the cervical surgery. This case suggests that neuroradiological evaluation should also be performed for an intradural spinal chordoma when an intracranial chordoma is detected. Careful determination of the tumor responsible for the symptoms is necessary if an intradural spinal chordoma is simultaneously detected with an intracranial chordoma.

Incidental Detection of Primary Spinal Malignant Melanoma before Central Nervous System Dissemination.

The present case illustrates the incidental detection of a primary malignant melanoma of the thoracic spinal cord before central nervous system dissemination. A 54-year-old female fell down and bruised the thoracolumbar region. The patient visited a local doctor and underwent magnetic resonance imaging (MRI) of the thoracic and lumbar spine to rule out vertebral fractures. MRI revealed no vertebral fracture, but an intradural extramedullary mass was observed at the T12 level. She was referred to our hospital in October 2008. MRI showed that the mass appeared hyperintense on T1-weighted images and hypointense on T2-weighted images. T1-weighted MRI with gadolinium showed a mild homogeneous enhancement of the lesion. The patient underwent laminectomy at T11-L1, along with the complete removal of the tumor, and she exhibited no remarkable symptoms after surgery. Histopathological examination confirmed the diagnosis of malignant melanoma. Malignant melanoma was not detected elsewhere in the body. Neither radiotherapy nor chemotherapy was performed after surgery. Her neurological examination was unremarkable 5 years after the surgery and no tumor recurrence was detected. The present case suggests that patients with primary spinal malignant melanoma may survive >5 years without recurrence after complete surgical removal of the tumor alone. Complete removal of the tumor before central nervous system dissemination may be critical for treatment in such cases. Precise diagnosis via MRI may increase the detection of primary spinal malignant melanoma before central nervous system dissemination, thus facilitating prompt surgical removal, improving the prognosis of patients.

Radiation-induced spinal cord anaplastic astrocytoma subsequent to radiotherapy for testicular seminoma.

A 54-year-old man presented with a very rare case of radiation-induced intramedullary spinal cord anaplastic astrocytoma, which developed 37 years after radiotherapy for testicular seminoma. The patient presented with weakness and numbness of the left lower extremity that had gradually aggravated for 3 months. Magnetic resonance imaging demonstrated an intramedullary mass lesion with syringomyelia at the T9 to T12 levels. Subtotal removal of the tumor was performed using standard microsurgical technique. Histological examination revealed anaplastic astrocytoma. Although radiotherapy was seriously considered, chemotherapy was employed as adjuvant therapy considering the previous treatment. Although his neurological status improved transiently after surgery, relentless neurological decline occurred and resulted in death 9 months following surgery. Considering that subtotal removal of the tumor and chemotherapy had little influence on the quality of life and the length of survival in our case, cordectomy may be the optimum treatment for patients with radiation-induced spinal intramedullary malignant astrocytoma.

Expression of MAGE and GAGE genes in medulloblastoma and modulation of resistance to chemotherapy. Laboratory investigation.

OBJECT: Cancer testis antigens (CTAs) were initially identified by their ability to elicit autologous T-cell-mediated immune responses in patients with melanoma. The CTA genes are widely expressed in a variety of human cancers, such as melanoma, breast cancer, lung cancer, esophageal cancer, and hepatocellular carcinoma; however, their expression in pediatric brain tumors, such as medulloblastoma (MB), has not been the subject of in-depth analysis. The MAGE proteins are members of the CTA family and have been shown to correlate with tumor development, aggressive clinical course, or resistance to chemotherapeutic agents. The authors undertook this study to examine the expression and role of MAGE proteins in human MB cell lines and specimens. METHODS: From a transcriptional profiling study in which 47,000 genes in MB cell lines were examined, the authors identified members of the MAGE and GAGE families as being highly expressed. A series of MB tumors was examined using both immunohistochemistry and Western blot analysis with antibodies to the MAGE-A family, MAGE-A1, and GAGE proteins. RESULTS: Western blot analysis showed expression of these 3 proteins (MAGE-A family, MAGE-A1, and GAGE) in 62, 46, and 84%, respectively, of MB specimens examined. In addition, a correlation was observed between the expression of MAGE and GAGE genes and resistance of MB cells to chemotherapeutic agents. The functional significance of this correlation was examined in MAGE knockdown studies, and increased drug-induced cytotoxicity was observed in UW426 MB cells following treatment with chemotherapeutic drugs. Cleaved caspase-3 was found in UW426/MAGE small interfering (si)RNA-inhibited cells treated with cisplatin, but not in UW426 cells treated with cisplatin alone at the same concentration. CONCLUSIONS: These data show that MAGE and GAGE family members are expressed in MB cell lines and specimens, and that inhibition of MAGE and GAGE genes by siRNA increases apoptosis of MB cells and sensitizes them to certain chemotherapeutic agents such as cisplatin and etoposide.

Detection of JC virus DNA sequences in brain tumors in pediatric patients.

OBJECT: The JC virus is a human neurotropic polyomavirus that causes progressive multifocal leukoencephalopathy and is closely related to simian virus 40. Several recent reports have indicated a possible association between the JC virus and the development of various human brain tumors. The authors examined the presence of JC virus DNA sequences in primary brain tumors in pediatric patients to evaluate the hypothesis that particular brain tumors can arise in the pediatric population as a consequence of infection with the JC virus. METHODS: Genomic DNA sequences were isolated from 62 brain tumors (32 medulloblastomas, 18 ependymomas, five choroid plexus papillomas, and seven pilocytic astrocytomas) and analyzed for the presence of JC virus DNA by Southern blot hybridization and direct sequencing. The JC virus DNA sequence was detected in five ependymomas and one choroid plexus papilloma. Immunohistochemical studies revealed nuclear expression of the large T-antigen in a choroid plexus papilloma. None of the medulloblastomas or pilocytic astrocytomas contained JC virus DNA. CONCLUSIONS: The results of this study provide molecular evidence of the association between JC virus and the development of certain ependymomas and choroid plexus papillomas.

Novel and orally bioavailable inducible nitric oxide synthase inhibitors: synthesis and evaluation of optically active 4,5-dialkyl-2-iminoselenazolidine derivatives.

We have previously reported that (4R,5R)-5-ethyl-2-imino-4-methylthiazolidine (3) strongly inhibits inducible nitric oxide synthase (iNOS). In a successive search for strong and selective iNOS inhibitors, we, herein, describe the synthesis of the selenium analogue of 3 (4: ES-2133) and its related optically active compounds and examine their in vitro and in vivo inhibitory activity against iNOS. In addition, an alternative synthetic method to the selected compound 4 and its pharmacokinetic profile is also reported.

A clinicobiological model predicting survival in medulloblastoma.

PURPOSE: The purpose of this study was to determine the relative contributions of biological and clinical predictors of survival in patients with medulloblastoma (MB). EXPERIMENTAL DESIGN: Clinical presentation and survival information were obtained for 119 patients who had undergone surgery for MB at the Hospital for Sick Children (Toronto, Ontario, Canada) between 1985 and 2001. A tissue microarray was constructed from the tumor samples. The arrays were assayed for immunohistochemical expression of MYC, p53, platelet-derived growth factor receptor-alpha, ErbB2, MIB-1, and TrkC and for apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling). Both univariable and multivariable analyses were conducted to characterize the association between survival and both clinical and biological markers. For the strongest predictors of survival, a weighted predictive score was calculated based on their hazard ratios (HRs). The sum of these scores was then used to give an overall prediction of survival using a nomogram. RESULTS: The four strongest predictors of survival in the final multivariable model were the presence of metastatic disease at presentation (HR, 2.02; P=0.01) and p53 (HR, 2.29; P=0.02), TrkC (HR, 0.65; P=0.14), and ErbB2 (HR, 1.51; P=0.21) immunopositivity. A linear prognostic index was derived, with coefficients equal to the logarithm of these HRs. The 5-year survival rate for patients at the 10th, 50th, and 90th percentiles of the score distribution was 80.0%, 71.0%, and 35.7%, respectively, with radiation therapy and 70.5%, 58.5%, and 20.0%, respectively, without radiation therapy. CONCLUSIONS: In this study, we demonstrate an approach to combining both clinical and biological markers to quantify risk in MB patients. This provides further prognostic information than can be obtained when either clinical factors or biological markers are studied separately and establishes a framework for comparing prognostic markers in future clinical studies.

Induction of the DNA repair gene O6-methylguanine-DNA methyltransferase by dexamethasone in glioblastomas.

OBJECT: The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) inhibits the cytotoxic effect of alkylating agents on tumor cells. The presence of two nonconsensus glucocorticoid-responsive elements in the human MGMT promoter region indicates the potential regulation of MGMT expression by glucocorticoid agents. This study was performed to elucidate whether dexamethasone affects the expression of MGMT in glioblastoma multiforme (GBM) cells, thereby limiting the benefit of chemotherapeutic alkylating agents. METHODS: Four GBM cell lines (A172, T98G, U138MG, and U87MG) were exposed to the alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) with or without dexamethasone. The expression levels of MGMT were correlated with the cytotoxic effects of ACNU in GBM cells. In the presence of ACNU alone, dexamethasone alone, and the combination of both agents, messenger RNA expression of MGMT was induced to varying degrees with the highest increases seen in the later conditions. This dexamethasone-dependent induction of the MGMT gene was even observed in U87MG cells in which the promoter is methylated, although the absolute expression of MGMT mRNA was the lowest in that cell line. The induction of MGMT by dexamethasone was associated with an increased resistance of these cells to ACNU. CONCLUSIONS: These results indicate that dexamethasone-mediated upregulation of MGMT limits the efficiency of alkylating agents in the treatment of malignant gliomas.