Weston-Hurst syndrome with acute hemorrhagic cerebellitis.

Weston-Hurst syndrome is an exceptional variant of ADEM characterized by brain hemorrhages. Lesions are usually supratentorial and death is a usual outcome. We report a cerebellar Weston-Hurst syndrome early treated by craniectomy, steroids and plasma exchange. This is the first case of infratentorial Weston-Hurst syndrome associated with a favorable outcome.

Diffusion tensor imaging and white matter lesions at the subacute stage in mild traumatic brain injury with persistent neurobehavioral impairment.

Mild traumatic brain injury (mTBI) can induce long-term behavioral and cognitive disorders. Although the exact origin of these mTBI-related disorders is not known, they may be the consequence of diffuse axonal injury (DAI). Here, we investigated whether MRI at the subacute stage can detect lesions that are associated with poor functional outcome in mTBI by using anatomical images (T(1) ) and diffusion tensor imaging (DTI). Twenty-three patients with mTBI were investigated and compared with 23 healthy volunteers. All patients underwent an MRI investigation and clinical tests between 7 and 28 days (D15) and between 3 and 4 months (M3) after injury. Patients were divided in two groups of poor outcome (PO) and good outcome (GO), based on their complaints at M3. Groupwise differences in gray matter partial volume between PO patients, GO patients and controls were analyzed using Voxel-Based Morphometry (VBM) from T(1) data at D15. Differences in microstructural architecture were investigated using Tract-Based Spatial Statistics (TBSS) and the diffusion images obtained from DTI data at D15. Permutation-based non-parametric testing was used to assess cluster significance at p < 0.05, corrected for multiple comparisons. Twelve GO patients and 11 PO patients were identified on the basis of their complaints. In PO patients, gray matter partial volume was significantly lower in several cortical and subcortical regions compared with controls, but did not differ from that of GO patients. No difference in diffusion variables was found between GO and controls. PO patients showed significantly higher mean diffusivity values than both controls and GO patients in the corpus callosum, the right anterior thalamic radiations and the superior longitudinal fasciculus, the inferior longitudinal fasciculus and the fronto-occipital fasciculus bilaterally. In conclusion, PO patients differed from GO patients by the presence of diffusion changes in long association white matter fiber tracts but not by gray matter partial volume. These results suggest that DTI at the subacute stage may be a predictive marker of poor outcome in mTBI.

Endocan expression and localization in human glioblastomas.

Glioblastomas (GBMs) are highly malignant tumors characterized by microvascular proliferation and the pseudopalisading pattern of necrosis. Investigations have, therefore, focused on vascular and endothelial cell biology in GBM. Endocan, also called endothelial cell-specific molecule-1, is a proteoglycan that is secreted by endothelial cells and upregulated by proangiogenic factors. We found that endocan is not only expressed in vitro by endothelial cells but also in the T98G and U118MG human GBM cell lines. In U118MG cells, tumor necrosis factor and fibroblast growth factor 2 upregulated endocan production, whereas exposure to hypoxia or cobalt chloride, an inducer of hypoxia inducible factor 1, increased endocan release without affecting cell viability. Endocan expression in 82 brain tumors was studied by immunohistochemistry. Endocan immunoreactivity was detected in hyperplastic endothelial cells in high-grade gliomas, mostly at the tumor margins; endothelial cells were mostly endocan negative in low-grade gliomas, and it was never detected in the cerebral cortex distant from the tumors. Tumor cells in high-grade but not low-grade gliomas also expressed endocan, and it was detected in palisading cells surrounding areas of necrosis in GBM. Endothelial cell endocan immunoreactivity also correlated with shorter survival in glioma patients. Taken together, these results suggest that endocan is associated with abnormal vasculature in high-grade gliomas.

Retrospective study of 19 patients with intramedullary spinal cord metastasis.

OBJECT: Intramedullary spinal cord metastasis (ISCM) is a rare but devastating complication of cancer. Due to both widespread MRI availability and longer survival of cancer patients, the probability of discovering an ISCM during the course of the disease has increased and raised issues regarding the management of these patients, and particularly the place of surgery. In this study, we assess predictive factors for surgical outcome and survival. PATIENTS AND METHODS: We retrospectively reviewed a series of 19 patients consecutively admitted in our institution from 1993 to 2006 for ISCM, representing the second largest series published in the literature. MRI was performed on all patients. Thirteen underwent microsurgical excision of ISCM. Functional outcome was evaluated and factors influencing survival were statistically analyzed. RESULTS: Median survival was statistically longer when surgery was performed (7.4 vs. 2.6 months). Preoperative neurological status, nature of primary cancer, presence of systemic and/or CNS metastases influenced survival, but differences were without statistical significance. Neurological status improved in 58% (11/19) of operated patients. CONCLUSIONS: Optimal management of patients with ISCM is difficult due to the wide variety of clinical situations and the lack of controlled studies on the results of different therapeutic options. Diagnosis should be made as early as possible and surgical resection should be considered as the primary treatment whenever feasible, particularly in the case of rapidly progressive neurological deficits and when a clear cleavage plane exists. Our study shows that surgery could result in both increased survival rate and significant improvement of neurological function.

Using human CD20-transfected murine lymphomatous B cells to evaluate the efficacy of intravitreal and intracerebral rituximab injections in mice.

PURPOSE: The treatment of primary central nervous system lymphoma (PCNSL) and its subset, primary intraocular lymphoma (PIOL), remains of limited efficiency, and salvage therapies are often used without prior testing in adequate animal models. Most PNCSL/PIOL are aggressive B-cell malignancies. Two animal models that closely mimic the human situation were established to evaluate the efficiency of intravitreal and intracerebral anti-CD20 monoclonal antibody (rituximab) injections. METHODS: Human CD20-transfected murine B-lymphoma cells (38C13 CD20(+)) were inoculated in the vitreous through the pars plana or in the caudate nucleus with the use of a stereotaxic frame in immunocompetent syngeneic mice. Animals were monitored clinically and by funduscopic and histologic examination. Rituximab was injected intravitreally or intracerebrally. Occurrences of exophthalmia, neurologic disturbance, and weight loss were monitored over 2 months. RESULTS: Inoculation of 38C13 CD20(+) cells in the eye or the brain resulted in tumor occurrence after a median of 15 days or 22 days, respectively, with histologic characteristics closely resembling those of PIOL and PCNSL. Local rituximab injections eradicated tumor colonization in more than half the graft recipients and inhibited tumor progression significantly in the others compared with progression in mice that underwent grafting with the control 38C13 cell line (no human CD20 expression) and in mice that underwent grafting with 38C13 CD20(+) cells that received local injections of an irrelevant antibody (trastuzumab). CONCLUSIONS: Inoculation of native or human CD20-transfected murine 38C13 cells in the vitreous or the brain of immunocompetent mice provides useful novel models for evaluating the biology and treatment of PIOL and PCNSL. Intravitreal and intracerebral rituximab injections reduced tumor occurrence and growth in each model.

Low HER2-expressing glioblastomas are more often secondary to anaplastic transformation of low-grade glioma.

BACKGROUND: Anti-Human Epithelial Receptor Type 2 (HER2) antibodies have the ability to induce in vitro apoptosis of glioblastoma (GBM) cells. This study was designed to evaluate the variability of HER2 expression in GBM and its role as a possible prognosis factor. METHODS: Data of 57 patients with GBM and 16 patients with grade III gliomas were retrospectively analyzed. The expression of HER2 was determined by immunohistochemistry and intensity was noted from 0+ to 3+. We compared the HER2 expression in de novo GBM and in GBM resulting from anaplastic transformation of low-grade glioma ("secondary GBM"). Statistical analysis was performed using univariate analysis and the Kaplan-Meier method. FINDINGS: All GBM expressing highly HER2 (2+ and 3+) were de novo GBM. All secondary GBM expressed HER2 with low intensity (0+ and 1+). Survival time was significantly longer when HER2 expression was low (Log Rank test P = 0.04). The patterns of HER2 expression were similar between grade III gliomas and secondary GBM. CONCLUSIONS: To our best knowledge, our study showed for the first time a significant association between HER2 expression and the type of GBM, with subsequent influence on survival rate. GBM with low-HER2 expression are more likely to be secondary GBM, carrying a better prognosis than de novo GBM.

Surgical resection of thalamic tumors in children: approaches and clinical results.

OBJECTIVES: Thalamic tumors are uncommon, and although gross total removal (GTR) is a prospective goal, its interest is debated because the thalamus constitutes a highly functional region. The relation of choice of the surgical approach, achievability of GTR, and operative morbidity to the anatomic location of the tumor has received little attention in the medical literature. MATERIALS AND METHODS: We reviewed retrospectively the cases of pediatric patients treated for thalamic tumor, with pre- and postoperative magnetic resonance imaging, and who were operated with the aim of maximal surgical removal. CONCLUSION: We reviewed 16 cases operated between 1992 and 2003. The clinical presentation was dominated by intracranial hypertension and hemiparesis. Fifteen children were operated through transcortical approaches: transfrontal in six cases, transparietal in six, and transtemporal in three. The remaining patient was operated through an infratemporal approach. All operations performed since 1998 used intraoperative neuronavigation. Complete or near-total resection was achieved in 11 cases; only subtotal resection was achieved in the remaining five cases. The most common postoperative morbidity was visual field defect. Hemiparesis was unchanged or improved in all the cases. Seven children died of tumor progression, in relation with high histological grade, and one died of acute hydrocephalus. The approach to thalamic tumors needs to be planned according to the location of critical neural structures. GTR of thalamic tumors in children bears acceptable morbidity and may even improve preoperative deficits. Surgery alone can be curative in low-grade tumors; in high-grade or infiltrating tumors, GTR is only part of the overall oncological management.

Increasing of HER2 membranar density in human glioblastoma U251MG cell line established in a new nude mice model.

Glioblastoma multiform (GBM) remains the most devastating primary tumour in neuro-oncology. Human Epithelial Receptor Type 2 (HER2) is a transmembrane tyrosine/kinase receptor that is important for cancer growth. HER2 is not expressed in adult glial cells, but its expression increases with the degree of astrocytomas anaplasia. We have recently demonstrated the ability of anti-HER2 antibodies to induce in vitro apoptosis GBM cell lines; this ability is correlated to HER2 density. A decreasing of tyrosine/kinase receptors density during in vitro culture was reported. No information exists about the variation of HER2 expression after in vivo implantation. For that, the two cell lines in vitro tested (U251MG, A172) were in vivo implanted. We established a U251MG in vivo model in balb/c nude mice showing an important increasing of HER2 density. The HER2 density is correlated to anti-HER2 antibody efficiency so this model will be useful for the evaluation of in vivo anti-HER2 antibody treatment.