Georgios Pantazis

Histological findings on fetal striatal grafts in a Huntington's disease patient early after transplantation.

Cell transplantation is a promising therapeutic approach that has the potential to replace damaged host striatal neurons and, thereby, slow down or even reverse clinical signs and symptoms during the otherwise fatal course of Huntingtons disease (HD). Open-labeled clinical trials with fetal neural transplantation for HD have demonstrated long-term clinical benefits for HD patients. Here we report a postmortem analysis of an individual with HD 6 months after cell transplantation and demonstrate that cells derived from grafted fetal striatal tissue had developed into graft-derived neurons expressing dopamine-receptor related phosphoprotein (32 kDa) (DARPP-32), neuronal nuclear antigen (NeuN), calretinin and somatostatin. However, a fully mature phenotype, considered by the expression of developmental markers, is not reached by engrafted neurons and not all types of interneurons are being replaced at 6 months, which is the earliest time point human fetal tissue being implanted in a human brain became available for histological analysis. Host-derived tyrosine hydroxylase (TH) fibers had already heavily innervated the transplants and formed synaptic contacts with graft-derived DARPP-32 positive striatal neurons. In parallel, the transplants contained a considerable number of immature neuroepithelial cells (doublecortin+, Sox2+, Prox-1+, ss3-tubulin+) that exhibited a pronounced migration into the surrounding host striatal tissue and considerable mitotic activity. Graft-derived astrocytes could also be found. Interestingly, the immunological host response in the grafted area showed localized increase of immunocompetent host cells within perivascular spaces without deleterious effects on engrafted cells under continuous triple immunosuppressive medication. Thus this study provides for a better understanding of the developmental processes of grafted human fetal striatal neurons in HD and, in addition, has implications for stem cell-based transplantation approaches in the CNS.

STEREOTACTIC INTERSTITIAL RADIOSURGERY WITH THE PHOTON RADIOSURGERY SYSTEM (PRS) FOR METASTATIC BRAIN TUMORS: A PROSPECTIVE SINGLE-CENTER CLINICAL TRIAL

PURPOSE To evaluate the efficacy and the treatment outcome of tumor patients being treated stereotactically with a miniature X-ray generator (Photon Radiosurgery System, PRS). METHODS AND MATERIALS Thirty-five patients with histologically diagnosed cerebral metastases were treated with a single fraction of stereotactic interstitial irradiation (median, 18 Gy). Clinical and neuroimaging evaluation were assessed at 2-, 6-, and 12-week intervals postoperatively and every 3 months thereafter. Survival, local control, and distant and overall brain freedom from progression were obtained using the Kaplan-Meier method. RESULTS Median survival was 7.37 months and the actuarial survival rates at 6 and 12 months were 60.0% and 34.3%, respectively. Acute complications on six patients were associated with shorter survival. Local tumor control at the initial stage and at the last follow-up were 82% and 50%. Eighteen patients (53%) developed distant brain metastases after treatment. At 1 year, the local control rate and distant and overall brain freedom from progression were 33.0%, 43.3%, and 14.7%, respectively. A shorter local tumor control was observed by PRS treatment of a recurrent tumor and by irregular tumor configuration. CONCLUSIONS Interstitial radiosurgery with the PRS requires continued investigation. It allows for an immediate and potentially cost-efficient treatment for patients with singular, small (<or= 6.36 cm(3); or <or= 2.3 cm) spherical brain metastasis subsequent to a stereotactic biopsy.

Primary cerebral low-grade B-cell lymphoma, monoclonal immunoglobulin deposition disease, cerebral light chain deposition disease and “aggregoma”: an update on classification and diagnosis

BackgroundThis work aims to add evidence and provide an update on the classification and diagnosis of monoclonal immunoglobulin deposition disease (MIDD) and primary central nervous system low-grade lymphomas. MIDD is characterized by the deposition of light and heavy chain proteins. Depending on the spatial arrangement of the secreted proteins, light chain-derived amyloidosis (AL) can be distinguished from non-amyloid light chain deposition disease (LCDD). We present a case of an extremely rare tumoral presentation of LCDD (aggregoma) and review the 3 previously published LCDD cases and discuss their presentation with respect to AL.Case presentationA 61-year-old woman presented with a 3½-year history of neurologic symptoms due to a progressive white matter lesion of the left subcortical parieto-insular lobe and basal ganglia. 2 former stereotactic biopsies conducted at different hospitals revealed no evidence of malignancy or inflammation; thus, no therapy had been initiated. After performing physiological and functional magnetic resonance imaging (MRI), the tumor was removed under intraoperative monitoring at our department. Histological analysis revealed large amorphous deposits and small islands of lymphoid cells.ConclusionLCCD is a very rare and obscure manifestation of primary central nervous system low-grade lymphomas that can be easily misdiagnosed by stereotactic biopsy sampling. If stereotactic biopsy does not reveal a definite result, a “wait-and-see” strategy can delay possible therapy for this disease. The impact of surgical removal, radiotherapy and chemotherapy in LCDD obviously remains controversial because of the low number of relevant cases.

Pineal germinoma with granulomatous reaction, often a pitfall in endoscopic biopsy. Report of two cases and review of the literature

Tumours of the pineal region are rare and account for 0.5–2% f all intracranial lesions. There is a higher incidence in male than n female and they are 10 times more common in children than n adults. Germinoma is the most common tumour in the pineal egion appearing up to 50% of all pineal tumours [1]. Intracranial erminomas are malignant neoplasms arising from remnants of rimitive germ cells, which have failed to migrate to the genital rest during embryonic stage. Therefore germinomas present the ame histology as seminomas and dysgerminomas, their gonadal ounterparts. Intracranial germinoma is commonly situated in he midline, occurring mostly in the pineal region. Their origin xplains this site of predilection [2]. Most of the patients suffer rom intracranial hypertension due to obstructive hydrocephalus nd/or symptoms due to pressure or infiltration of adjacent strucures. The duration of symptoms ranges from 1 week to 6 years mean 19 months). Granulomatous reaction is frequently found in seminomas nd dysgerminomas. However, it occurs rarely in germinomas approximately 5%). We present two cases of germinoma with ranulomatous reaction. The relevant literature is reviewed and iscussed.

Invasive fibroblasts: fundamental difference between sporadic inclusion body myositis and polymyositis.

Introduction: Sporadic inclusion body myositis (sIBM) is a progressive disease that leads to extensive muscle weakness. The aim of this study was to determine whether the number and distribution of fibroblasts differ in sIBM when compared with polymyositis. Methods: Immunofluorescence double labeling was performed on 35 biopsies with antibodies directed against perlecan and CD90, procollagen I, CD34, and CD105. In addition, nonserial ultrathin sections were studied from 3 biopsies of each condition. Results: Fibroblasts expressing CD90 and CD34 accumulated in the endomysial compartment in polymyositis and sIBM. In addition, cells expressing CD90 were found beneath the basal lamina in both conditions. At the ultrastructural level in polymyositis, fibroblasts invaded the myofiber, with focal destruction of the basement membrane. In sIBM, by contrast, invasive fibroblasts were ensheathed by the intact myofiber basement membrane. Conclusions: The impact of intruding fibroblasts on satellite cells remains to be established. Muscle Nerve 49: 175–180, 2014

Wertigkeit der MRT in der Diagnostik primärer und sekundärer zerebraler Infektionen

Cerebral infections may develop into a life-threatening condition. Fast and correct diagnosis is crucial for a differentiated therapy and MRI imaging is widely accepted as the method of choice. Both specific MR sequences and imaging characteristics of major cerebral infections are addressed in this overview. Furthermore, limitations and pitfalls of the method are discussed.

NFAT and T-Cell Response Play Major Roles in the Formation of Sporadic Vestibular Schwannomas

Introduction: Even though clinical and morphological differences of vestibular schwannomas are well documented, the knowledge on molecular mechanisms of development is limited. In this study, we examined differences in gene expression between tumor and control tissue in search of underlying disease-causing deregulated pathways. Material and Methods: We performed whole genome microarray expression profiling (HG-U219 Array Plate, Affymetrix) and pathway analysis of tissue samples from 36 patients with sporadic vestibular schwannomas versus 7 postmortem samples of the vestibulocochlear nerve. Results: We identified 2,694 genes that were deregulated over twofold: 1,471 were upregulated and 1,223 were downregulated. The most significantly deregulated pathways in vestibular schwannomas include the role of nuclear factor of activated T-cells (NFAT) in immune response, phospholipase C signaling and antigen presentation. Conclusion: An important role in vestibular schwannoma formation is attributed to nuclear factors of activated T-cells and their transcriptional partners, whose combined interactions result in a deranged T-cell response and may thereby lead to an imbalance between tumorigenesis and immune response.