No abstract

Chordoid meningiomas are predominantly tumors of young adults with predilection for supratentorial location. Intraventricular location, absence of systemic manifestations despite the presence of abundant B-lymphocytes, presence of mast cells and low MIB-1 LI are some of the interesting findings in the present series, which need documentation. Hence, larger number of cases with adequate follow-up data need to be studied further to establish the clinical significance of this variant.

We observed elevated levels of pro-inflammatory cytokine IL-1β in glioblastoma multiforme tumor samples. Since hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in linking inflammatory and oncogenic pathways, we investigated the effect of IL-1β on HIF-1α expression in glioma cells under normoxia. IL-1β-mediated elevation of HIF-1α transcriptional activity was dependent on Ras-induced NF-κB activation, as IL-1β failed to induce NF-κB and HIF-1α activity in cells transfected with dominant negative RasN17. Increased Ras expression was accompanied by increased phosphorylation of Ras effectors AKT, ERK, JNK, and p38MAPK. While inhibition of these effectors individually failed to block the IL-1β-mediated increase in HIF-1α induction, co-inhibition of both AKT and ERK resulted in a significant decrease in IL-1β-induced HIF-1α activation. Interestingly, IL-1β elevated Wnt-1 expression in a Ras-dependent manner, and small interfering RNA (siRNA)-mediated knockdown of Wnt-1 decreased HIF-1α activity. Although Wnt-1-mediated HIF-1α was independent of the canonical Wnt/β-catenin signaling pathway, it regulated HIF-1α through NF-κB. siRNA-mediated HIF-1α knockdown attenuated elevated IL-1β mRNA levels induced upon IL-1β treatment. This was accompanied by increased interaction of HIF-1α with HIF responsive element on the IL-1β promoter upon IL-1β treatment, under normoxia. Our studies highlights for first time that (1) Ras is a key mediator of IL-1β-induced NF-κB and HIF-1α activation, under normoxia; (2) Wnt-1 regulates IL-1β-mediated HIF-1α induction via NF-κB; (3) Ras and Wnt-1 are intermediaries in the canonical IL-1β-NF-κB signaling pathway downstream of MyD88; and (4) IL-1β-induced HIF-1α drives a HIF-1α-IL-1β autocrine loop to maintain persistently elevated IL-1β level.

Pediatric aneurysms have male predominance, higher incidence of clinical features of mass effect or seizures, high incidence of large, traumatic/mycotic aneurysms, associated illnesses and ICH/IVH and hydrocephalus, better Hunt and Hess grades at presentation, ICA bifurcation as the commonest site, and better outcome than their adult counterparts.

The precise role of different toll-like receptor (TLR) superfamily members is just beginning to get elucidated in glioblastoma multiforme (GBM). In this study, we observed heightened TLR4 levels in GBM tumor samples as compared to adjacent normal tissue. Since the pro-inflammatory cytokine tumor necrosis factor (TNF)α induces NF-κB activation in GBM, and as several common signaling mediators are involved in TNFα and TLR4-mediated NF-κB activation, we investigated the role of TLR4 in the regulation of NF-κB activation and inflammatory responses in TNFα-treated glioma cells. TNFα elevated TLR4 expression and inhibition of TLR4 signaling by either signaling inhibitor, neutralizing antibody, or small interfering RNA (siRNA)-attenuated TNFα-induced NF-κB activation. TLR4-mediated NF-κB activation was independent of canonical myeloid differentiation factor 88 signaling but involved toll/IL-1R homology domain-containing adaptor protein-inducing interferon-β. Inhibition of TLR4 signaling abrogated TNFα-induced increase in (1) transcription factors interferon (IFN) regulatory factor 3 and STAT-1 and (2) IFNβ and inflammatory cytokines/chemokines expression. Furthermore, TNFα-induced TLR4-dependent increase in AKT activation and HIF-1α transcriptional activation suggested the existence of TLR4-AKT-HIF-1α axis. Importantly, TNFα-induced TLR4 was abrogated in cells transfected with dominant negative IκB and HIF-1α siRNA. Our studies indicate that TNFα triggered TLR4-HIF-1α and NF-κB-TLR4 feed-forward loops act in tandem to sustain inflammatory response in glioma.

Three cases of ruptured intracranial aneurysm during pregnancy are presented. Rupture occurred near term in all three cases. Simultaneous elective cesarean section and clipping of the aneurysm was performed in two cases. Successful maternal and perinatal outcome was achieved in all three patients. The diagnosis and management of the cases are described and discussed.

No abstract

Extramedullary haematopoiesis associated with thalassaemia leading to spinal cord compression is an extremely rare event in the course of the disease. The efficacy of radiation therapy is advocated in the management of such a complication. Two patients with thalassaemia, who had presented with spinal cord compression, were successfully treated by a modest dose of local radiotherapy. In one of the patients, however, radiotherapy was resorted to after an initial decompressive laminectomy and partial removal of the intraspinal haematopoietic mass proved unsuccessfil. The other patient was managed solely by radiation therapy.Extramedullary haematopoiesis (EMH) is a common manifestation of severe thalassaemia and it may involve various organs of the body such as liver, spleen, and lymph nodes.'-6 The clinical features secondary to EMH are variable and depend on the site of formation of the haematopoietic tissue. The onset of unexpected clinical signs may be the first indication that haematopoiesis is spreading to an atypical area. Spinal cord compression (SCC) as a consequence of EMH in the intraspinal epidural space is an extremely rare complication. We report two cases of thalassaemia that had presented with SCC. A review of the literature is discussed highlighting the role of radiation therapy in the management of such patients.and there was a complete loss of touch and pinprick sensation below the level ofT7.The radiograph of the skull and spine demonstrated a diffuse osteoporosis but no well defined paravertebral mass was evident. Myelogram, however, revealed a complete extradural block at the level of T9. The CSF examination proved noncontributory. His haemoglobin (Hb) was 8-7 g/dl, haematocrit 28% and white blood cell count (WBC) 7.4 x 109/L. The differential count revealed a slight shift to the left (metamyelocyte 2%, myelocyte 2%). Platelets were adequate. The peripheral smear showed anisopoikilcytosis with microcytosis and hypochromia. A few target cells were also noticed. There were three normoblasts/100 WBC. The corrected reticulocyte count was 2%. A haemoglobin electrophoresis showed 21% Hb F and 2-6% Hb A2.At laminectomy a brownish, soft, vascular extradural mass was seen extending from T5-T9. Only a partial excision of the mass could be accomplished. The histopathological examination of the excised mass confirmed it to be haematopoietic tissue. The postoperative course was uneventful. However, in view of the incomplete excision of the mass and a negligible neurological recovery, radiotherapy was started two weeks after surgery. A total dose of 30 Gy was delivered by a telecobalt unit, over a period of three weeks in 15 sessions. There was a marked neurological improvement at the end of radiation treatment and the patient continued to improve. No complication was observed during or after radiotherapy. The patient has been doing well for a period of five years.