BackgroundPrevious research in animal seizure models indicates that the pleiotropic cytokine TNF is an important effector/mediator of neuroinflammation and cell death. Recently, it has been demonstrated that TNF downregulates Klotho (KL) through the nuclear factor kappa B (NFkB) system in animal models of chronic kidney disease and colitis. KL function in the brain is unclear, although Klotho knockout (Kl−/−) mice exhibit neural degeneration and a reduction of hippocampal synapses. Our aim was to verify if the triad KL-NFKB1-TNF is also dysregulated in temporal lobe epilepsy associated with hippocampal sclerosis (TLE(HS)) patients.FindingsWe evaluated TNF, NFKB1 and KL relative mRNA expression levels by reverse transcription quantitative PCR (RT-qPCR) in resected hippocampal tissue samples from 14 TLE(HS) patients and compared them to five post mortem controls. Four reference genes were used: GAPDH, HPRT1, ENO2 and TBP. We found that TNF expression was dramatically upregulated in TLE(HS) patients (P <0.005). NFKB1 expression was also increased (P <0.03) while KL was significantly downregulated (P <0.03) in TLE(HS) patients. Hippocampal KL expression had an inverse correlation with NFKB1 and TNF.ConclusionsOur data suggest that, similar to other inflammatory diseases, TNF downregulates KL through NFkB in TLE(HS) patients. The remarkable TNF upregulation in patients is a strong indication of hippocampal chronic inflammation. Our finding of hippocampal KL downregulation has wide implications not only for TLE(HS) but also for other neuronal disorders related to neurodegeneration associated with inflammation.

The cerebellum is an exquisite anatomic structure within the human brain, which needs to be considered from the surgical standpoint because of its functional importance and common pathologies that affect this area 1 . It is possible to reach the cerebellum avoiding damaging neural structures by approaches which target tentorial, petrosal, or suboccipital surfaces. Each has its microsurgical particularities in order to reach the desired region and preserve neural structures 2 . In this article, we have presented the microsurgical anatomy of the suboccipital and supracerebellar approaches to the cerebellar surfaces using comprehensives anatomic and functional relations with the final objective of performing better operations with less damage to the cerebellar nucli and important deep pathways. MetHODSThe dentate nucleus, cerebellar peduncles and their relationship with others cerebellar structures were studied in 20 adult cerebellar hemispheres, 12 male and 8 female corpses, obtained from São Paulo death verification service using X3 to X40 magnifications. AbStrActObjective: To define the anatomy of dentate nucleus and cerebellar peduncles, demonstrating the surgical application of anatomic landmarks in cerebellar resections. Methods: Twenty cerebellar hemispheres were studied. Results: The majority of dentate nucleus and cerebellar peduncles had demonstrated constant relationship to other cerebellar structures, which provided landmarks for surgical approaching. The lateral border is separated from the midline by 19.5 mm in both hemispheres. The posterior border of the cortex is separated 23.3 mm from the posterior segment of the dentate nucleus; the lateral one is separated 26 mm from the lateral border of the nucleus; and the posterior segment of the dentate nucleus is separated 25.4 mm from the posterolateral angle formed by the junction of lateral and posterior borders of cerebellar hemisphere. Conclusions: Microsurgical anatomy has provided important landmarks that could be applied to cerebellar surgical resections.Key words: cerebellum, anatomy, neurosurgery.reSuMO Objetivo: Definir a anatomia do núcleo denteado e dos pedúnculos cerebelares, demonstrando a aplicação dos marcos anatômicos em cirurgias cerebelares. Métodos: Foram estudados 20 hemisférios cerebelares. Resultados: A maioria dos núcleos denteados e pedúnculos cerebelares demonstraram relação anatômica constante com outras estruturas cerebelares, fato que proporcionou o estabelecimento de marcos anatômi-cos específicos a serem utilizados em acessos cirúrgicos. O bordo lateral do núcleo denteado é separado da linha média em 19,5 mm em ambos os hemisférios cerebelares. O bordo posterior do córtex é separado do segmento posterior do núcleo denteado por 23,3 mm. O bordo lateral do córtex é separado do bordo lateral do núcleo por 26 mm e o segmento posterior do núcleo denteado é separado por 25,4 mm do ângulo posterolateral, que é formado pela junção dos bordos lateral e posterior do hemisfério cerebelar. Conclusões: O estudo da anatomia microcirúrgic...

Pulmonary embolism; capnography; thrombolytic therapy. This is the first report of a patient submitted to chemical thrombolysis due to massive pulmonary embolism (PE) during the postoperative period of neurosurgery, in whom due to the lack of adequate clinical conditions, no imaging assessment was performed. Clinical, gasometric and capnographic data allowed the decision to perform the thrombolysis with safety. The P(a-et)CO 2 gradient decreased from 46.4 mmHg to 11.8 mmHg (normal < 5 mmHg) and the end-tidal alveolar dead space fraction decreased from 0.85 to 0.37 (normal < 0.15) from the pre-thrombolysis period to the 7 th day postthrombolysis. We conclude that the volumetric capnography (VC) was useful in the patient's diagnosis and clinical follow-up. Thrombolysis in Massive Pulmonary Case ReportA 22-year-old female patient, admitted at the Intensive Care Unit (ICU) of a tertiary hospital developed difficult-tocontrol diabetes insipidus after the excision of a frontal brain tumor (astrocytoma), together with septic conditions and mild hemodynamic alterations. On the 24 th postoperative day, the patient was going through the mechanical ventilation (MV) weaning process, with the following parameters: FiO 2 = 0.30; spontaneous breathing (30 rpm), PEEP = 5 cmH 2 O; apH = 7.50; PaO 2 = 62.2 mmHg; PaCO 2 = 27.6 mmHg; HCO 3 = 21.8 mmol/l; BE = -0.1 mmol/l; SatO 2 = 94.8%; PaO 2 /FiO 2 ratio= 207.The patient suddenly started to present respiratory difficulty, hypoxemia and hemodynamic worsening. With the diagnostic hypothesis of massive PE, a transthoracic echocardiogram was performed, which disclosed moderate dilation of the right chambers, moderate tricuspid regurgitation and pulmonary artery systolic pressure = 50 mmHg. The echocardiograma (ECG) showed the presence of S 1 Q 3 T 3 pattern.After this episode sthe MV was adjusted to: FiO 2 = 1; SIMV (12/38 rpm); PEEP = 8 cmH 2 O and TV = 500 ml; the subsequent arterial gasometry showed: pH = 7.26; PaO 2 = 44.5 mmHg; PaCO 2 = 54.6 mmHg; HCO 3 = 23.7 mmol/l; BE = -2.7 mmol/l; SatO 2 = 71.7%; PaO 2 /FiO 2 ratio = 44.5. Dobutamine was started, aiming at the hemodynamic function improvement. Three hours later, while still on mechanical ventilation, the patient presented the following parameters: FiO 2 = 1; SIMV (14/27 rpm); PEEP = 10 cmH 2 O; TV = 500 ml, arterial gasometry showed: pH = 7.22; PaO 2 = 50.7 mmHg; PaCO 2 = 54.7 mmHg; HCO 3 = 21.3 mmol/l; BE = -6.2 mmol/l; SatO 2 = 82.3%; PaO 2 /FiO 2 ratio= 50.7.Through the VC, the end-tidal CO 2 pressure (PetCO 2 ) was determined (CO 2 SMO PLUS 8100 Dixtal/Novametrix™) which, associated to the arterial gasometry (Radiometer ABL 700™), allowed the calculation of different derived indices, such as end-tidal alveolar dead space fraction ,(AVDSf), the late dead space fraction (fDlate), the CO 2 arterial-alveolar gradient [P(a-et) CO 2 ]; and the slope of phase III of the CO 2 spirogram (Slp III).Considering the patient's rapid deterioration, imminent risk of death and VC values indicative of increase in the alveolar dead space...

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules (21-24 nt) that negatively regulate gene expression, either by repression of translation or by degradation of messenger RNA. These molecules are involved in many important processes including cell differentiation, neurogenesis, formation of nervous system and others. Mesial temporal lobe epilepsy and epilepsy caused by cortical dysgenesis are among the leading causes of drug resistant epilepsy. OBJECTIVES: The objectives of this study were to characterize the expression profile of miRNAs and to investigate their regulation in mesial temporal lobe epilepsy (MTL) and in focal cortical dysplasias (FCDs). METHODS: Total RNA was extracted from hippocampal and neocortical tissue, maintained in paraffin or fresh-frozen, from patients who underwent surgery for seizure control. For comparison we used tissue obtained from autopsy. RNA was extracted and used in real time PCR reactions (157 miRNAs analyzed) or microarray chips (847 miRNAs analyzed). RESULTS: Bioinformatics analyzes identified three miRNAs with expression significantly different in patients with MTLE: let-7d, miR-29b and miR-30d; while in patients with FCDs we found 23 microRNAs differentially expressed. In addition, we found that different pathological forms of had different molecular signatures. CONCLUSIONS: The possible genes regulated by miRNAs with differential expression in tissue with mesial temporal sclerosis (MTS) are mainly related to neurogenesis and apoptosis. While in DCFs they were predominantly related to cell proliferation and migration. Our results demonstrate the importance of miRNA regulation the in molecular processes that lead to the lesions present in the MTS and the FCDs.

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Background:During glioma surgery “maximal safe resection” must be the main goal. Intraoperative magnetic resonance imaging (iMRI) associated with awake craniotomy (AC) is a valuable tool to achieve this objective. In this article, AC with a “next-door” iMRI concept is described in a stepwise protocol.Methods:This is a retrospective analysis of 18 patients submitted to AC using iMRI; a stepwise protocol is also discussed.Results:The mean age was 41.7 years. Hemiparesis, aphasia, and seizures were the main initial symptoms of the patients. Sixty-six percent of the tumors were located in the left hemisphere. All tumors were near or within eloquent areas. Fifty-three percent of the cases were glioblastomas multiforme and 47% of the patients had low grade gliomas. The mean surgical time and iMRI time were 4 h 4 min and 30 min, respectively. New resection was performed in 33% after iMRI. Extent of resection (EOR) higher than 95% was possible in 66.7% of the patients. The main reason of EOR lower than 95% was positive mapping of eloquent areas (6 patients). Eighty percent of the patients experienced improvement of their deficits immediately after the surgery or had a stable clinical status whereas 20% had neurological deterioration, however, all of them improved after 30 days.Conclusion:AC associated with “next-door” iMRI is a complex procedure, but if performed using a meticulous technique, it may improve the overall tumor resection and safety of the patients.

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