The nature and extent of recovery after traumatic brain injury (TBI) is heterogeneous. Apolipoprotein E (APOE) plays a major role in repair of cell membrane and growth of neurites following injury to ...cells. Studies done on the western population have shown that the APOE e4 genotype is associated with poor survival following neurotrauma.
To explore the association of APOE polymorphism and outcome following TBI in a patient population from a tertiary care hospital exclusive for neurological diseases in south India.
Ninety eight patients who sustained mild to moderate TBI (computed tomography (CT) scan brain showing traumatic parenchymal contusions) were the subjects of the study and the study period was from November 2003 to December 2008. APOE polymorphism status was determined by PCR technique using venous blood. Patients were assessed on follow-up with a battery of four neuropsychological tests as well as Glasgow outcome scale.
Of the 98 patients, 20 (20%) patients had at least one APOE e4 allele. A follow-up of minimum six months was available for 73 patients. None of the 12 patients who had at least one APOE e4 allele had a poor outcome at six-month follow-up whereas 11(18%) patients without an APOE e4 allele had a poor outcome (Fisher's Exact test, P=0.192). On the neuropsychological tests, performance of patients with APOE e4 allele did not differ significantly from those without these alleles.
This study does not support the current contention that the presence of APOE e4 allele should have a significant negative effect on the outcome after TBI.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract
Intracisternal papaverine instillation is being used across many centers after cerebral aneurysm clipping to prevent and treat cerebral vasospasm. Pupillary dilatation secondary to ...papaverine can interfere with the neurological assessment postoperatively. This report describes pupillary changes in three patients following the papaverine application after craniotomy and aneurysm clipping, with one patient developing contralateral pupillary dilatation and the other two having bilateral pupillary dilatation. The pupillary changes resolved over 30 min to 4 h postoperatively. We conclude that pupillary changes following papaverine instillation could be a transient phenomenon and should not be considered ominous in absence of new onset neurological deficits. Intraoperative somatosensory evoked potential monitoring also helped in postoperative decision making in all our cases.
Abstract We report on two patients with rare major intratumoral hemorrhage following ventriculoperitoneal shunt in posterior fossa tumors. A 28-year-old woman with a midline posterior fossa lesion, ...whose imaging features suggested a fourth ventricular ependymoma with obstructive hydrocephalus, was subjected to a right ventriculoperitoneal shunt. Her consciousness deteriorated, and she experienced massive intratumoral hemorrhage and later died. An eight-year-old girl presented with raised intracranial pressure and ataxia caused by vermian astrocytoma with obstructive hydrocephalus. She also developed a massive tumor bleed following a ventriculoperitoneal shunt and was subjected to emergency decompression of the tumor with the bleeding. She remained vegetative at discharge and died 18 months later. Intratumoral hemorrhage is a rare but important cause of morbidity and mortality in patients with posterior fossa tumors who undergo ventriculoperitoneal shunt.
Introduction. Ion channels are subjects of intense research, due to their easy access and potential for being drug targets. Kv1.5 is a voltage gated potassium channel, earlier thought to be cardiac ...specific. Recent studies have revealed that K+ channels play an important role in apoptosis, glial cell proliferation and biology of various cancers. No study has so far been performed to assess their expression in astrocytomas and correlate its impact on the clinical behaviour of gliomas. Methods. Sixty samples of astrocytoma which included 9 diffuse astrocytoma (DA) grade II, 11 anaplastic astrocytoma (AA) grade III and 40 glioblastoma (GBM), along with normal brain tissue (cerebral cortex; n = 5) were analysed for their Kv1.5 protein expression. Immunohistochemical expression of Kv1.5 in various grades was assessed semi quantitatively. The patients with GBM (n = 40) were treated with uniform protocol and their survival was documented.Results. The mean expression of Kv1.5 in DA, AA and GBM was 22.2 ± 9.71%, 11.81 ± 12.3% and 10.37 ± 11.05%, respectively, the difference being statistically significant (p = 0.004). The mean expression in low grade astrocytoma (WHO II) was significantly higher than higher grades (22.2% and 10.7%; p = 0.005). On analysing the influence of Kv1.5 expression on survival of GBM patients, we noted that increasing Kv1.5 labelling index (LI) correlated with a favourable prognosis, albeit not being significant (p = 0.310; HR = 0.901).Conclusions. Kv1.5 expression occurs more in DA, when compared to high grade astrocytoma. GBM patients with higher Kv1.5 expression had better survival, though not reaching statistical significance.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess the prognostic influence of EGFR amplification/overexpression, p53 immunoreactivity and their age-dependent prognostic effects in a large prospective cohort of uniformly treated adult ...patients with newly diagnosed glioblastoma.
Tumours from a uniformly treated prospective cohort of adult patients with newly diagnosed glioblastoma (n=140) were examined for EGFR amplification by fluorescence in situ hybridisation and EGFR/p53 expression by immunohistochemistry. Statistical methods were employed to assess the degree of association between EGFR amplification/overexpression and p53 immunopositivity. Survival analyses were performed by employing Cox proportional hazard models to assess the independent prognostic value of EGFR/p53 alterations and test the propensity for risk with age by assessing their interaction with patient age.
A strong positive correlation between EGFR amplification and EGFR overexpression (rho=0.5157; p<0.0001; CI 0.3783 to 0.6309) and a negative association of EGFR amplification (rho=-0.3417; p<0.0001; CI -0.4842 to -0.1816) and EGFR overexpression (rho=-0.3095; p<0.001; CI -0.4561 to -0.1465) with p53 immunopositivity was observed. Only patient age (HR: 1.029; p=0.004; CI 1.009 to 1.049) was associated with shorter survival by univariate Cox regression analysis. Multivariable Cox proportional hazards models revealed a statistically significant interaction between EGFR overexpression and age to be associated with shorter survival (HR: 1.001; p<0.0001; CI 1.000 to 1.002), thus predicting a higher hazard with increasing age. No age interaction of EGFR amplification status (HR: 1.001; p=0.642; CI 0.995 to 1.008) and p53 immunopositivity (HR: 1.000; p=0.841; CI 0.999 to 1.001) was noted in this cohort.
The prognostic value of EGFR overexpression is age-dependent, and there is a propensity for a higher hazard with increasing patient age. Identifying such groups of patients with more aggressive disease becomes mandatory, since they would benefit from intense therapeutic protocols targeting EGFR.
The search for molecular markers which predict response to chemotherapy is an important aspect of current neuro-oncology research. MGMT promoter methylation is the only proved marker of glioblastoma. ...The purpose of this study was to assess the effect of topoisomerase expression on glioblastoma survival and study the mechanisms involved. The transcript levels of all isoforms of the topoisomerase family in all grades of diffuse astrocytoma were assessed. A prospective study of patients with glioblastoma treated by a uniform treatment procedure was performed with the objective of correlating outcome with gene expression. The ability of TOP2A enzyme to relax the super coiled plasmid DNA in the presence of temozolomide was evaluated to assess its effect on TOP2A. The temozolomide cyctotoxicity of TOP2A-silenced U251 cells was assessed. The transcript levels of TOP2A, TOP2B, and TOP3A are upregulated significantly in GBM in comparison with lower grades of astrocytoma and normal brain samples. mRNA levels of TOP2A correlated significantly with survival of the patients. Higher TOP2A transcript levels in GBM patients predicted better prognosis (
P
= 0.043;
HR
= 0.889). Interestingly, we noted that temozolomide inhibited TOP2A activity in in-vitro enzyme assays. We also noted that siRNA knock down of TOP2A rendered a glioma cell line resistant to temozolomide chemotherapy. We demonstrated for the first time that temozolomide is also a TOP2A inhibitor and established that TOP2A transcript levels determine the chemosensitivity of glioblastoma to temozolomide therapy. Very high levels of TOP2A are a good prognostic indicator in GBM patients receiving temozolomide chemotherapy.
Focal intradural infections of the brain include empyema and abscess in the supratentorial and infratentorial spaces. These are amenable to surgical management. Various other issues may complicate ...the course of management, e.g. hydrocephalus with infratentorial lesions or cortical venous thrombosis with supratentorial lesions. Here, we review the management and identify factors affecting outcome in these patients.
This is a retrospective analysis of all children (aged <18 years) treated at the National Institute of Mental Health and Neurosciences, Bangalore, India, between 1988 and 2004. Case records were analyzed to obtain clinical, radiological, bacteriological and follow-up data.
There were 231 children who underwent treatment for focal intradural abscess/empyema at our institute. These included 57 children with cerebral abscess, 65 with supratentorial empyema, 82 with cerebellar abscess and 27 with infratentorial empyema. All patients underwent emergency surgery (which was either burr hole and aspiration of the lesion or craniotomy/craniectomy and excision/evacuation), along with antibiotic therapy, typically 2 weeks of intravenous and 4 weeks of oral therapy. The antibiotic regimen was empiric to begin with and was altered if any sensitivity pattern of the causative organism(s) could be established by culture. Hydrocephalus was managed with external ventricular drainage initially and with ventriculoperitoneal shunt if warranted. Mortality rates were 4.8% for cerebral abscess, 9.6% for cerebellar abscess, 10.8% for supratentorial subdural empyema and 3.7% for posterior fossa subdural empyema. The choice of surgery was found to have a strong bearing on the recurrence rates and outcome in most groups, with aggressive surgery with craniotomy leading to excellent outcomes with a low incidence of residual/recurrent lesions.
Antibiotic therapy, emergency surgery and management of associated complications are the mainstays of treatment of these lesions. We strongly advocate early, aggressive surgery with antibiotic therapy in children with focal intradural infections.
Cervical lesions compressing the spinal cord pose a significant risk of exacerbating the existing neurological condition during tracheal intubation and subsequent positioning. Awake ...fibreoptic-assisted intubation is a suitable option in such situations. We describe how the use of dexmedetomidine for sedation during awake fibreoptic intubation also facilitated self-positioning before surgery in a patient with a cervical cord compressive lesion and raised intracranial pressure undergoing excision of a cerebellopontine angle lesion in the lateral position, without any adverse neurological outcome.
A contrast ventriculogram revealed communication between the frontal horn of right ventricle and cystic orbital lesion Figure 1b. Subsequent magnetic resonance imaging (MRI) better delineated the ...communication of the ventricle to the orbital cyst and dural breach on T2-weighted (T2W) Figure 2b and CISS 3D sequences Figure 2c. The communicating tract margins were hyperintense on T1-weighted (T1W) image Figure 2a and hypointense on T2W image, suggesting subacute hemorrhage (representing hemorrhagic laceration of frontal lobe).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK