Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1(R132H) mutations. Patients harbouring IDH1(R132H) mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1(R132H) have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1(R132H) mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication.MTG6Molecular tumour pathology - and tumour genetic

Antiretroviral drugs and the central nervous system

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Operative treatment of anterior thoracic spinal cord herniation: three new cases and an individual patient data metaaAnalysis of 126 case reports

OBJECTIVE: Anterior thoracic spinal cord herniation is a rare cause of progressive myelopathy. Much has been speculated about the best operative treatment. However, no evidence in favor of any of the promoted techniques is available to date. Therefore, we decided to analyze treatment procedures and treatment outcomes of anterior thoracic spinal cord herniation to identify those factors that determine postoperative outcome. METHODS: An individual patient data meta-analysis was conducted, focusing on age, gender, vertebral segment of herniation, preoperative neurological status, operative interval, operative findings, operative techniques, intraoperative neurophysiological monitoring, postoperative imaging, neurological outcome and follow-up. Three cases from our own institution were added to the material collected. Bivariate analysis tests and multivariate logistic regression tests were used so as to define which variables were associated with outcome after surgical treatment of anterior thoracic spinal cord herniation. RESULTS: Brown-Sequard syndrome and release of the herniated spinal cord appeared to be strong independent factors, associated with favorable postoperative Outcome. Widening of the dura defect is associated with the highest prevalence of postoperative motor function improvement when compared with the application of an anterior dura patch (P < 0.036). CONCLUSION: Most patients with anterior thoracic spinal cord herniation require operative treatment because of progressive myelopathy. Patients with Brown-Sequard syndrome have a better prognosis with respect to postoperative motor function improvement, In this review, spinal cord release and subsequent widening of the dural defect were associated with the highest prevalence of motor function improvement. D-wave recording can be a very useful tool for the surgeon during operative treatment of this disorder,

Antimicrobial susceptibility of Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae isolates causing meningitis in the Netherlands 1993-1994

The increasing antimicrobial resistance among pathogens frequently isolated from patients with bacterial meningitis formed the rationale to perform a surveillance study to determine the prevalence of resistance in The Netherlands. Haemophilus influenzae strains (n = 316) isolated from cerebrospinal fluid (CSF), 1125 meningococcal strains isolated from blood or CSF and 398 pneumococcal strains isolated from CSF in 1993 and 1994 were tested by the Etest for susceptibility to commonly prescribed antibiotics for the treatment of community-acquired meningitis. In H. influenzae strains ampicillin-resistance occurred in 7.0%, resistance to chloramphenicol in 2.2%, and resistance to both antibiotics in 0.9%. The prevalence of intermediate penicillin-resistance in meningococci was 3.3%. Resistance to rifampicin was rarely found (0.1%). Intermediate penicillin-resistance in pneumococci was found in only 0.5% of isolates. All 1839 isolates were susceptible to ceftriaxone. Based on these results, we conclude that empirical therapy of childhood community-acquired bacterial meningitis with amoxycillin and chloramphenicol is no longer justified in children who have not been vaccinated against H. influenzae type b. In vaccinated or older children and adults, amoxycillin is a rational choice for empirical treatment of meningitis. The prophylactic use of rifampicin in contacts of patients with meningococcal disease is still applicabl

Neuralgic amyotrophy associated with Bartonella henselae infection

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