Familial autoimmunity in neurological patients with GAD65 antibodies: an interview-based study

Journal of Neurology - The common co-occurrence of autoimmune systemic diseases in patients with neurological disorders and antibodies against glutamic acid decarboxylase 65 (GAD65) suggests a...     

Primary brain tumours in adults

Important advances have been made in the understanding and management of adult gliomas and primary CNS lymphomas--the two most common primary brain tumours. Progress in imaging has led to a better analysis of the nature and grade of these tumours. Findings from large phase 3 studies have yielded some standard treatments for gliomas, and have confirmed the prognostic value of specific molecular alterations. High-throughput methods that enable genome-wide analysis of tumours have improved the knowledge of tumour biology, which should lead to a better classification of gliomas and pave the way for so-called targeted therapy trials. Primary CNS lymphomas are a group of rare non-Hodgkin lymphomas. High-dose methotrexate-based regimens increase survival, but the standards of care and the place of whole-brain radiotherapy remain unclear, and are likely to depend on the age of the patient. The focus now is on the development of new polychemotherapy regimens to reduce or defer whole-brain radiotherapy and its delayed complications.     

Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide

There is a growing evidence of using Temozolomide as upfront therapy for progressive low grade gliomas. No data exist on the efficacy of nitrosoureas as an alternative to radiotherapy in those patients who progress after Temozolomide. We retrospectively reviewed 30 patients with median age of 46 years. Twenty-one patients had pure oligodendrogliomas. Thirteen patients had a non-enhancing tumor at progression after Temozolomide. The chromosomes 1p/19q were co-deleted in 5 cases and retained in 10 cases. Response rate was 10% (3 minor responses achieved in non-enhancing tumors). Tolerance was acceptable (17% grade III and IV myelosupression). Median PFS was 6.5 months. Median OS from start of salvage treatment was 23.4 months. Tumors without contrast enhancement demonstrated a better prognosis than those with contrast enhancement both in term of PFS (P = 0.0003) and OS (P = 0.0006). Chromosomes 1p/19q codeletion was not predictive for objective response to salvage treatment but correlated with a better PFS (P = 0.02). In conclusion, salvage NU chemotherapy provide disappointing results in TMZ-pretreated low grade gliomas (LGG), which should be treated in priority by conventional radiotherapy especially in LGG that display contrast enhancement at progression.     

Combined analysis of MGMT methylation and dynamic-susceptibility-contrast MRI for the distinction between early and pseudo-progression in glioblastoma patients

IntroductionCurrently, no single diagnostic modality allows the distinction between early progression (EP) and pseudo-progression (Psp) in glioblastoma patients. Herein we aimed to identify the characteristics associated with EP and Psp, and to analyze their diagnostic value alone and in combination.Material and methodsWe reviewed the clinical, conventional magnetic resonance imaging (MRI), and molecular characteristics (MGMT promoter methylation, IDH mutation, and EGFR amplification) of glioblastoma patients who presented an EP (n = 59) or a Psp (n = 24) within six months after temozolomide radiochemotherapy. We analyzed relative cerebral blood volume (rCBV) and relative vessel permeability on K2 maps (rK2) in a subset of 33 patients using dynamic-susceptibility-contrast MRI.ResultsIn univariate analysis, EP was associated with neurological deterioration, higher doses of dexamethasone, appearance of a new enhanced lesion, subependymal enhancement, higher rCBV and rK2 values. Psp occurred earlier after radiotherapy completion and was associated with IDH1 R132H mutation, and MGMT methylation. In multivariate analysis, rCBV, rK2, and MGMT methylation status were independently associated with EP and Psp. All patients with a methylated MGMT promoter and a low rCBV (< 1.75) were classified as Psp while all patients with an unmethylated MGMT promoter and a high rCBV (≥ 1.75) were classified as EP. Among patients with discordant MGMT methylation and rCBV characteristics, higher rK2 values tended to be associated with EP.ConclusionCombined analysis of MGMT methylation, rCBV and vessel permeability on K2 maps seems helpful to distinguish EP from Psp. A prospective study is warranted to confirm these results.     

Isolated seizures are a common early feature of paraneoplastic anti-GABAB receptor encephalitis

Journal of Neurology - To report the clinical features and long-term outcome of 22 newly diagnosed paraneoplastic patients with GABAB receptor antibodies (GABABR-Abs). Retrospective clinical study...     

IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and microRNA-dependent gene regulation; comparative placentation; trophoblast differentiation; stem cells

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2011 there were twelve themed workshops, five of which are summarized in this report. These workshops related to various aspects of placental biology: 1) immunology; 2) epigenetics; 3) comparative placentation; 4) trophoblast differentiation; 5) stem cells.