Natural course of Myoclonus-Dystonia in adulthood: stable motor signs but increased psychiatry

Myoclonus‐dystonia (M‐D) is a rare hyperkinetic movement disorder characterized by upper body–predominant myoclonus and dystonia.1 A large proportion of cases are caused by autosomal‐dominant inherited mutations in the SGCE gene. In addition to the motor manifestations, psychiatric disorders are frequently reported.2 Several studies have suggested that they may form a primary component of the M‐D phenotype.3, 4 This study represents the first long‐term follow‐up study of both motor and psychiatric symptomatology in adults with M‐D (SGCE mutation), providing further insights into the natural history of M‐D and enabling more prognostic information

Internet-based guided self-help for glioma patients with depressive symptoms: a randomized controlled trial

Depressive symptoms are common in glioma patients, and can negatively affect health-related quality of life (HRQOL). We performed a nation-wide randomized controlled trial to evaluate the effects of an online guided self-help intervention for depressive symptoms in adult glioma patients. Glioma patients with depressive symptoms were randomized to a 5-week online course based on problem-solving therapy, or a waiting list control group. After having received the intervention, the glioma patient groups combined were compared with patients with cancer outside the central nervous system (non-CNS cancer controls), who also received the intervention. Sample size calculations yielded 63 participants to be recruited per arm. The primary outcome [depressive symptoms (CES-D)] and secondary outcomes [fatigue (Checklist Individual Strength (CIS)) and HRQOL (Short Form-36)], were assessed online at baseline, post-intervention, and 3 and 12 months follow-up. In total, 89 glioma patients (intervention N = 45; waiting list N = 44) and 26 non-CNS cancer controls were included, of whom 35 and 54% completed the intervention, respectively. Recruitment could not be extended beyond 3.5 years due to funding. On depression, no statistically significant differences between the groups were found. Fatigue decreased post-treatment in the glioma intervention group compared with the waiting list group (p = 0.054, d = 0.306). At 12 months, the physical component summary (HRQOL) remained stable in glioma patients, while scores improved in non-CNS cancer controls (p = 0.035, d = 0.883). In this underpowered study, no evidence for the effectiveness of online guided self-help for depression or HRQOL in glioma patients was found, but it may improve fatigue

Myoclonus-dystonia and spinocerebellar ataxia type 14 presenting with similar phenotypes: Trunk tremor, myoclonus, and dystonia

We describe three genetically confirmed myoclonus dystonia (M-D) patients and one spinocerebellar ataxia type 14 (SCA14) patient, presenting with a combination of trunk tremor, multifocal myoclonus and axial dystonia as predominant clinical features. We suggest that in patients with this M-D phenotype, without a mutation in the DYT11 gene, SCA14 should be considered. (C) 2009 Elsevier Ltd. All rights reserved

Prediction of spinal epidural metastases

Context: Early diagnosis and treatment of spinal epidural metastases (SEM) is of the utmost importance to prevent neurological deficit due to spinal cord compression. Magnetic resonance imaging (MRI) has become the final tool in that diagnostic process. However, access to MRI is still limited in the Netherlands, requiring cost-effective use. It is generally acknowledged that patients with systemic cancer who present with a radiculopathy or myelopathy should undergo an MRI. However, the diagnostic policy in patients with systemic cancer who present with recently developed back pain is still a matter of debate. Objective: To identify the patients with back pain in whom MRI can safely be omitted because of a low risk of SEM. Methods: In a prospective series of 170 consecutive patients with cancer with recently developed back pain, prediction of spinal metastatic disease (SMD) and especially SEM was studied by means of a multivariate risk analysis of the parameters of the standard neurological evaluation (medical history, neurological examination, and plain films of the whole spine). Magnetic resonance imaging was used as the criterion standard. We calculated the risk implications of omitting MRI in patients with an estimated risk below different cutoff points. Results: Spinal metastatic disease was diagnosed in 80 patients (47%); of these, 31 had SEM. A metastatic abnormality on plain films was the strongest independent predictor for SMD. Other important predictors were night pain, progressive pain, and Karnofsky score. Advanced age, exacerbation of pain during recumbency, and osteoporotic fracture imply a low risk of SMD. Night pain and the Karnofsky score proved to be the main predictors for SEM. A plain film showing an osteoporotic fracture strongly decreased the risk of SEM. The discriminating value of the multivariate analysis was too low, and too few patients can be excluded from undergoing MRI on the basis of the standard neurological checkup. To identify all the patients with SMD (P<.01), MRI would be excluded in only 7 patients. Identification of all patients with SEM (P<.001) reduced the number of MRIs by 21 at the expense of plain films of the whole spine for any patient. Conclusions: Selection of patients with cancer with back pain at risk of SEM was not possible with the standard neurological checkup. After intake by the neurologist, the next step should be MRI of the whole spine

Usefulness of multiplane transesophageal echocardiography to improve the assessment of severity of mitral regurgitation

This study was designed to examine the accuracy of multiplane transesophageal echocardiography (TEE) color Doppler measurements in comparison to monoplane or biplane measurements in estimating the severity of mitral regurgitation (MR). Multiplane TEE potentially increases diagnostic accuracy of transesophageal examinations; it is unknown if multiplane is more accurate in assessing the severity of MR than monoplane or biplane TEE. Left ventricular cineangiograms of 91 patients with MR (40 no or mild, 30 moderate, and 21 severe) were compared with systolic pulmonary venous flow reversal and transesophageal color Doppler measurements: jet area and length in the transverse and longitudinal plane, maximal and average of those 2 planes (biplane), and maximal and average of 11 different planes (multiplane). Flow reversal (16 patients) identified severe MR with a specificity of 96% and a sensitivity of 62%; these were 96% and only 10% to 43%, respectively, for color Doppler measurements. in the absence of flow reversal, multiplane maximal jet area predicted severe MR with a sensitivity of 88% and a specificity of 75%, which were 85% and 76%, respectively, for no or mild MR; this did not differ significantly from results obtained by monoplane or biplane measurements. Color Doppler measurements of eccentric jets were not reliable for identification of severe MR. Systolic pulmonary venous flow reversal identifies 2 of 3 patients with severe MR with a high accuracy. In patients without flow reversal, multiplane color Doppler TEE is very capable of assessing MR severity, but biplane and monoplane TEE are equally accurate. (C) 1996 by Excerpta Medica, Inc

Health-related quality of life and cognitive functioning in longterm anaplastic oligodendroglioma and oligoastrocytoma survivors

Overall survival of patients with anaplastic oligodendroglial tumors has been improved due to the addition of procarbazine, lomustine and vincristine (PCV) chemotherapy to radiotherapy (RT), especially in 1p/19q-codeleted tumors. With improved survival, quality of survival becomes pivotal. We evaluated cognitive functioning and health-related quality of life (HRQOL) in a cohort of long-term anaplastic oligodendroglioma survivors. Thirty-two out of 37 long-term survivors included in European Organisation for Research and Treatment of Cancer (EORTC) study 26951 in the Netherlands and France participated. Cognition was assessed using neuropsychological tests for 6 domains, and HRQOL with the EORTC Quality of Life Questionnaire (EORTC QLQ-C30) and Brain Cancer Module (EORTC QLQ-BN20). Fatigue and mood were evaluated. Results were compared to healthy controls and to patients' own HRQOL 2.5 years following initial treatment. At the time of assessment, median survival for the patients was 147 months, 27 were still progression- free since initial treatment. Of progression-free patients, 26 % were not, and 30 % were severely cognitively impaired; 41 % were employed and 81 % could live independently. Patients' HRQOL was worse compared to controls, but similar to 2.5 years after initial treatment. Initial treatment (RT versus RT + PCV) was not correlated with cognition or HRQOL. In conclusion, cognitive functioning in long-term anaplastic oligodendroglioma survivors is variable. However, most patients function independently. In progression-free patients, HRQOL is relatively stable during the disease course. In this small sample, no effect of the addition of PCV on cognition or HRQOL was identified

Barrett's oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel

Objective Reported malignant progression rates for low-grade dysplasia (LGD) in Barrett's oesophagus (BO) vary widely. Expert histological review of LGD is advised, but limited data are available on its clinical value. This retrospective cohort study aimed to determine the value of an expert pathology panel organised in the Dutch Barrett's Advisory Committee (BAC) by investigating the incidence rates of high-grade dysplasia (HGD) and oesophageal adenocarcinoma (OAC) after expert histological review of LGD. Design We included all BO cases referred to the BAC for histological review of LGD diagnosed between 2000 and 2011. The diagnosis of the expert panel was related to the histological outcome during endoscopic follow-up. Primary endpoint was development of HGD or OAC. Results 293 LGD patients (76% men; mean 63 years +/- 11.9) were included. Following histological review, 73% was downstaged to non-dysplastic BO (NDBO) or indefinite for dysplasia (IND). In 27% the initial LGD diagnosis was confirmed. Endoscopic follow-up was performed in 264 patients (90%) with a median followup of 39 months (IQR 16-72). For confirmed LGD, the risk of HGD/OAC was 9.1% per patient-year. Patients downstaged to NDBO or IND had a malignant progression risk of 0.6% and 0.9% per patient-year, respectively. Conclusions Confirmed LGD in BO has a markedly increased risk of malignant progression. However, the vast majority of patients with community LGD will be downstaged after expert review and have a low progression risk. Therefore, all BO patients with LGD should undergo expert histological review of the diagnosis for adequate risk stratification

IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group.

Item does not contain fulltextPURPOSE: Recent studies have shown the prognostic significance of IDH1 mutations in glioma. It is yet unclear if IDH1 mutations are predictive for outcome to chemotherapy. We determined the effect of IDH1 mutations on progression-free survival and overall survival (OS), and its correlation with other clinical and molecular features in the prospective randomized European Organization for Research and Treatment of Cancer study 26951 on adjuvant procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea, and vincristine (PCV) in anaplastic oligodendroglioma. EXPERIMENTAL DESIGN: IDH1 and IDH2 alterations of the mutational hotspot codons R132 and R172 were assessed by the bidirectional cycle sequencing of PCR-amplified fragments. MGMT promoter methylation was assessed using methylation-specific multiplex ligation-dependant probe amplification based on methylation-sensitive restriction analysis. Loss of chromosomes 1p, 19q, 10, and 10q and the gain of 7 and the EGFR gene were assessed with fluorescence in situ hybridization. RESULTS: From 159 patients, sufficient material was available for IDH1 analysis. In 151 and 118 of these patients, respectively, the 1p/19q status and the MGMT promoter methylation status were known. In 73 cases (46%), an IDH1 mutation was found and only one IDH2 mutation was identified. The presence of IDH1 mutations correlated with 1p/19q codeletion and MGMT promoter methylation, and inversely correlated with loss of chromosome 10, EGFR amplification, polysomy of chromosome 7, and the presence of necrosis. IDH1 mutations were found to be prognostic in the radiotherapy- and the radiotherapy/PCV-treated patients, for both progression-free survival and OS. With Cox proportional hazard modeling for OS with stepwise selection, IDH1 mutations and 1p/19q codeletion but not MGMT promoter methylation were independent prognostic factors. CONCLUSION: In this homogeneously treated group of anaplastic oligodendroglioma patients, the presence of IDH1 mutations was found to carry a very strong prognostic significance for OS but without evidence of a predictive significance for outcome to PCV chemotherapy. IDH1 mutations were strongly associated with 1p/19q codeletion and MGMT promoter methylation