Diffuse H3 K27M-mutant gliomas occur primarily in children but can also be encountered in adults. The aim of this study was to describe the characteristics of H3 K27M-mutant gliomas in adults.
We ...analyzed the characteristics of 21 adult H3 K27M-mutant gliomas and compared them with those of 135 adult diffuse gliomas without histone H3 and without isocitrate dehydrogenase (IDH) mutation (IDH/H3 wild type).
The median age at diagnosis in H3 K27M-mutant gliomas was 32 years (range: 18-82 y). All tumors had a midline location (spinal cord n = 6, thalamus n = 5, brainstem n = 5, cerebellum n = 3, hypothalamus n = 1, and pineal region n = 1) and were IDH and BRAF-V600E wild type. The identification of an H3 K27M mutation significantly impacted the diagnosis in 3 patients (14%) for whom the histological aspect initially suggested a diffuse low-grade glioma and in 7 patients (33%) for whom pathological analysis hesitated between a diffuse glioma, ganglioglioma, or pilocytic astrocytoma. Compared with IDH/H3 wild-type gliomas, H3 K27M-mutant gliomas were diagnosed at an earlier age (32 vs 64 y, P < .001), always had a midline location (21/21 vs 21/130, P < .001), less frequently had a methylated MGMT promoter (1/21 vs 52/129, P = .002), and lacked EGFR amplification (0/21 vs 26/128, P = .02). The median survival was 19.6 months in H3 K27M-mutant gliomas and 17 months in IDH/H3 wild-type gliomas (P = .3).
In adults, as in children, H3 K27M mutations define a distinct subgroup of IDH wild-type gliomas characterized by a constant midline location, low rate of MGMT promoter methylation, and poor prognosis.
Introduction
Most of our knowledge into autoimmune encephalitis (AE) comes from N-Methyl-D-Aspartate Receptor (NMDAR) encephalitis. The concentrations of cytokines in cerebrospinal fluid (CSF) ...including IL-17A have been found to be increased and associated with poor outcome. However, data on the cytokine concentration in CSF and its correlation with outcome is lacking for other types of AE.
Objective
To report the concentrations of CSF sIL-2R, IL-6, IL-8, IL-10 and IL-17A and to correlate it with acute disease severity and the 1-year outcome in non-NMDAR AE.
Methods
We measured the CSF concentration of each cytokine in 20 AE patients, and compared IL-6 and IL-17A concentrations with 13 patients with CNS demyelinating diseases and 20 non-inflammatory controls. Patients were > 18yr and had at least 1-year clinical follow-up. Intracellular and NMDAR antibody (Ab) -mediated encephalitis were excluded. A mRS ≤ 2 was retained as a 1-year good outcome.
Results
The IL-17A concentration in CSF was higher in AE patients than in both control groups (
p
<0.01). No difference was observed in CSF concentration of IL-6 between groups. At disease onset, a high CSF IL-17A concentration correlated with a high modified Rankin Scale (
p
<0.05), a high Clinical Assessment Scale for Autoimmune Encephalitis score (
p
<0.001) and ICU admission (
p
<0.01). There was no correlation between the concentration of all CSF cytokines and the 1-year clinical outcome.
Conclusion
Our results show that CSF IL-17A could be interesting to assess initial severity in non-NMDAR AE. Thus, CSF IL-17A could be an interesting therapeutic target and be useful to assess early selective immunosuppressive therapy.
Amyoplasia and distal arthrogryposis Griffet, Jacques; Dieterich, Klaus; Bourg, Véronique ...
Orthopaedics & traumatology, surgery & research,
February 2021, 2021-Feb, 2021-02-00, 20210201, Letnik:
107, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Arthrogryposis multiplex congenita (AMC) consists of congenital joint contractures that affect at least two joints. There are two types: in the first, arthrogryposis is an additional sign in the ...context of various pathologies (neuromuscular diseases); in the second, it is the main and constant symptom. In the first type, the progression of the causal underlying disease must be considered. In the second type, there are two specific forms: Amyoplasia corresponds to a significant congenital absence of muscles (epigenetic disease or vascular origin) while distal arthrogryposis has a genetic component and is transmissible. The orthopedic surgeon's purpose, which is usually to enhance movement, is not appropriate for an arthrogryposis patient. One must keep in mind that without muscle, movement is impossible. The goal differs between the upper and lower limbs: for the upper limb, it is to allow grasping, and, if possible, to bring the hand to the mouth; for the lower limb, it is to ensure ambulation with plantigrade support, and the knees extended, which is the only stable position possible with little to no muscles. The rehabilitation, orthoses and/or surgical techniques are chosen to achieve this singular aim. While it may appear modest, it is crucial for patients. The goal is to achieve useful mobility, not maximum mobility. This multidisciplinary treatment, which evolves over time, must be explained to the family to get its adherence.
Abstract Rituximab (RTX) has demonstrated efficacy in limiting relapses in myasthenia gravis (MG). We investigated the interest of CD27 + memory B cell monitoring in patients as a biological marker ...of clinical relapse. Twenty-four patients have been treated with RTX (375 mg
/m2 /week-month
as an induction treatment). Maintenance treatment consisted with either systematic treatment every 3 months or only when CD27 + memory B cells were detectable. After the induction treatment, the mean infusions were 1.3/year
compared with 4/year
. We suggest that RTX administration frequency can be decreased safely by monitoring the re-emerging CD27 + memory B cells.
Arthrogryposis multiplex congenita (AMC) refers to a clinical presentation of congenital contractures involving two or more body areas. More than 400 distinct conditions may lead to AMC, making the ...aetiological diagnosis challenging. The objective of this work was to set up evidence-based recommendations for the diagnosis of AMC by taking advantage of both data from our nation-wide cohort of children with AMC and from the literature.
We conducted a retrospective single-centre observational study. Patients had been evaluated at least once at a paediatric age in the AMC clinic of Grenoble University Hospital between 2007 and 2019. After gathering data about their diagnostic procedure, a literature review was performed for each paraclinical investigation to discuss their relevance.
One hundred and twenty-five patients were included, 43% had Amyoplasia, 27% had distal arthrogryposis and 30% had other forms. A definitive aetiological diagnosis was available for 66% of cases. We recommend a two-time diagnostic process: first, non-invasive investigations that aim at classifying patients into one of the three groups, and second, selected investigations targeting a subset of patients.
The aetiological management for patients with AMC remains arduous. This process will be facilitated by the increasing use of next-generation sequencing combined with detailed phenotyping. Invasive investigations should be avoided because of their limited yield.
work still needs to be done to measure the impact of sialorrhea on quality of life and define the efficacy of different therapies. The Drooling Impact Scale showed good validity and sensitivity to ...change, especially after botulinum toxin injection. The aim of this study is to present its French translation and to explore its validity, reliability and responsiveness to change in a group of children with Cerebral Palsy.
multicentre study at six rehabilitation centres in France. Children with Cerebral Palsy aged 4-18 years with sialorrhea problems were included (n = 55), either in a control group (n = 33) or in the intervention group (n = 22, with 3 drug treatment and 19 botulinum toxin injections). The French Drooling Impact Scale was administered twice, 1 month apart.
The French Drooling Impact Scale total score at inclusion was meanly 53.9 (Standard Deviation 11.9) in the stable control group and 66.0 (16.1) in the intervention group (p = 0.0058). The validity of the scale was established, as well as an adequate internal consistency (Cronbach's α = 0.71); correlations between each item and the total score were found between 0.5 and 0.71 except for item 5 (r = 0.38) and item 7 (0.41). The test-retest reliability in stable children was good (Lin coefficient = 0.83, bias correction factor = 0.92 and Pearson correlation coefficient = 0.89). There was a high responsiveness to change, mean change was -40.0 in the intervention group and -3.6 in the stable group (p < 0.0001), with Standard Error of Measurement = 2.6.
the French Drooling Impact Scale has shown sufficient clinometric properties to be used now by clinicians or researchers.
IMPLICATIONS FOR REHABILITATION
The Drooling Impact scale has now its French version.
The French version of the Drooling Impact Scale has shown its validity and a good test-retest reliability.
The responsiveness to change was explored in a group of children undergoing saliva-control interventions and the scale was able to show a big change.
The authors recommend to use this questionnaire in a semi-directed interview conducted by a health professional.
Background
Diagnostic value of 3,4-dihydroxy-6-
18
Ffluoro-L-phenylalanine (
18
FFDOPA) PET in patients with suspected recurrent gliomas is recognised. We conducted a multicentre prospective study to ...assess its added value in the practical management of patients suspected of recurrence of high grade gliomas (HGG).
Methods
Patients with a proven HGG (WHO grade III and IV) were referred to the multidisciplinary neuro-oncology board (MNOB) during their follow-up after initial standard of care treatment and when MRI findings were not fully conclusive. Each case was discussed in 2 steps. For step 1, a diagnosis and a management proposal were made only based on the clinical and the MRI data. For step 2, the same process was repeated taking the
18
FFDOPA PET results into consideration. A level of confidence for the decisions was assigned to each step. Changes in diagnosis and management induced by
18
FFDOPA PET information were measured. When unchanged, the difference in the confidence of the decisions were assessed. The diagnostic performances of each step were measured.
Results
107 patients underwent a total of 138 MNOB assessments. The proposed diagnosis changed between step 1 and step 2 in 37 cases (26.8%) and the proposed management changed in 31 cases (22.5%). When the management did not change, the confidence in the MNOB final decision was increased in 87 cases (81.3%). Step 1 had a sensitivity, specificity and accuracy of 83%, 58% and 66% and step 2, 86%, 64% and 71% respectively.
Conclusion
18
FFDOPA PET adds significant information for the follow-up of HGG patients in clinical practice. When MRI findings are not straightforward, it can change the management for more than 20% of the patients and increases the confidence level of the multidisciplinary board decisions.
Approximately 50% of newly diagnosed glioblastomas (GBMs) harbor epidermal growth factor receptor gene amplification (EGFR-amp). Preclinical and early-phase clinical data suggested efficacy of ...depatuxizumab mafodotin (depatux-m), an antibody-drug conjugate comprised of a monoclonal antibody that binds activated EGFR (overexpressed wild-type and EGFRvIII-mutant) linked to a microtubule-inhibitor toxin in EGFR-amp GBMs.
In this phase III trial, adults with centrally confirmed, EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo. Corneal epitheliopathy was treated with a combination of protocol-specified prophylactic and supportive measures. There was 85% power to detect a hazard ratio (HR) ≤0.75 for overall survival (OS) at a 2.5% 1-sided significance level (ie traditional two-sided p ≤ 0.05) by log-rank testing.
There were 639 randomized patients (median age 60, range 22-84; 62% men). Prespecified interim analysis found no improvement in OS for depatux-m over placebo (median 18.9 vs. 18.7 months, HR 1.02, 95% CI 0.82-1.26, 1-sided p = 0.63). Progression-free survival was longer for depatux-m than placebo (median 8.0 vs. 6.3 months; HR 0.84, 95% confidence interval CI 0.70-1.01, p = 0.029), particularly among those with EGFRvIII-mutant (median 8.3 vs. 5.9 months, HR 0.72, 95% CI 0.56-0.93, 1-sided p = 0.002) or MGMT unmethylated (HR 0.77, 95% CI 0.61-0.97; 1-sided p = 0.012) tumors but without an OS improvement. Corneal epitheliopathy occurred in 94% of depatux-m-treated patients (61% grade 3-4), causing 12% to discontinue.
Interim analysis demonstrated no OS benefit for depatux-m in treating EGFR-amp newly diagnosed GBM. No new important safety risks were identified.
Actionable fibroblast growth factor receptor 3 (FGFR3)-transforming acidic coiled-coil protein 3 fusions (F3T3) are found in approximately 3% of gliomas, but their characteristics and prognostic ...significance are still poorly defined. Our goal was to characterize the clinical, radiological, and molecular profile of F3T3 positive diffuse gliomas.
We screened F3T3 fusion by real-time (RT)-PCR and FGFR3 immunohistochemistry in a large series of gliomas, characterized for main genetic alterations, histology, and clinical evolution. We performed a radiological and radiomic case control study, using an exploratory and a validation cohort.
We screened 1162 diffuse gliomas (951 unselected cases and 211 preselected for FGFR3 protein immunopositivity), identifying 80 F3T3 positive gliomas. F3T3 was mutually exclusive with IDH mutation (P < 0.001) and EGFR amplification (P = 0.01), defining a distinct molecular cluster associated with CDK4 (P = 0.04) and MDM2 amplification (P = 0.03). F3T3 fusion was associated with longer survival for the whole series and for glioblastomas (median overall survival was 31.1 vs 19.9 mo, P = 0.02) and was an independent predictor of better outcome on multivariate analysis.F3T3 positive gliomas had specific MRI features, affecting preferentially insula and temporal lobe, and with poorly defined tumor margins. F3T3 fusion was correctly predicted by radiomics analysis on both the exploratory (area under the curve AUC = 0.87) and the validation MRI (AUC = 0.75) cohort. Using Cox proportional hazards models, radiomics predicted survival with a high C-index (0.75, SD 0.04), while the model combining clinical, genetic, and radiomic data showed the highest C-index (0.81, SD 0.04).
F3T3 positive gliomas have distinct molecular and radiological features, and better outcome.
•DTC decreases with advancing age in healthy children during balance and adults could benefit from dual-tasking for standing.•CP and healthy children were similarly affected by dual-task constraints ...during standing and walking.•Children with diplegia were more affected by the DT during the postural task than children with hemiplegia.
Simultaneous execution of motor and cognitive tasks is embedded in the daily life of children. 53 children of 7–12 years and 22 adults (study 1), 20 healthy children and 20 children of 7–12 years with cerebral palsy (study 2) performed a Stroop-animal task simultaneously with a standing or a walking task in order to determine the attentional demand of postural control and locomotion. Dual-task cost decreased with advancing age in healthy children during balance. CP and healthy children were similarly affected by dual-task constraints during standing and walking. Children with diplegia were more affected by the DT during the postural task than children with hemiplegia. We found that adults could benefit from dual-tasking for standing. The integrated model of task prioritization might explain our results regarding postural reserve of each population.
PDF
![Added value of [18F]FDOPA P...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1619-7070/small "Added value of [18F]FDOPA PET to the management of high-grade glioma patients after their initial treatment: a prospective multicentre study")
