Recent genetic evidence implicates glutamatergic-receptor variations in schizophrenia. Glutamatergic excess during early life in people with schizophrenia may cause excitotoxicity and produce structural deficits in the brain. Cortical thickness and gyrification are reduced in schizophrenia, but only a subgroup of patients exhibits such structural deficits. We delineate the structural variations among unaffected siblings and patients with schizophrenia and study the role of key glutamate-receptor polymorphisms on these variations.

Gaussian Mixture Model clustering was applied to the cortical thickness and gyrification data of 114 patients, 112 healthy controls, and 42 unaffected siblings to identify subgroups. The distribution of glutamate-receptor (GRM3, GRIN2A, and GRIA1) and voltage-gated calcium channel (CACNA1C) variations across the MRI-based subgroups was studied. The comparisons in clinical symptoms and cognition between patient subgroups were conducted.

We observed a “hypogyric,” “impoverished-thickness,” and “supra-normal” subgroups of patients, with higher negative symptom burden and poorer verbal fluency in the hypogyric subgroup and notable functional deterioration in the impoverished-thickness subgroup. Compared to healthy subjects, the hypogyric subgroup had significant GRIN2A and GRM3 variations, the impoverished-thickness subgroup had CACNA1C variations while the supra-normal group had no differences.

Disrupted gyrification and thickness can be traced to the glutamatergic receptor and voltage-gated calcium channel dysfunction respectively in schizophrenia. This raises the question of whether MRI-based multimetric subtyping may be relevant for clinical trials of agents affecting the glutamatergic system.

When cardiac muscle damage occurs, cardiac troponins are released to blood and their detection is used as a marker in clinical setting. The prognostic value of the quantitative levels of blood troponin I in cases of myocarditis and myopericarditis is unclear. The aim of this study was to analyse whether troponin quantitative blood levels can be correlated with the course of hospitalisation and prognosis.

Retrospective data was collected from all consecutive patients aged ≤30 hospitalised with a diagnosis of acute myocarditis or acute myopericarditis in our health Care Campus between the years 2010–2016.

Ninety-three patients with myocarditis and myopericarditis were identified. Higher peak troponin levels correlated with longer hospitalisation times in the cardiac or paediatric wards (p = 0.03, Pearson correlation: r −0.23), and median troponin level at admission correlated with longer overall hospitalisation (p = 0.026, Pearson correlation: r = 0.23). Patients admitted to ICU, received oral cardiac supportive therapy or that were discharged with cardiac drugs had higher median troponin compared to patients who were not but this was not statistically significant. A small group of patients that needed intravenous cardiac support had significantly lower median peak troponin levels (n = 4, 0.375ng/ml, p = 0.048). Only two patients needed extracorporeal membrane oxygenation support, and one died. The small number of patients precludes statistical analysis.

Higher troponin levels correlated significantly with longer hospitalisation, lower troponin values correlated with intravenous cardiac support, while other variables related to the severity of disease could not be significantly related to higher troponin levels.

Although previous studies have demonstrated that paediatric pulmonary arterial hypertension remains distinct from that in adults, there are limited studies evaluating a direct comparison between children and adults. The aim of this head-to-head comparison study was to compare the gender, haemodynamic parameters, and prognosis between paediatric and adult pulmonary arterial hypertension.

We retrospectively assessed the clinical differences in 40 childhood-onset (under 20 years old) patients and 40 adult-onset patients with idiopathic and heritable pulmonary arterial hypertension who were followed up at two centres. There was no female predominance among patients with childhood-onset pulmonary arterial hypertension (child female: 42.5%, adult female: 80%). The percent of New York Heart Association functional class IV in adult-onset pulmonary arterial hypertension tended to be higher than those in childhood-onset pulmonary arterial hypertension (22.5 and 10%, respectively), although children had worse haemodynamic parameters at diagnosis (mean pulmonary artery pressure (children versus adults); median 65 mmHg versus 49 mmHg, p < 0.001). There was no significant difference in the event-free survival rate between the two groups (95% vs. 85%) during the follow-up period (median, 96 months; range, 1–120 months).

Although paediatric pulmonary arterial hypertension patients had worse haemodynamic parameters at diagnosis than adults, children survived as long as adults with appropriate therapeutic strategies.

To examine neuropsychological functioning as a predictor of psychosocial adjustment difficulties at discharge from a postacute residential rehabilitation facility for traumatic brain injury (TBI) and depression as a potential mediator.

A retrospective record review was conducted of 172 adults who received rehabilitation services for TBI. Individuals completed a full battery of neuropsychological tests, depression assessment, and functional assessments at admission. Functional assessments were also obtained at discharge.

A two-phase structural equation model analysis was performed. The first phase specified a good fitting model of a cognitive functioning (CF) latent construct with four indicators of cognitive domains measuring verbal fluency, cognitive flexibility, verbal learning, and working memory. Worse CF was associated with greater psychosocial adjustment impairment at discharge, but not related to depression. Psychosocial adjustment impairment at admission was positively associated with depression when controlling for CF, however depression did not predict psychosocial adjustment at discharge. Thus, depression was not found to be a significant mediator of psychosocial adjustment impairment at discharge.

Results provide support for neuropsychological functioning at the start of postacute rehabilitation for TBI as an important predictor of psychosocial functioning difficulties that remain upon discharge and highlights the need to examine mechanisms beyond depression.

Half of Guillain–Barré syndrome (GBS) present elevated cerebrospinal fluid (CSF) protein levels within 1 week since symptom onset and 80% within 2 weeks. Our objective was to determine the clinical and prognostic implication of albuminocytological dissociation in early GBS.

An ambispective cohort study was conducted. Good outcome was considered if the patient was able to walk unaided (Guillain-Barré disability score [GDS] ≤ 2 points) at 3-month follow-up. Patients were classified into two groups: with and without albuminocytological dissociation; we compared clinical and paraclinic characteristics between the groups. We analyzed clinical and electrophysiological factors related to presenting early dissociation through a multivariate model.

We included 240 patients who fulfilled Asbury criteria for GBS. On further selection, only 94 patients fulfilled inclusion. Mean age was 45.94 ± 17.1 years and 67% were male. Median time from symptom onset to admission was 5 days (IQR 3–6). Regarding albuminocytological dissociation and electrophysiological variants, we found a significant difference: acute inflammatory demyelinating polyneuropathy (AIDP) [60.6% vs 26.2%, p = 0.002], acute motor axonal neuropathy (AMAN) [21.2% vs 49.1%, p = 0.009] and acute motor sensory axonal neuropathy (AMSAN) [12.1% vs 1.6%, p = 0.05]. We did not observe significant differences in recovery of independent walking in short term between both groups. The presence of conduction block in any variant (OR 3.21, 95% CI 1.12–9.16, p = 0.02) and absence of sural registration (OR 5.69, 95% CI 1.48–21.83, p = 0.011) were independent factors related to early dissociation.

Early dissociation (<7 days) is not associated with any particular clinical feature or unfavorable outcome. It is more common to see in AIDP rather than axonal variants.

This study aimed to investigate the safety, tolerability, and efficacy of selexipag in children and young adults with idiopathic and heritable pulmonary arterial hypertension.

This retrospective cohort study included clinical data from five children and six young adults with pulmonary arterial hypertension receiving selexipag as add-on therapy or as a transition from beraprost sodium or epoprostenol infusion therapy. Clinical efficacy was evaluated by measuring improvement in clinical variables from baseline, including hemodynamic parameters.

Of the 11 patients, 6 were switched from beraprost sodium to selexipag and one paediatric patient transitioned from epoprostenol to selexipag. The median maintenance dose of selexipag in children was 80 μg/kg/day. In nine patients undergoing repeat catheterisation, statistically significant improvements were observed after the initiation of selexipag in terms of mean pulmonary arterial pressure (p < 0.01), pulmonary vascular resistance index (p < 0.05), and cardiac index (p < 0.01). None of the patients had clinical worsening after selexipag during follow-up, but one young adult patient discontinued treatment due to severe headache. The most common side effect profiles were headache, nausea, abdominal pain, jaw pain, myalgia, and diarrhoea.

Selexipag may have a favourable safety profile and potential efficacy in children and young adults with pulmonary arterial hypertension.

To determine risk factors affecting mortality in acute invasive fungal sinusitis.

This observational cohort study was conducted over a five-year period.

Of 109 recruited patients, 90 (82.6 per cent) had diabetes mellitus. Predominant fungi were zygomycetes (72.6 per cent) with Rhizopus arrhizus being most common. Of the patients, 12.8 per cent showed a positive biopsy report from radiologically normal sinuses. Factors affecting mortality on multivariate analysis were: female sex (p = 0.022), less than two weeks between symptoms and first intervention (p = 0.01), and intracranial involvement (p = 0.034). Other factors significant on univariate analysis were: peri-orbital swelling (p = 0.016), restricted ocular movements (p = 0.053), intracranial symptoms (p = 0.008), posterior disease (p = 0.058), imaging showing ocular involvement (p = 0.041), fungus being zygomycetes (p = 0.050) and post-operative cavity infection (p = 0.032). Bilateral, palatal and retromaxillary involvement were not associated with poor prognosis.

Diagnosis of acute invasive fungal sinusitis requires a high index of clinical suspicion. Recognition of factors associated with poor prognosis can help when counselling patients, and can help initiate urgent intervention by debridement and antifungal therapy. Post-operative nasal and sinus cavity care is important to reduce mortality.

Strategies to modulate the tumor microenvironment (TME) have opened new therapeutic avenues with dramatic yet heterogeneous intertumoral efficacy in multiple cancers, including glioblastomas (GBMs). Therefore, investigating molecular actors of TME may help understand the interactions between tumor cells and TME. Immune checkpoint proteins such as a Cluster of Differentiation 80 (CD80) and CD86 are expressed on the surface of tumor cells and infiltrative tumor lymphocytes. However, their expression and prognostic value in GBM microenvironment are still unclear.

In this study, we investigated, in a retrospective local discovery cohort and a validation TCGA dataset, expression of CD80 and CD86 at mRNA level and their prognostic significance in response to standard of care. Furthermore, CD80 and CD86 at the protein level were investigated in the discovery cohort.

Both CD80 and CD86 are expressed heterogeneously in the TME at mRNA and protein levels. In a univariate analysis, the mRNA expression of CD80 and CD86 was not significantly correlated with OS in both local OncoNeuroTek dataset and TCGA datasets. CD80 and CD86 mRNA high expression was significantly associated with shorter progression free survival (PFS) (p < 0.05). These findings were validated using the TCGA cohort; higher CD80 and CD86 expressions were correlated with shorter PFS (p < 0.05). In multivariate analysis, CD86 mRNA expression was an independent prognostic factor for PFS in the TCGA dataset only (p < 0.05).

CD86 could be used as a potential biomarker for the prognosis of GBM patients treated with immunotherapy; however, additional studies are needed to validate these findings.

To identify sources of distress experienced by trainees when providing neuropalliative care and to explore the perceived and unperceived educational needs of trainees learning to deliver neuropalliative care.

This study is a post hoc analysis of a qualitative investigation performed at a single Canadian academic center with active clinical services in palliative medicine, neurology, and neurosurgery. Grounded theory methodology was used to explore trainees’ perspectives when learning neuropalliative care. This study used focus groups, using open-ended questions, to elicit participants’ experiences providing neuropalliative care as well as to explore the challenges in neuropalliative care.

Qualitative analysis identified multiple sources of distress for trainees in neuropalliative care and broad themes emerged: 1) a lack of experience and knowledge, 2) the emotional toll of learning neuropalliative care, and 3) prognostic uncertainty in neuropalliative care.

Our results suggest that palliative neurology curricula should focus not only on symptom management but also on strategies for improving communication about prognosis and managing clinical uncertainty. Improving trainee comfort and confidence in neuropalliative care throughout the illness trajectory may alleviate sources of distress during training and increase quality of care.