Standard 6-week chemoradiation for elderly patients with newly diagnosed glioblastoma

Glioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard 6-week chemoradiation (CRT) in particular, although this is the mainstay for younger patients. All patients with newly diagnosed GBM and age ≥ 70 who were referred to our institution for 6-week CRT were reviewed from 2004 to 2018. MGMT status was not available for treatment decision at that time. The primary endpoint was overall survival (OS). Secondary outcomes were progression-free survival (PFS), early adverse neurological events without neurological progression ≤ 1 month after CRT and temozolomide hematologic toxicity assessed by CTCAE v5. 128 patients were included. The median age was 74.1 (IQR: 72–77). 15% of patients were ≥ 80 years. 62.5% and 37.5% of patients fulfilled the criteria for RPA class I–II and III–IV, respectively. 81% of patients received the entire CRT and 28% completed the maintenance temozolomide. With median follow-up of 11.7 months (IQR: 6.5–17.5), median OS was 11.7 months (CI 95%: 10–13 months). Median PFS was 9.5 months (CI 95%: 9–10.5 months). 8% of patients experienced grade ≥ 3 hematologic events. 52.5% of patients without neurological progression had early adverse neurological events. Post-operative neurological disabilities and age ≥ 80 were not associated with worsened outcomes. 6-week chemoradiation was feasible for “real-life” elderly patients diagnosed with glioblastoma, even in the case of post-operative neurological disabilities. Old does not necessarily mean worse.

Old Does Not Necessarily Mean Worse: Standard 6-Week Chemoradiation For Elderly Patients (≥ 70 Years) With Newly Diagnosed Glioblastoma

IntroductionGlioblastoma (GBM) is frequent in elderly patients, but their frailty provokes debate regarding optimal treatment in general, and the standard 6-week chemoradiation in particular, although this is the mainstay for younger patients. MethodsAll patients with newly diagnosed GBM and age ≥ 70 who were referred to our institution for chemoradiation (RCT) were reviewed from 2004 to 2018. MGMT status was not available for treatment decision at that time. The primary endpoint was overall survival (OS). Secondary outcomes were progression-free survival (PFS), early adverse neurological events without neurological progression ≤ 1 month after RCT and temozolomide hematologic toxicity assessed by CTCAE v5. Results128 patients were included. The median age was 74.1 (IQR: 72-77). 15% of patients were ≥80 years. 62.5% and 37.5% of patients fulfilled the criteria for RPA class I-II and III-IV, respectively. 81% of patients received the entire RCT and 28% completed the maintenance temozolomide. With median follow-up of 11.7 months (IQR: 6.5-17.5), median OS was 11.7 months (CI95%: 10-13 months). Median PFS was 9.5 months (CI95%: 9-10.5 months). 8% of patients experienced grade ≥3 hematologic events. 52.5% of patients without neurological progression had early adverse neurological events. Post-operative neurological disabilities and age ≥80 were not associated with worsened outcomes. Conclusions6-week chemoradiation was feasible for “real-life” elderly patients diagnosed with glioblastoma, even in the case of post-operative neurological disabilities.

B-cells expressing NgR1 and NgR3 are localized to EAE-induced inflammatory infiltrates and are stimulated by BAFF

We have previously reported evidence that Nogo-A activation of Nogo-receptor 1 (NgR1) can drive axonal dystrophy during the neurological progression of experimental autoimmune encephalomyelitis (EAE). However, the B-cell activating factor (BAFF/BlyS) may also be an important ligand of NgR during neuroinflammation. In the current study we define that NgR1 and its homologs may contribute to immune cell signaling during EAE. Meningeal B-cells expressing NgR1 and NgR3 were identified within the lumbosacral spinal cords of ngr1+/+ EAE-induced mice at clinical score 1. Furthermore, increased secretion of immunoglobulins that bound to central nervous system myelin were shown to be generated from isolated NgR1- and NgR3-expressing B-cells of ngr1+/+ EAE-induced mice. In vitro BAFF stimulation of NgR1- and NgR3-expressing B cells, directed them into the cell cycle DNA synthesis phase. However, when we antagonized BAFF signaling by co-incubation with recombinant BAFF-R, NgR1-Fc, or NgR3 peptides, the B cells remained in the G0/G1 phase. The data suggest that B cells express NgR1 and NgR3 during EAE, being localized to infiltrates of the meninges and that their regulation is governed by BAFF signaling.

Medical Treatment in Spinal Cord Injury

Spinal cord injuries cause psychological in humans and require expensive care and treatments. In recent years, various pharmacological agents have been tested in acute spinal cord injuries. Prospective randomized controlled clinical trials on a large scale have failed to demonstrate significant neurological progression, in contrast to their success in the laboratory. The search for an effective neuroprotective pharmacological agent to prevent secondary damage in acute spinal cord injuries remains primary goals for basic sciences and clinicians.

Formation of a meningoencephalocele after removal of a frontal lobe meningioma by transfrontal craniotomy in a cat

Case summary A 10-year-old castrated male domestic shorthair cat was referred for surgical treatment of a left-sided frontal lobe meningioma diagnosed by CT. Clinically, the cat had generalised tonic–clonic seizures, which reduced in frequency after treatment was started with prednisolone. After definition of the anatomical landmarks of the feline skull, a bilateral transfrontal craniotomy allowed en bloc removal of the meningioma. While postoperative recovery was uneventful, right-sided proprioceptive deficits were still present 6 months after surgery. MRI detected a probable meningoencephalocele herniating through the surgical bone defect in the frontal sinus. Because of the mild neurological deficits and good quality of life, the meningoencephalocele was not treated. Thirty-one months after meningioma removal the cat was alive without further neurological progression. Relevance and novel information To our knowledge, this is the first report to describe, in detail, the technique of transfrontal craniotomy in cats. Iatrogenic meningoencephalocele is a complication that has not previously been described after meningioma removal in cats, and should be considered as a potential complication after craniotomy.

Two Pediatric Cases of Successful Management of Postictal Transient Urinary Retention

We report two cases of postictal urinary retention in pediatric patients with cognitive impairment. Two girls with intellectual disabilities, concomitant cerebral palsy (case 1) and Rett syndrome (case 2), developed urinary retention following seizures. Their caregivers brought them to the hospital with complaints of abdominal distension. After excluding neurological progression, they were referred to the rehabilitation clinic for the evaluation and management of postictal urinary retention. We followed two different approaches in each case to restore normal urination. While serial manual cystometrograms were performed in case 1, clean intermittent catheterization with a voiding diary was performed in case 2 until restoration of normal urination. Based on these pediatric cases of successfully managed postictal urinary retention, we suggest that more attention may be needed for children with cognitive impairment to diagnose and manage postictal urinary retention.

Predictors of Early Neurologic Deterioration in Acute Pontine Infarction

Background and Purpose— The relationship between infarct dimensions and neurological progression in patients with acute pontine infarctions remains unclear. This study aimed to investigate the morphometric predictive value of magnetic resonance imaging for early neurological deterioration (END) in acute pontine infarction. Methods— We included all patients admitted to our department having an acute ischemic stroke in the pons. The ventrodorsal length multiplied by thickness was measured as parameters of infarct size. END was defined as an incremental increase in the National Institutes of Health Stroke Scale score by ≥1 point in motor power, or ≥2 points in the total score within the first week after admission. Results— We enrolled 407 patients, and 114 (28.0%) patients were diagnosed with END. Adjusted logistic regression analyses showed the maximum length multiplied by thickness was independently associated with END (odds ratio, 4.580 [95% CI, 2.909–7.210]). The sensitivity, specificity, and area under the curve were 77.2%, 79.2%, and 0.843, respectively, in the receiver operating characteristic curve analysis of maximum length multiplied by thickness for predicting END. Conclusions— These results suggest that the maximum length multiplied by thickness may be a possible predictor in the evaluation of progression with isolated acute pontine infarction. The extent of the pontine infarction along the conduction tract may contribute to deterioration.

1170Tafamidis versus liver transplantation as first-line therapy for hereditary transthyretin amyloidosis

Introduction By stabilizing transthyretin tetramer, tafamidis delays neurological progression in mutated Transthyretin amyloidosis (mATTR) and has replaced liver transplantation (LT) as the first-line therapy in European patients with stage I mATTR. To date, no study compared these two therapeutic strategies. Material and methods Stage I mATTR patients treated either with tafamidis or with LT were compared using a propensity score. The primary endpoint was the all-cause mortality. Secondary endpoints were the neurological progression (assessed by a worsening in the PND score) and the cardiac progression of mATTR (defined by a cardiovascular death or the onset or the worsening of symptomatic heart failure). Results The files of 345 patients with proven mATTR were analyzed and 144 patients entered the final analysis (72 patients in each group, median age 54 years, 60% carrying the V30M mutation). Patients treated by tafamidis had a better survival than patients with LT (HR: 0.93; 95% CI: 0.17–0.91; P=0.029). Conversely, the worsening-free survival of the neurological status was significantly shorter for patients that received tafamidis than for LT patients (HR: 6.08; 95% CI: 2.97–12.45; P<0.0001). A similar non-significant trend was documented regarding the progression of the cardiac status (HR: 1.99; 95CI: 0.91–4.34; P=0.084). Conclusions In mATTR, first-line therapy with tafamidis was associated with a better survival than LT. Conversely, LT provided better neurological stabilization than tafamidis. These results confirm that LT remains a major treatment in mATTR. In patients treated with tafamidis, close follow up of the treatment efficacy is mandatory.