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Purpose:To explore a prognostic or predictive role of MRI and O-(2–18F-fluoroethyl)-L-tyrosine (18FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma.Patients and Methods:Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm.Results:Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm3 0.94; 95% confidence interval (CI), 0.89–0.99] and for higher ADC (HR 0.18; CI, 0.05–0.66). Higher 18FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only (P = 0.09). High 18FET-TBR of noncontrast-enhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16–30.8).Conclusions:Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent 18FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome.

Note S1, Figure S1-S4, Table S1-S3

Zusammenfassung. In der Neurologie als Disziplin finden sich klare Überschneidungen mit der Palliative Care. Dennoch findet eine frühe Integration von palliativer Versorgung begleitend zur neurologischen Behandlung eher selten statt, und weiterhin bestehen Missverständnisse in Bezug auf den Zeitpunkt des Einbezugs von Palliative Care und deren Rolle jenseits der oft verwechselten reinen «End-of-Life Care» und Hospizpflege. Ein weiterer Ausbau und die Nutzung der Synergien sollte in den kommenden Jahren integraler Bestandteil beider Disziplinen werden und eine entsprechende Schulung insbesondere junger ärztlicher Kolleginnen und Kollegen im Fokus der Ausbildung stehen.

Aim: Immune checkpoint inhibitor-induced encephalitis (ICI-iE) is a rare but life-threatening toxicity of immune checkpoint inhibitor treatment. We aim to identify the characteristics of ICI-iE and describe factors that discriminate it from herpes simplex virus (HSV)-1 encephalitis and anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis, as two alternative entities of encephalitis. Methods: In this retrospective multicentre cohort study, we collected patients with ICI-iE reported to the Side Effect Registry Immuno-Oncology from January 2015 to September 2021 and compared their clinical features and outcome with 46 consecutive patients with HSV-1 or anti-LGI1 encephalitis who were treated at a German neurological referral centre. Results: Thirty cases of ICI-iE, 25 cases of HSV-1 encephalitis and 21 cases of anti-LGI1 encephalitis were included. Clinical presentation of ICI-iE was highly variable and resembled that of HSV-1 encephalitis, while impairment of consciousness (66% vs. 5%, p = .007), confusion (83% vs. 43%; p = .02), disorientation (83% vs. 29%; p = .007) and aphasia (43% vs. 0%; p = .007) were more common in ICI-iE than in anti-LGI1 encephalitis. Antineuronal antibodies (17/18, 94%) and MRI (18/30, 60%) were mostly negative in ICI-iE, but cerebrospinal fluid (CSF) showed pleocytosis and/or elevated protein levels in almost all patients (28/29, 97%). Three patients (10%) died of ICI-iE. Early immunosuppressive treatment was associated with better outcome (r = 0.43). Conclusions: ICI-iE is a heterogeneous entity without specific clinical features. CSF analysis has the highest diagnostic value, as it reveals inflammatory changes in most patients and enables the exclusion of infection. Early treatment of ICI-iE is essential to prevent sequelae and death.

Introduction: The evaluation of symptom burden, performance status, and neurological function is still challenging in glioblastoma (GBM) patients. Patients may suffer from a wide spectrum of neurological symptoms like cognitive deficits, aphasia, or hemiparesis, which interfere to report to comprehensive questionnaires. However, an integrated and reliable neuro-oncological assessment is the key in the clinical management and in the evaluation of treatment benefits for GBM patients. Methods: We implemented an easy-to-use clinical toolkit for the prospective assessment and follow-up evaluation of GBM patients using the Karnofsky performance status (KPS), the National Institute of Health Stroke Scale (NIH-SS), and simple scores for the evaluation of key symptoms like fatigue, depression, and headache. Results: We prospectively followed 50 patients. The composite score (headache, depression, and fatigue), fatigue alone, the NIHSS, and the KPS were suitable biomarkers to evaluate symptom burden in GBM patients and indicate clinical disease progression. Discussion/Conclusion: The proposed clinical toolkit seems feasible in routine clinical practice and reflects changes in symptom burden in different stages of the postsurgical course of GBM patients in this monocentric clinical pilot trial.

AimTo analyse the increase in diameter of the nerve roots C5 and C6 in early childhood.MethodsThe nerve roots of 56 children subjects aged 0 days to 10 years (47 younger than 2 years) were examined by high-resolution ultrasound imaging. The correlation of diameter and age was statistically tested and a logarithmic regression analysis was performed to develop a logarithmic growth model.ResultsThe increase in nerve root diameter is greatest during the first two years of life and then the growth rate decreases steadily. The relationship between age and diameter follows a logarithmic curve (p < 10−8).InterpretationThe main increase in the diameter of the nerve roots happens in the first two years of life. Comparing data from a previous study, our data also suggest that the maturation of the proximal part of the median nerve is comparable to the maturation of its distal segments. This suggests a synchronous maturation of the axons and myelin sheath for the whole extent of the nerve, from the radix to its very distal part.What this paper addsNormative values for the size of the cervical nerve roots C5 and C6, an insight into the maturation of the proximal parts of the peripheral nervous system, and the correlation between age and cervical root diameter.Highlights-Maturation of the nerve roots C5 and C6 in children from 0 to two years of age.-Reference values from the diameter of the C5 and C6 nerve roots of children up to two years.

Objective: The aim of this study was to examine neurocognitive course over time among people with well treated HIV. Design: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up. Setting: Seven SHCS centres. Participants: Patients aged at least 45 years enrolled in the SHCS with fluency in the local language (French, German or Italian) and agreeing to participate in the NAMACO study: 981 participants at baseline, 720 at 2-year follow-up of whom 644 had complete data sets. Intervention: Standardized neuropsychological assessment at baseline and 2-year follow-up. Main outcome measure: Neurocognitive performance using Frascati criteria and mean z-scores. Results: Four participants (of 644, 0.6%) had plasma HIV-1 RNA more than 50 copies/ml; median CD4+ cell count was 660 cells/μl. According to Frascati criteria, 204 participants (31.7%) had neurocognitive impairment (NCI) at baseline. NCI severity in these participants changed little over 2 years and comprehensive models based on Frascati criteria were not feasible. Examining mean z-scores, however, we observed neurocognitive stability or improvement over two years in five of seven neurocognitive domains assessed. Age at least 65 years (P = 0.02) and cognitive complaints (P = 0.004) were associated with neurocognitive decline, while black race (P = 0.01) and dolutegravir treatment (P = 0.002) were associated with improvement. Conclusion: Frascati criteria were less sensitive in measuring NCI change and therefore unsuitable for following neurocognitive course in our cohort of people with well treated HIV. Examining neurocognitive course by mean z-score change, we observed stability or improvement.

Palliative Care in Neurology

INTRODUCTION The CeTeG/NOA-09 trial demonstrated superior median overall survival (mOS, 48.1 months) in MGMT-methylated glioblastoma treated with lomustine/temozolomide compared to temozolomide. We retrospectively analyzed an off-study cohort of patients treated with lomustine/temozolomide to gather real-world data on this new regimen. METHODS Adult patients from 20 centers in Germany, Austria and Switzerland were included. Inclusion criteria were MGMT-methylated IDHwt glioblastoma newly diagnosed prior to end of 2020, and lomustine/temozolomide treatment as part of first-line therapy. RESULTS 321 patients with a median age of 57 years (range, 21-78) and a median follow-up of 19.9 months were included. In the whole cohort, mOS was 41.0 months (95%CI, 33.0 – not reached). In patients starting lomustine/temozolomide immediately upon initiation of radiotherapy strictly following the CeTeG protocol (88%), mOS was 52.8 months (35.8 – not reached) as compared to 24.6 months (17.6 – not reached) in patients starting lomustine/temozolomide after completion of radiotherapy/concomitant temozolomide (12%, logrank test: p = 0.06). Patients with a KPS < 80 had a shorter mOS of 19.7 months (95%CI, 16.6 – not reached) compared to 41.0 months (33.0 – not reached, p = 0.009) in KPS 80-100. Gross total resection (GTR, 53.9%) was associated with longer mOS (52.8 months, 95%CI 24.1 – not reached) compared to partial resection/biopsy (30.5 months, 95%CI 36.8 – not reached, p=0.004). Multivariable Cox regression analysis confirmed GTR (HR 0.66, p = 0.033) and younger age ( ≤ 50 years: HR 0.42, p = 0.001), but not KPS (80-100 vs. lower: HR 0.66, p = 0.12) as independent prognostic factors. DISCUSSION In this real-world multicenter cohort, survival was similar to the promising results of CeTeG/NOA-09. Further analyses should investigate a potentially reduced benefit from lomustine/temozolomide in patients with low KPS/no GTR and a possible detrimental effect from deferred lomustine/temozolomide initiation. The median follow-up is admittedly short, updated data will be presented.

A 57-year-old female presented at the emergency room with acute onset aphasia but unremarkable cCT (incl. angiography and perfusion). Suspecting an ischemic stroke, she received thrombolysis with quick recovery of aphasia. Afterwards, myoclonic jerks of the face and right arm occurred leading to anticonvulsant therapy. Follow-up cMRI surprisingly demonstrated swollen T2w-hyperintense and Gd-enhancing left limbic, temporal and frontal lobes. Suspected herpes-simplex-encephalitis was treated with aciclovir despite unremarkable CSF results (no pleocytosis, no BBB disruption, negative HSV-PCR) on day 2 and follow-up (day 5). Due to persisting cognitive deficits, autoimmune limbic encephalitis was suspected, and intravenous immunoglobulin therapy was added. Three weeks later, she experienced new neurological symptoms (weakness, blurred vision, vomiting, headache). Follow-up brain MRI demonstrated a massive increase of multifocal Gd-enhancing lesions. Partial resection revealed the diagnosis of an IDH-wildtype glioblastoma (GB). Next generation oncogene panel testing demonstrated a GOPC-ROS1 fusion which is rarely found in GB. Due to the gliomatosis-like infiltration of both hemispheres, radiotherapy was deemed to be too toxic. Instead, she received two cycles of lomustine in absence of a MGMT-promotor methylation. Two months later cMRI showed a symptomatic second multilocular progression. 2nd-line therapy with a ROS-inhibitor was rejected, whereupon she died five weeks later. Our case is in several aspects peculiar: It demonstrates that rare GB-mimics (i.e. HSV- and autoimmune limbic encephalitis) can only be ruled out in a fast manner by brain biopsy. Watchful waiting may neglect fast progression of GB leading to the inability to provide optimal treatment (i.e. radiotherapy). Thrombolysis is strictly contraindicated in primary brain tumors, but was unharmful in our case most probably to the early tumor stage without relevant neoangiogenesis. Rare genetic abnormalities like ROS1-fusions which are reported mostly in childhood glioblastoma may be present and serve as a therapeutic target also in adult GB.