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Gliomas are the most common primary central nervous system (CNS) tumors and a major cause of cancer-related mortality in children (age <15 years), adolescents and young adults (AYA, ages 15-39 years), and adults (age >39 years). Molecular pathology has helped enhance the characterization of these tumors, revealing a heterogeneous and ever more complex group of malignancies. Recent molecular analyses have led to an increased appreciation of common genomic alterations prevalent across all ages. The 2021 World Health Organization (WHO) CNS tumor classification, 5th edition (WHO CNS5) brings forward a nomenclature distinguishing "pediatric-type" and "adult-type" gliomas. The spectrum of gliomas in AYA comprises both "pediatric-like" and "adult-like" tumor entities but remains ill-defined. With fragmentation of clinical management between pediatric and adult centers, AYAs face challenges related to gaps in medical care, lower rates of enrollment in clinical trials and additional psychosocial and economic challenges. This calls for a rethinking of diagnostic and therapeutic approaches, to improve access to appropriate testing and potentially beneficial treatments to patients of all ages.

We report two cases of olfactory neuropathy diagnosed at autopsy in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. One patient experienced anosmia. Information about anosmia was not available in the other patient. Patient 1, a man aged 70 years, and patient 2, a man aged 79 years, both tested positive for SARS-CoV-2. Patient 1 was a renal transplant recipient with coronary artery disease and arterial hypertension. He developed progressive respiratory failure due to COVID-19 pneumonia and required mechanical ventilation. He was treated with hydroxychloroquine (total 1600 mg). Patient 2 was previously diagnosed with severe pulmonary hypertension and was admitted with fever, cough, and increasing dyspnoea as well as loss of taste and smell. He was also treated with hydroxychloroquine (total 1600 mg); however, he declined invasive treatment. Patient 1 died 8 days after hospital admission; patient 2 died 6 days after hospital admission.

Interdisciplinary cooperation and interaction have grown extremely important and will soon become indispensable in clinical neuroscience. The constantly increasing degree of specialization may further compartmentalize the different clinical neuroscience disciplines, potentially altering a unified identity in the field. In 2016, the Swiss Federation of Clinical Neuro-Societies (SFCNS) encouraged the creation of the Young Clinical Neuroscientists (YouCliN) Network bringing together juniors from all specialties united in the SFCNS – that is, biological psychiatry, neurology, neuropathology, neuropediatrics, neuropsychology, neuroradiology and neurosurgery. The main YouCliN mission is to cultivate an interdisciplinary spirit among clinical neuroscience trainees – in order for them to be prepared to face future challenges in a shoulder-to-shoulder manner. Moreover, the YouCliN represents junior interests in current issues of Swiss clinical neuroscience and contributes to shaping interdisciplinary training and courses. Transversality, better integration between fundamental and clinical neuroscience as well as between psychiatry and clinical neuroscience, and equal gender opportunities are further important topics and fields of action. In this article, the YouCliN Steering Committee presents the Network, the disciplines’ specific concerns and hopes, and positions itself with respect to future challenges for clinical neuroscience.

Antibodies against the prion protein PrPC can antagonize prion replication and neuroinvasion, and therefore hold promise as possible therapeutics against prion diseases. However, the safety profile of such antibodies is controversial. It was originally reported that the monoclonal antibody D13 exhibits strong target-related toxicity, yet a subsequent study contradicted these findings. We have reported that several antibodies against certain epitopes of PrPC, including antibody POM1, are profoundly neurotoxic, yet antibody ICSM18, with an epitope that overlaps with POM1, was reported to be innocuous when injected into mouse brains. In order to clarify this confusing situation, we assessed the neurotoxicity of antibodies D13 and ICSM18 with dose-escalation studies using diffusion-weighted magnetic resonance imaging and various histological techniques. We report that both D13 and ICSM18 induce rapid, dose-dependent, on-target neurotoxicity. We conclude that antibodies directed to this region may not be suitable as therapeutics. No such toxicity was found when antibodies against the flexible tail of PrPC were administered. Any attempt at immunotherapy or immunoprophylaxis of prion diseases should account for these potential untoward effects.

Prions induce lethal neurodegeneration and consist of PrPSc, an aggregated conformer of the cellular prion protein PrPC. Antibody-derived ligands to the globular domain of PrPC (collectively termed GDL) are also neurotoxic. Here we show that GDL and prion infections activate the same pathways. Firstly, both GDL and prion infection of cerebellar organotypic cultured slices (COCS) induced the production of reactive oxygen species (ROS). Accordingly, ROS scavenging, which counteracts GDL toxicity in vitro and in vivo, prolonged the lifespan of prion-infected mice and protected prion-infected COCS from neurodegeneration. Instead, neither glutamate receptor antagonists nor inhibitors of endoplasmic reticulum calcium channels abolished neurotoxicity in either model. Secondly, antibodies against the flexible tail (FT) of PrPC reduced neurotoxicity in both GDL-exposed and prion-infected COCS, suggesting that the FT executes toxicity in both paradigms. Thirdly, the PERK pathway of the unfolded protein response was activated in both models. Finally, 80% of transcriptionally downregulated genes overlapped between prion-infected and GDL-treated COCS. We conclude that GDL mimic the interaction of PrPSc with PrPC, thereby triggering the downstream events characteristic of prion infection.