Clin. Transl. Neurosci., Volume 9, Issue 4 (December 2025) – 15 articles

The high attrition rates in glioblastoma (GB) therapeutic development stem largely from preclinical models that fail to adequately recapitulate the dynamic tumor–host ecosystem. Unlike previous reviews that characterize glioma cell lines in isolation, this article integrates tumor biology with the distinct neuro-immune–endocrine landscapes of major laboratory rat strains. We critically evaluate standard rat malignant glioma cell lines (C6, F98, RG2, 9L) alongside transplantable tissue models (GB 101.8, GB 15/47), which offer enhanced translational relevance, demonstrating that the predictive value of any model is contingent upon the specific “glioma model and host strain” pairing and the individual physiological characteristics of the host. We provide evidence that strain-specific hypothalamic–pituitary–adrenal (HPA) axis reactivity (e.g., hyper-reactive Fischer 344 versus normo-reactive Wistar) acts as a decisive, yet often overlooked, modulator of the tumor microenvironment and therapeutic response. The review delineates the utility and limitations of these models, specifically addressing the MHC incompatibilities of the widely used C6 model in immunotherapy research, while contrasting it with the immune-evasive phenotypes of RG2 and the GB 101.8 tissue model. Furthermore, we highlight the superiority of tissue transplants in preserving cellular polyclonality and diffuse infiltration patterns compared to the circumscribed growth often observed in cell line-derived tumors. Consequently, we propose a strategic selection paradigm wherein immunogenic models serve as bioindicators of host immunocompetence, while invasive, non-immunogenic systems (F98, RG2, and GB 101.8) are utilized to investigate therapeutic resistance and systemic host-tumor interactions. Full article

Considering the prevalence of migraine and its impact on everyday living, its evolutionary persistence remains puzzling. This essay reviews recent literature and conceptual perspectives that frame migraine attacks as a possible side-effect of prolonged stress and unmet needs. To illustrate this, the article compares the antithetical relationship of triggers and migraine symptoms: During the early phase of the attack, many eat, drink, rest and sleep more and tolerate less nuisance compared to the hours and days before; previously, however, there was too little time to eat, drink, rest, and sleep, and the nuisance had to be tolerated. A relevant characteristic of many migraineurs is that they are prone to stress, e.g., because of a character trait, an impaired adaptation to stress, the lack of habituation to sensory stimuli, and disturbances of the energy supply. In that way, the appearance of the attack during fading stress makes sense: the body seizes the opportunity and communicates its needs when circumstances permit. In this context, the concept of pain as an imperative—a signal designed to enforce behavioural change—provides an insightful framework. Understanding migraine in this way may help reframe its pathophysiology and its clinical and translational significance. Full article

Brain Health has become a global public health priority, driven mainly by the rapid aging of populations and the increasing burden of neurological and psychiatric disorders. This report presents the first activities of the Bern Brain Health Working Group, established to implement the Swiss Brain Health Plan (SBHP), published in 2023. The aim is to describe the development and initial outcomes of regional initiatives promoting Brain Health in Switzerland. Specifically, we outline the structure and objectives of the Bern Brain Health Consultation, the development process and conceptual framework of the Swiss Brain Health Questionnaire, and additional educational and research activities supporting the SBHP. By summarizing these first steps, this report provides a model for regional implementation of a national Brain Health strategy and contributes to building a foundation for broader national and international Brain Health efforts. Full article

Working memory training (WMT) has promising effects on cognitive and clinical outcomes in children with attention deficit hyperactivity disorder (ADHD). However, few studies have explored the effectiveness of such programs in developing countries with different populations and sociocultural backgrounds. This study aimed to pilot Cogmed WMT (CWMT) and examine its impact on clinical and cognitive outcomes in children diagnosed with ADHD in Saudi Arabia. We assessed 34 children with ADHD assigned to either a CWMT or standard-of-care group. Both groups were evaluated at baseline and five weeks for ADHD symptoms and cognitive function, including working memory (WM), sustained attention, and impulsivity. Compared with the baseline and the control group, the intervention group demonstrated improved parent ratings of ADHD clinical symptoms and cognitive function scores, including WM, sustained attention, and impulsivity. CWMT improved cognitive and clinical measures in our sample of Saudi children with ADHD and is a promising non-pharmacological therapy for treating children with ADHD in developing countries. Full article

Background: Traumatic Brain Injury (TBI) represents a growing cause of medical emergencies globally. Objective: This study evaluates whether healthcare outcomes for TBI patients differ between daytime and on-call (after-hours) admissions. Methods: A retrospective analysis was conducted using data from a hospital database spanning January 2015 to December 2019. Of the 670 cases reviewed, 45 patients over the age of 65 were admitted with head trauma. Data were analyzed using SPSS. Results: Surgical interventions were significantly less frequent during on-call hours. Admission type (elective vs. emergent) showed a statistically significant difference (p < 0.05). Postoperative ICU length of stay (LOS) was markedly longer for on-call admissions (p = 0.002). Due to a controlled sample size, p-value interpretations would need some discretion. TBI patients admitted during on-call hours had a 9.9-fold increase in ICU stay, a 2.5-fold increase in total hospital LOS, and a 475% higher complication rate compared to daytime admissions. Complication rates were 20% for daytime admissions versus 92% for on-call admissions. Furthermore, patients treated during on-call hours were 11 times more likely to be discharged in an unconscious state (GCS < 8). Conclusions: TBI outcomes are significantly worse during on-call hours. Enhancing imaging availability and staffing during these periods may help improve patient outcomes. Full article

Background: Severe traumatic brain injury (TBI) often leads to elevated intracranial pressure (ICP) that requires aggressive management. Inducing burst suppression with deep sedation is an established therapy for refractory intracranial hypertension. Traditionally, barbiturate coma has been used to achieve burst-suppression EEG in TBI patients, but alternative sedative agents (propofol, midazolam, ketamine, dexmedetomidine) are increasingly utilized in modern neurocritical care. This review compares barbiturates with these alternatives for inducing burst suppression in adult TBI, focusing on protocols, mechanisms, efficacy in controlling ICP, safety profiles, and impacts on neurological outcomes. Methods: A search of the literature was performed, including clinical trials, observational studies, and guidelines on deep sedation for ICP control in adult TBI. Studies comparing high-dose barbiturates to other sedatives (propofol, midazolam, ketamine, dexmedetomidine) in the context of burst suppression or severe TBI management were included. Data on sedative protocols (dosing and EEG targets), mechanisms of action, ICP-lowering efficacy, complications, and patient outcomes were extracted and analyzed qualitatively. Results: High-dose barbiturates (e.g., pentobarbital or thiopental) and propofol are both effective at inducing burst-suppression EEG and reducing ICP via cerebral metabolic suppression. Barbiturate coma remains a third-tier intervention reserved for ICP refractory to other treatments. Propofol infusion has become first-line for routine ICP control due to rapid titratability and shorter half-life, though it can also achieve burst suppression at high doses. Midazolam infusions provide sedation and seizure prophylaxis but yield less metabolic suppression and ICP reduction compared to barbiturates or propofol, and are associated with longer ventilation duration and delirium. Ketamine, once avoided for fear of raising ICP, has shown neutral or lowering effects on ICP when used in ventilated TBI patients, thanks to its analgesic properties and maintenance of blood pressure; however, ketamine alone does not reliably produce burst-suppression patterns. Dexmedetomidine offers sedative and anti-delirium benefits with minimal respiratory depression, but it is generally insufficient for deep burst-suppressive sedation and has only a modest effect on ICP. In comparative clinical evidence, propofol and barbiturates both effectively lower ICP, but neither has demonstrated clear improvement in long-term neurological outcome when used prophylactically. Early routine use of barbiturate coma may increase complications (hypotension, immunosuppression), and thus, current practice restricts it to refractory cases. Modern sedation protocols emphasize using the minimal necessary sedation to maintain ICP < 22 mmHg, with continuous EEG monitoring to titrate therapy to a burst-suppression target (commonly 2–5 bursts per minute) when deep coma is employed. Conclusions: In adult TBI patients with intracranial hypertension, propofol-based sedation is favored for first-line ICP control and can achieve burst suppression if needed, whereas high-dose barbiturates are reserved for ICP crises unresponsive to standard measures. Compared to barbiturates, alternative agents (propofol, midazolam, ketamine, dexmedetomidine) offer differing advantages: propofol provides potent, fast-acting metabolic suppression; midazolam adds anticonvulsant sedation for prolonged use at the cost of slower wake-up; ketamine supports hemodynamics and analgesia; dexmedetomidine aids lighter sedation and delirium control. The choice of agent is guided by the clinical scenario, balancing ICP reduction needs against side effect profiles. While all sedatives can transiently reduce ICP, careful monitoring and a tiered therapy approach are essential, as no sedative has conclusively improved long-term neurological outcomes in TBI. EEG monitoring for burst suppression and meticulous titration is required when employing barbiturate or propofol coma. Ongoing research into optimal combinations and protocols may further refine sedation strategies to improve safety and outcomes in severe TBI. Full article

Background and Objectives: The mechanisms of traumatic brain injury (TBI), patient characteristics, and long-term outcomes in elderly patients differ from those in other age groups. This study aims to evaluate the effectiveness of the Elderly Traumatic Brain Injury (eTBI) Scoring System, recently described in the literature, in predicting mortality, prognosis, and surgical indication. Materials and Methods: Patients diagnosed with TBI over the age of 65 between January 2017 and December 2024 were retrospectively analyzed, and their eTBI scores were calculated. Statistical analyses were conducted to assess mortality, prognosis, and surgical indication or benefit from surgery across low-, medium-, and high-risk groups. Results: In this cohort of 236 patients, the mortality rate was higher in the high-risk group according to the eTBI scoring system, compared to the medium- and low-risk groups. However, the scoring system does not appear to be effective in determining surgical indications. While the medium-risk group was most predictive of mortality, the low-risk group demonstrated better accuracy in predicting prognosis. Conclusions: The eTBI scoring system appears to be an effective tool for assessing mortality risk and predicting prognosis in specific subgroups of elderly TBI patients. Full article

Neuroradiology and neuro-oncology are rapidly emerging fields in the diagnosis and treatment of central nervous system (CNS) diseases, including brain tumors. This review presents a comprehensive look at the current imaging techniques, clinical applications, and therapeutic strategies, with a focus on gliomas, metastases, and functional brain mapping. Conventional modalities such as CT and MRI, as well as sophisticated approaches including functional MRI (fMRI), diffusion tensor imaging (DTI), MR spectroscopy, PET, and hybrid techniques, are discussed. On the therapeutic front, high-precision radiotherapy modalities such as stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT), and proton therapy are discussed, with a focus on radiation biology, dose planning, and the impact on neurocognitive outcomes. The interlink between neuroradiology and radiotherapy is highlighted through advanced image-guided treatment planning. Full article

Background: Neurorehabilitation plays a central role in restoring and maintaining brain health across lifespan. However, its contribution is often underestimated in public health policies. Aim: This paper aims to highlight the importance of neurorehabilitation within the brain health frameworks, advocating for its full integration into global and national health strategies. Main content: We discuss the unique characteristics of neurorehabilitation, including its interdisciplinary structure, long-term scope and role in prevention. We underline how the ICF model provides a bridge between clinical practice and public health policy. Key prevention strategies and the potential of digital technologies are also examined. Conclusion: A stronger integration of neurorehabilitation into brain health policy can yield individual and socio-economic benefits. We call for strategic political and structural efforts to expand its availability and recognition. Full article

Background: Deep vein thrombosis (DVT) is a serious thromboinflammatory complication of acute ischemic stroke (AIS). The true incidence, mechanistic risk factors, and optimal prophylactic strategies remain uncertain, particularly in the era of reperfusion therapy. Methods: This systematic review and meta-analysis (IRIS-DVT) searched PubMed, Embase, Cochrane, Scopus, and Web of Science for studies reporting DVT incidence, risk factors, or prophylaxis in AIS (2004–2025). Random-effects models were used to generate pooled prevalence and effect estimates, and the certainty of evidence was graded using the GRADE framework. Results: Forty-two studies (n = 6,051,729 patients) were included. The pooled prevalence of DVT was 7% (95% CI, 6–9%), approximately seventy-fold higher than in the general population, with wide heterogeneity influenced by screening timing and diagnostic modality. Pathophysiological risk factors included higher stroke severity (NIHSS; SMD 0.41; 95% CI, 0.38–0.43), older age (SMD 0.32; 95% CI, 0.18–0.46), elevated D-dimer (SMD 0.55; 95% CI, 0.38–0.72), female sex (OR 1.33; 95% CI, 1.19–1.50), and malignancy (OR 2.69; 95% CI, 1.56–5.22), supported by moderate-certainty evidence. Respiratory infection and admission hyperglycemia showed weaker, low-certainty associations. Traditional vascular risk factors (hypertension, diabetes, atrial fibrillation, dyslipidemia) were not significantly related to DVT risk. Evidence for prophylaxis with low-molecular-weight heparin, direct oral anticoagulants, or intermittent pneumatic compression was limited and graded very low certainty. Conclusions: DVT complicates approximately one in fourteen AIS cases, reflecting a distinct thromboinflammatory process driven more by acute neurological severity, systemic hypercoagulability, and malignancy than by conventional vascular risk factors. Early systematic screening (≤72 h) and consistent use of mechanical prophylaxis are warranted. Dedicated AIS-specific mechanistic and interventional trials are urgently needed to refine prevention strategies and improve post-stroke outcomes. Full article

We here delve into the intricate and evolving concepts of brain death and consciousness, particularly at the end of life. We examine the historical and technological advancements that have influenced our understanding of death, such as mechanical ventilation and resuscitation techniques. These developments have challenged traditional definitions of death, leading to the concept of brain death, defined as the irreversible loss of all brain functions, including the brainstem. We emphasize that consciousness exists on a continuum, ranging from full alertness to deep coma and complete cessation of brain activity. It explores various disorders of consciousness, including coma, vegetative state, minimally conscious state, and locked-in syndrome, each with distinct characteristics and levels of awareness. Neuroimaging techniques, such as EEG, fMRI, and DTI, are highlighted for their crucial role in diagnosing and understanding disorders of consciousness. These techniques help to detect covert consciousness, assess brain activity, and predict recovery potential. The phenomenon of the “wave of death,” which includes a paradoxical surge in brain activity at the point of death, is also discussed. We address the challenges in defining and understanding both death and consciousness, calling for biologically grounded, ethically defensible, and culturally sensitive definitions. We advocate for standardized neuroimaging protocols, longitudinal studies, and the integration of artificial intelligence to improve diagnosis and treatment. In conclusion, the document underscores the importance of an integrated, evidence-based approach to understanding the gray zones between life and death, recognizing that consciousness and death are dynamic processes with both biological and experiential dimensions. Full article

Background/Objectives: This study presents a case of chronic internal carotid artery [ICA] occlusion initially misinterpreted as ICA agenesis on magnetic resonance angiography (MRA). The report underscores the importance of retrospective review of prior imaging, particularly computed tomography angiography [CTA], in establishing the correct diagnosis. Case Report: A 70-year-old man presented with persistent headache, pulsatile tinnitus, and intermittent dizziness. Neurological examination and laboratory results were unremarkable. Initial cranial MRA demonstrated absence of flow in the left ICA, raising suspicion of congenital agenesis. However, retrospective evaluation of a CTA performed nine years earlier revealed a well-formed left carotid canal without ICA opacification, confirming the diagnosis of chronic ICA occlusion. Results: Current imaging again showed lack of enhancement in the left ICA, with adequate cerebral perfusion supplied via the contralateral ICA and vertebrobasilar system. Recognition of the preserved carotid canal on earlier CTA clarified the diagnosis as chronic occlusion rather than agenesis. Although surgical or endovascular revascularization was recommended, the patient opted for conservative management. At three months of follow-up, symptoms had improved and clinical monitoring continues. Conclusions: This case underscores the importance of distinguishing ICA agenesis from chronic occlusion, particularly by evaluating the carotid canal on CT. The presence of a carotid canal strongly indicates prior patency of the ICA and supports a diagnosis of occlusion. Careful differentiation is critical to avoid misinterpretation and to guide appropriate clinical management. In addition, reviewing prior imaging can be valuable when current findings are inconclusive or potentially misleading. Since this is a single case report, these observations should be regarded as hypothesis-generating rather than definitive, and further studies are needed to validate their broader applicability. Full article

Introduction: Genes in the endolysosome and autophagy pathways are major contributors to hereditary spastic paraplegia (HSP). A pathogenetic link between HSP and Alzheimer disease (AD) involving macroautophagy is well established. Sortilin-related receptor 1 (SORL1), an endosomal trafficking protein, plays a key role in glutamatergic neuron homeostasis and white matter tract integrity. Until now, SORL1 has only been associated with dominant AD and cerebral amyloid angiopathy. Methods: A case of HSP with cerebroretinal vasculopathy (CRV) negative on exome sequencing was further investigated using whole-genome sequencing. RNA-seq, Western blot, and immunofluorescence imaging were performed to explore a potential loss-of-function mechanism. Results: Sequencing revealed a biallelic SORL1 splice donor variant (c.1211 + 1G > A). Transcriptomics confirmed nonsense-mediated decay and aberrant splicing, predicting a disrupted reading frame. Reduced SORLA protein levels and significant enlargement of endolysosomes in patient-derived fibroblasts further cemented the pathogenicity of the variant. Conclusions: The probability that SORL1 acts as a recessive disease-causing gene gathers support from the following data: SORL1 genomic constraint score pRec = 1, high meiotic recombination rates on the locus, phenotype of Sorl1^−/− mice reminiscent of HSP with CRV, and endolysosomal enlargement in SORL1^−/− glutamatergic neurons in vitro. Taken together, SORL1 is probably a new candidate for a recessive form of complicated HSP. Full article

On behalf of the SFCNS, Swiss Federation of Clinical Neuro-Societies, we are pleased to present the Abstracts of the 6th SFCNS Congress, which will be held in Lausanne, Switzerland, 29–31 October 2025. In total, 182 abstracts were selected as ePosters, of which 60 abstracts are presented as short presentations during the ePoster Sessions and 2 abstracts are presented at the Neurosurgery Sessions. We congratulate all the presenters on their research work and contributions. Full article