Clinical and Translational Neuroscience

Uhthoff’s phenomenon (UP) is a transient, fully reversible exacerbation of pre-existing neurological deficits in multiple sclerosis (MS) patients, triggered by minor elevations in core body temperature. In clinical practice, UP is a frequent source of distress, often misidentified as an acute inflammatory disease relapse. This narrative review provides a critical analysis of UP, addressing methodological heterogeneity in its epidemiological estimates, its clinical presentation, and its differential diagnosis from true relapses. Mechanistically, we synthesize traditional concepts of temperature-dependent conduction block with modern insights into neuroenergetic failure, mitochondrial dysfunction, inflammatory mediators, and autonomic dysregulation. Furthermore, this work delineates current management strategies, establishing a clear distinction between robust evidence-based interventions and expert-informed practical guidance for patient education, physical rehabilitation planning, targeted active/passive cooling, and pharmacological approaches. Characterized as a pseudo-relapse, UP occurs independently of novel focal neuroinflammation. In conclusion, an isolated episode of Uhthoff’s phenomenon (UP) represents a transient, functional conduction block and does not inflict acute, permanent structural damage to the axon. However, emerging frameworks suggest that frequent, repeated episodes subject the already demyelinated axon to recurrent metabolic strain. Over time, these successive neuroenergetic crises do not directly destroy the fiber, but they may gradually exhaust the cell’s metabolic reserve. This cumulative stress potentially increases long-term secondary axonal vulnerability, making the axon more susceptible to the progressive neurodegenerative processes inherent to multiple sclerosis.

Recent developments in cognitive neuroscience, neuroimaging, and embodied cognition have stimulated growing interest in neuroscience-informed architecture. However, despite the rapid expansion of the field, neuroarchitectural scholarship remains conceptually fragmented and methodologically diverse, and its institutional evolution, thematic structure, and translational implications have not been comprehensively synthesised. Using a narrative critical synthesis supported by translational qualitative structuring and conceptual synthesis, this study examines foundational publications, institutional documents, conference outputs, and applied studies that have shaped neuroscience-informed architecture since the early 2000s. The review identifies recurring thematic domains, including sensory perception, spatial cognition, emotion, empathy, embodied cognition, environmental behaviour, healthcare design, and evidence-based architectural practice. It indicates that ANFA-related scholarship has played a significant role in legitimising neuroscience as a relevant framework for understanding architectural experience and informing design practices in therapeutic, educational, and behavioural contexts. The review also highlights persistent methodological challenges in translating neuroscientific findings into architectural research, particularly given that architectural experience is multisensory, embodied, socially situated, and temporally dynamic. The study concludes that neuroscience-informed architecture should be understood not as a deterministic explanatory model but as a translational framework that connects neuroscientific knowledge with architectural theory and practice. This expanding evidence base calls for more ecologically valid, interdisciplinary, and methodologically rigorous research, while encouraging architects and practitioners to adopt evidence-based, human-centred design strategies that enhance health, well-being, and user experience across diverse built environments.

Background: Same-day or post-admission cancellation of elective surgery is associated with inefficient operating room utilization, patient distress, and disruption of coordinated perioperative care. Functional neurosurgery is particularly vulnerable to late-stage cancellation because procedural readiness depends on parallel clinical, anatomical, medication-related, device-related, and systemic considerations. Objective: This paper aims to describe the implementation of a structured preoperative review framework for functional neurosurgery and to evaluate its association with late-stage surgical cancellation after patient admission. Methods: We performed a retrospective single-center before-and-after study of consecutive functional neurosurgical procedures scheduled at Sheba Medical Center between January 2020 and December 2025. The ABCDE framework was introduced in 2023 as a structured workflow model organized around five domains: Anatomy, Bacteria, Clotting, Devices, and Elsewhere. Included procedures were deep brain stimulation, vagus nerve stimulation, focused ultrasound, intrathecal pump implantation or replacement, implantable pulse generator replacement, spinal cord stimulation, peripheral nerve stimulation, and other palliative neuromodulation procedures. The primary endpoint was late-stage cancellation, defined as cancellation after hospital admission and initiation of operative preparation. The primary comparison was between 2020–2022 and 2023–2025. A sensitivity analysis excluded 2020 because of pandemic-era disruption. Results: A total of 867 procedures were scheduled. Late-stage cancellation occurred in 16 of 407 pre-implementation procedures and 5 of 460 post-implementation procedures, corresponding to rates of 3.9% and 1.1%, respectively. The absolute risk difference was −2.8 percentage points (95% CI, −5.2 to −0.8), and the relative risk for cancellation after implementation was 0.28 (95% CI, 0.10 to 0.75). A two-sided Fisher’s exact test comparing cancellation versus non-cancellation across the pre-implementation and post-implementation periods was statistically significant (16/407 vs. 5/460; p = 0.0074). After excluding 2020, the direction of effect remained similar, but the difference was not statistically significant: 8 of 302 procedures in 2021–2022 were canceled compared with 5 of 460 in 2023–2025 (2.6% vs. 1.1%; p = 0.15). Detailed source-level attribution was incomplete for 10 of 21 cancellation events, and domain-level analyses should therefore be interpreted descriptively. Conclusions: Implementation of the ABCDE framework was associated with fewer late-stage surgical cancellations in this single-center before-and-after study. Because the design is observational, the number of events is small, and the study period overlaps with pandemic-era disruption and post-pandemic service stabilization, the findings should be interpreted as hypothesis-generating rather than causal. The framework may provide a practical structure for standardizing preoperative review in functional neurosurgery, but prospective studies with formal adherence tracking and procedure-specific analyses are needed.