Faculty Bibliography

PURPOSE/OBJECTIVE:Cognitive motor dissociation (CMD) is associated with long-term recovery in acute brain injury, but CMD testing is only available in few centers. Our objective was to identify surface EEG patterns with high sensitivity or positive predictive value (PPV) for CMD in patients with acute disorders of consciousness to refine allocation of this resource-intensive test. METHODS:In this observational cohort study, we enrolled clinically unresponsive, acutely brain injured patients who underwent continuous surface EEG and CMD assessments. CMD was detected by applying a machine learning algorithm to EEG acquired during a motor command paradigm presentation. Electroencephalographers blinded to CMD test results applied standardized ACNS criteria to the EEGs acquired during CMD assessments. We calculated accuracy measures of surface EEG findings for CMD test results using generalized estimating equations, with an exchangeable matrix and accounting for repeated measures per patient. RESULTS:We included 185 patients (mean age: 62 ± 17; 85 [46%] female) and 282 CMD assessments. CMD testing was positive in 39 (14%) assessments. Sensitivity and PPV of normal background voltage, symmetry, and continuity were, respectively, 77% (95% CI: 60%-88%) and 19% (95% CI: 13%-26%), 74% (95% CI: 58%-86%) and 14% (95% CI: 10%-20%), and 74% (95% CI: 58%-86%) and 14% (95% CI: 9%-19%). All EEGs with burst suppression, suppression, sporadic epileptiform discharges, lateralized periodic discharges, bilateral independent periodic discharges, electrographic seizures, and brief potentially ictal rhythmic discharges had negative CMD tests. CONCLUSIONS:Surface EEG findings are not reliable to screen for CMD or to identify patterns conferring higher CMD pretest probability.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Withdrawal of life-sustaining treatment (WOLST) is a common factor leading to death in traumatic brain injury (TBI). Recent guidelines have supported delaying WOLST given data suggesting that even patients with severe injuries may have meaningful recovery. However, temporal trends in WOLST are not well described. Here we investigate trends in WOLST among patients with TBI. METHODS:We performed a retrospective cohort study using data from the American College of Surgeons Trauma Quality Program (ACS-TQP) between 2013 and 2023. We included all adults aged 18+ years with TBI defined by ICD-9/ICD-10-CM codes who died before discharge from the index hospitalization. We captured demographic factors including age, race/ethnicity, and comorbidities, as well as hospital/outcome variables including interfacility transfer, hospital size and teaching status, and major hospital complications. WOLST is recorded by each participating trauma center and captured as a discrete variable in the ACS-TQP. For each year, we calculated proportions of death after WOLST as well as time to WOLST. We repeated the analyses, including only patients with isolated TBI and stratifying by TBI severity. RESULTS:< 0.001). In sensitivity analyses of isolated TBI, the results were similar. DISCUSSION/CONCLUSIONS:The proportion of trauma patients with TBI who died after WOLST decreased modestly from 2013 to 2023 while time to WOLST increased. Although these may reflect shifting attitudes toward prognostication, WOLST nonetheless remains common and occurs early among patients with TBI.

Cyclin D-CDK4/6 complexes drive cell-cycle entry through an RB-E2F-dependent transcriptional program, but how they coordinate proliferation with the membrane and organelle protein supply required for growth is unclear. We identify DeSI1 as a cyclin D-CDK4/6 substrate whose phosphorylation at S25 converts a latent homodimer into an active monomeric deubiquitylase that recognizes hydrophobic proteins such as those bearing transmembrane domains and mitochondrial targeting sequences. Phosphorylated, active DeSI1 extends the lifetime of newly synthesized hydrophobic proteins that support membrane and mitochondrial capacity. Constitutive DeSI1 activation uncouples this proteostatic program from metabolic supply, creating a cytidine-nucleotide supply-demand imbalance associated with impaired CTP-dependent phospholipid homeostasis, cardiolipin depletion, and mitochondrial decompensation -defects that cytidine reverses. In mice, constitutive DeSI1 activation causes progressive cerebellar degeneration with membrane-protein accumulation, respiratory-chain loss, and phospholipid depletion. These findings define a post-translational mechanism coupling cell-cycle entry to membrane and mitochondrial capacity, and reveal the cost of uncoupling this program from its metabolic support.

Basal forebrain cholinergic neurons play a key role in cognition. This neuronal system is highly dependent on nerve growth factor (NGF) for its synaptic integrity and the phenotypic maintenance of its cell bodies. Basal forebrain cholinergic neurons progressively degenerate in Alzheimer's disease and Down's syndrome, and their atrophy contributes to the manifestation of dementia. Paradoxically, in Alzheimer's disease brains, the synthesis of NGF is not affected and there is abundance of the NGF precursor (proNGF). We have shown that this phenomenon is due to a deficit in NGF's extracellular metabolism which compromises proNGF maturation and exacerbates its subsequent degradation. We hypothesized that a similar imbalance should be present in Down's syndrome. Using a combination of quantitative reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting and zymography, we have investigated signs of NGF metabolic dysfunction in post-mortem brains from the temporal (n = 14), frontal (n = 34) and parietal (n = 20) cortex obtained from Down's syndrome subjects and age-matched controls (age range 31-68 years). We further examined primary cultures of human fetal Down's syndrome cortex (17-21 gestational age weeks). We report a significant increase in proNGF levels in human Down's syndrome brains, with a concomitant reduction in the levels of plasminogen and tissue plasminogen activator mRNA as well as an increment in neuroserpin expression; enzymes that partake in proNGF maturation. Down's syndrome brains also exhibited elevated zymogenic activity of MMP9, the major NGF-degrading protease. Our results indicate a failure in proNGF maturation in Down's syndrome brains and a likely enhanced proteolytic degradation of NGF, changes which can compromise the trophic support of basal forebrain cholinergic neurons. The alterations in proNGF and MMP9 were also present in cultures of Down's syndrome fetal cortex; suggesting that this trophic compromise may be amenable to rescue, before frank dementia onset. Our study thus provides a novel paradigm for cholinergic neuroprotection in Alzheimer's disease and Down's syndrome.

<p>Background: Salvador Dalí (1904-1989), the great Surrealist painter, developed a progressive parkinsonian syndrome during the last decade of his life that ended his artistic career and reduced him to near-total dependence. Multiple physicians documented tremor, rigidity, and progressive disability, yet no clinical account has been published in the neurological literature. Summary: Drawing on contemporaneous press reports, biographies based on primary sources, sworn medical testimony, and a published quantitative analysis of his paintings, this review compiles the chronological evolution of Dalí's neurological symptoms. Non-motor features (including nocturia without urological explanation and erectile dysfunction from at least 1974) were documented years before the onset of visible motor symptoms, a sequence consistent with, but not diagnostic of, prodromal synucleinopathy. The motor phase, beginning around 1980, was characterized by asymmetric resting tremor affecting the right upper extremity, rigidity, gait impairment, and progressive akinesia. Despite examinations by prominent neurologists including Lluís Barraquer Bordas and François Lhermitte, the diagnosis remained contested throughout Dalí's life. Drug-induced parkinsonism was implicated in the initial crisis, but the continued deterioration after drug withdrawal argues against a purely iatrogenic etiology. No autopsy was performed. Key Messages: This case illustrates a problem familiar to practicing neurologists: the difficulty of diagnosing parkinsonism in patients with complex premorbid personalities, where emerging neuropsychiatric symptoms are absorbed into longstanding behavioral patterns. Today, biomarkers detecting α-synuclein aggregates in peripheral tissues would greatly reduce such diagnostic uncertainty; these tools were not available in Dalí's lifetime. </p>.

Deep neural networks (DNNs) are promising computational models for understanding visual object recognition. Yet, whether DNNs use similar visual cues for object recognition as humans do remains unknown. We created an image set that systematically untangles global shape, internal parts, and texture information, and compared human recognition behavior against >200 DNNs spanning diverse architectures, training diets, and training objectives. No DNNs replicated humans' cue-reliance profile, including those with recurrence or specialized training. Fine-tuned text-image contrastive-trained models, regardless of architecture, were most human-like overall, but lost their human-alignment when the global shape was disrupted. Strikingly, all DNNs substantially underperformed humans when the global shape cue alone was critical to object recognition. Furthermore, alignment with ventral stream neural recordings in an existing database did not predict alignment to human behavior, and model performance does not always predict its human-alignment. Together, these findings reveal systematic and persistent differences between human and machine vision.

This manuscript presents the perspective of the International Society of Cartilage Repair of the Ankle (ICCRA) regarding a recent English High Court ruling that challenges established principles of evidence-based sports orthopaedic care. Following a legal case involving a professional footballer and the surgical management of an ankle fracture with concomitant arthroscopy, the authors highlight significant discrepancies between the legal conclusions and the current scientific literature. The ruling suggests that arthroscopic intervention contributed to the development of ankle arthritis and premature termination of the athlete's career. However, substantial evidence demonstrates that posttraumatic ankle arthritis is a well-recognised sequela of ankle fractures, particularly in the presence of prior injury and syndesmotic instability. Arthroscopy at the time of fracture fixation is widely regarded as the standard of care for identifying and managing intraarticular pathology. The judgement is critiqued for disregarding expert orthopaedic testimony, misinterpreting scientific evidence and endorsing unsupported theoretical mechanisms linking routine arthroscopic procedures to accelerated joint degeneration. The authors emphasise that such conclusions contradict accepted surgical practice and risk establishing harmful precedents that may deter appropriate management of similar injuries. This ICCRA statement highlights the need for alignment between medico-legal reasoning and scientific evidence to safeguard patient care and uphold the integrity of orthopaedic decision-making. LEVEL OF EVIDENCE: NA.

BACKGROUND:Autonomic dysfunction is associated with adverse cardiovascular outcomes, increased symptom burden, and impaired quality of life. Although it is increasingly recognized in patients with breast cancer, its prevalence has not been well established. METHODS:A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Databases used were Embase, PubMed/MEDLINE, Scopus, Web of Science, and LILACS (Latin American and Caribbean Health Sciences Literature). Studies were included if they assessed autonomic function in patients with breast cancer and reported or provided sufficient data to estimate the prevalence of autonomic dysfunction, published in English or Spanish from 1954 to February 2026. The quality of the studies was assessed using the Newcastle-Ottawa Quality Assessment Scale and the NIH Quality Assessment Tool. RESULTS: = 90.8%). CONCLUSIONS:Autonomic dysfunction affects nearly one in two patients with breast cancer, highlighting dysautonomia as a prevalent, often subclinical, and underrecognized complication with potential implications for cardiovascular health, symptom burden, and quality of life. PROSPERO registration number CRD420251253332.

BACKGROUND/UNASSIGNED:Although vertebral hemangiomas (VH) are relatively common, aggressive symptomatic VH are rarely reported (i.e. in up to 11% of cases). Multiple other benign and malignant primary bone tumors must be considered in the differential diagnosis. Here, we review the clinical diagnosis and surgical management for aggressive hemangiomas, while also presenting 2 patients with thoracic lesions requiring posterior surgical decompression/fusion, with/without vertebroplasty, embolization, and/or CyberKnife radiosurgery. METHODS/UNASSIGNED:The classification system for these tumors ranges from Types I-IV; I Occupy < 50% of a vertebral body (VB), II-Occupy > 50% VB (IIb Thoracolumbar - Symptomatic), III-Occupy 100% VB, and IV-Occupy 100% VB involved plus extension into the pedicles, laminae, spinous process, and epidural space. RESULTS/UNASSIGNED:Radiographically (i.e. X-rays, MR, CT) these lesions originate in the vertebral bodies, but aggressive VH extend into the pedicles, laminae, spinous processes, and epidural space causing both spinal cord/root (i.e., myelopathy/radiculopathy)) compression. Surgical options include anterior, posterior, or circumferential decompressions with/without fusions, percutaneous vertebroplasty, embolization, radiation, and/or chemotherapy. Early treatment maximizes neurological recovery and limits/avoids permanent injury. CONCLUSION/UNASSIGNED:Aggressive VH are rare lesions that most frequently occur in the thoracic spine. Notably, the subset of Type IV lesions that extend into the pedicles, laminae, spinous processes, and epidural space may cause symptomatic myelopathy/radiculopathy warranting early surgical intervention to optimize neurological outcomes.

BACKGROUND AND PURPOSE/OBJECTIVE: MATERIALS AND METHODS/METHODS: RESULTS: CONCLUSIONS:The dynamics of the CVR response can reveal differential and previously occult temporal signatures in the pharmacologic response of white matter to ACZ, suggesting potential interactions between macrovascular and microvascular hemodynamic impairment.