Faculty Bibliography

Neuroinflammation involving glial cell activation and BBB dysfunction has increasingly been recognized as a key feature of neuropsychiatric disorders. In vivo imaging methods, particularly translocator protein positron emission tomography (TSPO-PET) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), have advanced our understanding of glial activation and BBB permeability in conditions such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, Huntington's disease, schizophrenia, and depression. We present key findings from the clinical application of these imaging modalities and highlight critical methodological challenges-including variability in study protocols, tracer selection, input function derivation, and parameter estimation-that currently limit cross-study comparability and clinical translation. TSPO-PET and DCE-MRI provide valuable clinical insights on the inflammatory mechanisms contributing to CNS disease at various disease stages. Future methodological standardization, co-localization studies, and longitudinal multi-modal applications will be crucial for using these tools as markers of disease in the context of immune interventions in at-risk populations.

PURPOSE OF REVIEW/OBJECTIVE:Antithrombotic-associated intracerebral hemorrhage (ICH) is associated with high rates of morbidity and mortality. Rapid and effective antithrombotic reversal is critical for mitigating risk of hemorrhage expansion and neurological deterioration. This review provides an overview of the most recent advances in emergency antithrombotic reversal in ICH. RECENT FINDINGS/RESULTS:Rapid coagulopathy reversal within the first 60-90 min of hospital presentation may limit massive ICH expansion and improve outcomes. Current data suggests reversal of vitamin K antagonists with intravenous vitamin K and 4-factor prothrombin complex concentrates (4f-PCC), reversal of dabigatran with idarucizumab, and reversal or direct oral factor Xa inhibitors with either 4f-PCC or andexanet-alfa. While platelet transfusion is not suggested for antiplatelet-associated ICH, DDAVP may be reasonable, and a new reversal agent is under development for ticagrelor. Rapid reversal of antithrombotic-associated coagulopathy in the context of ICH may prevent ICH expansion and improve neurological outcomes.

Recent research demonstrates that large language models can predict neural activity recorded via electrocorticography during natural language processing. To predict word-by-word neural activity, most prior work evaluates encoding models within individual electrodes and participants, limiting generalizability. Here we analyze electrocorticography data from eight participants listening to the same 30-min podcast. Using a shared response model, we estimate a common information space across participants. This shared space substantially enhances large language model-based encoding performance and enables denoising of individual brain responses by projecting back into participant-specific electrode spaces-yielding a 37% average improvement in encoding accuracy (from r = 0.188 to r = 0.257). The greatest gains occur in brain areas specialized for language comprehension, particularly the superior temporal gyrus and inferior frontal gyrus. Our findings highlight that estimating a shared space allows us to construct encoding models that better generalize across individuals.

OBJECTIVE:NF2-related schwannomatosis (NF2-SWN) is an autosomal dominant genetic disorder characterized by the development of schwannomas, meningiomas, and spinal ependymomas. Treatment with bevacizumab, a monoclonal antibody against VEGF, has been shown to result in decreased vestibular schwannoma size and hearing improvement in ~50% of NF2-SWN patients. It is unknown whether the same degree of benefit is seen in younger patients compared with older patients. The objective of this study is to determine the association between age and bevacizumab treatment outcomes in NF2-SWN. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Thirty-seven patients with NF2-SWN. INTERVENTIONS/METHODS:Bevacizumab. MAIN OUTCOME MEASURES/METHODS:Change in tumor size of 20% or more. RESULTS:This study includes 37 patients with NF2-SWN who were treated with bevacizumab at our institution between 2014 and 2024. They were divided into 2 groups: 22 adults over the age of 25 (26 to 71 y) and 15 adolescent and young adult (AYA) patients under the age of 25 (12 to 24 y). The median treatment duration was 2.1 years. A significantly higher proportion of AYA schwannomas (37.5%, n=9) exhibited radiographic tumor progression during the treatment period compared with those of the older patient group (11.9%, n=5) (P=0.026), despite similar pre-treatment growth rates. There was no significant difference in the proportion of older and younger patients with hearing decline, improvement, or stability (P>0.05). CONCLUSIONS:AYA patients were significantly more likely to exhibit progression of tumor growth during bevacizumab treatment compared with older patients, though no significant differences were detected in hearing outcomes.

BACKGROUND:Arteriovenous malformations (AVMs) are uncommon cerebral lesions that can cause significant neurological complications. Surgical resection is the gold standard for treatment, but endovascular embolization and stereotactic radiosurgery (SRS) are viable alternatives. OBJECTIVE:To compare the outcomes of endovascular embolization versus SRS in the treatment of AVMs with Spetzler-Martin grades I-III. METHODS:This study combined retrospective data from 10 academic institutions in North America and Europe. Patients aged 1 to 90 years who underwent endovascular embolization or SRS for AVMs with Spetzler-Martin grades I-III between January 2010 and December 2023 were included. RESULTS:The study included 244 patients, including 84 who had endovascular embolization and 160 who had SRS. Before propensity score matching (PSM), complete obliteration at the last follow-up was achieved in 74.5% of the SRS group compared with 57.8% of the embolization group (OR=0.47; 95% CI 0.26 to 0.48; P=0.01). After propensity score matching, SRS still achieved significantly higher occlusion rates at last follow-up (78.9% vs 55.3%; OR=0.32; 95% CI 0.12 to 0.90; P=0.03).Hemorrhagic complications were higher in the embolization group than in the SRS group, although this difference did not reach statistical significance after PSM (13.2% vs 2.6%; OR=5.6; 95% CI 0.62 to 50.47; P=0.12). Similarly, re-treatment rate was higher in the embolization group (10.5% vs 5.3%; OR=2.11; 95% CI 0.36 to 12.31; P=0.40) compared with the SRS group. CONCLUSION/CONCLUSIONS:Our findings indicate that SRS has a significantly higher obliteration rate at last follow-up compared with endovascular embolization. Also, SRS has a higher tendency for fewer hemorrhagic complications and lower re-treatment rate. Further prospective studies are needed.

The semiology of clinical phenomena is central to neurological reasoning. When clinical manifestations occur in combination (e.g., weakness plus sensory loss), they are traditionally analyzed by considering anatomical localization (e.g., right-sided weakness and aphasia implicate the left cerebral cortex) and disease pattern recognition (e.g., tremor, bradykinesia, and rigidity indicate parkinsonism). The authors introduce a third, complementary approach-phenoconsonance-that relates neurological phenomena to each other not by their anatomical localization or disease pattern recognition but by their shared phenomenology. The authors identify the main components of the description of neurological phenomena in relation to where, what, and how neurological function is affected: examples for "where" include left-arm deficits in left brachial plexopathy or left hemispace neglect in right parietal lesions; examples for "what" include motor strength, visuospatial reasoning, or abstract planning; and examples for "how" include slowness, incoordination, or difficulty with initiation, because either the same function can be disrupted in qualitatively different ways-movement can be slowed or uncoordinated-or the same qualitative abnormality can apply to different functions-slowing may characterize movement, and it may also characterize thinking. The where, what, and how of neurological phenomenology correspond in the authors' synthesis to spatial phenoconsonance, domain phenoconsonance, and qualitative phenoconsonance, respectively. The historical context and conceptual underpinning of the notion of phenoconsonance are reviewed, as is its usefulness for the study of brain-behavior relationships in the evaluation and treatment of individuals with neurological and neuropsychiatric disorders.

Differential mRNA translation efficiency (mTE) of codons is important in regulating protein synthesis and cellular states and can change in response to amino acid availability. While the mTE of codons is canonically associated with their corresponding transfer RNA (tRNA) isoacceptors, its regulation by amino acids in mammalian cells remains unexplored. We found that ELAC2, a 3' tRNA maturation endonuclease, decreases the mTE of UC[C/U] serine (Ser) codons in response to Ser limitation. Ablation of ELAC2 restored UC[C/U] mTE but reduced the mTE of AG[U/C] Ser codons. Among the tRNA^Ser isoacceptors, tRNA^Ser(GCU) decreased the most in ELAC2-deficient cells. Unexpectedly, tRNA^Ser(GCU) delivery restored AG[U/C] mTE and reduced UC[C/U] mTE in ELAC2-deficient cells. Last, we deciphered the effects of Ser-sensitive codons on mRNA translation and the human proteome. Our study revealed that in response to Ser limitation, regulation of tRNA^Ser(GCU) levels fine-tune the mTE of UC[C/U] or AG[U/C] Ser-sensitive codons and shapes the proteome.

Understanding consciousness remains a significant challenge in science. What distinguishes conscious beings from unconscious systems, such as organoids, artificial intelligence or other non-sentient entities? Research on consciousness often focuses on identifying brain activity associated with conscious and non-conscious states, primarily in neurotypical human adults. However, this approach is limited in scope when applied to entities with developmental or evolutionary trajectories different from our own. How do we investigate consciousness in infants, whose brains are still maturing or in non-human animals, shaped by diverse ecological and evolutionary pressures? This opinion piece encourages consciousness studies to adopt a neuroethological perspective, drawing on Tinbergen's framework for studying behaviour. By examining the (1) mechanisms, (2) development, (3) adaptive functions and (4) evolutionary origins of consciousness, we can move beyond a human-centric focus to explore its diversity across life forms. Most investigators now accept that consciousness is not confined to humans alone but that some other animals have it, and it is a continuum shaped by evolutionary pressures. By adopting this broader approach, consciousness studies can better investigate and understand consciousness in its various forms and contexts, with significant scientific, ethical and societal implications.This article is part of the theme issue 'Evolutionary functions of consciousness'.

Chronic progressive external ophthalmoplegia (CPEO), a genetic syndrome characterized by slowly progressive paresis of extraocular muscles, is often due to single large-scale deletions of the mitochondrial genome (mtDNA). Owing to heteroplasmy, mtDNA variants are often not uniformly expressed across tissues. This genetic variability affects clinical presentation and diagnostic testing. We report a case of a 34-year-old woman who presented with symptoms suspicious for a genetic myopathy: chronic asymmetric ptosis, slowly progressive asymmetric weakness, and external ophthalmoplegia. After initial nondiagnostic peripheral genetic testing, whole-exome and mitochondrial genome sequencing of muscle revealed a single large-scale mtDNA deletion, consistent with a diagnosis of mtDNA deletion-associated CPEO. Of interest, electrophysiologic studies showed myotonia in select muscles, a rarely reported finding. We discuss the clinical presentation and diagnostic approach in suspected CPEO, with an emphasis on common pitfalls in genetic testing for mitochondrial myopathies and the need for appropriate tissue and genetic testing modality selection.