Faculty Bibliography

BACKGROUND/UNASSIGNED:Most patients with cervical synovial cysts (CSC) present with radiculopathy and/or myelopathy. MR studies are the gold standard for diagnosing CSC, and typically show hypointense T1/hyperintense T2 lesions, with occasional cyst-wall enhancement and additional cyst-wall calcification. Surgery typically warrants focal cyst resection/ decompression with/without an instrumented fusion. Here, we reviewed the diagnosis/treatment of a 76-year-old male with a CSC, and C5-C6/C6-C7 , and C7-T1 stenosis. We further provided a select review of the literature. METHODS/UNASSIGNED:For 3 months, a 76-year-old-male experienced progressive bilateral/arm pain (i.e., radiculopathy), and one week of increased right upper/right lower extremity weakness with loss of balance (i.e., myelopathy). The MR with/without contrast and non contrast CT studies documented moderate C5-C6/C6-C7 stenosis and a large, likely synovial cyst filling the right-side of the spinal canal at the C7-T1 level (i.e, 12 mm x 9 mmx 19 mm). RESULTS/UNASSIGNED:The patient urgently underwent excision of the large right C7-T1 synovial cyst, along with a C6-T2 laminectomy for stenosis, and a C4-T4 instrumented fusion. At 4-postoperative months, the patient was neurologically intact. The repeated X-rays performed at 2, 6, and 12 weeks postoperatively documented maintained alignment, while the MR scan confirmed adequate cord decompression without myelomalacia. CONCLUSION/UNASSIGNED:A 76-year-old male with increased right-sided myeloradiculopathy, successfully underwent resection of a right-sided C7-T1 synovial cyst filling the spinal canal, a C6-T2 laminectomy for stenosis, and a C4-T4 instrumented fusion. Four months postoperatively, the patient was neurologically intact, with postoperative X-rays showing stable alignment. Further, the follow-up MR documented no residual cord/root compression, or myelomalacia. Here, we have provided a review of this case and select literature regarding the diagnosis and surgery for CSC.

Huntington's disease (HD) is a rare, neurodegenerative disorder for which only symptomatic treatments are available. The PROOF-HD study was a randomized, double-blind, placebo-controlled phase 3 trial evaluating the efficacy and safety of pridopidine, a selective Sigma-1 receptor agonist, in HD. The primary and key secondary endpoints, change in total functional capacity (TFC) and composite Unified Huntington's Disease Rating Scale (cUHDRS) score at week 65, were not met in the overall population. The TFC least-squares mean difference between pridopidine and placebo was -0.18 (95% confidence interval -0.49 to 0.14; P = 0.26). The cUHDRS least-squares mean difference between pridopidine and placebo was -0.11 (95% confidence interval -0.40 to 0.18; P = 0.45). Sensitivity analysis in a subgroup of participants not treated with antidopaminergic medications at any time demonstrated a consistent pattern favoring pridopidine across multiple measures, including TFC and cUHDRS. Notably, pridopidine 45 mg twice daily demonstrated a favorable safety and tolerability profile. Taken together, pridopidine has the potential to address a critical unmet need in HD. ClinicalTrials.gov identifier: NCT04556656 .

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'.

BACKGROUND:CDKL5 deficiency disorder (CDD) is a rare developmental and epileptic encephalopathy (DEE) associated with multiple impairments and comorbidities. Outcome measures for disease-modifying clinical trials for DEEs should measurably capture a spectrum of caregiver priorities and be externally validated. METHODS:The International CDKL5 Clinical Research Network was the data source for this observational study. A Structural Equation Model was constructed with latent, exogenous variables related to observed clinical features to calculate a global severity score from the following assessments: the CDKL5 Clinical Severity Assessment-Clinician and -Caregiver, Communication and Symbolic Behavior Scales Developmental Profile Infant Toddler Checklist and the Sleep Disturbance Scale for Children. Quantitative EEG power was measured as a biomarker. The Quality of Life Inventory-Disability measured quality of life. RESULTS:Acceptable fit statistics for models were obtained using data from 206 subjects (median [range] age 6.8 [3 months to 40] years). Motor and communication measures were the most important weighted contributors to the global severity score which correlated well with the biomarker and quality of life to support external validation. CONCLUSIONS:The resultant global severity score provided evidence that the assessments formed a coherent set of measures that reliably and meaningfully captured the diversity of severity in CDD. The models illustrated how the symptoms form a measurable network of relationships which may be suitable as an outcome measure for CDD and DEEs more broadly in clinical trials.

INTRODUCTION/BACKGROUND:The Neighborhoods Study (TNS) is a novel investigation of adverse social exposome and brain health leveraging 22 Alzheimer's Disease Research Centers (ADRCs). TNS aims to understand if the adverse social exposures increase Alzheimer's disease and related dementias (ADRD) risk. METHODS:TNS uses innovative methods to determine lifetime addresses of living (n = ≈ 3116) and brain bank cohorts (n = ≈ 8637). Addresses are linked to time-concordant adverse social exposome using the Area Deprivation Index (ADI) and summarized over time. Brain health measures are provided by the National Alzheimer's Coordinating Center. RESULTS:We highlight a general overview and methodology of TNS. Data collection is ongoing; however, preliminary findings indicate that the adverse social exposome is related to ADRD biomarkers, neuropathology, and cognitive function. DISCUSSION/CONCLUSIONS:TNS is the largest study of adverse social exposome and ADRD, using the ADRC network to build robust scientific consortia. Its findings will inform ADRD interventions, precision medicine, and policy. HIGHLIGHTS/CONCLUSIONS:The Neighborhoods Study (TNS) investigates adverse social exposome and brain health. TNS is a collaboration among 22 Alzheimer's Disease Research Centers. TNS will give insight on environmental and exposomal factors which may be modifiable. Participant lifetime addresses are linked to temporal adverse social exposome metrics. This study's findings will inform precision approaches to mitigate dementia risk.

BACKGROUND:Age is the strongest factor determining disease expression in multiple sclerosis (MS). We previously demonstrated biological age acceleration in pediatric-onset MS (POMS) compared to controls with both epigenetic clocks (DNAm) and telomere length (TL). It is unknown whether these markers report overlapping or distinct aging-related processes. OBJECTIVES/OBJECTIVE:To determine the correlation between DNAm and TL aging markers. METHODS:We conducted a cross-sectional case-control study within the US Network of Pediatric MS Centers. We calculated age acceleration residuals for the Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks and measured TL from whole blood samples to estimate telomere to somatic DNA ratios (T/S ratio). We employed multivariable analysis of covariance to assess the correlation between DNAm estimates and TL. RESULTS: = 0.06). CONCLUSIONS:DNAm did not correlate with TL in this sample of POMS and controls, suggesting that these biomarkers may capture complementary and non-overlapping elements of aging-related biology.

Parsonage-Turner syndrome (PTS) is a spontaneous neuropathy characterized by severe upper extremity pain and muscle denervation and is considered to be a rare disease that is under-recognized. Quantitative MRI (qMRI) characterizes muscle denervation but has not been previously assessed in a longitudinal PTS cohort. The aims of this study are to prospectively and longitudinally characterize qMRI changes in PTS patients at baseline (< 6 months' symptom onset) and at follow-up timepoints (3, 6, and 12 months), to measure associations against electromyography (EMG) and muscle strength, and to predict muscle strength at follow-up. A total of 49 subjects (age = 47.2 ± 14.0 years, 31 M/18 F) underwent 3-Tesla qMRI with T2-mapping, diffusion-based muscle fiber diameter, volumetry, and fat fraction (FF) mapping. Image segmentation of involved muscles was performed by two raters. Linear regression between qMRI metrics and days from symptom onset (DSO) was performed. Pearson's correlation quantified correlations between qMRI metrics, and Kendall's tau assessed correlations between qMRI and EMG and muscle strength. For predictive modeling of muscle strength, a generalized linear model was used, and the coefficient of determination (r²) was compared for combinations of baseline inputs. Regression detected a mean T2 increase of 0.66 ms/week and a mean muscle fiber diameter decrease of 0.96 μm/week within DSO of 100. Muscle fiber diameter correlated with muscle volume (r = 0.850). T2 correlated with EMG (|τ| = 0.34-0.78) and muscle strength (|τ| = 0.40-0.83) in most muscles that could be analyzed. Muscle fiber diameter was correlated to EMG (|τ| = 0.43-0.72) and muscle strength in some muscles (|τ| = 0.39-0.56). The addition of baseline T2 values improved the prediction of muscle strength at 3-month (from r² = 0.57 to 0.67, with -0.057 to -0.068 muscle grade per ms T2), at 6-month (r² = 0.40-0.59, -0.057 to -0.071 grade per ms), and at 12-month follow-up (r² = 0.40-0.62, -0.053 to -0.080 grade per ms). Muscle qMRI measurements in PTS depict muscle denervation and provide complementary characterization of muscle quality for diagnosis and follow-up assessment.