Faculty Bibliography

BACKGROUND/UNASSIGNED:Can we document that posterior cervical surgery (i.e., Laminoforaminotomy (LF) and Laminectomy (L) with Posterior Fusion (PF)) exposes patients to fewer adverse events (i.e., including negligence, multiple risks, negligence, errors, and mistakes) vs. anterior cervical surgery (i.e., Anterior Cervical Diskectomy/Fusion (ACDF) or Anterior Corpectomy/Fusion (ACF))? METHODS/UNASSIGNED:Posterior cervical surgery avoids many of the adverse events uniquely attributed to anterior cervical operations. These include; avoiding fusions with LF vs. ACDF for disc herniations, a lower rate of pseudarthrosis, the avoidance of direct laceration/indirect traction-related carotid/jugular vascular and/or dysphagia/esophageal injuries, fewer neural/cord injuries, vertebral artery injuries, and cerebrospinal fluid (CSF) leaks/dural tears (i.e., particularly with Ossification of the Posterior Longitudinal Ligament (OPLL)). RESULTS/UNASSIGNED:Posterior cervical surgery also poses no direct risks to the following anteriorly-located nerves: recurrent laryngeal nerve (i.e., vocal cord paralysis), phrenic nerve (i.e., diaphragmatic paralysis), the Vagus nerve (i.e., hypotension, reflux, arrhythmias), and sympathetic trunk (i.e., Horner's Syndrome). However, posterior cervical surgery is generally associated with a higher risk of infection (i.e., 2-10%) vs. anterior surgery (i.e., > 1%), more posterior muscle pain, and a higher risk of kyphosis. CONCLUSIONS/UNASSIGNED:Posterior cervical surgery exposes patients to many fewer adverse events vs. anterior cervical surgery. We therefore recommend that in appropriately chosen patients, posterior cervical surgical approaches should be chosen over anterior surgery.

BACKGROUND/UNASSIGNED:A central vestibular neural mechanism known as velocity storage may be inappropriately conditioned in mal de débarquement syndrome (MdDS), a rare chronic vestibular disorder with a continuous false sensation of self-motion described as non-spinning vertigo. Visual-vestibular therapy approaches designed to recondition the three-dimensional properties of velocity storage have yielded much clinical success, but not without limitations. An alternative therapeutic approach, designed to attenuate the contribution of malfunctioning velocity storage in higher-order neural processing, has also yielded positive results, but at a lower success rate. We sought a possible explanation for the latter shortcoming using a mathematical model. METHODS/UNASSIGNED:The three-dimensional orientation properties of velocity storage can be modeled as a dynamical system using a 3 × 3 system matrix. For normal upright, the system matrix is diagonal, with its eigenvectors aligning with the head-fixed roll, pitch, and yaw axes, and the yaw eigenvector with gravity. A pull sensation of MdDS has been expressed with a system matrix with off-diagonal elements representing cross-axis coupling and interpreted as a misalignment between the yaw eigenvector and the head vertical. We manipulated the velocity storage's yaw time constant and output weight. RESULTS/UNASSIGNED:The model predicted that attenuating the velocity storage contribution could exaggerate the pull sensation. CONCLUSION/UNASSIGNED:The present model-based exploration points to a possible weakness in the MdDS treatment approach focused on velocity storage attenuation, while likely beneficial otherwise. When a pulling sensation is present, the treatment protocol may need to be supplemented with another approach that specifically counters this problem, such as optokinetic stimulation.

BACKGROUND/UNASSIGNED:Focal task-specific dystonia of the musicians' arm (FTSDma) is an unusual and challenging disorder, often causing significant disability with loss of performing careers. The etiology and optimal management of this disorder remains unclear. METHODS/UNASSIGNED:We reviewed records and videos of 173 patients with FTSDma, 50 patients with writer's cramp (WC), and 16 with other forms of arm dystonia (OD), evaluated by a single examiner in clinical practice over a 25-year period. Detailed analysis of clinical features and videotaped examinations in slow motion (what we call "deep phenotyping") allowed separation of patients into four categories: "precision-grip" dystonia (groups I and III); "power-grip" dystonia (group II); and "proximal dystonia" (group IV). We compared these results to deep phenotyping of patients with FTSDma, WC and OD patients reported in the literature. RESULTS/UNASSIGNED:FTSDma usually affects men, involves the right hand, and begins in the fourth decade. The precision hand of pianists and guitarists (digits 1, 2, 3) was preferentially affected in the right arm, and many of the remaining patients involved the power hand of either arm (digits 3, 4, 5). The dystonic phenotype of the bow arm of string players and drumming arm of stick drummers bore striking resemblance to WC and racquet dystonia, almost always involving the wrist, forearm or shoulder. CONCLUSIONS/UNASSIGNED:Deep phenotyping of FTSDma reveals similarities in dystonic phenotype between instrument classes, likely related to shared technical demands, and unexpected similarities between other forms of task-specific upper extremity dystonia. A network model to explain these findings is proposed.

INTRODUCTION/UNASSIGNED:Gait is a critical indicator of neurological health, with changes often signaling underlying decline. We developed a remote gait monitoring protocol using off-the-shelf shoe-based sensors (RunScribe) to assess gait parameters in real-world home settings. This protocol, known as Gait Assessment with Innovative Technologies - Home-based Use and Benefit (GAIT-HUB), was tested in individuals with multiple sclerosis (MS), a population at high risk for gait impairment due to the disease's variable progression. METHODS/UNASSIGNED:Participants with MS completed an in-clinic baseline gait assessment using a validated sensor (G-Sensor®) and three weekly, remotely supervised gait assessments at home using the RunScribe sensors. Gait parameters were compared across devices using intra-class correlation coefficients (ICCs) and Bland-Altman analyses. Longitudinal reliability of remote assessments and system usability score (SUS) were evaluated. RESULTS/UNASSIGNED:Twenty-nine participants (76% women, ages 19-67, PDDS range 0-5) successfully completed the home-based assessments. High agreement between devices was observed for gait speed, stride length, and cadence (ICCs >0.90), though phases like stance and swing showed more variability. Bland-Altman analyses indicated minimal bias in most parameters. Longitudinal assessments demonstrated strong reliability (ICCs >0.87) for key metrics, and SUS indicated good-to-excellent usability of the remote protocol. CONCLUSION/UNASSIGNED:The GAIT-HUB protocol enables reliable and feasible home-based gait monitoring using wearable sensors that patients can easily self-apply. This approach provides valuable insights into daily mobility patterns beyond clinical visits, supporting more precise and timely assessments of functional status between appointments and offering the potential for seamless integration into telemedicine routine care.

BACKGROUND/UNASSIGNED:High intensity focused ultrasound (HiFU) is a relatively new incisionless intervention used for treatment of essential tremor and Parkinson's disease tremor. Understanding the indications, benefits, risks and limitations of HiFU, as well as how it compares to deep brain stimulation (DBS), is important in guiding appropriate recommendations for prospective patients. METHODS/UNASSIGNED:Current literature on efficacy and safety of HiFU in essential tremor and Parkinson's disease was reviewed. We additionally reviewed data on the patients who presented to our center for HiFU consultation, including outcomes of patients with low skull density ratios, and distances traveled for the procedure. RESULTS/DISCUSSION/UNASSIGNED:HiFU is an effective and generally well-tolerated treatment for tremor. Adverse events, especially gait instability, are typically temporary but should be discussed with patients. The risk of tremor recurrence in certain patients with Parkinson's disease is also of note. Identifying appropriate candidates for either intervention remains crucial and involves considering each patient's circumstances and preferences, potential adverse effects, and practical aspects like access to follow-up and expectations. Data on bilateral HiFU lesioning, use of HiFU in patients with low skull density ratios, and emerging targets like the pallidothalamic tract are discussed as well.

Flickering light is a new promising, fully non-invasive brain stimulation technique that utilizes intermittent sensory stimulation to induce brainwave synchronization (entrainment). While the effects of 40 Hz externally induced neural entrainment have been extensively described, little is known about 60 Hz entrainment in humans. This study presents preliminary observations on the neural and somatic response to flickering 60 Hz light in healthy volunteers over a 3-week period. Fourteen volunteers were randomized to receive either 60 Hz flickering white light or constant light as sham (30-min sessions, 3 weeks, 5 days/week on weekdays). Neural entrainment was assessed with EEG on days 1, 5 and 19. Salivary cortisol and C-reactive protein (CRP) levels, measured with ELISA, assessed the somatic response to stimulation. Side effects and well-being were monitored via questionnaires. EEG recordings showed neural entrainment and synchrony in response to 60 Hz flickering light across multiple cortical regions, including occipital, central, temporal, and frontal areas. The entrainment power and synchronization between different cortical regions declined significantly by day 19 compared to day 1, indicating possible neural habituation. Cortisol and CRP salivary levels were unchanged, and minor side effects were reported with equal frequency in the active and sham groups. Our findings show that 60 Hz flickering light can induce significant neural entrainment and synchrony in healthy adults and is well tolerated. The decline in entrainment strength and neural synchrony observed with repeated 60 Hz stimulations suggests plastic changes in the cortex. To the best of our knowledge, this is the first study to characterize neural and somatic responses to repeated 60 Hz flickering visual stimuli. Given the well-known connection between 60 Hz brain oscillations and cognition, neuroplasticity, and their role in neuropsychiatric disorders, additional research in both preclinical and clinical settings is warranted.

High-dimensional multinomial regression models are very useful in practice but have received less research attention than logistic regression models, especially from the perspective of statistical inference. In this work, we analyze the estimation and prediction error of the contrast-based

Ubiquitin-dependent proteolysis regulates diverse cellular functions with high substrate specificity, which hinges on the ability of ubiquitin E3 ligases to decode the targets' degradation signals, i.e., degrons. Here, we show that BACH1, a transcription repressor of antioxidant response genes, features two distinct unconventional degrons encrypted in the quaternary structure of its homodimeric BTB domain. These two degrons are both functionalized by oxidative stress and are deciphered by two complementary E3s. FBXO22 recognizes a degron constructed by the BACH1 BTB domain dimer interface, which is unmasked from transcriptional co-repressors after oxidative stress releases BACH1 from chromatin. When this degron is impaired by oxidation, a second BACH1 degron manifested by its destabilized BTB dimer is probed by a pair of FBXL17 proteins that remodels the substrate into E3-bound monomers for ubiquitination. Our findings highlight the multidimensionality of protein degradation signals and the functional complementarity of different ubiquitin ligases targeting the same substrate.

BACKGROUND:) are associated with important clinical outcomes during hospitalization and improve the performance of clinical prediction models of potentially lethal malignant edema (PLME). METHODS:using area under the curve. RESULTS:was significantly associated with higher odds of PLME when adjusting for confounders (OR 1.69, 95% CI 1.49 to 2.0), and improved model discrimination compared with existing models and models using baseline ASPECTS. Deep territory involvement (OR 2.46, 95% CI 1.53 to 4.01) and anterior territory involvement (OR 3.23, 95% CI 1.88 to 5.71) were significantly associated with PLME. CONCLUSIONS:information improved discrimination of established edema prediction models and could be used immediately to help facilitate clinical management decisions and prognostication.