Faculty Bibliography

INTRODUCTION/UNASSIGNED:To ensure Alzheimer's disease-modifying treatments can be initiated in diverse populations, efficient pathways to obtain timely diagnoses are required. METHODS/UNASSIGNED:This interim sub-analysis of a multicenter US study included cross-sectional surveys and interviews with neurologists at 12 diverse sites to assess real-world lecanemab use. RESULTS/UNASSIGNED:testing to inform risk/benefit decisions. Infusions usually started within 6 months of diagnosis. Delayed/incomplete referrals were identified as the most significant barrier in the current patient pathway. DISCUSSION/UNASSIGNED:These findings demonstrate the feasibility of lecanemab integration in diverse clinical settings and highlight the importance of primary care physician engagement, optimization of referral pathways, and expanding BBM use in improving timely diagnosis, equitable access, and early treatment initiation.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic caused significant global harm. Seroprevalence studies detected antibody increases from SARS-CoV-2 infection, assessing transmission and risk from infection. These studies and epidemiological modeling informed public health policy and behavior. Biases in early seroprevalence analyses caused underestimation of fatality risk, including the risk posed to pediatric populations and to those in lower-income nations. The scope of the pandemic was clarified by seroprevalence studies that better assessed at-risk groups and by adjustment of seroprevalence data for known data biases. Reassessment of seroprevalence data confirms the accuracy of early modeling. Public health authorities should inform the public of this modeling success and of the limitations of early seroprevalence analyses. This will prepare the public to better assess global health risk during future pandemics.

OBJECTIVE:Diagnostic and treatment delays in infantile epileptic spasms syndrome (IESS) increase the risk of poor neurodevelopmental outcomes. Early clinical recognition of IESS is essential, especially in regions lacking expedited access to electroencephalograms (EEG). This study aimed to determine clinicians' accuracy at recognizing infantile epileptic spasms (ES) based on smartphone videos, and the impact of brief IESS education on accuracy, diagnostic confidence, and willingness to treat without EEG. METHODS:This multicenter prospective cohort study took place over seven sessions globally from 2022 to 2023. Smartphone videos of children from the US and South Africa with EEG-confirmed diagnoses of IESS (6 videos) and non-epileptic ES-mimickers (3 videos) were obtained. Staff physicians and trainee participants from multiple subspecialties worldwide viewed videos three times: (1) baseline viewing, (2) after brief IESS training, and (3) with clinical history. Surveys on diagnosis and management were completed after each viewing. RESULTS:Of 187 participants who attended a session and initiated a survey, 180 (80 trainees [44%]) met the inclusion criteria. Initial diagnostic accuracy averaged 64% (95% confidence interval [CI]: 62-66%) and improved to 72% (69-74%) after IESS training and clinical history (V + T + CHx). Area under the curve for diagnostic performance of smartphone videos was 0.80 (0.78-0.82), and sensitivity was 0.85 (0.83-0.88) after V + T + CHx. The odds of making a correct diagnosis increased by 86% (OR 1.86, CI 1.59-2.18, p < 0.001) after V + T + CHx. Diagnostic confidence and clinician comfort level treating ES without EEG also improved significantly after V + T + CHx (by 0.36 points and 0.45 points, respectively, on 5-point Likert scales, p < 0.001). Diagnostic accuracy correlated strongly with increased diagnostic confidence and increased clinician comfort level managing patients without an EEG (p < 0.001). Staff physicians had a 24% higher likelihood of making a correct diagnosis than trainees. SIGNIFICANCE/CONCLUSIONS:Smartphone videos, especially when enhanced by brief IESS training, can facilitate triage and early identification of infantile ES, reducing diagnostic delays in this time-sensitive condition. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:Infantile epileptic spasms syndrome is associated with severe developmental impacts, which can be worsened by delayed treatment. Rapid diagnosis is critical, especially in resource-limited settings lacking specialists and timely access to diagnostic tests. Our study found that clinician participants identified epileptic spasms, the hallmark seizure type of this condition, based on video alone with moderately high accuracy, and accuracy improved after education and clinical information. Thus, smartphone videos, particularly when enhanced by brief training, may be an effective tool to triage movements concerning for epileptic spasms, potentially improving resource allocation and reducing diagnostic delays in this urgent childhood epilepsy condition.

BACKGROUND:While genetic testing in Movement Disorders (MD) has expanded enormously, access to genetic testing and genetic counseling remains asymmetric at the global scale. Guidance on efficient testing strategies for clinicians, governments and stakeholders is crucial. OBJECTIVES/OBJECTIVE:Establish a list of genetic movement disorders considered essential as determined by a group of MD experts. METHODS:All genes associated with MD were searched using the OMIM and MDS Gene database. We collected all additional tests available at 4 different laboratories from the EuroGentest database. The results were compiled in 6 questionnaires. A genetic test was considered essential if molecular testing had a direct impact in the management of the patient, including treatment of the disease or its comorbidities, or genetic counseling of the patient and family members. Two Delphi rounds were conducted asking MD experts which specific tests they considered essential in an adult MD clinic. RESULTS:Fifty-nine disorders were considered essential to genetically identify by the MD experts. This included 25 genes associated with ataxia, 15 with parkinsonism, 14 with dystonia, eight with chorea, five with paroxysmal disorders, four with myoclonus, four with hereditary spastic paraparesis, and one with tremor. Sixteen disorders reached 100% consensus among experts: Huntington's disease, PxMD-PPRT2, Wilson's disease, DYT-SGCE, DYT-THAP1, DYT-TOR1A, DYT/PARK-GCH1, Fragile-X Tremor-ataxia syndrome, PARK-GBA, PARK-LRRK2, PARK-PINK1, PARK-PRKN, PARK-SNCA, Cerebrotendinous Xanthomatosis, Ataxia-Telangiectasia, and Niemann-Pick disease type C. CONCLUSION/CONCLUSIONS:This study provides a list of genetic MD that should be molecularly tested in adult centers with a compatible phenotype according to a group of MD experts.

UNLABELLED:<p>Introduction: Tremor-predominant Parkinson's disease (TPPD) generally responds favorably to deep brain stimulation (DBS) targeting the subthalamic nucleus (STN). However, traditional stereotactic targeting of the STN does not universally yield the anticipated intraoperative improvement, prompting exploration of additional targets to achieve optimal results prior to permanent implantation of electrodes. The posterior subthalamic area (PSA), including the caudal zona incerta (cZI), have been associated with tremor suppression and can be easily compared to the neighboring STN intraoperatively. METHODS:We retrospectively compared intraoperative and clinical outcomes in tremor-dominant PD patients who prospectively underwent dual trajectory microelectrode monitor targeting the STN and PSA/cZI. We compared the neurophysiology and tremor response of both the central (STN) and posterior (PSA) trajectories in 22 patients and analyzed outcomes in those who ultimately received traditional STN (16) or PSA/cZI lead implantation (12). RESULTS:While both groups achieved substantial overall motor improvement under chronic stimulation, intraoperative test stimulation through the posterior path produced more consistent tremor arrest compared with STN. These findings suggest that positioning the DBS lead further posteriorly to engage the PSA can augment tremor suppression in select cases of TPPD without compromising other parkinsonian symptom relief. CONCLUSION/CONCLUSIONS:Our results emphasize the value of intraoperative physiological feedback in trajectory selection in tremor-predominant patients and are consistent with emerging literature that PSA/cZI DBS is an effective and potentially superior target for management of tremor in PD. </p>.

Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two-week-long, on-site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16-89) hours of intensive and dedicated clinical training, coordinated by 2-3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on-site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post-training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on-site attendance by basic scientists in specialized clinical settings up-scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. PLAIN LANGUAGE SUMMARY: Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two-week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long-term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.

BACKGROUND/UNASSIGNED:Intraoperative Neural Monitoring (IONM) is mandatory for performing anterior (i.e., transthoracic) or lateral extracavitary approaches to significant anterior/anterolateral thoracic ossification of the posterior longitudinal ligament (TOPLL) (i.e. often misdiagnosed as calcified Thoracic Disc Herniations) (TDH). Notably, the remaining "posterior procedures" (i.e. laminectomy, transpedicular, and costotransversectomy) are contraindicated for treating significant anterior/anterolateral TOPLL as they result in unacceptably high frequencies of spinal cord injury (SCI) typically correlated with significant intraoperative IONM losses. METHODS/UNASSIGNED:A review of multiple studies documented that IONM (i.e. especially Tc-MEP (Transcranial Motor Evoked Potentials)) is mandatory when performing anterior transthoracic or lateral extracavitary approaches to TOPLL. This is because IONM alerts signaling the onset of SCI may likely be remediated (i.e. minized vs. limited) utilizing appropriate resuscitative maneuvers. Alternatively, extremely high frequencies of significant IONM losses occurring with "posterior procedures" carried a much higher risk of permanent/irreversible neurological injury. RESULTS/UNASSIGNED:Multiple studies documented that IONM should be used with anterior transthoracic or lateral extracavitary approaches to anterior/anterolateral TOPLL surgery, and that "posterior procedures" were largely contraindicated. In one series, significant amplitude Tc-MEP losses occurred in 73% of posterior decompressions; 39% developed Tc-MEP amplitude losses, that correlated with new SCI. In another study of 249 TOPLL patients undergoing "posterior only operations", 50 developed new significant IONM alerts (i.e. of deterioration); only 40% (20/50) were successfully resuscitated. Overall, initiating immediate resuscitative maneuvers in response to IONM occurring during various types of TOPLL surgery can avert SCI in up to 10.4%, to 40%, to 57% of cases. CONCLUSION/UNASSIGNED:IONM is mandatory for anterior/anterolateral TOPLL surgery utilizing anterior transthoracic or lateral extracavitary approaches.

BACKGROUND/UNASSIGNED:"Never Events" (<1/1000) likely never occur without a breach in the standard of care (SOC), while "Near Never Events" (<1/100) are typically not far behind. METHODS/UNASSIGNED:"Never Events" are described as "Harmful hospital-acquired conditions that the Center for Medicare and Medicaid Services identified in 2008." Here, we focused on wrong-site spine surgery (WSSS)/wrong-level spine surgery (WLSS), 3 select cases of Caspar Distraction Screws causing hematomas, and one medicolegal case involving multiple simultaneous "Never Events." RESULTS/UNASSIGNED:The spine literature documented the following frequencies of wrong-site spine surgery WSSS/"Never Events" as occurring in 4.5/10,000 lumbar, 6.8/10,000 cervical, and 2.2/10,000 cranial procedures; other series focused on the incidence of wrong-level spine surgery (WLSS). Three "Never Events" consisting of cervical epidural hematomas were attributed to Caspar Distraction Screws. A medicolegal case is also presented in which a spine surgeon caused multiple simultaneous "Never Events" (i.e., ipsilateral surgical errors) during an anterior cervical fusion. Finally, the definition of "Never Events" was newly expanded to better assess "Near Never Events", as the latter applied to varied frequencies of esophageal perforations, plate/screw migration/erosions/displacement, cerebrospinal fluid leaks, infection, and other factors. CONCLUSION/UNASSIGNED:"Never Events" (<1/1000) likely never occur without a breach in the SOC, while "Near Never Events" (<1/100) are typically not far behind.