Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neurology
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23427
Redefining diagnostic lesional status in temporal lobe epilepsy with artificial intelligence
Despite decades of advancements in diagnostic MRI, 30-50% of temporal lobe epilepsy (TLE) patients remain categorized as "non-lesional" (i.e., MRI negative or MRI-) based on visual assessment by human experts. MRI- patients face diagnostic uncertainty and significant delays in treatment planning. Quantitative MRI studies have demonstrated that MRI- patients often exhibit a TLE-specific pattern of temporal and limbic atrophy that may be too subtle for the human eye to detect. This signature pattern could be successfully translated into clinical use via artificial intelligence (AI) advances in computer-aided MRI interpretation, thereby improving the detection of brain "lesional" patterns associated with TLE. Here, we tested this hypothesis by employing a three-dimensional convolutional neural network (3D CNN) applied to a dataset of 1,178 scans from 12 different centers. 3D CNN was able to differentiate TLE from healthy controls with high accuracy (85.9% ± 2.8), significantly outperforming support vector machines based on hippocampal (74.4% ± 2.6) and whole-brain (78.3% ± 3.3) volumes. Our analysis subsequently focused on a subset of patients who achieved sustained seizure freedom post-surgery as a gold standard for confirming TLE. Importantly, MRI- patients from this cohort were accurately identified as TLE 82.7% ± 0.9 of the time, an encouraging finding since clinically these were all patients considered to be MRI- (i.e., not radiographically different than controls). The saliency maps from the CNN revealed that limbic structures, particularly medial temporal, cingulate, and orbitofrontal areas, were most influential in classification, confirming the importance of the well-established TLE signature atrophy pattern for diagnosis. Indeed, the saliency maps were similar in MRI+ and MRI- TLE groups, suggesting that even when humans cannot distinguish more subtle levels of atrophy, these MRI- patients are on the same continuum common across all TLE patients. As such, AI can identify TLE lesional patterns and AI-aided diagnosis has the potential to greatly enhance the neuroimaging diagnosis of TLE and redefine the concept of "lesional" TLE.
PMID: 39842945
ISSN: 1460-2156
CID: 5802322
Decoding words during sentence production with ECoG reveals syntactic role encoding and structure-dependent temporal dynamics
Sentence production is the uniquely human ability to transform complex thoughts into strings of words. Despite the importance of this process, language production research has primarily focused on single words. It remains a largely untested assumption that the principles of word production generalize to more naturalistic utterances like sentences. Here, we investigate this using high-resolution neurosurgical recordings (ECoG) and an overt production experiment where ten patients produced six words in isolation (picture naming) and in sentences (scene description). We trained machine learning classifiers to identify the unique brain activity patterns for each word during picture naming, and used these patterns to decode which words patients were processing while they produced sentences. Our findings confirm that words share cortical representations across tasks, but reveal a division of labor within the language network. In sensorimotor cortex, words were consistently activated in the order in which they were said in the sentence. However, in prefrontal cortex, the order in which words were processed depended on the syntactic structure of the sentence. In non-canonical sentences (passives), we further observed a spatial code for syntactic roles, with subjects selectively encoded in inferior frontal gyrus (IFG) and objects selectively encoded in middle frontal gyrus (MFG). We suggest that these complex dynamics of prefrontal cortex may impose a subtle pressure on language evolution, potentially explaining why nearly all the world's languages position subjects before objects.
PMCID:12133590
PMID: 40461573
ISSN: 2731-9121
CID: 5862322
Protocol for culture, purification, and target validation of a hybridoma-generated monoclonal antibody targeting Aβ truncated species
Alzheimer's disease (AD) is characterized by the deposition of full-length and truncated amyloid beta (Aβ) species within brain parenchyma and cerebral vessels. However, Aβ truncated species remain understudied. Here, we present a protocol for culture and characterization of a mouse monoclonal antibody targeting N-terminally truncated proteoforms starting at position 4. We describe a detailed procedure for hybridoma culture, antibody collection, and isolation via affinity chromatography. We then describe steps for target validation via dot blot, as well as potential applications. For complete details on the use and execution of this protocol, please refer to Cabrera et al. and Rostagno et al.1
PMID: 40465455
ISSN: 2666-1667
CID: 5862422
How Well do We Evaluate Small Fiber Neuropathy?: A Survey of American Academy of Neurology Members
BACKGROUND:Clinical evaluation of distal symmetric polyneuropathy (DSP), which can include small fiber neuropathy (SFN), differs among neurologists, neuromuscular specialists, and internists. The American Academy of Neurology (AAN) 2009 Practice Parameter guides evaluation of DSP, but there are no guidelines or AAN practice parameters for the evaluation of SFN. OBJECTIVE:Determine how neurologists evaluate and test for SFN in their clinical practice and compare responses between neuromuscular (NM) and non-neuromuscular specialists (non-NM). DESIGN/METHODS/METHODS:Eight hundred randomly selected AAN members, which included 400 members who indicated NM medicine to be a primary or secondary specialty, were selected to answer a survey about SFN. Respondents answered a survey instrument with a list of 44 serum tests and procedures for different neuropathy clinical scenarios. RESULTS:The survey response rate was 29.3% (234/798), with 48.8% (N = 114) indicating that their primary specialty was neuromuscular. For an initial evaluation of distal symmetric SFN, respondents ordered a mean of 12 tests (SD 5.8) with a range of 0-26 tests. There was no statistically significant difference between the mean number of tests ordered by neuromuscular versus non-neuromuscular specialists. The 5 most common overall responses were complete blood count (87%), vitamin B12 (86%), basic metabolic panel (84%), thyroid stimulating hormone (78%), and hemoglobin A1c (77%). For a secondary evaluation of etiologies of distal symmetric SFN, 52% of non-neuromuscular specialists (95% CI, 42%-61%) versus 35% of neuromuscular specialists (95% CI, 26%-45%) would order a paraneoplastic panel. There was significant disparity in ordering a skin biopsy for intraepidermal nerve fiber density, with 65% of neuromuscular specialists (95% CI, 55%-74%) indicating that they would order this test compared with 38% of non-neuromuscular specialists (95% CI, 29%-48%). CONCLUSIONS:The recommended studies with the highest yield for finding a cause of DSP were not universally ordered. There is variability in approaches to diagnosing SFN and searching for a possible etiology. The development of an AAN practice parameter for SFN may help promote consistent practice among neurologists of all subspecialties.
PMID: 40512966
ISSN: 1537-1611
CID: 5869842
Treatment of Acute Iatrogenic Cerebrovascular Injury Using Flow Diverter Stents
BACKGROUND AND OBJECTIVES/OBJECTIVE:Iatrogenic cerebrovascular injury can cause intracranial hemorrhage and pseudoaneurysm formation, putting patients at high risk for postoperative bleeding. No consensus for management exists. This study describes endovascular treatment of these acute injuries with flow diverter stents. METHODS:Electronic medical records were retrospectively reviewed for injury type and etiology, timing of diagnosis, and endovascular management, including antiplatelet regimens, embolization results, and clinical outcome. RESULTS:Six patients were included. Three suffered an injury to the internal carotid artery, 1 suffered an injury to the left anterior cerebral artery, 1 suffered an injury to the right posterior cerebral artery, and 1 suffered an injury to the basilar artery. Four of the 6 injuries occurred during attempted tumor resection, 1 occurred during cerebrospinal fluid leak repair, and 1 occurred during an ophthalmic artery aneurysm clipping. All injuries resulted in pseudoaneurysm formation. Four were immediately detected on angiography; 2 were initially negative on imaging. Five were treated with a pipeline embolization device, and 1 was treated with a Silk Vista Baby. Two were treated with 2 pipeline embolization devices telescopically overlapped across the pseudoaneurysm. All devices deployed successfully. No pseudoaneurysm recurrence or rebleeding occurred. No parent artery occlusion or stenosis was observed, and complete pseudoaneurysm occlusion was observed in 4 patients (in 2 patients, follow-up imaging could not be obtained). CONCLUSION/CONCLUSIONS:With proper antiplatelet regimens, flow diverter stents can be used safely to successfully treat complex acute iatrogenic injuries. Early repeat angiogram is needed when immediate postinjury imaging does not discover the point of vessel injury.
PMID: 39311570
ISSN: 2332-4260
CID: 5802862
Updated classification of epileptic seizures: Position paper of the International League Against Epilepsy
The International League Against Epilepsy (ILAE) has updated the operational classification of epileptic seizures, building upon the framework established in 2017. This revision, informed by the implementation experience, involved a working group appointed by the ILAE Executive Committee. Comprising 37 members from all ILAE regions, the group utilized a modified Delphi process, requiring a consensus threshold of more than two thirds for any proposal. Following public comments, the Executive Committee appointed seven additional experts to the revision task force to address and incorporate the issues raised, as appropriate. The updated classification maintains four main seizure classes: Focal, Generalized, Unknown (whether focal or generalized), and Unclassified. Taxonomic rules distinguish classifiers, which are considered to reflect biological classes and directly impact clinical management, from descriptors, which indicate other important seizure characteristics. Focal seizures and those of unknown origin are further classified by the patient's state of consciousness (impaired or preserved) during the seizure, defined operationally through clinical assessment of awareness and responsiveness. If the state of consciousness is undetermined, the seizure is classified under the parent term, that is, the main seizure class (focal seizure or seizure of unknown origin). Generalized seizures are grouped into absence seizures, generalized tonic-clonic seizures, and other generalized seizures, now including recognition of negative myoclonus as a seizure type. Seizures are described in the basic version as with or without observable manifestations, whereas an expanded version utilizes the chronological sequence of seizure semiology. This updated classification comprises four main classes and 21 seizure types. Special emphasis was placed on ensuring translatability into languages beyond English. Its aim is to establish a common language for all health care professionals involved in epilepsy care, from resource-limited areas to highly specialized centers, and to provide accessible terms for patients and caregivers.
PMID: 40264351
ISSN: 1528-1167
CID: 5832262
Factors Associated With Stroke Recurrence After Initial Diagnosis of Cervical Artery Dissection
BACKGROUND/UNASSIGNED:Patients presenting with cervical artery dissection (CAD) are at risk for subsequent ischemic events. We aimed to identify characteristics that are associated with increased risk of ischemic stroke after initial presentation of CAD and to evaluate the differential impact of anticoagulant versus antiplatelet therapy in these high-risk individuals. METHODS/UNASSIGNED:This was a preplanned secondary analysis of the STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection), a multicenter international retrospective observational study (63 sites from 16 countries in North America, South America, Europe, Asia, and Africa) that included patients with CAD predominantly between January 2015 and June 2022. The primary outcome was subsequent ischemic stroke by day 180 after diagnosis. Clinical and imaging variables were compared between those with versus without subsequent ischemic stroke. Significant factors associated with subsequent stroke risk were identified using stepwise Cox regression. Associations between subsequent ischemic stroke risk and antithrombotic therapy type (anticoagulation versus antiplatelets) among patients with identified risk factors were explored using adjusted Cox regression. RESULTS/UNASSIGNED:=0.01). CONCLUSIONS/UNASSIGNED:In this post hoc analysis of the STOP-CAD study, several factors associated with subsequent ischemic stroke were identified among patients with CAD. Furthermore, we identified a potential benefit of anticoagulation in patients with CAD with occlusive dissection. These findings require validation by meta-analyses of prior studies to formulate optimal treatment strategies for specific high-risk CAD subgroups.
PMID: 40143807
ISSN: 1524-4628
CID: 5816392
Differences in the soluble and insoluble proteome between primary tauopathies
INTRODUCTION/BACKGROUND:Primary tauopathies, including corticobasal degeneration (CBD), Pick's disease (PiD), and progressive supranuclear palsy (PSP), have aggregated tau pathology in the brain. Many other proteins are likely altered in disease; however, these have not been well characterized. METHODS:We performed sarkosyl fractionation of post mortem human brain tissue to enrich soluble and insoluble proteins from CBD, PiD, and PSP cases (n = 5/group). We assessed differences in the soluble fraction, insoluble fraction, and protein solubility changes between diseases, followed by enrichment and correlation analysis. RESULTS:CBD and PiD showed the greatest proteomic similarity in both the soluble and insoluble fractions, while PSP was the most divergent in comparison to other diseases. We observed critical changes in the solubility of lysosomal regulators, postsynaptic proteins, the extracellular matrix (ECM), and mitochondrial proteins. DISCUSSION/CONCLUSIONS:We have contrasted the solubility patterns of proteins across three tauopathies for the first time. Protein solubility differences reveal divergence in disease processes. HIGHLIGHTS/CONCLUSIONS:Tau isoforms are differentially soluble in primary tauopathies PSP proteomics profile was the most divergent of the tauopathies examined SORT1 is highly insoluble in CBD and aggregates to different extents in tauopathies There are shifts in solubility for key signalling pathways; ROCK1 and JAK2 Unique lysosomal proteins are more insoluble in distinct tauopathies.
PMCID:12183113
PMID: 40545554
ISSN: 1552-5279
CID: 5874652
Using Virtual Reality to Enhance Mobility, Safety, and Equity for Persons with Vision Loss in Urban Environments
This study explores the use of virtual reality (VR) as an innovative tool to enhance awareness, understanding of accessibility for persons with vision loss (VL), and acceptance. Through a VR-based workshop developed in collaboration with New York City's Department Of Transportation, participants experienced immersive simulations of VL and related immersive mobility challenges. The methodology included the development of a VR environment, simulations of vision loss, testing with the DOT team during the workshop, and an assessment of changes in participants' knowledge, confidence in addressing accessibility challenges, and overall perception through pre- and post-intervention questionnaires. Participants included urban planners, designers, and architects. Results showed a significant increase in awareness of VL-related challenges that affect design guidelines, as well as improved confidence in addressing such challenges. Participants also expressed strong support for VR as a pedagogical tool, noting its potential for reshaping professional practices, improving capacity building, and enhancing inclusive design. The study demonstrates the effectiveness of VR as an experiential learning platform, fostering empathy and a long-term commitment to integrating VL considerations into urban design. These findings highlight the transformative potential of VR in advancing equity and accessibility in urban environments.
PMID: 40014220
ISSN: 1468-2869
CID: 5801222
Education Research: A Behavioral Intervention to Improve Group-Based Diagnostic Quality and Educational Experience Among Neurology Trainees: A Feasibility Study
BACKGROUND AND OBJECTIVES/UNASSIGNED:"Brain-writing" is a technique in which group members write down ideas individually, before a group discussion, to improve idea generation and individual engagement in group discussions. We assessed the feasibility of studying the impact of brain-writing on diagnostic quality and educational experience among neurology residents in a small case-based learning environment. METHODS/UNASSIGNED:We conducted a repeated-measures study, conducted over 6 sessions consisting of groups of 3 to 5 neurology residents from different years of training. During each session, 3 cases were treated as control, "brainstorming," cases, and 3 were intervention, "brain-writing," cases, in which the group wrote down possible diagnoses and tests before engaging in a group discussion. Tests and diagnoses from the brain-writing exercise and group discussion as well as a post case survey on participant experience were recorded through a Qualtrics survey, and video recordings were reviewed to determine speaking order and number of tests and diagnoses verbalized by each member. Feasibility was determined by recruitment and ability to complete the study procedures in a pragmatic fashion that incorporated resident education. The primary outcome was accuracy of diagnoses, and secondary outcomes included number of tests and diagnoses generated, percent of "can't miss diagnoses mentioned," speaking order and psychological reactions of group members. RESULTS/UNASSIGNED:= 0.07). Junior residents spoke later and verbalized significantly fewer diagnoses and tests than senior residents in both brainstorming and brain-writing groups. There was no statistically significant difference in psychological outcomes of junior and senior residents in each group. DISCUSSION/UNASSIGNED:It is feasible to examine the impact of a behavioral-based intervention among medical trainees in a small case-based learning environment. This study, limited by a small sample size, did not find that brain-writing improved decision quality.
PMCID:11985166
PMID: 40212892
ISSN: 2771-9979
CID: 5824292
