Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Neurology
Total Results:
23548
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
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
Considerations and recommendations from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 3-Ex vivo imaging: Data processing, comparisons with microscopy, and tractography
Preclinical diffusion MRI (dMRI) has proven value in methods development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. While dMRI enables in vivo non-invasive characterization of tissue, ex vivo dMRI is increasingly being used to probe tissue microstructure and brain connectivity. Ex vivo dMRI has several experimental advantages that facilitate high spatial resolution and high SNR images, cutting-edge diffusion contrasts, and direct comparison with histological data as a methodological validation. However, there are a number of considerations that must be made when performing ex vivo experiments. The steps from tissue preparation, image acquisition and processing, and interpretation of results are complex, with many decisions that not only differ dramatically from in vivo imaging of small animals, but ultimately affect what questions can be answered using the data. This work concludes a three-part series of recommendations and considerations for preclinical dMRI. Herein, we describe best practices for dMRI of ex vivo tissue, with a focus on image pre-processing, data processing, and comparisons with microscopy. In each section, we attempt to provide guidelines and recommendations but also highlight areas for which no guidelines exist (and why), and where future work should lie. We end by providing guidelines on code sharing and data sharing and point toward open-source software and databases specific to small animal and ex vivo imaging.
PMID: 40008460
ISSN: 1522-2594
CID: 5800922
Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI: Part 1: In vivo small-animal imaging
Small-animal diffusion MRI (dMRI) has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the resultant data. This work aims to present selected considerations and recommendations from the diffusion community on best practices for preclinical dMRI of in vivo animals. We describe the general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss why some may be more or less appropriate for different studies. We, then, give recommendations for in vivo acquisition protocols, including decisions on hardware, animal preparation, and imaging sequences, followed by advice for data processing including preprocessing, model-fitting, and tractography. Finally, we provide an online resource that lists publicly available preclinical dMRI datasets and software packages to promote responsible and reproducible research. In each section, we attempt to provide guides and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should focus. Although we mainly cover the central nervous system (on which most preclinical dMRI studies are focused), we also provide, where possible and applicable, recommendations for other organs of interest. An overarching goal is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.
PMID: 40008568
ISSN: 1522-2594
CID: 5800952
Minimum Technical Preanalytical, Patient, and Clinical Context Data Elements for Cerebrospinal Fluid Liquid Biopsy: Recommendations for Public Database Submissions
PURPOSE/OBJECTIVE:Blood-based liquid biopsy has enabled minimally invasive molecular profiling in patients with solid tumors. For cancers of the CNS, however, the use of peripheral blood for cell-free DNA (cfDNA) detection and sequencing has proved challenging because of scant levels of tumor-derived material shed into systemic circulation. An alternative is to use cerebrospinal fluid (CSF), which contains a greater concentration of tumor-derived cfDNA in patients with brain tumors (BTs). CSF liquid biopsy is a relatively nascent field, with critical unanswered questions regarding preanalytical variables that may affect assay performance. In an effort to identify and standardize key preanalytical variables, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium launched a BT Working Group in 2022. METHODS:We reviewed protocols for CSF sample collection and processing used by expert Working Group members at their respective academic institutions and diagnostic companies, as well as the available literature on CSF liquid biopsy. Through a collaborative and iterative process, we developed a list of key preanalytical variables for cfDNA-based CSF liquid biopsy in patients with primary and metastatic brain malignancies. RESULTS:The Working Group agreed on a recommended list of preanalytical minimum technical data elements, clinical context data elements, and patient context data elements for cfDNA-based CSF liquid biopsy in patients with CNS malignancies. A subset of variables were considered to be of critical priority and are designated as required annotations to submissions of cfDNA-based CSF liquid biopsy sample data into the BLOODPAC Data Commons. CONCLUSION/CONCLUSIONS:We propose a list of preanalytical variables relevant for cfDNA-based CSF liquid biopsy, with the overarching goal of encouraging routine collection and reporting of these variables in future studies.
PMID: 40570259
ISSN: 2473-4284
CID: 5962032
Dravet syndrome: From neurodevelopmental to neurodegenerative disease?
OBJECTIVE:Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy caused by SCN1A haploinsufficiency in the majority of cases. Caregivers of adults with DS often complain about the loss of previously acquired skills. We set out to explore these perceptions and determine whether abnormalities reported were detectable in validated tests. We also investigated possible correlations between symptoms, age, and exposure to sodium channel blockers (SCBs). METHODS:This cross-sectional, multicenter study used the Vineland Adaptive Behavior Scales, 3rd edition (raw scores) for behavior analyses and Moss-Psychiatric Assessment Schedules checklist to screen for psychiatric symptoms. The Social Communication Questionnaire screened for social communication deficits. Parkinsonian features were evaluated with the modified Unified Parkinson's Disease Rating Scale. For gait evaluation, we validated the use of home videos, using instrumental gait analysis in a subgroup of patients, and then used the home videos for the remainder. RESULTS:A total of 92 patients were enrolled (age range = 18-51 years, mean = 27.93 ± 8.59 years). Sixty percent of caregivers observed a decline in previously acquired skills, including intelligence, speech, interaction with others, ability to climb stairs and walk without support, and hand coordination. Adaptive skills, parkinsonian symptoms, and gait were worse in older patients and those exposed to SCBs for longer periods of time. Fourteen percent of patients screened positive for affective disorders, 11.6% for dementia, and 10.5% for a psychotic disorder. Fifty-three percent screened positive for social communication deficits. SIGNIFICANCE/CONCLUSIONS:This is the largest group of adults with DS to be systematically evaluated. They had severe nonseizure symptoms. Older age and longer use of SCBs were associated with worse adaptive skills, gait, and parkinsonism. Some older adults screened positive for depression and dementia. Caregivers identified functional decline in activities of daily living (ADLs). Taken together, the risk of dementia, parkinsonian gait, and decline in ability to perform previously mastered ADLs support that some adults with DS may be developing a neurodegenerative disorder.
PMID: 40034086
ISSN: 1528-1167
CID: 5842702
