Neurology Commons^™

Case Report: Dementia Sensitivity To Altitude Changes And Effective Treatment With Hyperbaric Air And Glutathione Precursors, Edward F. Fogarty, Paul G. Harch

School of Medicine Faculty Publications

A 78-year-old man with dementia experienced waxing and waning of symptoms with changes in altitude as he traveled from his home in the Rocky Mountains to lower elevations and back. To replicate the improvement in his symptoms with travel to lower elevations (higher pressure), the patient was treated with a near-identical repressurization in a hyperbaric chamber using compressed air. With four 1-h treatments at 1.3 Atmospheres Absolute (ATA) and concurrent administration of low-dose oral glutathione amino acid precursors, he recovered speech and showed improvement in activities of daily living. Regional broadcast media had documented his novel recovery. Nosocomial COVID-19 and …

Fate-Mapping And Functional Dissection Reveal Perilous Influence Of Type I Interferon Signaling In Mouse Brain Aging, Ethan R Roy, Sanming Li, Sepideh Saroukhani, Yanyu Wang, Wei Cao

Faculty, Staff and Student Publications

Background: Aging significantly elevates the risk of developing neurodegenerative diseases. Neuroinflammation is a universal hallmark of neurodegeneration as well as normal brain aging. Which branches of age-related neuroinflammation, and how they precondition the brain toward pathological progression, remain ill-understood. The presence of elevated type I interferon (IFN-I) has been documented in the aged brain, but its role in promoting degenerative processes, such as the loss of neurons in vulnerable regions, has not been studied in depth.

Methods: To comprehend the scope of IFN-I activity in the aging brain, we surveyed IFN-I-responsive reporter mice at multiple ages. We also examined 5- …

Meningioma Transcriptomic Landscape Demonstrates Novel Subtypes With Regional Associated Biology And Patient Outcome, H Nayanga Thirimanne, Damian Almiron-Bonnin, Nicholas Nuechterlein, Sonali Arora, Matt Jensen, Carolina A Parada, Chengxiang Qiu, Frank Szulzewsky, Collin W English, William C Chen, Philipp Sievers, Farshad Nassiri, Justin Z Wang, Tiemo J Klisch, Kenneth D Aldape, Akash J Patel, Patrick J Cimino, Gelareh Zadeh, Felix Sahm, David R Raleigh, Jay Shendure, Manuel Ferreira, Eric C Holland

Faculty, Staff and Students Publications

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest …

Small-Molecule Inhibition Of Kras Through Conformational Selection, Bharti Manwani, Nivetha Brathaban, Abiya Baqai, Yashee Munshi, Hilda W Ahnstedt, Mengqi Zhang, Kajsa Arkelius, Ted Llera, Edilberto Amorim, Fanny M Elahi, Neel S Singhal

Faculty, Staff and Student Publications

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms. Interestingly, small RNA sequencing of plasma L1EVs from patients with stroke and control patients (n = 28) identified micro(mi)RNAs known to be enriched in the brain. Weighted gene co-expression network analysis (WGCNA) revealed small RNA …

Rigor And Reproducibility In Human Brain Organoid Research: Where We Are And Where We Need To Go, Soraya O Sandoval, Gerarda Cappuccio, Karina Kruth, Sivan Osenberg, Saleh M Khalil, Natasha M Méndez-Albelo, Krishnan Padmanabhan, Daifeng Wang, Mark J Niciu, Anita Bhattacharyya, Jason L Stein, André M M Sousa, Elisa A Waxman, Elizabeth D Buttermore, Dosh Whye, Carissa L Sirois, Cross-Iddrc Human Stem Cell Consortium, Aislinn Williams, Mirjana Maletic-Savatic, Xinyu Zhao

Faculty, Staff and Students Publications

Human brain organoid models have emerged as a promising tool for studying human brain development and function. These models preserve human genetics and recapitulate some aspects of human brain development, while facilitating manipulation in an in vitro setting. Despite their potential to transform biology and medicine, concerns persist about their fidelity. To fully harness their potential, it is imperative to establish reliable analytic methods, ensuring rigor and reproducibility. Here, we review current analytical platforms used to characterize human forebrain cortical organoids, highlight challenges, and propose recommendations for future studies to achieve greater precision and uniformity across laboratories.

Hemojuvelin-Mediated Hepcidin Induction Requires Both Bone Morphogenetic Protein Type I Receptors Alk2 And Alk3, Deniz Y Dogan, Eugen I Urzica, Isabelle Hornung, Philipp Kastl, David Oguama, Franca M Fette, Lien H Nguyen, Frank Rosenbauer, Kai Zacharowski, Ursula Klingmüller, Elise Gradhand, Andreas Von Knethen, Rüdiger Popp, Ingrid Fleming, Lisa Schrader, Andrea U Steinbicker

Faculty, Staff and Student Publications

Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) …

Feasibility Of Achieving Nutritional Adequacy In Critically Ill Children With Critical Neurological Illnesses (Cnis)?-A Quaternary Hospital Experience, Marwa Mansour, Nicole Knebusch, Jennifer Daughtry, Thomas P Fogarty, Fong Wilson Lam, Renan A Orellana, Yi-Chen Lai, Jennifer Erklauer, Jorge A Coss-Bu

Faculty, Staff and Students Publications

The literature on the nutritional needs and outcomes of critically ill children is scarce, especially on those with critical neurological illnesses (CNIs). Current evidence shows a lower mortality in patients who achieve two-thirds of their nutritional needs during the first week of pediatric intensive care unit (PICU) admission. We hypothesized that achieving 60% of the recommended dietary intake during the first week of a PICU stay is not feasible in patients with CNI. We designed an observational retrospective cohort study where we included all index admissions to the PICU in our institution of children (1 month to 18 years) with …

The Impact Of Mechanical Thrombectomy On The Blood-Brain Barrier In Patients With Acute Ischemic Stroke: A Non-Contrast Mr Imaging Study Using Dp-Pcasl And Noddi, Nikolaos Mouchtouris, Isaiah Ailes, Ki Chang, Adam Flanders, Feroze Mohamed, Stavropoula Tjoumakaris, Michael Gooch, Pascal Jabbour, Robert Rosenwasswer, Mahdi Alizadeh

Department of Neurosurgery Faculty Papers

Background and purpose: While mechanical thrombectomy (MT) achieves restoration of cerebral blood flow to the area at risk in patients with acute ischemic stroke (AIS), the influx of blood flow may exacerbate the blood-brain barrier (BBB) disruption and extravasation across the BBB, and it therefore remains unclear how reperfusion impacts the blood-brain barrier integrity. In this study, we use diffusion-prepared pseudocontinuous ASL (DP-pCASL) and Neurite Orientation Dispersion and Density Imaging (NODDI) sequence to measure the water exchange rate (k_w) in patients who underwent either MT or medical management and determine its impact on the brain tissue microstructure in …

Improved Liver Disease Prediction From Clinical Data Through An Evaluation Of Ensemble Learning Approaches, Shahid Mohammad Ganie, Pijush Kanti Dutta Pramanik, Zhongming Zhao

Faculty, Staff and Student Publications

PURPOSE: Liver disease causes two million deaths annually, accounting for 4% of all deaths globally. Prediction or early detection of the disease via machine learning algorithms on large clinical data have become promising and potentially powerful, but such methods often have some limitations due to the complexity of the data. In this regard, ensemble learning has shown promising results. There is an urgent need to evaluate different algorithms and then suggest a robust ensemble algorithm in liver disease prediction.

METHOD: Three ensemble approaches with nine algorithms are evaluated on a large dataset of liver patients comprising 30,691 samples with 11 …

Cost-Effectiveness And Threshold Analysis Of Deep Brain Stimulation Vs Treatment-As-Usual For Treatment-Resistant Depression, Katherine E Kabotyanski, Ricardo A Najera, Garrett P Banks, Himanshu Sharma, Nicole R Provenza, Benjamin Y Hayden, Sanjay J Mathew, Sameer A Sheth

Faculty, Staff and Students Publications

Treatment-resistant depression (TRD) affects approximately 2.8 million people in the U.S. with estimated annual healthcare costs of $43.8 billion. Deep brain stimulation (DBS) is currently an investigational intervention for TRD. We used a decision-analytic model to compare cost-effectiveness of DBS to treatment-as-usual (TAU) for TRD. Because this therapy is not FDA approved or in common use, our goal was to establish an effectiveness threshold that trials would need to demonstrate for this therapy to be cost-effective. Remission and complication rates were determined from review of relevant studies. We used published utility scores to reflect quality of life after treatment. Medicare …

Perturbations In Risk/Reward Decision Making And Frontal Cortical Catecholamine Regulation Induced By Mild Traumatic Brain Injury, Christopher P Knapp, Eleni Papadopoulos, Jessica A Loweth, Ramesh Raghupathi, Stan B Floresco, Barry D Waterhouse, Rachel L Navarra

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mild traumatic brain injury (mTBI) disrupts cognitive processes that influence risk taking behavior. Little is known regarding the effects of repetitive mild injury (rmTBI) or whether these outcomes are sex specific. Risk/reward decision making is mediated by the prefrontal cortex (PFC), which is densely innervated by catecholaminergic fibers. Aberrant PFC catecholamine activity has been documented following TBI and may underlie TBI-induced risky behavior. The present study characterized the effects of rmTBI on risk/reward decision making behavior and catecholamine transmitter regulatory proteins within the PFC. Rats were exposed to sham, single (smTBI), or three closed-head controlled cortical impact (CH-CCI) injuries and …

Methylthioadenosine Phosphorylase Genomic Loss In Advanced Gastrointestinal Cancers, Natalie Y L Ngoi, Tin-Yun Tang, Catia F Gaspar, Dean C Pavlick, Gregory M Buchold, Emma L Scholefield, Vamsi Parimi, Richard S P Huang, Tyler Janovitz, Natalie Danziger, Mia A Levy, Shubham Pant, Anaemy Danner De Armas, David Kumpula, Jeffrey S Ross, Milind Javle, Jordi Rodon Ahnert

Faculty, Staff and Student Publications

BACKGROUND: One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker.

MATERIALS AND METHODS: We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI …

A Process To Reanalyze Clinical Dna Sequencing Data For Biomarker Matching In The Lung-Map Master Protocol, Joel W Neal, Katherine Minichiello, Ryan Brennick, Richard S P Huang, Matthew C Hiemenz, Cornel Amler, Jyoti Patel, Roy Herbst, Karen L Reckamp, Hossein Borghaei, Louise Highleyman, Mary W Redman, Lincoln W Pasquina, David E Kozono

Faculty, Staff and Student Publications

For cancer clinical trials that require central confirmation of tumor genomic profiling, exhaustion of tissue from standard-of-care testing may prevent enrollment. For Lung-MAP, a master protocol that requires results from a defined centralized clinical trial assay to assign patients to a therapeutic substudy, we developed a process to repurpose existing commercial vendor raw genomic data for eligibility: genomic data reanalysis (GDR). Molecular results for substudy assignment were successfully generated for 369 of the first 374 patients (98.7%) using GDR for Lung-MAP, with a median time from request to result of 9 days. During the same period, 691 of 791 (87.4%) …

The Field Of Interventional Neurology (In) In Pakistan: Scope And Challenges, Ahmed Wali

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

A Rare Presentation Of Brain Cystic Disease Linked With Ectodermal Dysplasia (Cerebrum Polycystica Vera): A Novel Neurocutaneous Syndrome, Sana Ghous, Alam Ibrahim Siddiqui, Abdul Rahman Soomro, Anjlee Shankar, Asif Ali, Shaheen Bhatty

Pakistan Journal of Neurological Sciences (PJNS)

Neurocutaneous syndromes comprise a diverse group of conditions affecting both the nervous system and the integumentary system. Within this spectrum, we present a rare and compelling case of cerebrum polycystica vera associated with ectodermal dysplasia in a 30-year-old male. The patient's clinical journey includes a sequence of seizures progressing to left-sided weakness, accompanied by compelling dermatological manifestations. Extensive neuroimaging studies, including MRI and CT scans, reveal the presence of multiple cysts in the brain, highlighting the distinct nature of this novel neurocutaneous syndrome. Based on the authors’ knowledge, this represents the first documented case report from Pakistan, while a few …

Recurrent Intraosseous Myxoma: A Case Report, Alma Corazon T De La Cruz, Michael N Sabalza

Pakistan Journal of Neurological Sciences (PJNS)

Myxomas are rare, benign but locally aggressive neoplasms that are of mesenchymal origin. These tumors are usually diagnosed only when they have grown enough to cause symptoms because of their indolent nature, hence imaging plays a large role in the diagnosis of these tumors. Imaging findings may include well-circumscribed multinodular masses with destruction of adjacent bony structures. Treatment of these tumors is complete resection and close follow up. Early recognition with physical examination and imaging studies, close follow up and multidisciplinary treatment are needed to achieve the best results for patients. We present a 34-year-old male who presented with proptosis …

Video Gaming Addiction In Pakistani Adolescents: A Growing Concern, Hamza Imran, Batool Mujtaba, Hamza Waheed, Muhammad Ibrahim

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Video game addiction, or gaming disorder, is marked by impaired control over gaming, prioritizing gaming over other activities, and continuing despite negative consequences. This can lead to psychological, social, and occupational impairments. Despite its high prevalence among adolescents, research in Pakistan is limited. This review aims to compare international research on video game addiction and raise awareness about its impact on Pakistani adolescents.

Methods: Using the PubMed, Google Scholar, and Cochrane databases, a thorough literature search was carried out to find research on video game addiction among teenagers in Pakistan, the USA, Canada, India, and China, aged …

Treatment And Outcome Of Non-Convulsive Status Epilepticus In Children: A Cross-Sectional Study, Shaila Ali, Natasha Ghani, Tipu Sultan

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Incidence and prevalence of non-convulsive status epilepticus is difficult to know, especially in developing countries where access to diagnostic tools like EEG is limited. The objective of this study was to determine the treatment and outcome of non-convulsive status epilepticus in children.

Methods: A total of 38 children were included in this prospective cross-sectional study, having EEG suggestive of non-convulsive status epilepticus. Response of the treatment given was measured by doing EEG after treatment to see resolution of non-convulsive status and improvement in clinical features too. Outcome was also assessed in terms of morbidity and mortality. The …

Causes And Presentations Of Bilateral Thalamic Lesions: A Retrospective Cross-Sectional Study From A Tertiary Care Hospital, Shafaq Saleem, Muhammad Saleem, Fatima Mubarak, Salman Farooq

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Bilateral thalamic lesions present a significant diagnostic and therapeutic challenge due to their critical role in sensory, motor, and cognitive functions. The objective of this study was to study the causes and presentations of bilateral thalamic lesions among patients presenting to a tertiary care hospital. Methods: This retrospective study reviewed 40 patients aged 18–80 years admitted to Aga Khan University Hospital between 2006 and 2023 with MRI-confirmed bilateral thalamic lesions. Data collected included demographics, clinical presentations, radiological findings, and final diagnoses. The data was analyzed through SPSS 22.0.

Results: Of the 40 cases analyzed, the most common …

Gender Differences In Risk Factor Profiles And Predictors Of Poor Outcomes Among Acute Stroke Patients: A Pilot Study From Egypt, Ahmed Abualhasan, Foad Abd-Allah, Sahar Salaheldin, Enas Alsayyad

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Stroke remains a leading cause of mortality and long-term disability worldwide, with significant socioeconomic implications. This study aimed to investigate gender-based differences in acute stroke patients regarding baseline characteristics, clinical presentation, and predictors of poor outcome Among Egyptian population.

Methods: We prospectively recruited 116 acute stroke patients admitted to the stroke unit at Cairo University Hospitals from January 2020 to June 2020. Detailed data on demographics, clinical characteristics, diagnostic workup, hospital course, and functional outcomes were collected. Poor outcome was defined as a modified Rankin Scale (mRS) ≥ 3 at discharge. Data were analyzed using SPSS version …