Medical Specialties Commons^™

A Peptide Blocking The Adora1-Neurabin Interaction Is Anticonvulsant And Inhibits Epilepsy In An Alzheimer's Model, Shalini Saggu, Yunjia Chen, Liping Chen, Diana Pizarro, Sandipan Pati, Wen Jing Law, Lori Mcmahon, Kai Jiao, Qin Wang

Faculty, Staff and Student Publications

Epileptic seizures are common sequelae of stroke, acute brain injury, and chronic neurodegenerative diseases, including Alzheimer's disease (AD), and cannot be effectively controlled in approximately 40% of patients, necessitating the development of novel therapeutic agents. Activation of the A1 receptor (A1R) by endogenous adenosine is an intrinsic mechanism to self-terminate seizures and protect neurons from excitotoxicity. However, targeting A1R for neurological disorders has been hindered by side effects associated with its broad expression outside the nervous system. Here we aim to target the neural-specific A1R/neurabin/regulator of G protein signaling 4 (A1R/neurabin/RGS4) complex that dictates A1R signaling strength and response outcome …

De Novo Fzr1 Loss-Of-Function Variants Cause Developmental And Epileptic Encephalopathies, Sathiya N Manivannan, Jolien Roovers, Noor Smal, Candace T Myers, Dilsad Turkdogan, Filip Roelens, Oguz Kanca, Hyung-Lok Chung, Tasja Scholz, Katharina Hermann, Tatjana Bierhals, Hande S Caglayan, Hannah Stamberger, Mae Working Group Of Euroepinomics Res Consortium, Heather Mefford, Peter De Jonghe, Shinya Yamamoto, Sarah Weckhuysen, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

FZR1, which encodes the Cdh1 subunit of the anaphase-promoting complex, plays an important role in neurodevelopment by regulating the cell cycle and by its multiple post-mitotic functions in neurons. In this study, evaluation of 250 unrelated patients with developmental and epileptic encephalopathies and a connection on GeneMatcher led to the identification of three de novo missense variants in FZR1. Whole-exome sequencing in 39 patient-parent trios and subsequent targeted sequencing in an additional cohort of 211 patients was performed to identify novel genes involved in developmental and epileptic encephalopathy. Functional studies in Drosophila were performed using three different mutant alleles of …

Churg Strauss Syndrome With Neuropathy: A Case Report, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

A 24 years old man with known history of asthma came with acute presentation of ascending weakness for four days following flu like symptoms and worsening of asthma. His complete blood counts showed elevated eosinophil count. Nerve conduction showed neuropathy. He was diagnosed as Churg Strauss syndrome due to presence of asthma, eosinophilia, neuropathy and pulmonary infiltrates. Churg Strauss is a systemic eosinophilic vasculitis involving multiple organ systems that may present with neuropathy, as in this case.

Post Covid-19 Vaccine (Sinovac) Cerebral Venous Sinus Thrombosis, Soban Khan, Maryam Khalil, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

SINOVAC is an inactivated virus COVID 19 vaccine given emergency authorization for COVID-19 Pandemic. Different adverse reactions have been seen in after-marketing of COVID-19 vaccines. Here we present a case of patient who developed cerebral venous sinus thrombosis two weeks after the first dose of SINOVAC vaccine.

Molecular Analyses Of Phenylketonuria In The Intellectually Disabled Children From Faisalabad, Punjab, Pakistan, Habiba Hussain, Muhammad Wasim, Haq Nawaz Khan, Hina Ayesha, Fazli Rabbi Awan

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT Background and Objective: Phenylketonuria (PKU) is a rare inherited metabolic disorder, caused by mutations in the phenylalanine hydroxylase (PAH). It is a treatable disorder if diagnosed earlier in life. The objective was to identify PKU patient(s) amongst the intellectually disabled children. Methods: Blood samples (n=100) were collected from intellectually disabled children from Faisalabad, Pakistan. Screening was performed on plasma samples through High Performance Liquid Chromatography (HPLC), and DNA samples were examined for mutation analysis of PAH through direct PCR and SSCP analyses. Results: In the current study, 85% consanguinity rate was observed, with the average BMI (16.15 kg/m2) and …

Prevalence Of Depression In Caregivers Of Stroke Patients In Karachi, Pakistan, Marium Mansoor, Shahina Pirani, Rabeeka Aftab, Tania Nadeem

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT Background and Objective: Caregivers of patients with chronic debilitating illnesses are at risk of developing mental health problems. The objective of this study is to determine the frequency of depression in caregivers of stroke patients at a tertiary care teaching hospital in Karachi, Pakistan. Methods: A cross-sectional study was conducted among caregivers of stroke, who were recruited from the Aga Khan University Hospital between January 2018 to October 2018. Data was collected through the Urdu Hamilton rating scale for depression (HAM-D-U) and it was analyzed using descriptive and inferential statistics. Results: A total of 136 caregivers participated in the …

Practical Measures For Disabled’S Empowerment-Time For Economic Growth!, Mahnoor Hafeez

Pakistan Journal of Neurological Sciences (PJNS)

The objective of this article is to advocate for persons with disabilities’ (PWD) rights, to discuss issues solutions, social awareness and to promote diversity and inclusion. The word ‘Disability’ covers a wide range of irreversible permanent impairments including physical and mobility difficulties, hearing, visual impairment, specific learning disabilities including dyslexia, medical conditions and mental health problems that may hinder their full and effective participation in society on an equal basis with others.1 Handicap is the condition of being unable to perform due to physical or mental unfitness.

Pediatric Nemaline Myopathy: A Systematic Review Using Individual Patient Data, Briana Christophers, Michael A Lopez, Vandana A Gupta, Hannes Vogel, Mary Baylies

Faculty, Staff and Student Publications

Nemaline myopathy is a skeletal muscle disease that affects 1 in 50 000 live births. The objective of this study was to develop a narrative synthesis of the findings of a systematic review of the latest case descriptions of patients with NM. A systematic search of MEDLINE, Embase, CINAHL, Web of Science, and Scopus was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the keywords pediatric, child, NM, nemaline rod, and rod myopathy. Case studies focused on pediatric NM and published in English between January 1, 2010, and December 31, …

Interdisciplinary Patient-Centred Poststroke Care In Follow-Up After Stroke, Screening And Treatment (Fasst) Clinic Model: A Proof-Of-Concept Pilot Study, Min Sun Kim, Sean V Cleymaet, Seung Kim, Jennifer Andres, Charles Ruchalski, Yongwoo Kim, S Ausim Azizi, Anjail Z Sharrief, Imama A Naqvi

Faculty, Staff and Student Publications

BACKGROUND: Although secondary stroke prevention is important, the optimal outpatient model that improves risk factor control and decreases post-stroke complications effectively has not been established. We created Follow-up After Stroke, Screening and Treatment (FASST), an interdisciplinary clinic involving stroke physicians and pharmacists to address poststroke complications and secondary stroke prevention systemically. We present our approach to assess its proof-of-concept in our pilot study.

METHODS: We included the patients attending FASST clinic after their hospital discharge. We used validated survey screens to assess for complications: depression, anxiety, sleep disorders, cognitive impairment, disability, social support, quality of life and functional status. Data …

Post Covid-19 Vaccine Guillain Barre Syndrome, Soban Khan, Maryam Khalil, Zaid Waqar, Sajid Khan, Zakir Jan

Pakistan Journal of Neurological Sciences (PJNS)

The Guillain Barre Syndrome (GBS) is an acute immune-mediated progressive polyneuropathy having an acute monophasic illness leading to paralysis. The clinical features are progressive ascending symmetrical muscle weakness that may lead to respiratory failure. Diagnosis is based upon clinical presentation and is supported by a lumbar puncture with CSF analysis demonstrating albumin-cytological dissociation, and electrophysiological studies. Our patient presented to us with progressive ascending paralysis after receiving COVID 19 vaccine.

Succinic Semialdehyde Dehydrogenase Deficiency – A Rare Cause Of Metabolic Stroke, Areeba Wasim, Javeria Raza Alvi, Tipu Sultan

Pakistan Journal of Neurological Sciences (PJNS)

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare neurometabolic disorder characterized by defective degradation of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter of the brain. Children with SSADH deficiency present with motor and mental delay, intractable seizures, infantile onset hypotonia, speech disturbances, extrapyramidal symptoms and ataxia. This wide spectrum results from increased accumulation of 4hydroxy butyric acid (4HBA) leading to down regulation of GABA receptors, which likely explain epileptogenesis but the pathophysiology of stroke in SSADH deficiency is not much elucidated. Here, we report an infant aged 11 months, product of consanguineous marriage with significant family history of motor delay …

Risk Factors Of Intracerebral Hemorrhage – A Cross Sectional Study, Mir Jalal-Ud-Din, Raheel Jehangir Jadoon, Syed Affan Ali, Samia Wazir Khawaja, Zahid Gul Jadoon, Ibtisam .

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT Background and Objective: Stroke is the major cause of disability and one of the top causes of death in the globe. Though the rate is decreasing in the West, it is most likely growing in Asia. In Pakistan, the burden of stroke risk factors is substantial. Although data on the incidence and prevalence of stroke in Pakistan is limited, there are several published case studies demonstrating major disparities in stroke epidemiology, risk factors, kinds, and patterns. This study aims to identify risk factors of intracerebral hemorrhage among patients presenting to a teaching hospital. Methods: From August 2019 to February …

Iranian Stroke Model-How To Involve Health Policymakers, Mehdi Farhoudi, Ehsan Sharifipour

Pakistan Journal of Neurological Sciences (PJNS)

Stroke in Iran, with more than 83 million population, is a leading cause of disability and mortality in adults. Stroke has higher incidence in Iran comparing the global situation and unfortunately the onset age of first ever stroke is dropping about 10 years.1 Intravenous thrombolysis, as an approved treatment in ischemic stroke, has been used only in some university or private hospitals in Iran since 2008.2 The main limit for this therapy in Iran was the lack of coverage by health insurance companies for tPA. A project for situation analysis of stroke cases entering to Imam Reza Hospital, a tertiary …

Adopting Clinical Practice Guidelines For Pharmacologic Management Of Acute Spinal Cord Injury From A Developed World Context To A Developing Global Region, Seyed Behnam Jazayeri, Seyed Farzad Maroufi, Zahra Ghodsi, Heshmatollah Ghawami, Ahmad Pourrashidi, Abbas Amirjamshidi, Mojtaba Mojtahedzadeh, Jalil Arabkheradmand, Farzin Farahbakhsh, Maryam Shabany, Morteza Faghih-Jouibari, Michael G Fehlings, Brian K Kwon, James Harrop, Vafa Rahimi-Movaghar

Department of Neurosurgery Faculty Papers

Background: Proper utilization of high-quality clinical practice guidelines (CPGs) eliminates the dependence of patients' outcomes on the ability and knowledge of "individual" health care providers and reduces unwarranted variation in care. The aim of this study was to adapt/adopt two CPGs for pharmacologic management of acute spinal cord injury (SCI) using guideline adaptation methods.

Methods: This study was conducted based on the ADAPTE process. Following establishment of an organizing committee and choosing the health topics, we appraised the quality of the CPGs using the Appraisal of Clinical Guidelines for Research & Evaluation II (AGREE II). Then, the authors extracted and …

Modelmatcher: A Scientist-Centric Online Platform To Facilitate Collaborations Between Stakeholders Of Rare And Undiagnosed Disease Research, J Michael Harnish, Lucian Li, Sanja Rogic, Guillaume Poirier-Morency, Seon-Young Kim, Kym M Boycott, Michael F Wangler, Hugo J Bellen, Philip Hieter, Paul Pavlidis, Zhandong Liu, Shinya Yamamoto

Duncan NRI Faculty and Staff Publications

Next-generation sequencing is a prevalent diagnostic tool for undiagnosed diseases and has played a significant role in rare disease gene discovery. While this technology resolves some cases, others are given a list of possibly damaging genetic variants necessitating functional studies. Productive collaborations between scientists, clinicians, and patients (affected individuals) can help resolve such medical mysteries, and provide insights into in vivo function of human genes. Furthermore, facilitating interactions between scientists and research funders, including non-profit organizations or commercial entities, can dramatically reduce the time to translate discoveries from bench to bedside. Several systems designed to connect clinicians and researchers with …

Parental Mosaicism For Apparent De Novo Genetic Variants: Scope, Detection, And Counseling Challenges, Roni Zemet, Ignatia B Van Den Veyver, Paweł Stankiewicz

Duncan NRI Faculty and Staff Publications

The disease burden of de novo mutations (DNMs) has been evidenced only recently when the common application of next-generation sequencing technologies enabled their reliable and affordable detection through family-based clinical exome or genome sequencing. Implementation of exome sequencing into prenatal diagnostics revealed that up to 63% of pathogenic or likely pathogenic variants associated with fetal structural anomalies are apparently de novo, primarily for autosomal dominant disorders. Apparent DNMs have been considered to primarily occur as germline or zygotic events, with consequently negligible recurrence risks. However, there is now evidence that a considerable proportion of them are in fact inherited from …

A Wireless Millimetric Magnetoelectric Implant For The Endovascular Stimulation Of Peripheral Nerves, Joshua C Chen, Peter Kan, Zhanghao Yu, Fatima Alrashdan, Roberto Garcia, Amanda Singer, C S Edwin Lai, Ben Avants, Scott Crosby, Zhongxi Li, Boshuo Wang, Michelle M Felicella, Ariadna Robledo, Angel V Peterchev, Stefan M Goetz, Jeffrey D Hartgerink, Sunil A Sheth, Kaiyuan Yang, Jacob T Robinson

Faculty, Staff and Student Publications

Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries. The device can be delivered through a percutaneous catheter and leverages magnetoelectric materials to receive data and power through tissue via …

Nexmif Pathogenic Variants In Individuals Of Korean, Vietnamese, And Mexican Descent, Elizabeth Langley, Laura S Farach, Mary K Koenig, Hope Northrup, David F Rodriguez-Buritica, Kate Mowrey

Faculty, Staff and Student Publications

NEXMIF pathogenic variants have been known to produce a wide spectrum of X-linked intellectual disability (ID) in both males and females. Thus far, few individuals from diverse populations have been described with NEXMIF-related disorders. Herein, we report three individuals with NEXMIF pathogenic variants, the first two are the only males of Korean and Vietnamese descent described with this disorder to our knowledge. The last patient is a Hispanic female who harbors the same pathogenic variant as a previously described Caucasian individual, but with differing clinical presentation. These patients present with many classic symptoms of NEXMIF-related disorders including ID, epilepsy, developmental …

Prognosticators Of Visual Acuity After Indirect Traumatic Optic Neuropathy, Alex J Wright, Joanna H Queen, Emilio P Supsupin, Alice Z Chuang, John J Chen, Rod Foroozan, Ore-Ofe O Adesina

Faculty, Staff and Student Publications

BACKGROUND: The purpose of this study is to determine whether there are radiographic and systemic clinical characteristics that can predict final visual outcomes in patients with indirect traumatic optic neuropathy (iTON).

METHODS: This study is a retrospective, multicenter case series of adult patients with iTON treated initially at large, urban, and/or academic trauma centers with follow-up at an affiliated ophthalmology clinic. In addition to detailed cranial computed tomography characteristics, demographics, systemic comorbidities, coinjuries, blood products administered, and intracranial pressure, along with other factors, were gathered. LogMAR visual acuity (VA) at the initial presentation to the hospital and up to 12 …

Prune1 C933g>A Synonymous Variant Induces Exon 7 Skipping, Disrupts The Dhha2 Domain, And Leads To An Atypical Nmihba Syndrome Presentation: Case Report And Review Of The Literature, Christina L Magyar, David R Murdock, Lindsay C Burrage, Hongzheng Dai, Seema R Lalani, Richard A Lewis, Yuezhen Lin, Marcela F Astudillo, Jill A Rosenfeld, Alyssa A Tran, James B Gibson, Undiagnosed Diseases Network, Carlos A Bacino, Brendan H Lee, Hsiao-Tuan Chao

Faculty, Staff and Students Publications

Prune exopolyphosphatase-1 (PRUNE1) encodes a member of the aspartic acid-histidine-histidine (DHH) phosphodiesterase superfamily that regulates cell migration and proliferation during brain development. In 2015, biallelic PRUNE1 loss-of-function variants were identified to cause the neurodevelopmental disorder with microcephaly, hypotonia, and variable brain abnormalities (NMIHBA, OMIM#617481). NMIHBA is characterized by the namesake features and structural brain anomalies including thinning of the corpus callosum, cerebral and cerebellar atrophy, and delayed myelination. To date, 47 individuals have been reported in the literature, but the phenotypic spectrum of PRUNE1-related disorders and their causative variants remains to be characterized fully. Here, we report a novel homozygous …

Co-Transmitting Neurons In The Lateral Septal Nucleus Exhibit Features Of Neurotransmitter Switching, Patrick J Hunt, Mikhail Kochukov, Brandon T Pekarek, Benjamin D W Belfort, Juan M Romero, Jessica L Swanson, Benjamin R Arenkiel

Faculty, Staff and Students Publications

The lateral septal nucleus (LSN) is a highly interconnected region of the central brain whose activity regulates widespread circuitry. As such, the mechanisms that govern neuronal activity within the LSN have far-reaching implications on numerous brain-wide nuclei, circuits, and behaviors. We found that GABAergic neurons within the LSN express markers that mediate the release of acetylcholine (ACh). Moreover, we show that these vGATLSN neurons release both GABA and ACh onto local glutamatergic LSN neurons. Using both short-term and long-term neuronal labeling techniques we observed expression of the cholinergic neuron marker Choline Acetyltransferase (ChAT) in vGATLSN neurons. These findings provide evidence …

Real-Time Fmri Neurofeedback And Ptsd: Efficacy In Symptom Relief And Neural Circuit Restoration, Sophia F. Ryker

University Honors Theses

Background: Posttraumatic stress disorder (PTSD) is recognized by the DSM-V as resulting from exposure to a traumatic event and the subsequent, prolonged experience of intrusive symptoms, avoidance behavior, altered cognitive functioning and hyperarousal. Current treatments often do not provide relief from symptoms and there is a need for neuro-scientifically informed interventions.

Methods: Through the review of all available studies using real-time fMRI neurofeedback (rt-fMRI-NF) as a treatment for PTSD, the efficacy of this therapeutic intervention was analyzed in order to make specific recommendations for the neurofeedback protocols of future studies.

Results: Evidence demonstrated successful reduction in symptom severity and normalizing …

Making The Case For The Accelerated Withdrawal Of Aducanumab, Peter J. Whitehouse

Faculty Scholarship

U.S. Food and Drug Administration-s (FDA) approval of aducanumab (Aduhelm® in the US) as a treatment for mild cognitive impairment of the Alzheimer type and Alzheimer-s disease has raised such major concerns about efficacy, safety, FDA processes, and regulatory capture that Biogen-s license to market this biologic should be immediately withdrawn. Aducanumab has not demonstrated benefit to patients, failed to meet regulatory guidelines, and is likely to cause both individual and societal harm.

Discovery Of Potent Bet Bromodomain 1 Stereoselective Inhibitors Using Dna-Encoded Chemical Library Selections, Ram K Modukuri, Zhifeng Yu, Zhi Tan, Hai Minh Ta, Melek Nihan Ucisik, Zhuang Jin, Justin L Anglin, Kiran L Sharma, Pranavanand Nyshadham, Feng Li, Kevin Riehle, John C Faver, Kevin Duong, Sureshbabu Nagarajan, Nicholas Simmons, Stephen S Palmer, Mingxing Teng, Damian W Young, Joanna S Yi, Choel Kim, Martin M Matzuk

Duncan NRI Faculty and Staff Publications

BRDT, BRD2, BRD3, and BRD4 comprise the bromodomain and extraterminal (BET) subfamily which contain two similar tandem bromodomains (BD1 and BD2). Selective BD1 inhibition phenocopies effects of tandem BET BD inhibition both in cancer models and, as we and others have reported of BRDT, in the testes. To find novel BET BD1 binders, we screened >4.5 billion molecules from our DNA-encoded chemical libraries with BRDT-BD1 or BRDT-BD2 proteins in parallel. A compound series enriched only by BRDT-BD1 was resynthesized off-DNA, uncovering a potent chiral compound, CDD-724, with >2,000-fold selectivity for inhibiting BRDT-BD1 over BRDT-BD2. CDD-724 stereoisomers exhibited remarkable differences in …

Efficacy Of Cenobamate For Uncontrolled Focal Seizures In Patients With Previous Epilepsy-Related Surgery: Post Hoc Analysis Of A Phase 3, Multicenter, Open-Label Study, Bassel Abou-Khalil, Sami Aboumatar, Pavel Klein, Gregory L Krauss, Michael R Sperling, William E Rosenfeld

Department of Neurology Faculty Papers

Objective: This post hoc analysis of 10 US study sites from a long-term open-label phase 3 study of adjunctive cenobamate evaluated the efficacy of cenobamate in patients with prior epilepsy-related surgery.

Methods: Patients with uncontrolled focal seizures despite taking stable doses of 1-3 concomitant antiseizure medications (ASMs) received increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) at 2-week intervals over 12 weeks (target dose, 200 mg/day). Further increases up to 400 mg/day using biweekly 50-mg/day increments were allowed during the maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. Data were assessed until the last …

Crel And Wnt5a/Frizzled 5 Receptor-Mediated Inflammatory Regulation Reveal Novel Neuroprotectin D1 Targets For Neuroprotection, Jorgelina M. Calandria, Khanh V. Do, Sayantani Kala-Bhattacharjee, Andre Obenaus, Ludmila Belayev, Nicolas G. Bazan

School of Medicine Faculty Publications

Abstract: Wnt5a triggers inflammatory responses and damage via NFkB/p65 in retinal pigment epithelial (RPE) cells undergoing uncompensated oxidative stress (UOS) and in experimental ischemic stroke. We found that Wnt5a-Clathrin-mediated uptake leads to NFkB/p65 activation and that Wnt5a is secreted in an exosome-independent fashion. We uncovered that docosahexaenoic acid (DHA) and its derivative, Neuroprotectin D1 (NPD1), upregulate c-Rel expression that, as a result, blunts Wnt5a abundance by competing with NFkB/p65 on the Wnt5a promoter A. Wnt5a increases in ischemic stroke penumbra and blood, while DHA reduces Wnt5a abundance with concomitant neuroprotection. Peptide inhibitor of Wnt5a binding, Box5, is also neuroprotective. DHA-decreased …

Berenice Final Analysis: Cardiac Safety Study Of Neoadjuvant Pertuzumab, Trastuzumab, And Chemotherapy Followed By Adjuvant Pertuzumab And Trastuzumab In Her2-Positive Early Breast Cancer, Chau Dang, Michael S Ewer, Suzette Delaloge, Jean-Marc Ferrero, Ramon Colomer, Luis De La Cruz-Merino, Theresa L Werner, Katherine Dadswell, Mark Verrill, Daniel Eiger, Sriparna Sarkar, Sanne Lysbet De Haas, Eleonora Restuccia, Sandra M Swain

Duncan NRI Faculty and Staff Publications

Simple Summary

A combination of pertuzumab, trastuzumab, and chemotherapy is a standard treatment for patients with a type of breast cancer called HER2-positive. Before the BERENICE study, little was known about the safety and effectiveness of pertuzumab with trastuzumab after surgery. Cardiac safety was a particular concern, especially when the chemotherapy given before surgery included drugs called anthracyclines. BERENICE was designed to assess the cardiac safety of pertuzumab with trastuzumab before surgery in combination with two different types of anthracycline-based chemotherapies. This paper describes additional safety and effectiveness data from BERENICE after patients had undergone surgery and when they had …

Electrographic Seizures In Neonates With A High Risk Of Encephalopathy, Wan-Hsuan Chen, Oi-Wa Chan, Jainn-Jim Lin, Ming-Chou Chiang, Shao-Hsuan Hsia, Huei-Shyong Wang, En-Pei Lee, Yi-Shan Wang, Cheng-Yen Kuo, Kuang-Lin Lin, On The Behalf Of The Icns Group

Faculty, Staff and Student Publications

Background: Neonatal encephalopathy is caused by a wide variety of acute brain insults in newborns and presents with a spectrum of neurologic dysfunction, such as consciousness disturbance, seizures, and coma. The increased excitability in the neonatal brain appears to be highly susceptible to seizures after a variety of insults, and seizures may be the first clinical sign of a serious neurologic disorder. Subtle seizures are common in the neonatal period, and abnormal clinical paroxysmal events may raise the suspicion of neonatal seizures. Continuous video electroencephalographic (EEG) monitoring is the gold standard for the diagnosis of neonatal seizures. The aim of …

Expression Of 4e-Bp1 In Juvenile Mice Alleviates Mtor-Induced Neuronal Dysfunction And Epilepsy, Lena H Nguyen, Youfen Xu, Travorn Mahadeo, Longbo Zhang, Tiffany V Lin, Heather A Born, Anne E Anderson, Angélique Bordey

Faculty, Staff and Students Publications

Hyperactivation of the mTOR pathway during foetal neurodevelopment alters neuron structure and function, leading to focal malformation of cortical development and intractable epilepsy. Recent evidence suggests a role for dysregulated cap-dependent translation downstream of mTOR signalling in the formation of focal malformation of cortical development and seizures. However, it is unknown whether modifying translation once the developmental pathologies are established can reverse neuronal abnormalities and seizures. Addressing these issues is crucial with regards to therapeutics because these neurodevelopmental disorders are predominantly diagnosed during childhood, when patients present with symptoms. Here, we report increased phosphorylation of the mTOR effector and translational …

Treatment Of Gravitational Pulling Sensation In Patients With Mal De Debarquement Syndrome (Mdds): A Model-Based Approach, Sergei B. Yakushin, Theodore Raphan, Catherine Cho

Publications and Research

Perception of the spatial vertical is important for maintaining and stabilizing vertical posture during body motion. The velocity storage pathway of vestibulo-ocular reflex (VOR), which integrates vestibular, optokinetic, and proprioception in the vestibular nuclei vestibular-only (VO) neurons, has spatio-temporal properties that are defined by eigenvalues and eigenvectors of its system matrix. The yaw, pitch and roll eigenvectors are normally aligned with the spatial vertical and corresponding head axes. Misalignment of the roll eigenvector with the head axes was hypothesized to be an important contributor to the oscillating vertigo during MdDS. Based on this, a treatment protocol was developed using simultaneous …