Neurology Commons^™

Acute Flaccid Myelitis Caused By Enterovirus Infection- A Case Report, Ahmad Bilal, Tipu Sultan, Zia Ur Rehman, Arshad Mehmood, Amber Shabir, Javeria Raza

Pakistan Journal of Neurological Sciences (PJNS)

Enterovirus is a member of the Picornaviridae family, an enterovirus. It is suspected of causing a polio-like disorder called acute flaccid myelitis (AFM). This case report aims to present a 10-year-old boy who presented with neurological manifestations of weakness of lower limbs and urinary retention. He had reduced tone, absent reflexes, and palpable bladder. MRI spine revealed inflammation in grey matter of spinal cord. He was treated with high dose steroids and IVIG but no improvement was observed. Enterovirus was isolated from his stool sample. The patient received supportive care and physiotherapy with gradual improvement after months, having no evidence …

Myosin Xva Isoforms Participate In The Mechanotransduction-Dependent Remodeling Of The Actin Cytoskeleton In Auditory Stereocilia, Ana I. López-Porras, Ava M. Kruse, Mark T. Mcclendon, A. Catalina Vélez-Ortega

Neurology Faculty Publications

Auditory hair cells form precise and sensitive staircase-like actin protrusions known as stereocilia. These specialized microvilli detect deflections induced by sound through the activation of mechano-electrical transduction (MET) channels located at their tips. At rest, a small MET channel current results in a constant calcium influx which regulates the morphology of the actin cytoskeleton in the shorter ‘transducing’ stereocilia. However, the molecular mechanisms involved in this novel type of activity-driven plasticity in the stereocilium cytoskeleton are currently unknown. Here, we tested the contribution of myosin XVA (MYO15A) isoforms, given their known roles in the regulation of stereocilia dimensions during hair …

Exercise As A Therapeutic Intervention And Its Effects On The Quality Of Life Of Those Diagnosed With Amyotrophic Lateral Sclerosis, Theresa Stettner, Helen Carey, Cynthia Haynes

Fall 2024 OTD Capstone Symposium

The standard of care for those with ALS includes range of motion, limb relaxation, trunk balance, and gait training (Braga et al., 2018). This study examines perceived quality of life in ALS clients before and after an in-person exercise program and home exercise program to evaluate the benefits of exercise as exercise does not exacerbate symptoms of ALS (Meng et al., 2020). Daily occupation performance requires functional ability which may be preserved through exercise (Kalron et al., 2021).

Blood Biomarkers In Down Syndrome: Facilitating Alzheimer's Disease Detection And Monitoring, Melissa Petersen, Lisi Flores-Aguilar, Elizabeth Head, Laia Montoliu-Gaya, Andre Strydom, Sarah Pape, Juan Fortea, Nicholas Ashton, Chinedu Momoh, Sid O'Bryant

Brain and Mind Institute

Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer's Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work …

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Lam-Ha T. Dang, Alice Lee, Sharon Krinsky-Mchale, Deborah Pang, Lisa Melilli, Sid E. O’Bryant, Rachel L. Henson, Charles Laymon, Florence Lai, H. Diana Rosas, Beau Ances, Ira Lott, Christy Hom, Bradley Christian, Sigan Hartley, Shahid Zaman, Elizabeth Head, Mark Mapstone, Zhezhen Jin, Wayne Silverman, Nicole Schupf, Benjamin Handen, Joseph H. Lee, Alzheimer’S Biomarker Consortium – Down Syndrome (Abc-Ds)

Neurology Faculty Publications

Background Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer’s disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

Methods We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium–Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Targeted Long-Read Sequencing To Quantify Methylation Of The C9orf72 Repeat Expansion, Evan Udine, Nicole Finch, Mariely Dejesus-Hernandez, Jazmyne L. Jackson, Matthew C. Baker, Siva Arumugam Saravanaperumal, Eric Wieben, Mark T. W. Ebbert, Jaimin Shah, Leonard Petrucelli, Rosa Rademakers, Björn Oskarsson, Marka Van Blitterswijk

Neurology Faculty Publications

Background The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method. Our primary goal was to determine the presence and subsequent quantification of observed methylation in the C9orf72 repeat expansion. In addition, we measured the repeat length and purity of the expansion. To do this, we sequenced DNA extracted from …

An Innovative Community‐Led Education And Recruitment Program To Increase Clinical Research Participation Among Black Americans, Bahar Niknejad, Ethlyn Mcqueen Gibson, Travonia Brown-Hughes, Katie Mcdonough, Ebony Andrews, Deborah Hudson, Hamid Okhravi

Glennan Center for Geriatrics and Gerontology Faculty Publications

Background: Previous studies attest to a lack of awareness about Alzheimer’s Disease (AD) and limited participation of Black Americans in AD clinical trials. The AHEAD Study is a multicenter trial focused on preventing AD by evaluating the effectiveness and safety of Lecanemab in individuals with preclinical AD. The study aims to recruit at least 15% from underrepresented populations, including Black Americans. To achieve this goal, our study site utilizes a community-based participatory research (CBPR) approach and developed a Community Education and Recruitment Program (CERP) designed to increase the participation of Black individuals in the AHEAD Study.

Method: In a collaborative …

Burden Of Vascular Neurological Disorders: A Cross-Sectional Multicenter Study, Shafaq Saleem, Safia Awan, Ibrar Rafiq, Muhammad Hassan Shaikh, Anjum Farooq, Maimoona Siddiqui, Zainab Aslam Saeed Memon, Alam Ibrahim Siddiqui

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective

Stroke remains a leading cause of morbidity and mortality worldwide, with a particularly high burden in low- and middle-income countries (LMICs) such as Pakistan. Despite its growing prevalence, limited nationwide data exist on vascular diseases, their risk factors, and disability outcomes. The objective of this study was to identify the frequency and age-stratified type of vascular disease incidence among in-patient hospital admissions.

Methods

A retrospective observational study was conducted across 39 neurology centers in Pakistan, spanning both public and private sectors from August 2017 to December 2019. Data on demographics, comorbidities, and stroke type were systematically collected …

Electrographic Significance Of Periodic Discharges And Association With Etiology And Outcome In A Tertiary Care Hospital: A Retrospective Cohort Study, Hina Imtiaz, Zainab Memon, Ayisha Farooq Khan, Dureshahwar Kanwar, Safia Awan

Pakistan Journal of Neurological Sciences (PJNS)

Background and Objective

Periodic discharges on electroencephalograms (EEGs) are rhythmic waveforms that may indicate acute or subacute brain injury. This aim of this study was to determine the frequency distribution of periodic discharge subtypes on EEG and to assess their association with underlying etiologies and clinical outcomes in a tertiary care hospital.

Methods

This retrospective observational cohort study included neurological patients aged ≥18 years admitted to the medical ICU or ward of Aga Khan University Hospital between January 1, 2021, and January 1, 2023, with periodic discharges on EEG. Patients with prior traumatic brain injury were excluded. Data on demographics, …

Epilepsy In Pakistani Adolescents Amid The Vaping Epidemic, Maheen Kalwar, Eisha Tur Raazia, Harmain Naz Shaikh

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

New Onset Seizures Evolving Into Refractory Status Epilepticus In The Setting Of Covid-19: A Case Report, Mahira Mushtaq, Zuha Amin, Shafaq Saleem, Fowzia Siddiqui

Pakistan Journal of Neurological Sciences (PJNS)

The novel Coronavirus disease (COVID-19) has been shown to involve the nervous system (both central and peripheral), with or without respiratory involvement in multiple ways. Although not much is known about this disease yet, seizures and status epilepticus which may evolve into refractory status epilepticus have been associated with it along with other manifestations like encephalopathy, neuropathies etc. The mechanism for development of seizures with COVID-19 related disease is not entirely known however it can be the consequence of “cytokine release syndrome” or “cytokine storm” which has been associated with this virus. Patients with COVID-19 infection who develop resistant status …

Pakistan Ischemic Stroke Guidelines, Anjum Farooq, Maria Khan, Ayesha Zafar, Husnain Hashim, Fozan Khan, Abdul Malik, Ayeesha Kamran Kamal Aga Khan University, Karachi, Mohammad Wasay

Pakistan Journal of Neurological Sciences (PJNS)

Stroke is the second leading cause of death and disability. Mortality related to stroke is very high in low- and middle-income countries. Stroke imposes a great socioeconomical burden in Pakistan. It is important to take important steps for prevention and proper management of stroke in country. Purpose of developing stroke guidelines is to improve stroke care in Pakistan. Guidelines are designed to help neurologists and general practitioners for treating stroke. American stroke guidelines, NICE guidelines, Canadian guidelines and multiple important articles including those emphasizing stroke care in low- and middle-income countries were studied, and these current guidelines were designed in …

Focused Ultrasound: A New Era In Tremor Control, Sajid Hameed

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Tocilizumab In The Management Of Neuromyelitis Optica Spectrum Disorder: A Narrative Review Of Literature And Critical Appraisal, Salman Mansoor, Samar Iltaf Mairajuddin, Saqib Gul

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective

Neuromyelitis Optica Spectrum disorder (NMOSD) mostly affects the spinal cord and optic nerves. This manuscript aims to explore the treatment potential of tocilizumab, a monoclonal antibody that targets the interleukin-6 (IL-6) receptor and regulates inflammatory cytokines implicated in the pathophysiology of NMOSD. Methods

A thorough search of the pertinent literature was done for this research utilising electronic databases, specifically PubMed, Cochrane Library, and Embase, which contained studies published from 2016 to 2024.

Results Clinical studies show that tocilizumab improves clinical outcomes and lowers recurrence rates in people with NMOSD, especially those who don't respond to traditional treatments. …

Chorea As A Rare Manifestation Of Neuropsychiatric Systemic Lupus Erythematosus: A Case Report, Qurat Ul Ain, Ashfeen Ishfaq, Farzana Kouser, Rabia Rasool

Pakistan Journal of Neurological Sciences (PJNS)

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multisystemic involvement. It has variable clinical presentations and a relapsing and remitting course. Clinical manifestations are broad, ranging from mild mucocutaneous involvement to major organ involvement. We present a case of a 32-year-old female with repeated movements of the right arm, and confusion with a background of pains in multiple joints. She was diagnosed as a case of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). She was managed with pulse therapy of cyclophosphamide (CYC) along with other supportive medications. After six months of intensive immunosuppressive therapy, she remained well and continued maintenance …

Biological Validation Of Peak-Width Of Skeletonized Mean Diffusivity As A Vcid Biomarker: The Markvcid Consortium, Alison M Luckey, Saptaparni Ghosh, Chen-Pin Wang, Alexa Beiser, Rebecca Bernal, Zhiguang Li, Djass Mbangdadji, Elyas Fadaee, Haykel Snoussi, Angel Gabriel Velarde Dediós, Hector A Trevino, Monica Goss, Laura J Hillmer, Christopher E Bauer, Adam M Staffaroni, Lara Stables, Marilyn Albert, Jayandra J Himali, Thomas H Mosley, Lars Forsberg, Vilmundur Guðnason, Baljeet Singh, Herpreet Singh, Kristin Schwab, Joel H Kramer, Gary A Rosenberg, Karl G Helmer, Steven M Greenberg, Mohamad Habes, Danny J J Wang, Brian T Gold, Hanzhang Lu, Arvind Caprihan, Myriam Fornage, Lenore J Launer, Konstantinos Arfanakis, Sudha Seshadri, Charles Decarli, Pauline Maillard, Claudia L Satizabal

Faculty, Staff and Student Publications

BACKGROUND: Peak-width of skeletonized mean diffusivity (PSMD), a neuroimaging marker of cerebral small vessel disease (SVD), has shown excellent instrumental properties. Here, we extend our work to perform a biological validation of PSMD.

METHODS: We included 396 participants from the Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID-1) Consortium and three replication samples (Cohorts for Heart and Aging Research in Genomic Epidemiology = 6172, Rush University Medical Center = 287, University of California Davis Alzheimer's Disease Research Center = 567). PSMD was derived from diffusion tensor imaging using an automated algorithm. We related PSMD to a composite measure …

Excellent Registry: A Prospective, Multicenter, Global Registry Of Endovascular Stroke Treatment With The Embotrap Device., Raul G Nogueira, Tommy Andersson, Diogo C Haussen, Albert J Yoo, Ricardo A Hanel, Osama O Zaidat, Werner Hacke, Tudor G Jovin, Jens Fiehler, Simon F De Meyer, Waleed Brinjikji, Karen M Doyle, David F Kallmes, David S Liebeskind, Renu Virmani, Malgosia A Kokoszka, Violiza Inoa, William Humphries, Keith B Woodward, Pascal M Jabbour, Olivier François, Elad I Levy, Hormozd Bozorgchami, Stephan Boor, Jose E Cohen, Shervin R Dashti, Muhammad A Taqi, Ronald F Budzik, Clemens M Schirmer, M Shazam Hussain, Laurent Estrade, Reade A De Leacy, Ajit S Puri, Rohan V Chitale, Caspar Brekenfeld, Adnan H Siddiqui

Neuroscience Articles

BACKGROUND: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots.

METHODS: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee.

RESULTS: After screening 3799 patients, a total of 997 subjects (mean age, …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Faculty, Staff and Student Publications

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10

DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Brain Gray Matter Changes In Children At Risk For Sudden Unexpected Death In Epilepsy, Bhaswati Roy, Jennifer A Ogren, Luke A Allen, Beate Diehl, Raman Sankar, Samden D Lhatoo, Rajesh Kumar, Ronald M Harper

Faculty, Staff and Student Publications

Background: Potential failing adult brain sites, stratified by risk, mediating Sudden Unexpected Death in Epilepsy (SUDEP) have been described, but are unknown in children.

Methods: We examined regional brain volumes using T1-weighted MRI images in 21 children with epilepsy at high SUDEP risk and 62 healthy children, together with SUDEP risk scores, calculated from focal seizure frequency. Gray matter tissue type was partitioned, maps normalized, smoothed, and compared between groups (SPM12; ANCOVA; covariates, age, sex, and BMI). Partial correlations between regional volumes and seizure frequency were examined (SPM12, covariates, age, sex, and BMI); 67% were at high risk for SUDEP. …

Safety And Clinical Outcomes Of Endovascular Therapy Versus Medical Management In Late Presentation Of Large Ischemic Stroke, Adnan Mujanovic, Daniel Strbian, Jelle Demeestere, João Pedro Marto, Volker Puetz, Raul G Nogueira, Mohamad Abdalkader, Simon Nagel, Jean Raymond, Marc Ribo, Patrik Michel, Shinichi Yoshimura, Osama O Zaidat, Simon Winzer, Santiago Ortega-Gutierrez, Sunil A Sheth, James E Siegler, Anne Dusart, Diogo C Haussen, Hilde Henon, Bettina L Serrallach, Mahmoud H Mohammaden, Markus A Möhlenbruch, Marta Olive-Gadea, Ajit S Puri, Nobuyuki Sakai, Piers Klein, Liisa Tomppo, Francois Caparros, João Nuno Ramos, Mouhammad Jumaa, Syed Zaidi, Tomas Dobrocky, Nicolas Martinez-Majander, Stefania Nannoni, Flavio Bellante, Aaron Rodriguez-Calienes, Sergio Salazar-Marioni, Pekka Virtanen, Daniel Po Kaiser, Rita Ventura, Jessica Jesser, Alicia C Castonguay, Muhammad M Qureshi, Hesham E Masoud, Milagros Galecio-Castillo, Manuel Requena, Riikka Lauha, Wei Hu, Eugene Lin, Zhongrong Miao, Daniel Roy, Hiroshi Yamagami, David J Seiffge, Davide Strambo, Peter A Ringleb, Robin Lemmens, Urs Fischer, Thanh N Nguyen, Johannes Kaesmacher

Faculty, Staff and Student Publications

Introduction: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings.

Patients and methods: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022. The extended time-window was defined as 6-24 h from last-seen-well to treatment. The primary outcome was shift of the 3-month modified Rankin scale (mRS) score. Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality. Outcomes were analyzed …