Neurology Commons^™

Houge-Janssens Syndrome-1 Associated With Protein Phosphatase 2 Regulatory Subunit B’ Delta And Epilepsy: A Case Report, Dua Saleem, Fizza Akbar, Noor Zeeshan, Rabab Jafry, Salman Kirmani, Sidra Kaleem Jafri

Pakistan Journal of Neurological Sciences (PJNS)

Houge-Janssens syndrome 1 is a rare autosomal dominant disorder with approximately 100 case reports worldwide. Here, we present a case of a Pakistani toddler who presented with epilepsy and developmental delay. Family history was significant with reported and documented developmental delays in both father and elder sister, with subsequent improvement. Trio-whole-genome sequencing (WGS) and Sanger sequencing were performed, revealing a heterozygous LP variant NM_006245.4: c.626A>C, p.(His209Pro) in the girl. The same variant was also identified in her father and sister. This case sheds light on the variability of phenotypic expression amongst affected individuals and recommends the need for further …

High Dose Methylprednisolone In Children With Severe Headache In Viral Encephalitis: A Case Series, Abia Abdullah, Jay Kumari, Prem Chand

Pakistan Journal of Neurological Sciences (PJNS)

Severe headache is a common symptom in children with viral encephalitis (VE), yet effective symptom-specific therapies are limited. In this case series, we present three children of ages 15, 14, and seven diagnosed with VE who presented with severe headaches unresponsive to standard analgesics but showed significant clinical improvement following high-dose methylprednisolone therapy. Although this is not first line treatment, these cases suggest a possible role for methylprednisolone in alleviating severe VE-associated headaches. Further controlled studies are needed to establish its effectiveness and safety in such settings.

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 …

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 …

Endovascular Thrombectomy For Childhood Stroke (Save Childs Pro): An International, Multicentre, Prospective Registry Study, Peter B. Sporn, Kartik Bhatia, Todd Abruzzo, Lisa Pabst, Stuart Fraser, Melissa G. Chun, Warren Lo, Ahmed Othman, Sebastian Steinmetz, Ameer E. Hassan

School of Medicine Publications

Background

Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke.

Methods

In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular …

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 …

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 …

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 …

A Comprehensive Perspective On Intracranial Pressure Monitoring And Individualized Management In Neurocritical Care: Results Of A Survey With Global Experts, Sérgio Brasil, Daniel Agustín Godoy, Walter Videtta, Andrés Mariano Rubiano, Davi Solla, Fabio Silvio Taccone, Chiara Robba, Frank Rasulo, Marcel Aries, Peter Smielewski, Geert Meyfroidt, Denise Battaglini, Mohammad I Hirzallah, Robson Amorim, Gisele Sampaio, Fabiano Moulin, Cristian Deana, Edoardo Picetti, Angelos Kolias, Peter Hutchinson, Gregory W Hawryluk, Marek Czosnyka, Ronney B Panerai, Lori A Shutter, Soojin Park, Carla Rynkowski, Jorge Paranhos, Thiago H S Silva, Luiz M S Malbouisson, Wellingson S Paiva

Faculty, Staff and Students Publications

BACKGROUND: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and …