Medical Specialties Commons^™

Insights Into The Influence Of Income Variability On Cardiovascular Risk In Non-Elderly Adults With Type 2 Diabetes, Ketrell Mcwhorter

UK CARES Faculty Publications

No abstract provided.

Neural Mechanisms Of Respiratory Interoception, Pei-Ying Sarah Chan, Lu-Yuan Lee, Paul W. Davenport

UK CARES Faculty Publications

Respiratory interoception is one of the internal bodily systems that is comprised of different types of somatic and visceral sensations elicited by different patterns of afferent input and respiratory motor drive mediating multiple respiratory modalities. Respiratory interoception is a complex system, having multiple afferents grouped into afferent clusters and projecting into both discriminative and affective centers that are directly related to the behavioral assessment of breathing. The multi-afferent system provides a spectrum of input that result in the ability to interpret the different types of respiratory interceptive sensations. This can result in a response, commonly reported as breathlessness or dyspnea. …

Post-Operative Diagnosis Of Anomalous Left Coronary Artery From The Right Pulmonary Artery Via Transthoracic Echocardiogram, Lavina Desai, Sanket Shah, Edo Bedzra, Christopher Mathis

Posters

A term infant female was diagnosed with a ventricular septal defect (VSD) and aortic coarctation. Preoperative echocardiography and computed tomography angiography (CTA) showed a normal right coronary artery origin, but inconclusive left coronary artery (LCA) origin. There was a normal flow profile in the LCA by echocardiography. She underwent repair with extended end-to-end anastomosis and VSD closure during which surgical inspection revealed a usual appearing, retro pulmonary path of the LCA towards the left sinus of Valsalva. Postoperative echocardiogram revealed mild global dysfunction but no regional wall motion abnormalities.   Repeat echocardiogram revealed severe dysfunction most prominent in the anterolateral and …

Intussusception, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

Quiet Time On Family Maternity Center, Deanna Conley, Shelbie Clement

Articles, Abstracts, and Reports

Background: A stay at the hospital is full of interruptions from family visitors, lab draws, hearing screens, nurses and doctors, social workers, and environmental services. All these interruptions during the postpartum stay negatively affect parents and newborns by interrupting breastfeeding, sleep, and family bonding time. Evidence from AWHONN (Association of Women's Health Obstetric and Neonatal Nurses) research, in the articles referenced, demonstrates overwhelming support of Quiet Time in the Postpartum period. Quiet Time has been shown to improve exclusive breastfeeding rates, decrease emotional and physical exhaustion, enhance shared decision making and set realistic expectations, increase nurse satisfaction, decrease nursing stress …

“Effects Of Semaglutide With And Without Concomitant Sglt2 Inhibitor Use In Participants With Type 2 Diabetes And Chronic Kidney Disease In The Flow Trial.”, Katherine Tuttle

Articles, Abstracts, and Reports

No abstract provided.

“The Garabedians: Father And Son Cardiologists Share Legacy In The Critical Care Of Spokane’S Children”, Carl Garabedian

Articles, Abstracts, and Reports

No abstract provided.

Rhabdomyolysis As A Cause Of Pth Independent Hypocalcemia In A Child With Acute Influenza Infection, Samhita Bhattarai, Kelsee Halpin

Posters

INTRODUCTION Hypocalcemia is characterized by abnormally low level of calcium in the blood. Normal reference range for calcium for children between 12- 19-year-old is 8.5-10.6 mg/dl . Severe hypocalcemia is considered as serum calcium level of <7 mg/dl and can present with tetany, seizures, and life-threatening cardiac arrhythmias. Etiology of hypocalcemia varies but hypoparathyroidism, pseudohypoparathyroidism and Vitamin D deficiency are some of the most common causes encountered by pediatrician endocrinologists. Association of rhabdomyolysis with hypocalcemia and elevated PTH is a rare presentation that should be considered, particularly for those children presenting with acute viral illness. We present a rare case of rhabdomyolysis associated with hypocalcemia not related to hypoparathyroidism. CASE A 12-year-old female presented to the emergency department with body ache, decreased oral intake and vomiting. She was found to be influenza positive. Electrolytes showed hypocalcemia (4.8 mg/dl). She subsequently had an undetectable 25-OH vitamin D level (<5 ng/ml) and elevated iPTH level (609 pg/ml). We discussed the possibility of her etiology of hypocalcemia to be Vitamin D deficiency although her presentation was atypical at an older age with a negative imaging for rickets, hyperphosphatemia (6.0 mg/dl), and normal alkaline phosphatase (334 unit/L). She also did not have any phenotypic features of Albright’s hereditary osteodystrophy and renal function was within normal limits. She was identified to have elevated creatinine kinase (4829 U/L) supporting rhabdomyolysis secondary to acute influenza as a cause of her hypocalcemia. Rhabdomyolysis, a known complication of influenza infection, causes cell membrane destruction which impairs the normal function of Na-K-ATPase channel. This leads to increase in intracellular sodium activating Na/Ca exchanger which in turn causes influx of calcium intracellularly causing hypocalcemia. Additionally, any injury or infection leads to high phosphorus release from cells due to cell lysis. High phosphorus is also caused by reduced oxidative metabolism in muscles impairing phosphate use. This excess of phosphate then combines with calcium and causes calcium-phosphate complex in soft tissues. Hyperphosphatemia also additionally inhibits 1 alpha hydroxylase limiting formation of calcitriol leading to hypocalcemia. CONCLUSION Our patient had severe hypocalcemia due to influenza-related rhabdomyolysis. Rhabdomyolysis is an important consideration as a cause of hypocalcemia in children, especially with acute viral illness. Accordingly, it is also important to obtain serum electrolytes in patients presenting with rhabdomyolysis as hypocalcemia may lead to complications like seizures and cardiac arrhythmia if not appropriately recognized and treated.

Pediatric Cancers And Family Financial Toxicity In The Philippines: Insights For Southeast Asia And Similarly Resourced Settings, Rod Carlo Columbres, Erin Jay G. Feliciano, Kathleen Joy Taleon-Tampo, Katelyn Edelwina Y. Legaspi, Michelle Ann B. Eala, Kenrick Ng, Fumiko Chino, Frederic Ivan L. Ting, Edward Christopher Dee

Ateneo School of Medicine and Public Health Publications

Cancer is a leading cause of death among children in the Philippines, a low-middle-income country of over 110 million people. In this Comment, we describe how financial toxicity affects families of pediatric patients with cancer in the Philippines. We explore direct costs of care, indirect costs such as transportation and lodging, and psychosocial sequelae, in the Filipino medical system and sociocultural contexts. We present examples of successful interventions in the Philippines and in similarly resourced settings, with the goal of galvanizing further research, clinical interventions, and policy-level changes, aimed at mitigating family financial toxicity for pediatric patients with cancer in …

Catheter-Directed Thrombolysis, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

Periacetabular Osteotomy Eras, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

Limbic-Predominant Age-Related Tdp-43 Encephalopathy (Late-Nc): Co-Pathologies And Genetic Risk Factors Provide Clues About Pathogenesis, Peter T. Nelson, David Fardo, Xian Wu, Khine Zin Aung, Matthew D. Cykowski, Yuriko Katsumata

Neurology Faculty Publications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is detectable at autopsy in more than one- third of people beyond age 85 years and is robustly associated with dementia independent of other pathologies. Although LATE-NC has a large impact on public health, there remain uncertainties about the underlying biologic mechanisms. Here, we review the literature from human studies that may shed light on pathogenetic mechanisms. It is increasingly clear that certain combinations of pathologic changes tend to coexist in aging brains. Although “pure” LATE-NC is not rare, LATE-NC often coexists in the same brains with Alzheimer disease neuropathologic change, brain arteriolosclerosis, …

Comprehensive Assessment Of Tdp‑43 Neuropathology Data In The National Alzheimer’S Coordinating Center Database, Davis C. Woodworth, Katelynn M. Nguyen, Lorena Sordo, Kiana A. Scambray, Elizabeth Head, Claudia H. Kawas, María M. Corrada, Peter T. Nelson, S. Ahmad Sajjadi

Neurology Faculty Publications

TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer’s Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by …

Smart Cushion Device For Elderly Aging In Place, Anna Dion, Nate Colley, Leonardo Bravo

Biomedical Engineering

Our task at hand is to develop a consumer-focused solution for improving elder care to provide additional peace of mind for seniors and caregivers using technology to extend independent living. We intend to create a device that will improve the quality of life of elderly individuals living alone by encouraging periodical movement throughout the day, along with monitoring pressure distribution and alerting when pressure concentration is potentially harmful. It will also alert users to the presence of moisture which can arise from spills or incontinence. The key stakeholders of this project include elderly adults over the age of 65 who …

Labrad : Vol 49, Issue 1 - June 2024, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• EDITORIAL
• ARTICLES
• Empowering Donors Through Technology
• Impact of Clinical Laboratories on Greenhouse gas emissions
• Embracing Digitalization and Sustainability: Streamlining Laboratory Reporting
• Accelerating Productivity and Performance: Transition from Transcribers to Working with Speech Recognition.
• ECO-Friendly Molecular Pathology Laboratory Practices
• Let’s Work to Build A Sustainable Histopathology Lab
• Laboratory Sustainability -Things to Promote Eco-Conscious Laboratory Environment
• A Guide to Develop the current and future Eco-Friendly Molecular Lab practices
• The Role of Microbiology Laboratories in Seaweed Reduction and Sustainable Agar Production
• The Role of Behavioral Change in Reducing Energy Use in Microbiology Laboratories
• Reducing Pathology’s Environmental Impact – What can we do?
• Water …

Two Decades Of Research Capacity Strengthening And Reciprocal Learning On Sexual And Reproductive Health In East Africa – A Point Of (No) Return, Caroline Frisendahl, Emelie Looft-Trägårdh, Amanda Cleeve, Susan Atuhairwe, Elin Larsson, Othman Kakaire, Herbert Kayiga, Annette Aronsson, Anne Kihara, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

As the world is facing challenges such as pandemics, climate change, conflicts, and changing political landscapes, the need to secure access to safe and high-quality abortion care is more urgent than ever. On 27th of June 2023, the Swedish government decided to cut funding resources available for developmental research, which has played a fundamental role in the advancement of sexual and reproductive health and rights (SRHR) globally, including abortion care. Withdrawal of this funding not only threatens the fulfilment of the United Nations sustainable development goals (SDGS) – target 3.7 on ensuring universal access to SRHR and target 5 on …

Reversal Of Propofol-Induced Depression Of The Hypoxic Ventilatory Response By Bk-Channel Blocker Ena-001: A Randomized Controlled Trial, Simone Jansen, Maarten Van Lemmen, Erik Olofsen, Laurence Moss, Joseph Pergolizzi, Thomas Miller, Robert Colucci, Monique Van Velzen, Philip Kremer, Albert Dahan, Rutger Van Der Schrier, Marieke Niesters

Department of Medicine Faculty Papers

BACKGROUND: The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion. They hypothesize that ENA-001 is able to fully restore the hypoxic ventilatory response.

METHODS: In this randomized, double-blind crossover trial, 14 male and female healthy volunteers were randomized to receive placebo and low- and high-dose ENA-001 on three …

Effect Of Home-Based Transcranial Direct Current Stimulation On Cognitive Function In Patients With Mild Cognitive Impairment: A Two-Week Intervention, Jaesub Park, Kyungmi Chung, Yoonkyung Oh, Kwang Joon Kim, Chang Oh Kim, Jin Young Park

Faculty, Staff and Student Publications

PURPOSE: Repeated transcranial direct current stimulation (tDCS) is expected to have the potential to improve cognitive function in patients with mild cognitive impairment (MCI). We aimed to evaluate the efficacy and safety of at-home tDCS for elderly patients with MCI.

MATERIALS AND METHODS: Patients aged 60-80 years, who maintained normal daily living but reported objective memory impairments, were enrolled. Active or sham stimulations were applied to the dorsal frontal cortex (left: anode; right: cathode) at home for 2 weeks. Changes in cognitive function were assessed using visual recognition tasks and the Mini-Mental State Exam (MMSE), and safety and efficacy were …

Jak-Stat Signaling And Beyond In The Pathogenesis Of Spondyloarthritis And Their Clinical Significance, Siba P Raychaudhuri, Ruchi J Shah, Sneha Banerjee, Smriti K Raychaudhuri

Faculty, Staff and Student Publications

Purpose of Review

Janus kinase–signal transducers and activators of transcription cell signaling proteins (JAK-STATs) play a key regulatory role in functioning of several inflammatory cytokines. JAK-STAT signaling proteins are the key regulators of the cytokine/cytokine receptor system involved in the pathogenesis of various autoimmune disease including spondyloarthritis (SpA). This article mainly highlights the JAK-STAT signaling system, its association with the relevant cytokine/cytokine-receptor system, and its regulatory role in pathogenesis of SpA. Also, we have briefly addressed the principle for the use JAKi in SpA and the current status of use of JAK inhibitors (JAKi) in SpA.

Recent Findings

Recent developments …

Cardiovascular Imaging, Climate Change, And Environmental Sustainability., Suvai Gunasekaran, Andrew Szava-Kovats, Thomas Battey, Jonathan Gross, Eugenio Picano, Subha V Raman, Emil Lee, Malenka M Bissell, Mirvat Alasnag, Adrienne E Campbell-Washburn, Kate Hanneman

Heart and Vascular Articles

Environmental exposures including poor air quality and extreme temperatures are exacerbated by climate change and are associated with adverse cardiovascular outcomes. Concomitantly, the delivery of health care generates substantial atmospheric greenhouse gas (GHG) emissions contributing to the climate crisis. Therefore, cardiac imaging teams must be aware not only of the adverse cardiovascular health effects of climate change, but also the downstream environmental ramifications of cardiovascular imaging. The purpose of this review is to highlight the impact of climate change on cardiovascular health, discuss the environmental impact of cardiovascular imaging, and describe opportunities to improve environmental sustainability of cardiac MRI, cardiac …

Treatment Of Recalcitrant Hailey-Hailey Disease With Naltrexone And Dupilumab: A Report Of Two Cases., Breanna Santoso, Rachel Krevh, Alexa Israeli, Austin Cusick, Dawn Merritt, Michael Holsinger

Ambulatory and Primary Care Articles

This report presents two cases of patients with long-standing, treatment-resistant Hailey-Hailey disease (HHD) who experienced significant symptom relief through a combination therapy of oral naltrexone and dupilumab injections. The therapeutic potential of targeting the Th2 pathway and Ca

Incidence And Prevalence Of Hypertension In 18-40-Year-Old Patients Referred For Palpitations With Normal Cardiac Monitor Findings., Christopher Wasco, Zeryab Khan, Aimee Willett, Andrew Volio, Cody Carter, Aditya Kesari, Shaili Kothari, Andrew Scheidemantel, Katelyn Bennett, Jessalyn Schafer, Marie Lockhart, Nagesh Chopra

Ambulatory and Primary Care Articles

Sixteen percent of patients referred for cardiology evaluation are found to have no cause for palpitations. Studies show that hypertension intricately influences "heart rate" and "contractility,?" the key components of "palpitation." While the prevalence of hypertension is 22.4% in 18-39-year-olds, the relationship between palpitations and hypertension remains unknown in this age group. In our study, we assessed the incidence and prevalence of hypertension over 5 years in 18-40-year-olds referred for palpitations who had no known arrhythmic cause for palpitations between January 1, 206 and December 31, 2017. We found that over a period of 2.2 (0.7-4.1) years, an additional 56% …

Polygenic Liability For Anxiety In Association With Comorbid Anxiety In Multiple Sclerosis, Kaarina Kowalec, Arvid Harder, Casandra Dolovich, Kathryn C Fitzgerald, Amber Salter, Yi Lu, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Joel Gelernter, Lesley A Graff, Sara Hägg, Carol A Hitchon, Daniel F Levey, Fred D Lublin, Kyla A Mckay, Scott Patten, Amit Patki, Murray B Stein, Hemant K Tiwari, Jerry S Wolinsky, Ruth A Marrie

Faculty, Staff and Student Publications

OBJECTIVE: Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS.

METHODS: Using a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed …

A Proposed Addition To The Modified Wells Criteria: Exploring Thrombosis In The E-World, Nidhin John, Amanda Kileen

School of Podiatric Medicine - Student Research

The advancement of technology and over-reliance on electronics have led to "e-thrombosis." This review investigates the link between prolonged sedentary behavior due to extensive electronic use and the risk of venous thromboembolism (VTE) and deep vein thrombosis (DVT). The term "e-thrombosis" was introduced in 2003 by Beasley et al., highlighting the risk of immobility associated with electronics. E-thrombosis is particularly relevant post-COVID-19, with increased remote working and online learning. This review evaluates recent studies to determine if e-thrombosis should be considered in updated screening tools like the Wells Score.

A systematic literature review was conducted using PubMed, Direct Science, and …

Nutritional Supplementation In Children With Severe Pneumonia In Uganda And Kenya (Coast-Nutrition): A Phase 2 Randomised Controlled Trial, Sarah Kiguli, Peter Olupot-Olupot, Mainga Hamaluba, Elisa Giallongo, Karen Thomas, Florence Alaroker, Robert Opoka, Abner Tagoola, Shela Oyella, Damalie Nalwanga

Paediatrics and Child Health, East Africa

Background Severe pneumonia in African children results in poor long-term outcomes (deaths/readmissions) with undernutrition as a key risk factor. We hypothesised additional energy/protein-rich Ready-to-Use Therapeutic Foods (RUTF) would meet additional nutritional requirements and improve outcomes.

Methods COAST-Nutrition was an open-label Phase 2 randomised controlled trial in children (aged 6 months-12 years) hospitalised with severe pneumonia (and hypoxaemia, SpO2 <92%) in Mbale, Soroti, Jinja, Masaka Regional Referral Hospitals, Uganda and Kilifi County Hospital, Kenya (ISRCTN10829073 (registered 6th June 2018) PACTR202106635355751 (registered 2nd June 2021)). Children were randomised (ratio 1:1) to enhanced nutritional supplementation with RUTF (plus usual diet) for 56 days vs usual diet (control). The primary outcome was change in mid-upper arm circumference (MUAC) at 90 days as a composite with mortality. Secondary outcomes include anthropometric status, mortality, and readmissions at Days 28, 90 and 180.

Findings Between 12 August 2018 and 22 April 2022, 846 eligible children were randomised, 424 to RUTF and 422 to usual diet, and followed for 180-days [12 (1%) lost-to-follow-up]. RUTF supplement was initiated in 417/419 (>99%). By Day 90, there was …

International Consensus On Standard Outcome Measures For Neurodevelopmental Disorders: A Consensus Statement, Melissa Mulraney, Umanga De Silva, Andria Joseph, Maria Da Luz Sousa Fialho, Iain Dutia, Natalie Munro, Jonathan M. Payne, Tobias Banaschewski, Cláudia Bandeira De Lima, Susan Wamithi

Paediatrics and Child Health, East Africa

Importance: The use of evidence-based standardized outcome measures is increasingly recognized as key to guiding clinical decision-making in mental health. Implementation of these measures into clinical practice has been hampered by lack of clarity on what to measure and how to do this in a reliable and standardized way.

Objective: To develop a core set of outcome measures for specific neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD), communication disorders, specific learning disorders, and motor disorders, that may be used across a range of geographic and cultural settings.

Evidence Review: An international working group composed of clinical and research experts …

Radiogenomics-Based Risk Prediction Of Glioblastoma Multiforme With Clinical Relevance, Xiaohua Qian, Hua Tan, Xiaona Liu, Weiling Zhao, Michael D Chan, Pora Kim, Xiaobo Zhou

Faculty, Staff and Student Publications

Glioblastoma multiforme (GBM)is the most common and aggressive primary brain tumor. Although temozolomide (TMZ)-based radiochemotherapy improves overall GBM patients' survival, it also increases the frequency of false positive post-treatment magnetic resonance imaging (MRI) assessments for tumor progression. Pseudo-progression (PsP) is a treatment-related reaction with an increased contrast-enhancing lesion size at the tumor site or resection margins miming tumor recurrence on MRI. The accurate and reliable prognostication of GBM progression is urgently needed in the clinical management of GBM patients. Clinical data analysis indicates that the patients with PsP had superior overall and progression-free survival rates. In this study, we aimed …

Thyroid Cartilage Metastases From Prostate Cancer On 18f Psma Pet Ct: A Case Series, Poonamjeet Loyal, Samuel Gitau, Khalid Makhdomi

Imaging & Diagnostic Radiology, East Africa

Prostate cancer metastases to the thyroid cartilage is an extremely rare phenomenon. We report three cases of advanced prostate carcinoma with metastases to the thyroid cartilage identified on 18F prostate-specific membrane antigen-1007 (PSMA-1007) positron emission tomography (PET)/computed tomography (CT). The pathophysiology and possibility for under-reporting are also discussed. Prostate cancer metastases to the larynx should be considered in the differential diagnosis of thyroid cartilage lesions in patients with advanced prostate cancer and is associated with poor prognosis.

A Case Of Charcot-Marie-Tooth Disease Type 2o (Cmt 20) Associated With Dync1h1 And Slc12a6 Mutations, Tehreem Arshad, Muhammad Jawad Hassan, Arsalan Ahmad

Pakistan Journal of Neurological Sciences (PJNS)

Charcot-Marie-Tooth disease (Charcot Marie-Tooth) comprises of a variety of hereditary diseases affecting the peripheral nervous system. Charcot Marie-Tooth2 is a subgroup caused by defects in the axon of the peripheral nerve cells. Charcot Marie-Tooth Type 2O is an uncommon type that affects less than one in a million people and is linked to specific genetic abnormalities. We report a case study of a 66-year-old individual with Charcot Marie-Tooth Type 2O, diagnosed on clinical presentation and identified through genetic analysis. Electromyography and nerve conduction studies supported the diagnosis of an axonal sensorineural neuropathy. A comprehensive genetic neuropathies panel led to the …

Hurdles In Diagnosis Of Familial Amyotrophic Lateral Sclerosis With Anticipation Catastrophe Across Three Generations: A Case Report, Sana Ghous, Alam Ibrahim Siddiqui

Pakistan Journal of Neurological Sciences (PJNS)

Familial amyotrophic lateral sclerosis (F-ALS), a rare hereditary variant of ALS, is characterized by a genetic predisposition to the disease. In this case report, we reveal a compelling instance of F-ALS within a three-generation family, involving a grandfather, son, and grandson, all manifesting early-onset symptoms and progressive upper and lower motor neuron findings. The clinical diagnosis was confirmed through electromyography fulfilling El Escorial criteria of ALS. Our investigation highlights the familial connection in this case, emphasizing the hereditary aspect of ALS. This report underscores the significance of considering familial ALS in cases of successive generational involvement with early onset, a …