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Open Access Publications from the University of California

Scholarly Works (93 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2019)

Background:

Amytrophic lateral sclerosis (ALS) is a fatal neurologic disease that is projected to double in worldwide incidence in the next 20 years. The heterogenic nature of the disease and relatively limited research data, compared to non-rare diseases, have made it difficult for clinician researchers to alter the course of the disease within the short life expectancy after symptom onset.

Method:

This was a mixed-method retrospective review and live sampling study using three distinct data sources. Retrospective data was abstracted from the electronic medical record systems for a select group of ALS patients seen at the University of California, Irvine Neuromuscular Center (UCI NMC). Additional retrospective datasets curated by the Pooled Resources Open-Access Clinical Trials (PRO-ACT) database were also analyzed. Observational data was collected using a 9-item survey developed on Google Forms and disseminated through the ALS Association Golden West Chapter. The items measured symptom onset, diagnostic journey, and patient demographics.

Results:

The analyses confirmed current reports of higher disease incidence in Caucasian populations, usually comprising at least 60% of each dataset. The gender prevalence towards males was only observed in the PRO-ACT dataset. There was also a difference in mean age between PRO-ACT (56 years), UCI (61 years), and Online Questionnaire respondents (66 years).

Discussion:

Ultimately retrospective data analyses were limited by substantial missing, not at random data. Large data repositories can bridge the gap between non-rare and rare disease research, but only with robust and methodologic data collection across all participating sites.

    Cover page: Understanding Disease Heterogeneity and Patient Characteristics in Patients with Amyotrophic Lateral Sclerosis (ALS)
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2015)

    Objective

    Macroglossia is a well-known feature of amyloidosis; however, tongue atrophy and fasciculations are rarely seen and can lead to the misdiagnosis of amyotrophic lateral sclerosis (ALS).

    Methods

    We identified 2 unrelated patients with atypical features of tongue atrophy and fasciculations in the setting of a severe neuropathy.

    Results

    Both patients were confirmed to have transthyretin-related familial amyloid polyneuropathy (TTR-FAP) by genetic testing.

    Conclusions

    TTR-FAP should be considered as a possible mimicker of ALS when tongue atrophy and fasciculations are seen in the setting of a severely progressive polyneuropathy. Other atypical mimickers of ALS include polyglucosan body disease, hexosaminidase A deficiency, multisystem proteinopathy, and Allgrove syndrome.
      Cover page: Tongue atrophy and fasciculations in transthyretin familial amyloid neuropathy
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2015)
        Cover page: Diagnostic value of MRI in inflammatory myositisCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2022)
        PURPOSE OF REVIEW: To discuss recent developments in our understanding of epidemiology, diagnostics, biomarkers, pathology, pathogenesis, outcome measures, and therapeutics in inclusion body myositis (IBM). RECENT FINDINGS: Recent epidemiology data confirms a relatively higher prevalence in the population aged above 50 years and the reduced life expectancy. Association with cancer and other systemic disorders is better defined. The role of magnetic resonance imaging (MRI) and ultrasound in diagnosis as well as in following disease progression has been elucidated. There are new blood and imaging biomarkers that show tremendous promise for diagnosis and as outcome measures in therapeutic trials. Improved understanding of the pathogenesis of the disease will lead to better therapeutic interventions, but also highlights the importance to have sensitive and responsive outcome measures that accurately quantitate change. SUMMARY: There are exciting new developments in our understanding of IBM which should lead to improved management and therapeutic options.
          Cover page: Inclusion body myositis: evolving concepts.
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2021)
          This scientific commentary refers to ‘Predictors of functional outcomes in patients with facioscapulohumeral muscular dystrophy’ by Katz et al. (doi:10.1093/brain/awab326).
            Cover page: Random forest: random results or meaningful insights for patients with facioscapulohumeral muscular dystrophy?
            • Thesis
            • Peer Reviewed
            UC Irvine Electronic Theses and Dissertations (2022)

            ABSTRACT OF THE THESIS

            Clinical Improvement Mirrored Antibody Reduction in Myasthenia Gravis by Isela Stephanie Hernandez Master of Science in Biomedical and Translational Science University of California, Irvine, 2022 Professor Tahseen Mozaffar, Chair

            Introduction: The relationship of anti-acetylcholine receptor (AChR) antibody levels to treatment response remains unclear in seropositive myasthenia gravis (MG) patients.Objective: To examine whether changes in AChR antibody level (ΔAb) correlate with clinical response in subjects in the Thymectomy in Myasthenia Gravis Trial (MGTX). Methods: Post-hoc analysis of the MGTX antibody level dataset at baseline, 12, 24, 36 months. Changes in Myasthenia Gravis Activities of Daily Living (ΔMG-ADL) and Quantitative Myasthenia Gravis (ΔQMG) scores compared to ΔAb between the thymectomy+prednisone versus prednisone only groups. Statistical methods included bivariate linear regression, Spearman correlation and Mann-Whitney test. Results: Data from 86/126 enrolled subjects, including outliers, was analyzed. Correlation with ΔMG-ADL was statistically significant at 12 and 24 months (P 0.0397 and 0.0008 respectively). ΔQMG and ΔAb directly correlated at all 3 timepoints [P= 0.0032, P= 0.0031, P=0.0005, respectively]. Conclusion: Reductions in AChR antibody level generally correlated, in both treatment arms, with improvement in QMG and MG-ADL scores, confirming the utility of monitoring antibody levels in clinical practice to follow treatment response.

              Cover page: Clinical Improvement Mirrored Antibody Reduction in Myasthenia GravisCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2022)

              Purpose of review

              This review summarizes the clinical presentation and provides an update on the current strategies for diagnosis of Pompe disease. We will review the available treatment options. We examine newly approved treatments as well as upcoming therapies in this condition. We also provide commentary on the unmet needs in clinical management and research for this disease.

              Recent findings

              In March 2015, Pompe disease was added to the Recommended Uniform Screening Panel (RUSP) and since then a number of states have added Pompe disease to their slate of diseases for their Newborn Screening (NBS) program. Data emerging from these programs is revising our knowledge of incidence of Pompe disease. In 2021, two randomized controlled trials involving new forms of enzyme replacement therapy (ERT) were completed and one new product is already FDA-approved and on the market, whereas the other product will come up for FDA review in the fall. Neither of the new ERT were shown to be superior to the standard of care product, alglucosidase. The long-term effectiveness of these newer forms of ERT is unclear. Newer versions of the ERT are in development in addition to multiple different strategies of gene therapy to deliver GAA, the gene responsible for producing acid alpha-glucosidase, the defective protein in Pompe Disease. Glycogen substrate reduction is also in development in Pompe disease and other glycogen storage disorders.

              Summary

              There are significant unmet needs as it relates to clinical care and therapeutics in Pompe disease as well as in research. The currently available treatments lose effectiveness over the long run and do not have penetration into neuronal tissues and inconsistent penetration in certain muscles. More definitive gene therapy and enzyme replacement strategies are currently in development and testing.
                Cover page: Pompe Disease: a Clinical, Diagnostic, and Therapeutic Overview
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2022)
                GNE myopathy is an ultrarare muscle disease characterized by slowly progressive muscle weakness. Symptoms typically start in early adulthood, with weakness and atrophy in the tibialis anterior muscles and with slow progression over time, which largely spares the quadriceps muscles. Muscle biopsy shows atrophic fibers and rimmed vacuoles without inflammation. Inherited in an autosomal recessive manner, patients with GNE myopathy carry mutations in the GNE gene which affect the sialic acid synthesis pathway. Here, we look at the history and clinical aspects of GNE myopathy, as well as focus on prior treatment trials and challenges and unmet needs related to this disorder.
                  Cover page: GNE myopathy: History, etiology, and treatment trials
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2022)

                  Background

                  Proper evaluation of ocular fundi is an integral part of neurological examination. Unfortunately, neurology residents are increasingly uncomfortable performing fundoscopy and interpreting findings because of diminishing skills and lack of experience. This became more prominent during the COVID-19 pandemic as fundoscopy requires proximity to the patient. With the recent dramatic improvement of smartphone cameras, fundus photography using the PanOptic Ophthalmoscope (Welch Allyn, Skaneateles Falls, NY) with a smartphone adapter offered an alternative to direct fundoscopic examination. We present the first experience with our own design of a universal smartphone adapter.

                  Methods

                  This is a single-center case series, consecutive for a single user and certain presenting neurological symptoms, which is aimed to evaluate the feasibility and practicality of a new, universal PanOptic smartphone adapter. Presenting symptoms included headache, ocular symptoms, seizure, or encephalopathy. We used 3D modeling and printing techniques to create the adapter. We also developed a methodology of capturing stereoscopic images of the optic disc using a single smartphone camera, but the method was not systematically evaluated in this paper.

                  Results

                  Here we present our initial experience of fundus video/photography in patients, who presented with encephalopathy, headache, seizure, vision loss, and other ocular symptoms. Fundoscopic abnormalities were discovered in 11 out of 100 patients. Some were incidental findings and were unrelated to the presentation. In one case, fundoscopy played a critical role in establishing the correct diagnosis.

                  Conclusions

                  Our custom-designed smartphone adapter allowed obtaining high-quality video and photo recordings using PanOptic Ophthalmoscope. The acquisition of high-quality photos enables a high-yield diagnostic tool and allows revisiting the image in the patient's chart. Improvement of smartphone cameras opens vast horizons for stereo-fundoscopy and 3D reconstruction of the ocular fundus without using sophisticated and costly equipment. Microscopic eye movements allow taking snapshots of two side-by-side photos for 3D reconstruction and stereoscopic image viewing, which is the next level of optic disc assessment.
                    Cover page: Utility of video-fundoscopy and prospects of portable stereo-photography of the ocular fundus in neurological patients
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2015)
                    Polymyositis and dermatomyositis are inflammatory myopathies that differ in their clinical features, histopathology, response to treatment, and prognosis. Although their clinical pictures differ, they both present with symmetrical, proximal muscle weakness. Treatment relies mainly upon empirical use of corticosteroids and immunosuppressive agents. A deeper understanding of the molecular pathways that drive pathogenesis, careful phenotyping, and accurate disease classification will aid clinical research and development of more efficacious treatments. In this review we address the current knowledge of the epidemiology, clinical characteristics, diagnostic evaluation, classification, pathogenesis, treatment, and prognosis of polymyositis and dermatomyositis.
                      Cover page: An overview of polymyositis and dermatomyositis
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