Holli A Horak

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Scholarly Contributions

Books

• Horak, H. A. (2016). Practical Neurology, 5th Edition. Chapter 31: Lippincott.
• Horak, H. A., & Mandler, R. (2016). Practical Neurology, 5th Edition. Chapter 52: Lippincott.

Chapters

• Horak, H. A. (2017). Approach to the patient with acute muscle weakness. In Practical Neurology. Wolters Kluwer Health Pharma Solutions (Europe) Ltd.
• Horak, H. A., & Mandler, R. N. (2017). Myopathy. In Practical Neurology. Wolters Kluwer Health Pharma Solutions (Europe) Ltd.
• Tiryaki, E., & Horak, H. A. (2014).

  ALS and Other Motor Neuron Diseases

  . In ALS Handbook. doi:10.1212/01.con.0000455886.14298.a4
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• Horak, H. A. (2012). Approach to the patient with acute muscle weakness. In Practical Neurology. Wolters Kluwer Health Pharma Solutions (Europe) Ltd.
• Horak, H. A., & Mandler, R. N. (2012). Myopathy. In Practical Neurology. Wolters Kluwer Health Pharma Solutions (Europe) Ltd.

Journals/Publications

• Anandan, C., Horak, H., & Patel, K. (2025). Diabetic Neuropathies. Muscle & nerve, 72(Issue 6). doi:10.1002/mus.70015
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  Diabetic neuropathy is a frequent complication of diabetes, presenting with a wide range of symptoms. These include symmetric distal motor dysfunction, sensory abnormalities (including positive and negative sensory symptoms), radiculoplexus neuropathies, mononeuropathies, and autonomic dysfunction. The condition can manifest in various forms, each with distinct characteristics. There is now more understanding regarding the pathophysiology of diabetic neuropathies with regard to what makes sensory neurons more susceptible to injury and bioenergetic failure in peripheral nervous system neurons. This monograph provides an overview of the different types of diabetic neuropathy, addresses the management of more common forms associated with diabetes, and highlights recent updates in the field, including nutraceuticals.
• Howard, I. M., Horak, H., Weigert, B., & Narayanaswami, P. (2025). Gender Gap or Data Gap? How the AANEM Measures Up in Supporting Women. Muscle and Nerve, 72(Issue). doi:10.1002/mus.28429
• Ritter, J., Marco, T., Angeletti, M., Barnett, D., Horak, H., & Husnain, M. (2025). Autologous hematopoietic stem cell transplantation in severe, refractory stiff person syndrome: a case series. Bone Marrow Transplantation, 60(Issue 10). doi:10.1038/s41409-025-02686-z
• Roychaudhury, A., Lee, Y. R., Choi, T. I., Thomas, M. G., Khan, T. N., Yousaf, H., Skinner, C., Maconachie, G., Crosier, M., Horak, H., Constantinescu, C. S., Kim, T. Y., Lee, K. H., Kyung, J. J., Wang, T., Ku, B., Chodirker, B. N., Hammer, M. F., Gottlob, I., , Norton, W. H., et al. (2024). SRPK3 Is Essential for Cognitive and Ocular Development in Humans and Zebrafish, Explaining X-Linked Intellectual Disability. Annals of neurology, 96(5), 914-931.
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  Intellectual disability is often the outcome of neurodevelopmental disorders and is characterized by significant impairments in intellectual and adaptive functioning. X-linked intellectual disability (XLID) is a subset of these disorders caused by genetic defects on the X chromosome, affecting about 2 out of 1,000 males. In syndromic form, it leads to a broad range of cognitive, behavioral, ocular, and physical disabilities.
• Roychaudhury, A., Lee, Y., Choi, T., Thomas, M., Khan, T., Yousaf, H., Skinner, C., Maconachie, G., Crosier, M., Horak, H., Constantinescu, C., Kim, T., Lee, K., Kyung, J., Wang, T., Ku, B., Chodirker, B., Hammer, M., Gottlob, I., , Norton, W., et al. (2024). SRPK3 Is Essential for Cognitive and Ocular Development in Humans and Zebrafish, Explaining X-Linked Intellectual Disability. Annals of Neurology, 96(5). doi:10.1002/ana.27037
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  Objective: Intellectual disability is often the outcome of neurodevelopmental disorders and is characterized by significant impairments in intellectual and adaptive functioning. X-linked intellectual disability (XLID) is a subset of these disorders caused by genetic defects on the X chromosome, affecting about 2 out of 1,000 males. In syndromic form, it leads to a broad range of cognitive, behavioral, ocular, and physical disabilities. Methods: Employing exome or genome sequencing, here we identified 4 missense variants (c.475C > G; p.H159D, c.1373C > A; p.T458N, and c.1585G > A; p.E529K, c.953C > T; p.S318L) and a putative truncating variant (c.1413_1414del; p.Y471*) in the SRPK3 gene in 9 XLID patients from 5 unrelated families. To validate SRPK3 as a novel XLID gene, we established a knockout (KO) model of the SRPK3 orthologue in zebrafish. Results: The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Together, these data indicate a pathological role of SRPK3 in neurodevelopmental disorders. In post-fertilization day 5 larvae (free swimming stage), KO zebrafish exhibited severe deficits in eye movement and swim bladder inflation, mimicking uncontrolled ocular movement and physical clumsiness observed in human patients. In adult KO zebrafish, cerebellar agenesis and behavioral abnormalities were observed, recapitulating human phenotypes of cerebellar atrophy and intellectual disability. Interpretation: Overall, these results suggest a crucial role of SRPK3 in the pathogenesis of syndromic X-linked intellectual disability and provide new insights into brain development, cognitive and ocular dysfunction in both humans and zebrafish. ANN NEUROL 2024;96:914–931.
• Lee, Y. R., Thomas, M. G., Roychaudhury, A., Skinner, C., Maconachie, G., Crosier, M., Horak, H., Constantinescu, C. S., Choi, T. I., Kyung, J. J., Wang, T., Ku, B., Chodirker, B. N., Hammer, M. F., Gottlob, I., Norton, W. H., Chudley, A. E., Schwartz, C. E., & Kim, C. H. (2023). Eye movement defects in KO zebrafish reveals as a causative gene for an X-linked intellectual disability. Research square.
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  Intellectual disability (ID) is a common neurodevelopmental disorder characterized by significantly impaired intellectual and adaptive functioning. X-linked ID (XLID) disorders, caused by defects in genes on the X chromosome, affect 1.7 out of 1,000 males. Employing exome sequencing, we identified three missense mutations (c.475C>G; p.H159D, c.1373C>A; p.T458N, and c.1585G>A; p.E529K) in the gene in seven XLID patients from three independent families. Clinical features common to the patients are intellectual disability, agenesis of the corpus callosum, abnormal smooth pursuit eye movement, and ataxia. SRPK proteins are known to be involved in mRNA processing and, recently, synaptic vesicle and neurotransmitter release. In order to validate as a novel XLID gene, we established a knockout (KO) model of the orthologue in zebrafish. In day 5 of larval stage, KO zebrafish showed significant defects in spontaneous eye movement and swim bladder inflation. In adult KO zebrafish, we found agenesis of cerebellar structures and impairments in social interaction. These results suggest an important role of in eye movements, which might reflect learning problems, intellectual disability, and other psychiatric disorders.
• Patel, K., & Horak, H. A. (2021). Electrodiagnosis of Common Mononeuropathies: Median, Ulnar, and Fibular (Peroneal) Neuropathies.. Neurologic clinics, 39(4), 939-955. doi:10.1016/j.ncl.2021.06.004
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  This article addresses common mononeuropathies seen in the electrodiagnostic laboratory. The most common mononeuropathies-median neuropathy at the wrist (carpal tunnel syndrome), ulnar neuropathy at the elbow, and fibular (peroneal) neuropathy at the fibular head-are reviewed. The causes, clinical presentations, approached to the electrodiagnostic studies (including nerve conduction studies and needle electromyography), and the typical findings are discussed.
• Horak, H. A., Johnston, C. B., Scherer, K., Ibarra, B., Shane, B., Mortel, D., Barcelo, B., & Yogendran, L. (2020). When the Timing is Right: Is There an Association Between Willingness to Discuss Palliative Care and the Severity of ALS? (2788). Neurology.
• Horak, H., Patel, K., & Tiryaki, E. (2020). Diabetic neuropathies. Muscle & Nerve, 63(1), 22-30. doi:10.1002/mus.27014
• Johnston, C. B., Horak, H. A., Scherer, K., Ibarra, B., Shane, B., Mortel, M. D., Barcelo, B., & Yogendran, L. (2020). Identifying Important Palliative Topics and Communication Preferences Among ALS Patients (QI618). Journal of Pain and Symptom Management. doi:10.1016/j.jpainsymman.2019.12.227
• Horak, H. A. (2018). Entrustable Professional Activities. Neurology, 90(7), 326-332. doi:10.1212/WNL.0000000000004947
• Horak, H. A., Tiryaki, E., Soni, M., Kraakevik, J. A., Barratt, D., & Englander, R. (2018). Entrustable professional activities. Neurology. doi:10.1212/wnl.0000000000004947
• Horak, H. A., & Tiryaki, E. (2014). ALS and Other Motor Neuron Diseases. Continuum. doi:10.1212/01.con.0000455886.14298.a4
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  This review describes the most common motor neuron disease, ALS. It discusses the diagnosis and evaluation of ALS and the current understanding of its pathophysiology, including new genetic underpinnings of the disease. This article also covers other motor neuron diseases, reviews how to distinguish them from ALS, and discusses their pathophysiology.In this article, the spectrum of cognitive involvement in ALS, new concepts about protein synthesis pathology in the etiology of ALS, and new genetic associations will be covered. This concept has changed over the past 3 to 4 years with the discovery of new genes and genetic processes that may trigger the disease. As of 2014, two-thirds of familial ALS and 10% of sporadic ALS can be explained by genetics. TAR DNA binding protein 43 kDa (TDP-43), for instance, has been shown to cause frontotemporal dementia as well as some cases of familial ALS, and is associated with frontotemporal dysfunction in ALS.The anterior horn cells control all voluntary movement: motor activity, respiratory, speech, and swallowing functions are dependent upon signals from the anterior horn cells. Diseases that damage the anterior horn cells, therefore, have a profound impact. Symptoms of anterior horn cell loss (weakness, falling, choking) lead patients to seek medical attention. Neurologists are the most likely practitioners to recognize and diagnose damage or loss of anterior horn cells. ALS, the prototypical motor neuron disease, demonstrates the impact of this class of disorders. ALS and other motor neuron diseases can represent diagnostic challenges. Neurologists are often called upon to serve as a "medical home" for these patients: coordinating care, arranging for durable medical equipment, and leading discussions about end-of-life care with patients and caregivers. It is important for neurologists to be able to identify motor neuron diseases and to evaluate and treat patients affected by them.
• Merlin, L. R., Horak, H. A., Milligan, T. A., Kraakevik, J. A., & Ali, I. I. (2014). A competency-based longitudinal core curriculum in medical neuroscience. Neurology, 83(5), 456-62.
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  Current medical educational theory encourages the development of competency-based curricula. The Accreditation Council for Graduate Medical Education's 6 core competencies for resident education (medical knowledge, patient care, professionalism, interpersonal and communication skills, practice-based learning, and systems-based practice) have been embraced by medical schools as the building blocks necessary for becoming a competent licensed physician. Many medical schools are therefore changing their educational approach to an integrated model in which students demonstrate incremental acquisition and mastery of all competencies as they progress through medical school. Challenges to medical schools include integration of preclinical and clinical studies as well as development of learning objectives and assessment measures for each competency. The Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN) assembled a group of neuroscience educators to outline a longitudinal competency-based curriculum in medical neuroscience encompassing both preclinical and clinical coursework. In development of this curriculum, the committee reviewed United States Medical Licensing Examination content outlines, Liaison Committee on Medical Education requirements, prior AAN-mandated core curricula for basic neuroscience and clinical neurology, and survey responses from educators in US medical schools. The newly recommended curriculum provides an outline of learning objectives for each of the 6 competencies, listing each learning objective in active terms. Documentation of experiences is emphasized, and assessment measures are suggested to demonstrate adequate achievement in each competency. These guidelines, widely vetted and approved by the UES membership, aspire to be both useful as a stand-alone curriculum and also provide a framework for neuroscience educators who wish to develop a more detailed focus in certain areas of study.
• Tiryaki, E., & Horak, H. A. (2014). ALS and other motor neuron diseases. Continuum (Minneapolis, Minn.), 20(5 Peripheral Nervous System Disorders), 1185-207.
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  This review describes the most common motor neuron disease, ALS. It discusses the diagnosis and evaluation of ALS and the current understanding of its pathophysiology, including new genetic underpinnings of the disease. This article also covers other motor neuron diseases, reviews how to distinguish them from ALS, and discusses their pathophysiology.
• Foroud, T., Pankratz, N., Batchman, A. P., Pauciulo, M. W., Vidal, R., Miravalle, L., Goebel, H. H., Cushman, L. J., Azzarelli, B., Horak, H., Farlow, M., & Nichols, W. C. (2005). A mutation in myotilin causes spheroid body myopathy. Neurology, 65(Issue 12). doi:10.1212/01.wnl.0000188872.28149.9a
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  BACKGROUND: Spheroid body myopathy (SBM) is a rare, autosomal dominant, neuromuscular disorder, which has only been previously reported in a single large kindred. Identification of the mutated gene in this disorder may provide insight regarding abnormal neuromuscular function. METHODS: The authors completed a detailed clinical evaluation on an extensive kindred diagnosed with SBM. Genome-wide linkage analysis was performed to localize the disease gene to a specific chromosomal region. Further marker genotyping and screening of a positional, functional candidate gene were completed to detect the disease-causing mutation. Pathologic analysis of muscle biopsy was performed on three individuals. Biochemical studies were performed on one muscle biopsy specimen from an affected individual. RESULTS: Linkage to chromosome 5q23-5q31 was detected with a lod score of 2.9. Genotyping of additional markers in a larger sample of family members produced a maximum lod score of 6.1 and narrowed the critical interval to 12.2 cM. Screening of the candidate gene titin immunoglobulin domain protein (TTID, also known as MYOT) detected a cytosine-to-thymine mutation in exon 2 of all clinically affected family members. Similar pathologic changes were present in all muscle biopsy specimens. Immunohistologic and biochemical analysis revealed that the TTID protein, also known as myotilin, is a component of the insoluble protein aggregate. CONCLUSIONS: A novel mutation in the TTID gene results in the clinical and pathologic phenotype termed "spheroid body myopathy." Mutations in this gene also cause limb-girdle muscular dystrophy 1A and are associated with myofibrillar myopathy. Copyright © 2005 by AAN Enterprises, Inc.
• Horak, H. A., & Pourmand, R. (2000). Endocrine myopathies. Neurologic Clinics, 18(Issue 1). doi:10.1016/s0733-8619(05)70186-9
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  As discussed, endocrine disorders of all types can cause muscle disease, ranging from complaints of cramps and aches to tetraparesis. The muscle illness may be the initial manifestation, such as in thyrotoxic periodic paralysis, or the primary complaint, such as weakness in Cushing's disease. The muscle complaints may be nonspecific (aching and cramps in hypothyroidism) or very specific (thyroid ophthalmopathy). Each endocrinologic disorder tends to produce a certain pattern of muscle dysfunction, but clinical presentations vary. When evaluating a patient with a known endocrine disturbance, one should examine carefully for weakness. Inversely, when examining someone with a presentation of muscle weakness, cramps, or atrophy, a thorough review of systems for endocrinopathies is warranted. Screening for thyroid disease is easily done with TSH and T4 levels. A calcium level in a patient with a history of renal failure will assist in elucidating a parathyroid disturbance. Cushing's disease has an obvious phenotype; when indicated, check for an elevated serum ACTH level to confirm the condition. Any patient taking steroids chronically may develop a steroid myopathy, so new onset (or increased) weakness or fatigue in a steroid-dependent individual should justify an evaluation for steroid myopathy. Replacement of the appropriate hormone (or removing the excessive hormone) usually results in resolution of symptoms. Some of the effects of the diseases may be irreversible, or may be only partially reversible. Hyperparathyroidism, in addition to causing muscle cramps and fatigue, is implicated by some authors as possibly leading to, or causing, motor neuron disease. Steroid myopathy may cause diagnostic confusion because of overlap with underlying muscle disease. The most common muscle manifestations associated with hormonal disturbances are fatigue, appreciable muscle weakness, cramping, and atrophy.
• Pema, P., Horak, H., & Wyatt, R. (1998). Myelopathy caused by nitrous oxide toxicity. American Journal of Neuroradiology, 19(5).
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  We describe a case of myeloneuropathy resulting from nitrous oxide abuse. MR imaging of the spine revealed symmetric abnormal signal in the posterior columns of the cervical cord. Myeloneuropathy is caused by inactivation of vitamin B12 by nitrous oxide. This syndrome can also be seen in patients with borderline vitamin B12 deficiency who have recently been anesthetized with nitrous oxide.

Presentations

• Meka, J., Ditillo, M., Horak, H. A., & Corral, J. (2021, April). Workplace-Based Assessment in Clinical Education: An Adoption Cycle of Experience. AAMC GEA 2021. Virtual: AAMC.
• Horak, H. A. (2015, April). CNCD Directors Workshop. AAN Annual Meeting.

Poster Presentations

• Arumaithurai, K., Kapoor, A., Horak, H. A., Scherer, K., Arumaithurai, K., Kapoor, A., Horak, H. A., Scherer, K., Arumaithurai, K., Kapoor, A., Horak, H. A., Scherer, K., Arumaithurai, K., Kapoor, A., Horak, H. A., Scherer, K., Arumaithurai, K., Kapoor, A., Horak, H. A., & Scherer, K. (2014, October). Celiac Disease: Neurological Manifestations in 2 undiagnosed patients. AANEM Annual Meeting. Savannah, Georgia: AANEM.

Other Teaching Materials

• Horak, H. A., & Tiryaki, E. (2016. AAN EMG workshop. American Academy of Neurology.
• Horak, H. A., & Tiryaki, E. (2016. Living with ALS Resource Guide. ALS Association.
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  Manual Written by ALS physicians/ care providers for patients living with ALS and their caregivers. Edited and reviewed for content.