Bio


Dr. Miglis is a Clinical Associate Professor in the departments of Neurology and Neurological Sciences and Psychiatry and Behavioral Sciences. He received his MD from the University of Florida. After serving as a medical intern at Washington Hospital Center/Georgetown University, he completed his neurology residency at New York University. He then completed two fellowships, the first in Autonomic Disorders at the Beth Israel Deaconess Medical Center of Harvard Medical school, and the second in Sleep Medicine at the Stanford Sleep Medicine Center. He is director of the Stanford Multiple System Atrophy Center of Excellence and the Stanford Parasomnia Sleep Disorders Clinic, and is extensively involved in the multidisciplinary Stanford Post-Acute COVID Syndrome (PACS) clinic.

Dr. Miglis treats a wide variety of neurological diseases and has a special interest in Autonomic Disorders, Sleep Disorders, and the interaction between these conditions. His research efforts are currently focused on mechanisms of autonomic dysfunction in Long-COVID/PASC and the central nervous system hypersomnias, in particular Idiopathic Hypersomnia. He is also site principle investigator of the North American Prodromal Synucleinopathy Study and has several ongoing studies evaluating skin biopsy and autonomic testing as markers of disease progression in isolated REM sleep behavior disorder.

Clinical Focus


  • Autonomic Disorders
  • Sleep Medicine
  • Clinical Neurophysiology

Academic Appointments


Boards, Advisory Committees, Professional Organizations


  • Advisory Board Member, Mission MSA (2021 - Present)
  • Vice-Chair, Autonomic Section, American Academy of Neurology (2022 - Present)
  • Member, NIH RECOVER Long COVID Executive Committee (2022 - Present)
  • Editorial Board, Clinical Autonomic Research (2021 - Present)
  • Member, CDC Long-COVID Interim Guidance Committee (2021 - Present)
  • Advisory Board Member, Dysautonomia International (2021 - Present)
  • Member, American Academy of Neurology Sleep Medicine Educational Committee (2018 - Present)
  • Member, NIH POTS Task Force (2019 - Present)
  • Member, International REM Sleep Behavior Study Group (2018 - Present)

Professional Education


  • Board Certification: American Board of Psychiatry and Neurology, Sleep Medicine (2013)
  • Board Certification: American Board of Psychiatry and Neurology, Neurology (2011)
  • Fellowship, Stanford University Medical Center, Sleep Medicine (2013)
  • Fellowship, Beth Israel Deaconess Medical Center/Harvard Medical School, Autonomic Disorders and Clinical Neurophysiology (2012)
  • Residency, New York University, Neurology (2011)
  • Internship, Washington Hospital Center/Georgetown University (2008)
  • Medical Education: University of Florida College of Medicine (2007) FL

Current Research and Scholarly Interests


Prodromal markers of neurodegeneration in REM sleep behavior disorder
Autonomic dysfunction in Long-COVID
Postural tachycardia syndrome

Clinical Trials


  • Natural History Study of Synucleinopathies Recruiting

    Synucleinopathies are a group of rare diseases associated with worsening neurological deficits and the abnormal accumulation of the protein α-synuclein in the nervous system. Onset is usually in late adulthood at age 50 or older. Usually, synucleinopathies present clinically with slowness of movement, coordination difficulties or mild cognitive impairment. Development of these features indicates that abnormal alpha-synuclein deposits have destroyed key areas of the brain involved in the control of movement or cognition. Patients with synucleinopathies and signs of CNS-deficits are frequently diagnosed with Parkinson disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA). However, accumulation of alpha-synuclein and death of nerve cells can also begin outside the brain in the autonomic nerves. In such cases, syncucleinopathies present first with symptoms of autonomic impairment (unexplained constipation, urinary difficulties, and sexual dysfunction). In rare cases, hypotension on standing (a disorder known as orthostatic hypotension) may be the only clinical finding. This "pre-motor" autonomic stage suggests that the disease process may not yet have spread to the brain. After a variable period of time, but usually within 5-years, most patients with abnormally low blood pressure on standing develop cognitive or motor abnormalities. This stepwise evolution indicates that the disease spreads from the body to the brain. Another indication of this spread is that acting out dreams (i.e., REM sleep behavior disorder, RBD) a problem that occurs when the lower part of the brain is affected, may also be the first noticeable sign of Parkinson disease. The purpose of this study is to document the clinical features and biological markers of patients with synucleinopathies and better understand how these disorders evolve over time. The study will involve following patients diagnosed with a synucleinopathy (PD/DLB and MSA) and those believed to be in the "pre-motor" stage (with isolated autonomic impairment and/or RBD). Through a careful series of follow-up visits to participating Centers, we will focus on finding biological clues that predict which patients will develop motor/cognitive problems and which ones have the resilience to keep the disease at bay preventing spread to the brain. We will also define the natural history of MSA - the most aggressive of the synucleinopathies.

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  • A Novel Noninvasive Thermoregulatory Device for Postural Tachycardia Syndrome Not Recruiting

    The investigators hope to learn the feasibility and preliminary efficacy of the Embr device for improving thermal comfort in individuals with POTS and impaired thermoregulation. Feasibility will be assessed via usage of the Embr device and participant feedback. Preliminary efficacy measures will include temperature-related symptoms and temperature- related quality of life in individuals with POTS and impaired thermoregulation.

    Stanford is currently not accepting patients for this trial.

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All Publications


  • IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study. Neurology(R) neuroimmunology & neuroinflammation Postuma, R., Vorasoot, N., St Louis, E. K., Pelletier, A., Lim, M. M., Elliott, J., Gagnon, J. F., Gan-Or, Z., Forsberg, L. K., Fields, J. A., Ross, O. A., Singer, W., Huddleston, D. E., Bliwise, D. L., Avidan, A. Y., Howell, M., Schenck, C. H., McLeland, J., Davis, A. A., Criswell, S. R., Videnovic, A., During, E. H., Miglis, M. G., Boeve, B. F., Ju, Y. S., McKeon, A. 2024; 11 (6): e200311

    Abstract

    Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5.Of 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease.Our finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings.NCT03623672.

    View details for DOI 10.1212/NXI.0000000000200311

    View details for PubMedID 39270144

  • Intrasubject reproducibility of supine norepinephrine plasma concentrations in patients with cardiovascular sympathetic failure. Autonomic neuroscience : basic & clinical Carrozzo, G., Miglis, M. G., Contin, M., Cani, I., Cortelli, P., Guaraldi, P., Calandra-Buonaura, G. 2024; 256: 103216

    Abstract

    BACKGROUND: Plasma levels of the catecholamine norepinephrine (NE) has emerged as a useful tool to help differentiate pre- and post-ganglionic disorders in patients with cardiovascular autonomic failure (AF). However, data on intrasubject reliability in individuals with these conditions are limited. We evaluated the intrasubject reproducibility of supine plasma NE levels drawn across two consecutive time points under controlled conditions during head-up table testing in a large cohort of patients with alpha-synucleinopathies and both pre- and post-ganglionic cardiovascular AF.METHODS: Antecubital venous blood drawn via an indwelling cannula with the subject supine was assayed for plasma level of catecholamines. We collected two consecutive samples, the first after 20min of supine rest (NE1) and the second 5min later (NE2), from a group of 279 participants including 57 with Parkinson's disease/Lewy body dementia (44 M; 65.5±11.1y), 131 with multiple system atrophy (81 M; 63.2±8.5y), 41 with pure autonomic failure (25 M, 65.1±9.3y), and 50 healthy controls (27 M; 46.7±19.4y).RESULTS: We found no difference between NE1 and NE2 (p=0.645), with a mean intrasubject reproducibility (NE maximum-NE minimum)*100/NE maximum) of 11.5%±10.64. This finding was confirmed when controlling for diagnosis (p=0.669), gender (p=0.493), age (p=0.865), disease duration (p=0.596) or considering all factors together (p=0.527).CONCLUSIONS: We found excellent test-retest reliability of consecutive supine NE measurements in patients with alpha-synucleinopathies and cardiovascular AF, independent of age, gender and disease duration. This lends evidence to support the use of a single supine NE measurement in these conditions.

    View details for DOI 10.1016/j.autneu.2024.103216

    View details for PubMedID 39260098

  • Cognitive, motor, and autonomic function among individuals with serotonergic versus isolated REM sleep behavior disorder. Sleep Reddy, N. V., Berns, M., Berns, R., Olson, H., Cui, E., Miglis, M. G., Postuma, R., Boeve, B., Ju, Y. E., Howell, M. 2024

    View details for DOI 10.1093/sleep/zsae192

    View details for PubMedID 39158284

  • Nirmatrelvir-Ritonavir and Symptoms in Adults With Postacute Sequelae of SARS-CoV-2 Infection: The STOP-PASC Randomized Clinical Trial. JAMA internal medicine Geng, L. N., Bonilla, H., Hedlin, H., Jacobson, K. B., Tian, L., Jagannathan, P., Yang, P. C., Subramanian, A. K., Liang, J. W., Shen, S., Deng, Y., Shaw, B. J., Botzheim, B., Desai, M., Pathak, D., Jazayeri, Y., Thai, D., O'Donnell, A., Mohaptra, S., Leang, Z., Reynolds, G. Z., Brooks, E. F., Bhatt, A. S., Shafer, R. W., Miglis, M. G., Quach, T., Tiwari, A., Banerjee, A., Lopez, R. N., De Jesus, M., Charnas, L. R., Utz, P. J., Singh, U. 2024

    Abstract

    There is an urgent need to identify treatments for postacute sequelae of SARS-CoV-2 infection (PASC).To assess the efficacy of a 15-day course of nirmatrelvir-ritonavir in reducing the severity of select PASC symptoms.This was a 15-week blinded, placebo-controlled, randomized clinical trial conducted from November 2022 to September 2023 at Stanford University (California). The participants were adults with moderate to severe PASC symptoms of 3 months or longer duration.Participants were randomized 2:1 to treatment with oral nirmatrelvir-ritonavir (NMV/r, 300 mg and 100 mg) or with placebo-ritonavir (PBO/r) twice daily for 15 days.Primary outcome was a pooled severity of 6 PASC symptoms (fatigue, brain fog, shortness of breath, body aches, gastrointestinal symptoms, and cardiovascular symptoms) based on a Likert scale score at 10 weeks. Secondary outcomes included symptom severity at different time points, symptom burden and relief, patient global measures, Patient-Reported Outcomes Measurement Information System (PROMIS) measures, orthostatic vital signs, and sit-to-stand test change from baseline.Of the 155 participants (median [IQR] age, 43 [34-54] years; 92 [59%] females), 102 were randomized to the NMV/r group and 53 to the PBO/r group. Nearly all participants (n = 153) had received the primary series for COVID-19 vaccination. Mean (SD) time between index SARS-CoV-2 infection and randomization was 17.5 (9.1) months. There was no statistically significant difference in the model-derived severity outcome pooled across the 6 core symptoms at 10 weeks between the NMV/r and PBO/r groups. No statistically significant between-group differences were found at 10 weeks in the Patient Global Impression of Severity or Patient Global Impression of Change scores, summative symptom scores, and change from baseline to 10 weeks in PROMIS fatigue, dyspnea, cognitive function, and physical function measures. Adverse event rates were similar in NMV/r and PBO/r groups and mostly of low grade.The results of this randomized clinical trial showed that a 15-day course of NMV/r in a population of patients with PASC was generally safe but did not demonstrate a significant benefit for improving select PASC symptoms in a mostly vaccinated cohort with protracted symptom duration. Further studies are needed to determine the role of antivirals in the treatment of PASC.ClinicalTrials.gov Identifier: NCT05576662.

    View details for DOI 10.1001/jamainternmed.2024.2007

    View details for PubMedID 38848477

  • Is it time to move beyond blood pressure and heart rate during head-up tilt testing? Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Syed, N., Cortez, M. M., Viser, F. C., van Campen, C. L., Novak, P. 2024

    View details for DOI 10.1007/s10286-024-01036-1

    View details for PubMedID 38755465

    View details for PubMedCentralID 1514613

  • Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients With Synucleinopathies. JAMA Gibbons, C. H., Levine, T., Adler, C., Bellaire, B., Wang, N., Stohl, J., Agarwal, P., Aldridge, G. M., Barboi, A., Evidente, V. G., Galasko, D., Geschwind, M. D., Gonzalez-Duarte, A., Gil, R., Gudesblatt, M., Isaacson, S. H., Kaufmann, H., Khemani, P., Kumar, R., Lamotte, G., Liu, A. J., McFarland, N. R., Miglis, M., Reynolds, A., Sahagian, G. A., Saint-Hillaire, M. H., Schwartzbard, J. B., Singer, W., Soileau, M. J., Vernino, S., Yerstein, O., Freeman, R. 2024

    Abstract

    Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies.To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF.This blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis.Skin biopsy for detection of phosphorylated α-synuclein.Rates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy.Of 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected.In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.

    View details for DOI 10.1001/jama.2024.0792

    View details for PubMedID 38506839

  • Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study. Brain : a journal of neurology Millar Vernetti, P., Norcliffe-Kaufmann, L., Palma, J. A., Biaggioni, I., Shibao, C. A., Peltier, A., Freeman, R., Gibbons, C., Goldstein, D. S., Low, P. A., Singer, W., Coon, E. A., Miglis, M. G., Wenning, G. K., Fanciulli, A., Vernino, S., Betensky, R. A., Kaufmann, H. 2024

    Abstract

    We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at 8 Centers (7-US based and 1 European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive, and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson disease (PD), dementia with Lewy bodies (DLB), or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3-10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB, and 23% to MSA). Faster phenoconversion from study enrollment to any diagnosis was associated with urinary and sexual dysfunction [HR 5.9, 95%CI: 1.6-22, and HR: 3.6, 95%CI: 1.1-12] followed by subtle motor signs [HR: 2.7, 95%CI: 1.2-6], trouble swallowing [HR 2.5, 95%CI: 1.4-4.5], and changes in speech [HR:2.4, 95%CI:1.1-4.8] at enrollment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95%CI: 1.1-5.9, ) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95%CI: 1.2-38). Patients with a younger age of PAF onset [HR: 11, 95%CI: 2.6-46], preserved olfaction [HR: 8.7, 95%CI: 1.7-45], anhidrosis [HR: 1.8, 95%CI: 1-3.1, p=0.042], and severe urinary problems [HR 1.6, 95%CI: 1-2.5, p=0.033] were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95%CI: 1.4-26). Patients with PAF have an estimated 12% (95% CI: 9%-15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.

    View details for DOI 10.1093/brain/awae033

    View details for PubMedID 38366572

  • Validation of the RBD Symptom Severity Scale in the North American Prodromal Synucleinopathy Consortium. Neurology Choudhury, P., Lee-Iannotti, J. K., Busicescu, A. O., Rangan, P., Fantini, M. L., Avidan, A. Y., Bliwise, D. L., Criswell, S. R., During, E. H., Elliott, J. E., Fields, J. A., Gagnon, J. F., Howell, M. J., Huddleston, D. E., McLeland, J., Mignot, E., Miglis, M. G., Lim, M. M., Pelletier, A., Schenck, C. H., Shprecher, D., St Louis, E. K., Videnovic, A., Ju, Y. S., Boeve, B. F., Postuma, R. 2024; 102 (3): e208008

    Abstract

    REM sleep behavior disorder (RBD) is a parasomnia characterized by dream enactment. The International RBD Study Group developed the RBD Symptom Severity Scale (RBDSSS) to assess symptom severity for clinical or research use. We assessed the psychometric and clinimetric properties of the RBDSSS in participants enrolled in the North American Prodromal Synucleinopathy (NAPS) Consortium for RBD.NAPS participants, who have polysomnogram-confirmed RBD, and their bedpartners completed the RBDSSS (participant and bedpartner versions). The RBDSSS contains 8 questions to assess the frequency and severity/impact of (1) dream content, (2) vocalizations, (3) movements, and (4) injuries associated with RBD. Total scores for participant (maximum score = 54) and bedpartner (maximum score = 38) questionnaires were derived by multiplying frequency and severity scores for each question. The Clinical Global Impression Scale of Severity (CGI-S) and RBD symptom frequency were assessed by a physician during a semistructured clinical interview with participants and, if available, bedpartners. Descriptive analyses, correlations between overall scores, and subitems were assessed, and item response analysis was performed to determine the scale's validity.Among 261 study participants, the median (interquartile range) score for the RBDSSS-PT (participant) was 10 (4-18) and that for the RBDSSS-BP (bedpartner) was 8 (4-15). The median CGI-S was 3 (3-4), indicating moderate severity. RBDSSS-BP scores were significantly lower in women with RBD (6 vs 9, p = 0.02), while there were no sex differences in RBDSSS-PT scores (8 vs 10.5, p = 0.615). Positive correlations were found between RBDSSS-PT vs RBDSSS-BP (Spearman rs = 0.561), RBDSSS-PT vs CGI-S (rs = 0.556), and RBDSSS-BP vs CGI-S (rs = 0.491, all p < 0.0001). Item response analysis showed a high discriminatory value (range 1.40-2.12) for the RBDSSS-PT and RBDSSS-BP (1.29-3.47).We describe the RBDSSS with adequate psychometric and clinimetric properties to quantify RBD symptom severity and good concordance between participant and bedpartner questionnaires and between RBDSSS scores and clinician-assessed global severity.

    View details for DOI 10.1212/WNL.0000000000208008

    View details for PubMedID 38181331

  • Comorbid neurotrauma increases neurodegenerative-relevant cognitive, motor, and autonomic dysfunction in patients with REM sleep behavior disorder: A substudy of the North American Prodromal Synucleinopathy Consortium. Sleep Elliott, J. E., Ligman, B. R., Bryant-Ekstrand, M. D., Keil, A. T., Powers, K., Olivo, C., Neilson, L., Postuma, R. B., Pelletier, A., Gagnon, J. F., Gan-Or, Z., Yu, E., Liu, L., St Louis, E. K., Forsberg, L. K., Fields, J. A., Ross, O. A., Huddleston, D. E., Bliwise, D. L., Avidan, A. Y., Howell, M. J., Schenck, C. H., McLeland, J., Criswell, S. R., Videnovic, A., During, E. H., Miglis, M. G., Shprecher, D. R., Lee-Iannotti, J. K., Boeve, B. F., Ju, Y. S., Lim, M. M. 2024

    Abstract

    Rapid eye movement (REM) sleep behavior disorder (RBD) is strongly associated with phenoconversion to an overt synucleinopathy, e.g., Parkinson's disease (PD), Lewy Body Dementia (LBD), and related disorders. Comorbid traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) - henceforth "neurotrauma" (NT) - increase the odds of RBD by ~2.5-fold and is associated with an increased rate of service-connected PD in Veterans. Thus, RBD and NT are both independently associated with PD; however, it is unclear how NT influences neurological function in patients with RBD.Participants ≥18 years with overnight-polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 through the North American Prodromal Synucleinopathy (NAPS) Consortium. Standardized assessments for RBD, TBI, and PTSD history, as well as cognitive, motor, sensory and autonomic function were completed. This cross-sectional analysis compared cases (n=24; RBD+NT) to controls (n=96; RBD), matched for age (~60 years), sex (15% female), and years of education (~15 years).RBD+NT reported earlier RBD symptom onset (37.5±11.9 vs. 52.2±15.1 years of age) and a more severe RBD phenotype. Similarly, RBD+NT reported more severe anxiety and depression, greater frequency of hypertension, and significantly worse cognitive, motor, and autonomic function compared to RBD. No differences in olfaction or color vision were observed.This cross-sectional, matched case:control study shows individuals with RBD+NT have significantly worse neurological measures related to common features of an overt synucleinopathy. Confirmatory longitudinal studies are ongoing; however, these results suggest RBD+NT may be associated with more advanced neurological symptoms related to an evolving neurodegenerative process.

    View details for DOI 10.1093/sleep/zsae007

    View details for PubMedID 38181205

  • New Alcohol Sensitivity in Patients With Post-acute Sequelae of SARS-CoV-2 (PASC): A Case Series. Cureus Eastin, E. F., Tiwari, A., Quach, T. C., Bonilla, H. F., Miglis, M. G., Yang, P. C., Geng, L. N. 2023; 15 (12): e51286

    Abstract

    Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, is characterized by persistent symptoms after acute SARS-CoV-2 infection that can vary from patient to patient. Here, we present a case series of four patients with a history of SARS-CoV-2 infection referred to the Post-Acute COVID-19 Syndrome (PACS) Clinic at Stanford University for evaluation of persistent symptoms, who also experienced new-onset alcohol sensitivity. Alcohol reactions and sensitivity are not well characterized in the literature as it relates to post-viral illness. While there have been some anecdotal reports of new alcohol sensitivity in PASC patients in the media, there is a paucity of published data in the medical literature about this topic. During their medical consultation, the patients self-reported new changes in their symptoms or behaviors following the use of alcohol. A new onset of alcohol sensitivities should be assessed along with other post-COVID-19 symptoms and may provide novel avenues to explore the pathobiology of illness and potential interventions.

    View details for DOI 10.7759/cureus.51286

    View details for PubMedID 38288178

    View details for PubMedCentralID PMC10823305

  • Prospective association of occupational and leisure-time physical activity with orthostatic blood pressure changes in older adults SCIENTIFIC REPORTS Kujawska, A., Kujawski, S., Dani, M., Miglis, M. G., Hallman, D. M., Fudim, M., Soysal, P., Husejko, J., Hajec, W., Skierkowska-Kruszynska, N., Kwiatkowska, M., Newton, J. L., Zalewski, P., Kedziora-Kornatowska, K. 2023; 13 (1)
  • Prospective association of occupational and leisure-time physical activity with orthostatic blood pressure changes in older adults. Scientific reports Kujawska, A., Kujawski, S., Dani, M., Miglis, M. G., Hallman, D. M., Fudim, M., Soysal, P., Husejko, J., Hajec, W., Skierkowska-Kruszyńska, N., Kwiatkowska, M., Newton, J. L., Zalewski, P., Kędziora-Kornatowska, K. 2023; 13 (1): 20704

    Abstract

    Orthostatic hypotension (OH) is common in older people. We examined the influence of self-reported occupational-related physical activity (PA) and leisure-time physical exercise (PE) on orthostatic response in a sample of older people over a 2 year period. Supine and orthostatic systolic blood pressure (sBP), diastolic blood pressure (dBP), and mean blood pressure (mBP) were assessed in response to Active Stand (AS) test in 205 older subjects (> 60 years old) at baseline and 2-year follow-up. OH was found in 24 subjects (11.71%) at baseline and 20 subjects (9.76%) after 2 years, with a significant degree of variability in the occurrence of OH after 2 years. Twenty-two subjects who had OH at baseline were free of it after 2 years, two subjects had persistent OH at baseline and after 2 years. After 2 years, adults with occupational PA showed no significant decrease of blood pressure in response to AS test, while lack of undertaking an occupation-related PA was significantly related with a greater decrease in sBP and mBP in response to AS testing in the 1st min. Occupation-related PA and leisure-time-related PE were related to an increase in the response of BP on AS in change between baseline and after 2 years. High between-subjects variance in OH over 2 years was noted. Occupations that involved continuous physical activity and leisure-time physical exercise in middle age were both protective for BP decline on orthostatic stress test within 2 years.

    View details for DOI 10.1038/s41598-023-46947-7

    View details for PubMedID 38001151

    View details for PubMedCentralID 4849675

  • Frequency of Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder: The North American Prodromal Synucleinopathy Cohort. Neurology Elliott, J., Bryant-Ekstrand, M. D., Keil, A. T., Ligman, B. R., Lim, M. M., Zitser, J., During, E. H., Gagnon, J. F., St Louis, E. K., Fields, J. A., Huddleston, D. E., Bliwise, D. L., Avidan, A. Y., Schenck, C. H., McLeland, J., Criswell, S. R., Davis, A. A., Videnovic, A., Lee-Iannotti, J. K., Postuma, R., Boeve, B. F., Ju, Y. E., Miglis, M. G. 2023

    Abstract

    Although orthostatic hypotension (OH) can be an early feature of autonomic dysfunction in isolated rapid eye movement sleep behavior disorder (iRBD), no large-scale studies have examined the frequency of OH in iRBD. In this study we prospectively evaluated the frequency of OH in a large multicenter iRBD cohort.Participants ≥18 years of age with video polysomnogram-confirmed iRBD were enrolled through the North American Prodromal Synucleinopathy consortium. All participants underwent 3-minute orthostatic stand testing to assess the frequency of OH, and a Δ heart rate/Δ systolic blood pressure (ΔHR/ΔSBP) ratio <0.5 was used to define reduced HR augmentation, suggestive of neurogenic OH. All participants completed a battery of assessments including the Scales for Outcomes in Parkinson's Disease-Autonomic Dysfunction (SCOPA-AUT) and others assessing cognitive, motor, psychiatric and sensory domains.Of 340 iRBD participants (65±10 yrs., 82% male), 93 (27%) met criteria for OH (ΔHR/ΔSBP 0.37±0.28; range: 0.0-1.57) and of these, 72 (77%) met criteria for OH with reduced HR augmentation (ΔHR/ΔSBP 0.28±0.21; range: 0.0-0.5). Supine hypertension (sHTN) was present in 72% of those with OH. Compared to iRBD participants without OH, those with OH were older, reported older age of RBD symptom onset, and had worse olfaction. There was no difference in autonomic symptom scores as measured by SCOPA-AUT.OH and sHTN are common in iRBD. However, as patients may have reduced autonomic symptom awareness, orthostatic stand testing should be considered in clinical evaluations. Longitudinal studies are needed to clarify the relationship between OH and phenoconversion risk in iRBD.

    View details for DOI 10.1212/WNL.0000000000207883

    View details for PubMedID 37857496

  • Low-dose naltrexone use for the management of post-acute sequelae of COVID-19. International immunopharmacology Bonilla, H., Tian, L., Marconi, V. C., Shafer, R., McComsey, G. A., Miglis, M., Yang, P., Bonilla, A., Eggert, L., Geng, L. N. 2023; 124 (Pt B): 110966

    Abstract

    The global prevalence of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) stands at approximately 43 % among individuals who have previously had acute COVID-19. In contrast, in the United States, the National Center for Health Statistics (NCHS) estimates that around 11 % of individuals who have been infected with SARS-CoV-2 go on to experience long COVID. The underlying causes of PASC remains under investigation, and there are no currently established FDA-approved therapies. One of the leading hypotheses for the cause of PASC is the persistent activation of innate immune cells with increase systemic inflammation. Naltrexone is a medication with anti-inflammatory and immunomodulatory properties that has been used in other conditions that overlap with PASC. We performed a retrospective review of a clinical cohort of 59 patients at a single academic center who received low-dose naltrexone (LDN) off-label as a potential therapeutic intervention for PASC. The use of LDN was associated with a fewer number of symptoms, improved clinical symptoms (fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep pattern), and a better functional status. This observation warrants testing in rigorous, randomized, placebo-controlled clinical trials.

    View details for DOI 10.1016/j.intimp.2023.110966

    View details for PubMedID 37804660

  • Images: Benign myoclonus of sleep associated with K-complexes on EEG. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine Silverman, A., Miglis, M. G., Gallentine, W. 2023

    Abstract

    In this brief case report on paroxysmal sleep-related movements, we describe an adolescent patient's presentation of brief jerking movements during sleep and the accompanying differential diagnosis. In examining the patient's overnight electroencephalogram (EEG), we utilize hallmark sleep architecture to provide reassurance to the patient and her family.

    View details for DOI 10.5664/jcsm.10822

    View details for PubMedID 37772703

  • Differential Findings on Anorectal Manometry in Patients with Parkinson's Disease and Defecatory Dysfunction. Movement disorders clinical practice Zhou, W., Triadafilopoulos, G., Gurland, B., Halawi, H., Becker, L., Garcia, P., Nguyen, L., Miglis, M., Muppidi, S., Sinn, D. I., Jaradeh, S., Neshatian, L. 2023; 10 (7): 1074-1081

    Abstract

    Gastrointestinal dysfunction, particularly constipation, is among the most common non-motor manifestations in Parkinson's Disease (PD). We aimed to identify high-resolution anorectal manometry (HR-ARM) abnormalities in patients with PD using the London Classification.We conducted a retrospective review of all PD patients at our institution who underwent HR-ARM and balloon expulsion test (BET) for evaluation of constipation between 2015 and 2021. Using age and sex-specific normal values, HR-ARM recordings were re-analyzed and abnormalities were reported using the London Classification. A combination of Wilcoxon rank sum and Fisher's exact test were used.36 patients (19 women) with median age 71 (interquartile range [IQR]: 69-74) years, were included. Using the London Classification, 7 (19%) patients had anal hypotension, 17 (47%) had anal hypocontractility, and 3 women had combined hypotension and hypocontractility. Anal hypocontractility was significantly more common in women compared to men. Abnormal BET and dyssynergia were noted in 22 (61%) patients, while abnormal BET and poor propulsion were only seen in 2 (5%). Men had significantly more paradoxical anal contraction and higher residual anal pressures during simulated defecation, resulting in more negative recto-anal pressure gradients. Rectal hyposensitivity was seen in nearly one third of PD patients and comparable among men and women.Our data affirms the high prevalence of anorectal disorders in PD. Using the London Classification, abnormal expulsion and dyssynergia and anal hypocontractility were the most common findings in PD. Whether the high prevalence of anal hypocontractility in females is directly related to PD or other confounding factors will require further research.

    View details for DOI 10.1002/mdc3.13755

    View details for PubMedID 37476327

    View details for PubMedCentralID PMC10354598

  • Differential Findings on Anorectal Manometry in Patients with Parkinson's Disease and Defecatory Dysfunction MOVEMENT DISORDERS CLINICAL PRACTICE Zhou, W., Triadafilopoulos, G., Gurland, B., Halawi, H., Becker, L., Garcia, P., Nguyen, L., Miglis, M., Muppidi, S., Sinn, D., Jaradeh, S., Neshatian, L. 2023

    View details for DOI 10.1002/mdc3.13755

    View details for Web of Science ID 000982806800001

  • The Synuclein-One Study: Skin Biopsy Detection of Phosphorylated alpha-synuclein for Diagnosis of the Synucleinopathies Gibbons, C., Bellaire, B., Wang, N., Freeman, R., Adler, C., Miglis, M., Isaacson, S., Evidente, V., Soileau, M., Gudesblatt, M., Lamotte, G., Kumar, R., Petrossian, M., Duarte, M., Khemani, P., Saint-Hilaire, M., McFarland, N., Pandey, H., Yerstein, O., Barboi, A., Liu, A., Levine, T. LIPPINCOTT WILLIAMS & WILKINS. 2023
  • Neurogenic Orthostatic Hypotension is Common in Isolated REM Sleep Behavior Disorder Miglis, M., Lim, M. M., Zitser, J., During, E., Bliwise, D., Huddleston, D., Howell, M., St Louis, E., Gagnon, J., Videnovic, A., Avidan, A., Schenck, C., Postuma, R., Boeve, B., Ju, Y., Elliott, J. E. LIPPINCOTT WILLIAMS & WILKINS. 2023
  • Sodium Oxybate in Treatment-Resistant REM Sleep Behavior Disorder. Sleep During, E. H., Hernandez, B., Miglis, M. G., Sum-Ping, O., Hekmat, A., Cahuas, A., Ekelmans, A., Yoshino, F., Mignot, E., Kushida, C. A. 2023

    Abstract

    Symptomatic therapies for REM sleep behavior disorder (RBD) are limited. Sodium oxybate (SXB), a gamma-aminobutyric acid (GABA)-B agonist, could be effective but has not been evaluated against placebo.This double-blind, parallel-group, randomized, placebo-controlled trial in 24 participants was conducted at the Stanford Sleep Center. Patients were adults with definite iRBD or Parkinson's disease and probable RBD (PD-RBD), and persistence of ≥ 2 weekly episodes despite standard therapy. Patients were randomized 1:1 to receive SXB during a 4-week titration followed by a 4-week stable dosing period. Primary outcome was number of monthly RBD episodes according to a diary filled by patients and partners. Secondary outcomes were severity, number of severe RBD episodes, and objective RBD activity on video-polysomnography.12 iRBD and 12 PD-RBD participated (mean 65.8 years), and 22 (n = 10 SXB, 12 placebo) completed the study. Although no significant between-group difference was found, SXB showed reduction of monthly RBD episodes by 23.1 (95% CI -36.0, -10.2; P=0.001) versus 10.5 with placebo (95% CI, -22.6, 1.6; P=0.087). Improvement from baseline was similarly observed for RBD overall severity burden (each episode weighted for severity), number of severe episodes, and objective RBD activity per video-polysomnography. Two participants receiving SXB withdrew due to anxiety and dizziness. The majority of adverse events otherwise resolved with dose adjustment.SXB could reduce RBD symptoms; however, response was inconsistent and a large placebo effect was observed across patient-reported outcomes. Larger studies using objective endpoints are needed.

    View details for DOI 10.1093/sleep/zsad103

    View details for PubMedID 37052688

  • Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic. Frontiers in neurology Bonilla, H., Quach, T. C., Tiwari, A., Bonilla, A. E., Miglis, M., Yang, P. C., Eggert, L. E., Sharifi, H., Horomanski, A., Subramanian, A., Smirnoff, L., Simpson, N., Halawi, H., Sum-Ping, O., Kalinowski, A., Patel, Z. M., Shafer, R. W., Geng, L. C. 2023; 14: 1090747

    Abstract

    The global prevalence of PASC is estimated to be present in 0·43 and based on the WHO estimation of 470 million worldwide COVID-19 infections, corresponds to around 200 million people experiencing long COVID symptoms. Despite this, its clinical features are not well-defined.We collected retrospective data from 140 patients with PASC in a post-COVID-19 clinic on demographics, risk factors, illness severity (graded as one-mild to five-severe), functional status, and 29 symptoms and principal component symptoms cluster analysis. The Institute of Medicine (IOM) 2015 criteria were used to determine the Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) phenotype.The median age was 47 years, 59.0% were female; 49.3% White, 17.2% Hispanic, 14.9% Asian, and 6.7% Black. Only 12.7% required hospitalization. Seventy-two (53.5%) patients had no known comorbid conditions. Forty-five (33.9%) were significantly debilitated. The median duration of symptoms was 285.5 days, and the number of symptoms was 12. The most common symptoms were fatigue (86.5%), post-exertional malaise (82.8%), brain fog (81.2%), unrefreshing sleep (76.7%), and lethargy (74.6%). Forty-three percent fit the criteria for ME/CFS, majority were female, and obesity (BMI > 30 Kg/m2) (P = 0.00377895) and worse functional status (P = 0.0110474) were significantly associated with ME/CFS.Most PASC patients evaluated at our clinic had no comorbid condition and were not hospitalized for acute COVID-19. One-third of patients experienced a severe decline in their functional status. About 43% had the ME/CFS subtype.

    View details for DOI 10.3389/fneur.2023.1090747

    View details for PubMedID 36908615

    View details for PubMedCentralID PMC9998690

  • Baseline characteristics of the North American prodromal Synucleinopathy cohort. Annals of clinical and translational neurology Elliott, J. E., Lim, M. M., Keil, A. T., Postuma, R. B., Pelletier, A., Gagnon, J., St Louis, E. K., Forsberg, L. K., Fields, J. A., Huddleston, D. E., Bliwise, D. L., Avidan, A. Y., Howell, M. J., Schenck, C. H., McLeland, J., Criswell, S. R., Videnovic, A., During, E. H., Miglis, M. G., Shprecher, D. R., Lee-Iannotti, J. K., Boeve, B. F., Ju, Y. S., North American Prodromal Synucleinopathy (NAPS) Consortium, Ju, Y. S., Boeve, B. F., Avidan, A. Y., Bliwise, D. L., Choudhury, P., Criswell, S. R., During, E. H., Elliott, J. E., Fields, J. A., Forsberg, L. K., Gagnon, J., Howell, M. J., Huddleston, D. E., Lee-Iannotti, J. K., Lim, M. M., Miglis, M. G., Postuma, R. B., Shprecher, D. R., St Louis, E. K., Videnovic, A., McLeland, J., Amudson-Huffmaster, S., Brushaber, N., Chung, J. W., De Kam, J., Ekelmans, A., Keane, M., Keil, A. T., Kraft, R., Ligman, B. R., MacKinnon, C., Miner-Rose, D., Murphy, S., Pelletier, A., Powers, K. L., Stauder, M., Rivera, A., Sanchez, S., Summers, R., Tiegan, L., Timm, P., Tucker, K. A., Tran, P., Galasko, D., Mignot, E., Schenck, C. 2023

    Abstract

    OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment.METHODS: Participants ≥18years of age with overnight polysomnogram-confirmed RBD without Parkinson's disease, dementia, multiple system atrophy, or narcolepsy were enrolled from nine sites across North America (8/2018 to 4/2021). Data collection included family/personal history of RBD and standardized assessments of cognitive, motor, sensory, and autonomic function.RESULTS: Outcomes are primarily reported based on sex (361 total: n=295 male, n=66 female), and secondarily based on history of antidepressant use (n=200 with, n=154 without; with correction for sex differences) and based on extent of synucleinopathy burden (n=56 defined as isolated RBD, n=305 defined as RBD+ [i.e., exhibiting ≥1 abnormality]). Overall, these participants commonly demonstrated abnormalities in global cognition (MoCA; 38%), motor function (alternate tap test; 48%), sensory (BSIT; 57%), autonomic function (orthostatic hypotension, 38.8%), and anxiety/depression (BAI and PHQ-9; 39.3% and 31%, respectively).INTERPRETATION: These RBD participants, assessed with extensive history, demographic, cognitive, motor, sensory, and autonomic function demonstrated a lack of sex differences and high frequency of concomitant neurological abnormalities. These participants will be valuable for future longitudinal study and neuroprotective clinical trials.

    View details for DOI 10.1002/acn3.51738

    View details for PubMedID 36751940

  • Autonomic Dysfunction in the Central Nervous System Hypersomnias CURRENT SLEEP MEDICINE REPORTS Miglis, M. G. 2023
  • Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection. JAMA Thaweethai, T., Jolley, S. E., Karlson, E. W., Levitan, E. B., Levy, B., McComsey, G. A., McCorkell, L., Nadkarni, G. N., Parthasarathy, S., Singh, U., Walker, T. A., Selvaggi, C. A., Shinnick, D. J., Schulte, C. C., Atchley-Challenner, R., Horwitz, L. I., Foulkes, A. S., RECOVER Consortium, Alba, G. A., Alicic, R., Altman, N., Anglin, K., Argueta, U., Ashktorab, H., Baslet, G., Bassett, I. V., Bateman, L., Bedi, B., Bhattacharyya, S., Bind, M., Blomkalns, A. L., Bonilla, H., Bush, P. A., Castro, M., Chan, J., Charney, A. W., Chen, P., Chibnik, L. B., Chu, H. Y., Clifton, R. G., Costantine, M. M., Cribbs, S. K., Davila Nieves, S. I., Deeks, S. G., Duven, A., Emery, I. F., Erdmann, N., Erlandson, K. M., Ernst, K. C., Farah-Abraham, R., Farner, C. E., Feuerriegel, E. M., Fleurimont, J., Fonseca, V., Franko, N., Gainer, V., Gander, J. C., Gardner, E. M., Geng, L. N., Gibson, K. S., Go, M., Goldman, J. D., Grebe, H., Greenway, F. L., Habli, M., Hafner, J., Han, J. E., Hanson, K. A., Heath, J., Hernandez, C., Hess, R., Hodder, S. L., Hoffman, M. K., Hoover, S. E., Huang, B., Hughes, B. L., Jagannathan, P., John, J., Jordan, M. R., Katz, S. D., Kaufman, E. S., Kelly, J. D., Kelly, S. W., Kemp, M. M., Kirwan, J. P., Klein, J. D., Knox, K. S., Krishnan, J. A., Kumar, A., Laiyemo, A. O., Lambert, A. A., Lanca, M., Lee-Iannotti, J. K., Logarbo, B. P., Longo, M. T., Luciano, C. A., Lutrick, K., Maley, J. H., Marathe, J. G., Marconi, V., Marshall, G. D., Martin, C. F., Matusov, Y., Mehari, A., Mendez-Figueroa, H., Mermelstein, R., Metz, T. D., Morse, R., Mosier, J., Mouchati, C., Mullington, J., Murphy, S. N., Neuman, R. B., Nikolich, J. Z., Ofotokun, I., Ojemakinde, E., Palatnik, A., Palomares, K., Parimon, T., Parry, S., Patterson, J. E., Patterson, T. F., Patzer, R. E., Peluso, M. J., Pemu, P., Pettker, C. M., Plunkett, B. A., Pogreba-Brown, K., Poppas, A., Quigley, J. G., Reddy, U., Reece, R., Reeder, H., Reeves, W. B., Reiman, E. M., Rischard, F., Rosand, J., Rouse, D. J., Ruff, A., Saade, G., Sandoval, G. J., Schlater, S. M., Shepherd, F., Sherif, Z. A., Simhan, H., Singer, N. G., Skupski, D. W., Sowles, A., Sparks, J. A., Sukhera, F. I., Taylor, B. S., Teunis, L., Thomas, R. J., Thorp, J. M., Thuluvath, P., Ticotsky, A., Tita, A. T., Tuttle, K. R., Urdaneta, A. E., Valdivieso, D., VanWagoner, T. M., Vasey, A., Verduzco-Gutierrez, M., Wallace, Z. S., Ward, H. D., Warren, D. E., Weiner, S. J., Welch, S., Whiteheart, S. W., Wiley, Z., Wisnivesky, J. P., Yee, L. M., Zisis, S. 2023

    Abstract

    Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.Exposure: SARS-CoV-2 infection.Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds).Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

    View details for DOI 10.1001/jama.2023.8823

    View details for PubMedID 37278994

  • AUTONOMIC REFLEX TESTING CONFIRMS AUTONOMIC DISTURBANCES IN A COHORT OF PATIENTS WITH IDIOPATHIC HYPERSOMNIA Koren, J., Aviv, R., Chiaro, G., Guaraldi, P., Miglis, M. G. ELSEVIER. 2022: S102
  • Imaging in autonomic failure: a window into real-time physiological mechanisms and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Larsen, N., Muppidi, S. 2022

    View details for DOI 10.1007/s10286-022-00910-0

    View details for PubMedID 36409381

  • High Resolution Anorectal Manometry Findings in Men and Women With Parkinson's Disease, Using London Classification Zhou, W., Sinn, D., Jaradeh, S., Muppidi, S., Miglis, M., Triadafilopoulos, G., Halawi, H., Becker, L., Garcia, P., Nguyen, L., Neshatian, L. LIPPINCOTT WILLIAMS & WILKINS. 2022: S407-S408
  • Comparison of Gastrointestinal Symptoms and Gastric Emptying Scintigraphy Between Postural Orthostatic Tachycardia Patients With and Without Small Fiber Neuropathy Zhou, W., Sinn, D., Jaradeh, S., Muppidi, S., Miglis, M., Neshatian, L., Nguyen, L. LIPPINCOTT WILLIAMS & WILKINS. 2022: S408-S409
  • Multi-Disciplinary Collaborative Consensus Guidance Statement on the Assessment and Treatment of Autonomic Dysfunction in Patients with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). PM & R : the journal of injury, function, and rehabilitation Blitshteyn, S., Whiteson, J., Abramoff, B., Azola, A., Bartels, M. N., Bhavaraju-Sanka, R., Chung, T., Fleming, T. K., Henning, E., Miglis, M. G., Sampsel, S., Silver, J. K., Tosto, J., Verduzco-Gutierrez, M., Putrino, D. 2022

    View details for DOI 10.1002/pmrj.12894

    View details for PubMedID 36169154

  • POTS May Be Underestimated in Post-COVID Assessments. Journal of the American College of Cardiology Miglis, M. G., Stiles, L. E., Raj, S. R. 2022; 80 (13): e103

    View details for DOI 10.1016/j.jacc.2022.04.068

    View details for PubMedID 36137679

  • Autonomic function testing in multiple system atrophy: a prognostic biomarker? and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2022

    View details for DOI 10.1007/s10286-022-00883-0

    View details for PubMedID 35907042

  • Implantable neurostimulators for neurogenic orthostatic hypotension: the wave of the future? and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Larsen, N., Muppidi, S. 2022

    View details for DOI 10.1007/s10286-022-00871-4

    View details for PubMedID 35655044

  • AUTONOMIC REFLEX TESTING CONFIRMS AUTONOMIC DISTURBANCES IN A COHORT OF PATIENTS WITH IDIOPATHIC HYPERSOMNIA Aviv, R., Zitser, J., Miglis, M., Chiaro, G., Guaraldi, P. OXFORD UNIV PRESS INC. 2022: A178
  • A case series of cutaneous phosphorylated alpha-synuclein in Long-COVID POTS. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Seliger, J., Shaik, R., Gibbons, C. H. 2022

    View details for DOI 10.1007/s10286-022-00867-0

    View details for PubMedID 35570247

  • Mechanisms of post-prandial symptoms in postural tachycardia syndrome and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Larsen, N., Muppidi, S. 2022

    View details for DOI 10.1007/s10286-022-00863-4

    View details for PubMedID 35316450

  • Inappropriate sinus tachycardia in long-COVID and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Larsen, N., Muppidi, S. 2022

    View details for DOI 10.1007/s10286-022-00854-5

    View details for PubMedID 35129713

  • Characterization of autonomic symptom burden in long COVID: A global survey of 2,314 adults. Frontiers in neurology Larsen, N. W., Stiles, L. E., Shaik, R., Schneider, L., Muppidi, S., Tsui, C. T., Geng, L. N., Bonilla, H., Miglis, M. G. 2022; 13: 1012668

    Abstract

    Background: Autonomic dysfunction is a known complication of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID, however prevalence and severity are unknown.Objective: To assess the frequency, severity, and risk factors of autonomic dysfunction in PASC, and to determine whether severity of acute SARS-CoV-2 infection is associated with severity of autonomic dysfunction.Design: Cross-sectional online survey of adults with PASC recruited through long COVID support groups between October 2020 and August 2021.Participants: 2,413 adults ages 18-64 years with PASC including patients who had a confirmed positive test for COVID-19 (test-confirmed) and participants who were diagnosed with COVID-19 based on clinical symptoms alone.Main measures: The main outcome measure was the Composite Autonomic Symptom 31 (COMPASS-31) total score, used to assess global autonomic dysfunction. Test-confirmed hospitalized vs. test-confirmed non-hospitalized participants were compared to determine if the severity of acute SARS-CoV-2 infection was associated with the severity autonomic dysfunction.Key results: Sixty-six percent of PASC patients had a COMPASS-31 score >20, suggestive of moderate to severe autonomic dysfunction. COMPASS-31 scores did not differ between test-confirmed hospitalized and test-confirmed non-hospitalized participants [28.95 (15.62, 46.60) vs. 26.4 (13.75, 42.10); p = 0.06].Conclusions: Evidence of moderate to severe autonomic dysfunction was seen in 66% of PASC patients in our study, independent of hospitalization status, suggesting that autonomic dysfunction is highly prevalent in the PASC population and independent of the severity of acute COVID-19 illness.

    View details for DOI 10.3389/fneur.2022.1012668

    View details for PubMedID 36353127

  • The 2021 Nobel Prize in Medicineandits relevance toautonomicmedicine-and otherupdates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Larsen, N., Muppidi, S. 2021

    View details for DOI 10.1007/s10286-021-00838-x

    View details for PubMedID 34751840

  • Biomarkers of conversion to alpha-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder. The Lancet. Neurology Miglis, M. G., Adler, C. H., Antelmi, E., Arnaldi, D., Baldelli, L., Boeve, B. F., Cesari, M., Dall'Antonia, I., Diederich, N. J., Doppler, K., Dusek, P., Ferri, R., Gagnon, J., Gan-Or, Z., Hermann, W., Hogl, B., Hu, M. T., Iranzo, A., Janzen, A., Kuzkina, A., Lee, J., Leenders, K. L., Lewis, S. J., Liguori, C., Liu, J., Lo, C., Ehgoetz Martens, K. A., Nepozitek, J., Plazzi, G., Provini, F., Puligheddu, M., Rolinski, M., Rusz, J., Stefani, A., Summers, R. L., Yoo, D., Zitser, J., Oertel, W. H. 2021; 20 (8): 671-684

    Abstract

    Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving alpha-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal alpha-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest alpha-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of alpha-synucleinopathy patients with isolated RBD might develop.

    View details for DOI 10.1016/S1474-4422(21)00176-9

    View details for PubMedID 34302789

  • Biomarkers of conversion to alpha-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder LANCET NEUROLOGY Miglis, M. G., Adler, C. H., Antelmi, E., Arnaldi, D., Baldelli, L., Boeve, B. F., Cesari, M., Dall'Antonia, I., Diederich, N. J., Doppler, K., Dusek, P., Ferri, R., Gagnon, J., Gan-Or, Z., Hermann, W., Hoegl, B., Hu, M. T., Iranzo, A., Janzen, A., Kuzkina, A., Lee, J., Leenders, K. L., Lewis, S. G., Liguori, C., Liu, J., Lo, C., Martens, K., Nepozitek, J., Plazzi, G., Provini, F., Puligheddu, M., Rolinski, M., Rusz, J., Stefani, A., Summers, R. S., Yoo, D., Zitser, J., Oertel, W. H. 2021; 20 (8): 671-684
  • Cutaneous Alpha-Synuclein is Correlated with Autonomic Impairment in Isolated REM Sleep Behavior Disorder. Sleep Miglis, M. G., Zitser, J., Schneider, L., During, E., Jaradeh, S., Freeman, R., Gibbons, C. H. 2021

    Abstract

    STUDY OBJECTIVES: To define the clinical implications of cutaneous phosphorylated alpha-synuclein (p-syn) and its association with subjective and objective measures of autonomic impairment and clinical features including antidepressant use in isolated REM sleep behavior disorder (iRBD).METHODS: Twenty-five iRBD patients had quantified neurological and cognitive examinations, olfactory testing, questionnaires, autonomic function testing, and 3 punch skin biopsies (distal thigh, proximal thigh, neck). Skin biopsies were stained for the pan-axonal marker PGP 9.5 and co-stained with p-syn, and results were compared to 28 patients with Parkinson's disease (PD) and 18 healthy controls. Equal numbers of iRBD patients on and off antidepressants were recruited. The composite autonomic severity scale (CASS) was calculated for all patients.RESULTS: P-syn was detected in 16/25 (64%) of iRBD patients, compared to 27/28 (96%) of PD and 0/18 controls. The presence of p-syn at any biopsy site was correlated with both sympathetic (CASS adrenergic r = 0.6, p < 0.05) and total autonomic impairment (CASS total r = 0.6, p < 0.05) on autonomic reflex testing in iRBD patients. These results were independent of the density of p-syn at each site. There was no correlation between p-syn and antidepressant use.CONCLUSIONS: In patients with iRBD, the presence of cutaneous p-syn was detected in most patients and was associated with greater autonomic dysfunction on testing. Longitudinal follow-up will aid in defining the predictive role of both skin biopsy and autonomic testing in determining phenoconversion rates and future disease status.

    View details for DOI 10.1093/sleep/zsab172

    View details for PubMedID 34244806

  • Holiday heart syndrome: do not drink during this holiday! and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Larsen, N., Muppidi, S. 2021

    View details for DOI 10.1007/s10286-021-00818-1

    View details for PubMedID 34244877

  • Preparing for the long-haul: Autonomic complications of COVID-19. Autonomic neuroscience : basic & clinical Larsen, N. W., Stiles, L. E., Miglis, M. G. 2021; 235: 102841

    Abstract

    As global numbers of COVID-19 grow, chronic neurological symptoms, including those of autonomic dysfunction, are being reported with increasing frequency. Mounting evidence suggests that many patients experience chronic and sometimes debilitating symptoms long after their acute infectious period, leading to the new diagnostic category of post-acute COVID syndrome. Many symptoms of post-acute COVID syndrome appear autonomic in nature, suggesting that autonomic impairment may play a central role in the underlying pathophysiology. In this review, we discuss the autonomic symptoms and manifestations of post-acute COVID syndrome, potential mechanisms involved, and future directions for a better understanding of this novel condition.

    View details for DOI 10.1016/j.autneu.2021.102841

    View details for PubMedID 34265539

  • Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2. Autonomic neuroscience : basic & clinical Raj, S. R., Bourne, K. M., Stiles, L. E., Miglis, M. G., Cortez, M. M., Miller, A. J., Freeman, R., Biaggioni, I., Rowe, P. C., Sheldon, R. S., Shibao, C. A., Diedrich, A., Systrom, D. M., Cook, G. A., Doherty, T. A., Abdallah, H. I., Grubb, B. P., Fedorowski, A., Stewart, J. M., Arnold, A. C., Pace, L. A., Axelsson, J., Boris, J. R., Moak, J. P., Goodman, B. P., Chemali, K. R., Chung, T. H., Goldstein, D. S., Darbari, A., Vernino, S. 2021: 102836

    Abstract

    The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.

    View details for DOI 10.1016/j.autneu.2021.102836

    View details for PubMedID 34246578

  • Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1. Autonomic neuroscience : basic & clinical Vernino, S., Bourne, K. M., Stiles, L. E., Grubb, B. P., Fedorowski, A., Stewart, J. M., Arnold, A. C., Pace, L. A., Axelsson, J., Boris, J. R., Moak, J. P., Goodman, B. P., Chemali, K. R., Chung, T. H., Goldstein, D. S., Diedrich, A., Miglis, M. G., Cortez, M. M., Miller, A. J., Freeman, R., Biaggioni, I., Rowe, P. C., Sheldon, R. S., Shibao, C. A., Systrom, D. M., Cook, G. A., Doherty, T. A., Abdallah, H. I., Darbari, A., Raj, S. R. 2021: 102828

    Abstract

    Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.

    View details for DOI 10.1016/j.autneu.2021.102828

    View details for PubMedID 34144933

  • Do not sweat it: we test while you rest and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Larsen, N., Muppidi, S. 2021

    View details for DOI 10.1007/s10286-021-00811-8

    View details for PubMedID 33978866

  • Towards more evidenced-based therapies for postural tachycardia syndrome and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2021

    View details for DOI 10.1007/s10286-021-00795-5

    View details for PubMedID 33709266

  • Orthostatic intolerance with Klippel-Trenaunay syndrome. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Sinn, D. I., Shaik, R., Miglis, M. G., Muppidi, S., Jaradeh, S. 2021

    View details for DOI 10.1007/s10286-021-00791-9

    View details for PubMedID 33655381

  • Myasthenia Symptom Burden, Fatigue, and Sleep: Are They Related? Journal of clinical neuromuscular disease Yang, S., Miglis, M. G., Jaradeh, S., Muppidi, S. 2021; 22 (3): 123–28

    Abstract

    OBJECTIVE: Our aim is to explore the relationship between myasthenia gravis (MG)-related symptom burden, sleep quality, and fatigue in a diverse group of self-identified MG patients.METHODS: Patients provided relevant myasthenia disease data and completed the MG QOL-15, Epworth sleepiness scale, Pittsburgh Sleep Quality Index, and fatigue severity score (FSS) online. MG activities of daily living scale (MG-ADL) was completed on a follow-up telephone interview.RESULTS: One hundred ninety-six patients completed the online survey and 99 provided MG-ADL data. The mean age was 52 ± 15.34 years, 88 were acetylcholine receptor antibody positive, and 21 were muscle specific kinase positive. The mean MG-ADL was 6.81, indicating a moderate MG disease burden. Forty-seven (24%) reported high Epworth sleepiness scale scores, 152 (77%) reported high Pittsburgh Sleep Quality Index scores, and 162 (82%) reported high FSS scores. Correlation analysis correcting for body mass index and sleep apnea revealed a moderate positive correlation between MGQOL-15, MG-ADL, and FSS.CONCLUSIONS: There is a moderate positive correlation between various MG-specific outcome measures and fatigue severity.

    View details for DOI 10.1097/CND.0000000000000321

    View details for PubMedID 33595995

  • RT-QUiC in multiple system atrophy: the biomarker of the future? and otherupdates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Larsen, N., Muppidi, S. 2021

    View details for DOI 10.1007/s10286-021-00767-9

    View details for PubMedID 33515140

  • Autonomic function test during the COVID-19 pandemic: the Stanford experience. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Sinn, D. I., Muppidi, S. n., Miglis, M. G., Jaradeh, S. n. 2021

    View details for DOI 10.1007/s10286-020-00752-8

    View details for PubMedID 33387099

  • The shock of it: sympathetic activation promotes hair greying, and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Larsen, N., Muppidi, S. 2020

    View details for DOI 10.1007/s10286-020-00746-6

    View details for PubMedID 33210247

  • A case report of postural tachycardia syndrome after COVID-19. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Prieto, T., Shaik, R., Muppidi, S., Sinn, D., Jaradeh, S. 2020

    View details for DOI 10.1007/s10286-020-00727-9

    View details for PubMedID 32880754

  • Response to post-COVID-19 chronic symptoms: a post-infectious entity? Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases Miglis, M. G., Goodman, B. P., Chemali, K. R., Stiles, L. 2020

    View details for DOI 10.1016/j.cmi.2020.08.028

    View details for PubMedID 32891765

  • Can skin biopsy differentiate Parkinson disease from multiple system atrophy? And other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2020

    View details for DOI 10.1007/s10286-020-00712-2

    View details for PubMedID 32648015

  • The quest for biomarkers in postural tachycardia syndrome and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2020

    View details for DOI 10.1007/s10286-020-00694-1

    View details for PubMedID 32418032

  • Symptom Recognition Is Impaired in Patients With Orthostatic Hypotension. Hypertension (Dallas, Tex. : 1979) Freeman, R., Illigens, B. M., Lapusca, R., Campagnolo, M., Abuzinadah, A. R., Bonyhay, I., Sinn, D., Miglis, M., White, J., Gibbons, C. H. 2020: HYPERTENSIONAHA11913619

    Abstract

    Failure to recognize symptoms of orthostatic hypotension (OH) may result in falls, syncope, and injuries. The relationship between orthostatic changes in blood pressure and symptom occurrence and severity is not known. The goal of the present study was to define the relationship between the occurrence and severity of the symptoms of orthostatic hypotension (OH) and (1) the upright systolic blood pressure (SBP) and (2) the fall in SBP after tilting in patients with OH. We prospectively studied 89 patients with OH. Reported BP values include the lowest BP in the first 3 minutes of tilt and the change in blood pressure during tilt. Subjects were queried about symptoms of orthostatic intolerance while supine and during the first 3 minutes of tilt testing using Question 1 of the Orthostatic Hypotension Questionnaire. Mean tilted SBP was 101.6±26.1 mm Hg and mean SBP fall 47.9±18.1 mm Hg. Mean symptom scores when upright were: light-headedness (2.3/10±2.7), dizziness (1.6/10±2.5), and impending blackout (0.8/10±1.9). The majority of patients were asymptomatic or mildly symptomatic and no discrete cutoff for symptoms was observed. The magnitude of the SBP fall (r=-0.07, P=NS) and the lowest upright SBP (r=0.08, P=NS) did not correlate with any reported symptom. These results suggest a poor relationship between the magnitude of the orthostatic BP fall, the upright orthostatic BP, and symptoms. Many patients are asymptomatic despite substantial SBP falls and low orthostatic blood pressures. These findings have implications for clinical care of patients with OH and clinical trials to treat patients with OH.

    View details for DOI 10.1161/HYPERTENSIONAHA.119.13619

    View details for PubMedID 32223377

  • Synuclein in red blood cells: a potential biomarker for multiple system atrophy, and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2020

    View details for DOI 10.1007/s10286-020-00680-7

    View details for PubMedID 32189166

  • The role of tissue biopsy as a biomarker in REM sleep behavior disorder. Sleep medicine reviews Zitser, J., Gibbons, C., Miglis, M. G. 2020; 51: 101283

    Abstract

    Patients with idiopathic REM-sleep behavior disorder (iRBD) are at substantial risk of progressive neurodegenerative disease of alpha-synuclein pathology. Longitudinal studies have demonstrated that abnormal alpha-synuclein deposition occurs early in the course of disease and may precede the appearance of motor symptoms by several decades. This provides rationale for the use of a reliable biomarker to both follow disease progression and to assess treatment response, once disease-modifying treatments become available. Tissue alpha-synuclein has emerged as a promising candidate, however the utility of alpha-synuclein detection in tissues accessible to biopsy in iRBD remains unclear. This article summarizes the current literature on the role of tissue biopsy in iRBD, with specific focus on its potential role as a biomarker of disease progression and its role in future clinical trials.

    View details for DOI 10.1016/j.smrv.2020.101283

    View details for PubMedID 32187564

  • Frequency and Severity of Autonomic Symptoms in Idiopathic Hypersomnia. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine Miglis, M. G., Schneider, L., Kim, P., Cheung, J., Trotti, L. M. 2020

    Abstract

    STUDY OBJECTIVES: We aimed to quantify the symptoms of autonomic nervous system (ANS) dysfunction in a large online cohort of patients with IH, and to determine how the severity of these symptoms interacts with sleepiness, fatigue, and quality of life.METHODS: One hundred thirty-eight IH patients and 81 age- and sex-matched controls were recruited through the website of the Hypersomnia Foundation, a U.S.-based patient advocacy group. Twenty-four confirmed IH patients were selected by the study investigators as a comparison group. All participants completed a battery of online sleep, autonomic, and quality of life questionnaires including the composite autonomic symptom score-31 (COMPASS-31).RESULTS: Online and confirmed patients reported significantly higher COMPASS-31 scores (43.6 [33.6-52.7] & 32.9 [21.7- 46.8] vs. 17.6 [11.7-27.9], p<0.001), with the greatest symptom burden in the orthostatic and vasomotor domains. Online and confirmed patients reported more sleepiness (ESS), whereas only online patients reported more fatigue (CFQ). Both the ESS and CFQ positively correlated with COMPASS-31 scores. Patients reported lower quality of life as reflected by lower scores across all domains of the RAND-36, which was negatively correlated with COMPASS-31 scores.CONCLUSIONS: Symptoms of ANS dysfunction are common in IH. In addition, ANS symptom burden was positively correlated with sleepiness and negatively correlated with quality of life.

    View details for DOI 10.5664/jcsm.8344

    View details for PubMedID 32039754

  • Quantitative sudomotor abnormalities in clinically isolated rapid eye movement sleep behavior disorder. Autonomic neuroscience : basic & clinical Zitser, J., Muppidi, S., Sinn, D. I., Jaradeh, S., Miglis, M. G. 2020; 224: 102645

    Abstract

    BACKGROUND: Post-ganglionic sudomotor abnormalities are common in Parkinson's disease (PD), however data in clinically isolated REM sleep behavior disorder (iRBD) are limited.OBJECTIVE: To determine the prevalence of sudomotor abnormalities in a cohort of patients with iRBD.METHODS: We performed a retrospective review of patients seen in our autonomic clinic who underwent testing with the quantitative sudomotor axon reflex test (QSART). We identified three groups for comparison: 1.) iRBD, 2.) PD with RBD (PDwRBD) 3.) PD without RBD (PDwoRBD).RESULTS: PDwRBD (n=27) patients demonstrated the greatest sudomotor abnormalities (sudomotor CASS 1.44±1.24), followed by PDwoRBD (n=23, 0.57±0.5) and iRBD (n=20, 0.55±0.94) (p=0.015). Twenty percent of patients with iRBD had an abnormal result, compared to 67% PDwRBD and 35% PDwoRBD.DISCUSSION: Sudomotor abnormalities are common in patients with iRBD, supporting the concept that peripheral autonomic impairment occurs early in the course of disease.

    View details for DOI 10.1016/j.autneu.2020.102645

    View details for PubMedID 32062418

  • Is postural tachycardia syndrome an autoimmune disorder? And other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2020

    View details for DOI 10.1007/s10286-019-00661-5

    View details for PubMedID 31938977

  • Autonomic impairment in sleep: An introduction to the special edition. Autonomic neuroscience : basic & clinical Calandra-Buonaura, G. n., Cortelli, P. n., Miglis, M. n., Palma, J. A. 2020; 224: 102638

    View details for DOI 10.1016/j.autneu.2020.102638

    View details for PubMedID 31978844

  • Effect of artificial dawn light on cardiovascular function, alertness, and balance in middle-aged and older adults. Sleep Gabel, V. n., Miglis, M. n., Zeitzer, J. M. 2020

    Abstract

    When arising in the morning, many older people experience dizziness and difficulty maintaining proper balance, as the cardiovascular system is not able to compensate to the postural shift (standing) and maintain sufficient blood flow to the brain. Such changes in cardiovascular function are observed in young individuals exposed to a dawn simulation light. In this study, we examined whether exposure to a dawn simulation light could impact cardiovascular function and consequent changes in balance in middle-aged and older adults.Twenty-three participants (67.3±8.8 y), 12 of whom reported a history of dizziness in the morning, underwent two overnight stays in our laboratory. During both nights, they slept in complete darkness, except for the last 30 minutes of one of the nights during which a dawn simulation light was used. Continuous blood pressure and heart rate were monitored. Subjective and objective alertness, salivary cortisol, and mobile and standing balance were examined upon arising.Dawn simulation light decreased (33%) the amount of sleep before morning awakening, lowered blood pressure (6.24 mmHg), and increased heart rate (0.93 bpm). Despite these changes in physiology, there was no significant impact of dawn simulation on subjective or objective alertness, measures of standing or ambulatory balance, morning cortisol awakening response, or cardiovascular function after awakening.While the dawn simulation did cause an increase in wake and a change in cardiovascular function prior to morning arousal in older adults, we could find no evidence of a functional change in either cardiovascular function or balance upon standing.

    View details for DOI 10.1093/sleep/zsaa082

    View details for PubMedID 32307533

  • Autonomic impairment in REM sleep behavior disorder: a potential biomarker of phenoconversion? Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G. 2020

    View details for DOI 10.1007/s10286-020-00688-z

    View details for PubMedID 32410081

  • AUTONOMIC SYMPTOMS ARE COMMON IN IDIOPATHIC HYPERSOMNIA Miglis, M., Kim, P., Schneider, L., Cheung, J., Trotti, L. M. ELSEVIER. 2019: S255
  • SUDOMOTOR ABNORMALITIES IN IDIOPATHIC REM SLEEP BEHAVIOR DISORDER Zitser, J., Muppidi, S., During, E., Sinn, D., Jaradeh, S., Miglis, M. ELSEVIER. 2019: S255–S256
  • The microbiome in autonomic medicine and other updates in recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2019

    View details for DOI 10.1007/s10286-019-00621-z

    View details for PubMedID 31363881

  • Autonomic impairment as a potential biomarker in idiopathic REM-sleep-behavior disorder. Autonomic neuroscience : basic & clinical Zitser, J., During, E. H., Chiaro, G., Miglis, M. G. 2019; 220: 102553

    Abstract

    Autonomic dysfunction is common in REM-sleep behavior disorder (RBD). Several studies have demonstrated abnormalities in heart rate variability, cardiac scintigraphy, and cardiovascular autonomic reflex testing. In addition, the type and severity of these abnormalities may correlate with rate of phenoconversion from idiopathic RBD (iRBD) to manifest neurodegenerative disease. This article summarizes the current literature on autonomic impairment in iRBD, with specific focus on the role of autonomic impairment as a potential biomarker of disease progression. REM sleep physiology and relevant anatomy is also discussed in relation to the central autonomic network and autonomic neurodegeneration.

    View details for DOI 10.1016/j.autneu.2019.05.005

    View details for PubMedID 31219036

  • Do astronauts get postural tachycardia syndrome? And other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2019

    View details for DOI 10.1007/s10286-019-00613-z

    View details for PubMedID 31089931

  • Autonomic Symptom Burden in Idiopathic Hypersomnia Kim, P., Cheung, J., Schneider, L., Trotti, L., Miglis, M. LIPPINCOTT WILLIAMS & WILKINS. 2019
  • Dopamine transporter imaging versus myocardial MIBG scintigraphy for the diagnosis of prodromal synucleinopathies-and other updates on autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2019

    View details for DOI 10.1007/s10286-019-00600-4

    View details for PubMedID 30904961

  • The driver of sympathetic overactivity in obstructive sleep apnea: hypoxia or arousal? Sleep medicine Miglis, M. G. 2019

    View details for DOI 10.1016/j.sleep.2019.02.009

    View details for PubMedID 31530464

  • Ion channels PIEZOs identified as the long-sought baroreceptor mechanosensors for blood pressure control, and other updates on autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2019

    View details for DOI 10.1007/s10286-018-00588-3

    View details for PubMedID 30604163

  • Clinical trials in REM sleep behavior disorder: an urgent need for better evidence. Sleep medicine During, E. H., Miglis, M. G. 2019; 63: 1–2

    View details for DOI 10.1016/j.sleep.2019.06.001

    View details for PubMedID 31600655

  • Sleep disorders in patients with postural tachycardia syndrome: A review of the literature and guide for clinicians AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL Miglis, M. G., Barwick, F. 2018; 215: 62–69
  • A novel autosomal recessive orthostatic hypotension syndrome: and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2018

    View details for DOI 10.1007/s10286-018-0578-z

    View details for PubMedID 30415401

  • Orthostatic Hypotension JACC State-of-the-Art Review JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Freeman, R., Abuzinadah, A. R., Gibbons, C., Jones, P., Miglis, M. G., Sinn, D. 2018; 72 (11): 1294–1309

    Abstract

    Neurogenic orthostatic hypotension is a highly prevalent and disabling feature of autonomic failure due to both peripheral and central neurodegenerative diseases. Community-based epidemiological studies have demonstrated a high morbidity and mortality associated with neurogenic orthostatic hypotension. It is due to impairment of baroreflex-mediated vasoconstriction of the skeletal muscle and splanchnic circulation and is caused by damage or dysfunction at central and/or peripheral sites in the baroreflex efferent pathway. Nonpharmacological and pharmacological interventions may be implemented to ameliorate the symptoms of orthostatic intolerance and improve quality of life. Many patients will be adequately treated by education, counseling, removal of hypotensive medications, and other nonpharmacological interventions, whereas more severely afflicted patients require pharmacological interventions. The first stage of pharmacological treatment involves repletion of central blood volume. If unsuccessful, this should be followed by treatment with sympathomimetic agents.

    View details for PubMedID 30190008

  • Autonomic dysfunction in multiple sclerosis and other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2018

    View details for DOI 10.1007/s10286-018-0548-5

    View details for PubMedID 30014341

  • Reply to "Syncope is associated with electroencephalography changes" and to "Video-EEG during tilt-table testing is an invaluable aid for understanding syncope". Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology Muppidi, S., Miglis, M. G., Razavi, B. 2018; 129 (7): 1500–1501

    View details for DOI 10.1016/j.clinph.2018.04.601

    View details for PubMedID 29729888

  • Orthostatic hypotension: does the heart rate matter? And other updates on recent autonomic research. Clinical autonomic research : official journal of the Clinical Autonomic Research Society Miglis, M. G., Muppidi, S. 2018

    View details for DOI 10.1007/s10286-018-0532-0

    View details for PubMedID 29779066

  • Sleep disorders in patients with postural tachycardia syndrome: A review of the literature and guide for clinicians. Autonomic neuroscience : basic & clinical Miglis, M. G., Barwick, F. 2018

    Abstract

    Fatigue is common in POTS, and patients often report unrefreshing sleep. These symptoms are directly correlated with a reduced quality of life, however the treatment of sleep disorders in this population remains a challenge. This article will review the current literature on the prevalence of sleep disorders in POTS, their association with the underlying pathophysiology of POTS, and current treatment paradigms.

    View details for PubMedID 29773483

  • Postural Orthostatic Tachycardia: The Stanford experience Jaradeh, S., Muppidi, S., Miglis, M., Sinn, D., Krugomova, I., Prieto, T. LIPPINCOTT WILLIAMS & WILKINS. 2018
  • Myasthenia Symptom Burden, Sleep and Fatigue: Are they related? Yang, S., Miglis, M., Jaradeh, S., Muppidi, S. LIPPINCOTT WILLIAMS & WILKINS. 2018
  • The clinical utility of qualitative electroencephalography during tilt table testing - A retrospective study CLINICAL NEUROPHYSIOLOGY Muppidi, S., Razavi, B., Miglis, M. G., Jaradeh, S. 2018; 129 (4): 783–86

    Abstract

    To assess electroencephalography (EEG) changes during tilt table testing in syncope and other orthostatic syndromes.We retrospectively reviewed consecutive tilt table studies with simultaneous EEG from April 2014 to May 2016 at our center. All patients had video EEG during tilt table. All patients had at least 10 min of head up tilt unless they had syncope or did not tolerate the study. Video EEG was interpreted by epileptologists.Eighty-seven patients met the inclusion criteria. Mean age was 45 years, and 55 were women. Seven patients (∼8%) had syncope during tilt table, 11 patients (∼12%) had significant neurogenic orthostatic hypotension and a separate group of 11 patients (∼12%) had significant orthostatic tachycardia. Valsalva responses were abnormal in 7 of the 11 patients with orthostatic hypotension, suggesting an underlying neurogenic orthostatic hypotension. Visually discernable EEG changes were seen in only 3 patients (∼43%) who had syncope and in 1 patient (∼9%) with orthostatic tachycardia.Qualitative EEG analysis based on visual inspection during tilt table study revealed abnormalities in less than half the patients with syncope and a very small fraction with orthostatic tachycardia.Routine qualitative EEG recording might not be clinically useful during tilt table studies.

    View details for DOI 10.1016/j.clinph.2018.01.058

    View details for Web of Science ID 000427485900010

    View details for PubMedID 29448152

  • Is your autonomic function good enough to be an Olympian? And other updates on recent autonomic research CLINICAL AUTONOMIC RESEARCH Miglis, M. G., Muppidi, S. 2018; 28 (2): 177–79

    View details for DOI 10.1007/s10286-018-0521-3

    View details for Web of Science ID 000427880500006

    View details for PubMedID 29541877

  • Migraine and Autonomic Dysfunction: Which Is the Horse and Which Is the Jockey? CURRENT PAIN AND HEADACHE REPORTS Miglis, M. G. 2018; 22 (3): 19

    Abstract

    Symptoms of autonomic dysfunction are common in patients with migraine, both during and between migraine attacks. Studies evaluating objective autonomic testing in patients have found significant, though somewhat conflicting results. The purposes of this review are to summarize and interpret the key findings of these studies, including those evaluating heart rate variability, autonomic reflex testing, and functional imaging in patients with migraine. The neuroanatomy of the central autonomic network as it relates to migraine is also reviewed.Several studies have evaluated autonomic balance in migraineurs, with conflicting results on the magnitude of sympathetic versus parasympathetic dysfunction. Most studies demonstrate sympathetic impairment, with a lesser degree of parasympathetic impairment. Three trends have emerged: (1) migraine with aura tends to produce more significant autonomic dysfunction than migraine without aura, (2) sympathetic impairment is more common than parasympathetic impairment, and (3) sympathetic impairment is common in the interictal period, with increased sympathetic responsiveness during the ictal period, suggesting adrenoreceptor hypersensitivity.

    View details for PubMedID 29476276

  • Autonomic dysfunction predicts poor outcome in stroke: Updates on recent autonomic research CLINICAL AUTONOMIC RESEARCH Miglis, M. G., Muppidi, S. 2018; 28 (1): 9–11

    View details for DOI 10.1007/s10286-017-0498-3

    View details for Web of Science ID 000424641400004

    View details for PubMedID 29305815

  • A Case of Narcolepsy Type 2 and Postural Tachycardia Syndrome Secondary to Lesions of the Thalamus and Amygdala JOURNAL OF CLINICAL SLEEP MEDICINE Kim, P., During, E., Miglis, M. 2018; 14 (3): 479–81

    Abstract

    Although there are reports of narcolepsy type 1 caused by lesions of the central nervous system, there are far fewer reports of narcolepsy type 2 (NT2) caused by discrete brain lesions. We report a case of a patient in whom NT2 was diagnosed after a viral illness, and inflammatory lesions in the right thalamus and amygdala were found. In addition, symptoms of autonomic impairment developed and postural tachycardia syndrome was subsequently diagnosed in this patient. To our knowledge this is the first reported case of NT2 resulting from central nervous system lesions in these discrete locations, as well as the first reported case of postural tachycardia syndrome associated with narcolepsy.

    View details for PubMedID 29458703

    View details for PubMedCentralID PMC5837851

  • Postural tachycardia in hypermobile Ehlers-Danlos syndrome: A distinct subtype? AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL Miglis, M. G., Schultz, B., Muppidi, S. 2017; 208: 146–49

    Abstract

    It is not clear if patients with postural tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (hEDS) differ from patients with POTS due to other etiologies. We compared the results of autonomic testing and healthcare utilization in POTS patients with and without hEDS.Patients with POTS+hEDS (n=20) and POTS controls without hypermobility (n=20) were included in the study. All patients underwent autonomic testing, and the electronic medical records were reviewed to determine the number and types of medications patients were taking, as well as the number of outpatient, emergency department, and inpatient visits over the prior year.Patients with hEDS had twice as many outpatient visits (21 v. 10, p=0.012), were taking more prescription medications (8 vs. 5.5, p=0.030), and were more likely to see a pain physician (70% vs 25%, p=0.005). Autonomic testing demonstrated a slight reduction in heart rate variability and slightly lower blood pressures on tilt table testing in hEDS patients, however for most patients these variables remained within the range of normal. Orthostatic tachycardia on tilt table testing was greater in POTS controls (46bpm vs 39bpm, p=0.018). Abnormal QSweat responses were common in both groups (38% of POTS+hEDS and 36% of POTS controls).While autonomic testing results were not significantly different between groups, patients with POTS+hEDS took more medications and had greater markers of healthcare utilization, with chronic pain likely playing a prominent role.

    View details for PubMedID 28986003

  • SLEEP AND AUTONOMIC IMPAIRMENT IN EHLERS-DANLOS SYNDROME: A CASE SERIES Schultz, B. J., Miglis, M. G., Guilleminault, C. ELSEVIER SCIENCE BV. 2017: E296–E297
  • Is the answer just beneath the surface? And other updates on recent autonomic research CLINICAL AUTONOMIC RESEARCH Miglis, M. G., Muppidi, S. 2017; 27 (6): 357–59

    View details for DOI 10.1007/s10286-017-0475-x

    View details for Web of Science ID 000415130600002

    View details for PubMedID 28983689

  • Let's not forget about the vagus and other updates on recent autonomic research CLINICAL AUTONOMIC RESEARCH Muppidi, S., Miglis, M. G. 2017; 27 (4): 219–21

    View details for DOI 10.1007/s10286-017-0451-5

    View details for Web of Science ID 000406639200005

    View details for PubMedID 28725943

  • Is postural tachycardia syndrome in the head or in the heart? And other updates on recent autonomic research CLINICAL AUTONOMIC RESEARCH Miglis, M. G., Muppidi, S. 2017; 27 (3): 145–47

    View details for DOI 10.1007/s10286-017-0423-9

    View details for Web of Science ID 000401920400005

    View details for PubMedID 28502022

  • A Case Series of REM Sleep Behavior Disorder in Pure Autonomic Failure Miglis, M., During, E., Muppidi, S., Jaradeh, S. LIPPINCOTT WILLIAMS & WILKINS. 2017
  • Utility of Electroencephalography (EEG) during Tilt Table Evaluation for Syncope Muppidi, S., Razavi, B., Miglis, M., Jaradeh, S. LIPPINCOTT WILLIAMS & WILKINS. 2017
  • Is pure autonomic failure an early marker for Parkinson disease, dementia with Lewy bodies, and multiple system atrophy? And other updates on recent autonomic research CLINICAL AUTONOMIC RESEARCH Muppidi, S., Miglis, M. G. 2017; 27 (2): 71-73

    View details for DOI 10.1007/s10286-017-0408-8

    View details for Web of Science ID 000399093100003

    View details for PubMedID 28255741

  • A case series of REM sleep behavior disorder in pure autonomic failure CLINICAL AUTONOMIC RESEARCH Miglis, M. G., Muppidi, S., During, E., Jaradeh, S. 2017; 27 (1): 41-44

    Abstract

    Data on the prevalence of RBD in patients with PAF are limited, with discrepancies in the literature regarding prevalence. We aimed to provide further data on this association with a series of eight patients with PAF.We reviewed the electronic medical records of all patients seen at the Stanford neurology clinics from 2012 to 2016 who were given a provisional diagnosis of PAF (343 patients), and further screened by procedure codes to identify those patients who underwent both attended video-polysomonography and autonomic testing (18 patients), and met strict exclusionary criteria (8 patients).The mean age of our patients was 69 years, and 63 % were women. The mean duration of autonomic symptoms was 11.2 years, and the mean duration of dream enactment was 3.75 years. All patients demonstrated evidence of adrenergic failure on autonomic testing. Five out of 8 (63 %) met diagnostic criteria for RBD, confirmed on vPSG.Our series supports the concept that RBD in PAF may be more common than previously reported, and that the presence of RBD suggests brainstem involvement in some cases of PAF. In addition, the timing of RBD symptoms relative to the emergence of autonomic symptoms may be useful to help distinguish these conditions.

    View details for DOI 10.1007/s10286-016-0386-2

    View details for Web of Science ID 000394183100007

  • The sacral parasympathetic system is actually sympathetic-and other updates on recent autonomic research CLINICAL AUTONOMIC RESEARCH Miglis, M. G., Muppidi, S. 2017; 27 (1): 5–6

    View details for DOI 10.1007/s10286-017-0396-8

    View details for Web of Science ID 000394183100002

    View details for PubMedID 28108826

  • Sleep and the Autonomic Nervous System SLEEP AND NEUROLOGIC DISEASE Miglis, M. G., Miglis, M. G. 2017: 227–44
  • SLEEP AND NEUROLOGIC DISEASE Preface SLEEP AND NEUROLOGIC DISEASE Miglis, M. G., Miglis, M. G. 2017: XIII
  • A case series of REM sleep behavior disorder in pure autonomic failure. Clinical autonomic research Miglis, M. G., Muppidi, S., During, E., Jaradeh, S. 2016: -?

    Abstract

    Data on the prevalence of RBD in patients with PAF are limited, with discrepancies in the literature regarding prevalence. We aimed to provide further data on this association with a series of eight patients with PAF.We reviewed the electronic medical records of all patients seen at the Stanford neurology clinics from 2012 to 2016 who were given a provisional diagnosis of PAF (343 patients), and further screened by procedure codes to identify those patients who underwent both attended video-polysomonography and autonomic testing (18 patients), and met strict exclusionary criteria (8 patients).The mean age of our patients was 69 years, and 63 % were women. The mean duration of autonomic symptoms was 11.2 years, and the mean duration of dream enactment was 3.75 years. All patients demonstrated evidence of adrenergic failure on autonomic testing. Five out of 8 (63 %) met diagnostic criteria for RBD, confirmed on vPSG.Our series supports the concept that RBD in PAF may be more common than previously reported, and that the presence of RBD suggests brainstem involvement in some cases of PAF. In addition, the timing of RBD symptoms relative to the emergence of autonomic symptoms may be useful to help distinguish these conditions.

    View details for PubMedID 27757562

  • Kleine-Levin Syndrome CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS Miglis, M. G., Guilleminault, C. 2016; 16 (6)

    Abstract

    Kleine-Levin syndrome is a rare recurrent hypersomnia associated with symptoms of behavioral and cognitive impairment. This article reviews common presenting symptoms, differential diagnosis, diagnostic workup, and potential treatment options. Current updates on functional imaging studies and long-term neuropsychological studies are reviewed.

    View details for DOI 10.1007/s11910-016-0653-6

    View details for PubMedID 27137943

  • Autonomic dysfunction in primary sleep disorders SLEEP MEDICINE Miglis, M. G. 2016; 19: 40-49

    Abstract

    The autonomic nervous system plays an important role in the coordination of many important physiologic functions during sleep. Many patients with untreated sleep disorders will describe symptoms of autonomic impairment, and a majority of patients with autonomic impairment have some form of sleep disorder. This article will explore possible explanations for this connection, as well as review the current literature on autonomic impairment in common primary sleep disorders including obstructive sleep apnea, insomnia, restless legs syndrome, periodic limb movement disorder, narcolepsy, and rapid eye movement sleep behavior disorder.

    View details for DOI 10.1016/j.sleep.2015.10.001

    View details for Web of Science ID 000376518600008

    View details for PubMedID 27198946

  • Sleep disorders in patients with postural tachycardia syndrome. Clinical autonomic research Miglis, M. G., Muppidi, S., Feakins, C., Fong, L., Prieto, T., Jaradeh, S. 2016; 26 (1): 67-73

    Abstract

    Patients with postural tachycardia syndrome (POTS) often describe symptoms of fatigue, sleepiness, and lack of refreshing sleep. We aimed to provide further objective measures of sleep in patients with POTS.POTS patients (n = 18) were selected based on autonomic testing and evaluation at our center. Controls (n = 16) of similar age, gender, and BMI were selected from new patients referred to the Stanford Sleep Disorders Clinic for any sleep-related complaint. All patients underwent polysomnography and completed several sleep questionnaires and a 2-week sleep diary.POTS patients and control subjects were of similar age (27 ± 10.2 vs. 29 ± 5.4 years, p = 0.92) and Body Mass Index (21 ± 3.8 vs. 24 ± 4.1, p = 0.14). The majority of subjects in both groups were females (72 % POTS vs. 81 % controls). POTS patients scored higher on subjective fatigue scales but not sleepiness scales. POTS patients scored in the normal range on the BDI and the "evening" category on the MEQ. Their sleep diaries were not different from controls. With the exception of mild OSA, slightly reduced %REM and prolonged REM latency, their PSG data were normal and no different from controls.It is unlikely that the sleep-related complaints of POTS patients are the result of a primary sleep disorder unique to POTS. We propose that a combination of factors such as body fatigue, chronic pain, and other somatic symptoms common in POTS patients might be the underlying reason for sleep-related symptoms in POTS.

    View details for DOI 10.1007/s10286-015-0331-9

    View details for PubMedID 26695400

  • Autonomic dysfunction in primary sleep disorders Sleep Medicine Miglis, M. G. 2016; 19
  • Emerging Subspecialties in Neurology: Autonomic disorders. Neurology Palma, J., Cook, G. A., Miglis, M. G., Loavenbruck, A. 2015; 84 (10): e73-5

    View details for DOI 10.1212/WNL.0000000000001337

    View details for PubMedID 25754808

    View details for PubMedCentralID PMC4352100

  • Prevalence of REM sleep behavior disorder in multiple system atrophy: a multicenter study and meta-analysis CLINICAL AUTONOMIC RESEARCH Palma, J., Fernandez-Cordon, C., Coon, E. A., Low, P. A., Miglis, M. G., Jaradeh, S., Bhaumik, A. K., Dayalu, P., Urrestarazu, E., Iriarte, J., Biaggioni, I., Kaufmann, H. 2015; 25 (1): 69-75

    Abstract

    Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia frequently affecting patients with synucleinopathies, but its exact prevalence in multiple system atrophy (MSA) is unclear. Whether questionnaires alone are sufficient to diagnose RBD is also unknown.We performed a cross-sectional study of patients with probable MSA from six academic centers in the US and Europe. RBD was ascertained clinically and with polysomnography; we also performed a meta-analysis according to PRISMA guidelines for studies published before September 2014 that reported the prevalence of RBD in MSA. A random-effects model was constructed using weighted prevalence proportions. Only articles in English were included. Studies were classified into those that ascertained the presence of RBD in MSA clinically and with polysomnography. Case reports or case series (≤5 patients) were not included.Forty-two patients completed questionnaires and underwent polysomnography. Of those, 32 (76.1 %) had clinically suspected RBD and 34 (81 %) had polysomnography-confirmed RBD. Two patients reported no symptoms of RBD but had polysomnography-confirmed RBD. The primary search strategy yielded 374 articles of which 12 met the inclusion criteria. The summary prevalence of clinically suspected RBD was 73 % (95 % CI, 62-84 %) in a combined sample of 324 MSA patients. The summary prevalence of polysomnography-confirmed RBD was 88 % (95 % CI, 79-94 %) in a combined sample of 217 MSA patients.Polysomnography-confirmed RBD is present in up to 88 % of patients with MSA. RBD was present in some patients that reported no symptoms. More than half of MSA patients report symptoms of RBD before the onset of motor deficits.

    View details for DOI 10.1007/s10286-015-0279-9

    View details for Web of Science ID 000353286500009

    View details for PubMedID 25739474

  • Daytime Sleepiness SLEEP MEDICINE CLINICS Miglis, M. G., Kushida, C. A. 2014; 9 (4): 491-+
  • Kleine-Levin syndrome: a review. Nature and science of sleep Miglis, M. G., Guilleminault, C. 2014; 6: 19-26

    Abstract

    Kleine-Levin syndrome is a recurrent hypersomnia associated with symptoms of hyperphagia, hypersexuality, and cognitive impairment. This article reviews the current available research and describes common clinical symptoms, differential diagnosis, and acceptable workup and treatment. Although deficits have traditionally been thought to resolve between episodes, functional imaging studies and long-term neuropsychological testing in select patients have recently challenged this notion. This may suggest that Kleine-Levin syndrome is not as benign as previously considered.

    View details for DOI 10.2147/NSS.S44750

    View details for PubMedID 24470783

  • Sleep Disorders in Patients with Postural Tachycardia Syndrome Miglis, M., Gibbons, C., Freeman, R. LIPPINCOTT WILLIAMS & WILKINS. 2013
  • Right sided headache Case Based Neurology Miglis, M., Graber, J. Demo. 2013; 1: 261–5
  • A piece of my mind. Annie. JAMA Miglis, M. 2009; 306 (18): 1960-1.
  • Seropositive myasthenia and autoimmune autonomic ganglionopathy: Cross reactivity or subclinical disease? AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL Miglis, M. G., Racela, R., Kaufmann, H. 2011; 164 (1-2): 87-88

    Abstract

    Autoimmune autonomic ganglionopathy (AAG) and myasthenia gravis (MG) are both autoimmune channelopathies mediated by antibodies directed against nicotinic acetylcholine receptors. While both diseases target acetylcholine receptors, skeletal muscle and ganglionic receptor subtypes have key immunologic and genetic distinctions, and reports of patients with both AAG and MG are rare. We report a patient with antibody-confirmed AAG and elevated levels of ACh binding antibodies that did not meet clinical or electrodiagnostic criteria for MG. We presume that his skeletal muscle nAChR seropositivity was a false positive, perhaps due to the cross reactivity of the patient's ganglionic nAChR antibodies with skeletal nAChR subtypes.

    View details for DOI 10.1016/j.autneu.2011.06.005

    View details for Web of Science ID 000295346500013

    View details for PubMedID 21745762

  • Intracranial Venous Thrombosis After Placement of a Lumbar Drain NEUROCRITICAL CARE Miglis, M. G., Levine, D. N. 2010; 12 (1): 83-87

    Abstract

    Lumbar drains are frequently used in clinical neuroscience and are often managed in the neurointensive care unit. Complications are generally rare, and intracranial venous thrombosis (IVT) and infarction has not been reported.We report the case of a 45-year-old woman who developed a cerebrospinal fluid (CSF) leak after spinal surgery. Fifteen hours after placement of a lumbar drain she developed pure alexia and color agnosia caused by left lateral sinus thrombosis with hemorrhagic infarction in the posterior inferior left temporal lobe. We review the literature on the association of IVT with injury to the spinal dura, and we propose a mechanism whereby the lumbar drain may facilitate its development.We found 29 cases in which spinal dural injury was followed by IVT. The association is not coincidental, because nearly all cases were associated with post-dural puncture headache, which occurs in only a minority of cases of dural puncture. Injury to the spinal dura alters the distribution of craniospinal elasticity causing profound intracranial CSF hypotension on assuming the erect posture. This causes acute dilation of cerebral veins resulting in both orthostatic headache and venous stasis. We propose that placement of the lumbar drain and elevation of the head of the bed aggravated intracranial CSF hypotension and facilitated IVT.When a lumbar drain is placed for treatment of a spinal CSF leak, the patient should remain flat in bed. Any patient with post-dural injury headache that intensifies after an initial plateau, persists for longer than a week, or loses its orthostatic character should be evaluated for intracranial sinus or venous thrombosis.

    View details for DOI 10.1007/s12028-009-9278-9

    View details for Web of Science ID 000275742800015

    View details for PubMedID 19834826

  • Effect of taurine on platelets and the plasma coagulation system PLATELETS Miglis, M., Wilder, D., Reid, T., Bakaltcheva, I. 2002; 13 (1): 5-10

    Abstract

    It is not yet clear what exact mechanisms are at work in hibernating animals that prevent clot formation and maintain tissue perfusion under conditions of very slow blood flow and increased blood viscosity brought about by the low temperatures. It has been shown that the total amino acid pool increases more then two fold in hibernating animals with taurine accounting for about 50% of this increase [Storey et al., Proc Natl Acad Sci USA 1988; 85(21): 8350-4]. This work investigates the effect of taurine on platelets and the plasma coagulation system. Taurine was added at different concentrations in the range between 5 and 25 mM to donor plasma. Using STA/STA Compact coagulation analyzer the following tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). At the highest concentration tested (25 mM) taurine prolonged TT by 9%. The prolongation was statistically significant but not clinically significant retaining TT within normal limits (16.7-20.7 s). PT and APTT remained unchanged by taurine. The effect of taurine on platelets was assessed by platelet aggregation by thrombin, extent of platelet shape change (ESC) induced by ADP, and thrombelastography. Taurine at 5 mM final concentration inhibited platelet aggregation by 10%. Increasing taurine concentration to 25 mM did not result in a further augmentation of the inhibitory effect. ESC was unaffected by taurine. Clot strength determined by thrombelastography also remained unchanged by taurine.

    View details for Web of Science ID 000173601100001

    View details for PubMedID 11918831