Bio


Dr. Sarada Sakamuri specializes in neuromuscular medicine. Her interests are in peripheral nerve injury, neuromuscular ultrasound, EMG/NCS, neurogenetic disorders, clinical research, and medical education.

Dr. Sakamuri studied psychology at Rutgers University and she graduated with Phi Beta Kappa distinction. She obtained her medical degree from Rutgers New Jersey Medical School, where she lead multiple community service and medical education activities and was elected to the Alpha Omega Alpha and Gold Humanism Honor Societies. She moved to the Bay Area to pursue neurology residency at Stanford and later served as chief resident. She then completed two years of fellowship in EMG/Clinical Neurophysiology and Neuromuscular Medicine and research training at Forbes Norris MDA/ALS Research Center.

She serves as the Co-Director of the Center for Peripheral Nerve Surgery along with neurosurgeon Dr. Thomas J. Wilson. She performs advanced evaluations of peripheral nerve conditions by integrating nerve and muscle ultrasound and neurophysiologic testing (EMG/NCS) at the bedside. She has advanced training and particular interest in ultrasound, and sits on the Neuromuscular Ultrasound Committee of the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM).

She is board-certified in Neurology and Neuromuscular disorders by the American Board of Psychiatry and Neurology (ABPN). She is certified in EMG/NCS by the American Board of Electrodiagnostic Medicine (ABEM).

Dr. Sakamuri's other passion is medical education. She is the Associate Director of the Stanford Neuromuscular Medicine and Clinical Neurophysiology/EMG Fellowships. She supervises a weekly neurology resident continuity clinic and enjoys leading teaching sessions for neurology and physiatrist residents and medical students. She has also served as a clinical instructor at Jagiellonian University Medical College in Poland, and as a teaching fellow at Stanford School of Medicine.

Clinical Focus


  • Peripheral Nerve Trauma
  • Peripheral Nerve Injury
  • Neurology
  • ALS (Amyotrophic Lateral Sclerosis)
  • CIDP
  • Guillain-Barre Syndrome
  • Lambert-Eaton Myasthenic Syndrome
  • Muscular Dystrophies
  • Myasthenia Gravis
  • Myopathy
  • Rod Myopathy
  • Peripheral Neuropathy

Academic Appointments


Administrative Appointments


  • Co-Director, Center for Peripheral Nerve Surgery, Stanford University Departments of Neurosurgery and Neurology (2017 - Present)
  • Associate Director, Clinical Neurophysiology/EMG Fellowship, Stanford University School of Medicine (2015 - Present)
  • Associate Director, Neuromuscular Medicine Fellowship, Stanford University School of Medicine (2015 - Present)
  • Clinical Assistant Professor, Neuromuscular Disorders & General Neurology, Stanford University School of Medicine (2014 - Present)
  • Clinical Assistant Professor, Neuromuscular Disorders & General Neurology, University Healthcare Alliance, a physician network serving patients around the Bay Area (2014 - Present)

Honors & Awards


  • American Academy of Neurology Resident Scholarship, American Academy of Neurology (2012)
  • Neurology Medical Student Clerkship Teaching Award, Stanford Department of Neurology (2012)
  • Neurology Medical Student Clerkship Teaching Award, Stanford Department of Neurology (2010)
  • Nomination for Golden Apple Teaching Award, New Jersey Medical School (2009)
  • American Academy of Neurology Medical Student Prize, American Academy of Neurology (2008)
  • Member, Arnold P. Gold Humanism Honor Society (2008)
  • Member, Alpha Omega Alpha Medical Honor Society (2008)
  • Member, Phi Beta Kappa (2004)

Boards, Advisory Committees, Professional Organizations


  • Member, GME Committee, American Association of Neuromuscular and Electrodiagnostic Medicine (2017 - Present)
  • Member, American Association of Neuromuscular and Electrodiagnostic Medicine (2012 - Present)
  • Member, Ultrasound Committee, American Association of Neuromuscular and Electrodiagnostic Medicine (2016 - Present)
  • Member, American Academy of Neurology Neuromuscular Section (2012 - Present)
  • Member, American Academy of Neurology (2009 - Present)

Professional Education


  • Fellowship:Stanford University Neuromuscular Medicine Fellowship (2014) CA
  • Fellowship:Stanford University Clinical Neurophysiology Fellowship (2013) CA
  • Residency:Stanford University Neurology Residency (2012) CA
  • Internship:Rutgers New Jersey Medical School UMDNJ Internal Medicine Residency (2009) NJ
  • Medical Education:Rutgers New Jersey Medical School Office of the Registrar (2008) NJ
  • Board Certified, Electrodiagnostic Medicine, American Board of Electrodiagnostic Medicine (2015)
  • Board Certified, Neuromuscular Medicine, American Board of Psychiatry and Neurology (2014)
  • Board Certified, Neurology, American Board of Psychiatry and Neurology (2012)
  • Research Fellowship, Respiratory dysfunction in ALS, California Pacific Medical Center, Forbes Norris MDA/ALS Research Center (2014)
  • Fellowship, Neuromuscular Medicine, Stanford University School of Medicine (2014)
  • Fellowship, EMG/Clinical Neurophysiology, Stanford University School of Medicine (2013)
  • Residency, Neurology, Stanford Hospital & Clinics (2012)
  • Internship, Internal Medicine, New Jersey Medical School (2009)
  • Medical Education, New Jersey Medical School (2008)

Community and International Work


  • Clinical Instructor, Krakow, Poland

    Topic

    Clinical Neurology

    Partnering Organization(s)

    Jagiellonian University Medical College

    Populations Served

    Medical students

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Teaching Fellow, Stanford

    Topic

    Human Health and Disease INDE 223

    Partnering Organization(s)

    Stanford School of Medicine

    Populations Served

    Medical students

    Location

    Bay Area

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Co-Founder and Director, PINACLE (Partnership in Newark Advocating Community Leaders' Empowerment), Newark, NJ

    Topic

    Community Medical Education

    Partnering Organization(s)

    New Jersey Medical School

    Populations Served

    Patients and community members

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

  • Student Director, Mini-Med School, Newark, NJ

    Topic

    Community Medical Education

    Partnering Organization(s)

    New Jersey Medical School

    Populations Served

    Adults and high school students

    Location

    US

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

Clinical Trials


  • Embodied Virtual Reality Therapy for Functional Neurological Symptom/ Conversion Disorder Recruiting

    The purpose of this study is to design and test the safety and feasibility of virtual reality technologies and experiences of egocentric avatar embodiment in the application of physical and cognitive behavior therapy in functional neurological symptom/conversion disorder. Investigators hypothesize that patients will safely use and accept this modality of treatment and will show evidence of a decrease in symptom frequency.

    View full details

  • Prospective, Longitudinal Study of the Natural History and Functional Status of Patients With Myotubular Myopathy (MTM) Recruiting

    This is a prospective, non-interventional, longitudinal study of the natural history and function of approximately 60 patients with MTM from the United States, Canada and Europe. The duration of the study, including the enrollment period, will be 36 months. Data from the study will be used to characterize the disease course of MTM and determine which outcome measures will be the best to assess the efficacy of potential therapies.

    View full details

  • Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis (REGAIN Study) Recruiting

    The purpose of this study is to determine if eculizumab is safe and effective for the treatment of refractory generalized Myasthenia Gravis.

    View full details

  • A Phase 3 Study of Amifampridine Phosphate in Patients With Lambert Eaton Myasthenic Syndrome (LEMS) Not Recruiting

    A Phase 3 study to evaluate the efficacy and safety of Amifampridine Phosphate in patients with Lambert-Eaton Myasthenic Syndrome (LEMS).

    Stanford is currently not accepting patients for this trial.

    View full details

  • A Safety andTolerability Study of Multiple Doses of ISIS-DMPKRx in Adults With Myotonic Dystrophy Type 1 Not Recruiting

    This study will test the safety, tolerability, and pharmacokinetics of multiple escalating doses of ISIS-DMPKRx administered subcutaneously to adult patients with DM1.

    Stanford is currently not accepting patients for this trial. For more information, please contact Shirley Paulose, 650-725-4341.

    View full details

  • Diaphragm Pacing System (DPS) In Participants With Amyotrophic Lateral Sclerosis (ALS) Not Recruiting

    The study is being conducted to determine if DPS treatment for people with ALS and hypoventilation is associated with improved survival or diaphragm function. The primary objective of the study is to conduct a multi-center, randomized controlled clinical trial comparing standard of care (control) to diaphragm stimulator treatment with the NeuRx® Diaphragm Pacing System™ (DPS) with respect to survival. The secondary objective of the study is to conduct a multi-center, randomized controlled clinical trial to compare standard of care treatment (control) to DPS in ALS subjects with hypoventilation.

    Stanford is currently not accepting patients for this trial. For more information, please contact Shirley Paulose, 650-724-3792.

    View full details

Projects


  • Subject Database and Specimen Repository for Neuromuscular and Neurodegenerative Disorders, Stanford University

    This is a study that involves collecting clinical information of subjects (patients with any neurological condition or their close family member) and tissue samples to develop a subject database and tissue bank, which will be of great value in helping the investigators learn more about various related neurological conditions. This also includes a Biobank.

    Location

    Stanford, CA

    Collaborators

  • Clinical and Genetic Characterization of Myotonic Dystrophy, Stanford University

    This is an umbrella protocol for Myotonic Dystrophy to study various aspects of the disease including sleep abnormalities.

    Location

    Stanford, CA

    Collaborators

Graduate and Fellowship Programs


  • Neurophysiology (Fellowship Program)

All Publications


  • Long-term safety and efficacy of eculizumab in generalized myasthenia gravis. Muscle & nerve Muppidi, S., Utsugisawa, K., Benatar, M., Murai, H., Barohn, R. J., Illa, I., Jacob, S., Vissing, J., Burns, T. M., Kissel, J. T., Nowak, R. J., Andersen, H., Casasnovas, C., De Bleecker, J. L., Vu, T. H., Mantegazza, R., O'Brien, F. L., Wang, J. J., Fujita, K. P., Howard, J. F., REGAIN Study Group, Mazia, C. G., Wilken, M., Barroso, F., Saba, J., Rugiero, M., Bettini, M., Chaves, M., Vidal, G., Garcia, A. D., Van den Abeele, G., de Koning, K., De Mey, K., Mercelis, R., Mahieu, D., Wagemaekers, L., Van Damme, P., Depreitere, A., Schotte, C., Smetcoren, C., Stevens, O., Van Daele, S., Vandenbussche, N., Vanhee, A., Verjans, S., Vynckier, J., D'Hondt, A., Tilkin, P., Alves de Siqueira Carvalho, A., Dias Brockhausen, I., Feder, D., Ambrosio, D., Cesar, P., Melo, A. P., Martins Ribeiro, R., Rocha, R., Bezerra Rosa, B., Veiga, T., da Silva, L. A., Santos Engel, M., Goncalves Geraldo, J., Ananias Morita, M. d., Nogueira Coelho, E., Paiva, G., Pozo, M., Prando, N., Martineli Torres, D. D., Butinhao, C. F., Duran, G., Gomes da Silva, T. C., Otavio Maia Goncalves, L., Pazetto, L. E., Fialho, T. A., Renata Cubas Volpe, L., Souza Duca, L., Gheller Friedrich, M. A., Guerreiro, A., Mohr, H., Pereira Martins, M., da Cruz Pacheco, D., Ferreira, L., Macagnan, A. P., Pinto, G., Santos, A. d., Souza Bulle Oliveira, A., Amaral Andrade, A. C., Annes, M., Duarte Silva, L., Cavalcante Lino, V., Pinto, W., Assis, N., Carrara, F., Miranda, C., Souza, I., Fernandes, P., Siddiqi, Z., Phan, C., Narayan, J., Blackmore, D., Mallon, A., Roderus, R., Watt, E., Vohanka, S., Bednarik, J., Chmelikova, M., Cierny, M., Toncrova, S., Junkerova, J., Kurkova, B., Reguliova, K., Zapletalova, O., Pitha, J., Novakova, I., Tyblova, M., Jurajdova, I., Wolfova, M., Harbo, T., Vinge, L., Krogh, S., Mogensen, A., Hojgaard, J., Witting, N., Ostergaard Autzen, A., Pedersen, J., Eralinna, J., Laaksonen, M., Oksaranta, O., Harrison, T., Eriksson, J., Rozsa, C., Horvath, M., Lovas, G., Matolcsi, J., Szabo, G., Jakab, G., Szabadosne, B., Vecsei, L., Dezsi, L., Varga, E., Konyane, M., Antonini, G., Di Pasquale, A., Garibaldi, M., Morino, S., Troili, F., Fionda, L., Filla, A., Costabile, T., Marano, E., Sacca, F., Fasanaro, A., Marsili, A., Puorro, G., Antozzi, C., Bonanno, S., Camera, G., Locatelli, A., Maggi, L., Pasanisi, M., Campanella, A., Evoli, A., Alboini, P. E., D'Amato, V., Iorio, R., Inghilleri, M., Fionda, L., Frasca, V., Giacomelli, E., Gori, M., Lopergolo, D., Onesti, E., Frasca, V., Gabriele, M., Uzawa, A., Kanai, T., Kawaguchi, N., Mori, M., Kaneko, Y., Kanzaki, A., Kobayashi, E., Masaki, K., Matsuse, D., Matsushita, T., Uehara, T., Shimpo, M., Jingu, M., Kikutake, K., Nakamura, Y., Sano, Y., Nagane, Y., Kamegamori, I., Tsuda, T., Fujii, Y., Futono, K., Ozawa, Y., Mizugami, A., Saito, Y., Suzuki, H., Morikawa, M., Samukawa, M., Kamakura, S., Miyawaki, E., Shiraishi, H., Mitazaki, T., Motomura, M., Mukaino, A., Yoshimura, S., Asada, S., Yoshida, S., Amamoto, S., Kobashikawa, T., Koga, M., Maeda, Y., Takada, K., Takada, M., Tsurumaru, M., Yamashita, Y., Suzuki, Y., Akiyama, T., Narikawa, K., Tano, O., Tsukita, K., Kurihara, R., Meguro, F., Fukuda, Y., Sato, M., Okumura, M., Funaka, S., Kawamura, T., Makamori, M., Takahashi, M., Taichi, N., Hasuike, T., Higuchi, E., Kobayashi, H., Osakada, K., Imai, T., Tsuda, E., Shimohama, S., Hayashi, T., Hisahara, S., Kawamata, J., Murahara, T., Saitoh, M., Suzuki, S., Yamamoto, D., Ishiyama, Y., Ishiyama, N., Noshiro, M., Takeyama, R., Uwasa, K., Yasuda, I., van der Kooi, A., de Visser, M., Gibson, T., Kim, B., Lee, C. N., Koo, Y. S., Seok, H. Y., Kang, H. N., Ra, H., Kim, B. J., Cho, E. B., Choi, M., Lee, H., Min, J., Seok, J., Lee, J., Koh, D. Y., Kwon, J., Park, S., Choi, E. H., Hong, Y., Ahn, S., Koo, D. L., Lim, J., Shin, C. W., Hwang, J. Y., Kim, M., Kim, S. M., Jeong, H., Jung, J., Kim, Y., Lee, H. S., Shin, H. Y., Hwang, E. B., Shin, M., Alberti Aguilo, M. A., Homedes-Pedret, C., Julia Palacios, N., Diez Porras, L., Velez Santamaria, V., Lazaro, A., Diez Tejedor, E., Gomez Salcedo, P., Fernandez-Fournier, M., Lopez Ruiz, P., Rodriguez de Rivera, F. J., Sastre, M., Gamez, J., Sune, P., Salvado, M., Gili, G., Mazuela, G., Cortes Vicente, E., Diaz-Manera, J., Querol Gutierrez, L. A., Rojas Garcia, R., Vidal, N., Arribas-Ibar, E., Piehl, F., Hietala, A., Bjarbo, L., Sengun, I., Meherremova, A., Ozcelik, P., Balkan, B., Tuga, C., Ugur, M., Erdem-Ozdamar, S., Bekircan-Kurt, C. E., Acar, N. P., Yilmaz, E., Caliskan, Y., Orsel, G., Efendi, H., Aydinlik, S., Cavus, H., Kutlu, A., Becerikli, G., Semiz, C., Tun, O., Terzi, M., Dogan, B., Onar, M. K., Sen, S., Kirbas Cavdar, T., Veske, A., Norwood, F., Dimitriou, A., Gollogly, J., Mahdi-Rogers, M., Seddigh, A., Sokratous, G., Maier, G., Sohail, F., Sadalage, G., Torane, P., Brown, C., Shah, A., Sathasivam, S., Arndt, H., Davies, D., Watling, D., Amato, A., Cochrane, T., Salajegheh, M., Roe, K., Amato, K., Toska, S., Wolfe, G., Silvestri, N., Patrick, K., Zakalik, K., Katz, J., Miller, R., Engel, M., Forshew, D., Bravver, E., Brooks, B., Plevka, S., Burdette, M., Cunningham, S., Sanjak, M., Kramer, M., Nemeth, J., Schommer, C., Tierney, S., Juel, V., Guptill, J., Hobson-Webb, L., Massey, J., Beck, K., Carnes, D., Loor, J., Anderson, A., Pascuzzi, R., Bodkin, C., Kincaid, J., Snook, R., Guingrich, S., Micheels, A., Chaudhry, V., Corse, A., Mosmiller, B., Kelley, A., Ho, D., Srinivasan, J., Vytopil, M., Jara, J., Ventura, N., Scala, S., Carter, C., Donahue, C., Herbert, C., Weiner, E., Alam, S., McKinnon, J., Haar, L., McKinnon, N., Alcon, K., McKenna, K., Sattar, N., Daniels, K., Jeffery, D., Freimer, M., Hoyle, J. C., Agriesti, J., Chelnick, S., Mezache, L., Pineda, C., Muharrem, F., Karam, C., Khoury, J., Marburger, T., Kaur, H., Dimitrova, D., Gilchrist, J., Agrawal, B., Elsayed, M., Kohlrus, S., Andoin, A., Darnell, T., Golden, L., Lokaitis, B., Seelback, J., Goyal, N., Sakamuri, S., So, Y. T., Paulose, S., Pol, S., Welsh, L., Bhavaraju-Sanka, R., Tobon Gonzales, A., Dishman, L., Jones, F., Gonzalez, A., Padilla, P., Saklad, A., Silva, M., Nations, S., Trivedi, J., Hopkins, S., Kazamel, M., Alsharabati, M., Lu, L., Nozaki, K., Mumfrey-Thomas, S., Woodall, A., Mozaffar, T., Cash, T., Goyal, N., Roy, G., Mathew, V., Maqsood, F., Minton, B., Jones, H. J., Rosenfeld, J., Garcia, R., Echevarria, L., Garcia, S., Pulley, M., Aranke, S., Berger, A. R., Shah, J., Shabbir, Y., Smith, L., Varghese, M., Gutmann, L., Gutmann, L., Jerath, N., Nance, C., Swenson, A., Olalde, H., Kressin, N., Sieren, J., Dimachkie, M., Glenn, M., McVey, A., Pasnoor, M., Statland, J., Wang, Y., Liu, T., Emmons, K., Jenci, N., Locheke, J., Fondaw, A., Johns, K., Rico, G., Walsh, M., Herbelin, L., Hafer-Macko, C., Kwan, J., Zilliox, L., Callison, K., Young, V., DiSanzo, B., Naunton, K., Bilsker, M., Sharma, K., Cooley, A., Reyes, E., Michon, S., Sheldon, D., Steele, J., Karam, C., Chopra, M., Traub, R., Katzin, L., McClain, T., Harvey, B., Hart, A., Huynh, K., Beydoun, S., Chilingaryan, A., Doan, V., Droker, B., Gong, H., Karimi, S., Lin, F., McClain, T., Pokala, K., Shah, A., Tran, A., Akhter, S., Malekniazi, A., Tandan, R., Hehir, M., Waheed, W., Lucy, S., Weiss, M., Distad, J., Strom, S., Downing, S., Kim, B., Bertorini, T., Arnold, T., Hendersen, K., Pillai, R., Liu, Y., Wheeler, L., Hewlett, J., Vanderhook, M., Dicapua, D., Keung, B., Kumar, A., Patwa, H., Robeson, K., Yang, I., Nye, J., Vu, H. 2019

    Abstract

    INTRODUCTION: Eculizumab is effective and well tolerated in patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open-label extension of REGAIN evaluating eculizumab's long-term safety and efficacy.METHODS: 117 patients received eculizumab (1,200 mg every 2 weeks) for 22.7 months (median).RESULTS: The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. MG exacerbation rate was reduced by 75% from the year before REGAIN (p<0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who received placebo during REGAIN experienced rapid and sustained improvements during open-label eculizumab (p<0.0001).DISCUSSION: These findings demonstrate the long-term safety and sustained efficacy of eculizumab for refractory gMG. This article is protected by copyright. All rights reserved.

    View details for PubMedID 30767274

  • An Update on the Management of Adult Traumatic Nerve Injuries-Replacing Old Paradigms: A Review. The journal of trauma and acute care surgery Smith, B. W., Sakamuri, S., Spain, D. A., Joseph, J. R., Yang, L. J., Wilson, T. J. 2018

    Abstract

    Acute nerve injuries are routinely encountered in multisystem trauma patients. Advances in surgical treatment of nerve injuries now mean that good outcomes can be achieved. Despite this, old mantras associated with management of nerve injuries, including "wait a year to see if recovery occurs" and "there's nothing we can do", persist. Practicing by these mantras places these patients at a disadvantage.Changes begin to occur in the nerve, neuromuscular junction, and muscle from the moment a nerve injury occurs. These changes can become irreversible approximately 18-24 months following denervation. Thus, it is a race to reestablish a functional nerve-muscle connection prior to these irreversible changes. Good outcomes rely on appropriate acute management and avoiding delays in care. Primary nerve surgery options include direct primary repair, nerve graft repair, and nerve transfer. Acute management of nerve injuries proceeds according to the rule of 3s and requires early cooperation between trauma surgeons who recognize the nerve injury and consultant nerve surgeons.Care of patients with acute, traumatic nerve injuries should not be delayed. Awareness of current management paradigms among trauma surgeons will help facilitate optimal upfront management. With the ever-expanding surgical options for management of these injuries and the associated improvement of outcomes, early multidisciplinary approaches to these injuries has never been more important. Old mantras must be replaced with new paradigms in order to continue to see improvements in outcomes for these patients. The importance of this review is to raise awareness among trauma surgeons of new paradigms for management of traumatic nerve injuries.

    View details for PubMedID 30278019

  • Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy NEW ENGLAND JOURNAL OF MEDICINE Mercuri, E., Darras, B. T., Chiriboga, C. A., Day, J. W., Campbell, C., Connolly, A. M., Iannaccone, S. T., Kirschner, J., Kuntz, N. L., Saito, K., Shieh, P. B., Tulinius, M., Mazzone, E. S., Montes, J., Bishop, K. M., Yang, Q., Foster, R., Gheuens, S., Bennett, C. F., Farwell, W., Schneider, E., De Vivo, D. C., Finkel, R. S., CHERISH Study Grp 2018; 378 (7): 625–35

    Abstract

    Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills.In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P<0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P<0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively).Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials.gov number, NCT02292537 .).

    View details for PubMedID 29443664

  • Increased EEG Theta Spectral Power in Sleep in Myotonic Dystrophy Type 1. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine Cheung, J., Ruoff, C., Moore, H., Hagerman, K. A., Perez, J., Sakamuri, S., Warby, S. C., Mignot, E., Day, J., Sampson, J. 2018; 14 (2): 229–35

    Abstract

    Myotonic dystrophy type 1 (DM1) is a multisystemic disorder that involves the central nervous system (CNS). Individuals with DM1 commonly present with sleep dysregulation, including excessive daytime sleepiness and sleep-disordered breathing. We aim to characterize electroencephalogram (EEG) power spectra from nocturnal polysomnography (PSG) in patients with DM1 compared to matched controls to better understand the potential CNS sleep dysfunction in DM1.A retrospective, case-control (1:2) chart review of patients with DM1 (n = 18) and matched controls (n = 36) referred for clinical PSG at the Stanford Sleep Center was performed. Controls were matched based on age, sex, apnea-hypopnea index (AHI), body mass index (BMI), and Epworth Sleepiness Scale (ESS). Sleep stage and respiratory metrics for the two groups were compared. Power spectral analysis of the EEG C3-M2 signal was performed using the fast Fourier transformation.Patients with DM1 had significantly increased theta percent power in stage N2 sleep compared to matched controls. Theta/beta and theta/alpha percent power spectral ratios were found to be significantly increased in stage N2, N3, all sleep stages combined, and all wake periods combined in patients with DM1 compared to controls. A significantly lower nadir O2saturation was also found in patients with DM1 versus controls.Compared to matched controls, patients with DM1 had increased EEG theta spectral power. Increased theta/beta and theta/alpha power spectral ratios in nocturnal PSG may reflect DM1 pathology in the CNS.

    View details for DOI 10.5664/jcsm.6940

    View details for PubMedID 29394960

    View details for PubMedCentralID PMC5786842

  • Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study LANCET NEUROLOGY Howard, J. F., Utsugisawa, K., Benatar, M., Murai, H., Barohn, R. J., Illa, I., Jacob, S., Vissing, J., Burns, T. M., Kissel, J. T., Muppidi, S., Nowak, R. J., O'Brien, F., Wang, J., Mantegazza, R., REGAIN Study Grp 2017; 16 (12): 976–86

    Abstract

    Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial.We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators, staff, and outcome assessors were masked to treatment assignment. The primary efficacy endpoint was the change from baseline to week 26 in MG-ADL total score measured by worst-rank ANCOVA. The efficacy population set was defined as all patients randomly assigned to treatment groups who received at least one dose of study drug, had a valid baseline MG-ADL assessment, and at least one post-baseline MG-ADL assessment. The safety analyses included all randomly assigned patients who received eculizumab or placebo. This trial is registered with ClinicalTrials.gov, number NCT01997229.Between April 30, 2014, and Feb 19, 2016, we randomly assigned and treated 125 patients, 62 with eculizumab and 63 with placebo. The primary analysis showed no significant difference between eculizumab and placebo (least-squares mean rank 56·6 [SEM 4·5] vs 68·3 [4·5]; rank-based treatment difference -11·7, 95% CI -24·3 to 0·96; p=0·0698). No deaths or cases of meningococcal infection occurred during the study. The most common adverse events in both groups were headache and upper respiratory tract infection (ten [16%] for both events in the eculizumab group and 12 [19%] for both in the placebo group). Myasthenia gravis exacerbations were reported by six (10%) patients in the eculizumab group and 15 (24%) in the placebo group. Six (10%) patients in the eculizumab group and 12 (19%) in the placebo group required rescue therapy.The change in the MG-ADL score was not statistically significant between eculizumab and placebo, as measured by the worst-rank analysis. Eculizumab was well tolerated. The use of a worst-rank analytical approach proved to be an important limitation of this study since the secondary and sensitivity analyses results were inconsistent with the primary endpoint result; further research into the role of complement is needed.Alexion Pharmaceuticals.

    View details for PubMedID 29066163

  • Phrenic nerve conduction studies as a biomarker of respiratory insufficiency in amyotrophic lateral sclerosis AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION Jenkins, J. A., Sakamuri, S., Katz, J. S., Forshew, D. A., Guion, L., Moore, D., Miller, R. G. 2016; 17 (3-4): 213-220

    Abstract

    Our objective was to examine the value of phrenic nerve conduction studies (PNCS) in quantifying diaphragm dysfunction in ALS, as no ideal test of respiratory insufficiency exists in ALS. We prospectively recorded bilateral PNCS, forced vital capacity (FVC), maximum inspiratory pressure (MIP), sniff nasal inspiratory pressure (SNIP), respiratory rate, ALSFRS-R, and respiratory symptoms in 100 ALS patients attending our clinic over a nine-month period. Survival data were collected for two years. Results showed that PNCS were reproducible and well tolerated. When the Pamp was abnormal (<0.3 mV), the relative risk of a respiratory rate >18 was 7.2 (95% CI 2.2-37.2, p <0.01) compared with a Pamp ≥0.3 mV. Similarly, the relative risk of orthopnea was 3.5 (95% CI 1.6-8.7, p <0.01) and dyspnea 2.4 (95% CI 1.4-4.0, p <0.01). FVC had the strongest correlation with Pamp (R(2) = 0.48 (p <0.001)). Fourteen of 15 patients with a FVC <50% had a Pamp <0.3 mV. However, eight with a Pamp <0.3 had a FVC >80%. The median survival was 1.07 years when the Pamp was <0.3 mV and >2 years when the Pamp was >0.3 mV (p <0.001). In conclusion, the phrenic Pamp correlated closely with multiple symptoms, signs, and laboratory measures of respiratory insufficiency and may prove to be a useful biomarker of respiratory dysfunction in ALS.

    View details for DOI 10.3109/21678421.2015.1112406

    View details for Web of Science ID 000374776900008

    View details for PubMedID 26618854

  • Congenital muscular dystrophy and generalized epilepsy caused by GMPPB mutations. Brain research Raphael, A. R., Couthouis, J., Sakamuri, S., Siskind, C., Vogel, H., Day, J. W., Gitler, A. D. 2014; 1575: 66-71

    Abstract

    The alpha-dystroglycanopathies are genetically heterogeneous muscular dystrophies that result from hypoglycosylation of alpha-dystroglycan (α-DG). Alpha-dystroglycan is an essential link between the extracellular matrix and the muscle fiber sarcolemma, and proper glycosylation is critical for its ability to bind to ligands in the extracellular matrix. We sought to identify the genetic basis of alpha-dystroglycanopathy in a family wherein the affected individuals presented with congenital muscular dystrophy, brain abnormalities and generalized epilepsy. We performed whole exome sequencing and identified compound heterozygous GMPPB mutations in the affected children. GMPPB is an enzyme in the glycosylation pathway, and GMPPB mutations were recently linked to eight cases of alpha-dystroglycanopathy with a range of symptoms. We identified a novel mutation in GMPPB (p.I219T) as well as a previously published mutation (p.R287Q). Thus, our work further confirms a role for GMPPB defects in alpha-dystroglycanopathy, and suggests that glycosylation may play a role in the neuronal membrane channels or networks involved in the physiology of generalized epilepsy syndromes. This article is part of a Special Issue entitled RNA Metabolism 2013.

    View details for DOI 10.1016/j.brainres.2014.04.028

    View details for PubMedID 24780531

  • Perioperative ischemic optic neuropathy (POION). Spine Bennett, H. L., Origlieri, C., Sakamuri, S. 2005; 30 (23): 2706-?

    View details for PubMedID 16319759