Sarada Sakamuri, MD

All Publications

• The Neuromuscular Portal and Match: Working Toward a More Fair, Equitable, and Transparent Process. Neurology. Education Laughlin, R. S., Adkins, S., Baer, M., Dehbashi, S., Gable, K., Govindarajan, R., Guidon, A. C., Gwathmey, K. G., Hehir, M. K., Imperioli, M., Price, R. S., Sakamuri, S., Sokol, J., Tiongson, N., Wong, E. S., London, Z. 2023; 2 (3): e200086

  Abstract

  Prior to 2021, the neuromuscular medicine fellowship application process suffered from non-standardized timelines and substantial variability. To rectify this, the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) established a standardized application timeline and an online application portal in 2020-2021, followed by the introduction of a partial match process. In 2021-2022, AANEM launched a traditional, binding, two-way match system for fellowship positions allocation based on the Gale-Shapley stable matching algorithm. Surveys assessing perceptions of fairness in the application portal and match process were dispatched to applicants and program directors following the 2021 and 2022 recruitment cycles. In the 2020-21 cycle, 90% of program directors and 95% of applicants affirmed the standardized timeline benefited applicants. However, 57% of applicants deemed the process as unfair. All programs and most applicants (58%) favored a transition to a two-way match. The implementation of the two-way match in 2021-22 attracted participation from 97% of programs, with 80% of applicants and 95% of programs viewing the process as fair to applicants. A significant majority of both applicants (86%) and programs (94%) supported maintaining the standardized timeline and two-way match. We advocate for the universal adoption of the AANEM Match for neuromuscular fellowship recruitment and a standardized fellowship application timeline across all neurologic specialties to promote transparency, fairness, and equity for applicants.

  View details for DOI 10.1212/NE9.0000000000200086

  View details for PubMedID 39359710

  View details for PubMedCentralID PMC11446161

• Surgical Release of Ulnar and Median Nerves in CMT1A: Prevention and Treatment of a Second Hit McKeen, W., Katyal, N., Sakamuri, S., Wilson, T., Greene, M. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for DOI 10.1212/WNL.0000000000203307

  View details for Web of Science ID 001053672102220

• Neuromuscular ultrasound standardized scanning techniques and protocols: Expert panel recommendations. Muscle & nerve Tawfik, E. A., Cartwright, M. S., van Alfen, N., Axer, H., Boon, A. J., Crump, N., Grimm, A., Hobson-Webb, L. D., Kerasnoudis, A., Mandeville, R., Preston, D. C., Sakamuri, S., Shahrizaila, N., Shin, S., Shook, S. J., Wilder-Smith, E., Walker, F. O. 2023

  Abstract

  Neuromuscular ultrasound has become an integral part of the diagnostic workup of neuromuscular disorders at many centers. Despite its growing utility, uniform standard scanning techniques do not currently exist. Scanning approaches for similar diseases vary in the literature creating heterogeneity in the studies as reported in several meta-analysis. Moreover, neuromuscular ultrasound experts including the group in this study have different views with regards to technical aspects, scanning protocols, and the parameters that should be assessed. Establishing standardized neuromuscular scanning protocols is essential for the development of the subspeciality to ensure uniform clinical and research practices. Therefore, we aimed to recommend consensus-based standardized scanning techniques and protocols for common neuromuscular disorders using the Delphi approach. A panel of 17 experts participated in the study, which consisted of three consecutive electronic surveys. The first survey included voting on six scanning protocols addressing the general scanning technique and five common categories of suspected neuromuscular disorders. The subsequent surveys focused on refining the protocols and voting on new steps, rephrased statements, or areas of non-agreement. A high degree of consensus was achieved on the general neuromuscular ultrasound scanning technique and the scanning protocols for focal mononeuropathies, brachial plexopathies, polyneuropathies, amyotophic lateral sclerosis, and muscle diseases. In this study, a group of neuromuscular ultrasound experts developed six consensus-based neuromuscular ultrasound scanning protocols that may serve as references for clinicians and researchers. The standardized protocols could also aid in achieving high-quality uniform neuromuscular ultrasound practices.

  View details for DOI 10.1002/mus.27830

  View details for PubMedID 37074101

• Safety and efficacy of leriglitazone for preventing disease progression in men with adrenomyeloneuropathy (ADVANCE): a randomised, double-blind, multi-centre, placebo-controlled phase 2-3 trial. The Lancet. Neurology Kohler, W., Engelen, M., Eichler, F., Lachmann, R., Fatemi, A., Sampson, J., Salsano, E., Gamez, J., Molnar, M. J., Pascual, S., Rovira, M., Vila, A., Pina, G., Martin-Ugarte, I., Mantilla, A., Pizcueta, P., Rodriguez-Pascau, L., Traver, E., Vilalta, A., Pascual, M., Martinell, M., Meya, U., Mochel, F., ADVANCE Study Group, Mc Govern, E., Yazbeck, E., Barbier, M., Luton, M., Pousset, F., Hogrel, J., Adanyeguh, I., Then Bergh, F., Bergner, C., Unterlauft, A., Roicke, H., Hoffmann, K., Scherlach, C., Kalb, A., Meilick, B., Reuschel, M., Fenu, S., Mauro, E., Murphy, E., Krishna, G., Beyene, T., Sierra, A., Quinoa, S., Belen Canovas, A., Grosz, Z., Gyorgyi, B., van de Stadt, S. I., Huffnagel, I. C., van Ballegoij, W. J., Voermans, M. M., Seyedsadjadi, R., Corre, C., Godbole, N., Grant, N. R., Brito Pires, C. M., Trovato, M., Yeh, N., Goodman, J., Keller, J., Joseph, C., Van Haren, K., Sakamuri, S., Duong, T., Perrone, L., Tran, S., Dunaway Young, S., Hashmi, S. 2023; 22 (2): 127-136

  Abstract

  BACKGROUND: Adult patients with adrenoleukodystrophy have a poor prognosis owing to development of adrenomyeloneuropathy. Additionally, a large proportion of patients with adrenomyeloneuropathy develop life-threatening progressive cerebral adrenoleukodystrophy. Leriglitazone is a novel selective peroxisome proliferator-activated receptor gamma agonist that regulates expression of key genes that contribute to neuroinflammatory and neurodegenerative processes implicated in adrenoleukodystrophy disease progression. We aimed to assess the effect of leriglitazone on clinical, imaging, and biochemical markers of disease progression in adults with adrenomyeloneuropathy.METHODS: ADVANCE was a 96-week, randomised, double-blind, placebo-controlled, phase 2-3 trial done at ten hospitals in France, Germany, Hungary, Italy, the Netherlands, Spain, the UK, and the USA. Ambulatory men aged 18-65 years with adrenomyeloneuropathy without gadolinium enhancing lesions suggestive of progressive cerebral adrenoleukodystrophy were randomly assigned (2:1 without stratification) to receive daily oral suspensions of leriglitazone (150 mg starting dose; between baseline and week 12, doses were increased or decreased to achieve plasma concentrations of 200 mug·h/mL [SD 20%]) or placebo by means of an interactive response system and a computer-generated sequence. Investigators and patients were masked to group assignment. The primary efficacy endpoint was change from baseline in the Six-Minute Walk Test distance at week 96, analysed in the full-analysis set by means of a mixed model for repeated measures with restricted maximum likelihood and baseline value as a covariate. Adverse events were also assessed in the full-analysis set. This study was registered with ClinicalTrials.gov, NCT03231878; the primary study is complete; patients had the option to continue treatment in an open-label extension, which is ongoing.FINDINGS: Between Dec 8, 2017, and Oct 16, 2018, of 136 patients screened, 116 were randomly assigned; 62 [81%] of 77 patients receiving leriglitazone and 34 [87%] of 39 receiving placebo completed treatment. There was no between-group difference in the primary endpoint (mean [SD] change from baseline leriglitazone: -27·7 [41·4] m; placebo: -30·3 [60·5] m; least-squares mean difference -1·2 m; 95% CI -22·6 to 20·2; p=0·91). The most common treatment emergent adverse events in both the leriglitazone and placebo groups were weight gain (54 [70%] of 77 vs nine [23%] of 39 patients, respectively) and peripheral oedema (49 [64%] of 77 vs seven [18%] of 39). There were no deaths. Serious treatment-emergent adverse events occurred in 14 (18%) of 77 patients receiving leriglitazone and ten (26%) of 39 patients receiving placebo. The most common serious treatment emergent adverse event, clinically progressive cerebral adrenoleukodystrophy, occurred in six [5%] of 116 patients, all of whom were in the placebo group.INTERPRETATION: The primary endpoint was not met, but leriglitazone was generally well tolerated and rates of adverse events were in line with the expected safety profile for this drug class. The finding that cerebral adrenoleukodystrophy, a life-threatening event for patients with adrenomyeloneuropathy, occurred only in patients in the placebo group supports further investigation of whether leriglitazone might slow the progression of cerebral adrenoleukodystrophy.FUNDING: Minoryx Therapeutics.

  View details for DOI 10.1016/S1474-4422(22)00495-1

  View details for PubMedID 36681445

• Safety and efficacy of leriglitazone for preventing disease progression in men with adrenomyeloneuropathy (ADVANCE): a randomised, double-blind, multi-centre, placebo-controlled phase 2-3 trial LANCET NEUROLOGY Koehler, W., Engelen, M., Eichler, F., Lachmann, R., Fatemi, A., Sampson, J., Salsano, E., Gamez, J., Molnar, M., Pascual, S., Rovira, M., Vila, A., Pina, G., Martin-Ugarte, I., Mantilla, A., Pizcueta, P., Rodriguez-Pascau, L., Traver, E., Vilalta, A., Pascual, M., Martinell, M., Meya, U., Mochel, F., Adv Study Grp 2023; 22 (2): 127-136

  View details for Web of Science ID 000926094700001

• Physician Perceptions of Performance Feedback and Impact on Personal Well-Being: A Qualitative Exploration of Patient Satisfaction Feedback in Neurology. Joint Commission journal on quality and patient safety Vilendrer, S., Levoy, E., Miller-Kuhlmann, R., Amano, A., Brown-Johnson, C., De Borba, L., Luu, J. H., Sakamuri, S., Gold, C. A. 2022

  Abstract

  BACKGROUND: To understand neurologists' experiences and perspectives on patient satisfaction feedback and its impact on personal well-being and behavior.METHODS: From May to June 2021, the researchers conducted 19 semistructured interviews with neurologists from a large academic medical center. Clinical Performance Feedback Intervention Theory informed a combined inductive and deductive thematic analysis of the qualitative data, which focused on perceptions of current feedback practices, its impact on physician behavior, and recommendations for improvement.RESULTS: Participants tended to be female (n = 12/19, 63.2%), aged 30-39 (n = 8/19, 42.1%), white (n = 9/19, 47.4%), and were 10+ years into clinical practice (n = 18/19, 94.7%). Physicians were receptive to feedback overall, but perceptions varied by feedback type. Physicians preferred informal feedback (delivered unprompted directly by patients), given its tendency toward actionability. They disliked formal feedback (derived from anonymous surveys) due to low actionability, bias and validity issues, lack of contextual considerations, delivery through public reports, and links to financial incentives. Nearly all physicians reported formal feedback programs had the potential to negatively affect well-being and were not beneficial to their practice; a few reported adjusting their clinical practice to improve patient satisfaction performance. Five recommendations to improve patient satisfaction feedback programs emerged: Align on feedback intent, acknowledge survey limitations during program administration, increase actionability of feedback through specificity and control, support direct patient-physician feedback and problem resolution, and support empathetic integration of feedback.CONCLUSION: Understanding physician perceptions of current approaches to patient satisfaction feedback offers the opportunity to shape subsequent collection and distribution methods to improve physician performance and optimize professional fulfillment.

  View details for DOI 10.1016/j.jcjq.2022.12.003

  View details for PubMedID 36732115

• The neuromuscular fellowship portal and match. Muscle & nerve London, Z. N., Gable, K. L., Govindarajan, R., Guidon, A. C., Gwathmey, K. G., Hehir, M. K., Imperioli, M., Laughlin, R. S., Price, R. S., Sakamuri, S., Sokol, J., Baer, M. 2022

  Abstract

  For many years, Neuromuscular Medicine programs lacked a standardized means of handling fellowship applications and offering positions. Programs interviewed applicants and made offers as early as the first half of Post Graduate Year 3 (PGY3), a suboptimal timeline for applicants who may have had little prior exposure to neuromuscular or electrodiagnostic medicine. In 2021, the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) developed the Neuromuscular Fellowship Portal to standardize a later timeline and establish a process for fellowship applications and offers. In its first year, the Neuromuscular Fellowship Portal used a unique one-way match, in which the portal released serial offers to applicants based on rank order lists submitted by programs. Fifty-two Neuromuscular Medicine programs and seven electromyography (EMG)-focused Clinical Neurophysiology programs participated. Sixty-eight positions were filled, a similar number to previous years. A survey of fellowship directors and applicants following this process showed overwhelming support for the standardized timeline and application portal, but all program directors and most applicants favored moving to a traditional match. To maintain the existing application timeline and minimize costs for all parties, the AANEM Neuromuscular Fellowship Portal will host a two-way match, based on existing commercial match algorithms, in 2022. A match will afford a fair and efficient process for all involved. Both Neuromuscular Medicine and EMG-focused Clinical Neurophysiology programs will be encouraged to participate. The process undertaken by the AANEM can stand as an example for other neurologic subspecialties who are interested in standardizing their application timeline.

  View details for DOI 10.1002/mus.27525

  View details for PubMedID 35213933

• Research reporting in cubital tunnel syndrome studies: an analysis of the literature. Acta neurochirurgica Hug, N. F., Smith, B. W., Sakamuri, S., Jensen, M., Purger, D. A., Spinner, R. J., Wilson, T. J. 1800

  Abstract

  PURPOSE: There is a strong need for a set of consensus outcomes to be utilized for future studies on cubital tunnel syndrome. The goal was to assess the outcome measures utilized in the cubital tunnel syndrome literature as a way of measuring popularity/acceptability and then to perform a literature review for the most commonly used outcomes.METHODS: A literature search was performed using the pubmed.gov database and Medical Subject Headings (MeSH). For each article, the following data were abstracted: study type, motor outcome(s), sensory outcome(s), composite outcome(s), patient-reported outcome (PRO) metric(s), pain outcome(s), psychological outcome(s), electrodiagnostic outcome(s), and any other outcomes that were used.RESULTS: A composite outcome was reported in 52/85 (61%) studies, with the modified Bishop score (27/85; 32%) most common. A motor outcome was reported in 44/85 (52%) studies, with dynamometry (38/85; 45%) most common. The majority of studies (55%) did not report a sensory outcome. The majority of studies (52%) did not report a PRO. A specific pain outcome was reported in the minority (23/85; 27%), with the visual analogue scale (VAS) (22/85; 26%) most common. Pre- and postoperative electrodiagnostic results were presented in 22/85 studies (26%).DISCUSSION: Understanding current clinical practice and historical outcomes reporting provides a foundation for discussion regarding the development of a core outcome set for cubital tunnel syndrome. We hope that the data provided in the current study will stoke a discussion that will culminate in a consensus statement for research reporting in cubital tunnel syndrome studies.

  View details for DOI 10.1007/s00701-021-05102-9

  View details for PubMedID 34993620

• Small nerve fiber involvement in chilblain lupus erythematosus (late breaking abstract) Sakamuri, S., Muppidi, S., Leung, K. WILEY. 2021: 440

  View details for Web of Science ID 000696233800295

• Assessment of variability in motor grading and patient-reported outcome reporting: a multi-specialty, multi-national survey. Acta neurochirurgica Smith, B. W., Sakamuri, S., Flavin, K. E., Jensen, M., Purger, D. A., Yang, L. J., Spinner, R. J., Wilson, T. J. 2021

  Abstract

  BACKGROUND: The goal of this survey-based study was to evaluate the current practice patterns of clinicians who assess patients with peripheral nerve pathologies and to assess variance in motor grading on the Medical Research Council (MRC) scale using example case vignettes.METHODS: An electronic survey was distributed to clinicians who regularly assess patients with peripheral nerve pathology. Survey sections included (1) demographic data, (2) vignettes where respondents were asked to assess on the MRC scale, and (3) assessment of practice patterns regarding the use of patient-reported outcome measures. Inter-rater reliability statistics were calculated for the application of the MRC scale on example vignettes.RESULTS: There were 109 respondents. There was significant dispersion in motor grading seen on the example vignettes. For the raw responses grading the example vignettes on the MRC scale, Krippendorff's alpha was 0.788 (95% CI 0.604, 0.991); Gwet's AC2 was 0.808 (95% CI 0.683, 0.932); Fleiss' kappa was 0.416 (95% CI 0.413, 0.419). Most respondents reported not utilizing any patient-reported outcome measures across peripheral nerve pathologies.DISCUSSION: Our data show that there is significant disagreement among providers when applying the MRC scale. It is important for us to reassess our current tools for patient evaluation in order to improve upon both clinical evaluation and outcomes reporting. Consensus guidelines for outcomes reporting are needed, and domains outside of manual muscle testing should be included.

  View details for DOI 10.1007/s00701-021-04861-9

  View details for PubMedID 33990886

• Post-intervention status in patients with refractory myasthenia gravis treated with eculizumab during REGAIN and its open-label extension. Neurology Mantegazza, R., Wolfe, G. I., Muppidi, S., Wiendl, H., Fujita, K. P., O'Brien, F. L., Booth, H. D., Howard, J. F., REGAIN Study Group 2020

  Abstract

  OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) to achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN and its open-label extension.METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study.RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 87.1% of patients achieved improved status and 57.1% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected.CONCLUSIONS: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo.TRIAL REGISTRATION: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624 (ClinicalTrials.gov).

  View details for DOI 10.1212/WNL.0000000000011207

  View details for PubMedID 33229455

• Allograft Nerve Repair Reduces Postoperative Neuropathic Pain Following Nerve Biopsy. Neurosurgery Sakamuri, S., Wilson, T. J. 2020

  Abstract

  BACKGROUND: New or worsened neuropathic pain is common following nerve biopsy and significantly impacts quality of life.OBJECTIVE: To examine the impact of allograft nerve repair on the likelihood of postoperative worsened neuropathic pain following nerve biopsy.METHODS: A retrospective cohort study was performed comparing standard nerve biopsy to nerve biopsy with allograft repair. Consecutive patients (N=51) who underwent whole nerve biopsy between August 1, 2017, and August 1, 2019, by a single surgeon were evaluated for inclusion. The primary outcome was significant worsening of visual analog scale (VAS) score in the nerve distribution 6-mo postbiopsy. Secondary outcomes included significant worsening of VAS in the nerve distribution 3-wk postbiopsy and significant change in Zung Self-Rating Depression Scale 6-mo postbiopsy.RESULTS: In a multivariate model, allograft nerve repair significantly reduced the likelihood of increased neuropathic pain at 6-mo postbiopsy (odds ratio 0.02, P=.03). Worsened neuropathic pain occurred in 28% of the standard nerve biopsy cohort compared to 4% of the allograft nerve repair cohort. In a multivariate model, an increase in neuropathic pain was strongly associated with an increased likelihood of self-reported depression (odds ratio 57.4, P=.01).CONCLUSION: Allograft nerve repair significantly reduces the likelihood of postbiopsy worsened neuropathic pain compared to standard techniques. Neuropathic pain significantly impacts quality of life after nerve biopsy, and this is the first technique to demonstrate a significant reduction in neuropathic pain while maintaining the ability to harvest an adequate nerve specimen.

  View details for DOI 10.1093/neuros/nyaa250

  View details for PubMedID 32542326

• Imaging of Damaged Nerves. Clinics in plastic surgery Purger, D. A., Sakamuri, S., Hug, N. F., Biswal, S., Wilson, T. J. 2020; 47 (2): 245–59

  Abstract

  Nerve imaging is an important component in the assessment of patients presenting with suspected peripheral nerve pathology. Although magnetic resonance neurography and ultrasound are the most commonly utilized techniques, several promising new modalities are on the horizon. Nerve imaging is useful in localizing the nerve injury, determining the severity, providing prognostic information, helping establish the diagnosis, and helping guide surgical decision making. The focus of this article is imaging of damaged nerves, focusing on nerve injuries and entrapment neuropathies.

  View details for DOI 10.1016/j.cps.2019.12.003

  View details for PubMedID 32115050

• Neuromuscular ultrasound competency assessment: Consensus-Based survey. Muscle & nerve Tawfik, E. A., Cartwright, M. S., Grimm, A. n., Boon, A. J., Kerasnoudis, A. n., Preston, D. C., Wilder-Smith, E. n., Axer, H. n., Hobson-Webb, L. D., van Alfen, N. n., Crump, N. n., Shahrizaila, N. n., Inkpen, P. n., Mandeville, R. n., Sakamuri, S. n., Shook, S. J., Shin, S. n., Walker, F. O. 2020

  Abstract

  Neuromuscular ultrasound is a rapidly evolving specialty with direct application for patient care. Competency assessment is an essential standard needed to ensure quality for practitioners, particularly for those newly acquiring skills with the technique. Our aim was to survey experts' opinions regarding physician competency assessment of neuromuscular ultrasound and to identify minimal competency of knowledge and skills. The opinions of 18 experts were obtained through the Delphi method using two consecutive electronic surveys. A high degree of consensus was achieved on items regarding framework and the conduct of neuromuscular ultrasound assessment and the knowledge and skills that a candidate needs to attain minimal competency in neuromuscular ultrasound. In this study, a group of neuromuscular ultrasound experts developed a general framework for neuromuscular ultrasound competency assessment and recommended testable areas of knowledge and skills suitable for establishing minimal competency. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/mus.27163

  View details for PubMedID 33382094

• 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., Fujita, K. P., Howard, J. F., Kaya, A., Khursigara, G., Armstrong, R., Diab, D., Capocelli, K., Lane, C., Sanders, V., Gandolfo, R., REGAIN Study Grp 2019; 60 (1): 14–24

  View details for DOI 10.1002/mus.26447

  View details for Web of Science ID 000471831900011

• 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 JOURNAL OF TRAUMA AND ACUTE CARE SURGERY Smith, B. W., Sakamuri, S., Spain, D. A., Joseph, J. R., Yang, L., Wilson, T. J. 2019; 86 (2): 299–306

  View details for DOI 10.1097/TA.0000000000002081

  View details for Web of Science ID 000457577100017

• Guidelines for neuromuscular ultrasound training. Muscle & nerve Tawfik, E. A., Cartwright, M. S., Grimm, A. n., Boon, A. J., Kerasnoudis, A. n., Preston, D. C., Wilder-Smith, E. n., Axer, H. n., Hobson-Webb, L. D., van Alfen, N. n., Crump, N. n., Shahrizaila, N. n., Inkpen, P. n., Mandeville, R. n., Sakamuri, S. n., Shook, S. J., Shin, S. n., Walker, F. O. 2019

  Abstract

  Neuromuscular ultrasound has become an essential tool in the diagnostic evaluation of various neuromuscular disorders, and as such, there is growing interest in neuromuscular ultrasound training. Effective training is critical in mastering this modality. Our aim was to develop consensus-based guidelines for neuromuscular ultrasound training courses. A total of 18 experts participated. Expert opinion was sought through the Delphi method using 4 consecutive electronic surveys. A high degree of consensus was achieved with regard to the general structure of neuromuscular ultrasound training; the categorization of training into basic, intermediate and advanced levels; the learning objectives; and the curriculum for each level. In this study, a group of neuromuscular ultrasound experts established consensus-based guidelines for neuromuscular ultrasound training. These guidelines can be used in the development of the specialty and the standardization of neuromuscular ultrasound training courses and workshops. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/mus.26642

  View details for PubMedID 31335971

• 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. n., Ruoff, C. n., Moore, H. n., Hagerman, K. A., Perez, J. n., Sakamuri, S. n., Warby, S. C., Mignot, E. n., Day, J. n., Sampson, J. n. 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 PubMedID 29394960

• 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

• Increased EEG theta spectral power in polysomnography of myotonic dystrophy type 1 compared to matched controls. Ruoff, C., Cheung, J., Perez, J., Sakamuri, S., Mignot, E., Day, J., Sampson, J. LIPPINCOTT WILLIAMS & WILKINS. 2017

  View details for Web of Science ID 000577381503279

• Sleep and Neuromuscular Disease Sleep and Neurologic Disease Sakamuri, S., Day, J. W. Elsevier. 2017; 1: 183–200

  View details for DOI 10.1016/b978-0-12-804074-4.00010-8

• 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