Kristin Galetta, MD

All Publications

• Neurologic Outcomes in People With Multiple Sclerosis Treated With Immune Checkpoint Inhibitors for Oncologic Indications. Neurology Quinn, C. M., Rajarajan, P., Gill, A. J., Kopinsky, H., Wolf, A. B., de Camargo, C. S., Lamb, J., Bacon, T. E., Murray, J. C., Probasco, J. C., Galetta, K. M., Kantor, D., Coyle, P., Bhise, V., Alvarez, E., Conway, S. E., Bhattacharyya, S., Kister, I. 2024; 103 (11): e210003

  Abstract

  BACKGROUND AND OBJECTIVES: Immune checkpoint inhibitors (ICIs) are increasingly used against various cancers but are associated with immune-related adverse events (irAEs). Risk of irAEs may be higher in patients with certain preexisting autoimmune diseases, and these patients may also experience exacerbation of the underlying autoimmune disease following ICI initiation. People with multiple sclerosis (MS) have mostly been excluded from clinical trials of ICIs, so data on the safety of ICIs in MS are limited. This study aims to assess the rate of MS activity, as well as neurologic and nonneurologic irAEs in persons with MS treated with ICIs for cancer.METHODS: Participating sites were invited to this retrospective observational study through the Medical Partnership 4 MS+ listserv. Seven large academic centers participated in the study, each conducting a systematic search of their electronic medical record system for patients with MS and history of ICI treatment. The participating neurologist reviewed each chart individually to ensure the inclusion criteria were met. Demographics and data on MS and cancer history, treatments, and outcomes were abstracted from patient charts using a structured instrument.RESULTS: We identified 66 people with MS (median age 66 years, 73% female, 68% not on disease-modifying therapy for MS) who were treated with ICIs for lung cancer (35%), melanoma (21%), or another oncologic indication. During post-ICI follow-up (median: 11.7 months, range 0.2-106.3 months), 2 patients (3%) had relapse or MRI activity, 3 (5%) had neurologic irAEs, and 21 (32%) had nonneurologic irAEs. At the last follow-up, 25 (38%) participants had partial or complete remission of their cancer, while 35 (53%) were deceased.DISCUSSION: In this multi-institutional systematic retrospective study of predominantly older patients with MS, most of whom were not on disease-modifying therapy, MS activity and neurologic irAEs following ICI treatment were rare. These data suggest that preexisting MS should not preclude the use of ICIs for cancer in older patients, but the results may not be generalizable to younger patients with active MS. Prospective studies of ICI safety that enroll younger patients with MS are needed.

  View details for DOI 10.1212/WNL.0000000000210003

  View details for PubMedID 39541548

• Paraneoplastic myelitis associated with Waldenström macroglobulinemia responsive to treatment with ibrutinib - venetoclax: A case report. eNeurologicalSci Narasimhan, S., Galetta, K. M., Castillo, J. J., Bhattacharyya, S. 2024; 37: 100527

  Abstract

  Waldenström macroglobulinemia (WM) is a B-cell lymphoproliferative malignancy characterized by IgM paraproteinemia and presence of lymphoplasmacytic cells in the bone marrow. Isolated longitudinally extensive transverse myelitis (LETM) is a rare manifestation of WM. We report a rare case of paraneoplastic LETM in a 68-year-old male with treatment-naïve WM (MYD88 L265P mutation in bone marrow aspirate), who responded to ibrutinib and venetoclax therapy. Our patient presented with a two-month history of unsteadiness, tingling, and numbness in both hands and feet, that progressed to bilateral leg and arm weakness. Based on radiographic findings, a diagnosis of paraneoplastic LETM was made and he was treated acutely with IV methylprednisolone followed by a quick oral prednisone taper. However, he subsequently relapsed and symptomatically worsened while on rituximab therapy. Accounting for worsening anemia, our patient was enrolled in a Phase II trial evaluating the effects of ibrutinib-venetoclax therapy in treatment naïve WM. After three months of study therapy, he had a complete response of myelopathy symptoms and MRI lesions. Our observation of sustained disease response in this patient may support a role for concurrent BTK and BCL2 inhibition in paraneoplastic myelitis associated with B-cell lymphoproliferative disorders. However, this observation needs to be validated in larger cohort studies and potentially in clinical trials if further data are supportive.

  View details for DOI 10.1016/j.ensci.2024.100527

  View details for PubMedID 39309451

  View details for PubMedCentralID PMC11415854

• Inflammatory vaginitis in women with multiple sclerosis: a retrospective analysis of B-cell depleting therapy compared to other disease modifying therapies. Multiple sclerosis and related disorders Conway, S., Dodson, C., Hui, G., William Pike, C., Galetta, K. 2024; 92: 105921

  Abstract

  This study investigates the occurrence of inflammatory vaginitis in women with Multiple Sclerosis (wwMS) undergoing B-cell depleting therapy versus other disease-modifying therapies (DMTs). Retrospective analysis of medical records from Stanford University between 2015-2023 shows similar rates of vaginitis in both groups, suggesting no significant association with B-cell therapy. Despite this, inflammatory vaginitis remains prevalent in both treatment groups, warranting further investigation into its mechanisms and management.

  View details for DOI 10.1016/j.msard.2024.105921

  View details for PubMedID 39454471

• Perception of In-Person Prerounding Amongst Neurology Residents Across Two Academic Centers. The Neurohospitalist Chen, A., Prasad, S., Bowley, M., Krupat, E., Galetta, K. 2024; 14 (2): 140-146

  Abstract

  In-person prerounding has long been a routine practice for residents in the field of neurology. However, with the emergence of the COVID-19 pandemic, many institutions, including our two academic neurology centers, have shifted to computer rounding. This study aims to assess the effects of computer rounding alone compared to a combination of computer rounding and in-person prerounding from the perspective of neurology residents.A mixed-methods approach was employed, including a survey administered to 79 neurology residents and a qualitative thematic analysis of their responses.The quantitative analysis revealed that residents who engaged in inperson prerounding spent significantly more time on prerounding and computer rounding compared to those who did not. The majority of residents reported a neutral effect of in-person prerounding on their relationship with patients and bedside time, but a significant impact on personal lives and other tasks. Qualitative analysis identified four key themes: accessibility to team members, learning opportunities gained and lost, inefficiency, and sleep disturbance.Overall, residents perceived in-person prerounding as inefficient and causing sleep disruption for both patients and themselves. While some residents valued the face-to-face interaction and improved accessibility, others felt that computer rounding allowed for thorough review of patient data, improving preparedness and efficiency. The potential elimination of in-person prerounding from residents' routines may enhance their overall wellbeing. Further research is needed to assess the advantages and drawbacks of removing this classic approach to caring for patients from the perspective of residents, attendings and patients.

  View details for DOI 10.1177/19418744241228353

  View details for PubMedID 38666273

  View details for PubMedCentralID PMC11040615

• Disease modifying therapy in the treatment of tumefactive multiple sclerosis: A retrospective cohort study. Journal of neuroimmunology Galetta, K., Ham, A. S., Vishnevetsky, A., Bhattacharyya, S., Mateen, F. J. 2024; 388: 578299

  Abstract

  Tumefactive multiple sclerosis (TMS) is characterized by large demyelinating brain lesions. This was a retrospective cohort study of 67 patients with TMS between January 2015-2023, examining different disease modifying therapy impact on expanded disability scale score change at follow-up. Median age was 36 with a female predominance. Mean EDSS was 3.3 ± 2.3 at TMS onset, 2.1 ± 1.9 at year one, and 2.1 ± 1.9 at last follow-up. A multilinear regression model found higher presentation EDSS and post-diagnosis non-B-cell high efficacy therapies were each independently associated with higher EDSS at last follow up. Further research is needed to determine the value of B-cell therapy in TMS.

  View details for DOI 10.1016/j.jneuroim.2024.578299

  View details for PubMedID 38364529

• Perception of In-Person Prerounding Amongst Neurology Residents Across Two Academic Centers NEUROHOSPITALIST Chen, A., Prasad, S., Bowley, M., Krupat, E., Galetta, K. 2024

  View details for DOI 10.1177/19418744241228353

  View details for Web of Science ID 001142774100001

• Does GPT-4 have neurophobia? Localization and diagnostic accuracy of an artificial intelligence-powered chatbot in clinical vignettes. Journal of the neurological sciences Galetta, K., Meltzer, E. 2023: 120804

  Abstract

  This is an observational study of the performance of an artificial intelligence-powered chatbot tasked with solving unknown neurologic case vignettes. The primary objective of the study is to assess the current capabilities of widely-accessible artificial intelligence within the field of clinical neurology in order to determine how this technology can be deployed in clinical practice, and what insights can be learned from its performance and translated to clinical education.This observational study tested the accuracy of GPT-4, an artificial intelligence-powered chatbot, at appropriately localizing and generating a differential diagnosis for a series of 29 clinical case vignettes. The cases were from previously published educational material prepared for learners. No cases required more than text input, a current limitation of GPT-4. The primary outcome measures were ranked accuracy of localization and differential diagnosis based on clinical history and exam alone and after ancillary clinical data was provided. Secondary outcome measures included a comparison of accuracy by case difficulty.GPT-4 identified the correct localization less than 50% of the time and performed worse when provided ancillary testing. GPT-4 was more accurate with localization and diagnosis of easier versus harder cases. Diagnostic accuracy was independent of its ability to localize the lesion.GPT-4 did not perform as well on neurology clinical vignettes as compared to reported accuracy when provided other medical clinical vignettes. Incorporation of an AI chatbot into the practice of clinical neurology will require neurology-focused teaching.

  View details for DOI 10.1016/j.jns.2023.120804

  View details for PubMedID 37741773

• MYD88 L265P mutation in neurologic autoimmunity without evidence of malignancy MULTIPLE SCLEROSIS AND RELATED DISORDERS Oetjen, L. K., Bhattacharyya, S., Galetta, K. 2023; 77: 104868

  Abstract

  MYD88 mutation status is assessed in the evaluation of CNS lymphoma since the mutation MYD88 L265P is highly predictive of this disease. However, whether the MYD88 L265P mutation may lead to other diseases outside of malignancy is not well understood. Here we describe two patients with the MYD88 L265P mutation in the CSF with no additional evidence of neoplastic disease but were found to have two distinct neurologic autoimmune conditions (anti-GFAP astrocytopathy and multiple sclerosis). These cases suggest this activating mutation may predispose certain patients to autoimmune conditions and may have future therapeutic implications.

  View details for DOI 10.1016/j.msard.2023.104868

  View details for Web of Science ID 001046857000001

  View details for PubMedID 37451134

• Neurologic disease activity in people with multiple sclerosis treated with immune checkpoint inhibitors. Multiple sclerosis (Houndmills, Basingstoke, England) Conway, S. E., Pua, D. K., Holroyd, K. B., Galetta, K., Bhattacharyya, S. 2023; 29 (3): 471-474

  Abstract

  There is concern that immune checkpoint inhibitors (ICPIs) can provoke relapses in people with multiple sclerosis (pwMS).Analyze outcomes of pwMS who received ICPI treatment for malignancy.We electronically identified pwMS who received ICPI treatment at Mass General Brigham hospital system. We retrospectively obtained information about patients' MS, cancer, treatment, and outcomes.Sixteen patients were identified with an average (standard deviation (SD)) age of 67.4 (11.9) years. Eleven (68.8%) had no relapses since MS diagnosis. None had MS relapses after ICPI treatment or new MS lesions.ICPI use was not associated with increased clinical disease activity in this cohort of older patients with inactive MS.

  View details for DOI 10.1177/13524585221117949

  View details for PubMedID 35957594

• Humoral response to COVID-19 vaccination in MS patients on disease modifying therapy: Immune profiles and clinical outcomes. Multiple sclerosis and related disorders Holroyd, K. B., Healy, B. C., Conway, S., Houtchens, M., Bakshi, R., Bhattacharyya, S., Bose, G., Galetta, K., Kaplan, T., Severson, C., Singhal, T., Stazzone, L., Zurawski, J., Polgar-Turcsanyi, M., Saxena, S., Paul, A., Glanz, B. I., Weiner, H. L., Chitnis, T. 2022; 67: 104079

  Abstract

  Patients with multiple sclerosis (MS) on some disease modifying therapies (DMTs), particularly anti-CD20 and sphingosine-1-phosphate (S1P) modulators, are at increased risk of severe Coronavirus Disease 19 (COVID-19) and death. COVID-19 vaccinations are effective in preventing infection and severe disease, but humoral response to vaccination and outcomes of COVID-19 infection after vaccination in MS patients on DMTs remain less understood.In this retrospective single-center study, patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital) study and biorepository who had been vaccinated against COVID-19 and had SARS-CoV-2 spike antibody (anti-SARS-CoV-2 S Roche-Elecsys) testing were identified and compared to healthy controls. Demographic data, serum immune profiles including lymphocyte count, B-cell count, and immunoglobulins, and clinical outcome of COVID-19 infection were collected.254 patients (73.2% female, mean (SD) age 52.9 (11.2) years) were identified. When controlling for age, time since vaccination, and vaccine type, patients on fingolimod, ocrelizumab, rituximab, mycophenolate mofetil, natalizumab and teriflunomide had significantly lower levels of spike antibodies compared to healthy controls (n = 34). Longer duration of treatment was associated with lower spike antibody levels in patients on anti-CD20 therapy (p = 0.016) and S1P modulators (p = 0.016) compared to healthy controls. In patients on anti-CD20 therapy, higher spike antibody levels were associated with higher CD20 cell count (p<0.001), and longer time since last anti-CD20 therapy infusion (p<0.001). 92.8% (13/14) vaccine responders (spike antibody titer >100 ug/dL) on anti-CD20 therapy demonstrated B-cell reconstitution (mean CD20 3.6%). Only 1 out of 86 patients with CD20 of 0% had a measurable spike antibody response to vaccination. During follow-up (mean 270 days), five patients were diagnosed with COVID-19 after vaccination (incidence 1.9%), all of whom had spike antibody < 20 ug/dL. No patients required ICU care or died.Patients on some DMTs demonstrate reduced humoral immunity after Sars-CoV-2 vaccination. Longer duration of anti-CD20 therapy and reduced CD20 cell count is associated with blunted humoral response to vaccination. CD20 reconstitution >0.1% appears necessary, but not always sufficient, for humoral response to vaccination. Breakthrough COVID-19 infection in our cohort of MS patients on DMT was higher than in population studies. We propose that adjustment of B-cell therapy administration to allow for B-cell reconstitution prior to vaccination should be considered.

  View details for DOI 10.1016/j.msard.2022.104079

  View details for PubMedID 35952457

  View details for PubMedCentralID PMC9330583

• Treatment outcomes of first-ever episode of severe optic neuritis. Multiple sclerosis and related disorders Galetta, K., Ryan, S., Manzano, G., Chibnik, L. B., Balaban, D., Prasad, S., Chwalisz, B. K., Salazar-Camelo, A., Conway, S., Levy, M., Matiello, M. 2022; 66: 104020

  Abstract

  Severe optic neuritis (ON) is an acute inflammatory attack of the optic nerve(s) leading to severe visual loss that may occur in isolation or as part of a relapsing neuroinflammatory disease, such neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD), or more rarely multiple sclerosis (MS). In cases of first-ever severe ON of uncertain etiology best treatment strategies remain unclear.We reviewed records of all patients with a documented diagnosis of ON between 2004 and 2019 at Mass General Brigham (MGB) and Johns Hopkins University (JHU) hospitals. Out of 381 patients identified, 90 (23.6%) satisfied the study criteria for severe ON with visual acuity (VA) equal to or worse than 20/200 (logMAR=1) at nadir in the affected eye and had sufficient follow-up data. Treatment strategies with corticosteroids only or treatment escalation with therapeutic plasma exchange (PLEX) after steroids were compared and evaluated for differences in visual outcomes at follow-up.Of the 90 patients with severe optic neuritis, 71(78.9%) received corticosteroids only, and 19 (17.0%) underwent PLEX following corticosteroids. Of the 71 patients who received steroids without escalation to PLEX, 30 patients (42.2%) achieved complete recovery (VA 20/20 on the affected eye), whereas 35 (49.3%) had a partial recovery and 6 (8.4%) had no recovery. Among the 19 corticosteroid non-responders patients who underwent escalation treatment, 13 (68.4%) made complete recovery, 6 (31.6%) had partial visual recoveries (p=0.0434). The median delta logMAR of patients who underwent escalation of care was -1.2 compared with 2.0 for the ones who did not (p=0.0208). A change of delta logmar 2.0 is equivalent of going from hand motion to light perception and the positive delta value refers to intra-attack worsening. Other than not responding to steroids, patients who underwent PLEX tended to have more severe ON with significantly worse nadir visual acuity compared with those who received corticosteroids alone (logMAR 3.12 (min 2.0 - max 5.0) vs. 2.17 (min 1.3 - max 3.0); p=0.004).In our cohort of first-ever severe optic neuritis of unknown etiology, patients that did not respond adequately to corticosteroids benefited from treatment escalation to PLEX, followed in most cases by Rituximab, regardless of final etiology. Randomized controlled trials are needed to confirm the best treatment strategies.

  View details for DOI 10.1016/j.msard.2022.104020

  View details for PubMedID 35839615

• Rethinking the algorithm for fatigue management in MS-how the placebo effect can confound clinical expertise. Multiple sclerosis and related disorders Howard, D., Galetta, K. 2022; 65: 104021

  View details for DOI 10.1016/j.msard.2022.104021

  View details for PubMedID 35810722

• Disease modifying therapy management of multiple sclerosis after stem cell therapies: A retrospective case series. Multiple sclerosis and related disorders Manzano, G. S., Holroyd, K. B., Kaplan, T., Bhattacharyya, S., Chitnis, T., Hotan, G., Zurawski, J., Galetta, K. M., Mateen, F. J. 2022; 63: 103861

  Abstract

  Stem cell therapies (SCT) have not received formal regulatory approval for the treatment of people with multiple sclerosis (PwMS), but PwMS may seek various options on their own accord. The current literature largely focuses on the efficacy and safety of SCT in PwMS in clinical trials, in particular autologous hematopoietic stem cell transplantation (aHSCT), in carefully selected participants. There is little reported on the MS disease modifying therapy (DMT) management of PwMS who choose to undergo SCT outside of these trials.We identified PwMS from two academic centers who had MS diagnosis fulfilling 2017 McDonald criteria and received SCT (methodologies permitted: aHSCT, umbilical-derived mesenchymal stem cells and/or adipose-derived mesenchymal stem cells (AdMSC)), with the goal to treat MS, between 1/1/2015 and 11/30/2021.Nine PwMS (five females; age range at SCT treatment 25-69 years old; MS disease duration 1-12 years; six relapsing-remitting, three secondary progressive, one primary progressive) underwent a total of eleven SCTs (nine aHSCT, two AdMSC, one umbilical-derived MSC) with the goal to treat MS. Two of six PwMS who underwent SCT <10 years from MS diagnosis, and one of three PwMS who underwent stem cell therapies >10 years from MS diagnosis were clinically stable thereafter. An MS DMT was resumed in five PwMS afterwards, including rituximab, ocrelizumab, siponimod, and glatiramer acetate: one remained clinically stable, whereas four clinically progressed. Four PwMS remained off of a DMT: three were clinically stable, whereas one clinically progressed. All nine patients demonstrated radiographic stability by MRI after SCT. Only one met formal criteria to consider aHSCT for MS.We demonstrate the heterogeneous real-world experience of treating MS after patient-chosen experimental SCTs, detailing the range of DMT management in various patient circumstances. Limitations of our study include its small sample size and the variety of stem cell therapies received.

  View details for DOI 10.1016/j.msard.2022.103861

  View details for PubMedID 35576727

• COVID-19 severity is associated with worsened neurological outcomes in multiple sclerosis and related disorders. Multiple sclerosis and related disorders Conway, S. E., Healy, B. C., Zurawski, J., Severson, C., Kaplan, T., Stazzone, L., Galetta, K., Chitnis, T., Houtchens, M. K. 2022; 63: 103946

  Abstract

  Neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 is not well understood. The objective of this study was to investigate neurologic outcomes in patients with MSRD post-COVID-19.This was a retrospective medical records review study of adult patients with MSRD and COVID-19 infection at the Brigham MS Center. Neurologic worsening post-COVID-19 was defined as having a relapse, pseudorelapse, new brain MRI activity, worsening of preexisting MSRD symptoms, or development of other long-term neurologic symptoms.111 patients, 85 (76.6%) females, with a mean [SD] age of 49.3 [12.2] years and median [range] EDSS of 2.5 [0, 8.5] were identified. 41 patients (36.9%) had neurologic worsening post-COVID-19. Of those, 19 (46.3%) had pseudorelapses, 2 (4.8%) had relapses, and 24 (58.5%) patients reported worsening of preexisting MSRD symptoms, or other new long-term neurologic symptoms. Neurologic worsening was associated with hospitalized (moderate or severe) COVID-19 (p = 0.001), treatment for COVID-19 (p = 0.006), and incomplete COVID-19 recovery (p = 0.0267) but not with age, sex, MS type, race, disease duration, EDSS, vitamin D use, or disease modifying therapy use.COVID-19 severity and lack of complete systemic recovery were associated with new or worsening neurologic symptoms in 36.9% of MSRD patients.

  View details for DOI 10.1016/j.msard.2022.103946

  View details for PubMedID 35709663

  View details for PubMedCentralID PMC9556032

• Acute Neurologic Manifestations of Systemic Immune-Mediated Diseases. Seminars in neurology Galetta, K., Bhattacharyya, S. 2021; 41 (5): 541-553

  Abstract

  Systemic autoimmune diseases can affect the peripheral and central nervous system. In this review, we outline the common inpatient consultations for patients with neurological symptoms from rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, sarcoidosis, immunoglobulin G4-related disease, Behçet's disease, giant cell arteritis, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis, polyarteritis nodosa, and ankylosing spondylitis. We discuss the symptoms, diagnostic strategies, and treatment options.

  View details for DOI 10.1055/s-0041-1733790

  View details for PubMedID 34619780

• Electronic pill bottles to monitor and promote medication adherence for people with multiple sclerosis: A randomized, virtual clinical trial. Journal of the neurological sciences Rice, D. R., Kaplan, T. B., Hotan, G. C., Vogel, A. C., Matiello, M., Gillani, R. L., Hutto, S. K., Ham, A. S., Klawiter, E. C., George, I. C., Galetta, K., Mateen, F. J. 2021; 428: 117612

  Abstract

  We perform a randomized trial to test the impact of electronic pill bottles with audiovisual reminders on oral disease modifying therapy (DMT) adherence in people with MS (PwMS).Adults with multiple sclerosis (MS) taking an oral DMT were randomized 1:1 for 90 days to remote smartphone app- and pill bottle-based (a) adherence monitoring, or (b) adherence monitoring with audiovisual medication reminders. Optimal adherence was defined as the proportion of doses taken ±3 h of the scheduled time. Numbers of missed pills and pills taken early, on time, late, and extra were recorded. A multivariable regression model tested possible associations between optimal adherence and age, MS duration, cognitive functioning, and number of daily prescription pills.85 participants (66 female; mean age 44.9 years) took dimethyl/diroximel fumarate (n = 49), fingolimod (n = 26), or teriflunomide (n = 10). Optimal adherence was on average higher in the monitoring with reminders arm (71.4%) than the monitoring only arm (61.6%; p = 0.033). In a multivariable model, optimal adherence was less likely in younger participants (p < 0.001) and those taking more daily prescription pills (p < 0.001). In the monitoring only arm, 4.0% of doses were taken early, 61.6% on time, 5.6% late, 4.4% in excess, and 24.4% were missed. In the reminders arm, these proportions were 3.4%, 71.4%, 3.7%, 8.7%, and 12.8%, respectively.We map real-world oral DMT adherence patterns using mHealth technology. PwMS who received medication reminders had higher optimal adherence. Nonadherence was more nuanced than simply missing pills. Developing strategies to improve adherence remains important in longitudinal MS care.

  View details for DOI 10.1016/j.jns.2021.117612

  View details for PubMedID 34392138

• Reactivation of SARS-CoV-2 after Rituximab in a Patient with Multiple Sclerosis. Multiple sclerosis and related disorders Bose, G., Galetta, K. 2021; 52: 102922

  Abstract

  A 32-year-old woman with highly active MS was infected with SARS-CoV-2 while on treatment with rituximab. She recovered and was symptom-free for 21 days before receiving rituximab and IVIg for comorbid hypogammaglobulinemia. Three days after the infusion she redeveloped respiratory symptoms and required admission. Three SARS-CoV-2 nasopharyngeal swabs and antibody testing was negative; however, bronchial alveolar lavage detected SARS-CoV-2. Reactivation of SARS-CoV-2 after rituximab for MS has not been reported but is a known risk in other conditions. The timing of anti-CD20 treatment after SARS-CoV-2 infection requires further investigation and individual consideration to reduce the risk of reactivation.

  View details for DOI 10.1016/j.msard.2021.102922

  View details for PubMedID 33895693

  View details for PubMedCentralID PMC7992302

• Influence of Autoimmune Antibody Testing on the Use of Immunotherapy on an Inpatient Neurology Service. The Neurohospitalist Galetta, K., Gheihman, G., Rosen, A., Klein, J. P., Bhattacharyya, S. 2021; 11 (3): 214-220

  Abstract

  To determine the frequency of autoimmune antibody testing in an inpatient neurology setting and its influence on immunotherapy use on an inpatient neurology service.A retrospective descriptive cohort study of patients admitted to the neurology inpatient service at a large tertiary academic medical center who had autoimmune and/or paraneoplastic antibody testing performed between 10/1/2017 and 10/1/2018. Characteristics of patients' initial clinical presentation, antibody testing results, test timing in relation to initiating immunotherapy, and final diagnosis using consensus criteria were extracted and analyzed. Case reports of patients with positive antibody panels are presented.Of 1,604 patients, 50 patients (3.1%) had an antibody panel sent. Tests resulted after an average of 17 days (range 7-27). The most common clinical presenting symptom in those with a panel sent was encephalopathy. There were 5 (10%) positive serum panels and no positive CSF panels. Only one of these 5 patients had autoimmune encephalitis and was treated with immunotherapy. Of those with negative serum and CSF panels, 15 were treated acutely with empiric immunotherapy and the remainder with supportive care. Of those treated with immunotherapy, 14/15 (93%) were treated before the panel tests resulted. Four patients who had negative panels but were empirically treated met consensus criteria for an autoimmune-mediated neurologic process.Our study suggests that the results of antibody testing did not influence inpatient neurologists' decision to treat with immunotherapy as most treatments began prior to final results being available.

  View details for DOI 10.1177/1941874420977761

  View details for PubMedID 34163547

  View details for PubMedCentralID PMC8182399

• Serum neurofilament levels and patient-reported outcomes in multiple sclerosis. Annals of clinical and translational neurology Galetta, K., Deshpande, C., Healy, B. C., Glanz, B., Ziehn, M., Saxena, S., Paul, A., Saleh, F., Collins, M., Gaitan-Walsh, P., Castro-Mendoza, P., Weiner, H. L., Chitnis, T. 2021; 8 (3): 631-638

  Abstract

  Serum neurofilament light (sNfL) is a promising new biomarker in multiple sclerosis (MS). We explored the relationship between sNfL and health outcomes and resource use in MS patients.MS patients with serum samples and health-outcome measurements collected longitudinally between 2011 and 2016 were analyzed. sNfL values were evaluated across age and gender. Data were analyzed using correlation with log-transformed sNfL values.A total of 304 MS patients with a mean age of 32.9 years, average EDSS of 1.6 (SD = 1.5) and baseline sNfL of 8.8 (range 1.23-78.3) pg/mL were studied. Baseline sNFL values increased with age and were higher in females. Baseline sNfL correlated with baseline Multiple Sclerosis Quality of Life physical composite (mean = 49.4 (9.1), P = 0.035) and baseline EDSS (P = 0.002). Other PRO measures at baseline did not show a significant relationship with baseline sNfL. Average of baseline and follow-up sNfL correlated with MSQoL physical-role limitations (mean = 48.9 (10.8), P = 0.043) and social-functioning (mean = 52.3 (7), P = 0.034) at 24-month follow-up. We found a trend for numerically higher sNfL levels in nonpersistent patients compared to those who were persistent to treatment (11.13 vs. 8.53 pg/mL, P = 0.093) measured as average of baseline and 24-month values. Baseline NfL was associated with number of intravenous steroid infusions (mean = 0.2; SD = 3.0, P = 0.013), whereas the average of baseline and 12 months NfL values related to inpatient stays at 12 months (mean = 0.2; SD = 3.0 P = 0.053).Serum NfL is a patient-centric biomarker that correlated with MS patient health-outcomes and healthcare utilization measures in a real-world cohort.

  View details for DOI 10.1002/acn3.51305

  View details for PubMedID 33492760

  View details for PubMedCentralID PMC7951092

• Clinical Reasoning: A 58-year-old woman presents with progressive memory deficits, odd behavior, and falls. Neurology Carlisle, T. C., Galetta, K. M., McGinnis, S. M., Bockow Kaplan, T. 2020; 94 (5): e557-e561

  View details for DOI 10.1212/WNL.0000000000008896

  View details for PubMedID 31959711

• Multiple Sclerosis and Autoimmune Neurology of the Central Nervous System. The Medical clinics of North America Galetta, K. M., Bhattacharyya, S. 2019; 103 (2): 325-336

  Abstract

  Autoimmune disorders of the central nervous system are common and often affect people in the most productive years of their lives. Among primary autoimmune diseases of the central nervous system, multiple sclerosis is most prevalent in the United States. Many other autoantibody-mediated neurologic syndromes have been identified within the past 2 to 3 decades, including neuromyelitis optica and anti-N-methyl-D aspartate receptor encephalitis. Finally, the central nervous system can also be affected by systemic autoimmune diseases such as sarcoidosis. Many of these diseases are treatable when detected early.

  View details for DOI 10.1016/j.mcna.2018.10.004

  View details for PubMedID 30704684

• A Sticky Situation. The New England journal of medicine Vedula, R., Vaidya, A., Galetta, K., Laubach, J. 2018; 379 (13): e22

  View details for DOI 10.1056/NEJMimc1715097

  View details for PubMedID 30257165

• Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia. Alzheimer disease and associated disorders Galetta, K. M., Chapman, K. R., Essis, M. D., Alosco, M. L., Gillard, D., Steinberg, E., Dixon, D., Martin, B., Chaisson, C. E., Kowall, N. W., Tripodis, Y., Balcer, L. J., Stern, R. A. 2017; 31 (2): 152-158

  Abstract

  The King-Devick (K-D) test is a 1 to 2 minute, rapid number naming test, often used to assist with detection of concussion, but also has clinical utility in other neurological conditions (eg, Parkinson disease). The K-D involves saccadic eye and other eye movements, and abnormalities thereof may be an early indicator of Alzheimer disease (AD)-associated cognitive impairment. No study has tested the utility of the K-D in AD and we sought to do so. The sample included 206 [135 controls, 39 mild cognitive impairment (MCI), and 32 AD dementia] consecutive subjects from the Boston University Alzheimer's Disease Center registry undergoing their initial annual evaluation between March 2013 and July 2015. The K-D was administered during this period. Areas under the receiver operating characteristic curves generated from logistic regression models revealed the K-D test distinguished controls from subjects with cognitive impairment (MCI and AD dementia) [area under the curve (AUC)=0.72], MCI (AUC=0.71) and AD dementia (AUC=0.74). K-D time scores between 48 and 52 seconds were associated with high sensitivity (>90.0%) and negative predictive values (>85.0%) for each diagnostic group. The K-D correlated strongly with validated attention, processing speed, and visual scanning tests. The K-D test may be a rapid and simple effective screening tool to detect cognitive impairment associated with AD.

  View details for DOI 10.1097/WAD.0000000000000157

  View details for PubMedID 27299935

  View details for PubMedCentralID PMC5154783

• 20/40 or Better Visual Acuity After Optic Neuritis: Not as Good as We Once Thought? Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Sabadia, S. B., Nolan, R. C., Galetta, K. M., Narayana, K. M., Wilson, J. A., Calabresi, P. A., Frohman, E. M., Galetta, S. L., Balcer, L. J. 2016; 36 (4): 369-376

  Abstract

  Although patients with acute optic neuritis (ON) recover high-contrast visual acuity (HCVA) to 20/40 or better in 95% of affected eyes, patients with a history of ON continue to note subjective abnormalities of vision. Furthermore, substantial and permanent thinning of the retinal nerve fiber layer (RNFL) and the ganglion cell layer (GCL) is now known to occur early in the course of ON. We measured vision-specific quality of life (QOL) in patients with a history of acute ON and recovery of VA to 20/40 or better in their affected eyes to determine how these QOL scores relate to RNFL and GCL thickness and low-contrast letter acuity (LCLA) across the spectrum of visual recovery.Data from an ongoing collaborative study of visual outcomes in multiple sclerosis and ON were analyzed for this cross-sectional observational cohort. Patients and disease-free control participants completed the 25-Item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement to the NEI-VFQ-25, as well as VA and LCLA testing for each eye separately and binocularly. Optical coherence tomography measures for each eye included peripapillary RNFL thickness and macular GCL + inner plexiform layer (GCL + IPL) thickness.Patients with a history of acute ON and recovery to 20/40 or better VA (n = 113) had significantly reduced scores for the NEI-VFQ-25 (83.7 ± 15.4) and 10-Item Neuro-Ophthalmic Supplement (74.6 ± 17.4) compared with disease-free controls (98.2 ± 2.1 and 96.4 ± 5.2, P < 0.001, linear regression models, accounting for age and within-patient, intereye correlations). Most patients with 20/40 or better visual recovery (98/112, 88%) had monocular HCVA in their affected eye of 20/20 or better. Although patients with 20/50 or worse HCVA recovery demonstrated the worst performance on low-contrast acuity, affected eye RNFL and GCL + IPL thickness, and QOL scales, these measures were also significantly reduced among those with 20/40 or better HCVA recovery compared with controls.Patients with a history of ON and "good" visual recovery, defined in the literature as 20/40 or better HCVA, are left with clinically meaningful reductions in vision-specific QOL. Such patient-observed deficits reflect the underlying significant degrees of retinal axonal and neuronal loss and visual dysfunction that are now known to characterize ON even in the setting of maximal HCVA recovery. There remains an unmet therapeutic need for patients with ON.

  View details for DOI 10.1097/WNO.0000000000000421

  View details for PubMedID 27472185

• The King-Devick test of rapid number naming for concussion detection: meta-analysis and systematic review of the literature. Concussion (London, England) Galetta, K. M., Liu, M., Leong, D. F., Ventura, R. E., Galetta, S. L., Balcer, L. J. 2016; 1 (2): CNC8

  Abstract

  Vision encompasses a large component of the brain's pathways, yet is not represented in current sideline testing.We performed a meta-analysis of published data for a vision-based test of rapid number naming (King-Devick [K-D] test).Pooled and meta-analysis of 15 studies estimated preseason baseline K-D scores and sensitivity/specificity for identifying concussed versus nonconcussed control athletes.Baseline K-D (n = 1419) showed a weighted estimate of 43.8 s (95% CI: 40.2, 47.5; I2 = 0.0%; p=0.85 - indicating very little heterogeneity). Sensitivity was 86% (96/112 concussed athletes had K-D worsening; 95% CI: 78%, 92%); specificity was 90% (181/202 controls had no worsening; 95% CI: 85%, 93%).Rapid number naming adds to sideline assessment and contributes a critical dimension of vision to sports-related concussion testing.

  View details for DOI 10.2217/cnc.15.8

  View details for PubMedID 30202552

  View details for PubMedCentralID PMC6114024

• Zeroing in on zoster: A tale of many disorders produced by one virus. Journal of the neurological sciences Galetta, K. M., Gilden, D. 2015; 358 (1-2): 38-45

  Abstract

  While herpes zoster infection has been recognized since antiquity, chickenpox (varicella) was confused with smallpox until the 1800s, when both illnesses became better understood. In the 20th century, varicella zoster virus (VZV) was shown to cause varicella upon primary (first-time) infection and herpes zoster (shingles) after reactivation of latent VZV. Scientific progress over the past 50 years has rapidly advanced the understanding and prevention of disease produced by VZV. Combined imaging and virological studies continue to reveal the protean neurological, ocular and visceral disorders produced by VZV.

  View details for DOI 10.1016/j.jns.2015.10.004

  View details for PubMedID 26454371

  View details for PubMedCentralID PMC4628852

• Quality of life in idiopathic intracranial hypertension at diagnosis: IIH Treatment Trial results. Neurology Digre, K. B., Bruce, B. B., McDermott, M. P., Galetta, K. M., Balcer, L. J., Wall, M. 2015; 84 (24): 2449-56

  Abstract

  The study purpose was to examine vision-specific and overall health-related quality of life (QOL) at baseline in Idiopathic Intracranial Hypertension Treatment Trial patients who were newly diagnosed and had mild visual loss. We also sought to determine the associations between vision-specific QOL scores and visual symptoms, visual function, pain, headache-related disability, and obesity.We assessed QOL using the 36-Item Short Form Health Survey, National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25), and 10-Item NEI-VFQ-25 Neuro-Ophthalmic Supplement. We compared these results with those of previously reported idiopathic intracranial hypertension (IIH) QOL studies. We assessed relationships between QOL and other clinical characteristics.Among 165 participants with IIH (161 women and 4 men with a mean age ± SD of 29.2 ± 7.5 years), vision-specific QOL scores were reduced compared with published values for disease-free controls. Scores of participants were comparable to published results for patients with multiple sclerosis and a history of optic neuritis. A multiple linear regression model for the NEI-VFQ-25 composite score found that perimetric mean deviation in the best eye, visual acuity in the worst eye, visual symptoms, and pain symptoms (headache, neck pain), but not obesity, were independently associated with QOL.IIH affects QOL at time of diagnosis even in patients with mild visual impairment. Vision-specific QOL in patients with newly diagnosed IIH may be as decreased as that for patients with other neuro-ophthalmic disorders. IIH treatment should target visual loss and other symptoms of increased intracranial pressure associated with reduced QOL. Reduced QOL does not simply reflect obesity, an underlying IIH risk factor.

  View details for DOI 10.1212/WNL.0000000000001687

  View details for PubMedID 25995055

  View details for PubMedCentralID PMC4478032

• Vision testing is additive to the sideline assessment of sports-related concussion. Neurology. Clinical practice Marinides, Z., Galetta, K. M., Andrews, C. N., Wilson, J. A., Herman, D. C., Robinson, C. D., Smith, M. S., Bentley, B. C., Galetta, S. L., Balcer, L. J., Clugston, J. R. 2015; 5 (1): 25-34

  Abstract

  We examined the King-Devick (K-D) test, a vision-based test of rapid number naming, as a complement to components of the Sport Concussion Assessment Tool, 3rd edition (SCAT3) for diagnosis of concussion. Baseline and postconcussion data for the University of Florida men's football, women's soccer, and women's lacrosse teams were collected, including the K-D test, Standardized Assessment of Concussion (SAC), and Balance Error Scoring System (BESS). Among 30 athletes with first concussion during their athletic season (n = 217 total), differences from baseline to postinjury showed worsening of K-D time scores in 79%, while SAC showed a ≥2-point worsening in 52%. Combining K-D and SAC captured abnormalities in 89%; adding the BESS identified 100% of concussions. Adding a vision-based test may enhance the detection of athletes with concussion.

  View details for DOI 10.1212/CPJ.0000000000000060

  View details for PubMedID 29443175

  View details for PubMedCentralID PMC5764425

• Analysis of the visual system in Friedreich ataxia. Journal of neurology Seyer, L. A., Galetta, K., Wilson, J., Sakai, R., Perlman, S., Mathews, K., Wilmot, G. R., Gomez, C. M., Ravina, B., Zesiewicz, T., Bushara, K. O., Subramony, S. H., Ashizawa, T., Delatycki, M. B., Brocht, A., Balcer, L. J., Lynch, D. R. 2013; 260 (9): 2362-9

  Abstract

  To use optical coherence tomography (OCT) and contrast letter acuity to characterize vision loss in Friedreich ataxia (FRDA). High- and low-contrast letter acuity and neurological measures were assessed in 507 patients with FRDA. In addition, OCT was performed on 63 FRDA patients to evaluate retinal nerve fiber layer (RNFL) and macular thickness. Both OCT and acuity measures were analyzed in relation to genetic severity, neurologic function, and other disease features. High- and low-contrast letter acuity was significantly predicted by age and GAA repeat length, and highly correlated with neurological outcomes. When tested by OCT, 52.7% of eyes (n = 110) had RNFL thickness values below the fifth percentile for age-matched controls. RNFL thickness was significantly lowest for those with worse scores on the Friedreich ataxia rating scale (FARS), worse performance measure composite Z2 scores, and lower scores for high- and low-contrast acuity. In linear regression analysis, GAA repeat length and age independently predicted RNFL thickness. In a subcohort of participants, 21% of eyes from adult subjects (n = 29 eyes) had macular thickness values below the first percentile for age-matched controls, suggesting that macular abnormalities can also be present in FRDA. Low-contrast acuity and RNFL thickness capture visual and neurologic function in FRDA, and reflect genetic severity and disease progression independently. This suggests that such measures are useful markers of neurologic progression in FRDA.

  View details for DOI 10.1007/s00415-013-6978-z

  View details for PubMedID 23775342

• Sports-related concussion: Anonymous survey of a collegiate cohort. Neurology. Clinical practice Torres, D. M., Galetta, K. M., Phillips, H. W., Dziemianowicz, E. M., Wilson, J. A., Dorman, E. S., Laudano, E., Galetta, S. L., Balcer, L. J. 2013; 3 (4): 279-287

  Abstract

  Studies suggest that a lack of standardized knowledge may lead to underreporting and undertreatment of sports-related concussion. However, there has been little work done to establish how this knowledge may affect athletes' behaviors toward reporting their concussions and removing themselves from play. We conducted an anonymous online survey to assess athletes' knowledge of signs and symptoms of concussion, and also sought to estimate the potential frequency of underreporting in a collegiate athlete cohort. Among 262 athletes who responded to the survey, 43% of those with a history of concussion reported that they had knowingly hidden symptoms of a concussion to stay in a game, and 22% of athletes overall indicated that they would be unlikely or very unlikely to report concussion symptoms to a coach or athletic trainer in the future. These data suggest that there may be a substantial degree of underreporting of concussion among collegiate athletes, despite most acknowledging that they have been formally educated about the risks of concussion.

  View details for PubMedID 24195017

• Measures of visual pathway structure and function in MS: Clinical usefulness and role for MS trials. Multiple sclerosis and related disorders Galetta, K. M., Balcer, L. J. 2013; 2 (3): 172-82

  Abstract

  Over the past decade, the visual pathway in multiple sclerosis (MS) has become an important system for assessing both patient function and disease burden. Abnormalities of low-contrast acuity, long recognized as important correlates of driving, facial recognition, and other activities of daily living, are now noted to be common among patients with MS, even among those with no history of acute optic neuritis (ON). Low-contrast letter acuity scores correlate well with brain MRI lesion burden, visual-evoked potential (VEP) amplitudes, health-related quality of life (QOL), and retinal nerve fiber layer (RNFL) axonal and neuronal loss as measured by optical coherence tomography (OCT). Axonal and neuronal degeneration in MS is likely to be an important cause of visual impairment and disability, particularly among patients with progressive MS subtypes. With the advent of OCT and the use of low-contrast letter acuity charts in MS research and clinical trials, the structure-function correlations afforded by the anterior visual pathway can be assessed and potentially harnessed as a model for testing new therapies. Recent advances in OCT, such as high resolution spectral-domain techniques and computerized algorithms for image analysis, have allowed for measurement of specific retinal layers, including the ganglion cell (GCL) neuronal layer and its intimately associated, thin layer of interneurons, the inner plexiform layer (IPL). Longitudinal collaborative studies of GCL+IPL thinning and RNFL axonal loss are providing an in vivo view into neuroretinal pathology, and are providing new insights into how the visual pathway may reflect overall mechanisms of disease in MS.

  View details for DOI 10.1016/j.msard.2012.12.004

  View details for PubMedID 25877723

• Ganglion cell loss in relation to visual disability in multiple sclerosis. Ophthalmology Walter, S. D., Ishikawa, H., Galetta, K. M., Sakai, R. E., Feller, D. J., Henderson, S. B., Wilson, J. A., Maguire, M. G., Galetta, S. L., Frohman, E., Calabresi, P. A., Schuman, J. S., Balcer, L. J. 2012; 119 (6): 1250-7

  Abstract

  We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS).Cross-sectional study.A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment.The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined.The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score.Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P = 0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P≤0.001), 2.5% LCLA (P<0.001), and 1.25% LCLA (P≤0.001). Among OCT measurements, reductions in GCL+IPL (P<0.001), macular RNFL (P = 0.006), and the combination (macular RNFL+GCL+IPL; P<0.001) were most strongly associated with lower (worse) NEI-VFQ-25 and 10-Item Supplement QOL scores; GCL+IPL thinning was significant even accounting for macular RNFL thickness (P = 0.03 for GCL+IPL, P = 0.39 for macular RNFL).We demonstrated that GCL+IPL thinning is most significantly correlated with both visual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS.Proprietary or commercial disclosure may be found after the references.

  View details for DOI 10.1016/j.ophtha.2011.11.032

  View details for PubMedID 22365058

  View details for PubMedCentralID PMC3631566

• Vision in multiple sclerosis: the story, structure-function correlations, and models for neuroprotection. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society Sakai, R. E., Feller, D. J., Galetta, K. M., Galetta, S. L., Balcer, L. J. 2011; 31 (4): 362-73

  Abstract

  Visual dysfunction is one of the most common clinical manifestations of multiple sclerosis (MS). Just over a decade ago, MS clinical trials did not include visual outcomes, but experts recognized the need for more sensitive measures of visual function. Low-contrast letter acuity emerged as the leading candidate to measure visual disability in MS, and subsequent studies found low-contrast acuity testing to correlate well with brain MRI lesion burden, visual-evoked potentials, quality of life (QOL), and retinal nerve fiber layer (RNFL) loss, as measured by optical coherence tomography (OCT). OCT in MS has allowed for assessment of structure-function correlations that make the anterior visual pathway and acute optic neuritis (ON) ideal models for testing novel agents for neuroprotection and repair. New therapies that reduce axonal loss by neuroprotective or myelin repair mechanisms can now be assessed noninvasively by OCT and coupled with visual function data. Based on OCT studies in MS, RNFL thickness is reduced significantly among patients (92 μm) vs controls (105 μm) and is particularly reduced in MS eyes with a history of ON (85 μm). Worsening of visual function by a clinically significant ≥ 7 letters or approximately 1.5 lines for low-contrast acuity is associated with approximately 4.5 μm reductions in RNFL thickness in MS eyes. Longitudinal studies of OCT have also shown RNFL axonal loss over time that occurs even in the absence of acute ON and that correlates with clinically meaningful worsening of vision and QOL, even in patients with benign MS. The latest OCT investigations involve high-resolution spectral-domain (SD) OCT with segmentation and measurement of specific retinal layers using computerized algorithms. These methods allow quantitation of ganglion cell (neuronal) layer loss and axonal degeneration in MS in vivo. In this review, we examine the data from these studies and ongoing trials that highlight the entity of ON as a model to investigate neuroprotection and neurorepair. In doing so, we also present representative group data from studies that have examined visual function, OCT measures, and QOL scales in patients with MS and ON and disease-free controls. These data, and those from recent meta-analyses, may be used to provide reference values for the development of clinical trial protocols.

  View details for DOI 10.1097/WNO.0b013e318238937f

  View details for PubMedID 22089500

  View details for PubMedCentralID PMC3427931

• Optical coherence tomography (OCT): imaging the visual pathway as a model for neurodegeneration. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics Galetta, K. M., Calabresi, P. A., Frohman, E. M., Balcer, L. J. 2011; 8 (1): 117-32

  Abstract

  Axonal and neuronal degeneration are important features of multiple sclerosis (MS) and other neurologic disorders that affect the anterior visual pathway. Optical coherence tomography (OCT) is a non-invasive technique that allows imaging of the retinal nerve fiber layer (RNFL), a structure which is principally composed of ganglion cell axons that form the optic nerves, chiasm, and optic tracts. Since retinal axons are nonmyelinated until they penetrate the lamina cribrosa, the RNFL is an ideal structure (no other central nervous system tract has this unique arrangement) for visualizing the processes of neurodegeneration, neuroprotection and, potentially, even neuro-repair. OCT is capable of providing high-resolution reconstructions of retinal anatomy in a rapid and reproducible fashion and permits objective analysis of the RNFL (axons) as well as ganglion cells and other neurons in the macula. In a systematic OCT examination of multiple sclerosis (MS) patients, RNFL thickness and macular volumes are reduced when compared to disease-free controls. Conspicuously, these changes, which signify disorganization of retinal structural architecture, occur over time even in the absence of a history of acute demyelinating optic neuritis. RNFL axonal loss in MS is most severe in those eyes with a corresponding reduction in low-contrast letter acuity (a sensitive vision test involving the perception of gray letters on a white background) and in those patients who exhibit the greatest magnitude of brain atrophy, as measured by validated magnetic resonance imaging techniques. These unique structure-function correlations make the anterior visual pathway an ideal model for investigating the effects of standard and novel therapies that target axonal and neuronal degeneration. We provide an overview of the physics of OCT, its unique properties as a non-invasive imaging technique, and its potential applications toward understanding mechanisms of brain tissue injury in MS, other optic neuropathies, and neurologic disorders.

  View details for DOI 10.1007/s13311-010-0005-1

  View details for PubMedID 21274691

  View details for PubMedCentralID PMC3075740

• Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis. Annals of neurology Talman, L. S., Bisker, E. R., Sackel, D. J., Long, D. A., Galetta, K. M., Ratchford, J. N., Lile, D. J., Farrell, S. K., Loguidice, M. J., Remington, G., Conger, A., Frohman, T. C., Jacobs, D. A., Markowitz, C. E., Cutter, G. R., Ying, G. S., Dai, Y., Maguire, M. G., Galetta, S. L., Frohman, E. M., Calabresi, P. A., Balcer, L. J. 2010; 67 (6): 749-60

  Abstract

  Cross-sectional studies of optical coherence tomography (OCT) show that retinal nerve fiber layer (RNFL) thickness is reduced in multiple sclerosis (MS) and correlates with visual function. We determined how longitudinal changes in RNFL thickness relate to visual loss. We also examined patterns of RNFL thinning over time in MS eyes with and without a prior history of acute optic neuritis (ON).Patients underwent OCT measurement of RNFL thickness at baseline and at 6-month intervals during a mean follow-up of 18 months at 3 centers. Low-contrast letter acuity (2.5%, 1.25% contrast) and visual acuity (VA) were assessed.Among 299 patients (593 eyes) with >or=6 months follow-up, eyes with visual loss showed greater RNFL thinning compared to eyes with stable vision (low-contrast acuity, 2.5%: p < 0.001; VA: p = 0.005). RNFL thinning increased over time, with average losses of 2.9microm at 2 to 3 years and 6.1microm at 3 to 4.5 years (p < 0.001 vs 0.5-1-year follow-up interval). These patterns were observed for eyes with or without prior history of ON. Proportions of eyes with RNFL loss greater than test-retest variability (>or=6.6microm) increased from 11% at 0 to 1 year to 44% at 3 to 4.5 years (p < 0.001).Progressive RNFL thinning occurs as a function of time in some patients with MS, even in the absence of ON, and is associated with clinically significant visual loss. These findings are consistent with subclinical axonal loss in the anterior visual pathway in MS, and support the use of OCT and low-contrast acuity as methods to evaluate the effectiveness of putative neuroprotection protocols.

  View details for DOI 10.1002/ana.22005

  View details for PubMedID 20517936

  View details for PubMedCentralID PMC2901775