Clinical impact of EGFR and KRAS mutations in surgically treated unifocal and multifocal lung adenocarcinoma.

Background: Epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma (KRAS) are the two most common oncogenic drivers in lung adenocarcinoma, and their roles still need further exploration. Here we aimed to compare the clinical impact of EGFR and KRAS mutations on disease progression in resected unifocal and multifocal lung adenocarcinoma. Methods: Clinicopathologic and genomic data were collected for patients who underwent resection of lung adenocarcinoma from 2008 to 2022 at Stanford University Hospital. Retrospective review was performed in 241 patients whose tumors harbored EGFR (n=150, 62.2%) or KRAS (n=91, 37.8%) mutations. Clinical outcome was analyzed with special attention to the natural history of secondary nodules in multifocal cases wherein the dominant tumor had been resected. Results: We confirm that compared with EGFR mutations, patients with KRAS mutations had more smokers, larger tumor size, higher TNM stage, higher positron emission tomography (PET)/computed tomography (CT) standard uptake value max, higher tumor mutation burden, and worse disease-free survival and overall survival on univariate analysis. For patients with multifocal pulmonary nodules, the median follow-up of unresected secondary nodules was 55 months. Secondary nodule progression-free survival (SNPFS) was significantly worse for patients with KRAS mutations than those with EGFR mutations (mean 40.3±6.6 vs. 67.7±6.5 months, P=0.004). Univariate analysis showed tumor size, tumor morphology, pathologic TNM stage, and KRAS mutations were significantly associated with SNPFS, while multivariate analysis showed only KRAS mutations were independently associated with worse SNPFS (hazard ratio 1.752, 95% confidence interval: 1.017-3.018, P=0.043). Conclusions: Resected lung adenocarcinomas with KRAS mutations have more aggressive clinicopathological features and confer worse prognosis than those with EGFR mutations. Secondary pulmonary nodules in multifocal cases with dominant KRAS-mutant tumors have more rapid progression of the secondary nodules.

Pathologic RFC1 repeat expansions do not contribute to the development of inflammatory neuropathies.

Biallelic expansions of the AAGGG repeat in the replication factor C subunit 1 (RFC1) have recently been described to be responsible for cerebellar ataxia, peripheral neuropathy and vestibular areflexia syndrome. This genetic alteration has also allowed genetic classification in up to one-third of cases with idiopathic sensory neuropathy. Here, we screened a well-characterized cohort of inflammatory neuropathy patients for RFC1 repeat expansions to explore whether RFC1 was increased from background rates and possibly involved in the pathogenesis of inflammatory neuropathy. A total of 259 individuals with inflammatory neuropathy and 243 healthy controls were screened for the AAGGG repeat expansion using short-range flanking PCR and repeat-primed PCR. Cases without amplifiable PCR product on flanking PCR and positive repeat-primed PCR were also tested for the mostly non-pathogenic expansions of the AAAGG and AAAAG repeat units. None of the patients showed biallelic AAGGG expansion of RFC1, and their carrier frequency for AAGGG was comparable with controls [n = 27 (5.2%) and n = 23 (4.7%), respectively; P > 0.5]. Data suggest that the pathologic expansions of AAGGG repeats do not contribute to the development of inflammatory neuropathies nor lead to misdiagnosed cases. Accordingly, routine genetic screening for RFC1 repeat expansion is not indicated in this patient population.

Function and Circulation of the Retina and Choroid in Case of Indolent Nonprogressive Multifocal Choroidal Lesions.

Indolent nonprogressive multifocal choroidal lesions have been reported to be benign choroidal lymphatic lesions that do not affect the visual function. However, as best known, there are no reports on whether these lesions affect the circulation and function of the retina and choroid. We report a case of indolent nonprogressive multifocal choroidal lesions in which retinal images were available to assess the retinal and choroidal circulation and whether it impacted the retinal function. The patient was a 45-year-old man. Swept-source optical coherence tomography (OCT) showed multiple well-defined, uniform, hyporeflective cavernous lesions in the choroidal layer. Then a diagnosis of indolent nonprogressive multifocal choroidal lesions was made based on the similarity of the features with those reported. OCT angiography showed no blood flow signals in the lesions and reduced blood flow signals in the choroid and choriocapillaris directly above the lesions. Fundus autofluorescence showed retinal pigment epithelial damages that were colocalized with the choroidal lesions. We then performed static visual field testing and multifocal electroretinography (mfERG). The static visual field test showed no decrease in sensitivity in the entire visual field, and mfERG showed no decrease in the amplitudes or implicit times indicating normal retinal function. In indolent nonprogressive multifocal choroidal lesions, the photoreceptor function is preserved but a mild retinal pigment epithelium disorder is present. Thus, the follow-up examinations of indolent nonprogressive multifocal choroidal lesions should include retinal function tests.

Extrafacial Acquired Dermal Melanocytosis: An Exceptionally Rare Example With Bilateral Multifocal Disease.

Dermal melanocytoses are a group of cutaneous disorders characterized by the presence of ectopic melanocytes in the dermis; the most well-known example is the Mongolian spot. Acquired dermal melanocytosis (ADM) is a term used to describe the onset of dermal melanocytosis occurring after its usual age of presentation (i.e., birth and infancy). ADMs usually occur on the face and can less commonly affect extrafacial sites, such as the back and limbs. Purely extrafacial ADM is extremely uncommon and, when present, is usually unifocal. Herein, we present an exceptionally rare example of purely extrafacial ADM with extensive bilateral involvement in a 44-year-old female originally from the Philippines.

The induced defocus by Defocus Incorporated Soft Contact lenses is dependent on visual distance and ambient illuminance.

PURPOSE: Defocus Incorporated Soft Contact (DISC) lenses, a commonly used type of multifocal lens in clinical practice, may slow down myopia progression by inducing myopic retinal defocus. The purpose of this study was to explore whether the induced defocus across the retina could be affected by visual environments encountered in the real world, such as differences in viewing distance and ambient illuminance. METHODS: In this cross-over trial, 30 myopic adults wore both DISC lenses and single vision contact (SVC) lenses in random order. An open-view Hartmann-Shack scanning wavefront sensor was used to measure defocus at different retinal locations along the horizontal meridian under four experimental conditions: far target (3 m) and near targets (0.33 m) under scotopic (<1 lux) or photopic (~300 lux) conditions. RESULTS: The results showed that DISC lenses induced more myopic retinal defocus than SVC lenses in all conditions (all p < 0.05), except for the scotopic near target. In addition, for DISC lenses, the defocus was greater in the photopic than the scotopic conditions for both the far and near targets (both p < 0.05). CONCLUSION: In conclusion, the retinal defocus induced by these multifocal lenses was dependent on both visual distance and ambient illuminance, indicating that the visual conditions might affect the anti-myopia efficacy of these devices.

Traversing the Terrain: Potential Pitfalls within the AJCC 8th Edition Staging System for Lip and Oral Cavity Cancers.

In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.

Portable multi-focal visual evoked potential diagnostics for multiple sclerosis/optic neuritis patients.

PURPOSE: Multiple sclerosis (MS) is a neuro-inflammatory disease affecting the central nervous system (CNS), where the immune system targets and damages the protective myelin sheath surrounding nerve fibers, inhibiting axonal signal transmission. Demyelinating optic neuritis (ON), a common MS symptom, involves optic nerve damage. We've developed NeuroVEP, a portable, wireless diagnostic system that delivers visual stimuli through a smartphone in a headset and measures evoked potentials at the visual cortex from the scalp using custom electroencephalography electrodes. METHODS: Subject vision is evaluated using a short 2.5-min full-field visual evoked potentials (ffVEP) test, followed by a 12.5-min multifocal VEP (mfVEP) test. The ffVEP evaluates the integrity of the visual pathway by analyzing the P100 component from each eye, while the mfVEP evaluates 36 individual regions of the visual field for abnormalities. Extensive signal processing, feature extraction methods, and machine learning algorithms were explored for analyzing the mfVEPs. Key metrics from patients' ffVEP results were statistically evaluated against data collected from a group of subjects with normal vision. Custom visual stimuli with simulated defects were used to validate the mfVEP results which yielded 91% accuracy of classification. RESULTS: 20 subjects, 10 controls and 10 with MS and/or ON were tested with the NeuroVEP device and a standard-of-care (SOC) VEP testing device which delivers only ffVEP stimuli. In 91% of the cases, the ffVEP results agreed between NeuroVEP and SOC device. Where available, the NeuroVEP mfVEP results were in good agreement with Humphrey Automated Perimetry visual field analysis. The lesion locations deduced from the mfVEP data were consistent with Magnetic Resonance Imaging and Optical Coherence Tomography findings. CONCLUSION: This pilot study indicates that NeuroVEP has the potential to be a reliable, portable, and objective diagnostic device for electrophysiology and visual field analysis for neuro-visual disorders.

Identification of EGFR R776H germline mutations in a patient with multifocal lung adenocarcinoma: A case report and literature review.

The advancement of molecular pathology techniques has led to the discovery of rare EGFR mutations for targeted therapy in lung cancer. Additionally, a substantial body of evidence indicates a connection between the development of lung cancer and genetic variations in the EGFR gene. Here, we present a case report of a patient with multifocal lung adenocarcinoma who possessed a rare germline mutation, EGFR R776H. An investigation into the family history of the patient exposed the notable incidence of lung adenocarcinoma, indicating a plausible genetic vulnerability to the ailment. To be specific, the patient's older brother and sister both suffered from lung cancer, which underlines the hereditary predisposition. Furthermore, it should be noted that the patient's daughter has inherited the germline mutation and also presented with multiple lung ground-glass nodules, emphasizing the clinical importance of this genetic variation. Following the lobectomy, the patient received treatment with almonertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), and at the latest follow-up, the patient has achieved partial remission. This case highlights the significance of taking into account germline possibilities when multiple lesions carry the same mutation. It stresses the importance of acquiring a comprehensive family history and performing genetic testing on leukocytes. Moreover, for the infrequent EGFR R776H mutation, third generation EGFR-TKIs may be a viable option.

Discrimination of pediatric cryptogenic multifocal ulcerous stenosing enteritis from small bowel Crohn's disease and gastrointestinal tuberculosis: A retrospective study (with videos).

INTRODUCTION: Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare entity that mimics various inflammatory strictures of the small intestine. Pediatric literature is scarce. We analyzed the clinical, radiological, endoscopic and histopathological features of children with CMUSE that differentiate it from small bowel Crohn's disease (SBCD) and gastrointestinal tuberculosis (GITB). METHODS: CMUSE was diagnosed by the following criteria: (1) unexplained small bowel strictures with superficial ulcers, (2) chronic/relapsing ulcers of small bowel after resection, (3) no signs of systemic inflammation, (4) absence of other known etiologies of small bowel ulcers. SBCD and GITB were diagnosed based on standard criteria. The clinical features, laboratory parameters, radioimaging, endoscopy (including video capsule endoscopy [VCE], intra-operative endoscopy), histopathological features and treatment outcome were noted. RESULTS: Out of 48, CMUSE was diagnosed in 13 (27%) isolated small bowel and ileocecal strictures, while GITB and SBCD accounted for 41% and 21% cases, respectively. Common presentations were sub-acute obstruction (46%), obscure gastrointestinal bleeding (38%) and protein-losing enteropathy (38%). CMUSE patients had significantly longer disease duration compared to SBCD and GITB (p < 0.001). SBCD (90.0%) and GITB (85%) cases had elevated C-reactive protein (CRP), none with CMUSE had elevated CRP (p < 0.001). The disease was localized in jejunum (100%) and proximal ileum (56%) in CMUSE, ileocecal region (85%) in GITB, but evenly distributed in small intestine in SBCD. Endoscopy showed evenly placed, superficial, circumferential ulcers with strictures in CMUSE, deep linear ulcers in SBCD and circumferential ulcers in GITB. Upfront immunosuppression was given in four; three (75%) of them relapsed. Only surgery was done in three with one (25%) having relapse. Upfront surgery followed by immunosuppression was used in six, but all relapsed and two required repeat surgery. CONCLUSION: CMUSE is important but underdiagnosed in children. Lack of constitutional symptoms, normal inflammatory parameters and characteristic ulcers with strictures helped in differentiating CMUSE from GITB and SBCD.

Systemic juvenile idiopathic arthritis with chronic recurrent multifocal osteomyelitis in an adolescent: A case report.

Chronic recurrent multifocal osteomyelitis is a rare auto-inflammatory disease in children, with only a few reports of its association with other inflammatory diseases, such as systemic juvenile idiopathic arthritis. A 15-year-old boy was admitted due to fever, skin rash, arthritis, and high inflammatory factors and was finally diagnosed with systemic juvenile idiopathic arthritis. After 6 months of recovery from the disease, the patient was referred due to local pain and swelling in the arms and left thigh. In radiography, bone lesions were seen in the shoulders, left humerus, and left femoral diaphysis. A whole-body bone scan showed increased absorption in these areas, which suggested a tumor or osteomyelitis. A biopsy of the bone lesion of the left humerus confirmed sterile osteomyelitis. Although the co-incidence of chronic recurrent multifocal osteomyelitis with systemic juvenile idiopathic arthritis is rare, it should be considered in differential diagnosis.

Locoregional Management of Multiple Ipsilateral Breast Cancers: A Review.

The incidence of preoperatively diagnosed multiple ipsilateral breast cancer (MIBC) is increasing due to improved sensitivity of screening and preoperative staging modalities including digital breast tomosynthesis (3D breast mammography) and magnetic resonance imaging (MRI). The surgical management of MIBC remains controversial. Many surgeons continue to recommend mastectomy due to high local recurrence rates in patients with MIBC undergoing breast conservation therapy reported in historic, retrospective studies. More recent retrospective studies report acceptable rates of local recurrence. Yet concerns persist due to a paucity of prospective data regarding recurrence as well as concerns for margin positivity, cosmetic outcomes and the feasibility of adequate and safe delivery of radiation following breast conserving surgery. Breast conservation has emerged as the preferred surgical strategy for eligible patients with unifocal disease. Benefits include improved quality of life, body image and sexual function and lower surgical complication rates. A recent prospective clinical trial has corroborated a large body of retrospective data confirming the safety of breast conserving therapy and adjuvant radiation in women with MIBC with good oncologic control, low rates of conversion to mastectomy and satisfactory patient-reported cosmetic outcomes. With the current rise in MIBC diagnoses, it is imperative that surgeons understand the existent evidence in order to guide shared decision-making conversations with patients diagnosed with MIBC. This comprehensive review synthesizes the best available data and offers current recommendations for management of both the primary sites of disease as well as management of the axilla in patients with MIBC.

Pediatric cerebrospinal fluid rhinorrhea caused by low flow vascular anomaly of the temporal bone: A case series.

OBJECTIVE: Atraumatic cerebrospinal fluid (CSF) rhinorrhea is uncommon in children and necessitates a multi-disciplinary evaluation for an etiology. Underlying osseous abnormality due to extensive or multifocal low flow vascular anomaly should be considered as a potential cause of spontaneous CSF leak. Treatment of multifocal low flow vascular anomalies may include medical and surgical approaches. In this series, we seek to determine the presenting signs and symptoms and medical and surgical treatment options for multifocal or extensive low flow vascular anomalies. METHODS: A retrospective case series at a quaternary care children's hospital was compiled. All children with CSF rhinorrhea diagnosed and treated for multifocal low flow vascular anomalies at our institution were included. A total of four patients were identified. RESULTS: All four patients had delay in initial diagnosis of underlying cause of meningitis and CSF rhinorrhea. Average age at diagnosis of multifocal low flow vascular anomaly was 7 years. This was on average 4 years after initial presentation for medical attention. Treatment approach was multidisciplinary and included medical management with sirolimus and bisphosphonates as well as surgical approaches to the skull base (lateral and anterior) to prevent CSF egress. CONCLUSION: Consideration of multifocal low flow vascular anomaly should be included in any pediatric patient presenting with CSF rhinorrhea.

A case of a cerebellar form of progressive multifocal leukoencephalopathy in a patient undergoing peritoneal dialysis.

Progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system, is caused by the reactivation of the polyomavirus JC virus (JCV). It favors the cerebrum and typically occurs in patients with immunodeficiencies, with a progressive course and fatal outcome in the majority of cases. However, the cerebellar form of PML, characterized by isolated posterior fossa lesions, such as those in the cerebellum or brainstem at disease onset, is rare, and reports of its occurrence in peritoneal dialysis (PD) patients are lacking. In this paper, we describe a rare case of a cerebellar form of PML in a PD patient. A 64-year-old man undergoing PD was referred to our hospital for anorexia, nausea, and vomiting in the past month. He had finger-to-nose test abnormalities, gaze-directed nystagmus, and scanning speech. He was diagnosed with the cerebellar form of PML based on his progressive cerebellar symptoms, the typical magnetic resonance imaging findings, and the presence of JCV-DNA in the cerebrospinal fluid polymerase chain reaction test. He developed nocturnal delirium, aggravated disquiet, and died of pneumonia on the 69th day. Clinicians should consider the cerebellar form of PML as a differential diagnosis if PD patients develop progressive cerebellar symptoms.

Biometric factors associated with the postoperative visual performance of a multifocal intraocular lens.

Purpose: To identify the biometric factors associated with postoperative visual performance after uneventful phacoemulsification with multifocal intraocular lens (MIOL) implantation. Methods: In this retrospective cohort study, 72 eyes of 72 patients implanted with the HumanOptics Diff-aAY MIOL were included. Preoperative examination data including the white-to-white distance (WTW), anterior chamber depth (ACD), axial length and corneal astigmatism were gathered through the electronic medical records. One month postoperatively, the pupil parameters, corneal aberrations, corneal astigmatism, IOL tilts and IOL decentrations were measured using an OPD-Scan III aberrometer. Postoperative visual performance parameters were recorded as the visual acuity, depth of focus, modulation transfer function (MTF) and point spread function (PSF) values, area under log contrast sensitivity function (AULCSF), retinal straylight and visual function questionnaire scores. Univariate and multivariate linear regression analyses were then performed to evaluate the associations between the potential biometric factors and postoperative visual outcomes. Results: Younger age predicted greater MTF and PSF values, better AULCSF and better retinal straylight (P < 0.05). A lower corneal trefoil predicted better MTF and PSF values (P < 0.05). Smaller IOL decentration predicted better distance-corrected near visual acuity, greater AULCSF and better retinal straylight (P < 0.05). A less negative spherical equivalent (SE) predicted better MTF values (P = 0.017), while a more negative SE predicted better Visual Function Index-14 (VF-14) questionnaire scores and satisfaction scores (P < 0.05). A higher IOL power predicted better best corrected distance visual acuity (P = 0.005). Lower preoperative corneal astigmatism predicted greater MTF values (P = 0.020). Lower postoperative corneal astigmatism, smaller corneal high-order aberrations (HOAs), smaller photopic pupil size, larger WTW and deeper ACD predicted a better AULCSF (P < 0.05). Conclusions: IOL decentration, IOL power, age, preoperative and postoperative corneal astigmatism, SE, photopic pupil size, corneal trefoil, WTW, ACD and corneal HOAs were significantly associated with postoperative visual performance. These findings might aid in patient selection prior to MIOL implantation.

Comparison of the axial growth with multifocal and monofocal intraocular lenses in unilateral pediatric cataract surgery.

PURPOSE: To compare axial growth in pediatric cataract patients who underwent multifocal intraocular lens (IOL) implantation without anterior vitrectomy (AV) with that in pediatric patients who underwent monofocal IOL implantation with or without AV. METHODS: Patients who had unilateral pediatric cataracts and underwent surgery at 3-6 years of age from June 6, 2019, to June 30, 2020, at our institution were prospectively analyzed. The patients were categorized into Group A: multifocal IOL implantation with optic capture in Berger's space without AV; Group B: monofocal IOL implantation with optic capture in Berger's space without AV; and Group C: bag-in-the-lens monofocal IOL implantation with AV. Groups A', B' and C' consisted of the fellow eyes from the respective groups. Axial growth and monthly growth rates were compared among the 3 treatment groups, as well as between the treated eyes and the fellow eyes. RESULTS: Thirty-one, 23, and 14 children fulfilling the inclusion criteria, respectively, were included in the final analysis. There were no significant differences in patient age at the time of surgery or preoperative axial length (P > 0.05). After a mean follow-up of 35.57 ± 3.78 months, significant differences in the axial growth and the monthly growth rate were observed (P < 0.05), and Group A had the least axial elongation. Comparing treated eyes with fellow eyes, the amount and rate of axial growth were lower in Group A than in Group A' (P < 0.05), no significant differences were found in Group B (P > 0.05), and Group C had greater growth than did Group C' (P < 0.05). CONCLUSIONS: The implanting multifocal intraocular lenses and maintenance of vitreous body integrity may be protective factors against excessive axial growth in pediatric cataract patients. Clinical trial registration (prospective study): chiCRT1900023155; 2019-05-14.

Chemokine-mediated cell migration into the central nervous system in progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) has been associated with different forms of immune compromise. This study analyzes the chemokine signals and attracted immune cells in cerebrospinal fluid (CSF) during PML to define immune cell subpopulations relevant for the PML immune response. In addition to chemokines that indicate a general state of inflammation, like CCL5 and CXCL10, the CSF of PML patients specifically contains CCL2 and CCL4. Single-cell transcriptomics of CSF cells suggests an enrichment of distinct CD4+ and CD8+ T cells expressing chemokine receptors CCR2, CCR5, and CXCR3, in addition to ITGA4 and the genetic PML risk genes STXBP2 and LY9. This suggests that specific immune cell subpopulations migrate into the central nervous system to mitigate PML, and their absence might coincide with PML development. Monitoring them might hold clues for PML risk, and boosting their recruitment or function before therapeutic immune reconstitution might improve its risk-benefit ratio.

Routine MR Imaging Protocol and Standardization in Central Nervous System Demyelinating Diseases.

Standardized MR imaging protocols are important for the diagnosis and monitoring of patients with multiple sclerosis (MS) and the appropriate use of MR imaging in routine clinical practice. Advances in using MR imaging to establish an earlier diagnosis of MS, safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MR imaging for diagnostic, prognostic, and monitoring purposes suggest a changing role of MR imaging for the management and care of MS patients. The MR imaging protocol emphasizes 3 dimensional acquisitions for optimal comparison over time.

Clinical outcomes after use of checkpoint inhibitor immunotherapies in people with multiple sclerosis.

Background: Immune checkpoint inhibitors (ICIs) represent a novel class of agents approved for the treatment of several cancers and progressive multifocal leukoencephalopathy (PML). However, due to the risk of autoimmune side effects, their use in people with autoimmune diseases such as multiple sclerosis (MS) has been limited. Objective: To characterize outcomes in a cohort of adults with MS who received ICIs. Methods: A single-center retrospective review of medical record data was performed for people with MS treated with ICIs. Results: Seven people with MS were identified, with a mean (SD) age at ICI use of 55.4 (13.7) years and a mean MS duration of 18.2 (12.2) years. Six were treated for cancer; 1 was treated for PML. After mean (SD) follow-up of 1.76 (2.15) years after ICI, outcomes are: no evidence of disease (2), residual metastatic disease (1), death due to cancer (1), death due to PML (1), and lost to follow-up (2). Notably, 0 out of 7 patients experienced an MS relapse; two out of six had new asymptomatic demyelinating magnetic resonance imaging lesions. In the three patients with expanded disability status scale (EDSS) scores at baseline and follow-up, EDSS remained stable (mean delta 0.13). Conclusion: In this cohort, no people with MS experienced clinical relapses and one-third experienced asymptomatic radiological activity following ICI treatment.