A Common Embryonic Origin of Stem Cells Drives Developmental and Adult Neurogenesis.

New neurons arise from quiescent adult neural progenitors throughout life in specific regions of the mammalian brain. Little is known about the embryonic origin and establishment of adult neural progenitors. Here, we show that Hopx+ precursors in the mouse dentate neuroepithelium at embryonic day 11.5 give rise to proliferative Hopx+ neural progenitors in the primitive dentate region, and they, in turn, generate granule neurons, but not other neurons, throughout development and then transition into Hopx+ quiescent radial glial-like neural progenitors during an early postnatal period. RNA-seq and ATAC-seq analyses of Hopx+ embryonic, early postnatal, and adult dentate neural progenitors further reveal common molecular and epigenetic signatures and developmental dynamics. Together, our findings support a "continuous" model wherein a common neural progenitor population exclusively contributes to dentate neurogenesis throughout development and adulthood. Adult dentate neurogenesis may therefore represent a lifelong extension of development that maintains heightened plasticity in the mammalian hippocampus.

Evaluation of clinical predictors of postoperative outcomes in tegmen defect patients with and without concurrent superior semicircular canal dehiscence and cerebrospinal fluid leak.

OBJECTIVES: Tegmen and superior semicircular canal defects have been well studied, yet the factors contributing to their onset and progression are widely debated. The clinical utility of intraoperative intracranial pressure measurements has yet to be tested. This report aims to use intraoperative opening pressure and concurrent superior semicircular canal dehiscence (SSCD) to analyze factors influencing disease course and clinical outcomes in patients with tegmen dehiscence. METHODS: A retrospective analysis of 61 patients who underwent tegmen defect repair was performed. Multiple variables of interest including body mass index (BMI), presence of SSCD, presence of dural venous sinus stenosis, opening pressure, and acetazolamide therapy use were recorded. The cohort was divided into those with or without concurrent SSCD and those presenting with or without cerebrospinal fluid (CSF) leak for analysis. RESULTS: A linear relationship between opening pressure and BMI (p = 0.009) was noted; however, intraoperative opening pressure was not associated with disease outcome. Concurrent SSCD was present in 25 % of patients, while 62 % presented with CSF leak. The concurrent SSCD group exhibited higher opening pressure, higher likelihood of having dural sinus stenosis, and higher likelihood of being discharged on acetazolamide. The CSF leak group had higher likelihood of obstructive sleep apnea and persistent symptoms. CONCLUSIONS: In patients undergoing tegmen defect repair, concurrent SSCD suggests increased disease severity. The presence of preoperative CSF leak predicts persistent symptoms following repair. BMI is linearly correlated with intracranial pressure in these patients.

Iatrogenic haemoperitoneum requiring transfusion after ventriculoperitoneal shunt placement: case report.

Cerebrospinal fluid (CSF) diversion for hydrocephalus via ventriculoperitoneal (VP) shunting is one of the most commonly performed neurosurgical procedures. Unfortunately, VP shunting also carries a high complication rate. While long-term complications of VP shunting are generally well-described, the literature on more acute, iatrogenic injury during shunt placement is essentially limited to easily identifiable intracranial bleeds. Herein is presented the first reported case of iatrogenic abdominal wall vessel injury as a consequence of blind distal VP shunt catheter placement causing a critical haemoperitoneum that necessitated multiple transfusions. Presentation and recognition of this bleed was delayed as it occurred over a number of days. Injury to the inferior epigastric artery, or potentially a distal branch of the superficial epigastric artery, is suspected to have occurred during either blind subcutaneous tunnelling of the shunt catheter passage or during penetration of the peritoneum. Haemoperitoneum as a potential complication of procedures involving manipulation or penetration of the abdominal wall (i.e. paracentesis) is well-described in the medical and general surgical literature, and ultrasound-guidance has been widely adopted to mitigate bleeding in these cases. Familiarity with intra-abdominal haemorrhage as a potential complication of VP shunting and an understanding of its presentation is critical for timely identification of this phenomenon. Furthermore, the use of real-time ultrasound-guidance for tunnelling and distal shunt catheter placement may decrease the incidence of intrabdominal complications after shunt placement more generally and should be considered an area of future study.

Bibliometric analysis of the top 100 cited articles on stereotactic radiosurgery of intracranial meningiomas.

BACKGROUND: Sterotactic radiosurgery is becoming an integral modality in the management of intracranial meningiomas, both as the primary treatment or as adjuvant therapy. This study analyzes the scholarly impact of the top 100 cited articles on the stereotactic radiosurgical management of intracranial meningiomas. METHODS: A ranked list of the 100 most-cited articles was generated using the Scopus database by searching the keywords 'intracranial meningioma' and 'stereotactic radiosurgery'. All articles were then evaluated on multiple criteria regarding both the publication of the articles (year of publication, journal, country of origin, and authors) as well as their methods and foci (type of study, location of studied meningiomas, and type of radiosurgical modality). Quantitaitve and qualitative analyses were then performed from the collected data. RESULTS: The most frequently cited articles on stereotactic radiosurgical management of intracranial meningiomas were published between 1990 and 2016. The average citation-per-year across all papers in the list was 6.1. The most studied anatomic area of intracranial meningiomas was the skull base, with the cavernous sinus being the most well-studied specific site. The most utilized stereotactic radiosurgical modality was Gamma Knife radiosurgery. The country with the highest number of publications was the United States. Twenty-six percent of the articles were published in the journal Neurosurgery; Lunsford, Kondziolka, Flickinger, Sheehan, and Pollock were respectively the most frequent listed authors among this list. The most active academic institute publishing on this topic was the University of Pittsburgh Medical Center. CONCLUSION: Stereotactic radiosurgery is an integral modality in the management of intracranial meningiomas. This bibliometric analysis sheds the light on the ways in which intracranial meningiomas have been studied in the past two decades in order to identify trends among neurosurgeons and radiation oncologists and to reveal areas of rising and declining focus.

The role of endoscopic endonasal surgery in the management of prolactinomas based on their invasiveness into the cavernous sinus.

PURPOSE: To review our institutional experience with the surgical management of prolactinomas through the endoscopic endonasal approach with specific focus on cavernous sinus invasion. METHODS: Clinical and radiographic data were collected retrospectively from the electronic medical record of 78 consecutive patients with prolactinomas undergoing endoscopic endonasal resection from 2002 to 2019. Immediate and late post-operative remission were defined as prolactin < 20 ng/mL within 14 days and 1-year of surgery without adjuvant therapy, respectively. Cavernous sinus invasion was quantified by Knosp score. RESULTS: A total of 78 patients with prolactinoma, 59% being male, underwent surgical resection with a mean age of 37 ± 13 years. Indications for surgery were medication resistance in 38 patients (48.7%), medication intolerance in 11 (14.1%), and patient preference in 29 (37.2%). Patients with Knosp 0-2 achieved higher immediate remission rates (83.8%) compared to patients with Knosp 3 (58.8%) and Knosp 4 (41.7%) patients (p = 0.003). Long-term remission rates were 48.7% and increased to 71.8% when combined with adjuvant treatments. Knosp 4 prolactinomas had significantly higher tumor volumes, higher preoperative prolactin levels, higher recurrence rates, higher rates of adjuvant therapy utilization, and were more likely to have failed dopamine agonist therapy compared to other tumor grades (p < 0.05). We encountered 18 complications in our series, and no cerebrospinal fluid leaks. CONCLUSION: The endoscopic endonasal approach is a safe and effective modality that can be employed in properly selected patients with invasive prolactinomas. It is associated with improved control and remission rates despite cavernous sinus invasion, though at a lower rate than without invasion.

Paraspinal Desmoid Tumor in a Pediatric Patient with No Surgical History: A Case Report.

Desmoid tumors are locally aggressive, benign neoplasms originating in connective tissues. Although the exact pathophysiology remains unknown, antecedent trauma or surgery are believed to be important contributing factors. The occurrence of paraspinal desmoid tumor in pediatric patients is extremely uncommon. Here, we present an exceedingly rare case of a pediatric patient with no surgical or family history who developed a paraspinal desmoid tumor. A 9-year-old female patient presented with 4 months of progressive back pain, right lower extremity weakness, and numbness. Spinal imaging revealed a left epidural paraspinal mass compressing her thoracic spinal cord and extending into the left thoracic cavity. A multidisciplinary approach with neurosurgery and thoracic surgery enabled gross total resection of the lesion. The patient had complete resolution of her symptoms with no signs of residual tumor on postoperative imaging. Pathology revealed a desmoid tumor that avidly stained for beta-catenin. On her last follow-up, she developed a recurrence, to which she was started on sorafenib therapy. Desmoid tumors are rare connective tissue neoplasms that often occur after local tissue trauma, such as that caused by surgery. This report presents a rare case of a pediatric paraspinal desmoid tumor that occurred in a patient with no surgical or family history. Such tumors should undergo surgical resection for symptomatic relief and tissue diagnosis. Close clinical and radiographic surveillance are essential in these patients due to the high recurrence rates of desmoid tumor.

Idiopathic De Novo Arteriovenous Malformation: A Rare Acquired Intracranial Lesion.

The de novo development of cerebral arteriovenous malformations (AVMs) in adults is an exceedingly rare event that has prompted the theory that a "second hit" is required to induce AVM formation. The authors document development of an occipital AVM in an adult a decade and a half after a brain magnetic resonance imaging (MRI) disclosed no abnormality. A 31-year-old male with a family history of AVMs and a 14-year history of migraines with visual auras and seizures presented to our service. Because of the onset of a first seizure and migraine headaches at age 17, the patient underwent high-resolution MRI that showed no intracranial lesion. After 14 years of progressively worsening symptoms, he underwent a repeat MRI that demonstrated a new de novo Spetzler-Martin grade 3 left occipital AVM. The patient received anticonvulsants and underwent Gamma Knife radiosurgery for his AVM. This case suggests that patients with seizures or persistent migraine headaches should have periodic repeat neuroimaging to exclude the development of a vascular cause despite an initial negative MRI.

United States Neurosurgery Department Program Directors: A Cross-Sectional Evaluation of Current and Future Trends and Attributes.

BACKGROUND: While United States (U.S.) neurosurgery residency programs have been subject to many studies, none have focused solely on the program directors (PDs). We aim to analyze the demographic, educational, and academic attributes of this cohort to understand current and future trends of PDs. METHODS: One hundred sixteen neurosurgeons listed as PDs at U.S. accredited neurosurgical residency training programs as of August 2022 were assessed. Descriptive data including age upon acceptance of role, gender, and h-index were collected from publicly available sources. RESULTS: Most PDs matriculated to their positions before the age of 45 years, were male, and had been hired internally. Approximately 25% of PDs had earned an additional degree. Departments with higher aggregate h-indexes were more likely to hire PDs with higher average publications per year (P < 0.001) and have a higher h-index (P < 0.001). PD subspecialty influenced h-index (P < 0.05) and total average publications per year (P < 0.05) with neuro-oncology subspecialists having higher averages in both. More recently hired PDs had a higher average number of publications per year (P < 0.05) and were more likely to hold an additional degree (odds ratio 1.14, P < 0.05). Female PDs were hired at a younger age (P < 0.05). CONCLUSIONS: Neurosurgery PDs typically rise to their position after 10 years of practice and more recent PD hires are more likely to have additional degrees and more publications. As academic neurosurgery becomes more competitive, increased academic productivity and acquisition of additional degrees will become increasingly necessary.

Prevalence of Long-Term Low Back Pain After Symptomatic Lumbar Disc Herniation.

OBJECTIVE: Lumbar disc herniation (LDH) is a global issue associated with potentially debilitating long-term consequences, including chronic low back pain (LBP). Short-term outcomes (<2 years) of patients with LDH have been extensively studied and demonstrate improvements in back and leg pain for both operative and conservative management. However, these improvements may not be sustained long-term (>2 years); patients with LDH may develop recurrent disc herniations, progressive degenerative disc disease, and LBP regardless of management strategy. Therefore, our objective is to determine the prevalence of chronic LBP after LDH, understand the relationship between LDH and chronic LBP, and investigate the relationship between radiological findings and postoperative pain outcomes. METHODS: We performed a literature review on the PubMed database via a combination medical subject heading and keyword-based approach for long-term LBP outcomes in patients with LDH. RESULTS: Fifteen studies (2019 patients) evaluated surgical and/or nonoperative outcomes of patients with LDH . Regardless of surgical or nonoperative management, 46.2% of patients with LDH experienced some degree of LBP long-term (range 2-27 years) as compared to a point prevalence of LBP in the general population of only 11.9%. CONCLUSIONS: Patients with LDH are more likely to experience long-term LBP compared to the general population (46.2% vs. 11.9%). Additionally, understanding the relationship between radiological findings and pain outcomes remains a major challenge as the presence of radiological changes and the degree of LBP do not always correlate. Therefore, higher quality studies are needed to better understand the relationship between radiological findings and pain outcomes.

Adoption of adjuvant chemotherapy in high-risk salivary gland malignancies.

BACKGROUND: The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies. METHODS: The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004-2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan-Meier analysis (HR: 0.98; 95% CI: 0.86-1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78-1.09; p = 0.34). CONCLUSIONS: Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy.

Chronic Encapsulated Expanding Hematomas After Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: An International Multicenter Case Series.

BACKGROUND: Stereotactic radiosurgery (SRS) offers a minimally invasive treatment modality for appropriately selected intracranial arteriovenous malformations (AVMs). Recent reports have described the development of rare, delayed chronic encapsulated expanding hematomas (CEEHs) at the site of an angiographically confirmed obliterated AVM. OBJECTIVE: To elucidate the incidence, characteristics, and management of CEEH in patients with AVM after SRS. METHODS: The records of all patients who underwent SRS for an intracranial AVM at 4 institutions participating in the International Radiosurgery Research Foundation between 1987 and 2021 were retrospectively reviewed. Data regarding characteristics of the AVM, SRS treatment parameters, CEEH presentation, management, and outcomes were collected and analyzed. RESULTS: Among 5430 patients, 15 developed a CEEH at a crude incidence of 0.28%. Nine patients were female, and the mean age was 43 ± 14.6 years. Nine patients underwent surgical evacuation, while 6 were managed conservatively. The median CEEH development latency was 106 months after SRS. The patients were followed for a median of 32 months, and 9 patients improved clinically, while 6 patients remained stable. No intraoperative complications were reported after CEEH resection, although 1 patient recovered from postoperative meningitis requiring intravenous antibiotics. CONCLUSION: CEEH is a rare, late complication of AVM SRS with an incidence of 0.28% and a median latency of 106 months. In the presence of a delayed and symptomatic expanding hematoma in the bed of an angiographically obliterated AVM, surgical resection resulted in clinical improvement in most patients. Conservative management is possible in asymptomatic patients with stable, small-sized hematomas in deeply seated locations.

Bibliometric Analysis of the Top 100 Cited Articles on Stereotactic Radiosurgery for Trigeminal Neuralgia.

Background Stereotactic radiosurgical rhizolysis of the trigeminal nerve is an established modality increasingly employed to alleviate the symptoms of refractory trigeminal neuralgia. This study analyzes the academic impact of the top 100 cited articles on the radiosurgical management of trigeminal neuralgia. Methods The Scopus database was searched for articles containing "radiosurgery" and one or more of "trigeminal neuralgia," "trigeminus neuralgia," and "tic douloureux." The top 100 articles written in English were arranged in descending order by citation count. Documents were evaluated for authors, publication year, journal and impact factor, total citations, nationality, study type, radiosurgical modality, and the affiliated institution. Quantitative and qualitative analyses were performed on the data. Results The most cited articles were published between 1971 and 2019. The average citation per year was 4.3. The most targeted anatomic area was the "root entry zone" or proximal portion of the cisternal segment of the trigeminal nerve. The most utilized modality was Gamma Knife radiosurgery. The country with the highest number of publications was the United States. Thirty-six percent of the articles were published in the Journal of Neurosurgery . Lunsford, Kondziolka, Flickinger, and Régis, respectively, were the most frequently listed co-authors. The most prolific institute was the University of Pittsburgh Medical Center. Conclusion Stereotactic radiosurgery is an important modality in the management of medically or surgically refractory trigeminal neuralgia. This analysis assesses its contributions over the past five decades to identify trends in treatment practices for neurosurgeons and to highlight areas where further study is needed.

Minor Salivary Gland Biopsy in Diagnosis of Sjögren's Syndrome.

Objective: Previous studies have questioned the safety and efficacy of minor salivary gland biopsy in the diagnosis of Sjögren's syndrome, citing complications and difficulty of pathologic evaluation. This study aims to determine the rate of biopsy specimen adequacy and the risk of complications after minor salivary gland biopsy. Study Design: Case series. Setting: Single tertiary care center. Methods: We reviewed the records of all patients who underwent minor salivary gland biopsy at our institution from October 1, 2016, to September 1, 2021. Demographics, comorbidities, symptoms, and serologic results were recorded. The primary outcome was adequacy of the tissue sample. Complications of the procedure were recorded. Biopsies with at least one focus of ≥50 lymphocytes per 4-mm2 sample were considered positive. Results: We identified 110 patients who underwent minor salivary gland biopsy. Ninety-three (85%) were female, and the median age was 49.1 years (range, 18.7-80.5). Seventy-seven procedures (70%) were performed in the office setting, and 33 (30%) were performed in the operating room. Nearly all biopsy samples (n = 108, 98%) were adequate, and 33 (31%) were interpreted as positive. Four patients (4%) experienced temporary lip numbness, which resolved with conservative management. No permanent complications were reported after lip biopsy. Nineteen (58%) patients with positive biopsy results had no Sjögren's-specific antibodies. Most patients with positive biopsy results (n = 20, 61%) subsequently started immunomodulatory therapy. Conclusion: Minor salivary gland biopsy can be performed safely and effectively in both the office and the operating room. This procedure provides clinically meaningful information and can be reasonably recommended in patients suspected to have Sjögren's syndrome.

Qualitative assessment of online information available on accredited head and neck surgery fellowship programs.

BACKGROUND: The present study aims to assess the quality and availability of online information about fellowships accredited by the American Head & Neck Society (AHNS). METHODS: AHNS directory pages and institutional web sites of 50 AHNS-accredited fellowships were identified. Web pages were scored using 20 standardized criteria including general information, application information, alumni, surgical training, research, and quality-of-life. RESULTS: Median scores for AHNS directory pages and institutional web sites were 11 (range: 7-14) and 10 (4-15), respectively. Faculty listings, contact information, program location, number of positions, and breadth of surgical exposure were the most commonly listed criteria. Less common criteria included didactic schedule, protected academic time, previous research projects, year of accreditation, work-life balance, fellow selection criteria, interview information, and salary. CONCLUSIONS: The AHNS directory and institutional web sites are most comprehensive in general program information and details about surgical training. Information about the application process, work-life balance, and research opportunities were less common.

Sinonasal Undifferentiated Carcinoma with Failed Response to Induction Chemotherapy.

Sinonasal undifferentiated carcinoma (SNUC) is a rapidly growing malignancy with a propensity for extensive local invasion. Multimodal therapy, including surgery, radiotherapy, and chemotherapy, is the standard approach to treatment, but the optimal sequence and combination of these modalities are uncertain. Induction chemotherapy is being increasingly utilized based on recent reports that show better outcomes for patients who respond to chemotherapy and the ability to determine further course of treatment. We present a unique case of a patient with locally advanced SNUC that did not respond to induction chemotherapy and a review of the available literature relating to the management of this rare malignancy.

The Value of Intraoperative Magnetic Resonance Imaging in Endoscopic Endonasal Resection of Pituitary Adenoma.

Background Intraoperative magnetic resonance images (iMRIs) have been variably adopted by some centers to help increase the rate of gross total resection (GTR) of pituitary adenomas. In this comparative study, we report our institution's experience with using iMRIs for endoscopic endonasal approach (EEA) pituitary adenoma resection to better elucidate its role and potential value for pituitary surgery. Methods All adult patients who underwent EEA for a pituitary adenoma from January 2013 to September 2021 were retrospectively reviewed. GTR was defined as no residual tumor or recurrence on postoperative imaging within 6 months. Univariate analysis followed by multivariate analysis was performed with GTR as the categorical endpoint. To measure the independent effect of iMRI on GTR, propensity score matching was then performed. Results A total of 351 pituitary adenoma patients who underwent EEA were identified. The mean age was 51.2 (range: 18-90) years and 196 (55.8%) patients were female. iMRI was utilized in 87 (24.8%) cases. The overall rate of GTR was 69.2%. On multivariate analysis, low Knosp grade, low tumor volume, and the use of iMRI were predictive of GTR. There was no difference in the need for desmopressin or hydrocortisone at 90 days postoperatively. Conclusion At our institution, we report a significant absolute increase in GTR rates of 16.4% for patients undergoing an iMRI. Among iMRI patients who did not have GTR, the majority of residuals were intentionally left behind after being deemed too risky to pursue. Overall, this study suggests the high value that iMRI adds to endoscopic pituitary adenoma surgery.

Comparing Rates of Postoperative Meningitis After Endoscopic Endonasal Procedures Based on Methicillin-Resistant Staphylococcus aureus/Methicillin-Sensitive Staphylococcus aureus Colonization and Antibiotic Prophylaxis.

BACKGROUND: Endoscopic endonasal approach (EEA) procedures are inherently contaminated due to direct access through the nasopharyngeal mucosa. The reported rate of postoperative meningitis in EEA procedures is 0.7%-3%. A variety of methods exist to minimize the risk of meningitis with antibiotic prophylaxis, although their value is not completely understood. This study investigated whether there is a difference in rates of postoperative meningitis based on Staphylococcus aureus colonization and use of preoperative antibiotic prophylaxis. METHODS: All adult patients who underwent EEA resection at our institution from 2013 to 2021 were retrospectively reviewed. Patients with preoperative cerebrospinal fluid infections were excluded. Data including recent preoperative infections, preoperative colonization status, antibiotic administration, and postoperative outcomes were recorded for each patient. RESULTS: Of 483 patients identified (mean age, 51 years; range, 18-90 years; 274 [56.7%] female), 80 (16.6%) had a positive preoperative methicillin-resistant Staphylococcus aureus (MRSA)/methicillin-sensitive Staphylococcus aureus (MSSA) screening swab. Twenty-one (26.3%) colonized patients were treated with preoperative decolonizing antibiotics. Within 30 days of surgery, 13 (2.7%) patients developed culture-positive meningitis. There was no significant difference in meningitis rates based on MRSA/MSSA colonization status. Among colonized patients, there was no significant difference in rates of MRSA/MSSA meningitis based on preoperative antibiotic decolonization. CONCLUSIONS: Postoperative rates of meningitis after EEA surgery were not significantly changed based on MRSA/MSSA colonization status of the patient or preoperative decolonization. The utility of preoperative testing of MRSA/MSSA status and antibiotics for decolonization to prevent postoperative meningitis should be further investigated.

Sinonasal Glomangiopericytoma with Prolonged Postsurgical Follow-Up.

Sinonasal glomangiopericytoma is a rare vascular tumor of the respiratory epithelium. Treatment consists mainly of surgical resection, though there is no consensus regarding the use of adjuvant therapies or preoperative endovascular embolization. The postsurgical prognosis is favorable, though there is a high risk of delayed recurrence. Here, we present the case of a patient who underwent endoscopic resection of a sinonasal glomangiopericytoma and a review of the literature.

Endoscopic Techniques in Vascular Neurosurgery.

This section reviews the selection criteria and best practices for endoscopic cerebrovascular surgery, focusing on purely endoscopic endonasal approaches. Although these approaches still play a limited role in open vascular neurosurgery, they offer a robust and potentially safer technique for establishing visualization and vascular control of particular, well-selected pathologies, such as aneurysms of the proximal circulation; this requires strong, multidisciplinary experience with endoscopic anatomy and surgical technique, advanced reconstruction techniques, and instruments designed to be maneuvered within this relatively novel corridor and application.

Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies.

BACKGROUND: The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on 'numerator' data (i.e., COVID-19 cases) only. OBJECTIVE: To assess the risks of COVID-19 by DMT, this study aimed to assess both 'numerator' (patients with SARS-CoV-2 infection) and 'denominator' data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity. METHODS: We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator. RESULTS: We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19. CONCLUSIONS: Analysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.