Effect of different management strategies on outcomes in subarachnoid neurocysticercosis: a descriptive, multicentre, retrospective cohort study in the USA - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. 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Learn more: PMC Disclaimer | PMC Copyright Notice eClinicalMedicine . 2026 Apr 7;94:103861. doi: 10.1016/j.eclinm.2026.103861 Search in PMC Search in PubMed View in NLM Catalog Add to search Effect of different management strategies on outcomes in subarachnoid neurocysticercosis: a descriptive, multicentre, retrospective cohort study in the USA Janitzio J Guzmán Janitzio J Guzmán a Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA Find articles by Janitzio J Guzmán a , Megan M Duffey Megan M Duffey b Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA c Division of Tropical Medicine, National School of Tropical Medicine, Houston, TX, USA Find articles by Megan M Duffey b, c , Jill Weatherhead Jill Weatherhead b Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA c Division of Tropical Medicine, National School of Tropical Medicine, Houston, TX, USA Find articles by Jill Weatherhead b, c , Eva H Clark Eva H Clark b Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA c Division of Tropical Medicine, National School of Tropical Medicine, Houston, TX, USA Find articles by Eva H Clark b, c , Jesica Herrick Jesica Herrick d Division of Infectious Diseases, University of Illinois at Chicago, Chicago, IL, USA Find articles by Jesica Herrick d , Senate Amusu Senate Amusu d Division of Infectious Diseases, University of Illinois at Chicago, Chicago, IL, USA Find articles by Senate Amusu d , Felicia C Chow Felicia C Chow e Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA f Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA, USA Find articles by Felicia C Chow e, f , Paul R Allyn Paul R Allyn g Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Find articles by Paul R Allyn g , Noah Wald-Dickler Noah Wald-Dickler h Division of Infectious Diseases, Los Angeles General Medical Center, Los Angeles, CA, USA Find articles by Noah Wald-Dickler h , J Martin Rodriguez J Martin Rodriguez i Division of Infectious Diseases, UAB Heersink School of Medicine, Birmingham, AL, USA Find articles by J Martin Rodriguez i , Natalie M Bowman Natalie M Bowman j Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, USA Find articles by Natalie M Bowman j , Timothy J Hatlen Timothy J Hatlen k Department of Medicine, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA Find articles by Timothy J Hatlen k , Dannae Martin Dannae Martin k Department of Medicine, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA Find articles by Dannae Martin k , Travis Larsen Travis Larsen h Division of Infectious Diseases, Los Angeles General Medical Center, Los Angeles, CA, USA Find articles by Travis Larsen h , Anna M Cervantes-Arslanian Anna M Cervantes-Arslanian l Department of Neurology, Boston University Medical Center School of Medicine + Boston Medical Center, Boston, MA, USA m Department of Neurosurgery, Boston University Medical Center School of Medicine + Boston Medical Center, Boston, MA, USA n Department of Medicine (Infectious Diseases), Boston University Medical Center School of Medicine + Boston Medical Center, Boston, MA, USA Find articles by Anna M Cervantes-Arslanian l, m, n , Christina Coyle Christina Coyle o Department of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY, USA Find articles by Christina Coyle o , A Clinton White Jr A Clinton White Jr p Infectious Disease Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA Find articles by A Clinton White Jr p , Elliott Welford Elliott Welford q School of Medicine, University of California San Diego, La Jolla, CA, USA Find articles by Elliott Welford q , Annie N Cowell Annie N Cowell q School of Medicine, University of California San Diego, La Jolla, CA, USA Find articles by Annie N Cowell q , Jeffrey D Jenks Jeffrey D Jenks r Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA Find articles by Jeffrey D Jenks r , Andrés F Henao-Martinez Andrés F Henao-Martinez s Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Find articles by Andrés F Henao-Martinez s , Carlos Franco-Paredes Carlos Franco-Paredes t Hospital Infantil de México, Federico Gὁmez, México City, México Find articles by Carlos Franco-Paredes t , Glenn Mathisen Glenn Mathisen u Department of Infectious Diseases, Olive View-UCLA Medical Center, Sylmar, CA, USA Find articles by Glenn Mathisen u , Paola Lichtenberger Paola Lichtenberger v University of Miami Miller School of Medicine, Miami, FL, USA Find articles by Paola Lichtenberger v , Jose A Serpa Jose A Serpa w Department of Medicine, University of Texas at Tyler, Tyler, TX, USA Find articles by Jose A Serpa w , Rory Bouzigard Rory Bouzigard x Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center + Parkland Health, Dallas, TX, USA Find articles by Rory Bouzigard x , Laila M Castellino Laila M Castellino x Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center + Parkland Health, Dallas, TX, USA Find articles by Laila M Castellino x , Elise M O'Connell Elise M O'Connell a Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA Find articles by Elise M O'Connell a, ∗ Author information Article notes Copyright and License information a Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA b Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA c Division of Tropical Medicine, National School of Tropical Medicine, Houston, TX, USA d Division of Infectious Diseases, University of Illinois at Chicago, Chicago, IL, USA e Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA f Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, CA, USA g Division of Infectious Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA h Division of Infectious Diseases, Los Angeles General Medical Center, Los Angeles, CA, USA i Division of Infectious Diseases, UAB Heersink School of Medicine, Birmingham, AL, USA j Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, USA k Department of Medicine, The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA l Department of Neurology, Boston University Medical Center School of Medicine + Boston Medical Center, Boston, MA, USA m Department of Neurosurgery, Boston University Medical Center School of Medicine + Boston Medical Center, Boston, MA, USA n Department of Medicine (Infectious Diseases), Boston University Medical Center School of Medicine + Boston Medical Center, Boston, MA, USA o Department of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY, USA p Infectious Disease Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA q School of Medicine, University of California San Diego, La Jolla, CA, USA r Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA s Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA t Hospital Infantil de México, Federico Gὁmez, México City, México u Department of Infectious Diseases, Olive View-UCLA Medical Center, Sylmar, CA, USA v University of Miami Miller School of Medicine, Miami, FL, USA w Department of Medicine, University of Texas at Tyler, Tyler, TX, USA x Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center + Parkland Health, Dallas, TX, USA ∗ Corresponding author. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, 10 Center Dr. Bldg 10 Rm 11N206, Bethesda, MD, 20892, USA. [email protected] Received 2025 Sep 17; Revised 2026 Mar 16; Accepted 2026 Mar 18; Collection date 2026 Apr. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). PMC Copyright notice PMCID: PMC13087451 PMID: 42005930 Summary Background Subarachnoid neurocysticercosis (SANCC) is an uncommon but severe form of Taenia solium infection. There is limited evidence to guide clinical management. We aimed to describe the clinical and laboratory features of a cohort of patients with SANCC, and assess the impact of different management strategies on their clinical course. Methods We performed a multicentre retrospective cohort study with patients from 15 medical centres across nine states in the USA. SANCC was defined based on histopathology; the presence of cysts in the basilar subarachnoid spaces/sylvian fissures/spine with antibody positivity to T. solium /meeting Del Brutto criteria; or inflammatory cerebrospinal fluid (CSF) with positivity to T.solium antigen or qPCR and negativity to viral, fungal, and bacterial pathogens. Each site reported up to the most recent 7 sequential patients with SANCC based on institutional memory or systematic searching of the electronic medical records. Data entry was performed from Nov 12, 2021 to Nov 28, 2022. Minimal criteria for inclusion was a discharge summary for a hospitalisation due to SANCC. Data collection centred around the earliest hospitalisation associated with the SANCC. Data from prior and subsequent inpatient and outpatient visits were also collected. Data were analysed to assess the impact of treating with anthelmintics based on CSF biomarkers, the normalisation of imaging, or a fixed duration on SANCC recurrence rates. Diagnostic delay was defined as patients with prior hospitalisation or extensive workup for a complication (e.g. stroke, hydrocephalus, meningitis, mass) but without SANCC suspected. Those with a diagnostic delay and those with a diagnosis of SANCC but were initially managed without anthelmintics (e.g. shunt, cyst removal) were considered to have a delay in anthelmintic treatment. The effect of delay in anthelmintic treatment on subsequent Emergency Room visits and hospitalisations was assessed. Findings Data were collected on 75 patients with neurocysticercosis. Of whom, six patients were determined to not meet the definition of SANCC and were excluded; ultimately, 69 (40 male, 29 female) met the definition of SANCC. The year of case-defining SANCC hospitalisation ranged from 2009 to 2022, with a median year of 2016. Median 2.5 years, interquartile range (IQR) 0.94–4.0 years. SANCC was a new diagnosis in 59 patients. Of these, 18 (31%) had prior medical visits for SANCC manifestations (i.e. hydrocephalus [17%], stroke [5%], and/or meningitis [7%], brain mass [3.3%], TIA [1.6%], or intracranial hypertension without hydrocephalus [1.6%]) but SANCC was not considered. At the time of discharge, 9 (13%) patients were not given albendazole and/or praziquantel due to cost or availability. 52 patients had >60 of post-hospitalisation follow-up and completed the intended course of therapy. Use of CSF T. solium biomarkers (antigen [TsAg] and/or qPCR) to guide length of anthelmintic therapy decreased SANCC recurrence (0 [n = 0 of 17] vs. 23% [n = 8 of 33], p = 0.039, odds ratio [OR] 95% confidence interval [CI] 0.0–0.84), whereas use of magnetic resonance imaging normalisation to guide treatment length did not decrease recurrence (15% [n = 3 of 20] vs 16.67% [n = 5 of 30] p > 0.9, OR 95% CI 0.21–4.18). A delay in anthelmintic treatment was associated with an increase in subsequent SANCC-related Emergency Department visits or hospital admissions (median 1, IQR 1–2) compared to no anthelmintic delay (median 0.5, IQR 0–1; p = 0.018). Interpretation SANCC is commonly misdiagnosed and diagnostic and therapeutic delays may lead to more subsequent hospital encounters for SANCC-related problems. Use of CSF Ts biomarkers to guide anthelmintic therapy may decrease SANCC recurrence. However, given the small sample size, adjustment for confounders with regression analysis was not performed and we cannot exclude confounding as responsible for differences seen. Larger, prospective studies are needed to confirm these findings. Funding Division of Intramural Research, National Institute of Allergy and Infectious Diseases. Keywords: Neurocysticercosis, Cysticercosis, Subarachnoid neurocysticercosis, Racemose, Meningitis Research in context. Evidence before this study PubMed and Google Scholar were searched: (((“subarachnoid"[All Fields] OR “racemose” [All Fields] OR “meningitis” [All Fields]) AND (“Therapy"[All Fields] OR “albendazole” [All Fields] OR “praziquantel” [All Fields] OR “Treatment” [All Fields] OR “anthelmintic” [All Fields] OR “antihelminthic” [All Fields]) AND (“cysticercosis” [All Fields] OR “neurocysticercosis” [All Fields]) AND (excludepreprints[Filter])) NOT (review[Publication Type]) AND (excludepreprints[Filter])) NOT (case reports[Publication Type]) PubMed results were limited to humans. Scopus was searched with the terms “cysticercosis” OR “neurocysticercosis” AND “racemose” OR “subarachnoid” AND “treatment duration” within the article title, abstract, and keywords. Web of Science was searched with the terms “neurocysticercosis” (All Fields) and “subarachnoid” (All Fields) and “treatment” (All Fields). Searches were performed on Sept 9, 2025. While several studies have assessed the immediate radiologic improvements in cyst size with anthelmintic treatment, only one assessed recurrence rates following therapy in comparing strategies. The study was a single centre retrospective cohort by Angerri-Nadal et al. (2025) that included 15 patients (total) with SANCC, comparing anthelmintic treatment to corticosteroids only, with only two patients in the latter category. There was a high relapse rate in both groups (∼50%), but the study did not have enough patients in the corticosteroid treatment group to power the conclusion that there was no significant difference in using anthelmintics compared to steroids alone to prevent relapse. Added value of this study To our knowledge, this is the largest study in SANCC comparing treatment strategies to prevent SANCC recurrence. This multicentre retrospective cohort study reports 69 patients with SANCC, of which 50 had >60 days of post-hospital follow up and completed anthelmintic therapy. Treatment strategies were compared for differences in radiologic SANCC recurrences during follow-up. Patients whose anthelmintic treatment length was guided by Taenia solium CSF biomarkers ( T. solium antigen and/or qPCR [Ts biomarkers]) were less likely to experience SANCC recurrence compared to those where CSF Ts biomarkers were not part of the treatment strategy. Recurrence rates in patients whose treatment was guided by cyst resolution on imaging did not have a significantly different relapse rate than those whose treatment length was not guided by cyst resolution. Moreover, there was no significantly different length of anthelmintic treatment overall between these two groups, suggesting the need for individualised therapy length in SANCC. Implications of all the available evidence Anthelmintic therapy for SANCC causes short-term improvement in the size of cysts on neuroimaging. The higher the dose of albendazole and the longer the course, generally the more substantial the short-term improvement in cyst size. However, imaging can be misleading in determining cure, and overall prognosis is dependent on long term follow-up to capture relapse. Patients with SANCC treated with anthelmintics (albendazole and/or praziquantel) until CSF Ts biomarker negativity were significantly less likely to experience subsequent radiologic relapse than those where biomarkers were not used as part of the treatment strategy. Our findings show there was no relapse difference in those patients where imaging normalisation guided anthelmintic treatment compared with those where it was not. Neurocysticercosis guidelines have previously recommended SANCC anthelmintic use guided by radiologic resolution on magnetic resonance imaging. This study was limited by small total numbers and, therefore, lack of adjustment for confounders. Larger and prospective, randomised controlled trials in assessing treatment of SANCC are needed. Introduction Neurocysticercosis (NCC) develops when a person ingests ova that are shed from a T. solium intestinal tapeworm (“pork tapeworm”) carrier and the parasitic larva migrates into the central nervous system (CNS). NCC manifestations and clinical course are highly dependent on cyst burden and location. Cysts found in the brain parenchyma are a major cause of seizures in endemic regions. The global burden of NCC is conservatively estimated at 2.8 million disability adjusted life years due to seizures. 1 Not considered in this number is the significant morbidity and mortality caused by extraparenchymal NCC. In this form, cysts are found within the ventricles (“ventricular NCC”) or in the subarachnoid space (subarachnoid NCC [SANCC]). Not all cysts in the subarachnoid space behave the same. Subarachnoid cysts in the convexity of the brain present, and are treated, like parenchymal NCC. 2 Conversely, subarachnoid cysts originating in the basilar cisterns, Sylvian fissures, or around the spine have the potential to take on a multilobulated (“racemose”) form. The term SANCC is generally used to refer to cysts in these specific latter locations. 2 SANCC is associated with a higher mortality rate than parenchymal NCC due to the frequent development of increased intracranial pressure and shunt complications, particularly in areas with low access to neurosurgical services and brain imaging. 3 , 4 SANCC is also more difficult to treat than parenchymal NCC, likely due to the ability of the parasite to regenerate, low penetration of albendazole and praziquantel to the subarachnoid space, and the large burden of organism typical of SANCC. 5 , 6 , 7 SANCC cysts possess stem cells in their tegument enabling them to persist and regrow, resulting in relapsing meningitis and formation of new cysts over time in the absence of adequate anthelmintic therapy. 5 , 7 Current guidelines advise a strong recommendation to treat SANCC with antiparasitic drugs and initiate anti-inflammatories prior to starting. They do not offer specific recommendations regarding using albendazole, praziquantel, or combination therapy. They also offer a weak recommendation for continuing anthelmintic treatment until radiologic resolution of viable cysts on magnetic resonance imaging (MRI), but lack data to support this approach. 2 Moreover, since subarachnoid cysts have a similar appearance to the cerebrospinal fluid (CSF) and subarachnoid scarring permanently alter the appearance of the space, there is increasing evidence that imaging can be a misleading treatment endpoint. 8 , 9 Using imaging as the guide for treatment response, one study demonstrated a 10-day albendazole course caused complete cyst collapse in 26% of patients 6 months following therapy. 7 Additionally, short courses of anthelmintics similar to treatment for parenchymal disease are unlikely to cause durable cure in the majority of patients with SANCC. 7 A recent small retrospective study where 10–20 days of albendazole was the predominant treatment approach showed no difference in preventing recurrent SANCC meningitis compared with corticosteroids alone-seen in approximately 50% of both groups. 10 T. solium antigen (TsAg) and real-time polymerase chain reaction (qPCR) assays have shown promise in guiding anthelmintic therapy, but data have been limited to small numbers on banked samples retrospectively tested, small descriptions of the biomarkers decreasing with treatment, and a single centre experience with no comparison to other treatment strategies. 1 , 9 , 11 No prior study has compared outcomes of patients whose treatment was guided in real time by these biomarkers to other strategies to guide anthelminthic use. There is no current gold standard in SANCC to indicate cure. Historically, durable cure has only been demonstrated with prolonged follow-up demonstrating no new lesions on imaging or recurrent meningitis, 12 which is not available in most studies. Albendazole and praziquantel are very expensive in the United States (US), and frequently in short supply, precluding the widespread use of prolonged therapy. 13 , 14 Given the paucity of published data to guide SANCC treatment duration and other aspects of care, we utilised a collaborative multicentre approach to perform a retrospective cohort study to identify the impact of different management strategies on patient outcomes. Moreover, we wanted to quantify the frequency of SANCC misdiagnoses. Given our collective clinical experience, we hypothesised that delays in anthelmintic therapy would lead to increased medical encounters following the initial hospitalisation due to longer uncontrolled inflammation and parasite growth. Methods Study design and ethics Twenty-four US institutions were invited to contribute data from patients with SANCC based on their location and immigration patterns in the USA. 15 , 16 , 17 Of the 24 invited institutions, 15 received an institutional review board (IRB) waiver or IRB approval (see Supplemental Methods ) and completed data entry. Seven patients included from a natural history study (National Institute of Allergy and Infectious Diseases, USA, Natural History Neurocysticercosis study NCT00001205 ) signed informed consent, and all other institutions received waivers of informed consent prior to data collection. Full details on institutional review board waivers and approval numbers are given in Supplementary Table S7 . This report adheres to STROBE reporting guidelines. See Supplemental Data for study protocol. Participants Patients were defined as having SANCC if they fulfilled the criteria for at least one of three definitions, which are in line with current guidelines 2 ( Table 1 ). Each included patient was thoroughly vetted by data managers to ensure that provided radiologic and surgical data aligned with the purported reasons for study inclusion. Sites were instructed to find the earliest hospitalisation due to a known diagnosis of SANCC, or that led to the diagnosis, termed here “SANCC hospitalisation”. For a hospitalisation to be considered due to SANCC, either an MRI or an LP had to have been performed with compatible findings (see Supplemental Table S1 ) up to 2 months prior to hospitalisation. These definitions were used to avoid hospitalisations due to shunt infections or that may have been due to SANCC, but where the diagnosis was missed. The minimal data requirement for patient inclusion was a discharge summary from the SANCC hospitalisation. Past medical history at time of SANCC hospitalisation, the hospital course, subsequent hospitalisations, follow-up visits, and reporting institution information were collected. Among the participating sites the practice is to admit patients with SANCC to initiate treatment since this is a period at risk for clinical worsening, even if they have been diagnosed as an outpatient. Moreover, the diagnosis of SANCC typically requires awaiting testing results to return over several weeks. We thus used the admission date for the earliest SANCC admission as a way to establish a relatable timeline across patients for follow-up. Table 1. Demographics of patients with SANCC (n = 69). Characteristic Male, n(%) 49 (71) Female, n(%) 20 (29) Median age at hospitalisation (range), years 43 (15–76) Median year of admission (range) 2016 (2009–2022) Median years from US immigration to hospitalisation a (range) 20 (1–40) Country of origin, n (%) Cape Verde 2 (3) El Salvador 3 (4) Guatemala 10 (14) Honduras 3 (4) India 1 (1) Mexico 46 (67) Nicaragua 1 (1) United States b 1 (1) Unknown 2 (3) Prior diagnoses, n (%) Headaches 39 (57) Seizures 15 (22) Parenchymal NCC 4 (6) Extraparenchymal NCC (with or without concurrent parenchymal NCC) 10 (14) Prior NCC, unknown lesion location 3 (4) No known NCC 52 (75) Symptoms at hospital presentation, n(%) Headache 55 (80) Nausea and/or vomiting 32 (46) Blurry vision/diplopia 23 (33) Dizziness 30 (43) Focal neurologic symptoms 21 (30) Seizure 14 (20) Partial 4 (6) Generalised 11 (16) Confusion 13 (19) Weakness 12 (17) Loss of consciousness 6 (9) Fever 5 (7) Gait abnormality 4 (6) Urinary retention/incontinence 3 (4) Open in a new tab SANCC, subarachnoid neurocysticercosis; NCC, neurocysticercosis; US, United States. a Known year of immigration n = 54. b Travel to Central America and Mexico. Treatment of all patients was strictly at the discretion of each clinician. While clinicians within institutions may have adopted more similar treatment approaches, no institution had a universal approach that it applied to all patients. Each site submitted a maximum of the seven most recent (sequentially seen) patients with the minimum required data. Each site was capped at seven to limit the time commitment of this project and facilitate participation. Procedures Deidentified study data were collected and managed using REDCap electronic data capture tools hosted at the National Institute of Allergy and Infectious Diseases. 18 Each site had access to their own raw data following data entry. Data entry was completed between November 12, 2021 and November 28, 2022. Once data from free text fields were further coded and further potential identifiers removed, all authors had access to the full dataset. The lead study site reviewed entries for accuracy. Following the SANCC hospitalisation, the follow-up period included any Emergency Department (ED) visits, hospital admissions, and outpatient Neurology and Infectious Diseases clinic visits until the conclusion of the data entry period. Each site searched electronic medical records for these visits. Definitions were constructed following data entry for consistent application of terminology in data analyses. These definitions were applied to each site's data and sent back to site investigators for confirmation prior to final data tabulation and analysis: Delay in SANCC Diagnosis: At the time of SANCC hospitalisation, the presence of a previous hospitalisation for an associated complication (e.g. shunt placement, ischaemic stroke, subarachnoid haemorrhage, aseptic meningitis) or a previous workup for CNS-related symptoms and a compatible lesion on imaging, but SANCC was not suspected. Patients with an established prior history of extraparenchymal NCC were excluded from this analysis. Delay in Anthelmintic Therapy : Patients with a diagnostic delay and those with diagnosis of SANCC managed without anthelmintics were together considered to have a delay in anthelmintic therapy. SANCC Recurrence : The appearance of new cysts on follow-up imaging, or a worsening of previously visualised leptomeningeal disease and worsening symptoms on follow-up that prompted re-initiation of treatment. New SANCC diagnosis : SANCC diagnosed within the prior 2 months of the SANCC hospitalisation AND the admission was either a planned admission (often for treatment purposes) or a transfer from an institution where the diagnosis was made. Relatedness of hospital visits to NCC during the follow up period was indicated by the reporting site. For consistency in consideration of SANCC-relatedness across sites, entries were reviewed independently by two authors (E.O. and J.G.) and deemed either unrelated to SANCC or possibly/probably related to SANCC. Disagreement on relatedness to SANCC was adjudicated by a third author (M.D.). Any symptoms or complications possibly or likely related to SANCC disease or side effects of corticosteroids were considered related to SANCC. ED visits for seizures due to parenchymal NCC, other documented infections, medication refills, or trauma were regarded as unrelated. Patients with less than 60 days of follow-up after SANCC hospitalisation were excluded from this analysis. Outcomes The influence of concurrent ventricular and parenchymal NCC on SANCC management was assessed post-hoc. We compared rates of therapeutic extraction of cysts in patients with ventricular disease to those without ventricular disease. We also assessed duration of anthelmintics and corticosteroids in those with coexisting non-calcified parenchymal NCC. Variables considered in influencing outcomes included a sex, a delay in diagnosis, delay in anthelmintic treatment, and the, and strategy guiding anthelmintic duration (normalisation of imaging, patient symptoms, fixed duration, CSF Ts antigen/qPCR, blood Ts antigen/qPCR, or other factors), and 6 month post-hospitalisation MRI findings. Factors guiding anthelmintic duration were not mutually exclusive choices, and multiple selections were possible, as indicated in the patient chart. Since subarachnoid cysts have the propensity to take on the racemose phenotype, it is common to find additional cysts on high resolution imaging, even if only 1 is seen on imaging with standard MRI sequences. It is also not routine for radiologists provide measurements of every cyst in the subarachnoid space. Thus, the number of cysts and size of cysts were not systematically collected, nor adjusted for. Statistical analysis Contingency analysis assessing treatment strategy was performed using each treatment strategy individually compared with patients across all other treatment strategy categories. Outcomes analysed were SANCC-related rehospitalisations and ED visits, SANCC recurrence, total time on anthelmintics, and total time on corticosteroids. Sex was recorded from documentation on patient medical records. To assess for reporting bias in those with a delay in anthelmintic treatment, the number of non-SANCC hospital encounters was assessed as was the duration of follow-up between those with and without a delay in anthelmintic therapy. To assess for selection bias in treatment strategy comparisons and anthelmintic delay comparisons, follow up time was also compared between the groups. Since sites utilising CSF Ts biomarkers were generally regarded as higher volume SANCC centres than those that did not utilise CSF Ts biomarkers, a contingency analysis comparing number of SANCC recurrences at centres that used CSF Ts biomarkers for any patients included in this study, compared with centres that did not use CSF Ts biomarkers to guide treatment for any patients included in this study. As a descriptive study there were no sample size calculations. Statistics were performed using Prism GraphPad v10.2. Calculated P values were two-sided, and ≤0.05 were deemed significant. All variables were considered nonparametric for comparisons. Mann–Whitney U test was used to compare continuous numeric variables between dichotomous groups. Kruskal–Wallis test was used to compare continuous numeric variables across three or more groups. Categorical variables were compared using Fisher's exact test. Odds ratio confidence intervals were calculated using the Baptista-Pike method. Role of the funding source The funding source had no role in study design, data collection, data analysis, or data interpretation, the writing, nor the decision to submit the paper for publication. All authors had full access to the study data. EMO and JJG had final responsibility for the decision to submit for publication. Results In total, 15 medical centres across nine states (Texas [2], California [6], Illinois, North Carolina, Alabama, Massachusetts, Colorado, Florida, Maryland) in the United States participated in this study. All centres are teaching hospitals, and 11 are considered safety net hospitals. Further details on the participating institutions and source data can be found in the Supplemental Data . Data for a total of 75 patients were entered into REDCap. Six cases of cysts involving only the ventricles or subarachnoid space of the convexity of the brain without evidence of coexisting basilar cistern, Sylvian fissure, or spine disease, and did not otherwise meet the definition of SANCC ( Supplemental Table S1 ), were excluded from the analysis. Therefore, a total of 69 patients with SANCC were analysed, unless otherwise specified ( Fig. 1 ). Fig. 1. Open in a new tab Flow diagram of patient cohort . Cohort demographics are shown in Table 1 . Most patients were male (71%, n = 49) immigrants from Latin American countries (91%, n = 63). For those that immigrated to the US, median time from immigration to the US to hospitalisation was 20 years (range 1–40 years). The year of case-defining SANCC hospitalisation ranged from 2009 to 2022, with a median year of 2016. Headaches were the most common prior diagnosis (57%, n = 39), as well as the most common presenting symptom at the time of SANCC hospital admission (80% n = 55, Table 1 ). Most patients (75%, n = 52) did not carry a previous diagnosis of NCC. Median duration of continuous symptoms prior to hospitalisation was eight weeks (interquartile range [IQR] 2–37 weeks). Duration of hospitalisation was a median of nine days (IQR 5–14 days). While there were rare cases restricted to the spine (6%, n = 4) or meningitis without discernible cysts (1.5%, n = 1), 93% (n = 64) of patients had intracranial subarachnoid cysts found in locations defining SANCC (i.e. basilar cisterns, etc). Nearly half (46%, n = 32) had no parenchymal cysts or calcifications. Ventriculomegaly was seen on brain MRI in 59.4% (n = 41) of patients at hospital admission, most commonly due to non-communicating hydrocephalus (38%, n = 26). Communicating hydrocephalus was seen in 18.8% (n = 13). Twenty-four patients underwent a complete spine MRI, which demonstrated cysts, abnormal enhancement, and/or arachnoiditis in 11 (46%). The lumbosacral spine was most frequently affected with cysts and/or arachnoiditis seen in eight patients (33%). Additional MRI findings are described in Supplemental Table S2 . Twenty-eight patients underwent lumbar puncture around the time of hospitalisation and had available results ( Fig. 2 ). While the median CSF WBC was 43.5/mm 3 there were a few patients with counts greater than 500/mm 3 . Most patients had lymphocyte-predominant meningitis, although a few were neutrophilic. Elevated protein (CSF protein >60 mg/dL) and hypoglycorrhachia (CSF glucose <45 mg/dL) were common (39%, n = 11 and 36%, n = 10 out of 28, respectively). While not all laboratories comment on eosinophil presence in the CSF, 16 of the 24 patients (67%) with available data had eosinophils detected in the CSF. Most patients had positive immunoassays for Taenia -directed antibodies in either the serum or CSF. There were two cases of false negative serum antibody utilising a commercial Enzyme-Linked Immunosorbent Assay (ELISA), resulting in a sensitivity of 94.3% (33 positive out of 35), no false negatives for the serum Enzyme-linked Immunoelectrotransfer Blot ([EITB] sensitivity 100% [n = 12 out of 12]), and one false negative CSF EITB (sensitivity of 88.9% [n = 8 out of 9]). Fig. 2. Open in a new tab Lumbar puncture and laboratory parameters in subarachnoid neurocysticercosis (SANCC). A) Total cerebrospinal fluid (CSF) white blood cell counts ([WBC] left axis, cells/mm 3 ), and relative percentage of the cell differentials (right axis, %) of 28 patients who underwent lumbar puncture. Four patients had CSF processed at laboratories that do not quantify eosinophils in CSF, and eosinophils are classified as “other cells”. However, “other cells”, likely represents a variety of cell types. One patient did not have a differential available. B) CSF protein and glucose (left axis, mg/dL) and opening pressure (right axis, cm of H 2 O) are shown. Hash mark denotes median. C) Results of the serologic or CSF testing for Taenia-specific antibodies (n = 50). ELISA, Enzyme-Linked Immunosorbent Assay; EITB, Enzyme-linked Immunoelectrotransfer Blot. In most patients (n = 59, 86%), the earliest hospitalisation associated with a known diagnosis of SANCC with accessible records was also the hospitalisation when the patient received a diagnosis of SANCC. Thus, we had the opportunity to assess for complications related to undiagnosed SANCC and the impact of diagnostic delays on these patients. We sought to capture patients with a previous hospitalisation for an associated complication, or those who had undergone evaluation for CNS-related symptoms with a compatible lesion previously noted on imaging, but in whom SANCC was not suspected at that time. Often these patients had encountered multiple medical professionals and had undergone extensive diagnostic evaluations. Out of the 59 patients without a previously established diagnosis of extraparenchymal NCC, 18 (30%) experienced a delay in diagnosis that met our clinical definition. Most commonly, patients had a prior hospitalisation for hydrocephalus (n = 10), stroke (n = 3), and/or meningitis (n = 4) without consideration for SANCC ( Fig. 3 A). Table 2 lists the most common and unique clinical and radiographic features that should prompt consideration for the diagnosis of SANCC in a patient with compatible epidemiologic exposure. Fig. 3. Open in a new tab Delays in anthelmintic treatment and subsequent SANCC-related hospital encounters. A) Description of those patients with a delay in commencing anthelmintics. Out of 59 patients without a known history of extraparenchymal NCC, 18 met our definition for a delay in diagnosis. Patients could have more than one previous hospitalisation and diagnosis. Meningitis diagnoses included presumed cryptococcal, coccidiomycosis, tuberculosis, viral, and bacterial. Some patients treatment for multiple different presumptive meningitis etiologies. Out of the full 69 patient cohort, 6 were initially managed without anthelmintics. B)Sixty-five patients had more than 60 days of follow-up after their hospitalisation for SANCC, including 23 patients with a delay in anthelmintics. Compared to 42 patients who did not experience a delay in anthelmintics, those that did have a delay had significantly more SANCC-related Emergency Department (ED) visits or hospitalisations following their SANCC hospitalisation. C) Reasons and numbers of SANCC-related subsequent hospital visits are listed. Seizures were considered unrelated to SANCC if due to coexisting parenchymal NCC. Steroid related symptoms were steroid-related myopathy (n = 3) and gastritis (n = 1). Additional details on hospital visits unrelated to SANCC can be found in Supplemental Data . Table 2. Prevalence of the most common features of SANCC in 59 patients without a prior diagnosis. Clinical Presentation Imaging Symptom n (%) Median duration of symptoms, weeks (IQR) MRI finding a n (%) Headache 46 (78) 8 (2.5–39.5) Ventriculomegaly 34 (57.6) with nausea/vomiting 28 (47.5) Cysts in the basilar cisterns b 40 (67.8) with dizziness 24 (40.7) Sylvian Fissure cysts 23 (38.9) with blurry vision 21 (35.6) Absence of parenchymal calcifications or cysts 29 (49.1) Focal neurologic symptoms 14 (23.7) 7 (1–42) Lacunar infarct 6 (10.2) Hemiparesis, with or without dysarthria 7 (11.9) Large vessel infarct, aneurysm, or subarachnoid haemorrhage 3 (5.1) Difficulty walking and urinary incontinence 3 (5.1) Lumbosacral spine cysts or arachnoiditis 8 (33.3) c Open in a new tab IQR, interquartile range; MRI, magnetic resonance imaging. a See Supplemental Table S2 for complete MRI findings for full dataset. b Includes quadrigeminal, pre-pontine/medullary, cerebellopontine/medullary, interpeduncular, suprasellar cisterns, stalk of the sylvian fissure. c 8 Out of 24 patients with a complete spine MRI. Several patients in the cohort were initially managed following the SANCC diagnosis without anthelmintic therapy ( Fig. 3 A). Four patients with a previously established diagnosis of SANCC at the time of SANCC hospitalisation were managed without anthelmintic therapy. Three of these underwent shunt placement for symptom management (1 also had intraventricular cyst removal) an unknown period prior to study capture. The fourth patient was followed clinically for six months until SANCC admission. Ultimately, they were all started on anthelmintic therapy during the SANCC hospitalisation. An additional 2 patients with a new diagnosis of SANCC were managed with surgical removal of subarachnoid cysts without anthelmintic therapy at the time of SANCC hospitalisation. One was lost to follow-up after 128 days. The other required CSF diversion for hydrocephalus 2 years later and was subsequently treated with anthelmintics. We analysed the impact of a delay in anthelmintics with subsequent hospital encounters (ED visits or hospitalisations). Reasons for a delay in anthelmintic treatment are shown in Fig. 3 A. Patients with a delay in anthelmintic therapy were found to have significantly more hospital encounters possibly or likely due to SANCC following their SANCC hospitalisation (median 1, IQR 1–2) compared to those without anthelmintic delay (median 0.5 IQR 0–1 p = 0.02, Fig. 3 B). The reasons for these visits are shown in Fig. 3 C and were most commonly hydrocephalus or non-infectious shunt malfunction. To assess for reporting bias in those with a delay in anthelmintic treatment, the number of non-SANCC hospital encounters was assessed and found to be similar between the groups (p = 0.36), as was the duration of follow-up between those with and without a delay in anthelmintic therapy (p = 0.12 [ Supplemental Figure S1 ]). The most common anthelmintic regimen at the time of discharge was combination therapy with albendazole and praziquantel (47.8%, n = 33 of 69), followed by albendazole monotherapy (29%, n = 20). All but one patient received corticosteroids in addition to anthelmintics. No anthelmintic was prescribed at the time of hospital discharge in 18.8% (n = 13) for varied reasons ( Supplemental Table S3 ). Patients were not prescribed one or both anthelmintics in 8.6% due to cost, typically with further arrangements to be made as an outpatient. Combination therapy was desired but not utilised in 4.3% (n = 3) of patients due lack of drug availability in the pharmacy. Patients were discharged on monotherapy with the available alternative agent in these cases. The influence of coexisting ventricular and non-calcified parenchymal NCC on treatment was examined. Thirteen out of 69 patients underwent surgical cyst extraction for therapeutic purposes, only 4 of which had ventricular NCC. There was no difference in the frequency of surgical extraction of cysts for therapeutic purposes in those with ventricular cysts as compared to those without ventricular cysts (p > 0.999, odds ratio [OR] 1.11, 95% confidence interval [CI] 0.34–3.8). However, the median year of hospitalisation for the 20 patients with ventricular disease was 2016. Prior to 2018, 6.25% (1 of 16) ventricular cases underwent therapeutic cyst removal, but this increased to 75% (3 of 4) after 2018 (p = 0.013, OR 45, 95% CI 1.79–599). Duration of anthelmintic therapy and use of corticosteroids in the 50 patients with complete data was compared for those with and without ventricular cysts and was not statistically significantly different (median 10.5 weeks and 21 weeks, p = 0.086, 95% CI of difference −1 to 50 weeks and median of 9 weeks and 16 weeks, p = 0.268, 95% CI of difference −4 to 22 weeks, respectively). Similarly, those with concurrent non-calcified parenchymal NCC did not have a statistically significantly different duration of anthelmintics (mean 32 weeks) compared with those without concurrent non-calcified parenchymal NCC (mean 51.9 weeks, p = 0.27, [95% CI −16.49–56.3]), nor a difference in corticosteroid use (median 9 weeks and 14 weeks, respectively, p = 0.09, 95% CI −1–25 weeks). Fifty-two of 69 patients had more than 60 days of follow-up data and completed the intended course of therapy. There was one death during the follow-up period due to COVID-19. Eight (12.5%) were documented to have disease recurrence during the follow-up period, defined as the appearance of new cysts on follow-up imaging (n = 7), or a worsening of previously visualised leptomeningeal disease and symptoms prompting re-initiation of treatment (n = 1). SANCC recurrence occurred a median of 2.3 years following SANCC hospital discharge (IQR 1.0–2.9 years). Fifty patients had data on what guided anthelmintic duration ( Fig. 4 ). While the majority (n = 34, 68%) of patients had their symptoms taken into account in determination of the duration of their anthelmintic course, it was rare (n = 1, 2%) where this was the only factor driving treatment length. Use of blood TsAg and/or qPCR ( T. solium [Ts] biomarkers) was infrequent (n = 4, 8%) and in all cases the patients also had CSF Ts biomarkers. Therefore, patient symptoms and blood Ts biomarkers were not considered further as independent variables. Of these 50 patients, treatment length was guided by normalisation of brain imaging in 14 (28%), by CSF Ts biomarker in 13 (26%), both normalisation of imaging and CSF Ts biomarkers in 4 (8%), a fixed duration in 14 (28%), and other factors in 5 (10%). Patients whose treatment duration was guided by CSF Ts biomarker negativity had a significantly decreased risk of disease recurrence (0% of 17) compared with those whose treatment duration did not include the use of CSF Ts biomarkers to guide treatment course (n = 8 of 33, 23%, p = 0.039, odds ratio [OR] 95% CI 0.0–0.84). Conversely, those whose treatment was guided by MRI normalisation did not have a decreased risk of recurrence (n = 3 of 20, 15%) compared to those whose treatment was not guided by MRI normalisation (n = 5 of 30, 16.67%, p > 0.9, OR 0.88 95% CI 0.22–4.19). The median time on anthelmintics where CSF Ts biomarkers were used to guide therapy was 56 weeks (IQR 29.5–113.5 weeks), significantly longer than in patients whose treatment was prescribed for a fixed duration (median of four weeks, IQR 2–9 weeks, p = 0.0002). However, anthelmintic length in patients managed by following CSF Ts biomarkers was not significantly different than the length of therapy guided by MRI normalisation (median 55 weeks, IQR 10–156 weeks, p = 0.46). There was no significant difference in follow-up duration between the management groups that could account for differences in recurrence reporting ( Supplemental Figure S2 ). Contingency analysis did not show a statistically significant difference in SANCC recurrence rates in reporting sites utilising CSF Ts biomarkers during this study (n = 4, 11.1%) compared with those that did not utilise CSF Ts biomarker use during this study (n = 4, 16.7%, p = 0.7, OR 0.63, 95% CI 0.2–2.4). However, there is a non-significant difference in these recurrence rates, and given the small sample size, a true difference in recurrence rates in sites utilising CSF Ts biomarkers compared to sites that did not utilise biomarkers cannot be ruled out as a confounder. There was no significant difference in duration of corticosteroid use between treatment guided by CSF Ts biomarkers (median 40 days, IQR 14–60) compared to those where normalisation of imaging was used to stop treatment (median 18 days, IQR 5.5–60, p = 0.285). However, patients whose treatment was a fixed duration of anthelmintics did have a statistically significantly shorter course of corticosteroids (median 5 days IQR, 2.8–16 days) compared with those where CSF Ts biomarkers (median 40 days, IQR 14–60, p = 0.001) or normalisation of imaging (median 18 days, IQR 5.5–60, p = 0.02) guided anthelmintic length ( Supplemental Figure S3 ). Results assessing whether the six-month post-hospitalisation brain MRI is associated with disease outcomes are found in the Supplemental Data . Fig. 4. Open in a new tab SANCC recurrence in various treatment approaches and length of anthelmintic therapy. Fifty patients completed the intended course of anthelmintic therapy and had information on what guided treatment duration; eight experienced SANCC recurrence during follow-up. A) Comparison of those that experienced a recurrence using CSF Ts biomarkers to guide duration of anthelmintics with those patients whose treatment did not. B) Comparison of those who experienced a recurrence using MRI normalisation to guide duration of anthelmintics with those patients whose treatment was not determined by MRI normalisation. Red denotes patients with SANCC recurrence, black denotes patients without SANCC recurrence. C)The duration of cumulative anthelmintic therapy used (albendazole and/or praziquantel) during follow-up period for the 50 with treatment duration available is shown for each treatment strategy. Four patients whose treatment was guided both by MRI normalisation and Ts CSF biomarkers is shown with the CSF biomarker group. Two patients whose treatment course was guided both by imaging and a fixed course are shown with the imaging group. An additional five patients were managed by other strategies, including stabilisation of imaging (n = 3), patient symptoms only (n = 1), and one had premature halting of anthelmintic therapy. Closed circles represent no SANCC recurrence, open squares represent patients who experienced SANCC recurrence. Line and error bar represent geometric mean and 95% CI. We did not find a significant effect of sex on recurrence rates (female 5.6%, n = 1 of 18; male 20.6% n = 7 of 34, p = 0.24) or delays in anthelmintics (female 61.1% n = 11 of 18; male 38.2% n = 13 of 34, p = 0.149). Outpatient follow-up was available for 51 patients following the intended course of therapy, a median of 2.5 years following hospitalisation, IQR 0.94–4.0 years. At this visit 59% reported chronic symptoms. At final visits, the most common residual symptoms were headache (29%), chronic dizziness (16%), and cognitive complaints (14% [ Supplemental Figure S4 ]). Cumulative prevalence of ventriculomegaly in this cohort was 82% (57 of 69) detected at some point during their care. Other less common but serious cumulative complications in this cohort were lacunar cerebral infarcts in seven (10%), large vessel infarcts in five (7%), subarachnoid haemorrhage in two (3%), and brain herniation in one patient (1.4% [ Supplemental Table S4 ]). Discussion Relapsing and remitting meningoencephalitis has long been described as a manifestation of NCC that we now call SANCC. 19 Only recently, however, has the reason for the relapsing nature of the disease been ascribed to the presence of stem cells in the tegument of SANCC cysts, enabling the formation of new cysts over time without repeat exposure. 5 , 20 While there have been single centre series describing success in SANCC management, 7 , 12 to our knowledge this is the first study that compares different anthelmintic treatment strategies and their influence on SANCC recurrence rates. Most prior studies examining SANCC treatment have short follow-up periods and are not designed to assess for disease recurrence. Here we describe a 12% recurrence rate, conservatively defined as new cyst appearance on imaging or worsening radiographic disease with concurrent symptoms during and a median follow-up period of just over two years. A prior smaller case series reported recurrence rates of 3 individuals out of 34 (9%), but two patients were judged to have recurrences based on increase in CSF antigen alone. 12 The relative low recurrence rate in this prior study may be attributed to the prevailing management at this centre by continuing anthelmintics until negativity of the CSF antigen. Here we demonstrate a decreased odds of SANCC recurrence when CSF Ts biomarkers are used to guide treatment. While studies have demonstrated a reduction in size of subarachnoid cysts on imaging within the first few months of anthelmintic therapy, 12 , 21 , 22 using MRI to determine durable cure can be more complicated. Once cysts have collapsed and no longer cause mass effect, 3D volumetric MRI sequences are required to avoid missing small or collapsed cysts. 23 Conversely, scarring and CSF loculations seen on 3D volumetrics and standard MRI sequences can give the appearance of persistent cysts despite sterile cure, and localised enhancement can last for years. 8 In the context of these challenges, it is not surprising that recurrence rates in this study were similar in patients whose treatment was guided by MRI normalisation as those who did not. Moreover, this approach lead to a median of over a year of anthelmintic therapy, similar to those whose treatment was guided by CSF Ts biomarkers. The decreased relapse rate in the CSF Ts biomarker group suggests individualised approach is likely required to achieve durable cure, and this testing can assist in identifying the patients where longer courses are required, and also enable truncated courses in some patients that appear to have viable cysts, but in fact may have are areas scarring trapping CSF loculations. SANCC is typically regarded as the most difficult to treat form of NCC, and thus for patients with multiple forms of NCC, treatment duration is usually driven by SANCC. Similarly, we found no significant difference in duration of anthelmintic or corticosteroid treatment in those with and without coexisting ventricular NCC, and those with and without coexisting non-calcified parenchymal NCC. Per guidelines published in 2018, 2 it is recommended that, if possible, intraventricular cysts be managed with surgical extraction before starting anthelmintics so as to avoid the risk of obstruction or ventricular entrapment. While we found no difference between therapeutic cyst removal in those with and without ventricular cysts in the cohort as a whole, management appeared to change over time. Following the year of guideline publication there was a statistically significant increase in therapeutic cyst removal for patients with ventricular disease compared to years prior, likely reflecting management change as a result of guideline publication. Studies prior to the advent of anthelmintics suggest that symptomatic management of SANCC-related hydrocephalus with shunt placement alone leads to a high complication rate and a fatality rate of 40–50%, 4 mostly due to complications of infectious or non-infectious shunt failure. More recent data suggest that anthelmintic therapy 24 and corticosteroids 25 may reduce NCC-related shunt failure. We found that those with a substantial delay in anthelmintic use, as evidenced by a missed diagnosis of SANCC, or an initial treatment strategy directed only at symptom management (e.g. shunt placement, cyst removal), had significantly more subsequent hospital encounters than those that did not experience a delay in anthelmintics. The types of SANCC-related hospital encounters that were increased in the delayed anthelmintic group (non-infectious shunt malfunction, new hydrocephalus, SANCC recurrence, severe CNS symptoms, stroke) suggest that the disease may become more difficult to treat with an increase in inflammation-driven complications when there is a substantial delay in anthelmintic treatment. Improved treatment response with a low relative intracranial cyst volume has been reported, 7 supporting the hypothesis that early diagnosis could render disease easier to treat. Whether early diagnosis and treatment can prevent the eventual development of hydrocephalus in SANCC remains an important question. Access to care is an additional consideration for timely anthelmintic use. Both albendazole and praziquantel have been subject to tremendous price increases in the United States in recent years. 26 , 27 , 28 Nearly 13% of patients in this cohort had difficulty accessing medications at hospital discharge due to cost or drug shortages. SANCC is likely an under-recognised entity in patients, particularly in non-endemic areas where there is less awareness of the diagnosis. Besides the 31% who had a prior hospital encounter for hydrocephalus or increased intracranial pressure, stroke, meningitis, brain mass, or transient ischaemic attack without consideration for SANCC, more than half of patients already carried a diagnosis of headaches before they were diagnosed with SANCC. Three dimensional balanced gradient echo MRI sequences have been shown to greatly increase the sensitivity of detecting subarachnoid cysts, and should be utilised in suspected cases. 23 It is possible that under-utilisation of 3D volumetric sequences, which must be specifically asked for by suspecting clinicians, may have contributed to the delay in diagnosis in this cohort. Here we found that 67% of patients who underwent lumbar puncture had detectable eosinophils in the CSF, albeit typically not the most predominant cell type. Given the rarity of the presence of eosinophils in most neuroinflammatory and infectious aetiologies, and the high prevalence of cysticercosis worldwide, SANCC should be considered in any patient from an endemic area with the presence of eosinophils in the CSF. Importantly, the presence of non-inflammatory CSF does not rule out the presence of SANCC, and conversely CSF cell counts can occasionally rise above 500 cells/mm 3 . There are several limitations to this study. As a retrospective study, while attempts were made to limit and assess for bias in the dataset, it is inherent in this type of study. The median follow-up period was just over 2 years, which was just under the median time to SANCC recurrence. While this follow-up period remains longer than many SANCC series, uncaptured recurrences may have occurred after their final recorded follow-up. Given the small number of total patients in this cohort, regression analyses were not performed and so adjustment for confounders was not possible. Institutions utilising CSF Ts biomarkers to guide treatment may have been more experienced in the management of SANCC, confounding the driver of decreased recurrence rates. However, contingency analysis comparing sites that used CSF Ts biomarkers with those that did not showed no statistically significant difference in recurrence rates. Presentations to other healthcare facilities for SANCC-related illnesses, and non-emergent complications addressed during subsequent outpatient office visits were missed in this data set. Radiologic recurrences in the pre-symptomatic period in patients not routinely being imaged would have also been missed. The finding that there was no difference between treatment duration between patients where CSF Ts biomarkers were used compared to those where imaging guided therapy may indicate unaccounted for confounders. Type 1 error due to the large number of comparisons, and type 2 errors due to a small sample size cannot be excluded. We did not systematically collect adverse reactions to anthelmintic or corticosteroid treatments. While we collected data on symptoms documented at the final outpatient follow up visit, the degree of disability and impact on quality of life would not be able to accurately be extrapolated in this study. Prospective studies will be needed to better understand how SANCC affects quality of life and long-term disability. In conclusion, this study suggests that early diagnosis and treatment may decrease SANCC-related hospital visits, and use of CSF Ts Biomarkers in guiding anthelmintic therapy may prevent SANCC recurrences. Larger and prospective randomised-controlled trials are needed to confirm these findings and determine the optimal use of corticosteroids and steroid-sparing agents in treating SANCC. Contributors EMO and CC conceptualised the study. JJG, MMD, SA, FCC, PRA, NW, NMB, JMR, TL, DM, AMC, EW, JDJ, AFH, CF, GM, PL, RB were responsible for data curation. EMO, JW, EHC, JAS, JH, TJH, ANC, LMC supervised. Drafting of the original manuscript and formal analyses were conducted by EMO, JJG, and MMD. Reviewing and editing of the manuscript was performed by JJG, MMD, JW, EHC, JH, SA, FCC, PRA, NWD, JMR, NMB, TJH, DM, TL, AMC, CC, ACW, EW, ANC, JDJ, AFH, CF, GM, PL, JAS, RB, LMC, EMO. EMO and JJG accessed and verified the underlying study data. Data sharing statement Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices) will be available upon request to the corresponding author by investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose for the purposes of achieving the aims in the approved proposal. This will be available immediately upon publication until 5 years following publication. Study protocol is immediately available in the Supplemental Data . Declaration of interests A.C.W declares royalties from UpToDate for chapters on neurocysticercosis. All other authors declare no competing interests. Acknowledgements This research was supported, in part, by the Intramural Research Program of the National Institutes of Health (NIH). The contributions of the NIH authors were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services. 1ZIAAI001234. Footnotes Appendix A Supplementary data related to this article can be found at https://doi.org/10.1016/j.eclinm.2026.103861 . Appendix A. Supplementary data Supplementary Material mmc1.docx (378.9KB, docx) References 1. Corda M., Sciurba J., Blaha J., et al. A recombinant monoclonal-based Taenia antigen assay that reflects disease activity in extra-parenchymal neurocysticercosis. PLoS Neglected Trop Dis. 2022;16(5) doi: 10.1371/journal.pntd.0010442. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 2. White A.C., Coyle C.M., Rajshekhar V., et al. Diagnosis and treatment of neurocysticercosis: 2017 clinical practice guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of tropical medicine and hygiene (ASTMH) Am J Trop Med Hyg. 2018;98(4):945–966. doi: 10.4269/ajtmh.18-88751. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 3. Abanto J., Blanco D., Saavedra H., et al. Mortality in parenchymal and subarachnoid neurocysticercosis. Am J Trop Med Hyg. 2021;105(1):176–180. doi: 10.4269/ajtmh.20-1330. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 4. Sotelo J., Marin C. Hydrocephalus secondary to cysticercotic arachnoiditis A long-term follow-up review of 92 cases. J Neurosurg. 1987;66:686–689. doi: 10.3171/jns.1987.66.5.0686. [ DOI ] [ PubMed ] [ Google Scholar ] 5. Orrego M.A., Verastegui M.R., Vasquez C.M., et al. Identification and culture of proliferative cells in abnormal Taenia solium larvae: role in the development of racemose neurocysticercosis. PLoS Neglected Trop Dis. 2021;15(3) doi: 10.1371/journal.pntd.0009303. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 6. Vos T., Allen C., Arora M., et al. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388(10053):1545–1602. doi: 10.1016/S0140-6736(16)31678-6. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 7. Osorio R., Carrillo-Mezo R., Romo M.L., et al. Factors associated with cysticidal treatment response in extraparenchymal neurocysticercosis. J Clin Pharmacol. 2019;59(4):548–556. doi: 10.1002/jcph.1346. [ DOI ] [ PubMed ] [ Google Scholar ] 8. Sanchez Boluarte A.N., Farrell E., Wilson M., et al. Persistent MRI abnormalities after successful treatment of subarachnoid and intraventricular neurocysticercosis: a case series. Neurol Clin Pract. 2025;15(6) doi: 10.1212/CPJ.0000000000200553. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 9. Fleury A., Garcia E., Hernandez M., et al. Neurocysticercosis: HP10 antigen detection is useful for the follow-up of the severe patients. PLoS Neglected Trop Dis. 2013;7(3) doi: 10.1371/journal.pntd.0002096. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 10. Angerri-Nadal M., Arroyo-Pereiro P., Sauque G., et al. Is antiparasitic treatment beneficial in chronic subarachnoid neurocysticercosis? A comparative case series. Enferm Infecc Microbiol Clín. 2025;43(8):476–482. doi: 10.1016/j.eimce.2025.05.005. [ DOI ] [ PubMed ] [ Google Scholar ] 11. O'Connell E.M., Harrison S., Dahlstrom E., Nash T., Nutman T.B. A novel, highly sensitive quantitative polymerase chain reaction assay for the diagnosis of subarachnoid and ventricular neurocysticercosis and for assessing responses to treatment. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;70(9):1875–1881. doi: 10.1093/cid/ciz541. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 12. Nash T.E., O'Connell E.M., Hammoud D.A., Wetzler L., Ware J.M., Mahanty S. Natural history of treated subarachnoid neurocysticercosis. Am J Trop Med Hyg. 2020;102(1):78–89. doi: 10.4269/ajtmh.19-0436. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 13. Alpern J.D., Stauffer W.M., Kesselheim A.S. High-cost generic drugs--implications for patients and policymakers. N Engl J Med. 2014;371(20):1859–1862. doi: 10.1056/NEJMp1408376. [ DOI ] [ PubMed ] [ Google Scholar ] 14. Fleury A., Carrillo-Mezo R., Flisser A., Sciutto E., Corona T. Subarachnoid basal neurocysticercosis: a focus on the most severe form of the disease. Expert Rev Anti Infect Ther. 2011;9(1):123–133. doi: 10.1586/eri.10.150. [ DOI ] [ PubMed ] [ Google Scholar ] 15. Batalova J. Mexican immigrants in the United States. 2024. https://www.migrationpolicy.org/article/mexican-immigrants-united-states 16. Dasema R., Batalova J. Central American immigrants in the United States. 2025. https://www.migrationpolicy.org/article/central-american-immigrants-united-states 17. Montalvo J., Batalova J. South American immigrants in the United States. 2024. https://www.migrationpolicy.org/article/south-american-immigrants-united-states 18. Harris P.A., Taylor R., Thielke R., Payne J., Gonzalez N., Conde J.G. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42(2):377–381. doi: 10.1016/j.jbi.2008.08.010. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 19. Bickerstaff E. Cerebral cysticercosis: common but unfamiliar manifestations. BMJ. 1955;1:1055–1058. doi: 10.1136/bmj.1.4921.1055. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 20. Orrego M.A., Szczesniak M.W., Vasquez C.M., et al. Transcriptomic analysis of subarachnoid cysts of Taenia solium reveals mechanisms for uncontrolled proliferation and adaptations to the microenvironment. Sci Rep. 2024;14(1) doi: 10.1038/s41598-024-61973-9. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 21. Brutto O.H.D., Sotelo J., Aguirre R., Díaz-Calderón E., Alarcón T.A. Albendazole therapy for giant subarachnoid cysticerci. Arch Neurol. 1997;49(5):535–538. doi: 10.1001/archneur.1992.00530290123021. [ DOI ] [ PubMed ] [ Google Scholar ] 22. Proaño J.V., Madrazo I., Avelar F., López-Félix B., Díaz G., Grijalva I. Medical treatment for neurocysticercosis characterized by giant subarachnoid cysts. N Engl J Med. 2001;345(12):879–885. doi: 10.1056/NEJMoa010212. [ DOI ] [ PubMed ] [ Google Scholar ] 23. Carrillo M.R., Lara Garcia J., Arroyo M., Fleury A. Relevance of 3D magnetic resonance imaging sequences in diagnosing basal subarachnoid neurocysticercosis. Acta Trop. 2015;152:60–65. doi: 10.1016/j.actatropica.2015.08.017. [ DOI ] [ PubMed ] [ Google Scholar ] 24. Kelley R., Duong D.H., Locke G.E. Characteristics of ventricular shunt malfunctions among patients with neurocysticercosis. Neurosurgery. 2002;50(4):757–762. doi: 10.1097/00006123-200204000-00014. [ DOI ] [ PubMed ] [ Google Scholar ] 25. Suastegui Roman R.A., Soto-Hernandez J.L., Sotelo J. Effects of prednisone on ventriculoperitoneal shunt function in hydrocephalus secondary to cysticercosis: a preliminary study. J Neurosurg. 1996;84(4):629–633. doi: 10.3171/jns.1996.84.4.0629. [ DOI ] [ PubMed ] [ Google Scholar ] 26. Alpern J.D., Song J., Stauffer W.M. Essential medicines in the United States — why access is diminishing. N Engl J Med. 2016;374(20):1901–1904. doi: 10.1056/NEJMp1601559. [ DOI ] [ PubMed ] [ Google Scholar ] 27. Manciulli T., Vola A., Mariconti M., et al. Shortage of albendazole and its consequences for patients with cystic echinococcosis treated at a referral center in Italy. Am J Trop Med Hyg. 2018;99(4):1006–1010. doi: 10.4269/ajtmh.18-0245. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] 28. Lindrose A.R., Fraser J.A., Hickey P.W., Mitre E. Costs and prescribing patterns of anthelmintics in the United States military: a retrospective analysis. Open Forum Infect Dis. 2022;9(3) doi: 10.1093/ofid/ofac040. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Associated Data This section collects any data citations, data availability statements, or supplementary materials included in this article. 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