Cranial Nerve Neuropathies: a Rare Manifestation of Cat Scratch Disease

Cranial Nerve Neuropathies: a Rare Manifestation of Cat Scratch Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cranial Nerve Neuropathies: a Rare Manifestation of Cat Scratch Disease Michal Yakubovsky, Alex Kosman, Laliv Kadar, Yael Paran, Galia Grisaru-Soen, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7502685/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Jan, 2026 Read the published version in BMC Infectious Diseases → Version 1 posted 11 You are reading this latest preprint version Abstract Background: Cranial nerve neuropathies represent a rare manifestation of cat scratch disease (CSD). Only a few case reports have been published, and the full clinical spectrum remains poorly characterized. We aimed to describe the clinical presentation, diagnostic approach, and prognosis of cat scratch disease (CSD)-associated cranial nerve neuropathies, a manifestation that is poorly characterized. Methods: Using data from a national CSD surveillance study, we identified patients with CSD-associated cranial neuropathies confirmed by serology and/or PCR for Bartonella henselae. Clinical, epidemiological, and imaging data were analyzed. Follow-up was conducted. Results: Seven immunocompetent patients with cranial nerve neuropathies were identified among approximately 4100 CSD patients diagnosed over a 28-year period (1997–2025). Affected cranial nerves included the facial (n = 3), abducens (n = 2), oculomotor (n = 1), and glossopharyngeal (n = 1) nerves, the latter 2 not previously reported in patients with CSD. All patients reported cat exposure. Neuropathies were accompanied by other CSD-related features, including fever (71%), lymphadenitis (57%), neuroretinitis (43%), and encephalitis (14%). Three patients received antibiotic therapy and 5 were treated with systemic corticosteroids. Six patients fully recovered within a median of 4 weeks; 1 patient showed marked improvement after 3 months and was subsequently lost to follow-up. Conclusion: CSD-associated cranial neuropathies are rare and possibly underdiagnosed. Diagnostic clues include cat contact and concurrent CSD features such as fever, lymphadenopathy, or neuroretinitis. These findings are hardly observed in idiopathic cranial nerve palsies such as Bell’s palsy, for which guidelines recommend against routine serologic evaluation. Although outcomes are generally favorable, optimal treatment remains undefined. We suggest testing for B. henselae infection in patients with cranial neuropathies when CSD is suspected. Increased clinical awareness is warranted to facilitate timely diagnosis and management. Bartonella henselae cat scratch disease cranial nerve palsy Bell’s palsy Figures Figure 1 Figure 2 Background Cat scratch disease (CSD), caused by Bartonella henselae , is a zoonotic infection primarily transmitted through cat scratches or bites. Approximately 90% of CSD cases present with Typical CSD characterized by regional lymphadenopathy or lymphadenitis, often preceded by a primary inoculation skin lesion. Atypical CSD presentations are diverse and may include fever of unknown origin (FUO), erythema nodosum, neuroretinitis, osteomyelitis, hepatosplenic involvement, Parinaud’s oculoglandular syndrome, encephalitis and others [ 1 – 3 ]. CSD-associated cranial nerve neuropathy or palsy has been rarely described. Utilizing data from a large national CSD surveillance study conducted since 1991, and performing long-term follow-up, we aimed to characterize CSD-associated cranial nerve neuropathies with respect to diagnosis, clinical features, and long-term outcomes. Methods Patient Population and study design. A detailed description of the CSD National Surveillance Study patient population has been published before [ 1 ]. Briefly, a case of CSD was defined as a patient presenting with a clinical syndrome consistent with CSD, in the absence of another diagnosis, and meeting at least one of the following laboratory criteria: positive serology for anti– B. henselae antibodies (immunoglobulin [Ig] M and/ or IgG) utilizing enzyme immunoassay (EIA) [ 4 ] or a positive PCR for B. henselae DNA in clinical specimens, primarily lymph node tissue, lymph node pus aspirates, or primary skin lesions. EIA and PCR were performed and interpreted as previously reported [ 4 , 5 ]. Epidemiologic, demographic and clinical data were obtained from community and hospital-based physicians, medical records, and directly from patients and their families. Cranial nerve neuropathies were identified through the national registry. Clinical diagnosis was essentially based on neurologic examination. All patients were evaluated by a neurologist and underwent brain imaging. Follow-up was conducted using reports from hospital and outpatient clinics, and direct contact with the patients and their families by email/telephone surveys. Doxycycline, macrolides, rifampin, were considered as antimicrobials potentially active against B. henselae [ 6 ]. Results During a 28-year period (1997–2025), approximately 4500 patients were diagnosed with CSD in the National Surveillance Study. Eight, B. henselae -seropositive patients with cranial neuropathis were identified in the national registry. One, a 10-month-old with abducens nerve palsy, was excluded due to lacks proper validation in this age group, and preliminary evidence of increased false seropositivity in children ≤ 1 year-old (Giladi, personal communication)). All patients with cranial neuropathy were serologically tested for cytomegalovirus, Epstein Barr virus, West-Nile virus and Syphilis with no evidence of acute infection. Six patients were seronegative for human immunodeficiency virus (HIV); an additional 6-year-old patient who had no HIV risk factors was not tested but remained clinically well during 16 years of follow-up and was presumed to be HIV-negative. Lyme disease testing was not performed, as the disease is not endemic in Israel. Seven patients met inclusion creiteria; all but 1 were hospitalized for evaluation. Presentations included facial nerve palsy (n = 3; Fig. 1 ), abducens nerve palsy (n = 2; Fig. 2 ), oculomotor nerve palsy (n = 1) and glossopharyngeal nerve palsy (n = 1). All patients except the latter had unilateral involvement. The laterality of the glossopharyngeal nerve involvement was clinically difficult to assess. Clinical data are presented in Table 1 . Diagnosis was confirmed in all 7 patients by B. henselae serology, with IgG titers ranging from 100 to ≤ 800; lymph node PCR was performed and found positive in 1 patient and lymph node histopathology revealed necrotizing granulomatous lymphadenitis in another patient. Table 1 CSD patients with cranial nerve neuropathy: Characteristics of the current cohort and previously published cases a No. Source Age and Sex Lymph-adenopathy (Location) Fever Cat contact Involved Cranial Nerve Cranial Nerve Manifestations Other Clinical Findings Antibiotic Treatment Cortico-steroid Treatment Time to complete recovery (weeks) Duration of Follow-Up (months) 1 Present study 62 F Yes (Cervical) Yes Yes 7 Bell's palsy None None Yes Partial recovery after 12 weeks 3 2 Present study 42 M Yes (Cervical) Yes Yes 7 Bell's palsy Elevated liver enzymes None Yes 4 51 3 Present study 6 F No Yes Yes 7 Bell's palsy Neuroretinitis None Yes 4 188 4 Present study 53 M Yes (Axillary) Yes Yes 6 Horizontal diplopia Encephalitis Neuroretinitis DOX None 12 14 5 b Present study 47 F No Yes Yes 6 Horizontal diplopia Neuroretinitis DOX Yes 4 46 6 Present study 67 F No No Yes 3 Diagonal diplopia None None Yes 8 54 7 Present study 14 F Yes (Cervical) No Yes 9 Liquid regurgitation, week gag reflex, nasal voice, hoarseness None RIF None 2 120 8 Walter et al. Pediatrics 1998 3 M Yes (Axillary) Yes Yes 7 Bell's palsy None None Yes 2 ND 9 Thompson et al. J Neuroophthalmol 1999 40 F No Yes Yes 7 Bell's palsy Neuroretinitis None None 4 ND 10 Ganesan et al. Journal of Oral and Maxillofacial Surgery 2005 29 F Yes (intraparotis) Yes Yes 7 Bell's palsy Parinaud oculoglandular syndrome, headaches None None NR 4 11 Nakamura et al. Brain Dev 2018 7 M Yes (Cerival and intra-parotis) Yes Yes 7 Bell's palsy None AZ Yes 24 ND 12 Valor et al. BMJ Case Rep 2018 28 M Yes (Cerival and pre-auricular) Yes Yes 7 Incomplete Bell’s palsy Parinaud oculoglandular syndrome, headaches, myalgia AZ Yes 2 ND 13 Mutucumarana et al. Clin Pediatr (Phila) 2020 5 F No Yes Yes 7 Bell's palsy Hepato-splenic CSD AZ & RIF None 2 ND 14 Rességuier et al. Revue de Medecine Interne 2013 28 M Yes (Cervical and pre-auricular) Yes Yes 7 Bell's palsy Hepatomegaly; Elevated liver enzymes DOX & RIF None Partial recovery after 8 weeks ND 15 Sendi et al. Emerg Infect Dis 2017 46 F Yes (Axillary) NR Yes 7 Bell's palsy Meningo-encephalitis, transverse myelitis DOX Yes 24 6 Abbreviations: CSD, cat scratch disease; No, number, F, female, M, male; DOX, doxycycline; RIF, rifampin, ND, not done, NR, not reported, AZ, azithromycin. a Five previously published reports, including 3 of facial nerve palsy, 1 of trigeminal sensory neuropathy, and 1 of bilateral abducens nerve palsy were excluded from the literature review either due to lack of laboratory confirmation of CSD (Premachandra DJ et al. Br J Oral Maxillofac Surg. 1990, Chiu AG at al. Otolaryngology–Head and Neck Surgery 2001 and Roebuck DJ et al. AJNR Am J Neuroradiol. 1998) or because an alternative, more plausible diagnosis was favored (Pham G et al. Am J Ophthalmol Case Rep 2022 and Ameilia A at al. Asian Pac J Trop Dis 2015) b This case was reported previously (Levy-Neuman, J Neuroophthalmol, 2022). Patients ranged in age from 6 to 67 years (median 47); two patients were males (28%). One patient had diabetes mellitus and none was immunocompromised. All seven patients had reported close cat contact. Six of the 7 patients had additional manifestations, aside from cranial nerve neuropathy, all characteristic of Typical or Atypical CSD. Fever was reported in 5 patients (71%), including 1 patient with prolonged fever lasting few weeks and elevated liver enzymes. Notably, fever typically resolved prior to the onset of cranial neuropathy symptoms. Regional lymphadenopathy/lymphadenitis occurred in 4 patients (57%) and neuroretinitis was diagnosed in 3 patients (43%), including 1 with encephalitis, concomitantly with the cranial neuropathy. Oculomotor nerve palsy presented as diplopia and mild ptosis, abducens nerve palsy as diplopia and inward deviation of the affected eye, and facial nerve palsy presented as peripheral nerve involvement and was often diagnosed as Bell's palsy. The glossopharyngeal palsy was most strikingly observed in a 14-year-old girl who presented acutely with severe dysphagia, nasal regurgitation, hoarseness, nasal speech, a weak gag reflex, and unilateral cervical lymphadenopathy. PCR testing of a fine needle aspiration of the lymph node confirmed B. henselae infection. Brain imaging was performed in all seven patients. Four patients underwent CT or CT angiography, which were either normal or demonstrated incidental unrelated findings. Three patients underwent brain MRI, two of whom had abnormal findings. One patient with right oculomotor nerve palsy demonstrated contrast enhancement of the right third cranial nerve. A follow-up MRI performed four months later was normal, with resolution of the initial finding. Another patient, who presented with abducens nerve palsy and encephalitis, showed diffuse hyperintensities in the white matter of both cerebral hemispheres. A follow-up MRI was not performed due to the patient's refusal, likely related to claustrophobia. Three of the 7 patients were treated with appropriate antibiotics and 5 patients have received systemic corticosteroids (Table 1 ). Six patients fully recovered within a median time of 4 weeks (range: 2–8 weeks) and maintained recovery over a median follow-up period of 52 months (range 13–187), (Table 1 ). One patient with facial nerve palsy showed marked clinical improvement after 3 months and was subsequently lost to follow-up. Discussion Cranial nerve palsies are a rare, yet well-recognized complication of various infectious and non-infectious diseases, though their pathogenesis remains incompletely understood and lacks broad consensus [ 7 ]. Here, we described seven cases of CSD-associated cranial nerve neuropathies affecting the 3rd, 6th, 7th, and 9th nerves. To the best of our knowledge, oculomotor and glossopharyngeal neuropathy due to CSD are reported here for the first time. We believe that the centralized diagnosis of all CSD cases in the country, based on clinical information combined with confirmatory laboratory tests previously shown to have high specificity for CSD[ 4 , 5 ] enabled the identification of these patients over a 28-year period and contributed new information to the existing body of knowledge. Cranial nerve palsies have been rarely reported in association with CSD. Earlier reports of CSD-associated cranial neuropathies, published prior to the identification of B. henselae as the etiologic agent of CSD in 1992, were either based on a non-standardized skin test no longer in use or lacked microbiological confirmation. For example, Carithers and Margileth [ 8 ] described 2 children with transient facial nerve palsy lasting 4–5 weeks among 1,471 CSD patients diagnosed by skin test and observed between 1975–1990. A review of the more recent publications revealed 8 reports of CSD associated-facial nerve palsy, all confirmed by serology and in some cases, by PCR from a lymph node or CSD primary skin lesion, for B. henselae . Table 1 presents the 7 cases from the current study (patients 1–7), along with 8 previously reported cases of facial nerve palsy with valid CSD diagnosis (patients 8–15), totaling 15 patients. The most well-known and extensively studied cranial nerve palsy is Bell's palsy, an idiopathic peripheral seventh nerve neuropathy, where the leading suspected cause, accounting for up to 70% of cases, is herpes simplex virus infection of the facial nerve [ 9 , 10 ]. Nevertheless, it is well-recognized that not all cases of Bell’s palsy are attributable to herpesvirus infections. Despite the widely accepted view that Bell's palsy is a diagnosis of exclusion, with diagnostic certainty achievable only after the resolution of facial paralysis, there is no consensus on the necessity of diagnostic testing or routine serologic evaluation. Some guidelines explicitly recommend against routine serologic investigations in most cases, with few exceptions such as testing for Lyme disease serology in endemic areas [ 9 ]. We suggest that cranial nerve neuropathy caused by CSD should be added to these exceptions. As shown in Table 1 , it is noteworthy that cranial nerve involvement in CSD, in contrast to Bell’s palsy or other isolated cranial nerve palsies is consistently accompanied by features characteristic of CSD. Of the 15 reported cases of cranial nerve palsy (Table 1 ), 11 of whom involved the facial nerve, all had a documented history of close contact with cats; 80% presented with fever, which is not typical of Bell's palsy; 66% had lymphadenopathy or lymphadenitis; and 66% exhibited additional manifestations of Atypical CSD, including encephalitis, neuroretinitis, Parinaud’s oculoglandular syndrome, hepatosplenic involvement, and others. Challenging current diagnostic paradigms, we recommend testing for B. henselae infection all cases of cranial neuropathies with extensive cat contact, particularly when CSD is clinically suspected, given the potential benefit of antibiotic therapy. The importance of obtaining a history of cat contact cannot be overemphasized, as demonstrated in our 7 patients with cranial neuropathy, where such history prompted diagnostic testing for CSD. Nonetheless, 10–15% of CSD patients may deny such exposure [ 11 ]. We also suggest actively screening for regional lymphadenopathy or lymphadenitis, neuroretinitis and other characteristic features of CSD. In immunocompetent patients, the prognosis for Typical CSD and most of its extra-nodal manifestations is generally favorable. The infection typically follows a self-limiting course, with most patients achieving full recovery within a few weeks or months without lasting sequelae [ 3 ]. This study supports the observation that CSD-associated cranial neuropathies follow a benign course, while the effect of antibiotic and corticosteroid therapy remains uncertain. Conclusion CSD is a rare cause of cranial neuropathy, and the diagnosis can often be overlooked. Clues to diagnosis include a history of cat exposure and coexisting clinical manifestations such as fever, regional lymphadenopathy or lymphadenitis, neuroretinitis, or encephalitis, features that are not typical of idiopathic Bell's palsy. The prognosis is generally favorable, with complete recovery expected in most cases. Abbreviations CSD Cat Scratch Disease PCR Polymerase Chain Reaction Ig Immunoglobulin IgM Immunoglobulin M IgG Immunoglobulin G EIA Enzyme Immunoassay FUO Fever of Unknown Origin CMV Cytomegalovirus EBV Epstein–Barr Virus WNV West Nile Virus HIV Human Immunodeficiency Virus CT Computed Tomography MRI Magnetic Resonance Imaging Declarations Ethical Approval and consent to participate Ethics approval was granted by the Tel Aviv Sourasky Medical Center Ethics Committee (Helsinki Committee) under protocol number TLV-0147-08. The study was primarily a retrospective data analysis, for which the Ethics Committee waived the requirement for individual inform consents. However, follow-up data were frequently collected prospectively, and in these cases, informed consent was required. Overall, informed consents were obtained for 5 of the 7 patients included in the study. Consent for publication Additionally, 2 patients provided separate written consent for publication of identifying photographs. One of these patients, diagnosed with CSD-associated facial nerve palsy at the age of 6, signed the publication consent form after reaching the age of 18. Copies of the signed consent forms are available for review by the Editor upon request. Data availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests Funding The authors declare that no specific grant from any funding agency, commercial, or not-for-profit sectors was received for this research Authors' contributions MY and MG conceived the study. MY collected and analyzed the data and drafted the manuscript. MG supervised the study and contributed to data interpretation. AK, LK, YP, GGS, AG, DY, RBA, JS, OZ, and ME contributed patient data, assisted in clinical interpretation, and provided critical input on the analysis. All authors critically revised the manuscript for important intellectual content, and all authors read and approved the final version. Acknowledgements We sincerely thank the patients who agreed to participate in this study, provided follow-up information, shared their medical data, and consented to the publication of their clinical images. Their contribution was invaluable to this research. We thank Dr. Igor Pekelis for providing clinical and medical history information regarding one of the patients included in this study. References Landes M, Maor Y, Mercer D, et al. Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome. Clin Infect Dis 2020 ; 71:2818–2824. Carithers HA. Cat-scratch Disease An Overview Based on a Study of 1,200 Patients. Available at: http://archpedi.jamanetwork.com/. Murakami K, Tsukahara M, Tsuneoka H, et al. Cat scratch disease: Analysis of 130 seropositive cases. Journal of Infection and Chemotherapy 2002 ; 8:349–352. Giladi M, Kletter Y, Avidor B, et al. Enzyme Immunoassay for the Diagnosis of Cat-Scratch Disease Defined by Polymerase Chain Reaction. 2001. Available at: https://academic.oup.com/cid/article/33/11/1852/444949. Goaz S, Rasis M, Binsky Ehrenreich I, et al. Molecular Diagnosis of Cat Scratch Disease: a 25-Year Retrospective Comparative Analysis of Various Clinical Specimens and Different PCR Assays. Microbiol Spectr 2022 ; 10:e0259621. Rolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, Raoult D. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother 2004 ; 48:1921–33. Keane JR. Multiple Cranial Nerve Palsies. Arch Neurol 2005 ; 62:1714. Encephalopathy A, Manifestations ON, Carithers HA, Margileth AM. Cat-Scratch Disease. Available at: http://archpedi.jamanetwork.com/. Michael Ronthal, Patricia Greenstein. Bell’s palsy: Pathogenesis, clinical features, and diagnosis in adults. Murakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell Palsy and Herpes Simplex Virus: Identification of Viral DNA in Endoneurial Fluid and Muscle. Ann Intern Med 1996 ; 124:27–30. Bergmans AMC, Peeters MF, Schellekens JFP, et al. Pitfalls and Fallacies of Cat Scratch Disease Serology: Evaluation of Bartonella henselae-Based Indirect Fluorescence Assay and Enzyme-Linked Immunoassay. 1997. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 24 Jan, 2026 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 23 Oct, 2025 Reviews received at journal 03 Oct, 2025 Reviewers agreed at journal 25 Sep, 2025 Reviews received at journal 25 Sep, 2025 Reviewers agreed at journal 25 Sep, 2025 Reviewers agreed at journal 25 Sep, 2025 Reviewers invited by journal 25 Sep, 2025 Editor invited by journal 03 Sep, 2025 Editor assigned by journal 02 Sep, 2025 Submission checks completed at journal 02 Sep, 2025 First submitted to journal 31 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7502685","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":524928079,"identity":"53c99c40-dc01-4aea-b0f7-3cca0e1bdf30","order_by":0,"name":"Michal Yakubovsky","email":"","orcid":"","institution":"Tel Aviv University","correspondingAuthor":false,"prefix":"","firstName":"Michal","middleName":"","lastName":"Yakubovsky","suffix":""},{"id":524928080,"identity":"09df84f2-0b31-42af-a714-f94a29911f2b","order_by":1,"name":"Alex Kosman","email":"","orcid":"","institution":"Tel Aviv 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19:01:40","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1074,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/2620982ecaf06c5b8fdc6362.jpeg"},{"id":93075048,"identity":"98bcc15e-e330-41db-9af1-6c691107cd73","added_by":"auto","created_at":"2025-10-08 18:44:18","extension":"jpeg","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1074,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/cdf35cd8acda330f10ff55f9.jpeg"},{"id":93075044,"identity":"a0f19f4b-e25d-42f2-8140-fa024ef19491","added_by":"auto","created_at":"2025-10-08 18:44:18","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":179717,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/c1fca55dbd591cc1e51cde20.png"},{"id":93075043,"identity":"59c68dc8-7a6c-4a49-bb63-3c97bbf3800f","added_by":"auto","created_at":"2025-10-08 18:44:18","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":935,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/f31699e946695bc10e3ba3e2.png"},{"id":93075096,"identity":"439509f1-8c03-4d07-821e-f6dfdebb630c","added_by":"auto","created_at":"2025-10-08 19:01:43","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":935,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/06b6a4fd352684fc1fe0e7f8.png"},{"id":93075050,"identity":"756cf77f-91f1-4ffa-b9ec-557ff2d6cbce","added_by":"auto","created_at":"2025-10-08 18:44:18","extension":"xml","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":65168,"visible":true,"origin":"","legend":"","description":"","filename":"a6ff0ac9d91b49d6b778d2e9b1bc7b731structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/93ca2728bf320d6b41bb9fed.xml"},{"id":93075045,"identity":"36b0adc7-bf8f-422a-b6c9-52efa66127dd","added_by":"auto","created_at":"2025-10-08 18:44:18","extension":"html","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":72341,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/b64851fdc6863e03cdd12fec.html"},{"id":93075037,"identity":"a481be56-da37-47ce-900c-89142f7e5dc2","added_by":"auto","created_at":"2025-10-08 18:44:17","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":358115,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea.\u003c/strong\u003e A six-year-old girl, exposed to a house-hold cat, with right-sided peripheral seventh cranial nerve palsy due to cat scratch disease. Ophthalmologic examination revealed a left-sided neuroretinitis.\u003cbr\u003e\n \u003cstrong\u003eb.\u003c/strong\u003eThe same patient, three weeks later, showing complete recovery.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/916fa36a3701a3a649e3698d.png"},{"id":93075100,"identity":"21fcab0e-9b84-41f1-beeb-1256716e9f81","added_by":"auto","created_at":"2025-10-08 19:01:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":204689,"visible":true,"origin":"","legend":"\u003cp\u003eA 47-year-old woman with close cat contact presented with left sixth cranial nerve (abducens) palsy. The patient complained of binocular horizontal diplopia. Note the impaired abduction of the left eye, which \u003cstrong\u003eturns inward \u003c/strong\u003etoward the nose (esotropia) in primary gaze due to paralysis of the left lateral rectus muscle.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/36800d2cd03087ca122f6c88.png"},{"id":101151814,"identity":"9f956c06-d32e-4f53-a300-0ae2ede41868","added_by":"auto","created_at":"2026-01-26 16:06:03","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1601391,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7502685/v1/afac7c9f-ed05-4761-82ec-a7e9a733aa97.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cranial Nerve Neuropathies: a Rare Manifestation of Cat Scratch Disease","fulltext":[{"header":"Background","content":"\u003cp\u003eCat scratch disease (CSD), caused by \u003cem\u003eBartonella henselae\u003c/em\u003e, is a zoonotic infection primarily transmitted through cat scratches or bites. Approximately 90% of CSD cases present with Typical CSD characterized by regional lymphadenopathy or lymphadenitis, often preceded by a primary inoculation skin lesion. Atypical CSD presentations are diverse and may include fever of unknown origin (FUO), erythema nodosum, neuroretinitis, osteomyelitis, hepatosplenic involvement, Parinaud\u0026rsquo;s oculoglandular syndrome, encephalitis and others [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. CSD-associated cranial nerve neuropathy or palsy has been rarely described. Utilizing data from a large national CSD surveillance study conducted since 1991, and performing long-term follow-up, we aimed to characterize CSD-associated cranial nerve neuropathies with respect to diagnosis, clinical features, and long-term outcomes.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003ePatient Population and study design. A detailed description of the CSD National Surveillance Study patient population has been published before [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Briefly, a case of CSD was defined as a patient presenting with a clinical syndrome consistent with CSD, in the absence of another diagnosis, and meeting at least one of the following laboratory criteria: positive serology for anti\u0026ndash;\u003cem\u003eB. henselae\u003c/em\u003e antibodies (immunoglobulin [Ig] M and/ or IgG) utilizing enzyme immunoassay (EIA) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] or a positive PCR for \u003cem\u003eB. henselae\u003c/em\u003e DNA in clinical specimens, primarily lymph node tissue, lymph node pus aspirates, or primary skin lesions. EIA and PCR were performed and interpreted as previously reported [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Epidemiologic, demographic and clinical data were obtained from community and hospital-based physicians, medical records, and directly from patients and their families.\u003c/p\u003e\u003cp\u003eCranial nerve neuropathies were identified through the national registry. Clinical diagnosis was essentially based on neurologic examination. All patients were evaluated by a neurologist and underwent brain imaging.\u003c/p\u003e\u003cp\u003eFollow-up was conducted using reports from hospital and outpatient clinics, and direct contact with the patients and their families by email/telephone surveys. Doxycycline, macrolides, rifampin, were considered as antimicrobials potentially active against \u003cem\u003eB. henselae\u003c/em\u003e [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring a 28-year period (1997\u0026ndash;2025), approximately 4500 patients were diagnosed with CSD in the National Surveillance Study. Eight, \u003cem\u003eB. henselae\u003c/em\u003e-seropositive patients with cranial neuropathis were identified in the national registry. One, a 10-month-old with abducens nerve palsy, was excluded due to lacks proper validation in this age group, and preliminary evidence of increased false seropositivity in children\u0026thinsp;\u0026le;\u0026thinsp;1 year-old (Giladi, personal communication)). All patients with cranial neuropathy were serologically tested for cytomegalovirus, Epstein Barr virus, West-Nile virus and Syphilis with no evidence of acute infection. Six patients were seronegative for human immunodeficiency virus (HIV); an additional 6-year-old patient who had no HIV risk factors was not tested but remained clinically well during 16 years of follow-up and was presumed to be HIV-negative. Lyme disease testing was not performed, as the disease is not endemic in Israel.\u003c/p\u003e\u003cp\u003eSeven patients met inclusion creiteria; all but 1 were hospitalized for evaluation. Presentations included facial nerve palsy (n\u0026thinsp;=\u0026thinsp;3; Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), abducens nerve palsy (n\u0026thinsp;=\u0026thinsp;2; Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), oculomotor nerve palsy (n\u0026thinsp;=\u0026thinsp;1) and glossopharyngeal nerve palsy (n\u0026thinsp;=\u0026thinsp;1). All patients except the latter had unilateral involvement. The laterality of the glossopharyngeal nerve involvement was clinically difficult to assess. Clinical data are presented in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Diagnosis was confirmed in all 7 patients by \u003cem\u003eB. henselae\u003c/em\u003e serology, with IgG titers ranging from 100 to \u0026le;\u0026thinsp;800; lymph node PCR was performed and found positive in 1 patient and lymph node histopathology revealed necrotizing granulomatous lymphadenitis in another patient.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCSD patients with cranial nerve neuropathy: Characteristics of the current cohort and previously published cases\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"13\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo.\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSource\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAge and Sex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLymph-adenopathy (Location)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eFever\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCat contact\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eInvolved Cranial Nerve\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eCranial Nerve Manifestations\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eOther Clinical Findings\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eAntibiotic Treatment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003eCortico-steroid Treatment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eTime to complete recovery (weeks)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eDuration of Follow-Up (months)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62\u003c/p\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(Cervical)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePartial recovery after 12 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42 M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(Cervical)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eElevated liver enzymes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e51\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNeuroretinitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e188\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53 M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(Axillary)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHorizontal diplopia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eEncephalitis Neuroretinitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDOX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47\u003c/p\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHorizontal diplopia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNeuroretinitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDOX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e67\u003c/p\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eDiagonal diplopia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePresent study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14\u003c/p\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(Cervical)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eLiquid regurgitation, week gag reflex, nasal voice, hoarseness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eRIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e120\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWalter et al. Pediatrics 1998\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(Axillary)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eND\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThompson et al. J Neuroophthalmol 1999\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40\u003c/p\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNeuroretinitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eND\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGanesan et al. Journal of Oral and Maxillofacial Surgery 2005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29\u003c/p\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(intraparotis)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eParinaud oculoglandular syndrome, headaches\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNakamura et al. Brain Dev 2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7\u003c/p\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(Cerival and intra-parotis)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eAZ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eND\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eValor et al. BMJ Case Rep 2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28\u003c/p\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(Cerival and pre-auricular)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eIncomplete Bell\u0026rsquo;s palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eParinaud oculoglandular syndrome, headaches,\u003c/p\u003e\u003cp\u003emyalgia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eAZ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eND\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMutucumarana et al. Clin Pediatr (Phila)\u003c/p\u003e\u003cp\u003e2020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHepato-splenic CSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eAZ \u0026amp; RIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eND\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRess\u0026eacute;guier et al. Revue de Medecine Interne 2013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28\u003c/p\u003e\u003cp\u003eM\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(Cervical and pre-auricular)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eHepatomegaly; Elevated liver enzymes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDOX \u0026amp; RIF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eNone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003ePartial recovery after 8 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eND\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSendi et al. Emerg Infect Dis 2017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46\u003c/p\u003e\u003cp\u003eF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003cp\u003e(Axillary)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eBell's palsy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eMeningo-encephalitis, transverse myelitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eDOX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"13\"\u003eAbbreviations: CSD, cat scratch disease; No, number, F, female, M, male; DOX, doxycycline; RIF, rifampin, ND, not done, NR, not reported, AZ, azithromycin.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"13\"\u003e\u003csup\u003ea\u003c/sup\u003e Five previously published reports, including 3 of facial nerve palsy, 1 of trigeminal sensory neuropathy, and 1 of bilateral abducens nerve palsy were excluded from the literature review either due to lack of laboratory confirmation of CSD (Premachandra DJ et al. Br J Oral Maxillofac Surg. 1990, Chiu AG at al. Otolaryngology\u0026ndash;Head and Neck Surgery 2001 and Roebuck DJ et al. AJNR Am J Neuroradiol. 1998) or because an alternative, more plausible diagnosis was favored (Pham G et al. Am J Ophthalmol Case Rep 2022 and Ameilia A at al. Asian Pac J Trop Dis 2015)\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"13\"\u003e\u003csup\u003eb\u003c/sup\u003e This case was reported previously (Levy-Neuman, J Neuroophthalmol, 2022).\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePatients ranged in age from 6 to 67 years (median 47); two patients were males (28%). One patient had diabetes mellitus and none was immunocompromised. All seven patients had reported close cat contact.\u003c/p\u003e\u003cp\u003eSix of the 7 patients had additional manifestations, aside from cranial nerve neuropathy, all characteristic of Typical or Atypical CSD. Fever was reported in 5 patients (71%), including 1 patient with prolonged fever lasting few weeks and elevated liver enzymes. Notably, fever typically resolved prior to the onset of cranial neuropathy symptoms. Regional lymphadenopathy/lymphadenitis occurred in 4 patients (57%) and neuroretinitis was diagnosed in 3 patients (43%), including 1 with encephalitis, concomitantly with the cranial neuropathy.\u003c/p\u003e\u003cp\u003eOculomotor nerve palsy presented as diplopia and mild ptosis, abducens nerve palsy as diplopia and inward deviation of the affected eye, and facial nerve palsy presented as peripheral nerve involvement and was often diagnosed as Bell's palsy. The glossopharyngeal palsy was most strikingly observed in a 14-year-old girl who presented acutely with severe dysphagia, nasal regurgitation, hoarseness, nasal speech, a weak gag reflex, and unilateral cervical lymphadenopathy. PCR testing of a fine needle aspiration of the lymph node confirmed \u003cem\u003eB. henselae\u003c/em\u003e infection. Brain imaging was performed in all seven patients. Four patients underwent CT or CT angiography, which were either normal or demonstrated incidental unrelated findings. Three patients underwent brain MRI, two of whom had abnormal findings. One patient with right oculomotor nerve palsy demonstrated contrast enhancement of the right third cranial nerve. A follow-up MRI performed four months later was normal, with resolution of the initial finding. Another patient, who presented with abducens nerve palsy and encephalitis, showed diffuse hyperintensities in the white matter of both cerebral hemispheres. A follow-up MRI was not performed due to the patient's refusal, likely related to claustrophobia.\u003c/p\u003e\u003cp\u003eThree of the 7 patients were treated with appropriate antibiotics and 5 patients have received systemic corticosteroids (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Six patients fully recovered within a median time of 4 weeks (range: 2\u0026ndash;8 weeks) and maintained recovery over a median follow-up period of 52 months (range 13\u0026ndash;187), (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). One patient with facial nerve palsy showed marked clinical improvement after 3 months and was subsequently lost to follow-up.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCranial nerve palsies are a rare, yet well-recognized complication of various infectious and non-infectious diseases, though their pathogenesis remains incompletely understood and lacks broad consensus [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Here, we described seven cases of CSD-associated cranial nerve neuropathies affecting the 3rd, 6th, 7th, and 9th nerves. To the best of our knowledge, oculomotor and glossopharyngeal neuropathy due to CSD are reported here for the first time. We believe that the centralized diagnosis of all CSD cases in the country, based on clinical information combined with confirmatory laboratory tests previously shown to have high specificity for CSD[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] enabled the identification of these patients over a 28-year period and contributed new information to the existing body of knowledge.\u003c/p\u003e\u003cp\u003eCranial nerve palsies have been rarely reported in association with CSD. Earlier reports of CSD-associated cranial neuropathies, published prior to the identification of \u003cem\u003eB. henselae\u003c/em\u003e as the etiologic agent of CSD in 1992, were either based on a non-standardized skin test no longer in use or lacked microbiological confirmation. For example, Carithers and Margileth [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] described 2 children with transient facial nerve palsy lasting 4\u0026ndash;5 weeks among 1,471 CSD patients diagnosed by skin test and observed between 1975\u0026ndash;1990. A review of the more recent publications revealed 8 reports of CSD associated-facial nerve palsy, all confirmed by serology and in some cases, by PCR from a lymph node or CSD primary skin lesion, for \u003cem\u003eB. henselae\u003c/em\u003e. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the 7 cases from the current study (patients 1\u0026ndash;7), along with 8 previously reported cases of facial nerve palsy with valid CSD diagnosis (patients 8\u0026ndash;15), totaling 15 patients.\u003c/p\u003e\u003cp\u003eThe most well-known and extensively studied cranial nerve palsy is Bell's palsy, an idiopathic peripheral seventh nerve neuropathy, where the leading suspected cause, accounting for up to 70% of cases, is herpes simplex virus infection of the facial nerve [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Nevertheless, it is well-recognized that not all cases of Bell\u0026rsquo;s palsy are attributable to herpesvirus infections. Despite the widely accepted view that Bell's palsy is a diagnosis of exclusion, with diagnostic certainty achievable only after the resolution of facial paralysis, there is no consensus on the necessity of diagnostic testing or routine serologic evaluation. Some guidelines explicitly recommend against routine serologic investigations in most cases, with few exceptions such as testing for Lyme disease serology in endemic areas [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. We suggest that cranial nerve neuropathy caused by CSD should be added to these exceptions. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, it is noteworthy that cranial nerve involvement in CSD, in contrast to Bell\u0026rsquo;s palsy or other isolated cranial nerve palsies is consistently accompanied by features characteristic of CSD. Of the 15 reported cases of cranial nerve palsy (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), 11 of whom involved the facial nerve, all had a documented history of close contact with cats; 80% presented with fever, which is not typical of Bell's palsy; 66% had lymphadenopathy or lymphadenitis; and 66% exhibited additional manifestations of Atypical CSD, including encephalitis, neuroretinitis, Parinaud\u0026rsquo;s oculoglandular syndrome, hepatosplenic involvement, and others.\u003c/p\u003e\u003cp\u003eChallenging current diagnostic paradigms, we recommend testing for \u003cem\u003eB. henselae\u003c/em\u003e infection all cases of cranial neuropathies with extensive cat contact, particularly when CSD is clinically suspected, given the potential benefit of antibiotic therapy. The importance of obtaining a history of cat contact cannot be overemphasized, as demonstrated in our 7 patients with cranial neuropathy, where such history prompted diagnostic testing for CSD. Nonetheless, 10\u0026ndash;15% of CSD patients may deny such exposure [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. We also suggest actively screening for regional lymphadenopathy or lymphadenitis, neuroretinitis and other characteristic features of CSD.\u003c/p\u003e\u003cp\u003eIn immunocompetent patients, the prognosis for Typical CSD and most of its extra-nodal manifestations is generally favorable. The infection typically follows a self-limiting course, with most patients achieving full recovery within a few weeks or months without lasting sequelae [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This study supports the observation that CSD-associated cranial neuropathies follow a benign course, while the effect of antibiotic and corticosteroid therapy remains uncertain.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCSD is a rare cause of cranial neuropathy, and the diagnosis can often be overlooked. Clues to diagnosis include a history of cat exposure and coexisting clinical manifestations such as fever, regional lymphadenopathy or lymphadenitis, neuroretinitis, or encephalitis, features that are not typical of idiopathic Bell's palsy. The prognosis is generally favorable, with complete recovery expected in most cases.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCat Scratch Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePolymerase Chain Reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eImmunoglobulin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIgM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eImmunoglobulin M\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIgG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eImmunoglobulin G\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEnzyme Immunoassay\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFUO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFever of Unknown Origin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCytomegalovirus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEBV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eEpstein–Barr Virus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWNV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWest Nile Virus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHuman Immunodeficiency Virus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eComputed Tomography\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMagnetic Resonance Imaging\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was granted by the Tel Aviv Sourasky Medical Center Ethics Committee (Helsinki Committee) under protocol number TLV-0147-08. The study was primarily a retrospective data analysis, for which the Ethics Committee\u0026nbsp;waived the requirement for individual inform consents.\u0026nbsp;However, follow-up data were frequently collected prospectively, and in these cases, informed consent was required. Overall, informed consents were obtained for 5 of the 7 patients included in the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdditionally, 2 patients provided separate written consent for publication of identifying photographs. One of these patients, diagnosed with CSD-associated facial nerve palsy at the age of 6, signed the publication consent form after reaching the age of 18. Copies of the signed consent forms are available for review by the Editor upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no specific grant from any funding agency, commercial, or not-for-profit sectors was received for this research\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMY and MG conceived the study. MY collected and analyzed the data and drafted the manuscript. MG supervised the study and contributed to data interpretation. AK, LK, YP, GGS, AG, DY, RBA, JS, OZ, and ME contributed patient data, assisted in clinical interpretation, and provided critical input on the analysis. All authors critically revised the manuscript for important intellectual content, and all authors read and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe sincerely thank the patients who agreed to participate in this study, provided follow-up information, shared their medical data, and consented to the publication of their clinical images. Their contribution was invaluable to this research.\u003c/p\u003e\n\u003cp\u003eWe thank Dr. Igor Pekelis for providing clinical and medical history information regarding one of the patients included in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eLandes M, Maor Y, Mercer D, et al. Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome. Clin Infect Dis \u003cstrong\u003e2020\u003c/strong\u003e; 71:2818\u0026ndash;2824.\u003c/li\u003e\n \u003cli\u003eCarithers HA. Cat-scratch Disease An Overview Based on a Study of 1,200 Patients. Available at: http://archpedi.jamanetwork.com/.\u003c/li\u003e\n \u003cli\u003eMurakami K, Tsukahara M, Tsuneoka H, et al. Cat scratch disease: Analysis of 130 seropositive cases. Journal of Infection and Chemotherapy \u003cstrong\u003e2002\u003c/strong\u003e; 8:349\u0026ndash;352.\u003c/li\u003e\n \u003cli\u003eGiladi M, Kletter Y, Avidor B, et al. Enzyme Immunoassay for the Diagnosis of Cat-Scratch Disease Defined by Polymerase Chain Reaction. 2001. Available at: https://academic.oup.com/cid/article/33/11/1852/444949.\u003c/li\u003e\n \u003cli\u003eGoaz S, Rasis M, Binsky Ehrenreich I, et al. Molecular Diagnosis of Cat Scratch Disease: a 25-Year Retrospective Comparative Analysis of Various Clinical Specimens and Different PCR Assays. Microbiol Spectr \u003cstrong\u003e2022\u003c/strong\u003e; 10:e0259621.\u003c/li\u003e\n \u003cli\u003eRolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, Raoult D. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother \u003cstrong\u003e2004\u003c/strong\u003e; 48:1921\u0026ndash;33.\u003c/li\u003e\n \u003cli\u003eKeane JR. Multiple Cranial Nerve Palsies. Arch Neurol \u003cstrong\u003e2005\u003c/strong\u003e; 62:1714.\u003c/li\u003e\n \u003cli\u003eEncephalopathy A, Manifestations ON, Carithers HA, Margileth AM. Cat-Scratch Disease. Available at: http://archpedi.jamanetwork.com/.\u003c/li\u003e\n \u003cli\u003eMichael Ronthal, Patricia Greenstein. Bell\u0026rsquo;s palsy: Pathogenesis, clinical features, and diagnosis in adults.\u003c/li\u003e\n \u003cli\u003eMurakami S, Mizobuchi M, Nakashiro Y, Doi T, Hato N, Yanagihara N. Bell Palsy and Herpes Simplex Virus: Identification of Viral DNA in Endoneurial Fluid and Muscle. Ann Intern Med \u003cstrong\u003e1996\u003c/strong\u003e; 124:27\u0026ndash;30.\u003c/li\u003e\n \u003cli\u003eBergmans AMC, Peeters MF, Schellekens JFP, et al. Pitfalls and Fallacies of Cat Scratch Disease Serology: Evaluation of Bartonella henselae-Based Indirect Fluorescence Assay and Enzyme-Linked Immunoassay. 1997.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bartonella henselae, cat scratch disease, cranial nerve palsy, Bell’s palsy","lastPublishedDoi":"10.21203/rs.3.rs-7502685/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7502685/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground:\u003c/b\u003e\u003c/p\u003e\u003cp\u003eCranial nerve neuropathies represent a rare manifestation of cat scratch disease (CSD). Only a few case reports have been published, and the full clinical spectrum remains poorly characterized. We aimed to describe the clinical presentation, diagnostic approach, and prognosis of cat scratch disease (CSD)-associated cranial nerve neuropathies, a manifestation that is poorly characterized.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods:\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUsing data from a national CSD surveillance study, we identified patients with CSD-associated cranial neuropathies confirmed by serology and/or PCR for Bartonella henselae. Clinical, epidemiological, and imaging data were analyzed. Follow-up was conducted.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults:\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSeven immunocompetent patients with cranial nerve neuropathies were identified among approximately 4100 CSD patients diagnosed over a 28-year period (1997\u0026ndash;2025). Affected cranial nerves included the facial (n\u0026thinsp;=\u0026thinsp;3), abducens (n\u0026thinsp;=\u0026thinsp;2), oculomotor (n\u0026thinsp;=\u0026thinsp;1), and glossopharyngeal (n\u0026thinsp;=\u0026thinsp;1) nerves, the latter 2 not previously reported in patients with CSD. All patients reported cat exposure. Neuropathies were accompanied by other CSD-related features, including fever (71%), lymphadenitis (57%), neuroretinitis (43%), and encephalitis (14%). Three patients received antibiotic therapy and 5 were treated with systemic corticosteroids. Six patients fully recovered within a median of 4 weeks; 1 patient showed marked improvement after 3 months and was subsequently lost to follow-up.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion:\u003c/b\u003e\u003c/p\u003e\u003cp\u003eCSD-associated cranial neuropathies are rare and possibly underdiagnosed. Diagnostic clues include cat contact and concurrent CSD features such as fever, lymphadenopathy, or neuroretinitis. These findings are hardly observed in idiopathic cranial nerve palsies such as Bell\u0026rsquo;s palsy, for which guidelines recommend against routine serologic evaluation. Although outcomes are generally favorable, optimal treatment remains undefined. We suggest testing for B. henselae infection in patients with cranial neuropathies when CSD is suspected. Increased clinical awareness is warranted to facilitate timely diagnosis and management.\u003c/p\u003e","manuscriptTitle":"Cranial Nerve Neuropathies: a Rare Manifestation of Cat Scratch Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-08 18:44:12","doi":"10.21203/rs.3.rs-7502685/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-23T19:52:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-03T17:57:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"145359931177253405442212301342876336117","date":"2025-09-25T20:07:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-25T18:17:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160275189537107398950769351570348692879","date":"2025-09-25T15:33:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"302258613290696019669040239798563548852","date":"2025-09-25T15:10:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-25T14:41:59+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-03T21:07:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-02T09:41:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-02T09:40:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-08-31T20:19:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"30c80755-f4e7-410f-918b-97d3011d83c7","owner":[],"postedDate":"October 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-26T16:02:25+00:00","versionOfRecord":{"articleIdentity":"rs-7502685","link":"https://doi.org/10.1186/s12879-026-12628-9","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2026-01-24 15:59:05","publishedOnDateReadable":"January 24th, 2026"},"versionCreatedAt":"2025-10-08 18:44:12","video":"","vorDoi":"10.1186/s12879-026-12628-9","vorDoiUrl":"https://doi.org/10.1186/s12879-026-12628-9","workflowStages":[]},"version":"v1","identity":"rs-7502685","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7502685","identity":"rs-7502685","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}