Downbeat nystagmus is a type of jerk nystagmus that may be seen in patients with lesions affecting the vestibulocerebellum. This is a case of a 7-year-old girl presenting with a history of fever, headache, and episodic vertigo with downbeat nystagmus. The diagnosis of Epstein-Barr virus meningitis with acute cerebellitis was made by contrast magnetic resonance imaging, cerebrospinal fluid analysis, and serum Epstein-Barr virus titers. Contrast magnetic resonance imaging demonstrated enhancement of the meninges and inferior cerebellar folia, correlating with the neuroophthalmological symptom of downbeat nystagmus

Darpel, Kyle

Jones, Kimberly S.

Lightner, Donita D.

Toupin, David Neil

Wade, Cameron A.

English

University of Kentucky

University of Kentucky UKnowledge Neurology Faculty Publications Neurology 3-15-2021 Downbeat Nystagmus in a 7-Year-Old Girl with Epstein-Barr Virus-Associated Meningitis and Cerebellitis Cameron A. Wade University of Kentucky, cameron.wade@uky.edu David Neil Toupin University of Kentucky, d.n.toupin@uky.edu Kyle Darpel University of Kentucky, kyle.darpel@uky.edu Kimberly S. Jones University of Kentucky, Kimberly.Jones2@uky.edu Donita D. Lightner University of Kentucky, donita.lightner@uky.edu Follow this and additional works at: https://uknowledge.uky.edu/neurology_facpub  Part of the Neurology Commons Right click to open a feedback form in a new tab to let us know how this document benefits you. Repository Citation Wade, Cameron A.; Toupin, David Neil; Darpel, Kyle; Jones, Kimberly S.; and Lightner, Donita D., "Downbeat Nystagmus in a 7-Year-Old Girl with Epstein-Barr Virus-Associated Meningitis and Cerebellitis" (2021). Neurology Faculty Publications. 80. https://uknowledge.uky.edu/neurology_facpub/80 This Article is brought to you for free and open access by the Neurology at UKnowledge. It has been accepted for inclusion in Neurology Faculty Publications by an authorized administrator of UKnowledge. For more information, please contact UKnowledge@lsv.uky.edu. Downbeat Nystagmus in a 7-Year-Old Girl with Epstein-Barr Virus-Associated Meningitis and Cerebellitis Digital Object Identifier (DOI) https://doi.org/10.1177/2329048X211000463 Notes/Citation Information Published in Child Neurology Open, v. 8. © The Author(s) 2021 This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). This article is available at UKnowledge: https://uknowledge.uky.edu/neurology_facpub/80 Case ReportDownbeat Nystagmus in a 7-Year-Old GirlWith Epstein-Barr Virus-AssociatedMeningitis and CerebellitisCameron Alexander Wade, BS1 , David Neil Toupin, MD2, Kyle Darpel, MD3,Kimberly Jones, MD2 , and Donita Lightner, MD4AbstractDownbeat nystagmus is a type of jerk nystagmus that may be seen in patients with lesions affecting the vestibulocerebellum. This isa case of a 7-year-old girl presenting with a history of fever, headache, and episodic vertigo with downbeat nystagmus. Thediagnosis of Epstein-Barr virus meningitis with acute cerebellitis was made by contrast magnetic resonance imaging, cerebrospinalfluid analysis, and serum Epstein-Barr virus titers. Contrast magnetic resonance imaging demonstrated enhancement of themeninges and inferior cerebellar folia, correlating with the neuroophthalmological symptom of downbeat nystagmus.Keywordscerebellum, children, encephalitis, meningitis, MRI, neuroimaging, pediatricReceived January 07, 2021. Received revised January 07, 2021. Accepted for publication February 01, 2021.CaseA 7-year-old female with no history of neurological or beha-vioral disease presented to the emergency department for 2 daysof transient vertiginous episodes that affected her ability towalk and resulted in vomiting. These episodes lasted only min-utes at a time and occurred predominantly in the morning,shortly after waking up. This acute presentation followed a2-week course of waxing and waning fever with headaches.Prior to presentation at our emergency department, the patientwas seen by an outpatient provider for her fever, where aSARS-nCoV-2 nasopharyngeal PCR test was negative. Historywas significant for multiple exposures, including multiple tickbites over the past month (with at least 1 that lasted >48 hours),freshwater swimming, and both parents with a recent history offever and headache preceding the onset of the patient’s febrilesymptoms. This occurred amidst the SARS-nCoV-2 outbreakin the United States.Initial examination in the evening revealed an afebrilepatient without lymphadenopathy or rash. Neurological exam-ination was normal, including intact extraocular movementswithout inducible vertigo or nystagmus, no ataxia or dysmetria,and negative Romberg sign. Both Kernig and Brudzinskimaneuvers were normal. Fundoscopic exam did not showswelling of the optic discs. Intake labs demonstrated elevatedtransaminases with an AST of 141 and ALT of 268, elevatedabsolute reactive lymphocyte count to 0.1 k/mL, and whiteblood cell count 8.37 k/mL. Repeat SARS-nCoV-2 PCR testingwas negative. Non-contrast CT of the head did not show acuteintracranial pathology.The patient was admitted for observation given her historyand lab abnormalities. The next morning on repeat neurologicexamination, during assessment of gait the patient abruptly saton the floor with complaints of “dizziness” and described atumbling rotation of her surroundings. During the episode,fixed gaze elicited conjugate downbeat nystagmus. She then1 University of Kentucky College of Medicine, Lexington, KY, USA2 Department of Child Neurology, University of Kentucky, Lexington, KY, USA3 Department of Neurology, University of Kentucky, Lexington, KY, USA4 Department of Child Neurology and Pediatric Oncology, University ofKentucky, Lexington, KY, USACorresponding Author:Cameron Alexander Wade, Kentucky Neuroscience Institute, 740S.Limestone, Lexington, KY 40536, USA.Email: cameron.wade@uky.eduChild Neurology OpenVolume 8: 1-4ª The Author(s) 2021Article reuse guidelines:sagepub.com/journals-permissionsDOI: 10.1177/2329048X211000463journals.sagepub.com/home/cnoCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License(https://creativecommons.org/licenses/by-nc/4.0/) which permits any use, reproduction and distribution of the work without further permission providedthe original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).had an episode of emesis, and her symptoms spontaneouslyresolved over the next half hour.Our differential for new onset episodic downbeat nystagmusincluded central processes affecting the cerebellum and brain-stem including structural disturbances (such as spaceoccupying lesions, cervicomedullary malformations, cerebellardegeneration, and episodic ataxias), infectious and/or toxicencephalitides, and cerebellar stroke. The history of outdooractivities and prolonged tick exposure raised suspicion forlocally endemic arthropod-borne encephalitis. SubsequentFigure 1. T2 FLAIR magnetic resonance imaging of the head on day 4 of vertigo symptoms (day 18 of subjective fevers and headache) includingpre-contrast (A, C, E), and post-contrast (B, D, F) demonstrating leptomeningeal enhancement within the cerebellar folia. Images presentedfrom superior (A, B) to inferior (E, F).2 Child Neurology Openwork-up included magnetic resonance imaging with and with-out contrast, magnetic resonance angiography, and cerebrosp-inal fluid analysis with cytopathology and infectious work-up.Contrast-enhanced magnetic resonance imaging of the brainrevealed diffuse leptomeningeal enhancement and parenchy-mal enhancement affecting the inferior cerebellar folia(Figure 1). Same-day cerebrospinal fluid studies (collected fol-lowing imaging) demonstrated elevated protein, but otherwisehad a negative PCR panel for common causes of meningoen-cephalitis (not including Epstein-Barr virus) (Table 1). As thepatient was afebrile and clinically improving without furtherepisodes, she was discharged on an empiric short course ofdoxycycline with cerebrospinal and serum antibodies pending(Table 1).Cerebrospinal fluid cytopathology showed lymphocyticpleocytosis and results of infectious work-up found serumEpstein-Barr virus IgM and IgG positivity (Table 1), confirm-ing the diagnosis of Epstein-Barr virus meningitis. The doxy-cycline was discontinued, and the patient had resolution of hersymptoms without other treatments.DiscussionTo maintain vertically deviated gaze, the vestibulocerebellumprovides positive feedback to the vertical neural integrator(interstitial nucleus of Cajal).1–3 If vestibulocerebellar feed-back to the vertical neural integrator is disrupted, there isresultant centripetal ocular drift followed by saccadic down-ward jerks to correct the gaze, i.e. downbeat nystagmus.4Clinically, downbeat nystagmus is most often idiopathic, butcommon causes include cerebellar degenerative disorders (epi-sodic ataxia, spinocerebellar ataxia), cerebellar ectopia, auto-immune encephalitites (such as anti-GAD65), or as amedication side effect (namely anticonvulsants).4–7 A similarreport of downbeat nystagmus has been described in the settingof Epstein-Barr virus cerebellitis, albeit in a teenage male.8 Inour patient, contrast-enhanced magnetic resonance imagingdemonstrated meningeal and cerebellar enhancement, provid-ing an imaging correlate for the finding of downbeat nystagmus[Figure 1].Epstein-Barr virus is a well-known cause of central nervoussystem infections and may present with a wide range of diseasepresentation including acute meningitis and/or encephalitis,acute cerebellar ataxia, cranial neuritis, and acute disseminatedmyelitis.9 In children, neurologic sequelae may be the herald-ing symptoms of infectious mononucleosis such as cranialnerve palsies, peripheral neuropathies, perceptual disturbances,and behavioral changes prior to the onset of other infectioussymptoms.10–12 In our case, it is likely that the history ofwaxing-and-waning fever with headache were the first symp-toms of Epstein-Barr virus infection, although at presentationher complaints were only subjective, with initial exam notsuggestive of a neurological pathology. Our patient improvedwith only supportive care (aside from the brief course ofTable 1. Infectious Work-Up Including Cerebrospinal Fluid and Serum Labs Demonstrating Borderline Low Cerebrospinal Fluid Glucose andElevated Protein, and Elevated Serum Epstein-Barr Virus IgM and IgG.Source Lab Result Reference RangeCerebrospinal Fluid Glucose 53* mg/dL 60-80 mg/dLProtein 63* mg/dL 15-45 mg/dLRed Blood Cell Count 0/microL 0-10/microLNucleated Cell Count 4/microL 0-10/microLGram Stain Few PMNs, no organisms N/ACytopathology Lymphocytic pleocytosis* N/ACulture No growth day 4 N/AMeningoencephalitis panel PCR: E. coli K1, H. flu, L. monocytogenes,N. meningitidis, S. agalactiae, S. pneumoniae, C. neoformans/gattii,Cytomegalovirus, Enterovirus, HHV 6, HSV 1, HSV 2, Humanparechovirus, and VZVNegative for all analytes N/AWest Nile Virus IgM Not Detected N/AWest Nile Virus IgG Not Detected N/ASerum Epstein-Barr Virus IgM 85.5 0.0-43.9 U/mLEpstein-Barr Virus IgG 86.9 0.0-21.9 U/mLCytomegalovirus PCR Not detected N/ARocky Mountain Spotted Fever IgM and IgG Not detected <1:64St. Louis Encephalitis IgM and IgG Not detected <1:16California Encephalitis IgM and IgG Not detected <1:16Eastern Equine Encephalitis IgM IgG Not detected <1:16Western Equine Encephalitis IgM and IgG Not detected <1:16West Nile Virus IgM and IgG Not detected <1:16Erlichia and Anaplasma PCR Not detected N/ABabesia PCR Not detected N/A“*” Indicates an Abnormal Lab Finding.Wade et al 3empiric doxycycline), reflecting historically reported cases ofEpstein-Barr virus infection with neurologic stigmata.11ConclusionThis case demonstrates the neuroophthalmological conse-quence of vestibulocerebellar dysfunction through the findingof downbeat nystagmus in a patient with Epstein-Barr virusinfection affecting the inferior cerebellar folia. Epstein-Barrvirus infection is a known cause of neurologic symptoms inchildren and can be diagnosed with the combination ofcontrast-enhanced magnetic resonance imaging and serology.Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect tothe research, authorship, and/or publication of this article.FundingThe author(s) received no financial support for the research, author-ship, and/or publication of this article.ORCID iDsCameron Alexander Wade https://orcid.org/0000-0002-1141-0705Kimberly Jones https://orcid.org/0000-0002-4256-2429References1. Beh SC, Frohman TC, Frohman EM. Cerebellar control of eyemovements. J Neuroophthalmol. 2017;37(1):87-98. doi:10.1097/WNO.00000000000004562. Sanchez K, Rowe FJ. Role of neural integrators in oculomotorsystems: a systematic narrative literature review. Acta Ophthal-mol. 2018;96(2):e111-e118. doi:10.1111/aos.133073. Leigh RJa, Zee DSa. The Neurology of Eye Movements. 5th ed.Oxford University Press; 2015.4. Beh SC, Frohman TC, Frohman EM. Neuro-ophthalmic manifes-tations of cerebellar disease. Neurol Clin. 2014;32(4):1009-1080.doi:10.1016/j.ncl.2014.07.0025. Osborne D, Theodorou M, Lee H, et al. Supranuclear eye move-ments and nystagmus in children: a review of the literature andguide to clinical examination, interpretation of findings and age-appropriate norms. Eye (Lond). 2019;33(2):261-273. doi:10.1038/s41433-018-0216-y6. Halmagyi GM, Rudge P, Gresty MA, Sanders MD. Downbeatingnystagmus. A review of 62 cases. Arch Neurol. 1983;40(13):777-784. doi:10.1001/archneur.40.13.7777. Vale TC, Pedroso JL, Alquéres RA, Dutra LA, Barsottini OG.Spontaneous downbeat nystagmus as a clue for the diagnosis ofataxia associated with anti-GAD antibodies. J Neurol Sci. 2015;359(1-2):21-23. doi:10.1016/j.jns.2015.10.0248. Yoshimoto Y, Koyama S. A case of acquired nystagmus alternansassociated with acute cerebellitis. Acta Otolaryngol Suppl. 1991;481:371-373.9. Fujimoto H, Asaoka K, Imaizumi T, Ayabe M, Shoji H, Kaji M.Epstein-Barr virus infections of the central nervous system. InternMed. 2003;42(1):33-40. doi:10.2169/internalmedicine.42.3310. Häusler M, Ramaekers VT, Doenges M, Schweizer K, Ritter K,Schaade L. Neurological complications of acute and persistentEpstein-Barr virus infection in paediatric patients. J Med Virol.2002;68(2):253-263. doi:10.1002/jmv.1020111. Connelly KP, DeWitt LD. Neurologic complications of infectiousmononucleosis. Pediatr Neurol. 1994;10(3):181-184. doi:10.1016/0887-8994(94)90021-312. Hashemian S, Ashrafzadeh F, Akhondian J, Beiraghi Toosi M.Epstein-Barr virus encephalitis: a case report. Iran J ChildNeurol. 2015;9(1):107-110.4 Child Neurology Open

Downbeat Nystagmus in a 7-Year-Old Girl with Epstein-Barr Virus-Associated Meningitis and Cerebellitis

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Downbeat Nystagmus in a 7-Year-Old Girl with Epstein-Barr Virus-Associated Meningitis and Cerebellitis

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