Virginia Research Day 2021

Neuroborreliosis resulting in CIDP Kenneth Brand, MD Farhan Shah, MD Asad Choudhury, MD, Gretchen Junko, DO Ryan Curfiss, DO JoBeth Bingham, OMS-4

Discussion

Introduction

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Borrelia Burgdorferi is a spirochete responsible for Lyme Disease, characterized by three stages, the third of which has primarily neurological manifestations. At the same time, Borrelia has been implicated in variants of Guillain-Barré syndrome, notably Chronic Inflammatory Demyelinating Polyradiculopathy (CIDP), a peripheral nerve pathology.

Epidemiology

Treatment

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CIDP’s estimated incidence is 0.7 to 1.6 cases per 100,000 persons per year, with an estimated prevalence of 4.8 to 8.9 cases per 100,000 persons 1,2 . Studies on the epidemiology of Neuroborreliosis are limited, but estimated to be at 10/100,000 inhabitants/year in affected areas 3 . Neuroborreliosis presents as a meningitis, cranial neuritis, and/or radiculoneuritis secondary to the spirochete Borrelia Burgdorferi, transmitted by the Ixodes Scapularis tick, in the final stage of Lyme disease 4 . Meningeal seeding of spirochetes leads to a lymphocytic meningitis or encephalomyelitis, with a peripheral multifocal axonal process secondary to an active infection 5 CIDP is a Chronic Inflammatory Demyelinating Polyradiculopathy due to humoral or cell-mediated responses to axonal, myelin, or schwann cell antigens. This is usually secondary to an infection, but can be, rarely, due to medications as well. CIDP progresses in a span of time greater than eight weeks. 6 The diagnosis relies on clinical suspicion and laboratory testing. The patient should have a possible exposure to an Ixodes tick bite, evidence of nervous system involvement, and serologies that support the diagnosis. Facial nerve palsy, radiculoneuritis, and/or central nervous system involvement presenting as a lymphocytic meningitis or encephalomyelitis should raise suspicion. Serologic testing should include antibodies to B. Burgdorfei via ELISA or Western Blot. CSF studies should be performed, with typical findings including lymphocytic pleocytosis, modestly elevated protein of <2-3g/L, and a normal glucose concentration. CSF antibody testing is insufficient to rule in or out the diagnosis 7 . The diagnosis of CIDP is made in the setting of clinical suspicion and confirmed by electrodiagnostic tests showing peripheral nerve demyelination. Criteria for the diagnosis of typical CIDP includes a chronic, progressive weakness and sensory dysfunction that is symmetrical, and absent/reduced deep tendon reflexes in all extremities. Lumbar puncture evaluation usually shows an albuminocytologic dissociation with elevated CSF protein >45mg/dL with normal white blood cell count 8 . Pathophysiology Diagnosis Neuroborreliosis CIDP

Neuroborreliosis as a late stage complication of Lyme Disease can be treated with oral or parenteral antibiotics. Of the oral agents, doxycycline has the greatest CNS penetration, and is recommended as first line treatment in patients who do not have encephalitis or allergies to it. In those for whom parenteral treatment is indicated, expert opinion prefers the use of Ceftriaxone (2g/day) for two to four weeks 9 . CIDP as a demyelinating disorder is treated primarily with steroids and IVIG, the latter being preferred in patients who have less mild symptoms. IVIG is typically 2g/kg over five days with repeats every three weeks for at least two months 10 .

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Case Report

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A 51 year-old female with a past medical history of tick bites presented with fever, altered mental status, rash, and worsening lower extremity dysesthesias with ataxia 10 days after beginning outpatient IV Ceftriaxone treatment for Lyme Disease via a Peripherally Inserted Central Catheter. The patient stated she lived by a lake in the woods, and has often had to remove ticks from her body. Upon the patient’s arrival to the ED, her temperature was 103 ° Fahrenheit, and her rash had developed as erythematous, macular, morbilliform, and pruritic; it was distributed from her head down to her waist without evidence of bullae, desquamation, or pus. She was alert and oriented to person, place, time, and location, though had poor insight and answered questions with inappropriate affect. Electromyographic and Nerve Conduction Studies collected the previous week had been negative. Imaging with MRI had failed to reveal any acute demyelinating processes or radiographic evidence of infection. However, CSF studies revealed specific antibodies to Borrelia, namely: p93 p41, p39, p28, and p18. CSF analysis was suggestive of albuminocytologic dissociation with WBC count of 0/uL, Protein count 294 mg/dL, albumin 225 mg/dL, glucose 68 mg/dL, and RBC’s 0/ uL. The PICC tip was removed (cultured negative), Ceftriaxone was switched to oral Doxycycline, and the patient’s fever subsided. She was started on five rounds of IVIG, which resulted in symptomatic amelioration of her lower extremity dysesthesias and gait, diagnosed as CIDP secondary to Neuroborreliosis.

Figures

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References

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Laughlin RS, Dyck PJ, Melton LD 3rd, Leibson C, Ransom J. Incidence and prevalence of CIDP and the association of diabetes mellitus. Neurology. 2009;73(1):39-4 doi: 10.1212/WNL.0b013e3181aaea47. Rajabally YA, Simpson BS, Beri S, Bankart J, Gosalakkal JA. Epidemiologic variability of chronic inflammatory demyelinating polyneuropathy with different diagnostic criteria: study of a UK population. Muscle Nerve. 2009;39(4):432-438. doi: 10.1002/mus.21206. Lyme neuroborreliosis epidemiology in Sweden 2010 to 2014: clinical microbiology laboratories are a better data source than the hospital discharge diagnosis registerDahl, Viktor and Wisell, Karin T and Giske, Christian G and Tegnell, Anders and Wallensten, Anders, Eurosurveillance, 24, 1800453 (2019), https://doi.org/10.2807/1560-7917.ES.2019.24.20.1800453 Reik L, Steere AC, Bartenhagen NH, Shope RE, Malawista SE. Neurologic abnormalities of Lyme disease. Medicine (Baltimore). 1979 Jul;58(4):281-94. doi: 10.1097/00005792-197907000-00001. PMID: 449663. Luft BJ, Steinman CR, Neimark HC, Muralidhar B, Rush T, Finkel MF, Kunkel M, Dattwyler RJ. Invasion of the central nervous system by Borrelia burgdorferi in acute disseminated infection. JAMA. 1992 Mar 11;267(10):1364-7. Erratum in: JAMA 1992 Aug 19;268(7):872. PMID: 1740859. Ruts L, van Koningsveld R, van Doorn PA. Distinguishing acute-onset CIDP from Guillain-Barré syndrome with treatment related fluctuations. Neurology. 2005 Jul 12;65(1):138-40. doi: 10.1212/01.wnl.0000167549.09664.b8. PMID: 16009902 European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society – First Revision Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis. 1999 Aug;180(2):377-83. doi: 10.1086/314860. PMID: 10395852. https://www.cdc.gov/lyme/diagnosistesting/index.html

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This research was supported (in whole or in part) by HCA and/or an HCA affiliated entity. The views expressed in this publication represent those of the author(s) do not necessarily represent the official views of HCA or any of its affiliated entities.

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