Elsberg syndrome

Objective: Elsberg syndrome (ES) is an established but often unrecognized cause of acute lumbosacral radiculitis with myelitis related to recent herpes virus infection. We defined ES, determined its frequency in patients with cauda equina syndrome (CES) with myelitis, and evaluated its clinical, radiologic, and microbiologic features and outcomes. Methods:We searched theMayo Clinic medical records for ES and subsequently for combinations of index terms to identify patients with suspected CES and myelitis. Results: Our search yielded 30 patients, 2 diagnosed with ES and an additional 28 with clinical or radiologic evidence of CES retrospectively suspected of having ES. We classified patients in 5 groups according to diagnostic certainty. MRI and EMG confirmed that 2 had only myelitis, 5 only radiculitis, and 16 both. Two had preceding sacral herpes infection and 1 oral herpes simplex. Spinal cord lesions were commonly multiple, discontinuous, not expansile, and centrally or ventrally positioned. Lesions generally spared the distal conus. Nerve root enhancement was occasionally prominent and was smooth rather than nodular. Lymphocytic CSF pleocytosis was common. Thirteen patients (43%) had viral isolation studies, which were commonly delayed; the delay may have accounted for the low rate of viral detection. Acyclovir was administered to 6 patients. Most patients recovered with sequelae; 1 patient experienced encephalomyelitis and died. Conclusion: ES is a definable condition likely responsible for 10% of patients with combined CES and myelitis. Radiologic findings are not entirely specific but may help in differentiating ES from some competing diagnostic considerations. We propose criteria to facilitate diagnosis. Neurol Neuroimmunol Neuroinflamm 2017;4:e355; doi: 10.1212/NXI.0000000000000355 GLOSSARY CES 5 cauda equina syndrome; ES5 Elsberg syndrome; HSV2 5 herpes simplex virus 2; ICD 5 International Classification of Disease; NMO 5 neuromyelitis optica; VZV 5 varicella zoster virus. Elsberg syndrome (ES) is a presumed infectious syndrome consisting of acute or subacute bilateral lumbosacral radiculitis, often accompanied by myelitis confined to the lower spinal cord, and is frequently a manifestation of reactivation, or occasionally, primary herpes simplex virus 2 (HSV2) infection. Clinicians often do not consider ES in the differential diagnosis of acute cauda equina syndrome (CES) and do not perform appropriate testing for HSV infection in a timely way to facilitate definitive diagnosis. However, especially when accompanied by clinical or radiologic findings of myelitis, ES is not a rare cause of CES. ES has been the subject of case reports and small series, the largest of which included 17 patients. A formal case definition that defines the minimum criteria to diagnose this syndrome and identifies exclusionary findings that suggest alternative diagnoses does not exist. Sarcoidosis, lymphoma, other neoplasms, and vascular disorders (dural arteriovenous fistula) may mimic ES and are in the differential diagnosis. From the Departments of Neurology (F.S., E.P.F., M.T., B.G.W.), and Neuroradiology (T.J.K.), Mayo Clinic, Rochester, MN; and Neuroimaging Research Unit (F.S.), Department of Neurology, San Raffaele Scientific Institute and University, Milan, Italy. Funding information and disclosures are provided at the end of the article. Go to Neurology.org/nn for full disclosure forms. The Article Processing Charge was funded by the authors. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Neurology.org/nn Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. 1 We conducted a retrospective review of lumbosacral myeloradiculitis evaluated at the Mayo Clinic to assess the frequency of ES, determined retrospectively as well as prospectively. Among cases who did not have other established diagnoses and who met certain minimum criteria, we reviewed Mayo clinical records to classify the level of diagnostic certainty using a scheme we derived based on a review of the medical literature (table 1). We identified clinical, demographic, and radiologic findings of ES, concentrating on distinction from other causes of lower thoracic/conus myelitis. METHODS We performed a retrospective review of Mayo electronic medical records from 2000 to March 2016 interrogating for the term “Elsberg” in the history, examination, review of systems, impression, and final diagnosis and thereby identified only 4 patients. To find unrecognized cases, we searched again for a combination of key terms common to those of the 4 ES cases in patients evaluated in the neurology, urology, gynecology, or infectious disease departments who had both myelitis and radiculitis (figure 1). After testing several possible combinations of terms, we selected patients identified by at least 1 of 4 searches of the medical records, components of which are highlighted in flow chart in figure 1, and thereby identified 1,035 patients. We excluded patients with an International Classification of Disease (ICD) diagnosis of MS or neuromyelitis optica (NMO), reducing the cohort to 837 subjects. Exclusion of cases without terms referring to urinary retention or sacral sensory symptoms further reduced the cohort to 337 subjects. A review of individual clinical records identified 213 patients with other definitive alternative diagnoses (table 2). Subsequently, we conducted a detailed review of clinical records to confirm the presence of urinary retention or other sacral symptoms (saddle anesthesia, paresthesias, neuralgic pain, constipation, impotence, urinary incontinence, and fecal incontinence) yielding 49 patients who were strongly suspected to have ES (figure 1). We abstracted their demographic characteristics, neurologic examination findings, CSF, viral, EMG, and MRI results from clinical records. The Mayo Clinic Institutional Review Board granted approval to review retrospectively obtained patient clinical information. We defined diagnostic criteria for ES with 5 levels of diagnostic certainty based on the review of the medical literature: laboratory-supported definite, clinically definite, clinically probable, clinically possible, and excluded (table 1). Radiculitis, defined either clinically (table 1, A1) or by MRI and/or electrophysiologic evidence (table 1, A2), was required to establish a diagnosis of ES. A neurologist (B.G.W.) categorized each case according to these criteria and with special attention to potential alternative diagnoses. A neuroradiologist (T.K.) reviewed abnormal radiology to confirm and further characterize the abnormalities in each case and to consider whether there were unique or characteristic radiologic features of ES after the review of the entire cohort. We report the frequencies of key clinical and radiologic features and summarize distinctive radiologic features. RESULTS Forty-nine patients satisfied the inclusion and exclusion criteria. Clinical and MRI findings are summarized in table 3 and the clinical course in table 4. Three patients met criteria for laboratorysupported definite, 9 for clinically definite, 10 for clinically probable, and 8 for clinically possible ES. Nineteen patients were excluded, 16 (84%) because of exclusionary criteria (table 1) and 3 (16%) because they failed to satisfy any of the established levels of diagnostic certainty (table 1), including 2 of the 4 diagnosed with ES at the time of their clinical evaluation but with insufficient information to confirm the diagnosis. Based on MRI and EMG, available in 29 and 21 cases respectively, 2 patients had only myelitis, 5 only radiculitis, and 16 both. Only 2 included patients had been diagnosed with ES at the time of their clinical evaluation. Of the 30 patients with a diagnosis of lab-supported, definite, probable, or possible ES, 24 (80%) were men and 6 women (20%) and their median age was 53 years. Five patients (17%) experienced prodromal symptoms, including fever, headache, Table 1 Elsberg syndrome according to diagnostic certainty Categories Criteria No. of patients 1. Laboratory-supported definite (A1 OR A2) AND B5 3 2. Clinically definite A1 OR A2; B1 AND two of B2–B4; B1 and B2 (if concomitant) 9 3. Clinically probable A1 OR A2; B1 AND one of B2–B4 10 4. Clinically possible A1 OR A2; one of B1–B4 8 5. Excluded Neither of A1 nor of A2; any of D1–D3 19