Citations

Abstract Background The Venereal Disease Research Laboratory (VDRL) test performed in cerebrospinal fluid (CSF) is considered highly specific for the diagnosis of neurosyphilis, but algorithms to diagnose neurosyphilis require positive syphilis serologic testing prior to obtaining CSF-VDRL. Inappropriate use of diagnostic tests depletes healthcare resources, and contributes to rising healthcare expenditures. CSF-VDRL has historically been improperly utilized; however there is no recent evaluation of its use in clinical practice. We aimed to quantify rates of appropriate CSF-VDRL testing, determine the CSF-VDRL false-positivity rate and describe causes of false-positive CSF-VDRL reactivity. Methods In this retrospective cohort study of three Mayo Clinic sites (Rochester, MN, Jacksonville, FL, and Scottsdale, AZ), we measured the rate of appropriate CSF-VDRL test utilization in patients with negative testing from January 1, 2011 to December 31, 2017. We then identified all patients with positive CSF-VDRL testing from January 1, 1994 to February 28, 2018, characterized true- and false-positive rates and described causes of CSF-VDRL false-positivity. Results Among 8,553 persons with negative CSF-VDRL results, testing was unnecessarily ordered in 8,399 (98.2%). The word “syphilis” or “neurosyphilis” appeared in the notes of only 1,184 (13.8%) individuals with a negative CSF-VDRL result. From January 1994 through February 2018, 33,933 CSF-VDRL tests were performed on 32,626 individual patients. Among 60 positive CSF-VDRL results, 41 (68.3%) were true-positives, 2 (3.3%) were indeterminate, and 17 (28.3%) were false-positives. Every patient with true-positive CSF-VDRL had positive serologic syphilis testing prior to CSF testing. All patients with false-positive CSF-VDRL results were inappropriately tested. Neoplastic meningitis was a common cause of false-positive CSF-VDRL results. Conclusion This is the first study in decades to review CSF-VDRL utilization for the diagnosis of neurosyphilis. Inappropriate use of CSF-VDRL testing for diagnosis of neurosyphilis remains problematic in clinical practice. Following recommended testing algorithms would prevent unnecessary testing, preserve resources, and minimize false-positive results. Disclosures All Authors: No reported disclosures

Abstract Objectives To describe CSF‐defined neuronal intermediate filament (NIF) autoimmunity. Methods NIF‐IgG CSF‐positive patients (41, 0.03% of 118599 tested, 1996–2019) were included (serum was neither sensitive nor specific). Criteria‐based patient NIF‐IgG staining of brain and myenteric NIFs was detected by indirect immunofluorescence assay (IFA); NIF‐specificity was confirmed by cell‐based assays (CBAs, alpha internexin, neurofilament light [NF‐L]), heavy‐[NF‐H] chain). Results Sixty‐one percent of 41 patients were men, median age, 61 years (range, 21–88). Syndromes were encephalopathy predominant (23), cerebellar ataxia predominant (11), or myeloradiculoneuropathies (7). MRI abnormalities (T2 hyperintensities of brain, spinal cord white matter tracts. and peripheral nerve axons) and neurophysiologic testing (EEG, EMG, evoked potentials) co‐localized with clinical neurological phenotypes (multifocal in 29%). Thirty patients (73%) had ≥ 1 immunological perturbation: cancer (paraneoplastic), 22; systemic infection (parainfectious [including ehrlichosis, 3] or HIV), 7; checkpoint‐inhibitor cancer immunotherapy, 4; other, 5. Cancers were as follows: neuroendocrine‐lineage carcinomas, 12 (small cell, 6; Merkel cell, 5; pancreatic, 1 [11/12 had NF‐L‐IgG detected, versus 8/29 others, P = 0.0005]) and other, 11. Onset was predominantly subacute (92%) and accompanied by inflammatory CSF (75%), and immunotherapy response (77%). In contrast, CSF controls (15684 total) demonstrated NIF‐IgG negativity (100% of test validation controls), and low frequencies of autoimmune diagnoses (20% of consecutively referred clinical specimens) and neuroendocrine‐lineage carcinoma diagnosis (3.1% vs. 30% of NIF cases), P < 0.0001. Median NF‐L protein concentration was higher in 8 NF‐L‐IgG‐positive patients (median, 6718 ng/L) than 16 controls. Interpretation Neurological autoimmunity, defined by CSF‐detected NIF‐IgGs, represents a continuum of treatable axonopathies, sometimes paraneoplastic or parainfectious.

Shotgun metagenomic sequencing can detect nucleic acids from bacteria, fungi, viruses, and/or parasites in clinical specimens; however, little data exist to guide its optimal application to clinical practice. We retrospectively reviewed results of shotgun metagenomic sequencing testing requested on cerebrospinal fluid samples submitted to an outside reference laboratory from December 2017 through December 2019. Of the 53 samples from Mayo Clinic patients, 47 were requested by neurologists, with infectious diseases consultation in 23 cases.

‘Query encephalitis’ is a common neurological consultation in hospitalised patients. Identifying the syndrome is only part of the puzzle. Although historically encephalitis has been almost synonymous with infection, we increasingly recognise parainfectious or postinfectious as well as other immune-mediated causes. We must also distinguish encephalitis from other causes of encephalopathy, including systemic infection, metabolic derangements, toxins, inherited metabolic disorders, hypoxia, trauma and vasculopathies. Here, we review the most important differential diagnoses (mimics) of patients presenting with an encephalitic syndrome and highlight some unusual presentations (chameleons) of infectious encephalitis.

Introduction: Elsberg syndrome (ES) is a rarely recognized cause of cauda equina syndrome and lower thoracic myelitis, mainly linked to reactivation, or occasionally primary, infection with herpes simplex virus type 2. West Nile virus neuroinvasive disease is rarely considered in the differential diagnosis of patients with ES. Case Report: A 63-year-old man with pancreatic cancer in remission and polymyalgia rheumatica on low-dose prednisone presented with a 10-day history of low-back pain and a viral-type illness with low-grade fever, nausea, and vomiting. Days later, he developed left leg monoparesis, neurogenic bladder, and bowel. Magnetic resonance imaging of the lumbar spine revealed a hyperintense signal abnormality within the central spinal cord and conus medullaris with mild swelling of the conus. Cells, proteins, and glucose in cerebrospinal fluid were 67/mm 3 , 70 mg/dL, and 58 mg/dL, respectively. Serology was positive for West Nile virus IgM. Nerve conduction studies and electromyography showed an acute motor neurogenic process affecting left lumbosacral segments. Conclusions: West Nile virus neuroinvasive disease is an uncommon condition that should be considered in patients with ES. Determining the etiology of ES in the acute setting may avoid unnecessary diagnostic investigations and treatments.

Background: Episodic hypothermia (EH) can occur in multiple sclerosis (MS). The putative mechanism is impairment of thermoregulation due to a presumed demyelinating hypothalamic lesion. Objective: To describe a cohort of patients with MS, who developed EH. Methods: Patients were identified through review of the Mayo Clinic electronic medical record (1996 to July 2015). Search terms were [multiple sclerosis] or [MS] within the diagnoses field and [hypothermia] within any field. We reviewed records for accuracy of diagnoses and abstracted relevant data. Magnetic resonance imaging (MRI) was reviewed for presence of hypothalamic lesions. Results: Of 156 patients, 34 had concurrent MS and hypothermia. Thirty-two (94%) had progressive disease at EH onset. Median MS duration was 19.9 years, and median expanded disability status scale (EDSS) was 8.0. Most patients presented with alterations in consciousness. Infection was suspected as the precipitating factor in 19 (56%), but clinically/laboratory supported in only 9 (28%). MRI lesions were evident within the hypothalamus in only 4 (14%). Conclusion: EH occurs predominantly in patients with advanced secondary progressive MS. The major manifestation is altered consciousness. Infection is often suspected as causal, but infrequently confirmed. Although commonly implicated, hypothalamic lesions were rarely evident on MRI and were absent in two post-mortem evaluations.