SHORT COMMUNICATION Diagnosing acute encephalitis in patients with hematological disorders: caveats and pitfalls Elisa Vegezzi 1,2 & Giulia Berzero 1 & Desiree Barbetta 3 & Anna Amelia Colombo 4 & Oscar Borsani 4,5 & Paolo Bernasconi 4,5 & Francesca Compagno 6 & Marco Zecca 6 & Giulia Campanini 7 & Anna Simoncelli 8 & Matteo Paoletti 9 & Anna Pichiecchio 9,2 & Fausto Baldanti 7,10 & Enrico Brunetti 3,10 & Enrico Marchioni 1 Received: 8 July 2019 /Revised: 27 September 2019 /Accepted: 10 November 2019 # Journal of NeuroVirology, Inc. 2019 Abstract The aim of this study was to review the quality of the diagnostic work-up for acute encephalitis carried out at our center in a cohort of patients with hematological disorders. Our data showed substantial heterogeneity in investigating patients. Not all patients had their CSF tested for viruses commonly responsible for encephalitis in immunocompetent individuals (e.g., VZV, enterovirus). A blood sample for the calculation of the CSF/blood replication ratio was collected in 74% of cases. CSF cultures and immunophenotyping of CSF cells were performed in 77% and 21% of patients, respectively. A multidisciplinary consensus is needed to improve current guidelines and standardize diagnostic protocols. Keywords Acute encephalitis . Immunocompromised patients . Hematological disorders . Hematopoietic stem cell transplantation . Diagnosis Introduction Patients affected by hematological disorders, and especially hematopoietic stem cell transplant recipients, have a lifelong risk of developing neurological complications (Antonini et al. 1998; Azik et al. 2014; Colombo et al. 2017; Dowling et al. 2018; Maffini et al. 2017; Kang et al. 2015; Pruitt et al. 2013; Pruitt 2018). Despite their low incidence (Antonini et al. 1998; Colombo et al. 2017; Siegal et al. 2007; Guerrero et al. 1999), neurological complications are associated with high morbidi- ty, and early diagnosis and treatment are essential to reduce the risk of permanent sequelae. Among neurological complica- tions, acute encephalitis is one of the most fearful due to its high short-term mortality. Diagnosing this condition can be challenging in patients with hematological disorders, as they are exposed to uncommon pathogens, they can have atypical clinical presentations or lack inflammatory findings in the CSF (Saylor et al. 2015; Sonneville et al. 2017). Whereas clear Elisa Vegezzi and Giulia Berzero contributed equally to the manuscript. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13365-019-00817-z) contains supplementary material, which is available to authorized users. * Enrico Marchioni enrico.marchioni@mondino.it 1 Neuroncology Unit, IRCCS Mondino Foundation, Pavia, Italy 2 Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy 3 Infectious and Tropical Diseases Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 4 Bone Marrow Transplantation Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 5 Department of Molecular Medicine, University of Pavia, Pavia, Italy 6 Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 7 Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 8 Diagnostic Radiology, Interventional Radiology and Neuroradiology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy 9 Neuroradiology Unit, IRCCS Mondino Foundation, Pavia, Italy 10 Department of Clinical, Surgical, Diagnostic and Paediatric Sciences, University of Pavia, Pavia, Italy Journal of NeuroVirology https://doi.org/10.1007/s13365-019-00817-z