Abstract
Brainstem encephalitis (BE) is an uncommon condition. We sought to characterize clinical presentations, etiologies, response to treatment, and predictors of outcome. We performed a retrospective review of non–HIV infected patients diagnosed with BE at Johns Hopkins Hospital (January 1997–April 2010). We characterized clinical and paraclinical features, and used regression models to assess associations with poor outcome. BE was diagnosed in 81 patients. An etiology was identified in 58 of 81 (71.6 %) of cases, most of which were confirmed or probable inflammatory/autoimmune conditions. Of the remaining 23 cases in which a specific diagnosis remained undefined, clinical presentation, CSF, neuroimaging studies, and outcomes were similar to the inflammatory/autoimmune group. Brain biopsy identified a specific diagnosis in 7 of 14 patients (50 %). Fifteen patients (18.5 %) either died or had a poor outcome. In multivariate logistic regression models, a higher CSF protein (per 5 mg/dl, OR = 1.11, 95 % CI: 1.03–1.20), a higher CSF glucose (per 5 mg/dl, OR = 1.36, 95 % CI: 1.09–1.70), and higher serum glucose (per 5 mg/dl, OR = 1.27, 95 % CI: 1.06–1.52) were independently associated with increased odds of poor outcome. Inflammatory and non-infectious conditions accounted for most cases of BE. Higher CSF protein and glucose were independently associated with poor outcome. In immunocompetent patients with BE of undefined etiology despite extensive investigation, a trial of immunosuppressive treatment may be warranted, though deterioration clinically or on magnetic resonance imaging should prompt a brain biopsy.
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References
Glaser CA, Honarmand S, Anderson LJ et al (2006) Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis 43(12):1565–1577
Dalmau J, Graus F, Villarejo A et al (2004) Clinical analysis of anti-Ma2-associated encephalitis. Brain 127(Pt 8):1831–1844
Ito M, Kuwabara S, Odaka M et al (2008) Bickerstaff’s brainstem encephalitis and Fisher syndrome form a continuous spectrum: clinical analysis of 581 cases. J Neurol 255(5):674–682
Mylonakis E, Hohmann EL, Calderwood SB (1998) Central nervous system infection with Listeria monocytogenes. 33 years’ experience at a general hospital and review of 776 episodes from the literature. Medicine (Baltimore) 77(5):313–336
Moragas M, Martínez-Yélamos S, Majós C, Fernández-Viladrich P, Rubio F, Arbizu T (2011) Rhombencephalitis: a series of 97 patients. Medicine (Baltimore) 90(4):256–261
Krupp LB, Banwell B, Tenembaum S, Group IPMS (2007) Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 68(16 Suppl 2):S7–12
Krupp LB, Tardieu M, Amato MP et al (2013) International pediatric multiple sclerosis study group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler [Epub ahead of print]
Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302
Sejvar JJ, Kohl KS, Bilynsky R et al (2007) Encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine 25(31):5771–5792
Schwarz S, Mohr A, Knauth M, Wildemann B, Storch-Hagenlocher B (2001) Acute disseminated encephalomyelitis: a follow-up study of 40 adult patients. Neurology 56(10):1313–1318
Domingues RB, Fink MC, Tsanaclis AM et al (1998) Diagnosis of herpes simplex encephalitis by magnetic resonance imaging and polymerase chain reaction assay of cerebrospinal fluid. J Neurol Sci 157(2):148–153
Tan IL, McArthur JC, Venkatesan A, Nath A (2012) Atypical manifestations and poor outcome of herpes simplex encephalitis in the immunocompromised. Neurology 79(21):2125–2132
Wasay M, Mekan SF, Khelaeni B et al (2005) Extra temporal involvement in herpes simplex encephalitis. Eur J Neurol 12(6):475–479
Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC (2001) Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 32(10):2426–2432
Lackner P, Guengoer E, Beer R et al (2010) IgG-index predicts neurological morbidity in patients with infectious central nervous system diseases. BMC Infect Dis 10:202
Kennedy CR, Duffy SW, Smith R, Robinson RO (1987) Clinical predictors of outcome in encephalitis. Arch Dis Child 62(11):1156–1162
Mailles A, De Broucker T, Costanzo P et al (2012) Long-term outcome of patients presenting with acute infectious encephalitis of various causes in France. Clin Infect Dis 54(10):1455–1464
Rachinger W, Grau S, Holtmannspotter M, Herms J, Tonn JC, Kreth FW (2009) Serial stereotactic biopsy of brainstem lesions in adults improves diagnostic accuracy compared with MRI only. J Neurol Neurosurg Psychiatry 80(10):1134–1139
Fontaine D, Dormont D, Hasboun D et al (2000) Magnetic resonance-guided stereotactic biopsies: results in 100 consecutive cases. Acta Neurochir (Wien) 142(3):249–255 (discussion 255–246)
Apuzzo ML, Sabshin JK (1983) Computed tomographic guidance stereotaxis in the management of intracranial mass lesions. Neurosurgery 12(3):277–285
Samadani U, Judy KD (2003) Stereotactic brainstem biopsy is indicated for the diagnosis of a vast array of brainstem pathology. Stereotact Funct Neurosurg 81(1–4):5–9
Pittock SJ, Debruyne J, Krecke KN et al (2010) Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain 133(9):2626–2634
Granerod J, Ambrose HE, Davies NW et al (2010) Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis 10(12):835–844
Huppatz C, Durrheim DN, Levi C et al (2009) Etiology of encephalitis in Australia, 1990–2007. Emerg Infect Dis 15(9):1359–1365
Mailles A, Stahl JP (2009) Infectious encephalitis in france in 2007: a national prospective study. Clin Infect Dis 49(12):1838–1847
Schmidt A, Buhler R, Muhlemann K, Hess CW, Tauber MG (2011) Long-term outcome of acute encephalitis of unknown aetiology in adults. Clin Microbiol Infect 17(4):621–626
Granerod J, Tam CC, Crowcroft NS, Davies NW, Borchert M, Thomas SL (2010) Challenge of the unknown. A systematic review of acute encephalitis in non-outbreak situations. Neurology 75(10):924–932
Acknowledgments
Financial disclosure: Ellen M. Mowry: Funding NIH K23NS067055; National MS Society RG4407A2. Receipt of free study medication from Teva Neurological. Justin C. McArthur: Grants from NIH, Biogen-Idec, payment from lectures, speakers’ bureau in various universities, book royalties, stock option from Gliamed. Avindra Nath: Consultant to Biogen Idec and Diogenix. Arun Venkatesan: Grants from NIH, HHMI, Maryland Stem Cell Research Foundation, National Multiple Sclerosis Society. Ik Lin Tan, Sonya Steele, Carlos Pardo-Villamizar report no financial disclosure.
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Tan, I.L., Mowry, E.M., Steele, S.U. et al. Brainstem encephalitis: etiologies, treatment, and predictors of outcome. J Neurol 260, 2312–2319 (2013). https://doi.org/10.1007/s00415-013-6986-z
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DOI: https://doi.org/10.1007/s00415-013-6986-z