Journal of Neurology

, Volume 256, Issue 3, pp 396–404

Contemporary Encephalitis Lethargica: Phenotype, laboratory findings and treatment outcomes

  • Robert Lopez-Alberola
  • Michael Georgiou
  • George N. Sfakianakis
  • Carlos Singer
  • Spyridon Papapetropoulos



Encephalitis lethargica (EL) is a CNS disorder that manifests with lethargy sleep cycle disturbances, extrapyramidal symptomatology, neuropsychiatric manifestations, ocular features and cardio-respiratory abnormalities. Although there have been no reported outbreaks of EL recently, a number of reports show that cases of EL are still encountered regularly. Against this background we conducted a study aiming to elucidate the clinical characteristics, describe laboratory/ neuroimaging findings (MRI, PET) and present treatment options and outcomes in sporadic EL.


Patients were diagnosed over a period of 3 years using proposed diagnostic criteria. Extensive laboratory and imaging tests were performed for exclusion of other causes. Anti-neuronal antibodies against human basal ganglia were detected with western immunoblotting and 18F-FDG PET imaging was performed. Selected cases were videotaped.


Our patients (M/F: 5/3) ranged from 2–28 years (mean 9.3 ± 9.5). Encephalopathy, sleep disturbances and extrapyramidal symptoms were present in all cases. Laboratory investigations revealed CSF leukocytosis in 5/8 patients and anti-BG Ab in 4/7 patients. MRIs revealed structural abnormalities in 7/8 cases. 18F-FDG PET showed basal ganglionic hypermetabolism in 4/7 patients. Treatment approaches included immunomodulating and symptomatic therapies. We report no mortality from EL in our series.


There seems to be little doubt that cases of EL still occur. Diagnosis may be based on clinical suspicion and laboratory/imaging tests may lead to early initiation of immunomodulating and supporting therapies. We suggest that in addition to anti-BG Abs FDG PET should be considered as a diagnostic tool for EL.

Key words

Encephalitis Lethargica MRI PET anti-basal ganglia antibodies treatment 


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  1. 1.
    Anonymous (1966) Encephalitis oflethargica type in a mental hospital.Lancet 2:1014–1015Google Scholar
  2. 2.
    Blackman JA, Patrick PD, Buck ML,Rust RS Jr (2004) Paroxysmal autonomicinstability with dystonia afterbrain injury. Arch Neurol 61:321–328PubMedCrossRefGoogle Scholar
  3. 3.
    Blunt SB, Lane RJ, Turjanski N, PerkinGD (1997) Clinical features and managementof two cases of encephalitislethargica. Mov Disord 12:354–359PubMedCrossRefGoogle Scholar
  4. 4.
    Brenneis C, Scherfler C, Engelhardt K,Helbok R, Brossner G, Beer R, LacknerP, Walder G, Pfausler B, Schmutzhard E(2007) Encephalitis lethargica followingBartonella henselae infection.J Neurol 254:546–547PubMedCrossRefGoogle Scholar
  5. 5.
    Caparros-Lefebvre D, Cabaret M,Godefroy O, Steinling M, Remy P,Samson Y, Petit H (1998) PET studyand neuropsychological assessment ofa long-lasting post-encephalitic parkinsonism.J Neural Transm 105:489–495PubMedCrossRefGoogle Scholar
  6. 6.
    Church AJ, Cardoso F, Dale RC, Lees AJ,Thompson EJ, Giovannoni G (2002)Anti-basal ganglia antibodies in acuteand persistent Sydenham’s chorea.Neurology 59:227–231PubMedGoogle Scholar
  7. 7.
    Crookshank F (1919) Epidemicencephalomyelitis and influenza.Lancet i:79–80CrossRefGoogle Scholar
  8. 8.
    Dale RC, Church AJ, Surtees RA, LeesAJ, Adcock JE, Harding B, Neville BG,Giovannoni G (2004) Encephalitislethargica syndrome: 20 new cases andevidence of basal ganglia autoimmunity.Brain 127:21–33PubMedCrossRefGoogle Scholar
  9. 9.
    Dewar BK, Wilson BA (2005) Cognitiverecovery from Encephalitis Lethargica.Brain Inj 19:1285–1291PubMedCrossRefGoogle Scholar
  10. 10.
    Dolan JD, Kamil R (1992) Atypicalaffective disorder with episodic dyscontrol:a case of von Economo’s disease(encephalitis lethargica). Can JPsychiatry 37:140–142Google Scholar
  11. 11.
    Ghaemi M, Rudolf J, Schmulling S,Bamborschke S, Heiss WD (2000)FDG- and Dopa-PET in postencephaliticparkinsonism. J Neural Transm107:1289–1295PubMedCrossRefGoogle Scholar
  12. 12.
    Goldman S, Amrom D, Szliwowski HB,Detemmerman D, Goldman S, BidautLM, Stanus E, Luxen A (1993) Reversiblestriatal hypermetabolism in a caseof Sydenham’s chorea. Mov Disord8:355–358PubMedCrossRefGoogle Scholar
  13. 13.
    Howard RS, Lees AJ (1987) Encephalitislethargica. A report of four recentcases. Brain 110(Pt 1):19–33PubMedCrossRefGoogle Scholar
  14. 14.
    Kapadia F, Grant IS (1990) Encephalitislethargica. Intensive Care Med 16:338–339PubMedCrossRefGoogle Scholar
  15. 15.
    Kenney C, Jankovic J (2006) Tetrabenazinein the treatment of hyperkineticmovement disorders. Expertreview of neurotherapeutics 6:7–17CrossRefGoogle Scholar
  16. 16.
    Kiessling LS, Marcotte AC, Culpepper L(1993) Antineuronal antibodies inmovement disorders. Pediatrics 92:39–43PubMedGoogle Scholar
  17. 17.
    Kiley M, Esiri MM (2001) A contemporarycase of encephalitis lethargica.Clin Neuropathol 20:2–7PubMedGoogle Scholar
  18. 18.
    Kun LN, Yian SY, Haur LS, Tjia H(1999) Bilateral substantia nigrachanges on MRI in a patient withencephalitis lethargica. Neurology53:1860–1862PubMedGoogle Scholar
  19. 19.
    Lo KC, Geddes JF, Daniels RS, OxfordJS (2003) Lack of detection of influenzagenes in archived formalin-fixed,paraffin wax-embedded brain samplesof encephalitis lethargica patientsfrom 1916 to 1920. Virchows Arch442:591–596PubMedGoogle Scholar
  20. 20.
    McAuley J, Shahmanesh M, Swash M(1999) Dopaminergic therapy in acuteencephalitis lethargica. Eur J Neurol6:235–237PubMedCrossRefGoogle Scholar
  21. 21.
    McCall S, Henry JM, Reid AH, TaubenbergerJK (2001) Influenza RNA notdetected in archival brain tissues fromacute encephalitis lethargica cases orin postencephalitic Parkinson cases.J Neuropathol Exp Neurol 60:696–704PubMedGoogle Scholar
  22. 22.
    Ono Y, Manabe Y, Hamakawa Y, OmoriN, Abe K (2007) Steroid-responsiveencephalitis lethargica syndrome withmalignant catatonia. Intern Med 46:307–310PubMedCrossRefGoogle Scholar
  23. 23.
    Picard F, de Saint-Martin A, Salmon E,Hirsch E, Marescaux C (1996) Postencephaliticstereotyped involuntarymovements responsive to L-Dopa. MovDisord 11:567–570CrossRefGoogle Scholar
  24. 24.
    Pruskauer-Apostol B, Popescu-PretorR, Plaiasu D, Tataru E, Ciobanu I,Voiculescu V (1977) The present statusof encephalitis lethargica. NeurolPsychiatr (Bucur) 15:125–128Google Scholar
  25. 25.
    Raghav S, Seneviratne J, McKelvie PA,Chapman C, Talman PS, Kempster PA(2006) Sporadic encephalitis lethargica.J Clin Neurosci 14:696–700PubMedCrossRefGoogle Scholar
  26. 26.
    Rail D, Scholtz C, Swash M (1981) PostencephaliticParkinsonism: currentexperience. J Neurol Neurosurg Psychiatry44:670–676PubMedCrossRefGoogle Scholar
  27. 27.
    Reid AH, McCall S, Henry JM, TaubenbergerJK (2001) Experimenting on thepast: the enigma of von Economo’sencephalitis lethargica. J NeuropatholExp Neurol 60:663–670Google Scholar
  28. 28.
    Shill HA, Stacy MA (2000) Malignantcatatonia secondary to sporadicencephalitis lethargica. J NeurolNeurosurg Psychiatry 69:402–403CrossRefGoogle Scholar
  29. 29.
    Sridam N, Phanthumchinda K (2006)Encephalitis lethargica like illness:case report and literature review. J MedAssoc Thai 89:1521–1527Google Scholar
  30. 30.
    Tenembaum S, Chitnis T, Ness J, HahnJS (2007) Acute disseminated encephalomyelitis.Neurology 68:S23–S36PubMedCrossRefGoogle Scholar
  31. 31.
    Verschueren H, Crols R (2001) Bilateralsubstantia nigra lesions on magneticresonance imaging in a patient withencephalitis lethargica. J NeurolNeurosurg Psychiatry 71:275CrossRefGoogle Scholar
  32. 32.
    Vilensky JA, Foley P, Gilman S (2007)Children and encephalitis lethargica:a historical review. Pediatr Neurol37:79–84PubMedCrossRefGoogle Scholar
  33. 33.
    Vilensky JA, Goetz CG, Gilman S(2006) Movement disorders associatedwith encephalitis lethargica: a videocompilation. Mov Disord 21:1–8PubMedCrossRefGoogle Scholar
  34. 34.
    Vincent A (2004) Encephalitis lethargica:part of a spectrum of post-streptococcalautoimmune diseases? Brain127:2–3PubMedCrossRefGoogle Scholar
  35. 35.
    von Economo C (1919) A case ofchronic encephalitis lethargica withintermittent course. Remarks regardingflu encephalitis. Münchenermedizinische Wochenschrift 66:1311–1313Google Scholar
  36. 36.
    von Economo C (1917) Encephalitislethargica. Wiener Klinische Wochenschrift30:581–585Google Scholar
  37. 37.
    Von Economo C (1917) New contributionsto Encephalitis Lethargica.Neurol Centralblatt 63:866–878Google Scholar
  38. 38.
    Wolf G (1953) Sporadic incidence ofencephalitis lethargica (von Economo).Dtsch Med Wochenschr 78:968–970PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2009

Authors and Affiliations

  • Robert Lopez-Alberola
    • 1
    • 3
  • Michael Georgiou
    • 2
  • George N. Sfakianakis
    • 2
  • Carlos Singer
    • 3
  • Spyridon Papapetropoulos
    • 3
  1. 1.Dept. of PediatricsUniversity of Miami, Miller School of MedicineMiamiUSA
  2. 2.Dept. of Radiology, Division of Nuclear MedicineUniversity of Miami, Miller School of MedicineMiamiUSA
  3. 3.Division of Movement Disorders, Dept. of NeurologyUniversity of Miami, Miller School of MedicineMiamiUSA

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