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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1996 Nov;61(5):478–484. doi: 10.1136/jnnp.61.5.478

Cognitive impairment after acute encephalitis: comparison of herpes simplex and other aetiologies.

L Hokkanen 1, E Poutiainen 1, L Valanne 1, O Salonen 1, M Iivanainen 1, J Launes 1
PMCID: PMC1074045  PMID: 8937342

Abstract

OBJECTIVE: To compare the cognitive defects after acute acyclovir treated herpes simplex encephalitis with those after other types of acute encephalitis. METHODS: Seventy seven consecutive patients between 1985 and 1995 and 29 normal controls were studied. Of the 77 patients without concomitant neurological conditions, 17 had herpes simplex, one virus encephalitis (HSVE group), 27 had some other identified aetiology (non-HSVE group), and in 33 patients the cause was unknown. Acyclovir treatment was started less than four days after the first mental symptoms in 12 of 17 patients with HSVE. A thorough neuropsychological assessment was carried out about one month after the onset. RESULTS: The HSVE group had deficits in verbal memory, verbal-semantic functions, and visuoperceptual functions more often than the non-HSVE group. The risk for cognitive defects was twofold to four-fold in the patients with HSVE compared with the non-HSVE patients. Two (12%) of the patients with HSVE and 12 (44%) of the non-HSVE patients were cognitively intact. Six patients with HSVE (46%) and 17 (89%) non-HSVE patients later returned to work. The lesions on CT or MRI were bilateral only in one patient with HSVE. The defects in the three patients with adenovirus infection were severe and resembled the amnesia after HSVE. Cognitive impairment, not previously reported, was found in encephalitis after rotavirus infection and epidemic nephropathy. CONCLUSION: The recovery in the HSVE group was better than expected based on the medical literature. On the other hand there were surprisingly severe cognitive defects in encephalitis after other viruses. With early acyclovir treatment patients with the least severe HSVE were equivalent to those with non-HSV encephalitis with good outcome whereas those with the most severe non-HSV encephalitis were equivalent to those with HSVE with poor outcome.

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Selected References

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  1. Abramovitz P., Schvartzman P., Harel D., Lis I., Naot Y. Direct invasion of the central nervous system by Mycoplasma pneumoniae: a report of two cases. J Infect Dis. 1987 Mar;155(3):482–487. doi: 10.1093/infdis/155.3.482. [DOI] [PubMed] [Google Scholar]
  2. Ackermann R., Rehse-Küpper B. Die Zentraleuropäische Enzephalitis in der Bundesrepublik Deutschland. Fortschr Neurol Psychiatr Grenzgeb. 1979 Mar;47(3):103–122. [PubMed] [Google Scholar]
  3. Anderson N. E., Powell K. F., Croxson M. C. A polymerase chain reaction assay of cerebrospinal fluid in patients with suspected herpes simplex encephalitis. J Neurol Neurosurg Psychiatry. 1993 May;56(5):520–525. doi: 10.1136/jnnp.56.5.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Anderson N. E., Willoughby E. W., Synek B. J., Croxson M. C., Glasgow G. L. Brain biopsy in the management of focal encephalitis. J Neurol Neurosurg Psychiatry. 1991 Nov;54(11):1001–1003. doi: 10.1136/jnnp.54.11.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Aurelius E. Herpes simplex encephalitis. Early diagnosis and immune activation in the acute stage and during long-term follow-up. Scand J Infect Dis Suppl. 1993;89:3–62. [PubMed] [Google Scholar]
  6. Aurelius E., Johansson B., Sköldenberg B., Staland A., Forsgren M. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet. 1991 Jan 26;337(8735):189–192. doi: 10.1016/0140-6736(91)92155-u. [DOI] [PubMed] [Google Scholar]
  7. Beghi E., Nicolosi A., Kurland L. T., Mulder D. W., Hauser W. A., Shuster L. Encephalitis and aseptic meningitis, Olmsted County, Minnesota, 1950-1981: I. Epidemiology. Ann Neurol. 1984 Sep;16(3):283–294. doi: 10.1002/ana.410160304. [DOI] [PubMed] [Google Scholar]
  8. Büttner T., Dorndorf W. Virale Enzephalitiden. Erfahrungen mit 53 Patienten aus Mittelhessen. Fortschr Neurol Psychiatr. 1988 Oct;56(10):315–325. doi: 10.1055/s-2007-1001796. [DOI] [PubMed] [Google Scholar]
  9. Chou S. M., Roos R., Burrell R., Gutmann L., Harley J. B. Subacute focal adenovirus encephalitis. J Neuropathol Exp Neurol. 1973 Jan;32(1):34–50. doi: 10.1097/00005072-197301000-00003. [DOI] [PubMed] [Google Scholar]
  10. Counsell C. E., Taylor R., Whittle I. R. Focal necrotising herpes simplex encephalitis: a report of two cases with good clinical and neuropsychological outcomes. J Neurol Neurosurg Psychiatry. 1994 Sep;57(9):1115–1117. doi: 10.1136/jnnp.57.9.1115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Decaux G., Szyper M., Ectors M., Cornil A., Franken L. Central nervous system complications of Mycoplasma pneumoniae. J Neurol Neurosurg Psychiatry. 1980 Oct;43(10):883–887. doi: 10.1136/jnnp.43.10.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eslinger P. J., Damasio H., Damasio A. R., Butters N. Nonverbal amnesia and asymmetric cerebral lesions following encephalitis. Brain Cogn. 1993 Mar;21(2):140–152. doi: 10.1006/brcg.1993.1011. [DOI] [PubMed] [Google Scholar]
  13. FLEWETT T. H., HOULT J. G. Influenzal encephalopathy and postinfluenzal encephalitis. Lancet. 1958 Jul 5;2(7036):11–15. doi: 10.1016/s0140-6736(58)90003-5. [DOI] [PubMed] [Google Scholar]
  14. Fisher R. S., Clark A. W., Wolinsky J. S., Parhad I. M., Moses H., Mardiney M. R. Postinfectious leukoencephalitis complicating Mycoplasma pneumoniae infection. Arch Neurol. 1983 Feb;40(2):109–113. doi: 10.1001/archneur.1983.04050020071016. [DOI] [PubMed] [Google Scholar]
  15. Fishman R. A. No, brain biopsy need not be done in every patient suspected of having herpes simplex encephalitis. Arch Neurol. 1987 Dec;44(12):1291–1292. doi: 10.1001/archneur.1987.00520240063014. [DOI] [PubMed] [Google Scholar]
  16. Färkkilä M., Koskiniemi M., Vaheri A. Clinical spectrum of neurological herpes simplex infection. Acta Neurol Scand. 1993 Apr;87(4):325–328. doi: 10.1111/j.1600-0404.1993.tb05517.x. [DOI] [PubMed] [Google Scholar]
  17. GIBBONS J. L., MILLER H. G., STANTON J. B. Para-infectious encephalomyelitis and related syndromes; a critical review of the neurological complications of certain specific fevers. Q J Med. 1956 Oct;25(100):427–505. [PubMed] [Google Scholar]
  18. Gabrielson M. O., Joseph C., Hsiung G. D. Encephalitis associated with adenovirus type 7 occurring in a family outbreak. J Pediatr. 1966 Jan;68(1):142–144. doi: 10.1016/s0022-3476(66)80433-x. [DOI] [PubMed] [Google Scholar]
  19. Gordon B., Selnes O. A., Hart J., Jr, Hanley D. F., Whitley R. J. Long-term cognitive sequelae of acyclovir-treated herpes simplex encephalitis. Arch Neurol. 1990 Jun;47(6):646–647. doi: 10.1001/archneur.1990.00530060054017. [DOI] [PubMed] [Google Scholar]
  20. Halperin J. J., Luft B. J., Anand A. K., Roque C. T., Alvarez O., Volkman D. J., Dattwyler R. J. Lyme neuroborreliosis: central nervous system manifestations. Neurology. 1989 Jun;39(6):753–759. doi: 10.1212/wnl.39.6.753. [DOI] [PubMed] [Google Scholar]
  21. Hanley D. F., Johnson R. T., Whitley R. J. Yes, brain biopsy should be a prerequisite for herpes simplex encephalitis treatment. Arch Neurol. 1987 Dec;44(12):1289–1290. doi: 10.1001/archneur.1987.00520240061013. [DOI] [PubMed] [Google Scholar]
  22. Hawkins S. A., Lyttle J. A., Connolly J. H. Two cases of influenza B encephalitis. J Neurol Neurosurg Psychiatry. 1987 Sep;50(9):1236–1237. doi: 10.1136/jnnp.50.9.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hierons R., Janota I., Corsellis J. A. The late effects of necrotizing encephalitis of the temporal lobes and limbic areas: a clinico-pathological study of 10 cases. Psychol Med. 1978 Feb;8(1):21–42. doi: 10.1017/s0033291700006607. [DOI] [PubMed] [Google Scholar]
  24. Huttunen L. Adenovirus type 7--associated encephalitis. Scand J Infect Dis. 1970;2(2):151–153. doi: 10.3109/inf.1970.2.issue-2.13. [DOI] [PubMed] [Google Scholar]
  25. Ikemura Y., Akena H., Okada A. Postinfektiöse Röteln-Enzephalitis. Nervenarzt. 1984 Feb;55(2):83–85. [PubMed] [Google Scholar]
  26. Johnson R. T., Olson L. C., Buescher E. L. Herpes simplex virus infections of the nervous system. Problems in laboratory diagnosis. Arch Neurol. 1968 Mar;18(3):260–264. doi: 10.1001/archneur.1968.00470330050004. [DOI] [PubMed] [Google Scholar]
  27. Kahlon J., Chatterjee S., Lakeman F. D., Lee F., Nahmias A. J., Whitley R. J. Detection of antibodies to herpes simplex virus in the cerebrospinal fluid of patients with herpes simplex encephalitis. J Infect Dis. 1987 Jan;155(1):38–44. doi: 10.1093/infdis/155.1.38. [DOI] [PubMed] [Google Scholar]
  28. Kapur N., Barker S., Burrows E. H., Ellison D., Brice J., Illis L. S., Scholey K., Colbourn C., Wilson B., Loates M. Herpes simplex encephalitis: long term magnetic resonance imaging and neuropsychological profile. J Neurol Neurosurg Psychiatry. 1994 Nov;57(11):1334–1342. doi: 10.1136/jnnp.57.11.1334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kelsey D. S. Adenovirus meningoencephalitis. Pediatrics. 1978 Feb;61(2):291–293. [PubMed] [Google Scholar]
  30. Kelsey D. S., McLean W. T. Adenoviral meningoencephalitis in a patient with lead toxicity. Arch Neurol. 1979 Jun;36(6):384–385. doi: 10.1001/archneur.1979.00500420094016. [DOI] [PubMed] [Google Scholar]
  31. Kennard C., Swash M. Acute viral encephalitis: its diagnosis and outcome. Brain. 1981 Mar;104(Pt 1):129–148. doi: 10.1093/brain/104.1.129. [DOI] [PubMed] [Google Scholar]
  32. Kennedy P. G. A retrospective analysis of forty-six cases of herpes simplex encephalitis seen in Glasgow between 1962 and 1985. Q J Med. 1988 Jul;68(255):533–540. [PubMed] [Google Scholar]
  33. Klapper P. E., Cleator G. M., Longson M. Mild forms of herpes encephalitis. J Neurol Neurosurg Psychiatry. 1984 Nov;47(11):1247–1250. doi: 10.1136/jnnp.47.11.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Klapper P. E., Laing I., Longson M. Rapid non-invasive diagnosis of herpes encephalitis. Lancet. 1981 Sep 19;2(8247):607–609. doi: 10.1016/s0140-6736(81)92744-6. [DOI] [PubMed] [Google Scholar]
  35. Koskiniemi M., Ketonen L. Herpes simplex virus encephalitis: progression of lesion shown by CT. J Neurol. 1981;225(1):9–13. doi: 10.1007/BF00313456. [DOI] [PubMed] [Google Scholar]
  36. Koskiniemi M., Rautonen J., Lehtokoski-Lehtiniemi E., Vaheri A. Epidemiology of encephalitis in children: a 20-year survey. Ann Neurol. 1991 May;29(5):492–497. doi: 10.1002/ana.410290508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Krupp L. B., Masur D., Schwartz J., Coyle P. K., Langenbach L. J., Fernquist S. K., Jandorf L., Halperin J. J. Cognitive functioning in late Lyme borreliosis. Arch Neurol. 1991 Nov;48(11):1125–1129. doi: 10.1001/archneur.1991.00530230033017. [DOI] [PubMed] [Google Scholar]
  38. Lakeman F. D., Koga J., Whitley R. J. Detection of antigen to herpes simplex virus in cerebrospinal fluid from patients with herpes simplex encephalitis. J Infect Dis. 1987 Jun;155(6):1172–1178. doi: 10.1093/infdis/155.6.1172. [DOI] [PubMed] [Google Scholar]
  39. Lakeman F. D., Whitley R. J. Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis. 1995 Apr;171(4):857–863. doi: 10.1093/infdis/171.4.857. [DOI] [PubMed] [Google Scholar]
  40. Launes J., Hautanen A. Nephropathia epidemica encephalitis. Acta Neurol Scand. 1988 Sep;78(3):234–235. doi: 10.1111/j.1600-0404.1988.tb03652.x. [DOI] [PubMed] [Google Scholar]
  41. Laurent B., Allegri R. F., Michel D., Trillet M., Naegele-Faure B., Foyatier N., Pellat J. Encéphalites herpétiques à prédominance unilatérale. Etude neuropsychologique au long cours de 9 cas. Rev Neurol (Paris) 1990;146(11):671–681. [PubMed] [Google Scholar]
  42. Lewis J. L., Rabinovich S. The wide spectrum of cryptococcal infections. Am J Med. 1972 Sep;53(3):315–322. doi: 10.1016/0002-9343(72)90174-x. [DOI] [PubMed] [Google Scholar]
  43. Lähdevirta J., Savola J., Brummer-Korvenkontio M., Berndt R., Illikainen R., Vaheri A. Clinical and serological diagnosis of Nephropathia epidemica, the mild type of haemorrhagic fever with renal syndrome. J Infect. 1984 Nov;9(3):230–238. doi: 10.1016/s0163-4453(84)90464-x. [DOI] [PubMed] [Google Scholar]
  44. MEYER H. M., Jr, JOHNSON R. T., CRAWFORD I. P., DASCOMB H. E., ROGERS N. G. Central nervous system syndromes of "vital" etiology. A study of 713 cases. Am J Med. 1960 Aug;29:334–347. doi: 10.1016/0002-9343(60)90029-2. [DOI] [PubMed] [Google Scholar]
  45. McCONKEY B., DAWS R. A. Neurological disorders associated with Asian influenza. Lancet. 1958 Jul 5;2(7036):15–17. doi: 10.1016/s0140-6736(58)90004-7. [DOI] [PubMed] [Google Scholar]
  46. Miller J. D., Ross C. A. Encephalitis. A four-year survey. Lancet. 1968 May 25;1(7552):1121–1126. doi: 10.1016/s0140-6736(68)90188-8. [DOI] [PubMed] [Google Scholar]
  47. Morawetz R. B., Whitley R. J., Murphy D. M. Experience with brain biopsy for suspected herpes encephalitis: a review of forty consecutive cases. Neurosurgery. 1983 Jun;12(6):654–657. doi: 10.1227/00006123-198306000-00011. [DOI] [PubMed] [Google Scholar]
  48. Nahmias A. J., Whitley R. J., Visintine A. N., Takei Y., Alford C. A., Jr Herpes simplex virus encephalitis: laboratory evaluations and their diagnostic significance. J Infect Dis. 1982 Jun;145(6):829–836. doi: 10.1093/infdis/145.6.829. [DOI] [PubMed] [Google Scholar]
  49. Pachner A. R., Duray P., Steere A. C. Central nervous system manifestations of Lyme disease. Arch Neurol. 1989 Jul;46(7):790–795. doi: 10.1001/archneur.1989.00520430086023. [DOI] [PubMed] [Google Scholar]
  50. Pönkä A. The occurrence and clinical picture of serologically verified Mycoplasma pneumoniae infections with emphasis on central nervous system, cardiac and joint manifestations. Ann Clin Res. 1979;11 (Suppl 24):1–60. [PubMed] [Google Scholar]
  51. ROSE F. C., SYMONDS C. P. Persistent memory defect following encephalitis. Brain. 1960;83:195–212. doi: 10.1093/brain/83.2.195. [DOI] [PubMed] [Google Scholar]
  52. Rowley A. H., Whitley R. J., Lakeman F. D., Wolinsky S. M. Rapid detection of herpes-simplex-virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis. Lancet. 1990 Feb 24;335(8687):440–441. doi: 10.1016/0140-6736(90)90667-t. [DOI] [PubMed] [Google Scholar]
  53. Sköldenberg B., Forsgren M., Alestig K., Bergström T., Burman L., Dahlqvist E., Forkman A., Frydén A., Lövgren K., Norlin K. Acyclovir versus vidarabine in herpes simplex encephalitis. Randomised multicentre study in consecutive Swedish patients. Lancet. 1984 Sep 29;2(8405):707–711. doi: 10.1016/s0140-6736(84)92623-0. [DOI] [PubMed] [Google Scholar]
  54. Steiner I., Polacheck I., Melamed E. Dementia and myoclonus in a case of cryptococcal encephalitis. Arch Neurol. 1984 Feb;41(2):216–217. doi: 10.1001/archneur.1984.04050140118040. [DOI] [PubMed] [Google Scholar]
  55. Sulkava R., Rissanen A., Pyhälä R. Post-influenzal encephalitis during the influenza A outbreak in 1979/1980. J Neurol Neurosurg Psychiatry. 1981 Feb;44(2):161–163. doi: 10.1136/jnnp.44.2.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Tyler K. L. Polymerase chain reaction and the diagnosis of viral central nervous system diseases. Ann Neurol. 1994 Dec;36(6):809–811. doi: 10.1002/ana.410360602. [DOI] [PubMed] [Google Scholar]
  57. Wahlberg P., Saikku P., Brummer-Korvenkontio M. Tick-borne viral encephalitis in Finland. The clinical features of Kumlinge disease during 1959-1987. J Intern Med. 1989 Mar;225(3):173–177. doi: 10.1111/j.1365-2796.1989.tb00059.x. [DOI] [PubMed] [Google Scholar]
  58. Weinblatt M. E., Caplan E. S. Fatal Mycoplasma pneumoniae encephalitis in an adult. Arch Neurol. 1980 May;37(5):321–321. doi: 10.1001/archneur.1980.00500540099024. [DOI] [PubMed] [Google Scholar]
  59. West T. E., Papasian C. J., Park B. H., Parker S. W. Adenovirus type 2 encephalitis and concurrent Epstein-Barr virus infection in an adult man. Arch Neurol. 1985 Aug;42(8):815–817. doi: 10.1001/archneur.1985.04210090083023. [DOI] [PubMed] [Google Scholar]
  60. Whitley R. J., Alford C. A., Hirsch M. S., Schooley R. T., Luby J. P., Aoki F. Y., Hanley D., Nahmias A. J., Soong S. J. Factors indicative of outcome in a comparative trial of acyclovir and vidarabine for biopsy-proven herpes simplex encephalitis. Infection. 1987;15 (Suppl 1):S3–S8. doi: 10.1007/BF01650104. [DOI] [PubMed] [Google Scholar]
  61. Whitley R. J., Alford C. A., Hirsch M. S., Schooley R. T., Luby J. P., Aoki F. Y., Hanley D., Nahmias A. J., Soong S. J. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med. 1986 Jan 16;314(3):144–149. doi: 10.1056/NEJM198601163140303. [DOI] [PubMed] [Google Scholar]
  62. Yoneda Y., Mori E., Yamashita H., Yamadori A. MRI volumetry of medial temporal lobe structures in amnesia following herpes simplex encephalitis. Eur Neurol. 1994;34(5):243–252. doi: 10.1159/000117051. [DOI] [PubMed] [Google Scholar]
  63. Yu Y. L., Lau Y. N., Woo E., Wong K. L., Tse B. Cryptococcal infection of the nervous system. Q J Med. 1988 Jan;66(249):87–96. [PubMed] [Google Scholar]
  64. Ziebart-Schroth A. Frühsommermeningoenzephalitis (FSME). Klinik und besondere Verlaufsformen. Wien Klin Wochenschr. 1972 Dec 1;84(48):778–781. [PubMed] [Google Scholar]

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