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Journal of NeuroVirology

, Volume 11, Issue 1, pp 93–100 | Cite as

Pathophysiology of human paralytic rabies

  • Thiravat HemachudhaEmail author
  • Supaporn Wacharapluesadee
  • Erawady Mitrabhakdi
  • Henry Wilde
  • Kinjiro Morimoto
  • Richard A. Lewis
Mini-Review—The Rabies Virus

Abstract

Furious rabies is a well-recognized clinical disorder in humans but the paralytic form is not as easily identified. The mechanisms responsible for the weakness and longer survival periods are not clear. Several hypotheses have been proposed, including rabies virus variants associated with a particular vector, location of wounds, incubation period, influence of prior rabies vaccination, and virus localization in the central nervous system (CNS). However, none of these have been substantiated. Regarding molecular analyses of rabies viruses isolated from both furious and paralytic rabies patients, only minor genetic variations with no specific patterns in glyco-(G), phospho-(P), and nucleoprotein (N) sequences have been identified and arginine 333 in G protein was present in all samples. Regional distribution of rabies virus antigen in rabies patients whose survival periods were 7 days or less and magnetic resonance imaging (MRI) of the CNS indicated brainstem and spinal cord as predilection sites regardless of clinical presentations. There are clinical, electrophysiological, and pathological indications that peripheral nerve dysfunction is responsible for weakness in paralytic rabies whereas in furious rabies, even in the absence of clinical weakness, abundant denervation potentials with normal sensory nerve conduction studies and proximal motor latencies suggest anterior horn cell dysfunction. The lack of cellular immunity to rabies virus antigen accompanied by an absence of cerebrospinal fluid (CSF) rabies neutralizing antibody in most paralytic rabies patients may argue against role of an immune response against rabies virus—positive axons. Aberrant immune responses to peripheral nerve antigen, in particular those mediated by one or more cellular-dependent mechanisms, may be involved as is supported by the absence of putative anti-ganglioside antibodies commonly found in immune-mediated peripheral nerve diseases. Longer survival period in paralytic rabies may possibly be related to currently unidentified mechanism(s) on neuronal gene expression, required for virus transcription/replication and for maintaining neuronal survival.

Keywords

axonopathy demyelination encephalitis magnetic resonance imaging paralysis rabies RNA virus 

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Copyright information

© Journal of NeuroVirology, Inc. 2005

Authors and Affiliations

  • Thiravat Hemachudha
    • 1
    • 5
    Email author
  • Supaporn Wacharapluesadee
    • 1
  • Erawady Mitrabhakdi
    • 1
  • Henry Wilde
    • 2
  • Kinjiro Morimoto
    • 3
  • Richard A. Lewis
    • 4
  1. 1.Department of Medicine and the Molecular Biology Laboratory for Neurological DiseasesChulalongkorn University HospitalBangkokThailand
  2. 2.Queen Saovabha Memorial InstituteThai Red Cross SocietyBangkokThailand
  3. 3.The National Institute of Infectious DiseasesTokyoJapan
  4. 4.Department of NeurologyWayne State University School of MedicineDetroitUSA
  5. 5.Neurology Division, Department of MedicineChulalongkorn University HospitalBangkokThailand

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