Correspondence

Long-Term Follow-up after Treatment of Rabies by Induction of Coma

N Engl J Med 2007; 357:945-946August 30, 2007

Article

To the Editor:

Video

The Patient 18 Months after Exposure to Rabies.

In 2005, Willoughby and colleagues1 reported on a 15-year-old girl's survival from rabies encephalitis — the sixth such case that had been reported in humans — after treatment with a novel therapeutic regimen that included ketamine, ribavirin, and amantadine. Five months after exposure, she still had dysarthria, weakness in the left hand and foot, bilateral extensor plantar response, generalized choreoathetosis, intermittent dystonia, and a lurching gait. Here we report on the functional outcomes 18 months and 27 months after her initial exposure to a rabid bat.

Her generalized choreoathetosis completely resolved by 2006. A trial of therapy with carbidopa–levodopa caused worsening of abnormalities in her gait. A cerebrospinal fluid analysis in September 2005 showed normalization of the protein level and the white-cell count, with decreased levels of biopterin. Eighteen months after her exposure to rabies, her dysarthria and gait abnormalities had significantly improved, but she could not return to her previous level of participation in sports. She resumed classes full time in high school without having difficulties with either learning or memory.

On neurologic examination, the patient showed no choreoathetoid movements during four separate visits with three neurologists and two rehabilitation specialists. She had normal affect and cognition, ataxic dysarthria (see video, available with the full text of this letter at www.nejm.org), and normal cranial-nerve functions. Also evident in the video are both mild weakness in the left foot dorsiflexor and mild dystonia in the left hand, without weakness on surface electromyography. She also had slowed alternating movements in the left hand and fingers and paresthesia in the region of the bat bite. Her deep-tendon reflexes were symmetric throughout, and her plantar responses were flexor. She had mild ataxia, especially during running (see video). Analysis of the cerebrospinal fluid showed six unique oligoclonal bands. A mildly elevated level of neopterin and decreased levels of 5-hydroxyindoleacetic acid and homovanillic acid suggested decreased turnover of dopamine and serotonin. Magnetic resonance imaging of the brain showed resolution of the hyperintensities in the basal ganglia that had been seen on T₂-weighted images in November 2004.

Twenty-seven months after exposure, the patient continued to have fluctuating dysarthria and gait difficulties, plus an intermittent sensation of cold in the feet. She had no difficulties with her instrumental activities of daily living, including driving. In high school, she took college-level courses in English, physics, and calculus. She scored above average on a national college achievement test, graduated from high school in 2007, and planned to attend a local college in the fall. She had no problems with peer relations or mood disorders.

Of five other patients with well-documented survival after rabies encephalitis,2-7 all of whom received conventional care, only one had a satisfactory outcome,2 whereas the others had persistent cerebellar and striatal signs.7,8 The combined treatment with antiexcitatory agents (ketamine, midazolam, and phenobarbital) and antiviral agents (ketamine, amantadine, and ribavirin) used by Willoughby et al. may have contributed to this patient's favorable outcome, and such treatment warrants further evaluation.

William T. Hu, M.D., Ph.D.
Mayo Clinic College of Medicine, Rochester, MN 55905

Rodney E. Willoughby, Jr., M.D.
Medical College of Wisconsin, Milwaukee, WI 53226

Howard Dhonau, M.D.
Fond du Lac Regional Clinic, Fond du Lac, WI 54935

Kenneth J. Mack, M.D., Ph.D.
Mayo Clinic College of Medicine, Rochester, MN 55905

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Citing Articles (13)

Citing Articles

1. 1

   Claudius Malerczyk, Lisa DeTora, Dieter Gniel. (2011) Imported Human Rabies Cases in Europe, the United States, and Japan, 1990 to 2010. Journal of Travel Medicine 18:6, 402-407
   CrossRef

2. 2

   Jan M Vetter, Lars Frisch, Christian Drosten, R Stefan Ross, Michael Roggendorf, Bernd Wolters, Thomas Müller, H Burkhard Dick, Norbert Pfeiffer. (2011) Survival After Transplantation of Corneas From a Rabies-Infected Donor. Cornea 30:2, 241-244
   CrossRef

3. 3

   Alan C. Jackson. 2011. Therapy of Human Rabies. , 365-375.
   CrossRef

4. 4

   Todd G. Smith, Xianfu Wu, Richard Franka, Charles E. Rupprecht. 2011. Design of Future Rabies Biologics and Antiviral Drugs. , 345-363.
   CrossRef

5. 5

   Alan C Jackson. (2010) Why does the prognosis remain so poor in human rabies?. Expert Review of Anti-infective Therapy 8:6, 623-625
   CrossRef

6. 6

   Rodney E Willoughby. (2009) Are we getting closer to the treatment of rabies?. Future Virology 4:6, 563-570
   CrossRef

7. 7

   Alan C. Jackson. (2009) Update on rabies diagnosis and treatment. Current Infectious Disease Reports 11:4, 296-301
   CrossRef

8. 8

   R. E. Willoughby, T. Opladen, T. Maier, W. Rhead, S. Schmiedel, J. Hoyer, C. Drosten, C. E. Rupprecht, K. Hyland, G. F. Hoffmann. (2009) Tetrahydrobiopterin deficiency in human rabies. Journal of Inherited Metabolic Disease 32:1, 65-72
   CrossRef

9. 9

   (2008) Update on Emerging Infections: News From the Centers for Disease Control and Prevention. Annals of Emergency Medicine 52:5, 537-539
   CrossRef

10. 10

    Jacob W. Ufberg, David J. Karras. (2008) Commentary. Annals of Emergency Medicine 52:5, 539-540
    CrossRef

11. 11

    Henry Wilde, Thiravat Hemachudha, Alan C. Jackson. (2008) Viewpoint: management of human rabies. Transactions of the Royal Society of Tropical Medicine and Hygiene 102:10, 979-982
    CrossRef

12. 12

    Mary J Warrell. (2008) Emerging aspects of rabies infection: with a special emphasis on children. Current Opinion in Infectious Diseases 21:3, 251-257
    CrossRef

13. 13

    David Sharp. (2008) Hydrophobia phobia as social history. The Lancet 371:9615, 797-798
    CrossRef