Human rabies encephalitis following bat exposure: failure of therapeutic coma.

The case: A healthy 73-year-old man had pain in his left shoulder. He presented to a regional hospital 1 week later with fever, dysphagia, muscle spasms and progressive generalized weakness. His neurologic status deteriorated , which prompted transfer to a tertiary care hospital. Upon the patient's arrival at the ter-tiary care hospital, our initial evaluation showed irritability, lethargy and hypersalivation. After 48 hours, the patient exhibited multifocal myoclonus and decorticate posturing. Intubation and mechanical ventilation were performed with fluid resuscitation and therapy with vasopressors, corticoster-oids and broad-spectrum antibiotics. A computed tomography scan of his brain was unremarkable. An electro-encephalogram showed diffuse abnormalities consistent with metabolic en-cephalopathy. We investigated potential rabies exposure, and his family confirmed that he had sustained a bat bite on his left shoulder 6 months previously but had not sought treatment. We performed a nuchal skin biopsy and obtained saliva and serum samples for rabies virologic and serologic testing. Direct fluorescent antibody staining indicated that the skin biopsy contained rabies virus antigen, and reverse-transcriptase polymerase chain reaction indicated that both the skin and saliva samples contained the rabies virus. Diagnostic tests available for suspected rabies cases in Canada are described in Box 1. The patient received an intramuscular injection of 1200 IU of human rabies immune globulin. We started the Milwaukee Protocol 15 days after symptom onset (3 days after diagnosis). The Protocol consisted of inducing a therapeutic coma (infusions of ketamine, midazolam and propofol titrated to burst-suppression pattern on the electroencephalogram) and antiviral therapy (ribavirin, aman-tadine). 1 We also provided metabolic supplementation (with tetrahydro-biopterin and L-arginine). We monitored regional cerebral perfusion using transcranial Doppler ultrasonography. Serial serum, saliva and cerebrospinal fluid samples were assessed weekly for immune response and viral clearance. Over time, rabies virus-specific IgM and IgG and total antibody titres rose and viral excretion in the saliva fell. We stopped sedation on day 42, 3 weeks after initiation of the Milwaukee Protocol. Direct fluorescent antibody staining indicated that the repeat nuchal biopsy performed on day 43 was only weakly positive for rabies virus anti-gen, and reverse-transcriptase poly-merase chain reaction was negative. On the same day, transcranial Doppler ultrasonography showed only minor perfusion abnormalities, and the elec-troencephalogram was near isoelec-tric. By day 56, results of serial rabies virus tests suggested viral clearance; however, our patient's saliva still contained a low level of the virus. He remained comatose for 4 weeks after we stopped sedation. A …