Limbic system symptoms of rabies infection

Background

Rabies, which primarily involves the central nervous system (CNS), is the deadliest infection ever known to mankind, with the case fatality rate being nearly 100%.1 Dog bites contribute to 99% of all rabies transmission to humans, with bats, foxes, raccoons and skunks accounting for 1%.1 Rabies can present as furious rabies (with agitation, altered sensorium, hydrophobia, aerophobia and autonomic dysfunction) or dumb rabies (ascending type of flaccid paralysis), with the furious type having higher viral loads and lower immune response. To the best of our knowledge, there are hardly any cases reported with abnormal sexual behaviour being the presenting manifestation of rabies. We herein discuss a histopathologically proven case of rabies where the symptom onset was with recurrent episodes of spontaneous inappropriate ejaculation.

Case presentation

A man in his 40s presented to our emergency department with a 5-day history of spontaneous passage of semen and behavioural abnormalities, and in the 2 days prior to presentation, hydrophobia, aerophobia and an impending feeling of death. He reported hypersensitivity of the penis with spontaneous involuntary ejaculation 5–6 times per day initially, which progressed to 15–20 times per day at the slightest touch of the hand, underwear or during micturition, and increased sexual drive. Ejaculation was not accompanied or preceded by erection or orgasm. There was no associated priapism, fever, dysuria, pyuria or testicular pain. Three days later, he developed behavioural abnormalities with increased agitation and a feeling of impending doom. He could not swallow, getting agitated at the sight of water. He developed severe spasms with a choking sensation on trying to swallow water. His wife reported that he had developed hypersensitivity to light and sound 2 days before the presentation. There was no history of drug abuse or addiction, nor was there any history of consuming any complementary over-the-counter medication. There was no history of a dog bite, but on closer questioning, the caregivers reported an episode 2 years earlier when a stray dog had scratched the patient on the dorsum of the right foot. It was dismissed as a minor scratch, and he did not receive post-exposure rabies prophylaxis. The sequence of events is outlined in figure 1. On examination, he was dehydrated with reduced skin turgor and urine output. His vitals were stable with a heart rate of 96/min, blood pressure of 110/60 mm Hg and respiratory rate of 22/min with 98% saturation on room air. General and systemic examinations were unremarkable except for aerophobia and photophobia.

Laboratory investigations revealed normal blood cell counts (haemoglobin: 140g/L, white cell count: 8.9 x 10⁹/L and platelets: 423 x 10⁹/L with no atypical cells or abnormal cellular morphology on peripheral smear. Hyponatraemia (129 mmol/L) was noted, but renal and liver function tests were within normal limits. ECG was suggestive of normal sinus rhythm, and a chest X-ray did not reveal any abnormalities. On the evaluation of hyponatraemia, the patient was dehydrated with low plasma osmolarity of 260 mOsm/L and urine sodium of 14 mM. He was managed with adequate intravenous fluids with urine output monitoring. To rule out secondary causes of sexual disturbances, hormonal profiles including thyroid function (Thyroid Stimulating Hormone: 0.483 µIU/mL), serum cortisol levels (526 nmol/L), serum growth hormone (0.620 ng/mL), Follicle Stimulating Hormone (0.742 mIU/mL), serum prolactin (10 ng/mL) and testosterone levels (2.35 nmol/L) were sent, which were within normal limits. He also underwent Cerebrospinal fluid analysis given behavioural abnormalities, which revealed a normal picture (5 cells/100% lymphocytic) with protein of 34 mg/dL and sugar of 84 mg/dL levels. Contrast-enhanced MRI was also performed but did not reveal any abnormality.

Investigations

Differential diagnosis

Though the presenting ‘recurrent spontaneous ejaculation’ was unusual, the other clinical features of the patient, including hydrophobia, phonophobia and aerophobia with underlying background history of a dog bite, strengthened our suspicion of rabies encephalitis.

Treatment

The wife and close contacts of the victim were administered post-exposure rabies prophylaxis. The frequency of pharyngeal spasms in the hospital increased with the eventual development of painful inspiratory spasms with cough. It resulted in aspiration and hypoxia, necessitating mechanical ventilation on day 1 of admission. He was sedated with ketamine at 1 mg/kg/hour post-intubation with intermittent use of bolus midazolam. Euglycaemia was maintained with intravenous fluid administration, and prophylaxis against deep vein thrombosis was given with low molecular weight heparin. However, he developed autonomic dysfunction on day 2, with sinus bradycardia and a heart rate of 52/min, and fluctuating blood pressure ranging from 80/50 mm Hg to 120/86 mm Hg. He was managed with intermittent vasopressor support for the same. On the third day of admission, he succumbed to sudden cardiac death due to cardiac arrhythmia.

Outcome and follow-up

A postmortem brain biopsy revealed Negri bodies in the brain, thereby clinching the diagnosis of rabies.