Rabies encephalitis

Rabies encephalitis is a rapidly progressive CNS infection resulting from infection by a member of an RNA virus of the family Rhabdoviridae, genus Lyssavirus, most commonly transmitted to humans, from infected animals, via a bite. It results in rapid neurological deterioration and in almost all instances progresses to death. Dominant imaging features are high T2 signal in the thalami, basal ganglia, brainstem and spinal cord. 

Epidemiology

Infection results most frequently from transmission of the virus from an infected animal to a human via a bite. Occasionally infection can also occur via an open wound, mucous membranes or even as the result of organ transplantation or laboratory accidents ^1,2. 

In developed countries, most cases are the result of bites from rabid bats (or inhalation while visiting bat caves), whereas in the developing world, rabid dogs are the main source of human infection ^1,2. 

Clinical presentation

Typically there is an incubation period of 2 weeks to 2 months ². 

Before CNS manifestations, dorsal root ganglionitis can result in localised neuropathic pain in the region of exposure (bite) ³. 

Involvement of the CNS by rabies can take two forms, which do not appear to correlate with the site of the bite, previous immunisation, vector (bat, dog or other) or any other clinical feature ^1-3: 

1. classic rabies encephalitis (80%); equivalent to 'furious rabies' in dogs
2. paralytic rabies (20%); equivalent to 'dumb rabies' in dogs

Classic rabies encephalitis

Encephalitis is by far the most common presentation of CNS involvement by rabies, accounting for 80% of cases. Symptoms are initially non-specific with general systemic symptoms, anorexia, irritability, inspiratory spasms and cough, autonomic dysfunction and altered mental status. With time classic symptoms and rabies encephalitis develop including: hydrophobia, aerophobia and hypersalivation, agitation and even priapism ^1,2. 

Paralytic rabies

Paralytic rabies is relatively uncommon accounting only for 20% of CNS infections in humans. It is characterised by bilateral global motor weakness resulting in bilateral facial weakness and quadriparesis, with relative sparing of the sensory system ^1,3. It clinically resembles GuillianGuillain-Barré syndrome ^1,2. 

Pathology

Once introduced into the soft tissues, the virus enters unmyelinated nerve fibres and travels retrogradely up the axons to the dorsal root ganglia, which can result in neuropathic pain ³. Once it reaches the central nervous system dissemination is rapid accounting for the fulminant clinical course ^2,3. 

Radiographic features

As is the case with other encephalitides, MRI is the only modality of any use in the diagnosis of CNS rabies, as CT is usually normal. Unfortunately, the very rapid progression of symptoms in this disease resultresults in infrequent imaging, and a relative lack of literature on the imaging findings ^1-3. 

CT

Usually normal. Occasionally, non-specific hypoattenuation in the brainstem, mesial temporal lobes, basal ganglia and periventricular white matter may be evident ^1,2. If imaging is only obtained late in the course of the disease, haemorrhage and cerebral swelling may be evident ¹. 

MRI

The main imaging feature is an increase in T2 signal (best seen on FLAIR) in the affected parts of the brain and spinal cord, with a predilection for grey matter structures. As the disease progresses, swelling becomes more marked and petechial haemorrhages occur, as well as contrast enhancement ¹. The distribution of imaging changes, naturally, depends on the type of involvement. 

In classic rabies encephalitis, increased T2 signal has a predilection for the basal ganglia, thalami, hypothalami, brainstem, limbic system, and spinal cord as well as the frontal and parietal lobes ^1-3.  In paralytic rabies, the involvement of the spinal cord and medulla are more pronounced, although no specific imaging features exist to allow differentiation form classic encephalitic form ^1,2. 

Angiography

Reports of narrowing of terminal internal carotid arteries and distal basilar artery may be related to arterial spasm ². 

Treatment and prognosis

Unfortunately, to date, no predictably effective therapy for CNS involvement by rabies has been developed, and in almostmost cases, the disease results in a rapid decline of function, into coma and death ^1,2. 

Typical therapeutic attempts, which if instituted early have in some instances resulted in survival include: human human rabies immunoglobulin infusion, rabies vaccine, ribavirin, interferon alfa, and ketamine ¹. 

History and etymology

The word rabies has its origins in the Indian root word rabh; "to make violent" ². 

Differential diagnosis

The differential diagnosis depends on the form of CNS involvement. 

For classic rabies encephalitis, especially during the early phases, before the development of classic symptoms, imaging differential includes ^1-3:

• other viral encephalitides e.g. 
  • herpes simplex encephalitis: greater predilection for mesial temporal lobes and insular cortex, with sparing of the basal ganglia, thalami and brainstem
  • Japanese encephalitis
  • eastern equine encephalitis
• ​rhombencephalitis e.g. 
  • Listeria rhombencephalitis
• acute hemorrhagic leukoencephalitis
• acute disseminated encephalomyelitis (ADEM): mostly affecting white matter

For paralytic rabies, the main differential, and the cause of frequent delay in diagnosis, is Guillain Barre syndrome ¹.