Second edition

14.qxd 3/10/08 9:50 AM Page 503
symptoms generally resolve within a matter of weeks; in
the immunocompromised, however, protracted, and at
times fatal, courses may be seen.
One complication of a zoster rash, whether dermatomal
or cranial, is post-herpetic neuralgia, in which the pain
persists beyond resolution of the rash. This neuralgic pain
may be lancinating or burning in quality and may cause
considerable disability; although in some cases a gradual
remission may occur after many months, in others the pain
proves to be chronic.
Etiology
As indicated above, zoster may be complicated by a
myelitis, a cerebral vasculopathy or an encephalitis. The
myelitis results from retrograde spread from the sensory
ganglia. In all likelihood, the cerebral vasculopathy occurs
secondary to seeding of such large pial vessels as the middle
or anterior cerebral arteries by virus that spreads from the
gasserian ganglion up along sensory nerves destined for the
meninges; in such cases, there is often segmental narrowing
of the involved vessels (MacKenzie et al. 1981) and
virus has been found within the vessel walls (Linnemann
and Alvira 1980; Melanson et al. 1996); in some cases
thrombotic occlusion has been noted with little or no associated
inflammation (Eidelberg et al. 1986). As noted earlier,
the encephalitis occurs secondary to hematogenous
seeding of the cerebrum, generally occurring only during a
disseminated rash. In such cases one may find multifocal
areas of cerebritis (Weaver et al. 1999), primarily affecting
the white matter, with, at times, multiple areas of microinfarction
occurring secondary to small vessel vasculitis
(Kleinschmidt-DeMasters et al. 1996).
Differential diagnosis
The occurrence of a myelopathy, stroke or encephalitic
symptoms (e.g., delirium, seizures, etc.) in the setting of a
recent rash should immediately suggest a varicella-zoster
infection. As noted earlier, some of these manifestations may
occur in the absence of a rash, and in such cases one would
have to closely question the patient and family regarding any
complaints of pain, either in a dermatomal pattern or in the
ophthalmic division of the fifth cranial nerve.
Treatment
Treatment with an antiviral agent, such as acyclovir, valacyclovir,
famciclovir, or brivudin, should be immediately instituted
for all forms of zoster, and, in the case of large-vessel
vasculopathy, antiplatelet agents should also be started.
With regard to post-herpetic neuralgia, a number of
agents have been shown to be effective in double-blind
studies, including nortriptyline, amitriptyline, gabapentin,
and pregabalin. Importantly, with regard to nortriptyline
14.10 Rabies 503
and amitriptyline, patients get relief regardless of whether
they are depressed or not. Nortriptyline and amitriptyline
are equally effective, but nortriptyline is better tolerated
(Watson et al. 1998); nortriptyline may be given in doses
ranging from 10 to 75 mg, and amitriptyline in doses ranging
from 10 to 100 mg. Gabapentin is roughly equivalent in
effectiveness to nortriptyline but better tolerated (Chandra
et al. 2006); it may be given in doses ranging from 1200 to
3600 mg. Pregabalin is the most recently introduced agent
and it is unclear how effective it is compared with the others;
it may be given in doses ranging from 150 to 600 mg
(Dworkin et al. 2003). Regardless of which agent is used, a
week or more may be required before some relief is seen.
14.10 RABIES
Rabies typically occurs after being bitten by a rabid animal,
for example a dog, cat, wolf, fox, skunk, raccoon, or vampire
bat; cases have also been reported secondary to respiratory
transmission in spelunkers within bat-infested caves and in
a veterinarian who was working with the homogenized
brain of a rabid animal (Conomy et al. 1977); recently
rabies was also reported secondary to solid organ transplantation
from a donor with an unsuspected case (Srinivasan
et al. 2005). Although very rare in developed countries, rabies
remains a significant problem in India and parts of Asia.
Clinical features
After being bitten by an infected animal there is a latent,
asymptomatic period, generally of 1–3 months, with a
range of weeks to a year or more; the duration of the
latency appears related not only to the severity of the bite
but also to the distance from the bitten area to the brain,
with bites on the feet having the longest latency and facial
bites the shortest.
With resolution of the latent interval, there is usually a
prodrome, lasting days, characterized by headache and
malaise; pain or parasthesiae may also develop at the site of
the original bite. Subsequently, the illness may evolve in
one of two forms, namely ‘furious’ rabies or ‘dumb’ (also
known as ‘paralytic’) rabies.
Furious rabies (Adle-Biassette et al. 1996; Blatt et al. 1938;
Dupont and Earle 1965) is seen in perhaps 80 percent of cases
and is characterized by restlessness, agitation, excitability,
excessive startability, and convulsions; delirium is typical and
patients may engage in bizarre behavior, including biting.
The combination of excessive salivation and dysphagia
caused by pharyngeal spasm may literally cause the patient to
‘foam at the mouth’. Pharyngeal spasm may also be provoked
by swallowing water or even by the sight of water, giving
rise to the classic symptom of hydrophobia.
Dumb rabies (Chopra et al. 1980) is characterized by a
flaccid paralysis that typically begins in one limb and rapidly
becomes generalized and symmetric.