Viral Infections of the Nervous System, Chronic Meningitis, and Prion Diseases: Introduction

A number of viruses share the uniue tendency to !rimarily affect the human nervous system"
Included in this grou! are the human immunodeficiency viruses #$IV%& and $IV%'(, her!es
sim!le) viruses #$SV%& and $SV%'(, her!es *oster or varicella *oster virus #V+V(, ,!stein%
-arr virus #,-V(, cytomegalovirus #CMV(, !oliovirus, rabies, and several seasonal
arthro!od%borne viruses #.laviviruses(" Some of these are neurotro!ic, e)hibiting an affinity
for certain ty!es of neurons: for e)am!le, !oliomyelitis viruses and motor neurons, V+V and
!eri!heral sensory neurons, and rabies virus and brainstem neurons" /et others attac0
nonneuronal su!!orting cells1 2C virus causing !rogressive multifocal leu0oence!halo!athy
is the !rime e)am!le" .or many of the rest, the affinity is less selective in that all elements of
the nervous system are involved" $er!es sim!le), for e)am!le, may devastate the medial
!arts of the tem!oral lobes, destroying neurons, glia cells, myelinated nerve fibers, and blood
vessels1 and $IV, the cause of AIDS, may induce multi!le foci of tissue necrosis throughout
the cerebrum"
3hese relationshi!s and many others, 4hich are the sub5ect matter of this cha!ter, are of 4ide
interest in medicine" In some conditions, the systemic effects of the viral infection are
negligible1 it is the neurologic disorder that brings them to medical attention" In other 4ords,
the neural as!ects of viral infection are dis!ro!ortionate to the systemic illnesses" 3his as!ect
of neurology must therefore also be familiar to !ediatricians and internists, 4ho are li0ely to
be the first to see such !atients"
A detailed discussion of viral mor!hology and cell6virus interactions is beyond the sco!e of a
te)tboo0 about neurology" Authoritative overvie4s of this sub5ect can be found in the
introductory cha!ters of 7"3" 2ohnson8s monogra!h Viral Infections of the Nervous System"
Path4ays of Infection
Viruses gain entrance to the body by one of several !ath4ays" Mum!s, measles, and V+V
enter via the res!iratory !assages" Polioviruses and other enteroviruses enter by the oral6
intestinal route, and $SV enters mainly via the oral or genital mucosal route" 9ther viruses
are acuired by inoculation, as a result of the bites of animals #e"g", rabies( or mosuitoes
#arthro!od%borne or arbovirus infections(" 3he fetus may be infected trans!lacentally by
rubella virus, CMV, and $IV"
.ollo4ing entry into the body, the virus multi!lies locally and in secondary sites and usually
gives rise to a viremia" Most viruses are !revented from entering central nervous system
#CNS( tissues, !resumably by the blood6brain barrier" Moreover, most antibodies and
immunocom!etent cells are e)cluded from the CNS as 4ell, so that the same mechanism that
limits the entry of viruses also deters their removal" Viral !articles are cleared from the blood
by the reticuloendothelial system1 but if the viremia is massive or other conditions are
favorable, they 4ill invade the CNS !robably via the cerebral ca!illaries and the choroid
!le)uses" Viruses cross into the nervous system both 4ithin migrating lym!hocytes and
directly through areas of glial and vascular regions that are !ermeable to the organisms"
Another !ath4ay of infection is along !eri!heral nerves1 centri!etal movement of virus is
accom!lished by the retrograde a)o!lasmic trans!ort system" $SV, V+V, and rabies virus
utili*e this !eri!heral nerve !ath4ay, 4hich e)!lains 4hy the initial sym!toms of rabies
occur locally, at a segmental level corres!onding to the animal bite" In animals inoculated
subcutaneously 4ith V+V, sensitive DNA am!lification techniues identify fragments of viral
genome only in the dorsal root ganglion or ganglia corres!onding to the dermatome
containing the site of inoculation" It has been sho4n e)!erimentally that $SV may s!read to
the CNS by involving olfactory neurons in the nasal mucosa1 the central !rocesses of these
cells !ass through o!enings in the cribriform !late and syna!se 4ith cells in the olfactory
bulb #CNS(" Another !otential !ath4ay is the trigeminal nerve and gasserian ganglion,
ho4ever, the role of these !ath4ays in human infection is not certain" 9f the different routes
of infection, the hematogenous one is by far the most im!ortant for the ma5ority of viruses"
Mechanisms of Viral Infections
Viruses, once they invade the nervous system, have diverse clinical and !athologic effects"
9ne reason for this diversity is that different cell !o!ulations 4ithin the CNS vary in their
susce!tibility to infection 4ith different viruses" 3o be susce!tible to a viral infection, the host
cell must have on its cyto!lasmic membrane s!ecific rece!tor sites to 4hich the virus
attaches" 3hus, some infections are confined to meningeal cells, enteroviruses being the most
common, in 4hich case the clinical manifestations are those of ase!tic meningitis" 9ther
viruses involve !articular classes of neurons of the brain or s!inal cord, giving rise to the
more serious disorders such as ence!halitis and !oliomyelitis" In some infections, the
susce!tibility of !articular cell grou!s is even more s!ecific" 3he virus or its nucleoca!sid
must be ca!able of !enetrating the cell, mainly by the !rocess of endocytosis, and of
releasing its !rotective nucleo!rotein coating" .or viral re!roduction to occur, the cell must
have the metabolic ca!acity to transcribe and translate virus%coated !roteins, to re!licate viral
nucleic acid, and, under the direction of the virus8s genome, to assemble virions" Certain
agents de!end on cell%surface rece!tors to ingress into the cell1 these relationshi!s have
!otential thera!eutic interest as, for e)am!le, the use of serotonin rece!tor for entry of the 2C
virus into oligodendrocytes"
3he !athologic effects of viruses on susce!tible cells vary greatly" In acute ence!halitis,
susce!tible neurons are invaded directly by virus and the cells undergo lysis" 3here is a
corres!onding glial and inflammatory reaction" Neurono!hagia #!hagocytosis of affected
neurons and their degenerative !roducts by microglia( is a mar0 of this !henomenon" In
!rogressive multifocal leu0oence!halo!athy #PM:(, there is a selective lysis of
oligodendrocytes, resulting in foci of demyelination" V+V and $SV may remain latent in
neurons of the sensory ganglia for long !eriods, until some factor triggers reactivation and
retrograde s!read of virus to cutaneous dermatomes or mucocutaneous e!ithelium" 9nly then
4ill the inflammatory reaction to viral re!lication create sym!toms #!ain, 4ea0ness, sensory
loss(" In certain congenital infections, e"g", rubella and CMV, the virus !ersists in nervous
tissue for months or years" Differentiating cells of the fetal brain have !articular
vulnerabilities, and viral incor!oration may give rise to malformations and to hydroce!halus
#e)am!les are mum!s virus 4ith e!endymal destruction and aueductal stenosis("
In e)!erimental animals cerebral neo!lasms can be induced 4hen the viral genome is
incor!orated into the DNA of the host cell" 3here is suggestive evidence of such a mechanism
in humans relating to ,-V in -%cell lym!homa of the brain" In still other circumstances, a
viral infection may e)ist in the nervous system for a long !eriod before e)citing an
inflammatory reaction #e"g", !rogressive multifocal ence!halo!athy, subacute sclerosing
!anence!halitis(1 in these cases the disease may be so indolent as to simulate a degenerative
disease" 3he !rions have yet other means of affecting cells1 these do not conform to the
classical conce!ts of infection and are discussed in a later section of this cha!ter"
Clinical Syndromes
A large number of viruses are able to affect the nervous system" Among the enteroviruses
alone, nearly ;< distinct serologic ty!es are associated 4ith CNS disease, and additional
ty!es from this family of viruses and others are still being discovered" 3here is no need,
ho4ever, to consider them individually, as there are only a limited number of 4ays in 4hich
they e)!ress themselves clinically" Seven syndromes occur 4ith regularity: #&( acute ase!tic
#=lym!hocytic=( meningitis1 #'( recurrent meningitis1 #>( acute ence!halitis and
meningoence!halitis1 #?( ganglionitis #of her!es *oster(1 #@( chronic invasion of nervous
tissue by retroviruses, i"e", AIDS and tro!ical s!astic !ara!aresis #3SP(1 #A( acute anterior
!oliomyelitis1 and #;( chronic viral infections including the agent causing PM: and subacute
sclerosing !anence!halitis #SSP,(" 3he last grou! is distinguished from infections 4ith the
uniue !rion agents discussed later in the cha!ter"
Syndromes of $er!es +oster
$er!es *oster #=shingles,= =*ona=( is a common viral infection of the nervous system
occurring at an overall rate of > to @ cases !er &,<<< !ersons !er year, 4ith higher rates in the
elderly" Shingles is distinctly rare in childhood" It is characteri*ed clinically by radicular !ain,
a vesicular cutaneous eru!tion, and, less often, by segmental sensory and delayed motor loss"
3he !athologic changes consist of an acute inflammatory reaction in isolated s!inal or cranial
sensory ganglia and lesser degrees of reaction in the !osterior and anterior roots, the !osterior
gray matter of the s!inal cord, and the ad5acent le!tomeninges"
3he neurologic im!lications of the segmental distribution of the rash 4ere recogni*ed by
7ichard -right as long ago as &B>&" Inflammatory changes in the corres!onding ganglia and
related !ortions of the s!inal nerves 4ere first described by von -arens!rung in &BA'" 3he
conce!t that varicella and *oster are caused by the same agent 4as introduced by von -o0ay
in &C<C and 4as subseuently established by Deller and his associates #&C@B(" 3he common
agent, referred to as varicella or V+V, is a DNA virus that is similar in structure to the virus
of her!es sim!le)" 3hese and other historical features of her!es *oster 4ere revie4ed by
Denny%-ro4n, Adams, and .it*gerald and by Deller, Ditton, and -ell"
Pathology and Pathogenesis
3he !athologic changes in V+V infection consist of one or more of the follo4ing: #&( an
inflammatory reaction in several unilateral ad5acent sensory ganglia of the s!inal or cranial
nerves, freuently of such intensity as to cause necrosis of all or !art of the ganglion, 4ith or
4ithout hemorrhage1 #'( an inflammatory reaction in the s!inal roots and !eri!heral nerve
contiguous 4ith the involved ganglia1 #>( a less common !oliomyelitis that closely resembles
acute anterior !oliomyelitis but is readily distinguished by its unilaterality, segmental
locali*ation, and greater involvement of the dorsal horn, root, and ganglion1 and #?( a
relatively mild le!tomeningitis, largely limited to the involved s!inal or cranial segments and
nerve roots" 3hese !athologic changes are the substrate of the neuralgic !ains, the
!leocytosis, and the local !alsies that may attend and follo4 the V+V infection" 3here may
also be a delayed cerebral vasculitis #see further on("
As to pathogenesis, her!es *oster re!resents a s!ontaneous reactivation of V+V infection,
4hich becomes latent in the neurons of sensory ganglia follo4ing a !rimary infection 4ith
chic0en!o) #$o!e%Sim!son(" 3his hy!othesis is consistent 4ith the differences in the clinical
manifestations of chic0en!o) and her!es *oster, even though the same virus causes both"
Chic0en!o) is highly contagious by res!iratory aerosol, has a 4ell%mar0ed seasonal
incidence #4inter and s!ring(, and tends to occur in e!idemics" +oster, on the other hand, is
not communicable #e)ce!t to a !erson 4ho has not had chic0en!o)(, occurs s!oradically
throughout the year, and sho4s no increase in incidence during e!idemics of chic0en!o)" In
!atients 4ith *oster, there is !ractically al4ays a !ast history of chic0en!o)" Such a history
may be lac0ing in rare instances of her!es *oster in infants, but in these cases there has
usually been !renatal maternal contact 4ith V+V"
V+V DNA is locali*ed !rimarily in trigeminal and thoracic ganglion cells, corres!onding to
the dermatomes in 4hich chic0en!o) lesions are ma)imal and that are most commonly
involved by V+V #Mahalingam et al(" 3he su!!osition is that in both *oster and varicella
infections the virus ma0es its 4ay from the cutaneous vesicles along the sensory nerves to the
ganglion, 4here it remains latent until activated, at 4hich time it !rogresses do4n the a)on to
the s0in" Multi!lication of the virus in e!idermal cells causes s4elling, vacuoli*ation, and
lysis of cell boundaries, leading to the formation of vesicles and so%called :i!schEt* inclusion
bodies" Alternatively, the ganglia could be infected during the viremia of chic0en!o), but
then one 4ould have to e)!lain 4hy only one or a fe4 sensory ganglia become infected"
7eactivation of virus is attributed to 4aning immunity, 4hich 4ould e)!lain the increasing
incidence of *oster 4ith aging and 4ith lym!homas, administration of immunosu!!ressive
drugs, AIDS, and after radiation thera!y"
3he sub5ect of !athogenesis of her!es *oster has been revie4ed by Filden and colleagues
#'<<<( and in the monogra!h by 7entier, 4ho describes the molecular and immune
investigations !ertaining to V+V"
Clinical .eatures
As indicated above, the incidence of her!es *oster rises 4ith age" $o!e%Sim!son has
estimated that if a cohort of &,<<< !eo!le lived to B@ years of age, half 4ould have had one
attac0 of *oster and &< 4ould have had t4o attac0s" 3he notion that one attac0 of *oster
!rovides lifelong immunity is incorrect, although recurrent attac0s are rare and most locali*ed
re!eated her!etic eru!tions are caused by $SV" 3he se)es are eually affected, as is each side
of the body" $er!es *oster occurs in u! to &< !ercent of !atients 4ith lym!homa and '@
!ercent of !atients 4ith $odg0in diseaseG!articularly in those 4ho have undergone
s!lenectomy or received radiothera!y" Conversely, a!!ro)imately @ !ercent of !atients 4ho
!resent 4ith her!es *oster are found to have a concurrent malignancy #about t4ice the
number that 4ould be e)!ected(, and the !ro!ortion a!!ears to be even higher if more than
t4o ad5acent dermatomes are involved"
3he vesicular eru!tion is usually !receded for several days by itching, tingling, or burning
sensations in the involved dermatome, and sometimes by malaise and fever" 9r there is severe
locali*ed or radicular !ain that may be mista0en for !leurisy, a!!endicitis, cholecystitis, or,
uite often, ru!tured intervertebral disc, until the diagnosis is clarified by the a!!earance of
vesicles #nearly al4ays 4ithin ;' to CA h(" 3he rash consists of clusters of tense clear vesicles
on an erythematous base, 4hich become cloudy after a fe4 days #as a result of accumulation
of inflammatory cells(, and dry, crusted, and scaly after @ to &< days" In a small number of
!atients, the vesicles are confluent and hemorrhagic, and healing is delayed for several
4ee0s" In most cases, !ain and dysesthesia last for & to ? 4ee0s1 but in the others #; to >>
!ercent in different series( the !ain !ersists for months or, in different forms, for years, and
!resents a difficult !roblem in management" Im!airment of su!erficial sensation in the
affected dermatome#s( is common, and segmental 4ea0ness and atro!hy are added in
a!!ro)imately @ !ercent of !atients" In the ma5ority of !atients the rash and sensorimotor
signs are limited to the territory of a single dermatome, but in some, !articularly those 4ith
cranial or limb involvement, t4o or more contiguous dermatomes are involved" 7arely #and
usually in association 4ith malignancy( the rash is generali*ed, li0e that of chic0en!o), or it
is altogether absent #herpes sine herpete("
In half of the cases, the CS. sho4s a mild increase in cells, mainly lym!hocytes, and a
modest increase in !rotein content #although lumbar !uncture is not !erformed to establish
the diagnosis(" 3he her!etic nature of the eru!tion can be confirmed by direct
immunofluorescence of a bio!sied s0in lesion, using antibody to V+V, or inferred by finding
multinucleated giant cells in scra!ings from the base of an early vesicle #3*anc0 smear(" 3he
s!inal fluid also contains antibodies to the virus or evidence of the organism by PC7 testing
in >@ !ercent of cases according to a !ros!ective study by $aan!HH and colleagues"
Virtually any dermatome may be involved in *oster, but some regions are far more freuent
than others" 3he thoracic dermatomes, !articularly 3@ to 3&<, are the most common sites,
accounting for more than t4o%thirds of all cases, follo4ed by the craniocervical regions" In
the latter cases the disease tends to be more severe, 4ith greater !ain, more freuent
meningeal signs, and involvement of the mucous membranes"
3here are t4o rather characteristic cranial her!etic syndromesGo!hthalmic her!es and
geniculate her!es" In ophthalmic herpes, 4hich accounts for &< to &@ !ercent of all cases of
*oster, the !ain and rash are in the distribution of the first division of the trigeminal nerve,
and the !athologic changes are centered in the gasserian ganglion" 3he main ha*ard in this
form of the disease is her!etic involvement of the cornea and con5unctiva, resulting in corneal
anesthesia and residual scarring" Palsies of e)traocular muscles, !tosis, and mydriasis are
freuently associated, indicating that the third, fourth, and si)th cranial nerves are affected in
addition to the gasserian ganglion" 3he less common but also characteristic cranial nerve
syndrome consists of a facial !alsy in combination 4ith a her!etic eru!tion of the e)ternal
auditory meatus, sometimes 4ith tinnitus, vertigo, and deafness" 7amsay $unt #4hose name
has been attached to the syndrome( attributed this illness to her!es of the geniculate ganglion"
Denny%-ro4n, Adams, and .it*gerald found the geniculate ganglion to be only slightly
affected in a man 4ho died A? days after the onset of a so%called Ramsay Hunt syndrome
#during 4hich time the !atient had recovered from the facial !alsy(1 there 4as, ho4ever,
inflammation of the facial nerve"
$er!es *oster of the !alate, !haryn), nec0, and retroauricular region #herpes occipitocollaris(
de!ends on her!etic infection of the u!!er cervical roots and the ganglia of the vagus and
glosso!haryngeal nerves" $er!es *oster in this distribution may also be associated 4ith the
7amsay $unt syndrome" 3he relative freuency of distribution of *oster in these truncal
dermatomes and a !roclivity for facial eru!tion, suggests to us that her!etic neurological
syndromes are more li0ely to occur if the distance of the ganglia from the s0in is short"
Encephalitis and cerebral angiitis are rare but 4ell%described com!lications of cervicocranial
*oster, as discussed belo4, and a restricted but destructive myelitis is a similarly rare but
often uite serious com!lication of thoracic *oster" Devins0y and colleagues re!orted their
findings in &> !atients 4ith *oster myelitis #all of them immunocom!romised( and revie4ed
the literature on this sub5ect" 3he signs of s!inal cord involvement a!!eared @ to '& days after
the rash and then !rogressed for a similar !eriod of time" Asymmetrical !ara!aresis and
sensory loss, s!hincteric disturbances, and, less often, a -ro4n%SIuard syndrome 4ere the
usual clinical manifestations" 3he CS. findings 4ere more abnormal than in uncom!licated
*oster #!leocytosis and raised !rotein( but other4ise similar" 3he !athologic changes, 4hich
ta0e the form of a necroti*ing inflammatory myelo!athy and vasculitis, involve not 5ust the
dorsal horn but also the contiguous 4hite matter, !redominantly on the same side and at the
same segment#s( as the affected dorsal roots, ganglia, and !osterior horns" ,arly thera!eutic
intervention 4ith acyclovir a!!eared to be beneficial" 9ur e)!erience 4ith the !roblem
includes an elderly man 4ho 4as not immunosu!!ressed1 he remained 4ith an almost
com!lete transverse myelo!athy" Another rare com!lication of *oster, ta0ing the form of a
subacute amyotro!hy #*oster !aresis( of a !ortion of a limb, is !robably lin0ed to a restricted
form of V+V myelitis"
Many of the 4ritings on zoster encephalitis give the im!ression of a severe illness that occurs
tem!orally remote from the attac0 of shingles in an immunosu!!ressed !atient" Indeed, such
instances have been re!orted in !atients 4ith AIDS and may be concurrent 4ith the small
vessel vasculitis described belo4" $o4ever, our e)!erience is more in 0ee!ing 4ith that of
2emse0 and colleagues and of Peterslund, 4ho described a less severe form of ence!halitis in
!atients 4ith normal immune systems" 9ur > !atients, all elderly 4omen, develo!ed self%
limited ence!halitis during the latter stages of an attac0 of shingles" 3hey 4ere confused and
dro4sy, 4ith lo4%grade fever but little meningismus, and a fe4 had sei*ures" 7ecovery 4as
com!lete and the M7I 4as normal, in distinction to the vasculitic syndromes" In some
re!orted cases, V+V has been isolated from the CS. and s!ecific antibody to V+V membrane
antigen #VAMA( has been found in the CS. and serum, although it is hardly needed for
!ur!oses of diagnosis" #3he differential diagnosis in these elderly !atients also includes a
dro4sy confusional state induced by narcotics given for the control of !ain"( Varicella
cerebellitis, a !ost% or !arainfectious condition, 4as discussed earlier in the cha!ter"
+oster Angiitis
A cerebral angiitis that occasionally com!licates V+V infection is histologically similar to
granulomatous angiitis and to Degener granulomatosis" 3y!ically, ' to &< 4ee0s after the
onset s!ecifically of o!hthalmic *oster, the !atient develo!s an acute hemi!aresis,
hemianesthesia, a!hasia, or other focal neurologic or retinal deficits associated 4ith a
mononuclear !leocytosis in the s!inal fluid and elevated IgF indices in the CS." Nagel and
colleagues have found that s!ecific antibodies in the CS. to the virus 4ere more sensitive for
the diagnosis of this condition than 4as detection of viral DNA" C3 or M7I scans
demonstrate small, dee! infarcts in the hemis!here i!silateral to the outbrea0 of shingles on
the face" Angiograms sho4 narro4ing or occlusion of the internal carotid artery ad5acent to
the ganglia1 but in some cases, vasculitis is more diffuse, even involving the contralateral
hemis!here" Dhether the angiitis results from direct s!read of the viral infection via
neighboring nerves as !ostulated by :innemann and Alvira, or re!resents an allergic reaction
during convalescence from *oster, has not been settled" V+V%li0e !articles have been found in
the vessel 4alls, suggesting a direct infection and viral DNA has been e)tracted in a fe4
cases from affected vessels" -ecause the e)act !athogenetic mechanism is uncertain,
treatment 4ith both intravenous acyclovir and corticosteroids may be 5ustified" 3here are
occasional instances of a cerebral vasculitis follo4ing dermatomal *oster on the trun0"
An entirely different ty!e of delayed vasculitis that affects small vessels, 4ith 4hich 4e have
had no e)!erience, is being re!orted in !atients 4ith AIDS and other forms of
immunosu!!ression" In this condition, 4ee0s or months after one or more attac0s of *oster, a
subacute ence!halitis ensues, including fever and focal signs" Some cases a!!arently arise
4ithout a rash, but viral DNA and antibodies to V+V are found in the CS." 3he M7I sho4s
multi!le cortical and 4hite matter lesions, the latter being smaller and less confluent than in
!rogressive multifocal leu0oence!halo!athy" 3here is usually a mild !leocytosis" Almost all
cases have ended fatally" 3he vasculitic and other neurologic com!lications of *oster have
been revie4ed by Filden and colleagues #'<<'("
.inally, as mentioned earlier, a facial !alsy or !ain in the distribution of a trigeminal or
segmental nerve #usually lumbar or intercostal( as a result of her!etic ganglionitis, may occur
rarely 4ithout involvement of the s0in #zoster sine herpete(1 lumbar disc herniation may be
sus!ected" In a fe4 such cases, an antibody res!onse to V+V has been found #Mayo and
-ooss(, and Dueland and associates have described an immunocom!romised !atient 4ho
develo!ed a !athologically and virologically !roved *oster infection in the absence of s0in
lesions" Similarly, Filden and colleagues #'<<'( recovered V+V DNA from t4o other4ise
healthy immunocom!etent men 4ho had e)!erienced chronic radicular !ain 4ithout a *oster
rash" -ut !ractically no instances of -ell8s !alsy, tic douloureu), and intercostal neuralgia are
associated 4ith serologic evidence of activation of V+V #-ell8s !alsy has instead been
associated 4ith $SV, as indicated in Cha!" ?;("
3reatment
An im!ortant recent ince!tion has been a vaccine that can be administered to older adults" It
has been sho4n to reduce the emergence of shingles and to decrease the incidence of
!osther!etic com!lications by t4o%thirds #9)man et al("
During the acute stage of shingles, analgesics and drying and soothing lotions, such as
calamine, hel! to blunt the !ain" Nerve root bloc0s may !rovide very tem!orary relief" After
the lesions have dried, the re!eated a!!lication of ca!saicin ointment #derived from hot
!e!!ers( may relieve the !ain in some cases by inducing a cutaneous anesthesia" Dhen
a!!lied too soon after the acute stage, ho4ever, ca!saicin is highly irritating and should be
used cautiously" Acyclovir #B<< mg orally @ times daily for ; d( shortens the duration of acute
!ain and s!eeds the healing of vesicles, !rovided that treatment is begun 4ithin
a!!ro)imately ?B h #some authorities say ;' h( of the a!!earance of the rash #McJendric0 et
al, &CBA(" .amciclovir #@<< mg tid for ; d( or the better absorbed valacyclovir #' g orally id(
are alternatives" Several studies have suggested that the duration of !osther!etic neuralgia is
reduced by treatment during the acute !hase 4ith famciclovir or valacyclovir, but the
incidence of this com!lication is not mar0edly affected and a similar effect of shortening the
illness has not been sho4n for acyclovir #see belo4 on the sub5ect of !osther!etic neuralgia("
All !atients 4ith o!hthalmic *oster should receive acyclovir or valacyclovir orally1 in
addition, acyclovir a!!lied to!ically to the eye, in either a <"& !ercent solution every hour or a
<"@ !ercent ointment ? or @ times a day, is recommended by some o!hthalmologists" Patients
4ho are immunocom!romised or have disseminated *oster #lesions in more than >
dermatomes( should generally receive intravenous acyclovir for &< d" 3here is no4 available
#from state health agencies( a V+V immune globulin #V+IF( that shortens the course of the
cutaneous disease and may !rotect against its dissemination in immunosu!!ressed !atients"
Although it may reduce the incidence of !osther!etic neuralgia #$ugler et al(, this is not its
main !ur!ose and it does not a!!ear to !revent or ameliorate CNS com!lications"
Posther!etic Neuralgia
#See also Cha!s" B and &<(
3his severely !ainful syndrome follo4s shingles in @ to &< !ercent of !atients but occurs
almost three times more often among individuals older than age A< years" 3he !ossible effect
of acute treatment on the severity of !osther!etic neuralgia is mentioned above but !otential
!revention 4ith the vaccine is even more a!!ealing"
3he management of postherpetic pain and dysesthesia can be a trying matter for both the
!atient and the !hysician" It is li0ely that incom!lete interru!tion of nerves results in a
hy!er!athic state in 4hich every stimulus e)cites !ain" In a number of controlled studies,
amitri!tyline !roved to be an effective thera!eutic measure" Initially, it is given in doses of
a!!ro)imately @< mg at bedtime1 if needed, the dosage can be increased gradually to &'@ mg
daily" 3he addition of carbama*e!ine, gaba!entin, or val!roate may further moderate the
!ain, !articularly if it is of lancinating ty!e" Ca!saicin ointment can be a!!lied to !ainful
s0in, as noted above" A salve of t4o as!irin tablets, crushed and mi)ed 4ith cold cream or
chloroform #&@ m:( and s!read on the !ainful s0in, 4as re!orted to be successful in relieving
the !ain for several hours #Jing(" 3he effect of nerve root bloc0s is inconsistent, but this
!rocedure may afford tem!orary relief" In one randomi*ed trial, the !reem!tive use of
e!idural steroids at the onset of the rash had minimal effects #van Di5c0 et al(" It should be
em!hasi*ed that !osther!etic neuralgia eventually subsides even in the most severe and
!ersistent cases but the short%term use of narcotics is a!!ro!riate 4hen the !ain is severe"
Kntil the !ain subsides, the !hysician must e)ercise s0ill and !atience and avoid the
tem!tation of sub5ecting the !atient to one of the many surgical measures that have been
advocated for this disorder #see Cha!" C for further discussion of !ain management(" Many
!atients 4ith the most !ersistent com!laints, beyond a year, have sym!toms of a de!ressive
state and 4ill be hel!ed by antide!ressive medications"