Diapositiva 1 - Università degli Studi di Perugia

Università degli Studi di Perugia
Encefaliti
Prof. Paolo Calabresi
Corso Integrato di Neurologia

ENCEPHALITIS
1. Encephalitis, an inflammation of the brain parenchyma,
presents as diffuse and/or focal neuropsychological
dysfunction.
2. From an epidemiologic and pathophysiologic perspective,
encephalitis is distinct from meningitis, though on clinical
evaluation the 2 often coexist with signs and symptoms of
meningeal inflammation, such as photophobia, headache,
or a stiff neck.
3. Cerebritis describes the stage preceding abscess
formation and implies a highly destructive bacterial
infection of brain tissue, whereas acute encephalitis is
most commonly a viral infection with parenchymal damage
varying from mild to profound.

1. Of the subacute and chronic encephalopathies, the ED
physician is most likely to encounter toxoplasmosis in
immunocompromised patients.
2. No satisfactory treatment exists for the relatively common
acute arboviral encephalitides, which vary in epidemiology,
mortality, and morbidity, if not clinical presentation.
3. Clinically distinguishing these acute arboviral encephalitides
from the 2 potentially treatable acute viral encephalitides is
important. The latter encephalitides include herpes simplex
encephalitis (HSE), which is a sporadic and lethal disease of
neonates and the general population, and the less common
varicella-zoster encephalitis, which is deadly in
immunocompromised patients.

1. Swift identification and immediate treatment can be
lifesaving.
2. Most authorities advocate initiating ED treatment
with the relatively safe acyclovir in any patient
whose CNS presentations (particularly
encephalopathy and focal findings) have no
apparent explanation and in all neonates who
appear ill and are without a final diagnosis.

1. In 1999, a late summer outbreak of West Nile encephalitis
(WNE), an arbovirus not found previously in the United States,
was implicated in several deaths in New York.
2. By late summer 2002, West Nile virus has been identified
throughout the eastern and southeastern United States.
3. Following bird migration, the virus is presently extending
westward, and by April 2003, virus activity had been detected
in 46 states and the District of Columbia.
4. An updated Centers for Disease Control and Prevention (CDC)
report for 2007 (West Nile Virus Update) includes
information regarding viremic blood donors.
5. Throughout the world, outbreaks of WNE have been
associated with severe neurologic disease; though, in general,
only 1 in 150 affected patients develop symptomatic WNE.

1. Determining the true incidence is impossible because reporting policies
are neither standardized nor rigorously enforced.
2. In the United States, several thousand cases of viral encephalitis are
reported yearly. This is probably a fraction of the actual number of
cases.
3. HSE, the most common cause of sporadic encephalitis in Western
countries, is relatively rare; the overall incidence is 0.2 per 100,000
(neonatal HSV infection occurs in 2-3 per 10,000 live births).
4. Arboviruses are the most common causes of episodic encephalitis with
reported incidence similar to that of HSV.
5. These statistics may be even more misleading because most people
bitten by arbovirus-infected insects do not develop clinical disease, and
only 10% develop overt encephalitis.

1. Clinical presentation and course can be markedly variable. Acuity and severity
of presentation correlates with prognosis.
2. The patient may have history of animal bite for which antirabies treatment
may not have been obtained.
3. The general viral prodrome is several days long and consists of fever,
headache, nausea and vomiting, lethargy, and myalgias.
4. The specific prodrome in VZV, EBV, CMV, measles, and mumps includes
rash, lymphadenopathy, hepatosplenomegaly, and parotid enlargement.
5. Dysuria and pyuria are reported with St Louis encephalitis.
6. Extreme lethargy has been noted with WNE

Pathophysiology
1. Portals of entry are virus specific.
2. Many viruses are transmitted by humans, although
most cases of HSE are thought to be reactivation of
the herpes simplex virus (HSV) lying dormant in the
trigeminal ganglia.
3. Mosquitoes or ticks inoculate arbovirus, and rabies
virus is transferred via animal bite.
4. With some viruses, such as varicella-zoster virus (VZV)
and cytomegalovirus (CMV), an immunocompromised
host is a key risk factor.

1. In general, the virus replicates outside the CNS and gains entry either
by hematogenous spread or by traveling along neural (rabies, HSV,
VZV) and olfactory (HSV) pathways.
2. The etiology of slow virus infections, such as those implicated in the
measles-related subacute sclerosing panencephalitis (SSPE) and
progressive multifocal leukoencephalopathy (PML), is poorly
understood.
3. Once across the blood-brain barrier, the virus enters neural cells, with
resultant disruption in cell functioning, perivascular congestion,
hemorrhage, and inflammatory response diffusely affecting gray
matter disproportionately to white matter.
4. Focal pathology is the result of neuron cell membrane receptors found
only in specific portions of the brain and accounts for regional tropism
found with some viruses. For example, HSV has a predilection for the
inferior and medial temporal lobes.

1. Although most histologic features are nonspecific,
brain biopsies are the diagnostic criterion standard for
rabies.
2. Presence of Negri bodies in the hippocampus and
cerebellum are pathognomonic of rabies, as are HSV
Cowdry type A inclusions with hemorrhagic necrosis in
the temporal and orbitofrontal lobes.
3. In contrast to viruses that invade gray matter directly,
acute disseminated encephalitis and postinfectious
encephalomyelitis (PIE), secondary to measles (most
common), Epstein-Barr virus (EBV), and CMV, are
immune-mediated processes, which result in multifocal
demyelination of perivenous white matter.

The classic presentation is encephalopathy with diffuse or focal
neurologic symptoms, including the following:
1. Behavioral and personality changes, decreased level of
consciousness
2. Stiff neck, photophobia, and lethargy
3. Generalized or localized seizures (60% of children with California
encephalitis [CE])
4. Acute confusion or amnestic states
5. Flaccid paralysis (10% with WNE)
6. Less common symptoms include headache and other complaints of
meningismus.

Neonatal HSV infection symptoms (1-45 d) may occur in any combination.
1. Skin, eye, and mouth lesions (early presentation)
2. Encephalitis - Change in level of alertness, irritability, seizures, poor
feeding
3. Evidence of widespread, disseminated disease, such as rash or shock
HSE in older children and adults
1. Unrelated to history of oral lesions in infants
2. Acute onset of severe symptoms of encephalitis
Toxoplasma encephalopathy accounts for as many as 40% of patients who are
HIV positive with neurologic disease who present with a subacute headache,
encephalopathy, and, often, a focal neurological complaint. This may be the
presenting symptom of immunosuppression/HIV infection.

The signs of encephalitis may be diffuse or focal (80% of patients with HSE
present with focal findings) as follows:
•Altered mental status and/or personality changes (most common)
•Focal findings, such as hemiparesis, focal seizures, and autonomic dysfunction
•Movement disorders (St Louis encephalitis, EEE, WEE)
•Ataxia
•Cranial nerve defects
•Dysphagia (Rabies may account for foaming at the mouth and hydrophobia.)
•Meningismus (less common and less pronounced than in meningitis)
•Unilateral sensorimotor dysfunction (PIE)
HSV infection in the neonate (aged 1-45 d)
Herpetic skin lesions over the presenting surface from birth or with breaks in the
skin, such as those resulting from fetal scalp monitors
Keratoconjunctivitis
Oropharyngeal involvement, particularly buccal mucosa and tongue
Encephalitis symptoms, such as seizures, irritability, change in level of
attentiveness, bulging fontanels
Additional signs of disseminated HSV, such as shock, jaundice, and
hepatomegaly
Toxoplasma encephalopathy: In immunosuppressed patients, 75% present with a focal
neuropathology, about one half with encephalopathic changes.

Lab Studies
Complete blood count (CBC) with differential: Findings are usually within the
reference range.
Serum electrolytes: These are usually within the reference range. Syndrome of
inappropriate secretion of antidiuretic hormone (SIADH) occurs in 25% of patients
with St Louis encephalitis.)
Serum glucose level: Use this level as a baseline for determining normal CSF
glucose values. The result may be low if glycogen stores are depleted or high in
infected patients with diabetes mellitus.
BUN/creatinine and liver function tests (LFTs): Assess organ function and the need
to adjust the antibiotic dose.
Platelet test and a coagulation profile: These are indicated in patients with
chronic alcohol use, liver disease, or if disseminated intravascular coagulation
(DIC) is suspected. The patient may require platelets or fresh-frozen plasma (FFP)
before lumbar puncture (LP).
Urinary electrolyte test: Perform this assessment if SIADH is suspected.
Urine and/or serum toxicology screening: Perform 1 or both of these tests, if
indicated.

Other laboratory tests:
CSF polymerase chain reaction (PCR): A PCR for DNA HSV is 100% specific
and 75-98% sensitive within the first 25-45 hours. Types 1 and 2 cross-react,
but no cross-reactivity with other herpes viruses occurs. Arguably, a series of
quantitative PCRs documenting the decline of viral load with acyclovir
treatment may clinch diagnosis without brain biopsy.
HSV cultures: These are used to test lesions (also Tzanck smear), CSF (rarely
positive), and blood.
Viral serology: Complement fixation antibodies are useful in identifying
arbovirus. Cross-reactivity exists among one subgroup of arboviruses, the
flaviviruses (eg, St Louis encephalitis, JE, WNE), and with antibodies raised in
persons inoculated with the yellow fever vaccine.
Viral serology: Complement fixation antibodies are useful in identifying
arbovirus.
Heterophile antibody and cold agglutinins for EBV: These tests may be helpful.
Serologic tests for toxoplasmosis: These can be helpful in light of an abnormal
CT scan, particularly in the case of single lesions. However, the overlap in titer
between previously exposed but presently uninfected and reactivated groups
may complicate interpretation.

Imaging Studies
Perform head CT, with and without contrast agent, in virtually all patients with
encephalitis before LP to search for evidence of elevated intracerebral pressure
(ICP), obstructive hydrocephalus, or mass effect. It is helpful also in differential
diagnosis. MRI is more likely to show abnormalities earlier in disease course
than head CT.
In HSE, an MRI may show several foci of increased T2 signal intensity in medial
temporal lobes and inferior frontal gray matter. Head CT may show petechial
hemorrhage in the same areas.
EEE and tick-borne encephalitis may show similar increased signal intensity in
the basal ganglia and thalami.
In toxoplasmosis, contrast-enhanced head CT typically reveals several nodular
or ring-enhancing lesions. Because lesions may be missed without contrast, MRI
should be performed in patients for whom use of contrast material is
contraindicated.

Electroencephalography
Other Tests
In HSE, characteristic paroxysmal lateral epileptiform discharges (PLEDs)
often are observed, even before neuroradiographic changes.
Eventually, PLEDs are positive in 80% of cases. The presence of PLEDs is
not pathognomonic for HSE.
CSF analysis is essential.
General patterns in bacterial and fungal (cryptococcal) meningitis found
during the measurement of CSF pressure and CSF analysis may support a
diagnosis (see the Table below).
The most important diagnostic test in the ED to rule out bacterial meningitis
is well-performed Gram staining and, if available, polymerase chain
reaction of the CSF in patients with suspected HSV encephalitis.

Prehospital Care
1. Evaluate and treat for shock or hypotension. Administer a crystalloid
infusion until the patient is euvolemic.
2. Consider airway protection in patients with an altered mental status.
3. Consider seizure precautions. Treat seizures according to usual
protocol (ie, lorazepam 0.1 mg/kg given intravenously [IV]).
4. Stabilize alert patients with normal vital signs by administering oxygen,
securing IV access, and providing rapid transport to the ED.

Emergency Department Care
With the important exceptions of HSE and varicella-zoster encephalitis, the viral
encephalitides are not treatable beyond supportive care.
The goal of treatment for acutely ill patients is administration of the first dose or
doses acyclovir with or without antibiotics or steroids as quickly as possible.
The standard for acute bacterial meningitis is the initiation of treatment
within 30 minutes of arrival.
Consider instituting an ED triage protocol to identify patients at risk for HSE.
Collect laboratory samples and blood cultures before the start of IV therapy.
Even in uncomplicated cases of encephalitis, most authorities recommend a
neuroimaging study (eg, contrast-enhanced head CT scan) before LP.
Signs of hydrocephalus and increased ICP

Emergency Department Care
General measures: Manage fever and pain, control straining and coughing,
and avoid seizures and systemic hypotension.
In otherwise stable patients, elevating the head and monitoring neurologic
status usually are sufficient.
When more aggressive maneuvers are indicated, some authorities favor the
early use of diuresis (eg, furosemide 20 mg IV, mannitol 1 g/kg IV) provided
circulatory volume is protected. Dexamethasone 10 mg IV q6h helps in
managing edema surrounding space-occupying lesions. Hyperventilation
(PaCO2 30 mm Hg) may cause a disproportional decrease in cerebral blood
flow (CBF), but it is used to control increasing ICP on an emergency basis.
Look for and treat systemic complications, particularly in HSE, EEE, JE, such as
hypotension or shock, hypoxemia, hyponatremia (SIADH), and exacerbation of
chronic diseases.

Other Problems to be Considered
•Acute CNS events, such as hemorrhagic stroke
•Acute confusional states secondary to drugs, toxins, psychosis
•Amoeba (Naegleria, Acanthamoeba)
•Head trauma
•CNS syphilis
•Ehrlichiosis
•Intracranial hemorrhage
•Intracranial tumor
•Trauma

Background:
Herpes encephalitis is the most common cause of sporadic viral encephalitis,
with a predilection for the temporal lobes and a range of clinical presentations,
from aseptic meningitis and fever to a severe rapidly progressive form
involving altered consciousness.
In adults, herpes simplex virus type 1 (HSV-1) accounts for 95% of all fatal
cases of sporadic encephalitis and usually results from reactivation of the
latent virus.
The clinical findings and neuroimaging appearance are both consistent with
spread of the virus from a previously infected ganglion.
In children and neonates, herpes simplex virus type 2 (HSV-2) accounts for
80-90% of neonatal and almost all congenital infections.
An isolated case report of an immunocompromised adult patient developing
HSV-2 infection has been described.
MRI can play an important role in determining the diagnosis and extent of
disease.

On pathology, herpes viruses cause a fulminant
hemorrhagic and necrotizing meningoencephalitis.
Typical gross findings include severe edema and massive
tissue necrosis, with petechial hemorrhages and
hemorrhagic necrosis.
Often, the petechial hemorrhage is not observed on CT or
MRI.
On microscopy, a focal necrotizing vasculitis is observed
with perivascular and meningeal lymphocytic infiltration and
eosinophilic intranuclear inclusions in glial cells and
neurons.

Mortality/Morbidity:
Untreated patients with HSV-1 have a 70% mortality rate.
With early treatment, 40% of patients recover without significant neurologic
deficits; however, despite appropriate diagnosis and therapy, the mortality rate
remains at 30%.
Interestingly, HSV does not appear to be more common in
immunocompromised patients than in normal hosts. HSV-1 is rarely associated
with pregnancy.
HSV mortality in neonates with isolated CNS disease is 15%, and in those with
disseminated CNS disease, the rate is 57%.
Morbidity for these groups is also high.

Clinical Details:
In adults, the most common early symptoms are headache and fever. Additional
symptoms include intellectual impairment, aphasia, meningeal signs, seizures, and
paresthesias. Early treatment is crucial to a good outcome, and empiric acyclovir
therapy can be initiated before a definitive diagnosis is established. The virus
cannot be cultured routinely from CSF, though lymphocytic pleocytosis and
elevations in protein concentrations are observed. CSF viral cultures are positive
for HSV in fewer than 5% of patients. Anti-HSV antibodies often do not appear until
1-3 weeks after symptom onset; therefore, antibody culture is helpful only in
retrospective diagnosis. In some patients, a brain biopsy may be required for a
definitive diagnosis.
EEG also can reveal focal temporal abnormalities, which are seen in 80% of
patients; a normal EEG is believed to exclude the diagnosis. Periodic lateralized
epileptiform discharges also support the diagnosis, but this finding is nonspecific.
Historically, a brain biopsy provided a definitive diagnosis, but this procedure is not
highly sensitive and can result in complications, including hemorrhage and edema
at the biopsy site. An RNA polymerase test of CSF permits a more definitive
diagnosis because it is both sensitive and specific. In this test, 2 sets of
oligonucleotide primers amplify gene products from HSV-1 and HSV-2.

Picture 1. Axial proton density–
weighted image in a 62-year-old
woman with confusion and herpes
encephalitis shows T2
hyperintensity involving the right
temporal lobe.

Picture 2. Axial nonenhanced T1-
weighted image shows cortical
hyperintensity (arrows) consistent
with petechial hemorrhage. In
general, this is a common pathologic
finding but less commonly depicted
in herpes encephalitis.

Picture 3. Axial
gadolinium-enhanced T1-
weighted image reveals
enhancement of the right
anterior temporal lobe
and parahippocampal
gyrus. At the right anterior
temporal tip is a
hypointense, crescentic
region surrounded by
enhancement consistent
with a small epidural
abscess.

Picture 4. Axial diffusionweighted
image reveals
restricted diffusion in the
left medial temporal lobe
consistent with herpes
encephalitis. This patient
also had a positive result on
polymerase chain reaction
assay for herpes simplex
virus, which is both
sensitive and specific. In
addition, the patient had
periodic lateralized
epileptiform discharges on
EEG, which supports the
diagnosis of herpes
encephalitis.

Picture 5. Coronal T2-
weighted image reveals
hyperintensity in the left
temporal lobe (arrows) in
a distribution similar to
the restricted diffusion
abnormality seen in
Image 4. This finding is
typical for herpes
encephalitis.

La diagnosi viene fatta sulla base dei sintomi
clinici e per le caratteristiche
dell'elettroencefalogramma che presenta
particolari alterazioni (pseudoperiodismi) in
un numero rilevante di casi. L'aumentata
concentrazione della proteina 14-3-3 e della
proteina TAU nel fluido cerebrospinale. La
conferma diagnostica può essere fatta solo
mediante la dimostrazione delle
caratteristiche lesioni spongiformi
accompagnate dalla presenza di proteina
prionica (PrPres o PrPsc) in un prelievo di
tessuto nervoso.
La malattia di Creutzfeldt-Jacob, originariamente descritta negli anni '20 del XX
secolo da Hans Gerhard Creutzfeldt ed Alfons Maria Jakob, è una malattia
neurodegenerativa rara, che conduce ad una forma di demenza progressiva fatale. La
sindrome clinica è caratterizzata da perdita di memoria, cambiamenti di personalità,
allucinazioni, disartria, mioclonie, rigidità posturale e convulsioni. I sintomi ed i segni
sono dovuti alla progressiva perdita di neuroni causata da alterazione di una proteina
di membrana, espressa prevalentemente in cellule del sistema nervoso e del sistema
reticolo-endoteliale, il prione. La sua incidenza si è mantenuta relativamente costante
negli ultimi 80 anni, nell'ordine di 1-2/1000000. Ottiene gli onori della cronaca dopo la
descrizione dei primi casi di una forma variante, ancor più rara, legata all'epidemia di
Encefalopatia spongiforme bovina, la cosiddetta malattia della "mucca pazza".

Head CT (left) and MRI (right) both given with contrast of the same patient
with new seizures, focal weakness, and HIV infection. Multiple ring-enhancing
lesions are seen in the periventricular white matter. The lesions are consistent
with Toxoplasma encephalitis. The images point out the enhanced sensitivity
of MRI scanning over CT scanning in this instance.

MR Imaging of
Autopsy-
Proved
Paraneoplasti
c Limbic
Encephalitis in
Non-Hodgkin
Lymphoma
Initial MR images obtained 1 day after the first generalized seizure occurred.
A, Axial fluid-attenuated inversion recovery image (9000/110 [TR/TE]; inversion
time, 2261 ms) shows a slightly elevated signal intensity of both hippocampal
formations (black arrows) and amygdala (white arrows).
B, Coronal conventional T2-weighted turbo spin-echo image

Typical cranial magnetic resonance imaging (MRI) findings in patients with
paraneoplastic limbic encephalitis. Coronal fluid-attenuated inversion
recovery (FLAIR) MRI showing bilateral (left) and unilateral (middle) mesial
temporal signal abnormalities. Axial FLAIR MRI showing extralimbic signal
abnormalities involving the left operculum and insular cortex (right).

Brain magnetic resonance imaging (MRI) studies. A and B, Axial MRI fluidattenuated
inversion recovery images at presentation show increased signal in the cerebellar
vermis and periventricular white matter. C and D, Follow-up images (same sequences
and levels) 16 days later show progression of signal abnormality in the cerebellar
vermis and periventricular white matter with extension across the corpus callosum.

La Panencefalite sclerosante subacuta è una rara malattia degenerativa
del sistema nervoso centrale, causata dalla persistenza di un virus del
morbillo difettivo.
Si verifica in media a distanza di 9 anni dal morbillo.
La malattia cerebrale è evolutiva, subdola ed inesorabile ed è caratterizzata
da gravi lesioni cerebrali, con una progressiva perdita di tutte le funzioni
cognitive, con spasmi mioclonici e convulsioni.
È un’encefalite a lenta evoluzione, la cui frequenza è di circa 1 caso ogni
100.000 casi di morbillo, più frequente nei soggetti che lo avevano contratto
nei primi due anni di vita.
Sono stati segnalati anche 20 casi di panancefalite progressiva dopo rosolia.
I dati epidemiologici disponibili non documentano però un rischio legato al
vaccino.
Il vaccino contro il morbillo riduce in maniera significativa la possibilità di
sviluppare la PESS, così come dimostrato dalla sostanziale eliminazione dei
casi di PESS dopo l’introduzione del vaccino contro il morbillo, sebbene la
malattia è stata raramente riscontrata in bambini senza una storia d’infezione
morbillosa, ma che avevano ricevuto il vaccino contro il morbillo.
È da segnalare che i bambini di età inferiore ad 1 anno, o malnutriti,
immunocompromessi o affetti da patologie croniche, sono particolarmente
suscettibili all'infezione.

PESS: QUADRO CLINICO
• Deterioramento intellettivo. I primi segni sono spesso un ridotto rendimento
scolastico, perdita della memoria, cambiamenti repentini dell'umore, distrazione,
insonnia ed allucinazioni. Possono anche verificarsi crisi convulsive. I pazienti
mostrano quindi un ulteriore declino intellettuale, manifestando alterazioni della
parola.
• Convulsioni. Le convulsioni fanno seguito alle alterazioni mentali ed
inizialmente sono costituite da spasmi mioclonici.
• Anomalie motorie e movimenti involontari anomali. Possono comparire
movimenti distonici e periodi transitori di opistotono. Più tardivamente, si verifica
una rigidità della muscolatura corporea, difficoltà alla deglutizione, cecità
corticale e atrofia ottica. In molti pazienti si verificano corioretinite focale e
altre anomalie del fundus. Nelle fasi finali, il paziente diviene progressivamente
rigido, con segni intermittenti d'interessamento ipotalamico (per esempio,
ipertermia, sudorazione, disturbi della PA e del ritmo cardiaco).

PESS: MRI scans of the brain at
the time of presentation in the
neurology clinic (A and B) and 3
months later (C and D). Panels A
and C are T1-weighted images; B
and D are T2-weighted images.
The initial MRI scan (A and B)
reveals a focal abnormality in the
subcortical white matter of the left
frontal lobe, consisting of a
hypointense signal on the T1-
weighted image (arrow in A) and a
hyperintense signal on the T2-
weighted image (arrow in B). In the
followup scan, the focal
abnormality in the left frontal lobe
is less obvious than previously
(arrow in D), but advanced and
diffuse cortical atrophy is present,
signified by the ventriculomegaly
and markedly enlarged sulci
(arrowheads in C).

Acute disseminated encephalomyelitis (ADEM)
ADEM is an inflammatory demyelinating disease of the central nervous
system (CNS) that is known to occur spontaneously in association with
specific and nonspecific viral illnesses and after vaccination against
various pathogens.
Although it is often a self-limited monophasic illness, the fatality rate is
estimated to be as high as 30%, and many patients suffer residual
neurologic impairment.
Clinical improvement has been reported after initiation of corticosteroid
therapy, and relapse has occurred after discontinuation of therapy.

ADEM A and B, Axial
magnetic resonance
images, demonstrating
multifocal subcortical and
periventricular areas of
increased T2 signal, without
mass effect or surrounding
edema. C and D,
Corresponding axial T1-
weighted images after
administration of gadolinium.

Progressive multifocal leukoencephalopathy (PML)
PML was a fairly rare demyelinating disease of the white matter of the brain until
the AIDS epidemic started. As PML requires a weakened immune system to
develop, it is no wonder that AIDS has significantly increased its frequency.
PML is caused by the human
papovavirus, an RNA virus
called JC virus (=JCV). We
know from serological studies
on children where by age 10
about 50% of them have
antibody titers to JCV that this
virus is widely distributed.
Normally JCV infection stays
suppressed by the immune
system's cell mediated
immune response. In the case
of immune weakening
diseases such as leukemias,
lymphomas, AIDS and in
transplant patients JCV can
then be reactivated and cause
PML. About 5% of AIDS
patients are suffering from
PML.