Department of Pediatric Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey
INTRODUCTION
Subacute and chronic viral infections usually follow longlatency or incubation periods and are associated withpersistent reactive inflammation and degeneration inthe central nervous system (CNS).Main infections in thiscategory are progressive multifocal leukoencephalopa-thy, cytomegalovirus encephalitis, and subacute scleros-ing panencephalitis caused by measles virus.
CHRONICCENTRALNERVOUSSYSTEM INFECTIONS CAUSEDBY
MEASLESVIRUS
Measles virus (MV) is an RNA virus. Its neurologicalcomplications consist of three clinical pictures:
1. Acute measles encephalomyelitis, an autoimmune
*Cor
0610
disorder occurring in immunologically normal chil-dren, is a specific, measles-related acute dissemi-nated encephalomyelitis.
in a proportion of children who encounter measlesat a young age. Incubation and disease periods arein the range of years.
The latter two entities will be reviewed in this chapter.
Subacute measles encephalitis
Subacute measles encephalitis (SME) is a rare complica-tion of MV infection in immunosuppressed and rarelyimmunocompetent hosts. Because viral replication is
respondence to: Banu Anlar, Hacettepe University Faculty of M
not opposed by an immune response, it is usually fatalwithin weeks or months. MV can be recovered fromthe brain. Typically, symptoms start within a few weeksor months after measles infection in a child withcongenital or acquired immunodeficiency (Albertynet al., 2011). No history of recent measles infection orexposure can be obtained in 30% of patients. Symptomsand signs can be general or multifocal, including mentalchanges, altered consciousness, loss of vision, myoclo-nia, or epilepsia partialis continua. They worsen overweeks; death usually ensues within months. EEG showsslowing of the background rhythm and focal epilepticdischarges. T2-weighted magnetic resonance imaging(MRI) sequences demonstrate multifocal areas ofincreased signal intensity in the cortex, subcortical,and deep white matter, followed by progressive atrophy.Cerebrospinal fluid (CSF) analysis may be normal orreveal pleocytosis, increased protein, and oligoclonalbands. Antibodies against MV are either absent orlow-titer owing to the immunocompromised status.Because EEG andMRI findings are not diagnostic, brainbiopsy for histological examination and polymerasechain reactionmay be needed for definite diagnosis. His-topathologically, lymphocytic and histiocytic infiltrationin the meninges, and edema, astrocytic, and glial prolif-eration in the cortex and white matter are observed. Thediagnostic features are eosinophilic intranuclear inclu-sions of paramyxovirus nucleocapsids and MV antigendemonstrated in neuronal and glial cells by immunohis-tochemistry. These findings are similar to those observedin SSPE, with the difference that inflammatory infiltra-tion is milder and demyelination is absent in SME. Thedisorder is usually fatal. Occasional cases have beenreported to recover with serious sequelae; one was trea-ted with ribavirin (Mustafa et al., 1993).
edicine, Department of Pediatric Neurology, Ankara, Turkey
SSPE typically occurs in immunocompetent children whoencounter natural measles infection at a young age.The risk of developing SSPE after childhood measles isestimated as 1/25 000 in general, and as 1/5500 in childreninfected before the age of 1 year. However, these numbersare likely to be erroneous due to the lack of reliable report-ing. What is clear is that vaccine coverage over 90%arrests the transmission of measles in a population andreduces markedly the incidence of SSPE. Recent measlesoutbreaks have been observed in previously immunizedpopulations: tens of thousands of cases were reportedin central and western Europe in the late 2000s. Theseare mainly due to decreasing immunization rate becauseof (unjustified) concerns about the vaccine. The risk ofSSPE is also related to the age-specific incidence of mea-sles, and is higher in countries where measles occurs invery young children. Infants below the age of immuniza-tion (12months) are at risk of imported virus. Internation-ally adopted children are another candidate group.Crowded household, low maternal education, and lowincome have been associated with SSPE.
Theusualageofonset is6–14years,butvarieswith loca-tion and time:mean agehasdecreased from13 to 7.6 years,possiblydue toearliermeasles infection (Anlaretal., 2001).Rarely, SSPE can also occur in infants and adults: theyoungest and oldest cases reported so far are 5 monthsand 49 years old respectively. Infants with SSPE haveusually contracted measles from their mother during theperinatal period. Boys are more frequently affected.
The interval between measles infection and symptomonset is 1–10 years and correlates with age at infection; itcan exceed 10 years in adults and be as short as severalmonths when measles occurs in infancy.
ETIOLOGY
The etiological agent is the wild MV: no vaccine strain hasbeen isolated or amplified from brain tissue. SSPE in a pre-viously immunizedchild canbeattributed tovaccine failuredue to inadequate preservation of the vaccine or low sero-conversion of the host, or, alternatively, to subclinicalmeasles infection before the host was immunized. WildMV genotypes have been detected in brain tissue samplesfrom patients with SSPE, and matched the genotype circu-latingwhen thepatienthadacutemeasles (Miki etal., 2002).
PATHOGENESIS
Critical andmostly unanswered questions exist about thedevelopment of SSPE in a child who had acute measles.
● Route of entry of the MV to the brain during acute
infection. It is generally accepted that MV can reach
the brain by infecting circulating lymphocytes orendothelial cells. Transneuronal and axonal spreadare also considered.
● Persistence of MV in the brain. Although infective
virus is not produced in persistent viral infections,viral antigens are expressed and induce an anti-MV immune response. The stable persistent stateresults from the balance between viral replicationand the host immune response, as examined below.● Host-related factors. The reason MV is not
cleared after acute infection may be transientimmunosuppression caused by MV especiallyin an immunologically immature child; age,nutritional status, or concurrent infectionsmay contribute to inadequate immune response.
● Cell-related factors. The tendency of neural
cells to express MV proteins only partiallymay result in incomplete clearing by immuneresponse.
● Virus-related factors. Mutations in the MV
allow it to escape humoral immunity. MV iso-lated from patients with SSPE usually displaymutations in the matrix (M) and/or fusion (F)genes. Hypermutations in the M gene are notlethal for the virus, which can still replicateand spread with slow migration. The wild MVundergoes these mutations during its stay inthe host; shorter latent periods are associatedwith smaller number of mutations.
● Cause of reactivation of persistent MV. The MV
genome can be encountered in many asymptomaticsubjects, as demonstrated by autopsy studies. Thereason the virus becomes reactivated in some isunknown; alterations in the immune or hormonalsystem, minor head trauma, or infections might con-tribute. Immunological findings in patients withSSPE do not necessarily indicate a causal relation-ship: total lymphocyte counts, T cell numbers andsubsets, and skin tests are normal at the beginningof the disease but altered in late stages. Variousinflammatory mediators are detected in the CSF,although patient CSF has not been shown to inducepathology in intact animals (Beken and Anlar,unpublished data). Recent studies have concentratedon genetic polymorphisms likely to confer suscepti-bility to viral persistence. Several functional poly-morphisms of cytokine, cytokine signal molecule,or Toll-like receptor 3 genes have been demonstratedin different patient populations.
PATHOLOGY
Inclusion bodies in the cytoplasm or nuclei of neuronsand glia are diagnostic. Nuclear inclusions may containviral ribonucleoproteins or protein complexes. Other
Table 123.1
Staging system of Jabbour et al. (1969)
Stage I Cerebral signs: mental, behavioral changes
Stage II Convulsive motor signs (myoclonus,incoordination, choreoathetosis, and tremors)
Stage III Coma, opisthotonus, decerebrate rigidity, noresponse to stimuli
Stage IV Mutism, loss of cerebral cortex function, lessfrequent myoclonus, less hypertonia
TIS AND CHRONIC VIRAL ENCEPHALITIS 1185
histopathological changes vary according to the stage ofthe disease. In early stages, inflammation in the menin-ges, cortex, subcortical gray and white matter, andneuronal degeneration, gliosis, astrocytic proliferation,and demyelination are observed. Later, inflammationdiminishes while necrosis, neuronal degeneration, glio-sis, and neurofibrillary tangles predominate and corticalarchitecture is altered. Pathological and imaging studiesmay show progression of inflammation from occipital tofrontal.
Stage I Overt psychointellectual and/or nonspecific
neurological symptomsStage II Stereotyped jerksStage III Vegetative psychomotor condition
Stage IV Spontaneous improvement (modest in substageIVa, substantial in substage IVb)
Stage V Relapse
CLINICAL FINDINGS
SSPE can occur at any age, but most commonly in aschool-aged child who had normal neurological andbehavioral status until a few weeks or months beforepresentation. Initial findings are forgetfulness, behav-ioral changes, ataxia, or diminished speech. Cognitivechanges can be subtle: they may have been overlookedby parents and may be found only upon asking aboutschool perfomance in the current year compared to pre-vious years. The neurological examination can be normalat this stage unless completed by detailed mentalevaluation.
Myoclonus is the most common and frequently thefirst symptom bringing the child to medical attention.In the beginning slow, brief blinking or head droppingattacks, or asymmetrical upper body jerks can beobserved several times a day, more in the evening whenthe child is tired. They disappear during sleep and inten-sify with stress. Their frequency and amplitude increasein a few weeks or months. Rare and less typical presen-tations of SSPE include epileptic seizures, epilepsia par-tialis continua, acute encephalopathy, hemiparesis, acuteataxia, unilateral dystonia, or psychiatric disturbances.Isolated visual loss has been reported as the initial man-ifestation, especially in older patients; it may result fromretinopathy (characteristically macular), optic neuro-pathy/atrophy, or cortical involvement.
As the disease progresses, motor weakness, increasedpyramidal and extrapyramidal tone, and myoclonic jerksof the whole body become manifest. Gradual loss ofambulation and speech lead to a wheelchair or bedriddenstate. Periodic myoclonia diminishes; spastic quadripar-esis and a vegetative state develop in later stages. Auto-nomic disturbances such as fever, vasomotor changes,sweating, breathing difficulties, or cardivoascular impair-ment may occur. Death usually results from respiratoryimpairment due to bulbar dysfunction or infection.
Adult-onset SSPE tends to present with atypical fea-tures and progress is slower; clinical suspicion and diag-nosis can therefore be more difficult. In contrast, arapidly progressive course is more frequent in childrenyounger than 4 years old.
Symptoms and signs have been classified into clinicalstages for the purpose of research and follow-up.Two main staging systems are from Jabbour et al.(1969) (Table 123.1) and Risk and Haddad (1979)(Table 123.2).
In addition to staging, objective scales such as theNeurological Disability Index, SSPE Scoring Scale(SSS), or cognitive assessment scales are necessary forpurposes of research and follow-up (Dyken et al.,1982; Oktem et al., 1997; Anlar and Yalaz, 2012).
The clinical course is frequently subacute over 1–4years; other subtypes such as acute fulminant, slow, orfluctuating courses are observed at rates of 5–10% each.Prolonged remissions of several years occur in about 5%of children with SSPE. The bedbound stage may lastmany years.
DIAGNOSTIC TESTS
Diagnosis is based on:
● Clinical features
● EEG ● CSF examination for measles IgG and measles-
specific IgG index
EEG
The typical pattern of bilateral, symmetrical, periodic,high-amplitude slow waves, or sharp-and-slow-wavecomplexes is usually seen in the myoclonic phase
NLAR
(Fig. 123.1A). If the routine EEG is normal, it should berecorded in sleep or after injection of diazepam 5 mgintravenously (Fig. 123.1B). The discharges may ormay not be associated with clinically observable move-ments. The background rhythm, initially normal,becomes progressively slower and flatter over months.Less typical EEG findings are frontal rhythmic deltaactivity, diffuse sharp waves, and sharp-and-slow-wavecomplexes over frontal regions, and focal abnormalities(Fig. 123.2A,B).
1186 B. A
CSF analysis
Biochemistry and cell count are normal; pressure can benormal or, infrequently, elevated. Immunoglobulinindex is high; oligoclonal bands reacting with MV anti-gens are seen in almost all patients. Antimeasles IgGand measles-specific IgG index are diagnostic.Measles-specific IgM is usually negative. IgG remainselevated even during remission. MV RNA can some-times be detected by reverse transcription-polymerasechain reaction.
Fig. 123.1. (A) EEG in early stage: normal background rhythm and
of the patient on the same day.
Fig. 123.2. (A) Diffuse slow waves in awake patient, stage II. (B
Magnetic resonance imaging
There is no specific or even typical MRI finding forSSPE: the main role of MRI is to rule out other diagno-ses. MRI can be normal initially. Lesions are mostfrequently seen in the periventricular or subcorticalwhite matter. They tend to start in the cortex and subcor-tical region and progress medially to the periventricularwhite matter as areas of hyperintensity in T2-weightedand hypointensity in T1-weighted images. Topographi-cally they tend to start in the posterior and proceed toanterior regions; basal ganglia and cerebral pedunclesare involved later. Pial and parenchymal contrastenhancement and local mass effect of parenchymallesions may be observed. After 1–2 years diffuse cere-bral atrophy is usual (Anlar et al., 1996). Rarely, pontineedema or bilateral pontocerebellar peduncle lesions maybe the only abnormality. Diffusion-weightedMRI showsvariable findings within the white matter lesions or nor-mal appearing paranchyma. MR spectroscopy can showdecreased N-acetylaspartate and increased choline andmyoinositol, reflecting neuronal loss, glial proliferation,and inflammation, respectively.
periodic complexes at onset of the disease. (B) Sleep recording
) Periodic complexes appearing after injection of diazepam.
SUBACUTE SCLEROSING PANENCEPHALITIS
TREATMENT
No specific drug can clear the persistent MV from theCNS. Antiviral and immunomodulatory treatments canachieve partial remission or stabilization rates exceedingthose expected in the natural course. Most agents havenot been subjected to randomized controlled trials,which are difficult due to the low prevalence and vari-able course of SSPE. Response to any therapeutic agentappears best in patients with slow progression, forinstance those who are at stage I or II at 9–12 monthsafter onset.
Inosine pronobex (inosiplex), a synthetic compoundwith antiviral and immunomodulatory properties,70–100 mg/kg/day orally in divided doses has beenreported to prolong life in one-third of cases. Side-effects are mild gastric disturbance, hyperuricemia,and renal stones. Treatment is life-long even after appar-ent remission.
Interferons suppress viral replication and induceimmunologically active molecules. Intraventricularhuman lymphoblastoid IFN-a combined with oral inosi-plex induced improvement or stabilization in 44–55% ofcases, and longer survival (Yalaz et al., 1992). However,recombinant IFN-a is not significantly superior to oralinosiplex (Gascon et al., 1993). Intrathecal IFN-a mayalso be effective but side-effects such as meningealinflammation, neuropathy, and seizures are of concern.Interferon beta1a, 3 times/week subcutaneously withoral inosiplex, might also prolong survival and delayprogression.
Ribavirin has been applied intraventricularly in com-bination with IFN-a; however, its effect is not clear.Amantadine is an anti-RNA agent inhibiting viralreplication. Increased chance of remission and longersurvival have been observed in some series. Intravenousimmunoglobulin has been reported in single cases; in ourexperience, it sometimes produced temporary improve-ment in patients with SSPE with acute, febriledeterioration.
Corticosteroids are not indicated: deterioration fol-lowed whenever steroids were given to reduce edema-tous lesions or for an erroneous diagnosis of myoclonicepilepsy.
Among agents under investigation, small interferingRNA molecules and short hairpin RNAs can downregu-late specific viral RNA in vitro.
Symptomatic treatment and supportive care areimportant. Myoclonia responds to carbamazepine. Gen-eralized seizures are infrequent; clonazepam at lowdoses may be preferred because of additional benefiton sleep and spasticity. The benefit of complete controlof myoclonia should be weighed against oversedation bydrugs, and infrequent myoclonic jerks may be left
untreated in a nonambulatory patient. In stage 3, anti-spasticity and antirigidity medications and physical ther-apy delay spastic contractures: patients may even regainsome motor control with these measures. When chewingand swallowing become impaired, intermittent N/G tub-ing or gastrostomy may be needed to maintain propernutrition. Teeth and gum problems cause pain and reac-tive spasticity; maintenance of oral hygiene, regular den-tal check-ups, prevention of bed sores, positioning, andchest percussion techniques should be demonstrated toparents or caregivers and, if possible, home assistanceprovided on a regular basis.
PROGNOSIS
No factors predictive of remission or prolonged survivalhave been demonstrated except for very young age ofonset being associated with more rapid worsening.Treatment affects the outcome: median length of sur-vival and rate of remission are lower in untreatedpatients. Follow-up is done by clinical and EEG findings:the background rhythm and the frequency of periodiccomplexes on EEG correlate with, and may even pre-cede, clinical changes.
PREVENTION
SSPE is preventable by reaching and maintaining animmunization rate of over 90% against measles in a pop-ulation. Speculations over the safety of the MMR (mea-sles, mumps and rubella) vaccine, the general perceptionof measles as a benign infection of childhood, and theconsequent fall in immunization rates raise concernsabout the resurgence of SSPE in the long term. Evenin widely immunized populations, seronegativity isencountered due to failure to develop immunity aftervaccination, or secondary vaccine failure because ofwaning antibodies; particular risk groups are adultsimmunized in infancy whose MV antibody titers mightdiminish over time, and infants because of similarlywaning maternal immunity.
DIFFERENTIAL DIAGNOSIS
Epilepsy, particularly progressive myoclonic epilepsies,and less often juvenile myoclonic or absence epilepsiesor Lennox–Gastaut syndrome, can be confused withSSPE. In SSPE mental decline is more rapid; paroxsymaldischarges on EEG are not suppressed with diazepamand CSF measles antibodies are elevated. Some SSPEcases are misdiagnosed as Sydenham’s chorea becauseof similar age, irregular jerky limb movements, incoor-dination, and dysarthria. There is no mental deteriora-tion in chorea, and EEG and measles antibody levelsare normal. Degenerative/metabolic disorders of the
AND CHRONIC VIRAL ENCEPHALITIS 1187
NL
CNS such as leukodystrophies or neuronal ceroid lipo-fuscinosis should be considered in cognitive decline,especially if white matter lesions are symmetrical onMRI. They can be differentiated with CSF studies,EEG, MRI, and metabolic tests. Variant Creutzfeldt–Jakob disease (CJD) can present in young adults withmyoclonus, cognitive decline, and seizures. Myocloniain CJD is markedly related to auditory or tactile stimuli,while mostly spontaneous in SSPE. CSF studies areneeded to distinguish the two diseases. Space-occupyinglesions and vascular occlusion are considered whenSSPE starts with dystonia, especially hemidystonia,hemiparesis, or increased intracranial pressure. Psychiat-ric conditions, conversion disorder, andWilson’s diseasemay resemble SSPE because of behavioral disturbances,dystonia, rigidity, tremor, or ataxia. Especially adult-onset SSPE cases may receive the diagnosis of multiplesclerosis. SMEmay have similar clinical features but dif-fers in terms of the immunocompromised status of theSME patient, shorter interval between measles infectionand neurological symptoms, and rapid worsening. Like-wise, progressive multifocal leukoencephalopathyoccurs in immunocompromised hosts; paroxysmalEEG and measles antibodies are absent. Fulminant SSPEpresenting with loss of consciousness, short history ofneurological symptoms, and fever can be confusedwith acute viral encephalitis, bacterial meningoence-phalitis, or acute disseminated encephalomyelitis. Whenchorioretinitis occurs in SSPE, differentiation fromtoxoplasmosis must be made by serological studies. Pro-gressive rubella panencephalitis is similar to SSPE, butmuch rarer.
In a review of their 307 patients, Prashanth et al.(2007) observed various initial diagnoses in 78.8% ofcases: seizures, leukodystrophy, Schilder’s disease,cerebral palsy, parkinsonism, Wilson’s disease, vasculi-tis, spinocerebellar ataxia, motor neuron disease, nutri-tional amblyopia, retinitis, schizophrenia, andmalingering.
OTHERCHRONIC VIRAL INFECTIONSOF THECENTRALNERVOUS SYSTEM
Chronic cytomegalovirus encephalitis
Cytomegalovirus (CMV) is a ubiquitous member of theherpes family, usually contracted during childhood.Approximately 1% of newborns are infected, but pro-gression to systemic disease occurs in only 10% ofcases. CMV is markedly neurotrophic. Infection earlyin utero causes congenital malformations, vasculopa-thy resulting in ischemia and encephalomalacia, variousdegrees of gyral abnormalities, and microcephaly.Infection later in utero provokes subacute encephalitiswith tissue necrosis and calcium deposition. Postnatal
1188 B. A
infection occurs in immunocompromised and rarelyin immunocompetent patients. MRI reveals periventri-cular white matter involvement with increased signal onT2-weighted images and often low signal on T1-weighted images. Thin subependymal contrast enhance-ment around the ventricular walls and periventricularcalcifications are typical. Focal forms presenting withintractable epilepsy as Rasmussen’s encephalitis havebeen described. Ganciclovir, valganciclovir, and foscar-net may be used in the treatment of symptomaticpatients where viral DNA has been demonstrated inthe CSF fluid or brain tissue by polymerase chainreaction.
AR
Nipah virus encephalitis
Nipah virus and another closely related virus, Hendravirus, are zoonotic and endemic to certain geographicalregions. Like MV, they are in the paramyxovirus family.They typically cause acute encephalitis with altered con-sciousness, myoclonus, hypotonia, and cerebellar signs.However, a late-onset subacute form presenting up to 22months after initial exposure and a relapsing form havebeen reported in 7–10% of acute cases or contacts. Clin-ical findings include headache, fever, focal neurologicalsigns, seizures, or cranial nerve dysfunctions. Neurolog-ical sequelae are common. MRI demonstrates patchyand confluent cortical lesions, and, less frequently,infratentorial lesions (Sejvar et al., 2007). Likewise,human cases of Hendra virus encephalitis also can occuras late as 13 months after the initial exposure. Thesedelayed and relapsing forms are thought to arise fromrecurrent infection or from quiescent virus in the brain.Despite the presence of viral antigen in the CNS, no viruscan be isolated; such features are reminiscent of SSPEand might suggest a similar pathogenesis. Treatmentwith ribavirin may reduce mortality in acute Nipahencephalitis, but its effect in subacute and relapsingforms is unclear.
Brainstem encephalitis
Although brainstem encephalitis usually involves anacute and febrile clinical picture Yalaz Tınaztepe, Bick-erstaff‘s report of eight cases included one (Case 5) witha biphasic course at 6-month intervals (Bickerstaff,1957). Other reports exist on subacute brainstem enceph-alitis progressing for several months. The etiology is notwell defined; herpes and Epstein–Barr viruses predomi-nate. Reactivation of latent infection or immunologicalmechanisms have been proposed, supported by thesubacute or relapsing course, overlapping withGuillain–Barre and Fisher syndromes, and an occasionalrelationship with Campylobacter infection.
TIS
The differential diagnosis includes Miller Fishersyndrome, myasthenia, paraneoplastic syndromes,and brainstem tumors. Treatment includes intrave-nous immunoglobulin and steroids. Although antiviraltreatment is indicated only when virus can be demon-strated, in practice most patients receive antivirals.Outcome is usually good in children, with completerecovery.
Progressive rubella panencephalitis
Slow infection with rubella virus may manifest 10 yearsor longer after congenital or postnatal rubella virusinfection. Pathogenesis is unclear: the virus cannot berecovered from brain or CSF, indicating nonproductiveinfection. It closely mimics SSPE, but is much rarer:the literature contains about 20 patients aged 8–21 years.Clinical features are mental deterioration, ataxia, andmyoclonic seizures. EEG shows periodic complexesand altered background rhythm. The course is progres-sive and frequently fatal. Because all cases have beenreported in the pre-MRI era, imaging findings areunknown. Measurement of anti-rubella IgG in the CSFis diagnostic, and should be performed in a patient sus-pected of SSPE but whose CSF measles IgG results arenegative. No specific treatment is available.
Progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) is asubacute disease caused by the JC virus (JCV), a poly-omavirus that infects oligodendrocytes and results indemyelination. It occurs predominantly in immunocom-promised individuals, most commonly in HIV infection.JCV is widely distributed and usually encountered byadulthood. It remains in a latent state after primaryinfection, to be reactivated if the immune system isimpaired.
Common manifestations include focal signs andsymptoms: weakness, ataxia, speech or cognitive distur-bances, headache, and visual impairment. Corticalinvolvement and seizures are rare. MRI shows focalwhite matter areas of T2 hyperintensity including thesubcortical U-fibers. Contrast enhancement is infre-quent; when present, it may indicate a beneficial in-flammatory response. Pathologically the brain tissueshows demyelination, enlarged hyperchromatic nucleiin oligodendrocytes, and astrocytes. Diagnosis is madeafter exclusion of other causes of similar clinical andneuroradiological findings, especially other opportunis-tic infections and chemotherapeutic toxicity. Definitediagnosis is based on the demonstration of JCV DNAby polymerase chain reaction in the CSF, or, if negative,in brain tissue. The disease is often progressive and fatal,but prolonged survival and remission are possible. The
SUBACUTE SCLEROSING PANENCEPHALI
immunological status of the host affects outcome.Among various treatments, certain favorable responsesto cytarabine with or without interferon have beenreported.
AND CHRONIC VIRAL ENCEPHALITIS 1189
REFERENCES
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alties from themeasles outbreak in SouthAfrica. SAfrMed
J 101: 313–314, 316–317.Anlar B, Yalaz K (2012).Measles virus infection and subacute
sclerosing panencephalitis. In: AC Jackson (Ed.), Viral
ınfectious of the Human Nervous System, Birkhauser
Advances in Infectious Diseases. Springer, Basel, pp. 3–22.
Anlar B, Saatci I, K€ose G et al. (1996). MRI findings in
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