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| __NOTOC__
| | #REDIRECT [[Varicella zoster encephalitis]] |
| {{CMG}} {{AE}} {{AG}}
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| {{SK}} Varicella zoster virus encephalitis; Herpes zoster encephalitis; Varicella zoster encephalitis; Varicella encephalitis;
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| ==Overview==
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| VZV encephalitis is a viral infection of the [[central nervous system]]. Based on the duration of symptoms, VZV encephalitis may be classified into either acute or chronic. The exact pathogenesis of VZV encephalitis is not fully understood. The [[immune system]] eliminates the virus from most locations upon initial infection, but it remains [[viral latency|latent]] in the [[dorsal root ganglion]] and the [[trigeminal]] ganglion near the base of the [[skull]]. VZV encephalitis may be caused by either varicella ([[chickenpox]]) or herpes zoster ([[shingles]]). VZV encephalitis must be differentiated from other diseases that cause [[fever]], [[headache]], [[vomiting]], and [[altered mental status]]. The incidence of VZV encephalitis is approximately 10 per 100,000 individuals affected with [[varicella]], most often [[neonates]] and the [[elderly]].<ref name="pmid7658062">{{cite journal| author=Choo PW, Donahue JG, Manson JE, Platt R| title=The epidemiology of varicella and its complications. | journal=J Infect Dis | year= 1995 | volume= 172 | issue= 3 | pages= 706-12 | pmid=7658062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7658062 }} </ref> If left untreated, [[immunocompromised]] patients with VZV encephalitis may progress to [[mortality]]. Common complications include [[shock]], [[hypoxemia]], and [[meningitis]]. Signs of VZV encephalitis include [[fever]], [[headache]], [[ataxia]], and [[aphasia]]. Laboratory findings consistent with the diagnosis of VZV encephalitis include [[leukocytosis]] and [[pleocytosis]].<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> [[Magnetic resonance imaging]] is the imaging modality of choice for VZV encephalitis. [[Acyclovir]] is the drug of choice to treat VZV encephalitis.
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| ==Classification==
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| Based on the duration of symptoms, VZV encephalitis may be classified into either acute or chronic.
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| ==Pathophysiology==
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| The exact pathogenesis of VZV encephalitis is not fully understood. It is known that VZV encephalitis is the result of the [[varicella zoster virus]], a double-stranded [[DNA virus]] within the [[Herpesviridae]] family of viruses.<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> The [[immune system]] eliminates the virus from most locations upon initial infection, but it remains [[viral latency|latent]] in the [[dorsal root ganglion]] and the [[trigeminal]] ganglion near the base of the [[skull]]. Initial infection by VZV presents as [[chickenpox]], often in children between the ages of 1-9. VZV reactivation, which presents as [[shingles]] in adults, is the result of a decline in the frequency of VZV-specific [[T cell]]s.<ref name="pmid9300702">{{cite journal| author=Sadzot-Delvaux C, Kinchington PR, Debrus S, Rentier B, Arvin AM| title=Recognition of the latency-associated immediate early protein IE63 of varicella-zoster virus by human memory T lymphocytes. | journal=J Immunol | year= 1997 | volume= 159 | issue= 6 | pages= 2802-6 | pmid=9300702 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9300702 }} </ref> The molecular basis of reactivation remains unknown.<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref> Some histopathologic studies suggest of a postinfectious [[demyelinating]] process, while other findings cite direct viral cytopathology.<ref name="pmid6326714">{{cite journal| author=Bauman ML, Bergman I| title=Postvaricella encephalitis. | journal=Arch Neurol | year= 1984 | volume= 41 | issue= 5 | pages= 556-8 | pmid=6326714 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6326714 }} </ref><ref name="pmid4311227">{{cite journal| author=McCormick WF, Rodnitzky RL, Schochet SS, McKee AP| title=Varicella-Zoster encephalomyelitis. A morphologic and virologic study. | journal=Arch Neurol | year= 1969 | volume= 21 | issue= 6 | pages= 559-70 | pmid=4311227 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4311227 }} </ref><ref name="pmid582251">{{cite journal| author=Takashima S, Becker LE| title=Neuropathology of fatal varicella. | journal=Arch Pathol Lab Med | year= 1979 | volume= 103 | issue= 5 | pages= 209-13 | pmid=582251 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=582251 }} </ref>
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| ==Causes==
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| VZV encephalitis may be caused by either varicella ([[chickenpox]]) or herpes zoster ([[shingles]]).
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| ==Differentiating VZV Encephalitis from Other Diseases==
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| VZV encephalitis must be differentiated from other diseases that cause [[fever]], [[headache]], [[vomiting]], and [[altered mental status]], such as:<ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref><ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref><ref name="pmid13065322">{{cite journal| author=APPELBAUM E, RACHELSON MH, DOLGOPOL VB| title=Varicella encephalitis. | journal=Am J Med | year= 1953 | volume= 15 | issue= 2 | pages= 223-30 | pmid=13065322 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=13065322 }} </ref>
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| {| style="border: 0px; font-size: 90%; margin: 3px;" align=center
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| ! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
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| ! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''Other [[Viral encephalitis]] ([[Herpes simplex encephalitis]])'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |[[Viral encephalitis]] presents with acute [[inflammation]] of the [[brain]], caused by a [[viral infection]]; complications include severe [[brain]] damage as the inflamed [[brain]] pushes against the [[skull]], potentially leading to [[mortality]]. Other findings include [[fever]], [[confusion]], and [[aphasia]].
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Vector-borne encephalitis]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |[[Vector-borne encephalitis]] presents with acute [[inflammation]] of the [[brain]], caused by a [[bacterial infection]]; complications include severe [[brain]] damage as the inflamed [[brain]] pushes against the [[skull]], potentially leading to [[mortality]]. {{see also|Tick-borne encephalitis|West Nile encephalitis|St. Louis encephalitis|Japanese encephalitis}}
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Encephalopathy]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |[[Encephalopathy]] presents with steady [[depression]], generalized [[seizures]]. Generally absent are [[fever]], [[headache]], [[leukocytosis]], and [[pleocytosis]]; [[MRI]] often appears normal.
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Meningitis]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |[[Meningitis]] presents with [[headache]], [[altered mental status]], and [[inflammation]] of the [[meninges]]. It may have an indolent evolution, resolving on its own, or may present as an rapidly evolving [[inflammation]], causing neurologic damage and possible [[mortality]]. {{see also|bacterial meningitis|viral meningitis|fungal meningitis}}
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| | style="padding: 5px 5px; background: #DCDCDC;" |'''[[Brain abscess]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |[[Brain abscess]] presents with an [[abscess]] in the [[brain]] caused by the [[inflammation]] and accumulation of [[infected]] material from local or remote infectious areas of the body; the infectious agent may also be introduced as a result of head [[trauma]] or [[neurosurgery|neurological procedures]].
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Acute disseminated encephalomyelitis]] (ADEM)'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |[[Acute disseminated encephalomyelitis]] presents with scattered foci of [[demyelination]] and perivenular [[inflammation]]; it can cause focal neurological signs and decreased ability to focus.
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| |}
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| ==Epidemiology and Demographics==
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| ===Incidence===
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| The incidence of VZV encephalitis is approximately 10 per 100,000 individuals affected with [[varicella]].<ref name="pmid7658062">{{cite journal| author=Choo PW, Donahue JG, Manson JE, Platt R| title=The epidemiology of varicella and its complications. | journal=J Infect Dis | year= 1995 | volume= 172 | issue= 3 | pages= 706-12 | pmid=7658062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7658062 }} </ref>
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| ===Age===
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| VZV encephalitis most commonly affects infants or the [[elderly]].<ref name="pmid7658062">{{cite journal| author=Choo PW, Donahue JG, Manson JE, Platt R| title=The epidemiology of varicella and its complications. | journal=J Infect Dis | year= 1995 | volume= 172 | issue= 3 | pages= 706-12 | pmid=7658062 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7658062 }} </ref>
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| ===Gender===
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| Men and women are affected equally by VZV encephalitis.
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| ==Risk Factors==
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| Common risk factors in the development of VZV encephalitis include:<ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref><ref name="Mounsey">{{cite journal|title=Herpes zoster and postherpetic neuralgia: prevention and management|author=Mounsey AL, Matthew LG, & Slawson DC|date=2005|journal=American Family Physician|volume=72|issue=6|pages=1075-1080|pmid=16190505|url=http://www.aafp.org/afp/20050915/1075.html|accessdate=2007-06-15}}</ref><ref>{[cite journal|title=What does epidemiology tell us about risk factors for herpes zoster?|author=Thomas SL, Hall AJ|journal= Lancet Infect Dis.|date=2004|volume=4|issue=1|pages=26-33|pmid= 14720565}}</ref><ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>
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| *[[Varicella zoster virus]] infection
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| *[[Immunosuppression]]
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| *[[HIV]] or [[AIDS]]
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| *[[Age]] extremes
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| *[[Stress]]
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| *Chronic [[corticosteroid]] usage
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| *[[Skin]] [[inflammation]]
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| *[[Pregnancy]]
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| *Living in tropical climate
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| *Working as a [[physician]] or other [[health care provider]]
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| *Absence of [[varicella vaccine]]
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| ==Natural History, Complications, and Prognosis==
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| ===Natural History===
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| Herpes zoster usually clears in 2 to 3 weeks and rarely recurs. However, if left untreated, [[immunocompromised]] patients with VZV encephalitis may progress to [[mortality]].
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| ===Complications===
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| Common complications of VZV encephalitis include:<ref name="pmid14978145">{{cite journal| author=Kennedy PG| title=Viral encephalitis: causes, differential diagnosis, and management. | journal=J Neurol Neurosurg Psychiatry | year= 2004 | volume= 75 Suppl 1 | issue= | pages= i10-5 | pmid=14978145 | doi= | pmc=PMC1765650 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14978145 }} </ref>
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| *[[Shock]]
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| *[[Hypoxemia]]
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| *[[Hypotension]]
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| *[[Aphasia]]
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| *[[Seizures]]
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| *[[Meningitis]]
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| *Loss of [[motor skill]]s
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| *[[Coma]]
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| *[[Mortality]]
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| ===Prognosis===
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| Prognosis for VZV encephalitis is generally good in most individuals. Prognosis for VZV encephalitis is poor in [[immunocompromised]] individuals.
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| ==Diagnosis==
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| ===History and Symptoms===
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| If possible, a detailed and thorough history from the patient is necessary. Symptoms of VZV encephalitis include:<ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref>
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| *[[Fever]]
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| *[[Headache]]
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| *[[Ataxia|Loss of body control]]
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| *[[Aphasia|Inability to produce or comprehend language]]
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| *[[Seizure]]s
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| *[[Cough]]
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| *[[Dyspnea|Shortness of breath or labored breathing]]
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| *[[Hemoptysis|Coughing up blood]]
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| *[[Rash]]
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| *[[Lethargy]]
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| ===Physical Examination===
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| Common physical examination findings of VZV encephalitis include:<ref name="pmid12353193">{{cite journal| author=Gnann JW| title=Varicella-zoster virus: atypical presentations and unusual complications. | journal=J Infect Dis | year= 2002 | volume= 186 Suppl 1 | issue= | pages= S91-8 | pmid=12353193 | doi=10.1086/342963 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12353193 }} </ref>
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| *[[Fever]]
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| *[[Aphasia]]
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| *[[Ataxia]]
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| *[[Nuchal rigidity]]
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| *[[Nystagmus]]
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| *[[Hypertonia]] or [[hypotonia]]
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| *[[Hyperreflexia]] or [[hyporeflexia]]
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| *Positive [[plantar reflex]]es
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| *[[Hemiparesis]]
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| If [[rash]] and [[ataxia]] are present simultaneously, the clinical presentation is sufficient to establish a diagnosis.
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| ===Laboratory Findings===
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| Rapid diagnostic methods, which include [[polymerase chain reaction]] (PCR) and [[direct fluorescent antibody]] (DFA) assay, are the methods of choice. Polymerase chain reaction testing, the most sensitive test for VZV, can be used for detecting [[invasive]] disease, and detects varicella zoster virus in [[cytoplasm|vesicle fluid]], [[serum]], [[cerebrospinal fluid]], and other tissues. Direct fluorescent antibody assay is performed on scrapings taken from the base of a skin lesion, and is a rapid and reliable method for diagnosing VZV disease.<ref name="pmid20070670">{{cite journal| author=Pergam SA, Limaye AP, AST Infectious Diseases Community of Practice| title=Varicella zoster virus (VZV) in solid organ transplant recipients. | journal=Am J Transplant | year= 2009 | volume= 9 Suppl 4 | issue= | pages= S108-15 | pmid=20070670 | doi=10.1111/j.1600-6143.2009.02901.x | pmc=PMC2919834 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20070670 }} </ref> Cerebrospinal fluid analysis is essential (unless contraindicated) in all patients with encephalitis.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref> Therefore, [[lumbar puncture]] may be warranted. Laboratory findings consistent with the diagnosis of VZV encephalitis include [[leukocytosis]] and [[pleocytosis]].<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref>
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| ===CT===
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| [[Computed tomography]] may be helpful in the diagnosis of VZV encephalitis. Findings on [[CT]] suggestive of VZV encephalitis include subtle low density within the [[anterior]] and [[medial]] [[temporal lobe]] and the [[insular cortex]].<ref name=RadioHSE> Herpes simplex encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/herpes-simplex-encephalitis Accessed on February 9, 2016. </ref> Subtleties become more apparent over time and may progress to [[hemorrhage]], and may eventually spread to the other [[temporal lobe]] after 7-10 days.<ref name="pmid11853816">{{cite journal |author=Whitley RJ, Gnann JW |title=Viral encephalitis: familiar infections and emerging pathogens |journal=Lancet |volume=359 |issue=9305 |pages=507–13 |year=2002 |pmid=11853816 |doi=}}</ref>
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| ===MRI===
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| [[Magnetic resonance imaging]] is the imaging modality of choice for VZV encephalitis. Findings on [[MRI]] suggestive of VZV encephalitis include:<ref name=RadioHSE> Herpes simplex encephalitis. Radiopaedia.org (2016). http://radiopaedia.org/articles/herpes-simplex-encephalitis Accessed on February 9, 2016. </ref><ref name="pmid18319155">{{cite journal| author=Bulakbasi N, Kocaoglu M| title=Central nervous system infections of herpesvirus family. | journal=Neuroimaging Clin N Am | year= 2008 | volume= 18 | issue= 1 | pages= 53-84; viii | pmid=18319155 | doi=10.1016/j.nic.2007.12.001 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18319155 }} </ref>
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| *T1
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| **General [[edema]] in the affected region
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| **Hyperintense signal if complicated by subacute [[hemorrhage]]
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| *T1 C+ (Gd)
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| **Early, enhancement is generally absent
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| **Later, enhancement is variable and may appear as:
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| ***Gyral enhancement
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| ***[[Leptomeningeal]] enhancement
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| ***Ring enhancement
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| ***Diffuse enhancement
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| *T2
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| **Hyperintensity of affected [[white matter]] and [[cerebral cortex]]
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| *DWI/ADC
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| **More sensitive than T2 weighted images
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| **Restricted diffusion is common due to [[cytotoxic]] [[edema]]
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| *GE/SWI
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| **May demonstrate blooming if hemorrhagic
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| [[Image:VZV_Encephalitis_MRI_T2.jpeg|VZV Encephalitis MRI T2]]
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| ===Lumbar Puncture===
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| Cerebrospinal fluid analysis is essential (unless contraindicated) in all patients with encephalitis.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref> Therefore, lumbar puncture may be helpful in the diagnosis of VZV encephalitis. Findings on lumbar puncture suggestive of VZV encephalitis include [[pleocytosis]].<ref name=Mandell1> M.D. JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, Expert Consult Premium Edition. Saunders; 2014.</ref>
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| ==Treatment==
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| ===Medical Therapy===
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| The mainstay of therapy for VZV encephalitis is [[antiviral]] therapy. [[Acyclovir]] is the drug of choice to treat VZV encephalitis. [[Ganciclovir]] and adjunctive [[corticosteroid]]s can be considered as alternatives.<ref name=IDSAEnceph> The Management of Encephalitis: Clinical Practice Guidelines by the Infectious Diseases Society of America. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Encephalitis.pdf Accessed on February 16, 2016.</ref>
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| ===Prevention===
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| [[Varicella vaccine]] or [[zostavax]] is recommended for the most individuals to prevent VZV encephalitis. Other primary prevention strategies include avoiding contact with affected individuals, [[disinfectant|disinfecting surfaces]], and [[hand washing]].
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| ==References==
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| {{reflist|2}}
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| [[Category:Primary care]]
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| [[Category:Viral diseases]]
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| [[Category:Infectious disease]]
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| [[Category:Neurology]]
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