Encephalopathy Encephalitis Fever Uncommon Common

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Encephalitis

• Sariddet Charoenchai MD.

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Encephalitis

• An inflammation of the brain parenchyma, presents
  as diffuse and/or focal neuropsychological
  dysfunction
• Most commonly a viral infection with parenchymal
  damage varying from mild to profound

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Encephalitis

• Primary encephalitis
• Post - infectious or Para - infectious
  encephalitis

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Causes in Thailand

• Virus
• Arbovirus JEV Dengue virus
• Herpes virus (simplex , zoster)
• Enteroviruses including coxsackie virus,
  poliovirus, and echovirus
• Other causes include varicella (chickenpox),
  measles, mumps, rubella, adenovirus, rabies

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Japanese Encephalitis

• Most important cause of arboviral encephalitis
  worldwide, with over 45,000 cases reported
  annually
• Transmitted by culex mosquito, which breeds in
  rice fields
• Mosquitoes become infected by feeding on domestic
  pigs and wild birds infected with Japanese
  encephalitis virus
• Infected mosquitoes transmit virus to humans and
  animals during the feeding process

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History of Japanese Encephalitis

• 1800s recognized in Japan
• 1924 Japan epidemic. 6125 cases, 3797 deaths
• 1935 virus isolated in brain of Japanese
  patient who died of encephalitis
• 1938 virus isolated from Culex mosquitoes in
  Japan
• 1948 Japan outbreak
• 1949 Korea outbreak
• 1966 China outbreak
• Today extremely prevalent in South East Asia
  30,000-50,000 cases reported each year

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Distribution of Japanese Encephalitis in Asia,
1970-1998
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Encephalitis morbidity and mortality, Thailand
1976-2005
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Japanese B Encephalitis morbidity and mortality,
Thailand 1976-2005
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Encephalitis and Japanese Encephalitis situation
by Province 2006
Encephalitis
Japanese Encephalitis
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??????????????? Encephalitis unspecified (???
??????????) ????????????????? ?? ?.?. 2545 - 2549
??? ??????????
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??????????????? Japanese Encephalitis B (???
??????????) ????????????????? ?? ?.?. 2545 - 2549
??? ??????????
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Causes in Thailand

• Bacteria
• H. influenza
• S. pneumoniae
• N. meningitidis
• M. tuberculosis
• Mycoplasma pneumoniae
• Others
• Rickettsia, Spirochete Malaria

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Post immunization

• Measles
• 1 2,000,000 dose , 6-15 day after injection
• Mump Some species of virus
• Report
• Influenza
• Japanese B encephalitis
• Pertussis Whole cell
• Rabies

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Clinical manifestation

• Initial Signs
• Fever
• Headache
• Malaise
• Anorexia
• Nausea and Vomiting
• Abdominal pain

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Clinical manifestation

• Developing Signs
• Altered LOC mild lethargy to deep coma
• AMS confused, delirious, disoriented
• Mental aberrations
• hallucinations
• personality change
• behavioral disorders occasionally frank
  psychosis
• Focal or general seizures in gt50 severe cases.
• Severe focused neurologic deficits

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Clinical manifestation

• Neurologic Signs
• Most Common
• Aphasia
• Ataxia
• Hemiparesis with hyperactive tendon reflexes
• Involuntary movements
• Cranial nerve deficits (ocular palsies, facial
  weakness)

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Diagnosis

• Patient History
• Physical exam
• Work up

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Patient History

• Prodromal illness, recent vaccination,
  development of few days ? Acute Disseminated
  Encephalomyelitis (ADEM)
• Biphasic onset systemic illness then CNS
  disease ? Enterovirus encephalitis
• Abrupt onset, rapid progression over few days ?
  HSV encephalitis

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Patient History

• Recent travel and the geographical
• Africa ? Cerebral malaria
• Asia ? Japanese encephalitis
• High risk regions of Europe and USA ? Lyme
  disease
• Recent animal bites ? Tick borne encephalitis or
  Rabies
• Occupation
• Forest worker, exposed to tick bites
• Medical personnel, possible exposure to
  infectious diseases

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Patient History

• Season
• Japanese encephalitis rainy season
• Arbovirus infections are summer and fall
• Predisposing factors
• Immunosuppression caused by disease and/or drug
  treatment
• Organ transplant ? Opportunistic infections
• HIV ? CNS infections
• HSV-2 encephalitis and CMV infection
• Drug ingestion and/or abuse
• Trauma

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Physical exam

• Focal neurological deficit ? HSV encephalitis
• Hallucination or aphasia ? HSV encephalitis
• Local paresthesia ? Rabies encephalitis
• Brain stem signs, Unilateral peripheral motor
  weakness or Cerebellar sign ? Meliodosis
• Eschar ? Scrub typhus
• Parotitis ? Mumps
• Systemic sign eg. Rash ? Mycoplasma Enterovirus

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Work up

• CBC usually within the reference range
• Electrolytes usually within reference range
• Syndrome of inappropriate secretion of
  antidiuretic hormone (SIADH)
• Serum glucose Use this level as a baseline for
  determining normal CSF glucose values

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Work up

• BUN/creatinine and liver function tests (LFTs)
  Assess organ function and the need to adjust the
  antibiotic dose
• Platelet test and a coagulation profile
  indicated in patients with chronic alcohol use,
  liver disease, or if DIC is suspected
• Urinary electrolyte test Perform this
  assessment if SIADH is suspected
• Urine and/or serum toxicology screening

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Work up

• Lumbar puncture
• CSF examination (Polymorphonuclear cells may
  predominate early in the illness but are replaced
  by mononuclear cells within hours)
• Viral culture
• Viral PCR may identify the virus
• Serology tests antibodies to an specific virus ?
  JEV, Dengue, Mycoplasma (4 fold rising )

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CSF profile
Update on infectious disease 2548,
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CSF profile

• Viral meningitis ?????? meningoencephalitis
  pressure ?????
• Bacterial meningitis profile ??????????????????
  ??? Sugar ?????????? sugar ??????????????????????
  Bacterial meningitis ?????? ???????????
  ??????????? 24 -48 ????? ?????? profile ????????
  ?????????????????????????? ??????????????????????
  ?? bacterial meningitis

???????????????????? ??????????????????, ?????
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CSF profile

• Some bacteria (eg, Mycoplasma, Listeria,
  Leptospira, Borrelia burgdorferi Lyme disease)
  cause alterations in spinal fluid that resemble
  the viral profile
• An aseptic profile is also typical of partially
  treated bacterial infections (gt33, especially
  those in children, are treated with
  antimicrobials) and of the 2 most common causes
  of encephalitisthe arboviruses and the
  potentially curable HSV

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Traumatic LP

• There are several techniques for interpreting
• Comparing the peripheral WBC and red blood cell
  (RBC) count to that of the CSF
• Allows one white blood cell for every 700 RBCs
• Blood in the CSF increases the protein and it is
  estimated that 1000 RBCs may raise the CSF
  protein by 1 mg/dL

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Traumatic LP

• In any situation when a traumatic LP occurs and
  the interpretation is difficult, it is better to
  treat and wait for the results of the CSF culture
• When in doubt, treat and attempt the LP later

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EEG

• Certain EEG wave patterns can suggest
  encephalitis due to herpes
• Unilateral or Bilateral periodic focal spike with
  slow activity background

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Imaging
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Differential diagnosis

• Metabolic causes
• Drug Toxicology
• Mass lesion
• Epilepsy
• Subarachnoid hemorrhage
• Acute confusional migraine
• Autoimmune SLE
• CNS Vasculitis

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Differential diagnosis

• Encephalopathy Encephalitis
• Fever Uncommon Common
• Headache Uncommon Common
• AMS Steady deterioration May fluctuate
• Focal Neurologic Signs Uncommon Common
• Types of seizures Generalized Both
• Blood Leukocytosis Uncommon Common
• CSF Pleocytosis Uncommon Common
• EEG Diffuse slowing Common Focal
• MRI Often normal Focal Abn.

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Treatment

• No satisfactory treatment exists for the
  relatively common acute arboviral encephalitides,
  which vary in epidemiology, mortality, and
  morbidity, if not clinical presentation

Encephalitis, Emedicine.com
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Treatment

• Clinically distinguishing these acute arboviral
  encephalitis from the 2 potentially treatable
  acute viral encephalitis is important
• Herpes simplex encephalitis (HSE), which is a
  sporadic and lethal disease of neonates and the
  general population
• Less common varicella-zoster encephalitis, which
  is deadly in immunocompromised patients

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Treatment

• Specific treatment
• HSV encephalitis Neonate infant Acyclovir 60
  mg/kg/day IV div 8 hr 14 -21 days, Child Adult
  30 mg/kg/day 14 -21 days
• Varicella zoster encephalitis Acyclovir
• CMV encephalitis Gancyclovir or Foscanir
• Others depend on etiology

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Treatment

• Supportive treatment
• Reduce intracranial pressure restrict fluid ,
  hyperventilation( if on ventilator), low body
  temperature , steroid ? (Mycoplasma )
• Rest, nutrition, fluids (SIADH), antipyretic,
  Anticonvulsant
• Acute psychosis haloperidol

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Prognosis

• Depends the virulence of the virus and on
  variables associated with the patient's health
  status, such as extremes of age, immune status,
  and preexisting neurologic conditions
• Rabies, EEE, JE, and untreated HSE have high
  rates of mortality and severe morbidity,
  including mental retardation, hemiplegia, and
  seizures

Encephalitis, Emedicine.com
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Prognosis

• The mortality rate in treated HSE averages 20
  and is correlated with mental status changes at
  time of first dose of acyclovir
• Approximately 40 of survivors have
  minor-to-major learning disabilities, memory
  impairment, neuropsychiatric abnormalities,
  epilepsy, fine-motor-control deficits, and
  dysarthria

Encephalitis, Emedicine.com
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Prevention 

• Controlling mosquitoes Dengue
• Animal vaccination Rabies virus
• Human vaccination JEV

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Medical/Legal Pitfalls

• Failure to consider HSE in the diagnosis or to
  initiate administration of acyclovir in a timely
  fashion

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HSV encephalitis

• Current practice in common Infectious disease 2005

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???????????????????? HSVE ????????????
encephalitis ?????????????????? ?

• ??????????????????????????? ??????????????? viral
  encephalitis ????????? ???????????????????????????
  ?????????????
• ?????? olfactory ???? gustatory hallucination
  ???????????????????? ?????????????????????????????
  ???????????????

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Typical CSF finding in HSVE ?

• Profile Viral encephalitis
• Lymphocyte 20 200/cm3 /- PMN
• Protein 50 -200 mg/dl
• Normal CSF sugar (5 low)
• In systematic review RBC or Xanthochromia
  ????????????????????????????????????????
  encephalitis ??????????? ????????????????????????
  ???

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?????????? acute encephalitis ??? CSF ??????
????????? HSVE ?

• Viral encephalitis
• Rabies Dengue encephalitis most no
  pleocytosis or few lt 30/ cm3
• JE encephalitis 30 360 Lymphocyte
  predominant, rarely gt 1000
• ??????????? LP ????????????? ??????

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?????????? acute encephalitis ??? CSF ??????
????????? HSVE ?

• HSV encephalitis
• Biopsy 4/98 no pleocytosis
• Most in immunocompromised LP in first day of
  illness gtgtgt PCR
• ????????????????????? HSVE ???????? cell ??? rule
  out ????????? PCR negative ???????

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?????????? acute encephalitis ??? CT brain ??????
????????? HSVE ?

• ??? CT brain ????????????????????????? gt 5 ???
  ???????????????????? HSVE
• ??? CT brain ????????????????? ?? MRI
  ?????????????????????????? ?????????? imaging of
  choice ???????????????????????

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Gold standard for diagnosis ?

• CSF PCR for HSV

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?????? IV acyclovir ???? LP PCR
??????????????????? ?

• ????? 5-7 ??????? ?????????? PCR ????????????
• ????????? acyclovir 10 -12 ?????????????? PCR
  ??????? ??????????? ?????????????????????????????
  ??????????????????? course ??????? PCR
  ?????????? acyclovir ????? PCR negative ????
  ???????????

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CSF ??? PCR ???????????????? ?

• ?????????????????????????????????
• gt 24 ?? ???? -20oC ???? 4oC ?????

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HSV Antibody ??????????????????????????

• Confirm test
• ?????????????????????????????????????????? ?????
  ????????????????????????? gt 10 ??? ?????????????
  acyclovir gt 5-7 ???

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Thank you for your attention