Systemic Infections with Neurologic Manifestations
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Transcript of Systemic Infections with Neurologic Manifestations
Systemic Infections with Neurologic Manifestations
Arlene S. Dy-Co, MD, FPPS, FPIDSP
SYSTEMIC INFECTIONS
Infections in the bloodstream
Affecting the entire body
Diverse
Systemic infections with Neurologic Manifestations
Part of CNS syndromes
Systemic manifestations dominate clinical picture
Syndromic approach to diagnosis less effective
Systemic VIRAL infections
Systemic BACTERIAL infections
Systemic PROTOZOAL infections
With Neurologic Manifestations
Systemic viral infections with neurologic manifestations
Measles
Varicella
Dengue
Measles
Rash disease of childhood
Neurologic disease-
community-acquired infection
Fever, cough, diarrhea, rash
Significance
?
Low incidence
Long-term neurologic disabilities
Pathology
Direct viral invasion
Induction of autoimmune response
Neurologic manifestations
Acute disseminated encephalomyelitis
Measles inclusion body encephalitis
Subacute sclerosing panencephalitis
ADEM
• Incidence
Worldwide• Common after measles
1 in 1,000 • Common in children >2 years old• normal immune system
fever 2-7days
after onset of rash
Neurologic manifestations• Seizures • Altered mental
status• Multifocal
neurologic signs
Monophasic course
10-20 daysImprovement few days after
onset
Pathology
Autoimmune demyelinating disease triggered by measles
perivenular demyelinationNo evidence of measles
virus
swelling of cerebral vessels
Mononuclear cell infiltration
autoimmune response to
myelin -unexplained
Diagnosis
clinical MRI –multiple foci of demyelination
CSF –normal or slight increase in protein
EEF non-specific diffuse slowing
Treatment
Treatment not well established• Corticosteroid widely used
Higher mortality in steroid-treated • IVIG, plasma exchange some success
Ziegra SR. Corticosteroid treatment for measles encephalitis. J Pediatrics. 1961; 59:322
Prognosis
Fatality rate- 10-40%
Neurologic residua substantial• Almost always present
Johnson RT, et al. Measles encephalomyelitis –clinical and Immunologic studies. N Engl J med. 1984; 310:137-141
Prevention
To decrease the incidence
Vaccination highly effective
and safe
Varicella
Primary infection with varicella zoster virus
Common, extremely contagious
Generalized vesicular rash
Neurologic manifestations
1-3 per 10,000
Cerebellar ataxia 31%Encephalitis 20%• Transverse myelitis, aseptic meningitis, stroke
www.jwatch.org aug 11,2014
Cerebellar ataxia
1 per 4,000days before to 2 weeks after the
rash
VomitingHeadacheLethargy
ataxia
• Fever• Nuchal
rigidity• Nystagmus• seizures
Pathology
unknown• Lack of necropsy studies
Proposed mechanisms• Direct viral involvement of the cerebellum • Immunologically mediated
Antibodies to VZV in the CSF of patients with neurologic abnormalities
VZV specific DNA in the CSF of 3 children with varicella cerebellitis detected by PCR
Echevarria JM et al. Subclass distribution of the serum and intrathecal IgG antibody response in varicella-zoster virus infection. J Infect Dis 1990
Puchammer E, et al. Detection of VZVDNA by PCR in the CSF of patientsSuffering from neurological complications associated with chickenpox. J Clin Microbiol. 1991; 29:1513.
Diagnosis
Uncomplicated
Clinical presentation
No further evaluation
Complicated
CSF –normal or slight increase
in protein
EEG-diffuse slow wave
Prognosis
Cere
bella
r ata
xia
self-limited
Resolves in 1-3 weeks
Mortality -zero
Encephalitis
Less common
More severe
1-2 per 10,000
Most occur in children
Highest in infants less
than 1 y
Occurs 2 weeks
before up to weeks after
the rashAbrupt or gradual
HeadacheFever
VomitingAltered
sensoriumseizures
AtaxiaHypertonia/hypotonia
HemiparesisSensory changes
Pathology
Role of active viral replication- uncertain
Wide range of histopathologic findings
Diffuse cerebral edema
Diagnosis
CSF
• Frequently abnormal
EEG
• Slow wave activity
CT scan
• Cerebral edema
• Demyelination
Prognosis
Mortality 5-35%
Long-term sequela in 10-20% of survivors
59 cases of varicella with encephalitis -5% mortality
Lehman MD. J Pediatri 2014, Jul 22
Treatment and Prevention
Cerebellar ataxia Encephalitis
No evidence for antiviral therapy Antiviral therapy
Live, attenuated vaccine –effective
and safe
Dengue
4 serotypes
Viral hemorrhagic fever
Dengue
Cause and existence of neurologic manifestations has been a controversy• Neurologic manifestation reported from every
country
strong evidence to support neuroinvasion• non-specific encephalopathy, encephalitis
Soares CN et al. Dengue infection neurologic manifestationsand CSF. J Neurol Sci 2006; 249; 19.
150 CSF samples from fatal cases
Evidence of DENV in 41 CSF out of 84 positive patients
Araujo FMC, et al. CNS involvement in Dengue: a study of fatal cases from a dengue endemic area. Neurology2012,;78:736.
4% with suspected CNS infections were infected with dengue virus
18% of children with encephalitis were confirmed with dengue infection
Solomon, et al. Neurologic manifestations of dengue infection Lancet 2000
Kankirawatana et al. Dengue infection presenting with CNS manifestation J child Neurol 2000
3 types of Neurologic manifestations
Classic signs with
acute infection
Encephalitis with acute
infection
Post-infection disorder
Reduced level of
consciousness
SeizuresProlonged
coma
Other signs of severe dengue
infectionShock
Vascular leakage
hemorrhage
Metabolic disturbances
Diagnosis
CSF
• Moderate lymphocytic pleocytosis
CT/MRI
• Diffuse cerebral edema
CSF
• Viral isolation
trea
tmen
t No effective drugs
Fluid management
prev
entio
n Vaccine not yet available
Vector control
Mortality due to neurologicalInvolvement-low
Systemic bacterial infections with neurologic manifestations
Typhoid fever
Cat-scratch disease
Typhoid fever
Caused by S. ser. typhi
insidious
Incubation period 10-14 daysRelated to inoculum size
Fever malaise anorexia abdominal
pain
Dull, continuous
frontal headacheDrowsy Irritabledelirious
Relative bradycardiaToxic facies
Coated tongueDoughy
abdomenmeningismus
Typhoid with CNS manifestations
27% • Occurring 6 days after fever onset• Lasts for 8 days
Restlessness, confusion, disorientation• Resolution in 4 days
Typhoid delirium
state/toxemia
Specific neurological
complications
Pathogenesis
Not known
Metabolic disturbances, toxemia, hyperpyrexia
Cerebral edema, hemorrhage
Diagnosis
Isolation of Salmonella from cultures•Could not be isolated from
CSF
Relapse rate is 5-10%
Case fatality highest among children
Delay in instituting effective antibiotic
Mortality with neurologic illness 28.9%
encephalitisBhandari et al.Typhoid encephalopahty in children. Indian Journal child health 1990
Severe typhoid feverTreatment
• Parenteral• Ceftriaxone 100mkd OD x 5-7days• ciprofloxacin 20mkd BID x 7 days
• Oral• Cefixime 20mkd OD x 14 days• Ciprofloxacin 20mkd BID x 7 days• Azithromycin 20mkd OD x 7 days
Dexamethasone
Reduces mortality rate from 35-55 % to 10%
For severe typhoid
3mg/kg then 1mg/kg q6 for 48 hours
Control seizure
Manage increased ICP
Prev
entio
n Hand washingCareful food processing
Prev
entio
n Safe waterAppropriate sewage disposal
4 doses>6yo
Single dose>2yo
Oral live attenuated
Parenteral Vi capsular
polysaccharide
VaccinationHigh-risk groups
Cat-scratch diseaseTypical
90%
Cutaneous papule
lymphadenopathy
Atypical
Extranodal
Complicated
CSD with NEUROLOGIC MANIFESTATIONS
Neurologic manifestations
Encephalopathy Neuroretinitis
CSD with Encephalopathy
2-4%May be
fulminantOften
recover fully
Easily overlooked
Follows lymphadenopathy by days to months
Persistent headache
FeverSeizures
Neurologic deficits
Deficits usually self-limited
• Resolution-weeks to months
Death due to CSD encephalitis in 2 healthy children
Neuroretinitis
Seen in association with
bacteremiaAseptic
meningitisencephalopathy
Painless sudden loss of visual
acuityPapilledema
Macular exudates in star
formation
Prognosis goodVitrectomy
rarely indicated
Laboratory studies no
specific positive findings
CNS involvementParenteral
therapy
Short-term anti-
convulsant therapy
Role of antimicrobial
controversial
Neuro-retinitis
Steroid use difficult to evaluate
2 reports of 4yo given steroid
Encepha-lopathy
Systemic protozoal infection with neurologic manifestations
Malaria
Most important parasitic disease
Incidence and prevalence decreasing
Classic symptoms•High fever, chills, sweats
Plasmodium falciparum•Febrile non-specific illness
without localizing signs
Severe disease•Without exposure•young• immunocompromised
P. falciparum
Different clinical syndromes
Cerebral malaria
Cerebral Malaria
Unexplained coma • Patient with malaria parasitemia
Clinical case definition• High sensitivity, low specificity
Disease prodrome
FeverDiaphoresis
chills
Rapidly progresses
to comaBlantyre
scale<2
SeizuresBrainstem
dysfunction
Neurologic manifestations
Generalized seizures
Signs of increased ICP
Confusion, stupor, coma
Sequestration of parasitized RBC in microvasculature
Cytokine abnormalities
Abnormalities of blood-brain barrier
Histologic hallmark
Swollen discolored
brain
Cerebral vessels packed
with parasitized rbc
EEG
Generalized symmetrical
and asymmetrical
slowing
Focal slowing
CSF
Elevated opening pressure
Little cellular response
Treatment
• Antimalarials
• Early detection and treatment of complications
Dosing Schedule of Quinine Dihydrochloride in the Treatment for Severe Plasmodium falciparum Malaria Infection
Age Group Quinine dihydrochloride
Loading Dose Maintenance Dose
Children 8 years to 16 years
15 mg salt/kg IV drip for 4 hours in 10 ml/kg D5W or 0.9 NaCl (infusion rate must not exceed 5mg/kg per hour)
10 mg salt/kg IV drip for 4 hours every 8 hours in D5W or 0.9 NaCl
Children 7 years and younger
10 mg salt/kg in IV drip for 4 hours
10 mg salt/kg IV drip every 12 hours
Parenteral Quinine Dihydrocloride Infusion PLUS Tetracycline/Doxycycline/Clindamycin
Doxycycline3 mg/kg BW once a day (QD) for 7 days
Tetracycline250 mg 4 times a day (QID) for 7 days
Clindamycin10 mg/kg BW twice a day (BID) for 7 days
ICU• No adjunctive therapy decreased
mortality and morbidity
Parenteral therapy• Until parasite density decreases• Able to tolerate oral therapy
Therapy
Glucose correction
fluids
antipyretics
benzodiazepines
phenobarbital
Phenytoin
• fataluntreated
• Coma resolves rapidly
• Mortality 15-25%treated
Acute seizures increase mortality
Long-term neurologicdisability
60 -fold higher odds of adverse neurologic outcome
Prevention
Bed nets
chemoprophylaxis
Vaccine development
chemoprophylaxisDrugs Schedule Dose
Pregnant Adult Pediatric
A. For People Travelling To Endemic Areas
Doxycycline Tablet (100 mg)
Start two to three days prior to travel, daily while in the area and continue up to four weeks upon leaving the area
contraindicated < 8 years: contraindicated> 8 years old:2 mg/kg up to 100 mg daily
MefloquineTablet (250 mg base)
Start 1-2 weeks before travel; take weekly while in the area, and continue up to four weeks upon leaving the area
contraindicated 1 tablet weekly
< 45 kg: 5 mg/kg bw5-10 kg ⅛ tab
10-19 kg ¼ tab
20-30 kg ½ tab
31-45 kg ¾ tab
Choloroquine Start 2 weeks before travel, take weekly while in the area and continue 4 weeks after leaving the area
2 tablets NA < 8 years: 5 mg/kg b.w. > 8 years: 2 tablets
Summary
Systemic infections with Neurologic manifestationsbacterial
protozoal
viral