Infections Flashcards
Virus associated with Progressive Multifocal Leukoencephalopathy
JC Virus
The first proven viral polyneuritis in humans
HIV
In viral infection, _____ is an intermediate step to seeding the brain or CSF.
viremia
Aside from hematogenous spread, the HSV may spread to the CNS via these structures
olfactory neurons > cribriform plate > olfactotry bulbs
trigeminal ganglion > gasserian ganglion
the most important route of infection for the majority of viruses
hematogenous
To be susceptible to a viral infection, the host cell must have
on its cytoplasmic membrane specific receptor sites to which the virus attaches.
Differentiating cells of the fetal brain have particular vulnerabilities, and viral incorporation may give rise to malformations and to hydrocephalus; an example is
mumps virus which can lead to?
ependymal destruction and aqueductal stenosis
As a rule, in viral infections of the CNS, the glucose content of the CSF is normal, but infrequently, mild depression of the CSF glucose can be seen but never below
25 mg/dL
As a rule, in viral infections of the CNS, the glucose content of the CSF is normal, but infrequently, mild depression of the CSF glucose can be seen in which viral meningitides?
mumps
HSV-2
LCM
VZV
In viral CNSI, Bell’s palsy has been associated to whuch virus/es?
HSV-1
What is Mollaret meningitis?
is characterized by episodes of acute meningitis with severe headache and sometimes low-grade fever, lasting for about 2 weeks, and recurring over a period of several months or years
What is the most common cause of viral aseptic meningitis in adults?
enterovirus mainly echovirus & Coxsackie virus
Then followed by: HSV2 Varicella HIV Mumps EBV
What is the most common cause of viral aseptic meningitis in children?
enterovirus-echovirus and Coxsackie virus
Followed by HSV2 LCM HSV1 adenovirus
The natural host of LCM virus
Lymphocytic choriomeningitis
house mouse Mus musculus
The 5th disease is caused by
parvovirus
strain of parvovirus that can cause meningitis and encephalitis in children
B19
viruses associated with meningitis + cauda equina neuritis
HSV
HIV
viruses associated with meningitis + generalized lymphadenopathy, transient rash, mild icterisia
EBV
CMV
virus associated with aseptic meningitis + intense lymphocytic pleocytosis (1000 cells/mm3)
LCM
What is Vogt-Koyanagi Harada syndrome?
combinations of iridocyclitis, depigmentation of a thick swath of hair (poliosis circumscripta) and of the skin, vitiligo, around the eyes, loss of eyelashes, dysacusis, and deafness (the pathologic basis of the syndrome is not known)
Mollaret Syndrome has been associated to which viruses?
HSV-1
HSV-2
EBV
Herpes 6 in children
What is Elsberg Syndrome?
HSV2
lumbosacral radiculitis
urinary retention
HaNDL syndrome
headache neurologic deficit
lymphocytic pleocytosis
Behcet disease
a diffuse inflammatory disease of small blood vessels that has several other characteristic features such as oral and genital ulcers
acute inflammatory CNS disease
parkinsonism seen as residua of encephalitis from which viruses
Flaviviruses
In viral CNSI, you see thalamic signal changes in MRI, the associated viruses are
Japanese B, West Nile, Eastern Equine Encephalitis, rabies
The most serious arbovirus in the US because of its high mortality and morbitidy
EEE
eastern equine encephalitis
Among the viral encephalitides, this is the gravestt
HSV
Describe the pathology found in HSV encephalitis
intense hemorrhagic necrosis of the inferior & medial temporal lobes & the mediorbital parts of the frontal lobes
In the acute stages of HSV encephalitis,
eosinophilic inclusions are found in
intranuclear regionsn of neurons & glial cells
Two routes of entry of HSV to the CNS, which is more favored to be true?
latent virus in the trigeminal ganglia with reactivation:
1 infect the olfactory tract - olfactory bulb - CNS
2 spread along nerve fibers innervating anterior & middle fossae leptomeninges
2 more favored
EEG changes in HSV encephalitis
lateralized periodic high-voltage sharp waves in the temporal regions and slow-wave complexes at regular 2 to 3Hz
Sensitivity of nested PCR in HSV encephalitis for the first 3 weeks of illness
95%
Dose of acyclovir for HSV encephalitis
30 mg/kg/d for 10 to 14 days
if treatment is begun within ____ of onset of HSV encephalitis in an awake patient, survival is >90%
4 days
established cause of a limbic encephalitis in adult patients following allogenic hematopoietic stem cell bone marrow transplantation
HHV-6
limbic encephalitis, post bone marrow transplant associated with gray matter damage
adenoviruses
Aside from HHV-6, viral agents that can also cause encephalitis in transplant recipient patientts
CMV, EBV, adenovirus, HSV, and varicella zoster virus
Incubation period of rabies
20-60 days can be as short as 14 days
Describe the evolution of rabies infection
- incubation period of 20-60 days
- tingling numbness reflecting invasion of sensory ganglion
- prodromal symptoms, involvement of tegmental medullary nuclei
- psychosis, seizures
- death within 4-10 days for the paralytic form
Characteristic pathologic findings in rabies infection
Negri bodies - cytoplasmic eosinophilic inclusions, most prominent in pyramidal cells of the hippocampus & Purkenje cells
What are Babe nodules? where do you find these?
focal collections of microglia in the brainstem of rabies infected patients
This compound can inactivate the rabies virus so better wash bite wound with this!
Benzyl ammonium chloride
postexposure prophylaxis for rabies
Human rabies immune globulin (HRlG) 20 U/kg
1/2 infiltrated in the wound
1/2 intramuscular
active immunization for rabies
human diploid cell vaccine HDCV
1-mL injections on the day of exposure
days 3, 7, 14, and 28 after
Acute ataxia of childhood is most associated with this virus
VZV
but can be: enteroviruses (Coxsackie), EBV, CMV
vesicles in VZV are called
Lipschutz inclusion bodies
pathologic changes in VZV infection (4)
(1) inflammation in several unilateral sensory ganglia of the spinal or cranial nerves, (can cause necrosis /-hemorrhage)
(2) inflammation in the spinal roots & peripheral nerve contiguous with the involved ganglia
(3) poliomyelitis (different from acute anterior poliomyelitis because unilateral, segmental, involves dorsal horn, root, & ganglion)
(4) relatively mild leptomeningitis, limited to the involved spinal or cranial segments & nerve roots
True or False. one attack of zoster provides lifelong
immunity
FALSE
VZV DNA is localized primarily in
trigeminal & thoracic ganglion cells corresponding to the dermatomes in which chickenpox lesions are maximal and that are most commonly involved
In VZV, the vesicles always appear within
72-96 hours
In VZV, pain & dysesthesia last for
1-4 weeks
VZV infection can be confirmed by
1 Tzanck smear - inding multinucleated giant cells in scrapings from the base of an early vesicle
2 direct immunofluorescence of a biopsied skin lesion, using antibody to VZV
Most common dermatomes affected by VZV
T5-T10
then cranicervical
Acyclovir shortens the duration of acute pain and
speeds the healing of vesicles in VZV infection, provided that treatment is begun within approximately
48-72 h upon appearance of the rash
Treatment for postherpetic neuralgia
amitriptyline 50 mg at bedtime can be increased
gradually to 125 mg daily
True or False. postherpetic neuralgia eventually subsides even in the most severe and persistent cases
True
True or False. HIV results in a depressed cell-mediated immunity particularly decreasing the number of CD8+ lymphocytes
False
CD4+
In the later stages of HIV infection, the most common neurologic complication is
AIDS dementia complex
AIDS Dementia Complex
subacutely progressive dementia (loss of retentive memory, inattentiveness, language disorder, apathy), abnormalities of motor function
Without treatment, survival after the onset of AIDS dementia is
generally 3 to 6 months
True or False. In AIDS Dementia complex, treatment with antiretroviral drugs can result in cognitive improvement.
True
Most sensitive test in the early stages of AIDS Dementia complex
psychomotor speed testing
e.g., trail making, pegboard, and symbol-digit testing
MRI findings in AIDS Dementia Complex
patchy but confluent or diffuse white matter changes with ill-defined margins
Pathologic findings in AIDS Dementia Complex
diffuse & multifocal rarefaction of the cerebral white matter with scanty perivascular infiltrates of lymphocytes & clusters of a few foamy macrophages, microglial nodules & multinucleated giant cells
diffuse myelin breakdown, white matter pallor
diffuse poliodystrophy
True or False. AIDS dementia complex is due to secondary brain destruction due HIV infection elsewhere
False
It is a result of a direct virus invasion
Pathologic picture of HIV myelopathy
vacuolar degeneration
Most common form of peripheral neuropathy in HIV infection
distal, symmetrical, axonal polyneuropathy, predominantly sensory & dysesthetic in type
the first proven viral polyneuritis in humans
HIV
HIV myopathy
inflammatory myositis
Most frequent focal infectious complications in AIDS
toxoplasmosis
True or False. Asymptomatic Toxoplasma-seropositive AIDS patients should be treated with oral pyrimethamine & sulfonamide
True
Because Toxoplasmosis in AIDS usually represents a reactivation of a previous infection
Treatment of Toxoplasmosis?
if this is not tolearted, what can you give?
oral pyrimethamine (100 mg then 25 mg daily) + sulfonamide (4 to 6 g daily in four divided doses)
clindamycin
Most frequent nonfocal infectious complications in AIDS
CMV
crytococcosis
CMV encephalitis in AIDS is usually accompanied by
retinitis
MRI findings in AIDS with CMV encephalitis
T2 signal hyperintensity in the ventricular borders
Diagnostic test for CMV infection
PCR
Treatment for CMV infection
ganciclovir
foscarnet
Quaternary Syphilis
consists of an aggressive and rapidly progressive
necrotizing process that causes strokes and dementia as a result of involvement of brain parenchyma and vessels
Shingles involving several contiguous dermatomes is known to occur in AIDS with CD4 counts below
500
Forms of VZV infection AIDS patients
- multifocal lesions of the cerebral white matter like PML
- cerebral vasculitis with hemiplegia
- myelitis
A special result of HlV antiretroviral treatment may induce an intense inflammatory response to a coexistent infection
immune reconstitution inflammatory syndrome, or IRIS
Tropical Spastic Paraplegia
HTLV-1
Virus causing lower motor neuron paralysis + hemorrhagic conjunctivitis
enterovirus 70
Viruses that can cause acute anterior poliomyelitis
poliomyelitis
Coxsackie groups A and B
Japanese encephalitis
West Nile Virus
The polio virus multiplies in the
pharynx & intestinal tract
2 Types of Poliomyelitis
NonParalytic
Paralytic
Paralytic Poliomyelitis symptomatology
- weakness at the height of fever then improvement then rapid muscle weakness peak within 48 hours
- no progression of weakness after the temperature has been normal for 48 hours
- muscle atrophy 3 weeks, maximal 12-15 weeks
Pathologic reactions in poliomyelitis
- lesions are found i n the precentral gyrus, brainstem, spinal cord
- hypothalamus, thalamus, brainstem (motor nuclei of reticular formation), vestibular nuclei and roof nuclei of the cerebellum, spinal cord anterior & intermediate gray matter
Polio Vaccine
Sabin Vaccine
2 doses 8 weeks apart at 1 year of age then before schooling
“Inclusion body encephalitis”
SSPE
subacute sclerosing panencephalitis
Describe the symptomatic evolution of SSPE
- usually there is a primary measles infection before 2 years old then an asymptomatic period of 6-8 years
- progressive intellectual deterioration, seizures, mycolonus
- decorticate
progressive ataxic-myoclonic chronic dementia in a child
SSPE
subacute sclerosing panencephalitis
characteristic EEG in SSPE
periodic (every 5 to 8 s) bursts of 2 to 3/s highvoltage waves, followed by a relatively flat pattern
Histopathologic hallmark of SSPE
Eosinophilic inclusions in the cytoplasm & nuclei of neurons and glia cells
Oligoclonal bands found in the CSF of SSPE represent
measles-virus-specific antibody
Histopathologic picture of PML
- gigantic reactive astrocytes containing bizarre-shaped nuclei and mitotic figures (resemble high grade glioma)
- nuclei of oligodendrocytes are greatly enlarged & contain abnormal inclusions
CSF picture of PML
normal
MRI of PML
variable size & location of nonenhancing demyelinating lesions
Pathogenesis of PML
JC virus thought to be dormant in the kidney or bone marrow until an immunosuppressed state permits its active replication
True or False. approximately 70% of the normal adult population has antibodies vs JC virus
True
True or False. PML caused by JC virus is untreatable in non-AIDS patients but progression can be slowed down in AIDS patients
TRUE
for AIDS patients, give antiretroviral + protease inhibitor
Poor prognostic sign in JC Virus PML
CD4
First recognized slow virus infection
Encephalitis lethargica
but the virus is still not identified!
True or False. Parkinsonian syndrome seen in survivors of Encephalitis Lethargica / somnolent-ophthalmoplegic encephalitis have Lewy bodies similar to idiopathic PD
False
no Lewy bodies but with neurofibrillary changes
Rasmussen’s Encephalitis is associated to which viruses and which autoantibody
CMV, HSV1
anti-glutamine receptors3
What is a prion?
proteinaceous infectious particle that is devoid of nucleic acid, resists the action of enzymes that destroy RNA and DNA, fails to produce an immune response, and electron microscopically does not have the structure of a virus
PrP is normally encoded in
chromosome 20
True or False. An abnormally folded prion protein can act as a template for the conversion of normal PrP to PrPsc
True
How does a prion protein Prp acquire its infectivity?
change in the physical conformation in which its helical proportion diminishes and the proportion of the beta
pleated sheet increases
Another classification scheme proposed for Prions Disease is to base tion systems have been devised that
are based on both the presence of methionine (M) or
valine (V) at codon ?
129
EEG is SSE
changing over the course of the disease from one of diffuse and nonspecific slowing to one of stereotyped psuedoperiodic highvoltage slow- (1- to 2-Hz) and sharp-wave complexes on an increasingly slow and low-voltage background
MRI is SSE
hyperintensity of the lenticular nuclei on T2-weighted
and diffusion-weighted images in the basal ganglia and
cortex
CSF finding diagnostic of SSE
immunoassay of peptide fragments of normal brain
proteins, termed “14-3-3”
repeat this test up to 3x
Gerstmann-Straussler-Scheinker Syndrome
autosomal dominant , progressive cerebellar ataxia,
corticospinal tract signs, dysarthria, and nystagmus
+/- mild dementia
Fatal Insomnia
characterized by intractable insomnia, sympathetic overactivity, & dementia, leading to death in 7 to 15 months
- lesions mainly in the medial thalamic nuclei
- mutation in codon 178
Kuru histologic picture
noninflammatory loss of neurons and spongiform change throughout the brain, but predominantly in the cerebellar cortex, with astroglial proliferation and kuru plaques
Kuru symptomatology
afebrile, progressive cerebellar ataxia, with abnormalities of extraocular movements, weakness progressing to immobility, incontinence in the late stages, and death within 3 to 6 months
Vector of Zika Virus
Aedes
Zika virus can cause
microcephaly
GBS
Most common bacterial meningitides
Streptococcus pneumoniae Neisseria meningitides group B streptococcus in neonates Listeria monocytogenes Haemophilus influenza
Seizures in meningitis are most associated with
H influenza
Most common bacterial menigitides in the neonates
E. coli
group B streptococcus
One factor that predispose a patient to have bacterial meningitis
antecedent viral infections of the upper respiratory passages or infections of the lung
Rapid detioration in a patient with meningitis associated with petechial or purpuric rash
Meningococcemia
Echovirus serotype 9
Staphylococcus aureus
Meningitis + cranial nerve abnormalities
pneumococcal meningitis
Most significant factor in the pathogenesis of neonatal meningitis
maternal infection
Meningitis in splenectomized patients, most likely is caused by
Streptococcus pneumoniae
Meningitis after an ear infection or upper respiratory tract infection
H influenza
True or False. Infants with pneumococcal meningitis have the highest risk factor for developing subdural effusion
False
regardless of bacterial type
the simplest method of demonstrating effusion in a child
transillumination of the skull
an indispensable part ofthe examination of patients with the symptoms and signs of meningitis or of any patient in whom this diagnosis is suspected
lumbar puncture
CSF pleocytosis in bacterial meningitis ranges from
250-10000 cells/ mm3
CSF red cells in meningitis are seen in
anthrax Hantavirus dengue ebola amebic
CSF protein in bacterial meningitis ranges from
100-500 mg/dL
CSF glucose in bacterial meningitis
CSF cultures in bacterial meningitis are usually positive in
70-90%
Blood cultures in bacterial meningitis are usually positive in
40-60%
Most sensitive test of demonstrating bacterial infection in the CSF
PCR
other tests CIE LPA RIA ELISA
CSF LDH of >35 mg/dL. Fungal, bacterial or viral?
Fungal or bacterial
The most specific and sensitive test for CSF
otorrhea and rhinorrhea is the finding of
beta2-transferrin (tau), not found in fluids other than CS
empiric therapy for bacterial meningitis in 0-4 week old
Cefotaxime + ampicillin
empiric therapy for bacterial meningitis in 4-12 week old
3rd G Cephalosporin + ampicillin + dexamethasone
empiric therapy for bacterial meningitis in 3month - 50 years o ld
3rd G Cephalosporin + vancomycin
+/- ampicillin
empiric therapy for bacterial meningitis in >50 years old
3rd G Cephalosporin + vancomycin + ampicillin
empiric therapy for bacterial meningitis in immunocompromised patient
ceftazidime + vancomycin + ampicillin
empiric therapy for bacterial meningitis with basilar skull fracture
3rd G Cephalosporin + vancomycin
empiric therapy for bacterial meningitis with head trauma, or post neurosurgery, CSF shunt
ceftazidime + vancomycin
antibiotic to add if Listeria monocytogenes is suspected
ampicillin
Duration of treatment in bacterial meningitis
10-14 days
Dexamethasone dose for bacterial meningitits in a child
0.15 mg/kg qid for 4 days
Dexamethasone dose for bacterial meningitits in an adult
10mg IV initial then 5mg q6 x 4 days
True or False. Patients with bacterial meningitis with evidence of cortical vein thrombosis should be started on anti-seizure drugs
True
this neurologic sequelae of bacterial meningitis was shown to have decreased with dexamethasone
sensorineural hearing loss
Prophylaxis for patients exposed to meningococcal meningitis
Ciprofloxacin
Rifampicin mg q12 for adults; mg/kg q12 for children x 2 days
Prophylaxis for patients exposed to meningococcal meningitis >2 weeks
none
Osler triad
pneumococcal meningitis
pneumonia
endocarditis
What is Hurst Disease and which microorganism is it associated with?
Acute hemorrhagic leukoencephalitis
Associated with Mycoplasma pneumoniae
Symptomatology of Mycoplasma pneumoniae encephalitis
Cerebellitis Choreoathetosis Seizures Delirium Hemiparesis
How to establish the diagnosis of Mycoplasma pneumoniae encephalitis?
1 culture from respiratory tract
2 IgG IgM antibodies, cold agglutinin in blood CSF
3 PCR dna in CSF
Treatment of Mycoplasma pneumoniae encephalitis
Macrolide
Or
Tetracycline
Meningoencephalitis in an immunocompromised individual taking the form of a rhombencephalitis
Listeria monocytogenes
Treatment of Listeria monocytogenes encephalitis
Ampicillin 2g IV q4
+ Gentamicin 5mg/kg IV in 3 divided doses
Bacteria causing Melioidosis
Burkhorderia pseudomallei
A diabetic patient came from vacation from Cambodia and Thailand had encephalitis. Most likely culprit is?
Burkholderia pseudomallei causing melioidosis
Diagnositc test for melioidosis
Culture of organism from any body site
CSF pharynx blood urine or sputum
Treatment of melioidosis
1 intensive phase: Ceftazidime IV x 10-14days
2 eradication phase: cotrimoxazole +/- doxycycline
Diagnostic test for Legionella encephalitis
Urine antigen
Culture of blood CSF
Treatment for Legionella encephalitis
Levofloxacin
Moxifloxacin
Azithromycin
Rifampicin
Microorganism responsible for cat scratch disease
Bartonella henselae
Catscratch fever symptomatology
Unilateral axillary/cervical adenopathy
Encephalopathy
High fever
Seizures or status epilepticus
In AIDS: focal cerebral vasculitis, neuroretinitis
Catscratch fever diagnostic workup
PCR o silver staining from excised lymph node
Catscratch fever first line of treatment
Azithromycin or
Doxycycline
Hemorrhagic inflammatory spinal fluid formula
Necrosis of vessels
Bacillus anthracis
Treatment of anthrax
Ciprofloxacin +
Clindamycin or
Rifampin or
Meropenem
Acute meningoencephalitis
Papilledema
Increaee ICP
After drinking raw milk
Brucellosis
Diagnostic workup for brucellosis
Blood CSF antibody titers
Treatment of Brucellosis
Doxycyline +
Streptomycin or
Gentamicin or
Rifampin
Microorganism responsible for Whipple’s Disease
Tropheryma whipplei
Slowly progressive dementia Supranuclear ophthalmoplegia Ataxia Seizure Nystagmus Oculomasticatory movemebts / myorhtyhmja
Likely diagnosis? Microorganism that caused this?
Whipple Diseas
Tropheryma whipplei
Treatment for Whipple Disease
Penicillin or Ceftriaxone x 2 weeks then
TMP-SMX or or doxycycline or tetracycline x 1yr
Subdural empyema usually originates from
frontal or ethmoid sinuses
Subdural empyema pathogenesis
1 direct extension through bone & dura
2 spread from septic thrombosis of venous sinuses (superior longitudinal sinus
Most common causative bacteria in subdural empyema
Streptococci (nonhemolytic & viridans)
Empyema that follows meningitis in children tends to localize on the
undersurface of the temporal lobe
Empiric treatment for subdural empyema
3rd generation cephalosporin + metronidazole
Empiric treatment for epidural abscess
cephalosporin + vancomycin
The most commonly involved sinuses in septic thrombophlebitis
transverse
cavernous
petrous
Transverse sinus septic thrombophlebitis
usually follows a middle ear, mastoid, or petrous bone chronic infection
True or false.
Anticoagulation is the mainstay of treatment of septic thrombophlebitis
False
high doses of antibiotics
Septic Cavernous Sinus Thrombophlebitis is usually secondary to
ethmoid, sphenoid, or maxillary sinuses infection
True or False.
brain abscess is always secondary to bacteremia and a bacterial focus elsewhere in the body
False.
a small proportion is iatrogenic
Brain abscess originating from the ear usually are located in
2/3 inferomedial temporal lobe
Metastatic abscesses from hematogenous spread are
usually situated in
the distal territory of the middle cerebral arteries
Most common cardiac congenital anomaly to develop brain abscess
Tetralogy of Fallot
Most common organism causing bacterial cerebral abscess
virulent streptococci
2 stages in the pathogenesis of TB meningitis
1 bacterial seeding of the meninges and subpial regions of the brain with tubercle formation
2 rupture of one or more of the tubercles and the discharge of bacteria into the subarachnoid space
Histopathologic finding in meningeal tubercles
central zone of caseation surrounded by epithelioid cells and some giant cells, lymphocytes, plasma cells, and connective tissue
TB PCR sensitivity
80%
The single most effective drug in TB
isoniazid
HREZ dose in adults
5-10-15-20 mg/kg/day
HREZ dose in children
10-15-15-20 mg/kg/day
Dexamethasone dose in TB meningitis
0.4mg/kg/day x 1 week then taper 3-6 weeks
Sarcoidosis is
represents an exaggerated cellular immune response to a limited class of antigens or autoantigens
mainstay of treatment of sarcoidosis
steroids
Causative agent of neurosyphilis
Treponema pallidum
The initial event in neurosyphilis is
meningitis
CSF changes in neurosyphilis in order
cells - protein - gamma globulins
Principal Types of Neurosyphilis 8
Asymptomatic neurosyphilis meningeal syphilis meningovascular syphilis paretic neurosyphilis tabetic neurosyphilis syphilitic optic atrophy spinal syphilis syphilitic nerve deafness vestibulopathy
Treatment of neurosyphilis
-IV penicillin G 18-24M u/day x 10-14 days
Most common form of neurosyphilis
meningovascular syphilis