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Flashcards in CNS intro Deck (253):
1

Mass Lesions/Abscesses

Abscess – S. aureus, anaerobes

neurocysticercosis (cysts) -- Taenia solium

toxoplasmosis –(pseudocyts) - Toxoplasma gondii

2

Neurotoxic diseases

CNS – tetanus -- Clostridium tetani (rare only due to vaccination)

PNS – botulism -- Clostridium botulinum
(rare only due to proper food handling)

3

Peripheral Nervous System (PNS) diseases

Leprosy – Infection of sensory nerves – Mycobacterium leprae

Guillain-Barre’ Syndrome – demyelination of PNS - autoimmune disease –Campylobacter jejuni

Botulism – toxin inhibits nerves at the neuromuscular junction –Clostridium botulinum

Myasthenia gravis

4

Prion disease

new variant Creutzfeldt-Jacob Disease: Prion of bovine spongiform encephalitis

Creutzfeldt-Jacob Disease (CJD). Human Prions

5

Common cause of purulent/pyogenic meningitis: bacteria

Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae, type b

Streptococcus agalactiae
Escherichia coli K1
Klebsiella pneumoniae
Listeria monocytogenes

6

Bacterial encephalitis and/or mass lesions

Mycoplasma pneumoniae
Listeria monocytogenes
S. aureus
anaerobic [mixed] infections

7

viral encephalitis

HSV-1
arborviruses
rabies
polio

non-polio enteroviruses:
Echovirus
Coxsackie virus
enterovirus 68-71

HIV
JC virus
measles (rare only due to vaccination of humans) -SSPE
VZV
CMV

8

Bacteria are most common cause of typical - purulent/pyogenic meningitis

Streptococcus agalactiae
Escherichia coli K1
Klebsiella pneumoniae
Listeria monocytogenes
Streptococcus pneumonia
Neisseria meningitidis
Haemophilus influenzae, type b
Mycoplasma pneumoniae.

9

Viruses are the most common cause of meningitis (over all) and the cause of aseptic/viral meningitis

HHV 6,7
NPEs
arbovirus
HSV-2
LCMV
HIV
Mumps virus, unless countries immunize against it.
polio, ditto


10

tetanus

not meningitis, tetanus is a neurotoxemia, like botulism

11

Fungi that cause meningitis

Cryptococcus neoformans & C. grubii. (Cryptococcosis)

12

Other causes of meningitis

1. Lyme disease - B. burgdorferi.

2. M. tuberculosis.

3. syphilis - T. pallidum.

13

Encephalitis:

Viral cases have high mortality and incidence of severe neurological sequelae

14

Diffuse epidemic diffuse encephalitis in the summer/fall months:

Arbovirus:

Eastern equine encephalitis (EEE) virus.

Western equine encephalitis (WEE) virus.

Venezuelan equine encephalitis (VEE) virus.

St. Louis encephalitis (SLE) virus.

Powassan encephalitis (POW) virus.

California encephalitis serogroup: Jamestown canyon, La Cross viruses.

Colorado tick fever virus.

Mountain fever in Colorado virus.

West Nile encephalitis (Africa, Europe, USA) virus

Others: HSV-1 and the non-polio enteroviruses

15

year-round viral encephalitis

Herpes Simplex virus HSV (HSV-1 esp) sporadic, usually- focal encephalitis

16

non-polio enteroviruses

a. ECHO viruses,
b. Coxsackie viruses,
c. enteroviruses 6871.

17

other viral encephalitis agents

4. Lymphocytic choriomeningitis virus (LCM).

5. HIV - HIV-1-associated cognitive/motor complex (AKA AIDS Dementia Complex).

6. Cytomegalovirus (CMV).

7. Rabies virus (rare only due to vaccination of dogs and cats).

8. Polio, measles, mumps viruses (rare only due to vaccination)

18

Focal Viral encephalitis:

1. HSV-1(usually, not always) sporadic, focal encephalitis all year round.

2. Rabies virus – Rabies (rare only due to vaccination of dogs and cats)

3. Polio viruses (rare only due to vaccination of humans)

arboviruses and non-polio enteroviruses

Encephalomyelitis: WNV, Polio

CMV
VZV
JC virus and PML

19

bacterial agents of encephalitis

a. Mycoplasma pneumoniae.
b. Listeria monocytogenes

20

fungal agent of encephalitis

Cryptococcus neoformans var. grubii

21

Slow virus encephalitis diseases:

HIV - HIV-1-associated cognitive/motor complex (AKA AIDS Dementia Complex).

Progressive multifocal leukoencephalopathy (PML): polyomaviruses – papovavirus: JC
virus severe T-cell suppression/AIDS or transplant pt.

Subacute, sclerosing panencephalopathy (SSPE): Measles (Rubeola virus, rare in US (exc. immigrants)

22

protozoan agents of Meningoencephalitis/Mass lesions:

toxoplasmosis: Toxoplasma gondii.

amoebic meningoencephalitis:
a. Naegleria fowleri.
b. Acanthamoeba spp.
c. Balamuthia mandrillaris.
d. Vahlkampfia spp.
e. Hartmanella spp.

23

helminth agents of Meningoencephalitis/Mass lesions:

Neurocysticercosis -- Taenia solium.

Cystic Echinococcosis-hydatid cyst -- Echinococcus granulosus or multilocularis.

Raccoon Round Worm Encephalitis/Baylisascariasis -- Baylisascaris procyonis.

Toxocaria -- Toxocaria cannis or cati.

24

Peripheral neuropathies/Bell’s palsies, acute facial paralysis

HSV-1, VZV, B. burgdorferi

25

Guillain-Bare’ syndrome

Most common cause of generalized paralysis in US caused by
the host’s immune response to a mucosal infection of

GI tract - C. jejune;

RT
a. influenza virus
b. Chlamydia spp.;

G-UT - Chlamydia sp.

26

6? classes of CNS-PNS infections

Meningitis - CNS
Encephalitis - CNS
Mass Lesions/Abscesses – CNS
Neurotoxic diseases
Peripheral Nervous System (PNS) diseases
Prion disease

27

Meningitis - CNS: agents

viruses are the most common cause

bacteria are 2nd most common cause – 7 major agents

fungus are less common – Cryptococcus neoformans var. grubii

protozoa are less common – Toxoplasma ghondii, Naegleria fowleri

*Tetanus mimics some S & S of meningitis but tetanus is a neurotoxemia, like botulism.

28

meningitis is..

Meningeal inflammation resulting from an infection within the subarachnoid space

29

encephalitis is...

Inflammation of the brain parenchyma

30

focal encephalitis agents

primarily HSV-1 – HSV-1 disease is treatable by antiviral therapy

31

diffuse encephalitis

primarily arbovirus- supportive tx only

32

Encephalomyelitis

encephalitis with myelitis (spinal chord inflammation) – caused by poliovirus and West Nile virus – supportive therapy only

33

Mass Lesions/Abscesses – CNS –

Lesion is macroscopic in size and of sufficient mass/volume to press against the normal brain tissue → increased intracranial pressure →focal seizures

CT scan showing ring-enhancing (mass) lesion supports the diagnosis

34

Fungi: three common agents

Cryptococcus -- a meningoencehalitis

Candida. - meningitis

Coccidioides immitis -- a meningoencehalitis

35

parasites usually cause a..

meningoencephalitis

36

most common CNS parasites

1.Toxoplasma gondii (protozoan - Toxoplasmosis).
2. Taenia solium, agent of neurocysticercosis (NCC; helminth).
3. Echinococcus granulosus or multilocularis (Cystic Echinococcosis-hydatid cyst)
4. Baylisascaris procyonis (Raccoon Round Worm Encephalitis/Baylisascariasis)
5. Toxocaria cannis or cati (Toxocaria)
6.Naegleria fowleri predominate agent

37

other CNS parasites

Acanthamoeba spp.
Balamuthia mandrillaris.
Vahlkampfia spp.
Hartmanella spp.

38

encapsulated agents

S. pneumoniae;
S. agalactiae,
H. influenzae, type b;
N. meningitidis
E. coli K1,
K. pneumoniae,

Cryptococcus neoformans var. neoformans.

*require B cells (not crypto)

39

CMI required
(facultative or obligate intracellular agents)

Listeria monocytogenes.
Toxoplasma gondii.
Cryptococcus cytomegalovirus CMV
Mtb
JC virus and PML
HIV
LCMV.
E. coli K1??

40

predisposing factors: immunodificiency

immunodificiency:

T cell.
B cell.

Terminal complement deficiency (C5-9) and N. meningitides

Long-term corticosteroid therapy. Immunosuppression of solid organ transplant (SOT) patient.

Cancer due to chemotherapy or form of cancer, e.g., lymphoma
AIDS.

41

predisposing factor: chronic or debilitating disease

Advanced HIV/AIDS.
Sickle cell disease.
Lymphoma/cancer.

42

need high index of suspicion with oldies bc...

often hypothermic so don’t manifest with fever.

neck arthritis so already manifest with nuchal rigidity.

dementia masks lethargy and irritability.

43

newborns should be..

routinely tapped because so few S/S in this age group

44

nosocomial meningitis from..

Intraventricular catheters (IVC) and cochlear implant

45

Carriage is in nasopharynx and humans are only HOST for these bac

S. pneumoniae;
H. influenzae, type b;
N. meningitidis,
S. agalactiae (also in vagina, GIT, skin).

*Humans are only host for Mycobacterium tuberculosis

46

Carriage is in nares for this bac

Staphylococcus aureus

47

Carriage in humans is primarily on mucosal surfaces for these bac

endogenous anaerobic flora

48

Carriage in humans is primarily in the colon for these bac

Streptococcus agalactiae,
E. coli
K. pneumoniae
Listeria monocytogenes

49

Carriage in humans is primarily in the colon with migration to the vagina and vaginal colonization and migration to urethra → cystitis for these bac

Streptococcus agalactiae,
E. coli
K. pneumoniae

*can infect fetus: neonatal infection

50

Animals and/or humans are RESERVOIR for these bac

E. coli K1.
K. pneumonia.
L. monocytogenes.
M. leprae.
S. agalactiae,

Staphylococcus aureus: both but primarily humans

51

other bacteria

C. tetani, (soil reservoirs),
C. botulinum. (soil, water, animal reservoirs)
L. monocytogenes (ubiquitous).

52

viral agents: zoonosis

Arboviruses – animals (mammals and/or birds) and arthropods (mosquito or tick).
Rabies virus– mammals.
LCMV – mammals, especially rodents

53

viral agents that humans are sole reservoir for:

enteroviruses
measles virus
herpes viruses: HSV-1, HSV-2, HHV-6, HHV-7,
CMV
HIV.
JC and BK viruses.
mumps virus

54

other agents and epidemiology

Cryptococcus neoformans (soil and animal [bird] reservoirs) -- fungus

Toxoplasma gondii (animal reservoir) -- protozoan

Taenia solium (pig and humans reservoir) – tape worm.

Echinococcus granulosus or multilocularis (Cystic Echinococcosis-hydatid cyst)

Baylisascaris procyonis (Raccoon Round Worm Encephalitis/Baylisascariasis)

Toxocaria cannis or cati (Toxocaria) in cat or dog round worm

Amoebic meningoencephalitis: mainly Naegleria fowleri – warm water reservoir.

55

zoonosis

Arboviruses – animals (mammals and/or birds) and arthropods (mosquito or tick).
Rabies virus: Bat mostly, raccon-East Coast, skunk-mid-West in US – Dog,WW
LCMV from rodent.
Listeria monocytogenes.
Mycobacterium leprae?
Toxoplasma gondii (cysts bearing larvae),
Echinococcus granulosus or multilocularis (Cystic Echinococcosis-hydatid cyst)
Baylisascaris procyonis (Raccoon Round Worm Encephalitis/Baylisascariasis)
Toxocaria cannis or cati (Toxocaria)
Bovine spongiform encephalopathy prion (AKA new variant Creutzfeldt-Jacob Ds).
C. botulinum
*Cryptococcus neoformans (animal-bird mechanical vector)

56

Consumption of tainted food:

Bovine spongiform encephalopathy prion.
Taenia solium (cysts bearing larvae) – not directly to CNS, indirectly.
Toxoplasma gondii (cysts bearing trophs or bradyozoites).

57

Fecal-oral route / food is contaminated with feces

Taenia solium (ova) neurocysticercosis from human,
Toxoplasma gondii (ova) Toxoplasmosis from cat litter, soil.
enteroviruses (polio, ECHO & Coxsackie viruses, enteroviruses 68→71).
Listeria monocytogenes from many sources.
LCMV from rodent.
Echinococcus granulosus or multilocularis (Cystic Echinococcosis-hydatid cyst)
Baylisascaris procyonis (Raccoon Round Worm Encephalitis/Baylisascariasis)
Toxocaria cannis or cati (Toxocaria)

58

In utero (vertical) transmission:

Streptococcus agalactiae (less common than during parturition)

Listeria monocytogenes (more common than during parturition)

Non-polio enterovirus (Coxsackie, Echoviruses, enteroviruses 68→71).

LCMV.
Toxoplasma - Toxoplasma gondii.
rubella.
CMV.
HSV

59

During parturition:

Streptococcus agalactiae (more common than In utero transmission)
Listeria monocytogenes,
E. coli
K. pneumoniae
Herpes virus and CMV (more common In utero transmission)

60

Inhalation of infectious dust:

Cryptococcus neoformans.
LCMV

61

Agents of CNS disease associated with familial/close –contact outbreaks include

hib.
meningococcus. (N. meningitis)
Non-polio enterovirues.
T. solium – if someone is shedding ova.
Very rare, very, very uncommon agents that can cause outbreaks in USA are:
a. M. leprae (lepromatous form)
b. mumps virus
c. measles virus
d. rabies virus
e. polio virus

62

anaerobes

endogenous flora

63

arboviruses

exposure to mosquito; Ticks for two agents

64

Cryptococcus neoformans

bird droppings

65

HSV-1

disease is reactivation of latent infection

66

HSV-2

sexual contact

67

HIV

blood or bodily fluids

68

LCMV

exposure to rodents, droppings, secretions, fluids

69

Listeria monocytogenes

animal exposure, food

70

Measles virus -- SSPE

human, exposure before 1-y-of-age

71

Mumps

human exposure to agent

72

Mycobacterium leprae

human or animal exposure

73

Mycobacterium tuberculosis

human exposure

74

Neisseria meningitis

human exposure, terminal complement deficiency

75

nonpolio enteroviruses

human feces

76

Naegleria fowleri

exposure to fresh water with algae

77

polio enteroviruses

human feces

78

rabies virus

animal exposure, bat (USA) Dog (WW)

79

Staphylococcus aureus

Another person

80

Streptococcus agalactiae

low birth weight infant, rupture of membranes >24h before delivery, colonized vaginal canal

81

Streptococcus pneumoniae

congenital CSF leak

82

Taenia solium ova

human feces

83

Taenia solium cysticerci

undercooked or uncooked meat- pork

84

Toxoplasma gondii ova

cat feces

85

Toxoplasma gondii pseudocyst

raw or uncooked meat

86

??? are rare occurrences compared to other causes of morbidity and mortality, even among infectious diseases

Meningitis and encephalitis
M>E
viral>bacterial (less than 50%)
but viral not definitively dx

87

most common viral agents (children-->adults) in order

ECHO and Coxsackie viruses
then the arbovirues
HSV-2

88

Diffuse encephalitis>focal encephalitis

arboviruses: Most common agents of diffuse encephalitis

HSV-1: Most common agent (50%) of focal encephalitis

89

Most common agents of meningitis (viral)

Non-polio enteroviruses (ECHO viruses and Coxsackie viruses).
HHV-6, HHV-7

90

Less common agents of meningitis (after NPEs and HHV-6, 7)

Arboviruses – late summer→early fall seasonality, meningitis and diffuse encephalitis.
HSV-1 – no seasonality—focal encephalitis.
HSV-2 – if manifesting with primary symptomatic infection (genital herpes) -- meningitis.
LCMV – if winter seasonality and history of rodent exposure – meningitis.
Polio (late summer and early fall seasonality, meningitis primarily young children → adults) and Mumps (rare due to vaccination)

91

the most frequent cause of bacterial meningitis in infants, children, adolescents, and young adults in the United States

Meningococcal disease

3000 cases> 60% of the 3,000 cases are in individuals > 11 y-o-age and this age group has the highest mortality rate 25% versus 10 to 14% overall

11% to 19% of survivors are left with long-term disabilities: hearing loss, cognitive impairment, renal failure, limb amputations

92

the highest case mortality rate for any bacterial agent of meningitis
and
the most common infectious agent associated with patients with recurrent meningeal infections.

S. pneumoniae

(About 1/2 of all cases of meningitis in the US are nosocomial-acquired meningitis)

93

bacteria: year round seasonality

S. agalactiae.
E. coli K1
K. pneumoniae

94

bacteria: summer seasonality

protozoan: ?

L. monocytogenes

Neglaria fowleri

95

bacteria: late winter-early spring seasonality

H. influenzae type b
N. meningitidis
S. pneumoniae

96

viral: year-round seasonality

HHV-1
HHV-2
HHV-6; -7
CMV
HIV
Rabies

97

viral: Late summer and early fall seasonality

ECHO viruses and Coxsackie viruses
Polio virus
Arboviruses

98

viral: winter seasonality

LCMV

99

Congenital infections – The unborn child’ s infection is acquired in-utero and results in a diseased child at birth

TORCH agents:

TOxoplasma
Rubella
Cytomegalovirus [CMV]* (most common)
Herpes simplex virus [HSV]) -2 or -1

100

TORCH test -

a test to detect a congential (AKA intrauterine infection) infection in a neonate via presence of specific IgM in chord blood

101

the leading cause (by far) of infection and morbidity in the neonate

CMV infection

102

neonates: Highest incidence of infection and morbidity among procaryotes

S. agalactiae

103

neonates: highest incidence of infection andmorbidity of all agents.

cytomegalovirus (CMV)

104

other causes in neonates

E. coli K1
K. pneumoniae
L. monocytogenes
herpes simplex virus (HSV) 2 or 1
non-polio enterovirus (Coxsackie & Echoviruses)
Human herpes virus-6 and –7. (HHV-6 and HHV-7)

105

Infants and young children – all agents

HH-6, HH-7
non-polio enterovirus (Coxsackie; Echoviruses).
N. meningitides
S. pneumoniae
Mycobacterium tuberculosis.
Arboviruses
LCMV.
Mumps.

106

Adolscents →Elderly:

non-polio enterovirus (Coxsackie and Echoviruses).
Arboviruses.
N. meningitides,
S. pneumoniae
L. monocytogenes – those over 50-y-o-age.
Mycobacterium tuberculosis.
LCMV.
Mumps (Adolscents).

107

viral by age

Neonate: CMV (#1), HSV-2, 1, Non-polio enteroviruses

6 m-o-age up to 2-y-o-age HHV-6 & HHV-7.

2-y-o-age and older:
a. Non-polio enteroviruses.
b. HSV-1
c. Arboviruses.
d. HSV-2.
e. LCMV.


108

Bacterial Agent by Age:
nenonate

S. agalactiae (most common)
E. coli K1
L. monocytogenes
K. pneumoniae K1, K2 (least)

109

Bacterial Agent by Age:
Infant to adult

N. meningitides (most common)
S. pneumoniae

110

Bacterial Agent by Age: elderly

N. meningitides,
S. pneumoniae
L. monocytogenes

111

Pathogenesis -- Portal of entry for CNS disease
Secondary invasion of the CNS follows

bacteremia.
viremia.
fungemia.
parasitemia.

Entry into the subarachnoid space occurs via sites of minimal resistance:

choroid plexus.
dural venous sinuses.
cribriform plate.
cerebral capillaries.

112

Direct entry via damage to integrity of the CNS:

Penetrating injuries of the skull or spinal column.
congenital defects
*most common cause for both is S. pneumoniae, Hib, GAS

Ventricular shunts.

All children with cochlear implants, esp. those with implants with a positioner (rubber wedge) are at increased risk of infection for > 2 y post-implantation

113

Contiguous spread along vascular channels from:

Nasal sinuses -- Naegleria fowleri.
Malignant otitis externa (P. aeruginosa) or otitis media.
Mastoid.
Sites of parameningeal infection, e.g., epidural abscess.

114

Intra-axonal transport (retrograde flow) inside nerves:

rabies.
herpes.
polioviruses.
tetanus toxin.

115

Signs and symptoms of meningitis in the neonate are the same as those for neonatal sepsis and encephalitis, but are not the same as the adult and include

Fever.
Lethargy.
Poor feeding
GI disturbance (vomiting/diarrhea)/abdominal distension.
Respiratory abnormalities (e.g., dyspnea, cyanosis)
Cardiac abnormalities (tachycardia).
Bulging fontanelle (indicates pressure on brain), ONLY if CNS infection

116

Signs and Symptoms of any (bacterial, fungal, viral, etc.) meningitis in persons >2 y-o-age

Irritability
lethargy
fever

Others:
severe headache,
nuchal rigidity,
vomiting,
pressure on eyeball.
photophobia
meningeal inflammation/irritation

117

Meningeal inflammation/irritation elicits a protective response (5 different signs) to prevent stretching of inflamed, hypersensitive nerve roots:

Nuchal rigidity – meningismus, (e.g., The inability of a patient to place their chin to their chest passively without involuntary muscles spasms preventing it).

Kernig sign - extension of the leg at the knee when patient is supine with the thigh flexed at the hip → marked pain and resistance to extension of the leg.

Brudzinski sign - rapid flexion of the neck while patient is supine → involuntary brisk flexion of the knees.

Opisthotonos - head drawn backward, spasm of back muscles.

Tripod position (aka Amoss or Hoyne signs) knees and hips flexed, back arched lordotically, neck extended, and arms brought back to support the thorax.

118

S/S indicative of progression of severe symptoms indicate progression to meningoencephalitis:

decline in consciousness.
focal cerebral abnormalities (hemiparesis, monoparesis, aphasia)
Seizures.
convulsions.
coma.

119

Maculopapular rash

non-polio enteroviruses (ECHOvirus, Coxsackievirus, enteroviruses),
arboviruses
HSV.
S. pneumoniae.
N. meningitidis.
H. influenzae, type b

120

vesicular rash

HSV
fungi
non-polio enteroviruses.

121

Petechial / Purpuric:

S. pneumoniae.
N. meningitidis.
H. influenzae, type b.

122

Bacteria penetration of blood-brain barrier and into CSF leads to:

Local release of inflammatory cytokines in CSF

Adhesion of leukocytes to brain endothelium and diapedesis into CSF

Blood-brain barrier is further damaged and becomes permeable


123

Blood-brain barrier is further damaged, becomes permeable, which results in:

Exudation of albumin through opened intercellular junctions of meningeal venules.

Brain edema, increased intracranial pressure, cerebral vasculitis, altered cerebral blood flow.

Cranial nerve injury, seizures, hypoxic-ischemic brain damage, brain-stem herniation.

124

Mechanisms responsible for the encephalitic aspects of bacterial meningitis include:

metabolic encephalitis caused by endotoxin and TNF-α.
perivascular inflammation.
infarcts (strokes/seizures) caused by occluded blood

125

Encephalopathy is

is depressed or altered level of consciousness lasting >24 hours

126

Encephalitis is encephalopathy plus 2 or more of the following

fever (>38oC)
seizures
altered mental status,
severe headache

focal neurological findings (e.g., paralysis, cognitive disorders, if focal encephalitis is present),
CSF pleocytosis (> 5 WBC/ml),

electroencephalogram findings compatible with encephalitis,
abnormal results on neuroimaging.

Some manifestations of meningitis may also be present.

127

Arbovirus diffuse encephalitis

fever (>38oC), seizures, altered mental status, severe headache.

128

Polio focal encephalitis (Encephalomyelitis)

Acute osnet of a flaccid, ascending asymmetrical paralysis due to involvement of motor neuron in brain and spinal column with loss of superficial and deep reflexes, severe muscle aches or spasms, muscle pain, Sensory involvement - Abnormal sensations (but not loss of sensation) in an area, sensitivity to touch and paresthesia

129

Rabies focal encephalitis

dumb or furious forms

130

Rabies: Furious form

Sensory sensitivity to external stimuli, hyperactivity, agitation, anxiety, insomnia, loss of natural timidity - aggressive sexual behavior, hydrophobia and foaming at the mouth arise from excruciatingly painful, laryngeal spasms → confusion, delirium → coma → death

131

Rabies: Paralytic/Dumb rabies form

Signs and symptoms are indistinguishable from viral encephalitis, then the patient manifests with paralysis starting at extremities and spreading to the trunk as areas of the brain are destroyed. Paralysis → to hypoventilation/respiratory paralysis →hypotension/cardiac failure → eventually coma and death.

132

Herpes focal encephalitis with distinctive clinical features due to its remarkable localization:

*memory defects, psychosis, slurred speech, personality* changes from involvement of one *temporal lobe* - primarily the cerebral cortex with characteristic lesions (inflammation, focal hemorrhage, necrosis.

Treat with acyclovir.

133

Pathology of viral encephalitis:

Mononuclear accumulation in meningeal and perivascular spaces.

Fragility of brain blood vessels and the occurrence of perivascular hemorrhages and infarcts allow spillage of RBC, WBC and protein into the Virchow-Robin spaces that communicate with cerebrospinal fluid.

Viral replication in the brain parenchyma causes inflammation and severe CNS dysfunction. Few survive and those who do have serious emotional disorders and learning deficits.

134

During a viral infection in the CNS, viral agents are recognized by at least one of the

TLRs on neurons → neuronal death in the brain

(Neurons possess toll-like receptors that can activate a protein called SARM1 in neurons, which induces their death by affecting the function of mitochondria)

135

Focal sites of viral encephalitis:

Herpes virus
Polio

136

?? is the most common form of paralytic poliomyelitis; it results from viral invasion of the ???
which do what ??

Spinal polio

the motor neurons of the anterior horn cells, or the ventral (front) gray matter section in the spinal column

are responsible movement of the muscles, including those of the trunk, limbs and the intercostal muscles


137

Bulbar polio:

white matter pathway that connects the cerebral cortex to the brain stem

The destruction of these nerves weakens the muscles supplied by the cranial nerves, producing symptoms of encephalitis, and causes difficulty breathing, speaking and swallowing

138

Rabies:

predominates in the Grey matter.

localizes in the limbic regions (producing *focal symptoms*).

infects neurons in almost all areas of the brain:
cerebellum, the Purkinjes cells and also cells of the hippocampus, hypothlaamus and pontine nuclei

139

mass lesions s/s

Fever
Headaches (elevated intracranial pressure)

Seizures -- Focal or generalized tonic-clonic seizures.

Neurological deficits/focal signs (hemiparesis, visual loss, paraparesis).

Altered mental status (dementia, confusions, stupor)

140

CT scan showing ??


In severe cases ??

ring-enhancing (mass) lesion supports the diagnosis.

a mid-line shift, risk of brain stem herniation

141

an encapsulated structure grows in size (becomes visible to the naked eye) creating a

mass effect – displaces brain tissue and creates intracranial pressure

142

Etiology – Abscess:

Localized collection of purulent infectious agent material and host cell debris in a cavity formed by the disintegration of tissue

143

3 distinct abscess locations:

epidural (between vertebrae and dura)
subdural (between dura and arachnoid).
parenchyma (in the brain tissue)

144

Etiology of abscesses:

Procaryotic: S. aureus, anaerobic infections, L. monocytogenes.

Fungi agents: Candida albicans

145

Cystic lesions - humans as Intermediate hosts of parasites

A helminth (flat worm) produces a tissue cyst as part of its life cycle

146

2 distinct cystic lesion locations:

in the ventricles, subarachnoid space or meninges

parenchyma (in the brain tissue).

147

cystic lesion agents

Taenia solium (Neurocysticercosis)

Echinococcus granulosus or multilocularis (Cystic Echinococcosis-hydatid cyst).

148

Pseudocyst lesions humans as Intermediate hosts of parasites

a pseudocyst is formed in the brain parenchyma as a result of the human immune response to the parasitic/protozoan infection

149

Pseudocyst lesions caused by

Toxoplasma gondii (Toxoplasmosis) - protozoan

150

neurotoxins: Floppy (hypotonic)paralysis:

Guillain-Barre’ Syndrome – demyelination of PNS - autoimmune disease –primarily molecular mimicry of Ab first raised against Campylobacter jejuni antigens.

Botulism – an exotoxin/neurotoxin inhibits nerves at the neuromuscular junction / PNS – Clostridium botulinum elaborates the exotoxin

151

Botulism toxin acts at the ?? not the ??

myoneural/neuromuscular junction (not the CNS, unlike tetanus) paralyzing of the cholinergic nerve fibers at the point of release of acetylcholine

Toxin blocks both cholinergic transmission points in the autonomic system:
Synaptic ganglia
Parasympathetic motor end plates peripherally located in the junction between the nerve cell and muscle cell fibers

152

Botulism: Anticholinergic/inhibition of the parasympathetic with no effect on the ?? results in such symptoms as ??

sympathetic nerves

dilated and un-responsive pupils, dry mouth, and constipation

153

Botulism: Progressive neuromuscular blockade of muscles innervated by ?? occurs first, then ??

cranial nerves

the trunk (systemic generalized muscle weakness)

finally the extremities (peripheral motor weakness) and diaphragm

154

Later complications of botulism

paralytic ileus, severe constipation, and urinary retention

Ocular and cranial muscle weakness occurs first because neuromuscular junctions of these muscles have the lowest threshold for synaptic failure

155

Polio virus does what ??

kills neurons

156

Spastic (Rigid, hypertonic) paralysis

tetanus (mimics some S/S of meningitis)

exotoxin/neurotoxin inhibits nerves in the spinal column-CNS Clostridium tetani elaborates the exotoxin/neurotoxin.

157

tetanus is transported to inhibitory ??

interneurons e.g. Renshaw cells.

Interneurons: small neurons that that are involved in local processing of nerve signals and which generally have inhibitory activities

158

tetanus irreversibly inhibits the release of

inhibitory transmitter substances, γ-aminobutyric acid (GABA) and glycine,
(presynaptic blockade of these cells)

does not act on the synapses of Renshaw cells that handle
ACh transmission.

Absence of inhibitory Renshaw cell activity allows LMNs to increase muscle tone and rigidity and permits simultaneous contractions of both agonist and antagonist muscles

159

tetanus toxin is rapidly transported up the spinal column to reach the ??
where it ??

brain stem and/or hypothalamus

inhibits interneurons so that normal INHIBITORY feedback of the symp and parasym systems is disrupted and ONLY positive feedback of these systems occurs, resulting in severe disruption of autonomic function in late, severe, general tetanus

160

Lumbar puncture results are

clinical clues; not definitive diagnosis

161

Direct smear of CSF (~30% sensitive) that is stained by

Gram-stain (variable sensitivity)

A Gram stain of CSF is positive in 60% to 90% of cases, but results vary with the organism as well as with the concentration of bacteria in the CSF

In terms of bacterial concentrations, the CSF Gram stain is positive in up to 97% of cases when there are >10/ml, as opposed to around 25% when there are less than 10/ml

162

Gram-positive agents

Listeria monocytogenes
S. pneumoniae
S. agalactiae

163

Gram-negative agents

H. influenzae, type b
N. meningitidis
E. coli K1
K. pneumoniae

164

Sensitivity by organism

S pneumoniae, 90%;
H influenzae, 86%;
N meningitidis, 75%;
Gram-negative bacilli, 50%;
L monocytogenes, less than 50%.

165

other stains

acid-fast stain (Mycobacterium).
India ink preparation (Cryptococcus).
Saline wet mount (Naegleria fowleri).

166

Culture and sensitivity of sedimented CSF (~50% sensitive)

Order MIC and MBC
CSF cultures are positive in 70% to 85% of cases

167

other parameters

PMNs, lymphocytes, or monocytic lineage predominates?

RBC present?

Hypoglycorrhachia (low or normal levels of glucose) present?

Hyperproteinosis (elevated protein levels) or hypoproteinosis

Hyperglobulinorrachia - elevated antibodies in CSF present?


168

14-3-3 chaperone brain protein elevated (normal:

cerebrovascular events/acccidents (CVAs),
viral encephalitis,
Creutzfeldt-Jakob disease (prions)

169

Hypoglycorrhachia and Hyperproteinosis are related

In a patient with bacteria meningitis, albumin from the brain parenchyma enters the CSF and this protein movement disrupts the protein gradient that normally exists between the CSF and blood

The protein gradient between the blood and CSF is used to co-transport glucose from the blood to the CSF

high protein levels in the CSF stops co-transport of glucose so glucose levels are low in the CSF

*This is why a normal CSF glucose level is ~80% of the blood glucose level* : important to do simultaneous measurements of blood and CSF glucose*

170

Normal CSF is

a clear, colorless fluid
contains β2-transferrin

Not straw-colored like serous fluid

171

in a meningitis pt during Gram-staining of CSF specimens, CSF protein is

heat-fixed to the glass slide and stains pale pink, making detection of any Gram-negative bacteria in the CSF difficult.

172

Rapid test:

antigen testing/latex agglutination test:

*Latex spheres coated with antibody detects presence of capsular Ag in CSF*

Very low (@7%) sensitivity except with positive Gram-stain or culture positive specimen

173

antigen testing/latex agglutination test can detect

S. pneumoniae,
H. influenzae, type b
N. meningitidis
cryptococcal antigen

174

other tests

EIA test of a CSF specimen
*VDRL for syphilis
Procalcitonin: detection for bacterial meningitis

175

*PCR* – for specific agents:

enteroviruses (RT-PCR)
herpes simplex virus
JC virus
HIV (RT-PCR)

176

Skin specimen: vesicular

Tzanck or Papanicolaou stained skin biopsy specimen for HSV

177

Skin specimen: purpuric

Gram-stained smear of skin biopsy specimen:
S. pneumonia
N. meningitidis.

Culture and sensitivity (MIC, MBC)

178

blood tests:

*Culture and sensitivity* (MIC, MBC) of blood (2 samples from different sites)

positive culture:
most likely if pt is spiking a fever or fever is present!
establishes diagnosis in presence of negative CSF culture in symptomatic pt
40-90%

*PCR or RT-PCR of blood for specific viral agents*

Ag testing
serology: specific Abs

179

Other bodily fluids (e.g., urine):

*Order Gram-stain*

*Order culture and sensitivity* (MIC, MBC).

PCR of urine for specific viral agents may also be done.

Latex agglutination for cryptococcal antigen.

*Vaginal and Rectal swabs for GBS - Treat if culture positive* – Learn.

180

??? diagnostic tests are NOT feasible for CNS infectious diseases, so ???

sequential

order all appropriate tests right away – in parallel, NOT sequentially

181

EEG pattern indicative of

focal or diffuse problem

182

Neuroimaging: CT-scan or MRI

X-ray, CT scan, MRI – indicative of focal or diffuse problem

CT-scan will show contrast/ring-enhancing lesions for mass effect/lesion.

183

ddx

meningitis
encephalitis.

Non –Infectious → patient is usually afebrile:

a. (SAH or ICH) subarachnoid or intracerebral hemorrhage: Incidence is 40→50K/y in US, with the rate expected to double in next 50 y, thus *hemorrhage* is much more common than meningitis and/or encephalitis

b. (CVT) Cerebral venous thrombosis

c. Ischemic stroke.

Mass lesions.
paralysis – floppy vs spastic

184

Bacterial meningitis and viral meningitis have similar presentation, but

bacterial meningitis has a high mortality rate and survivors have serious neurological sequelae, viral meningitis doesn’t

so...
TRY to differentiate
and
treat all cases of meningitis as bacterial etiology until proven otherwise

185

For all cases of meningitis and encephalitis - until a definitive diagnosis is made use ??


and if clinical manifestations warrant add ??
until ??

combinational antibiotics efficacious for bacterial meningitis (but not necessarily exclusively for bacterial meningitis)

antifungal drugs and/or acyclovir
until diagnostic tests results and/or the patient fails to respond (fails to improve) to treatment over 1→2 days.

186

mportant to initiate combinational antimicrobial therapy within ?? of ?? via what route ?? even before ??

30 minutes of tap
via the parenteral route

before the results of culture, Gram-stain, PCR are known because mortality due to bacterial meningitis is high (10%) and long term neurological sequelae (subtle, moderate or serve) occur in many (>50%) survivors

187

For a patient with acute bacterial meningitis, antimicrobial therapy and the host immune response is thwarted by:

Acidic pH of CSF, this results in impaired PMN function and many antibiotics are less efficacious at acidic pH.

Elevated CSF proteins (albumin from brain) will bind to and inactivate many antibiotics

188

BIG CLUE TO ETIOLOGY: Normal vs. Disease:

(Selection of drugs for therapy should be based on Lab findings)

type WBC predominating [PMNs vs. Monocytic or lymphocytic lineage]

sugar, protein levels,

Stained smear reveals agent.

Gram-stain findings on spinal fluid, urine, skin lesions.

Latex agglutination tests of CSF, urine, etc.

189

Antimicrobial therapy must be ??

able to penetrate subarachnoid space (secreted in tears)

bactericidal: 10X the MBC

empiric, based on age (neonate, infant →middle age, elderly)

Combinational therapy: e.g., penicillin or ceftriaxone and an amino glycoside (empirical)
Switch to best drug when etiologic agent and susceptibility are determined.
MDR is documented

190

S. pneumoniae tx

IV cefotaxime (200 mg/kg/d) and continuous infusion vancomycin (60mg/kg/d after a loading dose of 15mg/kg) with adjunctive therapy with dexamethasone (10 mg every 6 hours)

*unless the strain is proven penicillin sensitive

191

For adults younger than 50 years, empiric treatment should consist of

for pts >50 yo add ?? for possible infection with L. monocytogene

ceftriaxone or 2 g of cefotaxime plus 1 g of vancomycin plus 10 mg of dexamethasone IV

Ampicillin 2 g IV

192

?? preferred over ?? in neonates

because ??

Cefotaxime over ceftriaxone

ceftriaxone may alter bilirubin metabolism in this population

193

Adults with gram-positive cocci on a CSF Gram stain who are receiving adjunctive corticosteroids should be treated with a ??

because ??

broad-spectrum cephalosporin plus rifampin (600 mg/d) instead of vancomycin


because of vancomycin's diminished CNS penetration in the presence of corticosteroids

194

If the etiologic agent is or suspected to be ?? or ?? in a person >17 y-o-age administer dexamethasone when ??

S. pneumo
Hib

15→ 30m before or at the same time as antibiotics are administered
NOT after

195

If the agent is S. pneumoniae that is resistant to penicillins or cephalosporins, then ?? is the drug of choice

BUT it must be used in ?? and the administered doses of said drug must be sufficient to ensure that ??

vancomycin

combinational therapy

appropriate concentrations are achieved in the CSF in the presence of dexamethasone

196

In children with pneumococcal meningitis, especially if there is a relapse, be aware of ??
what drogas ??

tolerance

Vancomycin, penicillin, aminoglycoside, quinolone --*antibiotics are static, not cidal

197

Do not administer dexamethasone to a person who has ?? or who is ??

already received antimicrobial therapy

manifesting with septic shock

198

Dexamethasone use in children

not associated with and any change in survival or time of hospital discharge

199

Clostridium tetenaii tx

metrodianazole

200

Haemophilus influenzae, type b tx

ceftriaxone, cefotaxime, cefuroxime or the alternative option is TMP-SMX.

201

Listeria monocytogenes tx

ampicillin plus gentamycin or TMP-SMX

202

Mycobacterium leprae tx

dapsone plus rifampin or clofazimine

203

Neisseria meningitidis tx

ceftriaxone or cefotaxime

204

Streptococcus pneumoniae tx

vancomycin + extended spectrum cephalosporin

205

Streptococcus agalactiae tx

penicillin G
(some abx resistance)

206

Toxoplasma gondii tx

sulfonamides or clindamycin + pyrimethamine

207

Cryptococcus neoformans tx

amphotericin B with 5-fluorocytosine

208

Herpes simplex virus tx

acyclovir

209

non polio Enteroviruses tx

pleconaril

210

Naegleria fowleri tx

Miltefosine

211

tx for GBS

all identified carriers and women who deliver pre-term before screening can be done should be offered intrapartum antimicrobial prophylaxis iv

212

Treatment of ?? as well as the protocol for treatment of an asymptomatically infected individual.

neurocysticercosis ??

213

Neurocysticercosis tx

Niclosamide, Praziquantel, Albendazole

214

obtain nasopharyngeal cultures to screen for carriers for ??

and tx with ??

H. influenzae, type b
N. meningitidis

meds for vacc and nonvacc:
rifampin or minocycline/doxycycline to prevent familial spread or spread in closed populations. Must use antimicrobial which will secreted in tears (i.e., present in mucosal surface).

215

Meningococcemia-induced purpura fulminans aka symmetrical peripheral gangrene (SPG) tx

*Drotecogin alfa (activated, recombinant protein C)* antibiotics, fluid resuscitation, inotropic drugs, mechanical ventilation

216

Cryptococcus treatment





for long-term (life-long) suppressive therapy??

high dose amphotericin B with 5-fluorocytosine (fluconazole [FLU]) for 2 weeks duration

Fluconazole or Itraconazole

217

Leprosy treatment



treatment of the lepromatous form??
to prevent ??

multidrug therapy for up to 2 years and is based on the form of disease (TT, LL, or borderline) manifested.

Thalidomide for treatment of the lepromatous form, to prevent ENL

218

Neurocysticercosis - Must treat both ?? and ??

asymptomatic and symptomatic patients

albendazole and/or praziquantel – antihelmenthic drugs

anticonvulsant

corticosteroids (dexamethasone) – to suppress the immune/inflammatory response


219

Toxoplasmosis treatment

2→4m combination of sulfonamides or clindamycin +pyrimethamine

220

Focal encephalitis is often caused by ??

treatable ??

HSV


IS treatable (but NOT curable) versus focal or diffuse encephalitis caused by other viral agents which are generally untreatable, except supportively

antiviral agents(s): acyclovir, vidarabine/adenosine arabinoside, idoxuridine, trifluridine, famciclovir, valacyclovir

221

Before the introduction of the measles and mumps vaccine

viral>bacterial meningitis/ meningoencephalitis
(still most common! but now not caused by measles/mumps)

measles and mumps vaccine has made the most significant reduction in the number of cases of meningitis

222

For bacterial meningitis, ??? originally accounted for majority of community-acquired cases and ??? was responsible for most of cases involving children until ???

then ??? became the nuevo numero uno until ???


and now ??? is the number one and ??? account for the majority of of community-acquired cases of bacterial meningits

children younger than 5 yrs
Hib
conjugated Hib vaccine

S. pneumoniae
pneumococcal vaccine



N. meningitidis
adults

*case rate hasn't changed much over time

223

Vaccines exist for CNS diseases caused by ??

S. pneumoniae
H. influenzae, type b
N. meningitidis
polio
rabies
botulism
tetanus
measles
mumps

224

Immunization with polysaccharide conjugate vaccines (T dependent antigen) does what ??

decrease carriage rate and disease incidence of disease

is recommended for children younger than 2 yrs

225

S. pneumoniae T dependent antigen vaccine

7/13 valent conjugated vaccine (PCV-7/13)

up to 5-y-o-age

prevents:
pneumococcal OM
meningitis
bacteremia

226

N. meningitidis T dependent antigen vaccine

Quadrivalent (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid (CRM197) conjugate vaccine

Menactra (MCV4; Sanofi-Pasteur) for all persons aged 11→ 18-y-o-age and for persons aged 2→55 years at increased risk for meningococcal disease.

Menveo (Novartis Pharmaceuticals, Inc) in people 11 to 55-y-o-age

227

H. flu T dependent antigen vaccine

(Hib) Conjugated vaccine

228

N. meningitidis group B vaccines (T dependent antigen vaccine)

4CMenB (Bexsero; composed of 3 recombinant proteins) and Trumenba (composed of 2 recombinant proteins)

229

Immunization with polysaccharide (Type II, T-independent antigen)vaccines

No decrease in carriage rate due to no class switching

decrease incidence of disease.

not recommended for children younger than 2 yrs

230

Type II, T-independent antigen vaccines

S. pneumoniae 23 valent (pnu-immune pnuemovax) (NOT prevenar: 7-valent, T-dependent)

N. meningitidis: Tetravalent/quadrivalent polysaccharide vaccine for Groups A, C, Y, W-135 ([MPSV4]; Menomune®, manufactured by Sanofi Pasteur, Inc.)

H. influenzae, type b (Hib). Pure polysaccharide vaccine

231

Immunoglobulin preps exist for ??

Rabies
Tetanus
Botulism

232

post-exposure prophylaxis to prevent rabies

rabies vaccine
IG
wound care
tetanus immunization

233

things to review ??

protocol for pre-exposure rabies vaccination followed by post-exposure prophylaxis with the rabies vaccine

polio vaccination protocol and why we administer e-IPOL and not the live attenuated vaccine, that is superior to e-IPOL

protocols for tetanus and botulism

234

If carriage of H. influenzae, type b and/or N. meningitidis is detected by nasopharyngeal cultures do what ??

eliminate the immune carrier state by chemoprophylaxis of both vaccinated and non-vaccinated individuals

Treat to prevent spread via:
familial spread

spread in closed populations:
daycare settings
college campuses

235

If carriage of H. influenzae, type b and/or N. meningitidis is detected by nasopharyngeal cultures: chemoprophylaxis ??

Ciprofloxacin, ceftriaxone, rifampin, or azithromycin

**if fluoroquinolone-resistant N. meningitidis is detected in the area do NOT administer ciprofloxacin

236

polio vaccine: IPV



Inactivated (killed) polio vaccine (IPV)

AKA Salk vaccine, AKA IPOL

Enhanced potency vaccine (e-IPV)-used in US

237

Oral polio vaccine

aka Sabin

A live attenuated virus which replicates in oropharynx and intestinal tract but cannot infect neuronal cells, less transimisable than wt virus

cheaper than e-IPV
may put others/unvaccinated ppl at risk

During viral replication in vaccinated children, the attenuated virus mutates back to the virulent/wt virus , but only causes extremely rare cases of vaccine-associated paralytic polio/poliomyelitis (VAPP) in the US (8→10 cases/year)
VAPP
cVDPV

238

current vaccine recommendation

4 doses e-IPV (IPOL) ONLY to eliminate any chance of vaccine-associated paralytic polio and in doing so, assure parents and thus obtain better vaccination compliance

in the past: e-IPV for first 2 doses (2, 6 months) and OPV for last 2 doses (6 → 12 m, 12 → 16 m)

239

Rabies management

Pre-exposure prophylaxis (vaccine) (animal-exposed pops) or postexposure treatment for rabies (vaccine + immunoglobulin)

*prevention is mainstay of controlling human rabies

240

purpose of rabies pre-exposure management and prophylaxis??

to prime immune system for an anamnestic response when booster is administered; this anamnestic response:

1. eliminates the need for passive immunization.

2. reduces number of doses of rabies vaccine needed for postexposure treatment (3 doses i.m., 3 days apart).

241

rabies pre and post-exposure ppx site

3 doses i.m. in deltoid muscle in adult or anterolateral zone of thigh in children

*NEVER done done as a gluteal injections → neuropathy, lower Ab titers

242

People provided pre-exposure vaccination, were bitten by a rapid dog and then ?? died!

failed to receive appropriate post-exposure prophylaxis

243

Must do both ?? unless pre-exposure prophylaxis is done (Rabies)

also give ??? unless pt is appropriately immunized

Vaccination + antirabies serum (Human antirabies immune globulin (HRIG))

tetanus ppx

244

Human antirabies immune globulin (HRIG)
site ??

HyperRab™ S/D
Imogam® Rabies-HT

Half of the dose i.m., in gluteal region.

Half of the dose should be injected in and around the wound site

245

rabies vaccine







when to admit post-ppx?

Human diploid cell strain rabies vaccine (HDCV)

purified chick embryo cell
vaccine (PCECV, RabAvert®)

*all are killed

on 5 days: 0, 3, 7, 14, 28→30.

246

prevention of tetanus

Primary immunization with DTaP at 2, 4, 6 and 15 months-of-ages

Boosters (dTaP) administered at:
-4→ 6-y-o-age.
-every 10 years thereafter.

247

Prevention of Neonatal tetanus is accomplished by either of...

Vaccination of pregnant women (2 doses of tetanus toxoid [TT2+]).

clean delivery and chord care procedures.

measles
mumps (vaccination?)

248

meningitis presentation

fever, lethargy, irritability, meningimus

249

encephalitis presentation

fever, altered mental status (cognitive disorders, focal changes)

250

meningoencephalitis presentation

fever, lethargy, irritability, meningimus, altered mental status

251

Mass lesions presentation

fever, headache, seizures

252

Transverse myelitis presentation

fever, motor and sensory loss at the same level

253

Poliomyelitis presentation

fever, asymmetric motor deficit and no sensory loss

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