CNS Infections Flashcards
1
Q
What are the four principle routes of CNS infection?
A
- hematogenous (most common, primarily arterial)
- direct implantation (trauma, congenital malformations)
- local extension (sinuses, teeth, osteomyelitis)
- PNS (rabies, herpes zoster)
2
Q
How does CSF contribute to brain infections?
A
- a complete exchange of CSF every 3-4 hours means that soon after infection, the brain is bathed in bacteria
note: 85% of the CSF is produced by the choroid plexus of the 3rd and 4th ventricles
3
Q
How does TB meningitis occur?
A
-subepidural or submeningeal granulomas seed CSF
4
Q
True or False: the CSF has lymphatics
A
False; but the epidural space has lymphatics.
Infections of the retropharyngeal space, posterior mediastinal space, or retroperitoneal space may produce spinal epidural abscesses.
5
Q
How do HSV and herpes zoster infect the CNS?
A
- they product latent infections of sensory ganglia
- replicate in Schwann cells
- ascend to the CNS within SENSORY nerves
6
Q
How does rabies infect the CNS?
A
-virus bind at/near Ach receptors at the neuromuscular junction and ascend to the CNS via MOTOR nerves
7
Q
What is the main way that molecules move across the capillary wall into the brain?
A
- active transport
- lipid solubility
8
Q
True or False: capillaries in the brain are permeable to immunoglobulins, complement and abx
A
False; capillaries are relatively IMpermeable
9
Q
True or False: when referring to bacterial meningitis and many viral encephalidites, widespread infection involving all tissue elements is characteristic
A
True
10
Q
What is the major determinant of the characteristic neurological symptoms associated with different infectious agents?
A
–which cell types and/or anatomic area is involved
–different cell populations and different neuro-anatomical regions have different functional specializations
11
Q
What are the categories of meningitis and their cause?
A
Chemical Meningitis: nonbacterial irritant in subarachnoid space
Acute Pyogenic Meningitis: bacterial
Aspetic Meningitis: acute or subacute viral (you’ll see lymphocytes in the CSF)
Chronic: TB, spirochetes (neurosyphilis and neuroborreliosis), cryptococcus
12
Q
What is meningoencephalitis?
A
inflammation of the meninges and brain parenchyma
13
Q
What does pyogenic meningitis look like on gross exam, which organisms are commonly associated with it, and what might you see on PE?
A
- suppurative exudate covering brainstem and cerebellum
- TB and syphilis
-papilledema d/t thickened leptomeninges not letting CSF circulate properly
14
Q
What is the cause of cerebral edema?
A
–infection/inflammation cause loss of capillary integrity and the blood-brain barrier
–transudation of intravascular fluid into brain and spinal cord
15
Q
What accelerates cerebral edema and what is a possible treatment for cerebral edema?
A
–accelerated by products released by living bacteria and by abx-lysed bacteria
Tx: corticosteroids slow and reverse process
16
Q
What are the symptoms of acute meningitis?
A
- HA, +Kernig, +Brudzinski, high fever, confusion, coma
- can develop over several days or just a few hours
17
Q
What is the most common location for exudate in Pneumococcal meningitis and a possible complication of the infection?
A
over convexities near sagittal sinus
possible complication: chronic adhesive arachnoiditis d/t capsular polysaccharides (“sticky”)
18
Q
What is the most common location for exudate in H. flu meningitis?
A
basal location
19
Q
What do you see on histology of acute suppurative meningitis?
A
PMN’s filling the subarachnoid space
20
Q
What is focal cerebritis?
A
-when inflammatory cells infiltrate walls of the veins and extend into the brain substance
21
Q
What is ventriculitis?
A
-fulminant infection w/ inflammation extending into the ventricles
22
Q
What are possible complications of phlebitis in a neuro setting?
A
-can lead to venous thrombosis and hemorrhagic infarction of the underlying brain
23
Q
What is a complication of leptomeningeal fibrosis?
A
hydrocephalus
24
Q
What are possible complications of bacterial meningitis?
A
- seizures
- encephalitis
- hearing loss
- blindness
- paralysis
- fulminant rash
- adrenal hemorrhage (Waterhouse-Friderichsen)
- death
25
What are the symptoms of Waterhouse-Friderichsen Syndrome?
- rapidly progressive hypotension leading to shock
- DIC associated w/ widespread purpura of the skin
- rapidly developing adrenocortical insufficiency
-more common in children
26
What tests should be performed when meningitis is suspected?
- lumbar puncture w/ Gram stain of CSF
- culture of CSF and blood
- Ag detection in CSF and urine
- PCR on CSF
27
What is the Gram stain of N. meningitidis?
Gram negative diplococci
28
What is the Gram stain of Strep pneumo?
Gram positive diplococci
29
What is the Gram stain of H. flu?
Gram negative pleomorphic (rods)
30
What is the Gram stain of Staph aureus and Staph epidermidis?
Gram positive cocci
31
What is the Gram stain of E. coli?
Gram negative bacilli
32
Where is the needle inserted in a lumbar puncture?
b/w the 3rd and 4th lumbar vertebrae
33
What are the characteristics of CSF in bacterial meningitis?
- cloudy/turbid
- neutrophils
- markedly decreased glucose
- moderately increased protein
34
What are the characteristics of CSF fluid in viral meningitis?
- clear/colorless
- lymphocytes/monocytes (early stage is PMN's)
- normal glucose
- slightly elevated protein
35
What are risk factors for developing meningitis?
- age <5yrs or >60yrs
- DM
- immunosuppression
- contiguous infection (ex: sinusitis)
- IV drug use
- bacterial endocarditis
- sickle cell
36
What are the most common pathogens for meningitis in neonates?
- Group B Strep
| - E. coli
37
What is the most common pathogen for unvaccinated young children?
H. flu
38
What is the most common pathogen for meningitis among adolescents and young adults?
Neisseria
39
What are the most common pathogens for meningitis in the elderly?
- Strep pneumo
| - Listeria
40
What are the most common pathogens for meningitis in immunocompromised patients?
- Strep pneumo
- Neisseria
- Listeria
- Pseudomonas
41
What are common pathogens for meningitis in a basilar skull fracture?
- -Strep pneumo
- -H. flu
- -Group A beta-hemolytic Strep
42
What are common pathogens for meningitis post-surgery or w/ head trauma?
- -Staph aureus and Staph epidermidis
| - -aerobic Gram-negative bacilli (ex: Pseudomonas)
43
What are common pathogens for meningitis in pt's w/ a CSF shunt?
- -Staph epidermidis and Staph aureus
- -aerobic Gram-negative bacilli ex: Pseudomonas)
- -Proprionibacterium acnes
44
What conditions would put pt's at risk of a brain abscess?
- acute bacterial endocarditis (multiple abscesses)
- chronic pulmonary sepsis (bronchiectasis)
- systemic dz w/ immunosuppression
- congenital heart dz
- -ex: R to L shunt removes pulmonary filtration
45
What pathogens are the most common causes of brain abscesses in non-immunocompromised pt's?
- Strep
| - Staph
46
How does a patient present with a brain abscess?
- progressive focal neurological deficits
- symptoms of increased intracranial pressure
- -HA, vomiting, AMS, papilledema
47
What is the composition of the CSF when a pt has a brain abscess?
- high WBC
- high protein
- normal glucose
48
What are possible complications of a brain abscess?
- abscess rupture w/ ventriculitis or meningitis
| - venous sinus thrombosis
49
What is the Tx for a brain abscess?
- surgical drainage
- abx
-<10% mortality w/ proper Tx
50
What is a subdural empyema?
-bacterial or fungal infection of skull bones or sinuses that spreads to the subdural space (arachnoid and subarachnoid usually not affected)
51
What is a complication of a subdural empyema?
thrombophlebitis of bridging vessels and infarction
52
What are the symptoms and CSF finding of a subdural empyema?
- progressive focal neurological deficits
- symptoms of increased intracranial pressure
- -HA, vomiting, AMS, papilledema
CSF: high WBC, high protein, normal glucose
53
What is the Tx for a subdural empyema?
- surgical drainage
- thick dura is the only residual evidence
untreated: lethargy, coma
54
What is the common cause of an extradural abscess?
osteomyelitis
-an extradural abscess of the spine may cause spinal cord compression (neurosurgical emergency)
55
How is Neisseria meningitidis spread?
- colonizes the oropharynx and rhinopharynx of asymptomatic carriers (colonization may be 2-3%, but may be higher in crowded populations like dorms)
- direct contact w/ contaminated resp. secretions
56
What is the clinical presentation of a pt. w/ meningitis d/t N. meningitidis?
- rapidly progressive septicemia
- fever
- hypotension
- DIC
- petechial and purpuric lesions
57
How might the purpuric lesions of N. meningitidis progress?
- purpura fulminans
| - -hemorrhagic skin lesions which progress to gangrene, occurring in the distal portions of limbs
58
What is the most serious condition associated with N. meningitidis?
Waterhouse-Friderichsen Syndrome
- -hemorrhagic infarction of the adrenal glands
- -rapidly progressive hypotension and shock
- -DIC w/ widespread purpura of the skin
59
What are the symptoms of chronic meningitis?
- fever
- HA
- lethargy
- confusion
- N/V
- stiff neck
60
What is the composition of the CSF in cases of chronic meningitis?
- elevated protein
- low glucose
- predominantly lymphocyte infiltrates
61
When can a Dx of chronic meningitis be made?
-symptoms and CSF abnormalities persist/progress for at least 4wks
62
What are common pathogens of chronic meningitis?
- TB
- T. pallidum
- Borrelia burgdorferi
63
Where does chronic meningitis d/t Mycobacterium tuberculosis typically affect?
- subarachnoid space (gelatinous or fibrous exudate)
- predilection for the base of the brain (arachnoiditis)
- obliterates the cisterns (hydrocephalus)
- encases CN's (CN symptoms)
64
What is obliterative (Heubner) endarteritis?
- inflammation that infiltrates vessel walls
- intimal thickening
- arterial occlusion and infarction
65
What is a tuberculoma?
- -well-circumscribed intraparenchymal mass
- -central caseous necrosis
- -inactive lesions may calcify
66
What kind of stain detects Mycobacterium tuberculosis?
acid-fast
67
In chronic meningitis caused by Borrelia burgdorferi, how long after the rash do the neurological symptoms appear?
4wks
68
What are the prominent characteristic symptoms of chronic meningitis d/t Borrelia burgdorferi?
- CN palsies
| - peripheral neuropathies
69
What is seen in the CSF of pt's w/ chronic meningitis d/t Borrelia burgdorferi?
- Ab's that can Xreact w/ mono, RA, SLE, and syphilis
| - use PCR to detect
70
What percentage of untreated pt's w/ syphilis (caused by Treponema pallidum) develop neurosyphilis?
10%
71
What is meningovascular neurosyphilis?
- chronic meningitis involving base of the brain
- -variable convexities and spinal leptomeninges
- causes communicating hydrocephalus
- causes obliterative endarteritis
- -noted by perivascular plasma cells and lymphocytes
72
What is paretic neurosyphilis?
- insidious, progressive mental deficits
- mood alterations
- delusions of grandeur
- severe dementia (general paresis of the insane)
73
What is seen on histology of paretic neurosyphilis?
- perivascular iron deposits
- granular ependymitis
- -proliferation of subependymal glia under damaged ependymal lining (causes hydrocephalus)
74
What is tabes dorsalis and its symptoms?
- dorsal root ganglion damage (sensory nn.)
- orthopedic (joint) damage and pain (Charcot Joints)
- reflexes diminished
- sharp pain ("lightning pain")
- ataxia
- loss of pain sensation
- impaired joint proprioception
- d/t syphyilis
75
What is the characteristic patient presentation of someone with aseptic meningitis?
- meningeal irritation
- fever
- alterations of consciousness
- acute onset
- absence of organisms in the CSF
76
What causes the majority of cases of aseptic meningitis?
80% are caused by enteroviruses
77
True or False: the clinical course of aseptic (viral) meningitis is more fulminant that pyogenic meningitis
False
78
What is seen in the CSF of aseptic meningitis?
- lymphocytic pleocytosis
- moderate increase in protein
- normal glucose
79
What is the Tx for aseptic (viral) meningitis?
-treat the symptoms; it's usually self-limiting
80
True or False: viruses can infect the CNS via both hematogenous spread and through the nerves
True
-nn. examples are olfactory and trigeminal sensory nerves or motor nerves
81
What type of cells comprise the inflammatory response?
lymphocytes
82
What are some examples of arthropod-borne viruses that can cause encephalitis in the Western Hemisphere?
- Eastern and Western Equine
- West Nile (involves spinal cord; polio-ish paralysis)
- Venezuelan
- St. Louis
- La Crosse
83
True or False: in arthropod-borne viral encephalitis, there are multiple foci of necrosis in both grey and white matter
True
84
What age groups are affected by HSV-1 to cause encephalitis?
children
| young adults
85
What types of damage does HSV-1 cause?
necrotizing
| hemorrhagic
86
What lobes of the brain are most commonly affected by HSV-1?
- inferior/medial temporal lobes
| - orbital gyri of the frontal lobes
87
What is seen on histology of HSV-1?
- Cowdry Type A
| - -intranuclear viral inclusions in neurons and glia
88
What age groups are affected by HSV-2 to cause encephalitis?
Neonates
| -50% delivered vaginally to women w/ active primary HSV genital infection develop severe encephalitis
89
Where does herpes zoster most commonly lie latent?
-trigeminal nerve
or
-sensory neurons of dorsal root
90
What is shingles?
-reactivation of herpes zoster that results in painful vesicular skin eruptions limited to a single dermatome
91
What is persistent post-herpetic neuralgia syndrome?
persistent pain as well as painful sensation following non-painful stimuli
92
What types of individuals are most commonly affected by CMV?
- fetuses
| - immunosuppressed (opportunistic infection w/ AIDS)
93
What damage does CMV cause in utero?
- periventricular necrosis
- microcephaly
- periventricular calcification
94
Where does CMV localize in the brain of non-neonates?
-paraventricular subependymal regions
95
What damage does CMV cause in non-neonates?
- severe hemorrhagic necrotizing ventriculoencephalitis
- choroid plexitis
- radiculoneuritis in lower spinal cord and roots
96
What is seen on histology in CMV?
-prominent enlarged cells w/ intranuclear and intracytoplasmic inclusions
97
What does poliomyelitis do to the brain and what major symptom does it produce?
- mononuclear cell perivascular cuffs
- neuronophagia of the anterior horn motor neurons
- -flaccid paralysis
-may extend to posterior horns and occasionally produce cavitation
98
What is post-polio syndrome?
- develops 30yrs after resolution of initial illness
| - progressive weakness w/ decrease muscle mass, pain
99
What is the incubation period of rabies (lyssa virus genus in the rhabdoviridae family)?
-1 to 3 months, depending on distance of the wound from the brain
100
How does rabies get from a wound to the brain?
-infection ascends along peripheral nerves
101
What are the symptoms of rabies?
- -non-specific (malaise, HA, fever)
- extraordinary CNS excitability, violent motor response
- convulsions
- flaccid paralysis and resp. ctr failure
- hydrophobia ("foaming at the mouth") d/t ctx of pharyngeal muscles that produce an aversion to swallowing even water
- local paresthesias (pins and needles) around wound
- -diagnostic
102
What types of intracellular inclusions are seen in rabies?
Negri bodies (cytoplasmic inclusions)
103
What proportion of HIV+ pts experience aseptic meningitis and when does it occur?
-occurs in about 10% of patients within 1 to 2 wks of seroconversion
104
What can be seen on histology of aseptic meningitis d/t HIV?
Vessels: prominent endothelial cells and perivascular foamy or pigment-laden macrophages
White Matter: multifocal or diffuse areas of MYELIN PALLOR, AXONAL SWELLING, and GLIOSIS
Acute - mild lymphocytes, PERIVASCULAR INFLAMMATION, myelin loss
Chronic - MICROGLIAL NODULES w/ MULTINUCLEATED GIANT CELLS
105
What is Immune Reconstitution Inflammatory Syndrome (IRIS)?
- paradoxical deterioration after starting antivirals
- exuberant inflammatory response
-paradoxical exacerbation of symptoms from opportunistic infection
106
What is HIV-associated dementia?
- inflammatory activation of microglial cells
| - no specific pathologic lesion
107
What cancer has increased incidence among pts who are HIV+?
primary CNS lymphoma
108
What virus causes Progressive Multifocal Leukoencephalopathy (PML)?
-JC Polyomavirus
- the primary infection is asymptomatic
- latency
- reactivation during immunosuppression
109
What types of cells does JC polyomavirus attack and what is the resulting pathology?
- -oligodendrocytes
- -demyelination is the primary pathological effect
- -irregular, ill-defined white matter destruction
- -subcortical demyelination w/ lipid-laden macrophages
110
What are the symptoms of Progressive Multifocal Leukoencephalopathy (PML)?
- loss of coordination
| - weakness
111
What is Subacute Sclerosing Panencephalitis (SSPE)?
--caused by a paramyxovirus in non-immunized children or young adults
--can occur months to years following early-age acute infection w/ measles (rubeola)
112
What are the symptoms of Subacute Sclerosing Panencephalitis (SSPE)?
- cognitive decline
- spasticity of limbs
- seizures
113
What is seen on histology of Subacute Sclerosing Panencephalitis (SSPE)?
- widespread gliosis
- myelin degeneration
- viral inclusions in nuclei of neurons and oligos
- variable inflammation of white and grey matter
- neurofibrillary tangles
114
What type of patients are normally affected by fungal meningoencephalitis?
immunocompromised
115
How is fungal meningitis spread?
hematogenously
116
What are typical pathogens responsible for fungal meningoencephalitis?
- candida albicans
- mucor
- aspergillis fumigatus
- cryptococcus neoformans
117
What fungal infection w/ neural involvement is commonly associated with diabetes patients?
mucormycosis
118
What two fungal pathogens are most often responsible for vasculitis?
- mucormycosis
- aspergillosis
- candida (occasionally)
119
What is a complication of fungal vasculitis?
-thrombosis that causes a hemorrhagic infarction and becomes septic
120
What are some examples of fungal endemic pathogens?
- Histoplasma capsulatum (Mississippi River Valley)
- Coccidioides immitis (SW US)
- Blastomyces dermatitidis (Ohio River Valley)
121
What fungal pathogens are most associated with parenchymal infections?
- candida
| - cryptococcus
122
What fungal pathogen is most associated with meningitis?
Cryptococcus neoformans
123
What patient population is most commonly affected by Cryptococcus meningitis and what is the prognosis of the disease?
- AIDS pts
- having an immune dysfunction predisposes
- fulminant and fatal within 2wks (up to yrs, though)
124
What is important in regards to the CSF in pts with Cryptococcus meningitis?
- India Ink preparation
- Cryptococcal polysaccharide antigen
- culture the CSF
--Also culture urine, sputum, blood, and stool
125
What are the neural implications of Toxoplasmosis gondii?
- parasitic protozoa
- opportunistic infection for HIV and immunosuppressed
- also causes problems during pregnancy
-brain abscess near grey/white junction of cerebral cortex and DEEP GREY NUCLEI
126
What do you see on histology of Toxoplasmosis?
- CENTRAL FOCI OF NECROSIS (ring-enhancing lesion)
- petechial hemorrhages surrounded by inflammation
- macrophage infiltration
- VASCULAR PROLIFERATION
-FREE TACHYZOITES and ENCYSTED BRADYZOITES at periphery of necrotic zones
127
What is cerebral amebiasis?
- caused by naegleria fowleri
- found in warm freshwater and soil
-infects people when contaminated water enters the brain through the nose
128
What is acanthamoeba?
- an amoeba that causes chronic granulomatous meningoencephalitis
- also can infect the eye and skin
129
How does Plasmodium falciparum affect the CNS?
- -cerebral malaria
| - -results in long-term cognitive defects in survivors
130
What is Creutzfeldt-Jakob Disease (CJD)?
- prion disease
- abnormal proteins (Prion Protein - PRP)
- rapidly progressive neurodegenerative disorder
- SPONGIFORM change w/ intracellular vacuoles
131
True or False: prion disease can be sporadic, familial, or transmitted
True
132
When do most cases of Creutzfeld-Jakob Disease appear?
-90% is the sporadic form that appears in the 60's
133
In addition to sporadic CJD, what is another mode of transmission?
- iatrogenic
- -corneal transplant
- -brain implantation of electrodes
- -contaminated preps of human growth hormone
134
What are the symptoms of Creutzfeld-Jakob Disease?
- rapidly progressive dementia
- startle myoclonus
- survive approx. 7 months after symptoms appear
135
True or False: there is abundant gross evidence of brain atrophy in CJD pts.
False; the progression is so rapid that there is little (if any) grossly evident brain atrophy.
136
What is the variant Creutzfeld-Jakob Disease?
- in young adults in the UK in 1995
- behavior changes early in the disease
- slower progression
- exposure to bovine spongiform encephalopathy
- Kuru Plaque in the cerebellum
137
What is seen on histology of Variant Creutzfeld-Jakob Disease?
Kuru Plaque
- extracellular deposits of aggregated abnormal protein
- Congo Red positive
- PAS+
- located in the cerebral cortex of vCJD
138
What is Fatal Familial Insomnia (FFI)?
- sleep disturbances initially
- aspartate substituted for asparagine at codon 129
- ataxia
- autonomic disturbances
- stupor (eventually coma)
- death within 3yrs
