CNS intro Flashcards
Mass Lesions/Abscesses
Abscess – S. aureus, anaerobes
neurocysticercosis (cysts) – Taenia solium
toxoplasmosis –(pseudocyts) - Toxoplasma gondii
Neurotoxic diseases
CNS – tetanus – Clostridium tetani (rare only due to vaccination)
PNS – botulism – Clostridium botulinum
(rare only due to proper food handling)
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
Prion disease
new variant Creutzfeldt-Jacob Disease: Prion of bovine spongiform encephalitis
Creutzfeldt-Jacob Disease (CJD). Human Prions
Common cause of purulent/pyogenic meningitis: bacteria
Neisseria meningitidis
Streptococcus pneumoniae
Haemophilus influenzae, type b
Streptococcus agalactiae
Escherichia coli K1
Klebsiella pneumoniae
Listeria monocytogenes
Bacterial encephalitis and/or mass lesions
Mycoplasma pneumoniae
Listeria monocytogenes
S. aureus
anaerobic [mixed] infections
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
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.
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
tetanus
not meningitis, tetanus is a neurotoxemia, like botulism
Fungi that cause meningitis
Cryptococcus neoformans & C. grubii. (Cryptococcosis)
Other causes of meningitis
- Lyme disease - B. burgdorferi.
- M. tuberculosis.
- syphilis - T. pallidum.
Encephalitis:
Viral cases have high mortality and incidence of severe neurological sequelae
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
year-round viral encephalitis
Herpes Simplex virus HSV (HSV-1 esp) sporadic, usually- focal encephalitis
non-polio enteroviruses
a. ECHO viruses,
b. Coxsackie viruses,
c. enteroviruses 6871.
other viral encephalitis agents
- Lymphocytic choriomeningitis virus (LCM).
- HIV - HIV-1-associated cognitive/motor complex (AKA AIDS Dementia Complex).
- Cytomegalovirus (CMV).
- Rabies virus (rare only due to vaccination of dogs and cats).
- Polio, measles, mumps viruses (rare only due to vaccination)
Focal Viral encephalitis:
- HSV-1(usually, not always) sporadic, focal encephalitis all year round.
- Rabies virus – Rabies (rare only due to vaccination of dogs and cats)
- Polio viruses (rare only due to vaccination of humans)
arboviruses and non-polio enteroviruses
Encephalomyelitis: WNV, Polio
CMV
VZV
JC virus and PML
bacterial agents of encephalitis
a. Mycoplasma pneumoniae.
b. Listeria monocytogenes
fungal agent of encephalitis
Cryptococcus neoformans var. grubii
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)
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.
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.
Peripheral neuropathies/Bell’s palsies, acute facial paralysis
HSV-1, VZV, B. burgdorferi
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.
6? classes of CNS-PNS infections
Meningitis - CNS Encephalitis - CNS Mass Lesions/Abscesses – CNS Neurotoxic diseases Peripheral Nervous System (PNS) diseases Prion disease
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.
meningitis is..
Meningeal inflammation resulting from an infection within the subarachnoid space
encephalitis is…
Inflammation of the brain parenchyma
focal encephalitis agents
primarily HSV-1 – HSV-1 disease is treatable by antiviral therapy
diffuse encephalitis
primarily arbovirus- supportive tx only
Encephalomyelitis
encephalitis with myelitis (spinal chord inflammation) – caused by poliovirus and West Nile virus – supportive therapy only
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
Fungi: three common agents
Cryptococcus – a meningoencehalitis
Candida. - meningitis
Coccidioides immitis – a meningoencehalitis
parasites usually cause a..
meningoencephalitis
most common CNS parasites
- Toxoplasma gondii (protozoan - Toxoplasmosis).
- Taenia solium, agent of neurocysticercosis (NCC; helminth).
- Echinococcus granulosus or multilocularis (Cystic Echinococcosis-hydatid cyst)
- Baylisascaris procyonis (Raccoon Round Worm Encephalitis/Baylisascariasis)
- Toxocaria cannis or cati (Toxocaria)
- Naegleria fowleri predominate agent
other CNS parasites
Acanthamoeba spp.
Balamuthia mandrillaris.
Vahlkampfia spp.
Hartmanella spp.
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)
CMI required (facultative or obligate intracellular agents)
Listeria monocytogenes. Toxoplasma gondii. Cryptococcus cytomegalovirus CMV Mtb JC virus and PML HIV LCMV. E. coli K1??
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.
predisposing factor: chronic or debilitating disease
Advanced HIV/AIDS.
Sickle cell disease.
Lymphoma/cancer.
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.
newborns should be..
routinely tapped because so few S/S in this age group
nosocomial meningitis from..
Intraventricular catheters (IVC) and cochlear implant
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
Carriage is in nares for this bac
Staphylococcus aureus
Carriage in humans is primarily on mucosal surfaces for these bac
endogenous anaerobic flora
Carriage in humans is primarily in the colon for these bac
Streptococcus agalactiae,
E. coli
K. pneumoniae
Listeria monocytogenes
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
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
other bacteria
C. tetani, (soil reservoirs),
C. botulinum. (soil, water, animal reservoirs)
L. monocytogenes (ubiquitous).
viral agents: zoonosis
Arboviruses – animals (mammals and/or birds) and arthropods (mosquito or tick).
Rabies virus– mammals.
LCMV – mammals, especially rodents
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
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.
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)
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).
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)
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
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)
Inhalation of infectious dust:
Cryptococcus neoformans.
LCMV
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
anaerobes
endogenous flora
arboviruses
exposure to mosquito; Ticks for two agents
Cryptococcus neoformans
bird droppings
HSV-1
disease is reactivation of latent infection
HSV-2
sexual contact
HIV
blood or bodily fluids
LCMV
exposure to rodents, droppings, secretions, fluids
Listeria monocytogenes
animal exposure, food
Measles virus – SSPE
human, exposure before 1-y-of-age
Mumps
human exposure to agent
Mycobacterium leprae
human or animal exposure
Mycobacterium tuberculosis
human exposure
Neisseria meningitis
human exposure, terminal complement deficiency
nonpolio enteroviruses
human feces
Naegleria fowleri
exposure to fresh water with algae
polio enteroviruses
human feces
rabies virus
animal exposure, bat (USA) Dog (WW)
Staphylococcus aureus
Another person
Streptococcus agalactiae
low birth weight infant, rupture of membranes >24h before delivery, colonized vaginal canal
Streptococcus pneumoniae
congenital CSF leak
Taenia solium ova
human feces
Taenia solium cysticerci
undercooked or uncooked meat- pork
Toxoplasma gondii ova
cat feces
Toxoplasma gondii pseudocyst
raw or uncooked meat
??? 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
most common viral agents (children–>adults) in order
ECHO and Coxsackie viruses
then the arbovirues
HSV-2
Diffuse encephalitis>focal encephalitis
arboviruses: Most common agents of diffuse encephalitis
HSV-1: Most common agent (50%) of focal encephalitis
Most common agents of meningitis (viral)
Non-polio enteroviruses (ECHO viruses and Coxsackie viruses).
HHV-6, HHV-7
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)
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
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
bacteria: year round seasonality
S. agalactiae.
E. coli K1
K. pneumoniae
bacteria: summer seasonality
protozoan: ?
L. monocytogenes
Neglaria fowleri
bacteria: late winter-early spring seasonality
H. influenzae type b
N. meningitidis
S. pneumoniae
viral: year-round seasonality
HHV-1 HHV-2 HHV-6; -7 CMV HIV Rabies
viral: Late summer and early fall seasonality
ECHO viruses and Coxsackie viruses
Polio virus
Arboviruses
viral: winter seasonality
LCMV
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
TORCH test -
a test to detect a congential (AKA intrauterine infection) infection in a neonate via presence of specific IgM in chord blood
the leading cause (by far) of infection and morbidity in the neonate
CMV infection
neonates: Highest incidence of infection and morbidity among procaryotes
S. agalactiae
neonates: highest incidence of infection andmorbidity of all agents.
cytomegalovirus (CMV)
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)
Infants and young children – all agents
HH-6, HH-7 non-polio enterovirus (Coxsackie; Echoviruses). N. meningitides S. pneumoniae Mycobacterium tuberculosis. Arboviruses LCMV. Mumps.
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).
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.
Bacterial Agent by Age:
nenonate
S. agalactiae (most common)
E. coli K1
L. monocytogenes
K. pneumoniae K1, K2 (least)
Bacterial Agent by Age:
Infant to adult
N. meningitides (most common)
S. pneumoniae
Bacterial Agent by Age: elderly
N. meningitides,
S. pneumoniae
L. monocytogenes
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.
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
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.
Intra-axonal transport (retrograde flow) inside nerves:
rabies.
herpes.
polioviruses.
tetanus toxin.
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
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
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.
S/S indicative of progression of severe symptoms indicate progression to meningoencephalitis:
decline in consciousness. focal cerebral abnormalities (hemiparesis, monoparesis, aphasia) Seizures. convulsions. coma.
Maculopapular rash
non-polio enteroviruses (ECHOvirus, Coxsackievirus, enteroviruses), arboviruses HSV. S. pneumoniae. N. meningitidis. H. influenzae, type b
vesicular rash
HSV
fungi
non-polio enteroviruses.
Petechial / Purpuric:
S. pneumoniae.
N. meningitidis.
H. influenzae, type b.
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
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.
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
Encephalopathy is
is depressed or altered level of consciousness lasting >24 hours
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.
Arbovirus diffuse encephalitis
fever (>38oC), seizures, altered mental status, severe headache.
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
Rabies focal encephalitis
dumb or furious forms
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
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.
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.
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.
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)
Focal sites of viral encephalitis:
Herpes virus
Polio
?? 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
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
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
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)
CT scan showing ??
In severe cases ??
ring-enhancing (mass) lesion supports the diagnosis.
a mid-line shift, risk of brain stem herniation
an encapsulated structure grows in size (becomes visible to the naked eye) creating a
mass effect – displaces brain tissue and creates intracranial pressure
Etiology – Abscess:
Localized collection of purulent infectious agent material and host cell debris in a cavity formed by the disintegration of tissue
3 distinct abscess locations:
epidural (between vertebrae and dura)
subdural (between dura and arachnoid).
parenchyma (in the brain tissue)
Etiology of abscesses:
Procaryotic: S. aureus, anaerobic infections, L. monocytogenes.
Fungi agents: Candida albicans
Cystic lesions - humans as Intermediate hosts of parasites
A helminth (flat worm) produces a tissue cyst as part of its life cycle
2 distinct cystic lesion locations:
in the ventricles, subarachnoid space or meninges
parenchyma (in the brain tissue).
cystic lesion agents
Taenia solium (Neurocysticercosis)
Echinococcus granulosus or multilocularis (Cystic Echinococcosis-hydatid cyst).
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
Pseudocyst lesions caused by
Toxoplasma gondii (Toxoplasmosis) - protozoan
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
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
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
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
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
Polio virus does what ??
kills neurons
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.
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
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
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
Lumbar puncture results are
clinical clues; not definitive diagnosis
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
Gram-positive agents
Listeria monocytogenes
S. pneumoniae
S. agalactiae
Gram-negative agents
H. influenzae, type b
N. meningitidis
E. coli K1
K. pneumoniae
Sensitivity by organism
S pneumoniae, 90%; H influenzae, 86%; N meningitidis, 75%; Gram-negative bacilli, 50%; L monocytogenes, less than 50%.
other stains
acid-fast stain (Mycobacterium).
India ink preparation (Cryptococcus).
Saline wet mount (Naegleria fowleri).
Culture and sensitivity of sedimented CSF (~50% sensitive)
Order MIC and MBC
CSF cultures are positive in 70% to 85% of cases
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?
14-3-3 chaperone brain protein elevated (normal:
cerebrovascular events/acccidents (CVAs),
viral encephalitis,
Creutzfeldt-Jakob disease (prions)
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*
Normal CSF is
a clear, colorless fluid
contains β2-transferrin
Not straw-colored like serous fluid
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.
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
antigen testing/latex agglutination test can detect
S. pneumoniae,
H. influenzae, type b
N. meningitidis
cryptococcal antigen
other tests
EIA test of a CSF specimen
*VDRL for syphilis
Procalcitonin: detection for bacterial meningitis
PCR – for specific agents:
enteroviruses (RT-PCR)
herpes simplex virus
JC virus
HIV (RT-PCR)
Skin specimen: vesicular
Tzanck or Papanicolaou stained skin biopsy specimen for HSV
Skin specimen: purpuric
Gram-stained smear of skin biopsy specimen:
S. pneumonia
N. meningitidis.
Culture and sensitivity (MIC, MBC)
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
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.
??? diagnostic tests are NOT feasible for CNS infectious diseases, so ???
sequential
order all appropriate tests right away – in parallel, NOT sequentially
EEG pattern indicative of
focal or diffuse problem
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.
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
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
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.
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
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
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.
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
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
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
?? preferred over ?? in neonates
because ??
Cefotaxime over ceftriaxone
ceftriaxone may alter bilirubin metabolism in this population
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
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
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
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
Do not administer dexamethasone to a person who has ?? or who is ??
already received antimicrobial therapy
manifesting with septic shock
Dexamethasone use in children
not associated with and any change in survival or time of hospital discharge
Clostridium tetenaii tx
metrodianazole
Haemophilus influenzae, type b tx
ceftriaxone, cefotaxime, cefuroxime or the alternative option is TMP-SMX.
Listeria monocytogenes tx
ampicillin plus gentamycin or TMP-SMX
Mycobacterium leprae tx
dapsone plus rifampin or clofazimine
Neisseria meningitidis tx
ceftriaxone or cefotaxime
Streptococcus pneumoniae tx
vancomycin + extended spectrum cephalosporin
Streptococcus agalactiae tx
penicillin G
some abx resistance
Toxoplasma gondii tx
sulfonamides or clindamycin + pyrimethamine
Cryptococcus neoformans tx
amphotericin B with 5-fluorocytosine
Herpes simplex virus tx
acyclovir
non polio Enteroviruses tx
pleconaril
Naegleria fowleri tx
Miltefosine
tx for GBS
all identified carriers and women who deliver pre-term before screening can be done should be offered intrapartum antimicrobial prophylaxis iv
Treatment of ?? as well as the protocol for treatment of an asymptomatically infected individual.
neurocysticercosis ??
Neurocysticercosis tx
Niclosamide, Praziquantel, Albendazole
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).
Meningococcemia-induced purpura fulminans aka symmetrical peripheral gangrene (SPG) tx
Drotecogin alfa (activated, recombinant protein C) antibiotics, fluid resuscitation, inotropic drugs, mechanical ventilation
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
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
Neurocysticercosis - Must treat both ?? and ??
asymptomatic and symptomatic patients
albendazole and/or praziquantel – antihelmenthic drugs
anticonvulsant
corticosteroids (dexamethasone) – to suppress the immune/inflammatory response
Toxoplasmosis treatment
2→4m combination of sulfonamides or clindamycin +pyrimethamine
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
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
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
Vaccines exist for CNS diseases caused by ??
S. pneumoniae H. influenzae, type b N. meningitidis polio rabies botulism tetanus measles mumps
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
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
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
H. flu T dependent antigen vaccine
(Hib) Conjugated vaccine
N. meningitidis group B vaccines (T dependent antigen vaccine)
4CMenB (Bexsero; composed of 3 recombinant proteins) and Trumenba (composed of 2 recombinant proteins)
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
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
Immunoglobulin preps exist for ??
Rabies
Tetanus
Botulism
post-exposure prophylaxis to prevent rabies
rabies vaccine
IG
wound care
tetanus immunization
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
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
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
polio vaccine: IPV
Inactivated (killed) polio vaccine (IPV)
AKA Salk vaccine, AKA IPOL
Enhanced potency vaccine (e-IPV)-used in US
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
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)
Rabies management
Pre-exposure prophylaxis (vaccine) (animal-exposed pops) or postexposure treatment for rabies (vaccine + immunoglobulin)
*prevention is mainstay of controlling human rabies
purpose of rabies pre-exposure management and prophylaxis??
to prime immune system for an anamnestic response when booster is administered; this anamnestic response:
- eliminates the need for passive immunization.
- reduces number of doses of rabies vaccine needed for postexposure treatment (3 doses i.m., 3 days apart).
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
People provided pre-exposure vaccination, were bitten by a rapid dog and then ?? died!
failed to receive appropriate post-exposure prophylaxis
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
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
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.
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.
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?)
meningitis presentation
fever, lethargy, irritability, meningimus
encephalitis presentation
fever, altered mental status (cognitive disorders, focal changes)
meningoencephalitis presentation
fever, lethargy, irritability, meningimus, altered mental status
Mass lesions presentation
fever, headache, seizures
Transverse myelitis presentation
fever, motor and sensory loss at the same level
Poliomyelitis presentation
fever, asymmetric motor deficit and no sensory loss
