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Brain

Spinal c r MeningesCNS

NervesPNS

Nervous System

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Terms related to Nervous Systemy CSF Cerebrospi al Fluid fou d i the surarach oid

spaces

y BBB (Blood Brai Barrier) supplyi utrie ts but otallowi lar er particles such as macromolecules

(CHON, a tibodies), cells of the immu e system, a dmicroor a isms to pass from the blood i to the brai .

y NO INDIGENOUSFLORA IN THE NERVOUSSYSTEM

y Microbial access: CNS throu h fracture/sur ery, blood

a d lymph to the CSF, alo peripheral erves.

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Infections ofthe CNS:yENCEPHALITIS: I flammatio of the BRAIN

yENCEPHALOMYELITIS: I flammatio of thebrai a d spi al cord

yMENINGITIS: I flammatio of the membra esof brai a d spi al cord

yMENINGOENCEPHALITIS: I flammatio ofthe brai a d me i es

yMYELITIS: I flammatio of the spi al cord.

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MeningitisyCaused by bacterial, fu al, viral,

pr0tozoa or a ism

yMajority of cases are bacterial:

Streptococcus pneumoniae (elderly)

Haemophilus influenzae (children)Neisseria meningitidis (adolescents)

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MeningitisyViral me i itis aseptic me i itis; 50%

of viral cases are u ide tified

yViruses i clude: e terovirus major viralcause

yOthers: coxsackievirus, echoviruses, mumps

virus, arbovirus, (arthropod), poliovirus,ade ovirus, measles virus, HSV, varicella

virus

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Haemophilus influenzae

y Gram negative, has LPS

y Common cause of ear, eye, throat infections

Manifestations:

y Fever

y Vomiting

y Nausea

y Tiredness

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Neisseria meningitidis

y Gram negative diplococcus

y Causes meningicoccal meningitis, epidemicmeningitis

y spread by direct contact, usually begins as a

throat infection

y can have asymptomatic carriers

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PathogenesisTransmission:

y spread throu h the excha e of saliva a d otherrespiratory secretio s.

Symptoms:

y Septicemia

y ausea, vomiti , weak ess, low blood pressure

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MeningitisMe i ococcal me i itis:N. meningitidis

causes i flammatio of the tissue

surrou di the brai a d spi al cord (theme i es)

y hi h fever

y

headachey stiff eck

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MeningococcemiaN. meningitidis

Me i ococcemia(blood):

y fever a d rash

y

purpura

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Streptococcus pneumoniae

(pneumococcal meningitis)

y Gram positive cocci

y Spread by droplet infection

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Treatment

y most broad spectrum antibiotics

y vaccine (Pnemoshot) made up of capsularpolysaccharide

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Listeria monocytogenes Listeriosis

y foodborne primarily unpasteurized dairy products

contaminated with animal feces, can grow in the

fridge

y are invasive, live in phagocytes, prefers those in

the central nervous system

y can be transferred through the placenta resulting

in spontaneous abortion andy still birth

Symptoms: range from asymptomatic to nausea to

septicemis to meningitis,etc.

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Other Symptomsy fever a d muscle aches

y diarrhea

y headache

y stiff eck

y co fusio

y

loss of bala cey co vulsio s

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Reservoirs and Mode ofTransmission

Reservoirs:

y Soily Water

y Mud

y I fected mammals

y I fected huma s

y Soft cheeses

Mode ofTransmission

y Via i estio of raw orco tami ated milk, softcheeses, a d ve etables

y

From mother to fetus iutero or duri passa ethrou h a i fected birthca al

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Treatmenty ampicillin in the early stages

y sulfa drugs in advanced infections

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Tetanus and Botulism

Clostridium tetani

y produces the tetanus

toxin which results incontinuous muscle

contraction, can lead to

systemic organ failure

and death

Clostridium botulinum

y produces the botulinum

toxin which causescontinuous muscle

relaxation

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Clostridium tetani

y causative a e t oftetanus

y or a ism is fou d i soil, especially heavily-ma uredsoils, a d i the i testi al tracts a d feces of variousa imals.

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Tetanusy from a pote t eurotoxi (tetanus toxin or

tetanospasmin)

y hi hly fatal disease

y Mortality rates reported vary from 40% to 78%

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http://en.wikipedia.org/wiki/Tetanus

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Pathogenesis

y result from small pu cture wou ds or laceratio s whichbecome co tami ated with C. tetani spores that ermi atea d produce toxi

y

toxi produced duri cell rowth, sporulatio a d lysis

y mi rates alo eural paths from a local wou d to sites ofactio i the CNS

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Neonatal tetanusy follows i fectio of the umbilical stump i i fa ts

bor to o immu e mothers (therefore, the i fa t has

ot acquired passive immu ity)

y usually results from a failure of aseptic tech iqueduri the birthi

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Toxin Action

y Teta ospasmi i itially bi ds to peripheral erve termi alsy tra sported withi the axo a d across sy aptic ju ctio s

u til it reaches the CNS

y becomes rapidlyfixed to gangliosides at the presynaptic

inhibitory motor nerve endings, a d is take up i to theaxo by e docytosis

y Effect of the toxi :block the release of inhibitoryneurotransmitters (glyci e a d gamma-ami o butyricacid) across the sy aptic cleft, which is required to checkthe ervous impulse

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y If ervous impulses ca ot be checked by ormali hibitory mecha isms, it produces thege eralized muscular spasms characteristic ofteta us.

y Teta ospasmi act by selective cleavage o f aprotei compo e t of sy aptic vesicles,

synaptobrevin II, a d this preve ts the release ofeurotra smitters by the cells

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Clinical pattern ofgeneralized tetanus

y severe pai ful spasms and rigidity of thevoluntary muscles

y "

lockjaw

y progressive rigidity a d viole t spasms of thetru k a d limb muscles

y spasms of the phary geal muscles causedifficulty i swallowi g

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Treatment

y Tetanus part of DPT vaccine, given pre-made

antitoxin antibodies which will bind and neutralize

toxin (passive immunization) plus a booster shot ofthe DT vaccine

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Clostridium botulinum

y large a aerobic bacillus that forms subtermi ale dospores

y

y widely distributed i soil, sedime ts of lakes a dpo ds, a d decayi g vegetatio , i testi al tracts ofbirds, mammals a d fish

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Pathogenesis of Botulism

Food-borne Botulism

y botuli um toxi is i gestedwith food

y absorbed by the upper partof the GI tract, passes i tothe blood stream by which itreaches the peripheral

euromuscular sy apses

y bi ds to the presy apticstimulatory termi als a dblocks the release of the

eurotra smitteracetylcholi e

Infant Botulism

y disease occurs ininfants 5 - 20 weeks ofage that have been

exposed to solid foods

y characterized byconstipation and weak

sucking ability andgeneralized weakness

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Botulinum Toxin

y Botuli um neurotoxins predomi a tly affect theperipheral nervous system reflecti g aprefere ce of the toxi for stimulatory motorneurons at a neuromuscular junction

y The toxi bi ds to the euro a d prevents therelease of acetylcholine across the sy aptic

cleft

y Primary symptom is weak ess or flaccidparalysis

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Clinical symptoms ofbotulism

y begi 18-36 hours after toxi i gestio withweak ess, dizzi ess a d dry ess of the mouth

y Nausea a d vomiti g may occur

y Neurologic features soo develop: blurred

visio , i ability to swallow, difficulty i speech,desce di g weak ess of skeletal muscles a drespiratory paralysis

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Prevention

y Proper food ha dli g a d preparatio

y The spores ofC. botulinum ca survive boili g(100 degrees at 1 atm) for more tha o e hour

although they are killed by autoclavi g

y Food co tai ers that bulge may co tai gasproduced byC. botulinum a d should ot be

ope ed or tasted

y Other foods that appear to be spoiled shouldot be tasted

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Treatment

y Botulism no vaccine, given antitoxin antibodies

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Mycobacterium leprae (Leprosy)

y relative ofMycobacterium tuberculosis

y lives in peripheral nerves and skin cells,intracellular pathogen

ygrows best at 30C so prefers extremities such asfingers, toes, nose

y produces enzymes that degrade the nerve cells

y loose sensation, tissue damage

y spread by prolonged direct contact with nasalsecretions carrying M. leprae

y not at all highly contagious

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http://www.google.com.ph/#hl=en&safe=active&q=Mycobacterium+leprae+%28Leprosy%29%0B&meta=&fp=a4738ba4588c5dff

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Treatment

y rifampin

y dapsone (a sulfa drug)

y vaccine trials with live, attenuated M. leprae totarget cell mediated response because this is an

intracellular pathogen and you need to kill both the

bacterium and the infected host cell

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Viral Diseases of the Nervous System

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Poliomyelitis, Polio, Infantile Paralysis

y a acute viral i fectious disease spread from perso to perso ,primarily via the fecal-oral route

y Symptoms: i flammatio of the CNS, especially the a teriorhor cells of the spi al cord a d the brai stem (the portio of thebrai betwee the cerebral hemispheres a d spi al cord)

y 80-90% of cli ical i fectio s, chiefly i you g childre , does oti volve the CNS

y Symptoms:slight fever, malaise, headache, sore throat, vomiti g3-5 days after exposure. Recovery occurs i 24-72 hours (abortivetype of polio)

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Polio Virusy virus lives in motor neurons

Reservoir: Infected humans

MOT:

y direct contact by ingestion of fecal contaminatedfood or water

y enters via the gastro-intestinal tract thenpenetrates to surrounding neurons

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Treatment

y OPV (oral polio vaccine) produces IgA

y new vaccine killed virus, given as an injection,targets the nervous system directly, produces IgG

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Rabies

y a viral euroi vasive disease that causes acutee cephalitis (i flammatio of the brai ) i warm-blooded a imals

y With me tal depressio , restless ess, headache,fever, malaise, paralysis, salivatio , spams of throatmuscles i duced vby a slight breeze or dri ki g

water, co vulsio s, death due to respiratory failure

y It is zoo otic (i.e. tra smitted by a imals)

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Rabies Virusy transmitted by bite from infected host or

aerosol from host, not contagious

y virus shed in saliva

y infection begins in the peripheral nerves andtravels to the brain

y long incubation period: 5-8 weeks beforesymptoms seen

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Treatment

1.passive immunization with pre-made anti-rabies abs

that will neutralize any free virus

2. active immunization by injection of live attenuatedvirus, stimulates cell mediated response, works welldue to the very long incubation period

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Arboviral Encephalitis

y arbo = arthropod borney by arthropod (insect) bite insect is unharmed but

carries the virus

y virus enters blood and peripheral nerves, travels to

the brain and causes encephalitis

y - e.g. Manitoba has Western Equine Encephalitis

(WEE) Virusy birds and horses are reservoirs

y spread by mosquitoes

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Symptoms

T

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Treatment

y none, 100% mortality, rare occurrence

y

horses given vaccine of attenuated virus

y mosquito control is the best prevention

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Lymphocytic Choriomeningitis

y A rode tbor e viral disease that prese ts as asepticmemi gitis, e cephalitis, or me i goe cephalitis

y

Maybe asymptomatic or symptomatic

y Fever, malaise, lack of appetite, headache, ausea,vomiti g, sore throat, coughi g, joi t pai , chest

pai , salivarygla d pai

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EtiologicAgent:

y Lymphocytic

Choriomem i gitisVirus (LCMV)

Reservoir:

y I fected rode ts,primarily commohouse mouse

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Mode ofTransmission

y Exposure to mouse uri e, droppi gs, saliva oresti g materials

y Virus ca e ter broke ski , the ose, the eyes, orthe mouth

y Via bite of a i fected rode t

y Orga tra spla tatio

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Disease Pathogen Reservoirs Vectors

Eastern Equine

Encephalitis

(EEE)

EEE virus(RNA

virus,Family

Togaviridae)

Birds, Horses Aedes, Coquilletida,

Culex, Culiseta

mosquitoes

California

Encephalitis

CEV (RNA

virus,Family

Bunyaviridae)

Rodents, Rabbits Aedes and Cules

mosquitoes

LaCrosse

Encephalitis

LaCrosse encephalitis

virus (RNAvirus,Family

Bunyaviridae)

Chipmunks,

Squirrels

Aedes mosquitoes

St. Louise

Encephalitis

St. Louise Encephalitis

virus(RNA virus,

Family Flaviviridae)

Birds Culex mosquitoes

West Nile Virus

Encephalitis

West Nile virus(RNA

virus, Family

Flaviviridae)

Birds, Pehaps Horses Culex mosquitoes

Western Equine

Encephalitis

(WEE)

WEE virus (RNA virus,

Family Togaviridae)Birds, Horses Aedes and Culex

mosquitoes

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Protozoan Diseases of the Nervous System

African Trypanosome Sleeping Sicknessy MOT: TseTse fly bite

y

Trypanosome enters the blood then travels to thecentral nervous system, then brain causingmeningitis or encephalitis

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Symptoms

y Main symptom: coma (sleeping sickness)

y Others: headache, stiff neck, sleep disturbance,

depression, followed by progressive mentaldeterioration, focal seizures, tremors, and

palsiesprogresses to coma and the ultimate

death of the patient often secondary to

pneumonia or sepsis. Without treatment, African trypanosomiasis is a universally fatalillness

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Two formsTrypanosoma brucei

gambiense

y fou d i west a dce tral Africa

y causes a chro ic

i fectio

Trypanosoma bruceirhodesiense

y fou d i easter a dsouther Africa

y causes a acute i fectio

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Treatmenty none, no vaccine as the trypanosome keeps

changing

y prevention is best: using mosquito netting and

insecticides

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AmericanTrypanosomiasisy k ow as Chagas disease

y Causative age t: Trypanosoma cruzi

Triatomine bug

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Signs & Symptoms

Acute Romaas sign, or swelling of the eye on one side of the face,

usually at the bite wound or where feces were rubbed into the eye

fatigue, fever, enlarged liver or spleen, and swollen lymph glands.

Sometimes, a rash, loss of appetite, diarrhea, and vomiting occur

last for 4-8 weeks

Indeterminate Eight to 10 weeks after infection, the indeterminate stage begins.

During this stage, people do not have symptoms.

Chronic Ten to 20 years after infectionCardiac problems, including an enlarged heart, altered heart rate

or rhythm, heart failure, or cardiac arrest are symptoms of chronic

disease, enlargement of parts of the digestive tract, which result in

severe constipation or problems with swallowing

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Leishmaniasis

y disease tra smitted by the bite of the phlebotomi esa dfly,

y

tra smits theA

mastigotes leishmania parasite

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Signs and symptoms

y ski sores which erupt weeks to mo ths after theperso affected is bitte by sa d flies

y Other co seque ces: ma ifest a ywhere from a fewmo ths to years after i fectio - fever, damage to thesplee a d liver, a d a aemia.

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Forms ofLeishmaniasisy Visceral leishma iasis (kala-azar, black fever, a d

Dumdumf

ever) the most serious form a d pote tially fatal ifu treated.

y Cuta eous leishma iasis the most commo form whichcauses a sore at the bite site, which heal i a few mo ths to a year, leavi g a u pleasa t looki g scar. This form caprogress to a y of the other three forms.

y Diffuse cuta eous leishma iasis this form produces widespread ski lesio s which resemble leprosy a d isparticularly difficult to treat.

y Mucocuta eous leishma iasis ( Espu dia," a d"Leishma iasis america a) comme ces with ski ulcers whichspread causi g tissue damage to (particularly) ose a d mouth

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Naegleria fowleriy

free-livi g amoeba typically fou d i warm fresh water,from 2535 C (7795 F) i a amoeboid or temporaryflagellate stage

y

ca i vade a d attack the huma ervous system viathe ose

y Causes primary amoebic me i goe cephalitis

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Signs and Symptomsy Fever

y Headache

y

Stiff ecky Lethargy

y Co fusio

y Altered level of co scious ess

y Seizures

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Brain tissue with Naegleria fowleri

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Acanthamoebay o e of the most commo protozoa i soil, a d also

freque tly fou d i fresh water a d other habitat

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Acanthamoeba granulomatous encephalitis

y altered me tal status

y Headaches

y Fever

y eck stiff ess

y seizures

y focal eurological signs such as cranial nerve palsiesand coma all leading to death within one week toseveral months

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