hi everybody in chapter 20 we will talk about some important infectious diseases of the nervous system to start your book has at the beginning of the chapter basic anatomy that you might want to review but we'll touch on a few points here keep in mind that your central nervous system is a zenic in other words it's sterile there are no normal microbiota and there should not be any microorganisms present in your cns so how do organisms get in there this usually happens through breaks or exposures of the cns for example if you experience a physical trauma or there's penetration of the meninges which are the membranes that cover and protect the brain and spinal cord it can also happen through a medical procedure that accidentally introduces organisms into your nervous system in other cases some organisms such as the one that causes rabies travel up through the peripheral neurons and gain access to the cns by causing infections and killing the cells of the meninges resulting in meningitis there are two basic ways which we can develop diseases that affect the central nervous system one is by direct infection on the cns cells or neurons as with meningitis both bacterial and viral in origin and hansen's disease more commonly known as leprosy the second is by production of toxins by bacteria in other places in the body that ultimately affect your nervous system these infections would include things like botulism and tetanus we're going to start by talking about bacterial meningitis which is the most common form of meningitis and is probably the most important and dangerous type of infection it's characterized by the sudden onset of high fever that is accompanied by inflammation of the meninges spread of the infection to deeper tissues can result in encephalitis which is infection of the brain and that can lead to coma and death there are five bacterial species that cause the most bacterial meningitis cases so we're going to talk about those in more detail they're listed down at the bottom of this slide as we review each pay attention to the differences in how they establish infection the first important organism that causes meningitis is streptococcus a galactia this organism causes meningitis in newborns because it's acquired drain birth streptococcus and galactia also referred to as group b strep is present in the normal vaginal microbiota of some women so a mom that is harboring the streptococcus species will transmit the organism dream birth and meningitis will ensue no streptococcus a galactia is a group b strep contrasting with group a strep which is streptococcus pyogenes listeria monocytogenes mentioned in earlier lesson lectures is a psychotrophic organism that replicates well in refrigerators and therefore is problematic because it may contaminate food especially at risk are elderly and immunocompromised individuals and pregnant women because the infection can traverse the placenta and infect the fetus this picture shows how listeria infects cells with a unique mechanism the organism establishes an intracellular infection and then pushes its way into neighboring cells to cause an infection in that cell by breaking through the membranes it possesses specific virulence factors to be able to do this it's very interesting refer to your book for more details if you're curious those at risk are told to avoid specific types of food like unpasteurized soft cheeses deli meats from the deli counter and other foods that could potentially be infected with the organism which exists in the environment the other three species are transmitted by respiratory droplets now streptococcus pneumoniae is present in the throat of 75 of people so the organism uses some mechanism to transverse into the cns niceria meningitidis also referred to as meningococcal meningitis is mostly linked to epidemic spread of bacterial meningitis for example when you think of an outbreak of people housed in a college dorm getting infected this would be the culprit there are vaccines available for three of the five organisms listed here that cause meningitis streptococcus pneumoniae haemophilus influenzae type b the hib vaccine and neisseria meningitidis further details of the five species that cause bacterial meningitis are summarized on this slide nyseria meningitis is a gram negative organism it releases lipid a into the body which can induce shock it's the form of meningitis that can cause epidemics and there is a vaccine available streptococcus pneumoniae is a gram-positive organism there's a vaccine available for it but it's the leading cause of meningitis in kids hemophilus influenzae is gram-negative and an intracellular pathogen and there is a vaccine available those three are the ones that cause meningitis and have vaccines available they are also similar in their respiratory transmission the last two do not have vaccines available however both have different and unique modes of transition transmission listeria monocytogenes is different because it's a foodborne transmission and streptococcus of galactia is perinatal or mother to child transmission during birth that summarized bacterial meningitis moving to hanson's disease otherwise known as leprosy this is a disease that is caused by a mycobacterium this genus has mycolic acid in the outer cell wall they are gram-positive acid fast organisms so these are the ones that are detected with that special staining technique interestingly the reservoir is armadillos so in the united states up to one in six armadillos carries this organism they like to grow in the cooler regions of the body so you will see areas like the nose and fingertips being affected most there are two forms of the disease tuberculoid is not progressive but develops these plaques on the skin lapromidus which is progressive results in tissue destruction like you see here on the bottom image what's the difference between the two in the non-progressive type which is less damaging to the patient your cytotoxic t cells are the main response to the organism it keeps organisms in check and prevents them from causing massive tissue destruction with lepromatous leprosy the individual has mounted primarily a b-cell antibody response which is not as effective as the cytotoxic t cells and this results in a lot more tissue destruction it's an infectious disease that's transmitted person to person through contact or through respiratory droplets but it is treatable and preventable the organism is found in the nostrils and can be tested for and confirmed by the acid-fast type of staining patients can be treated with antimicrobials but these are long-term treatments this is not a seven or ten day course of antimicrobials we're talking about many months not days to clear the organism there's also a vaccine available called the b c g vaccine which is really for tuberculosis that provides some protection but not 100 the bcg vaccine is used in other countries but not the united states now we're going to talk about diseases caused by organisms that aside from infection cause intoxication in other words a poisoning this is due to toxins produced by the organism and not by the organisms themselves replicating and cause tissue damage these toxins or rather neurotoxins can be produced in one part of the body and ultimately affect neurons in the central nervous system the first of these diseases is botulism and there are three principle ways of getting botulism first is the typical foodborne botulism that involves the direct ingestion of the toxin by a contaminated food and then there's infant botulism and wound botulism where the toxin is produced during an active infectious process who causes this the organism is clostridium botulinum clostridium being the genus botulinum is the species and you might remember from our discussions that clostridia are anaerobic gram-positive bacilli that form endospores clostridium botulinum produces the botulism toxin one of the most potent toxins naturally produced the toxin works on neurons which are prevented from stimulating muscle cells to contract this is the same toxin commercially known as botox that is used for cosmetic purposes as well as medical purposes to prevent muscle contractions or spasming of muscles of course the dose of the toxin would be very small to exert the medical effect and not a toxic effect in cases like cerebral palsy it has been used to prevent stimulation of a muscle and to allow muscle relaxation and on the cosmetic use they don't want you to contract or move a certain muscle on the face which promotes wrinkle formation by immobilizing specific facial muscles the effect is to minimize the wrinkles in those areas there are not many cases of botulism in the united states but worldwide it's a different situation botulism without some sort of intervention has a mortality of at least 10 percent how do you get it typically by ingesting food that has the organism's toxin in it for example improperly canned food contaminated with this organism provides a perfect anaerobic condition in which it can grow and produce the toxins that you will then ingest and inquire botulism here in the united states the fda regulates canning stringently you have to prove to the fda that your process will kill or have 12 logs or 12d if you remember devalues 12d reduction of any clostridium botulinum endospores in the process used to produce your food this is a huge level of reduction and it's to absolutely ensure no surviving sea botulism is in the product because if it is it will kill people as you might imagine these regulations were put into place after incidences of faulty processing led to widespread contamination and deaths in the past you don't see botulism in the united states from commercially canned products for this reason but you see it occasionally resulting from home canned products and in products sold covertly in places like farmer markets that escape regulatory scrutiny until an outbreak occurs in the united states infant botulism is more common type of botulism observed let's talk about that scenario the toxin causes flaccid paralysis which is the inability to stimulate the muscles and without stimulation you end up with floppy muscles if you look at the picture here you have a young child with what's called floppy baby syndrome the infant is being supported on its back and the baby is just flopping over with no muscle tone because all the muscles are affected these children can go into respiratory distress because they lose the ability to respire they can't breathe and will ultimately suffocate without intervention among the primary treatments for infant botulism is passive administration of antibodies to patients to help neutralize circulating unbound toxins neurons already affected and blocked by bound toxin will need to regenerate the surface where the toxin has bound and block the ability to release the neurotransmitters that will excite muscle cells these cell receptors must be replaced because once the toxin binds it's permanent acquisition of infant botulism is a little different than the typical foodborne botulism because the infant does not have a good microbiome to prevent establishment of clostridium in their gut so when the infant ingests endospores they can germinate in the intestine which is anaerobic the microorganisms replicate and start producing toxin within the intestines which is absorbed and exerts the effect on muscles in this case with infant botulism the young infants are ingesting the endospores and getting an actual infection from the organism which is producing the toxin in terms of prevention there are certain foods that they tell you to avoid feeding infants like honey honey is known to sometimes have endospores of toxin-producing clostridium so the recommendation is to not give honey to infants less than a year old because they don't have a good enough microbiome to prevent the establishment of a replicating population of clostridium in the gut lastly for wound botulism the scenario is this imagine a penetrating wound has caused enough damage that blood flow to the tissue has stopped the lack of oxygenated blood to the site creates an anaerobic environment which the organism can germinate and establish itself producing toxin then that's absorbed into and enters your system to produce the effects of botulism tetanus is similar in some ways because it's also caused by clostridia this one is clostridium tetani also gram-positive anaerobic endospore forming bacteria you acquire the organism through some sort of puncture wound that has created an anaerobic area in your tissue which allows the endospore forming organism to germinate and produce toxin however the toxin in this case is not botulinum toxin but tetanospasmin tetanospasm has the opposite effect of botulinum toxin on neurons and muscle cells the tetanus toxin tetanospasm blocks the release of inhibitory transmitters from an inhibitory neuron so the neuron that would cause your muscle to relax is able to not actually able to exert its effect as a result your muscles permanently go into contraction and this effect usually starts with a large muscle in your jaw hence the common name lockjaw you can see the clenching of the jaw that's happening in this child and you can see the painful spasming that's happening to the infant in this picture this is the condition known since ancient times and here's some earlier artwork depicting somebody that's believed to be in a tetanus spasm tetanus has a high mortality rate of 50 if not treated and even higher if we're talking about a newborn it's almost always fatal if you don't provide them passive protection with antibodies directed at the toxin the current treatment would consist of passively administering antibodies to the toxin and fighting the infection with antimicrobials there is of course a vaccine available for tetanus it's part of the dpt or tdap vaccine the t indicating protection against tetanus it's a toxoid vaccine antibodies are generated only to the toxin itself thus boosters are needed throughout life to maintain protection all right we'll stop here pick up with a second video