Neuro exam 1 part 2 Flashcards

Question

Diagnosis of Rabies

Answer 1

1. **Negri** bodies in CNS (brain) of animal, cytoplasmic inclusion, seen in cells from brainstem of infected humans 2. Detection of virus (viral antigens or viral RNA) from saliva, serum or “corneal impressions”, skin and brain biopsies **RT-PCR** used for detecting viral RNA, rapid and a preferred method; saliva is conducive to rapid testing RT = reverse transcriptase **Direct immunofluorescence test** (gold standard) of animal tissue, brain of animal is submitted to state health department or region lab for evaluation Rabies variants are associated with bat species, canine variants also recognized Rabies specific antibody appears late and its detection is not allow diagnosis

Answer 2

**Vaccine Historical Development** Long incubation period provides a window of time to immunize and produce high titer circulating antibodies Semple - rabiesvirus infected nervous tissue, which is inactivated with phenol - requires 7-14 daily injections - evokes allergic encephalomyelitis complications **Human diploid cell vaccine - 4 doses,** 0, 3, 7 , and 14 days - expensive - prophylactic ---animal handlers, 3 doses - ab levels elevated \> 2 yr IM route of administration of HDCV depending IM- Adults given deltoid ( IMOVAX RABIES) - Children given in anterolateral aspect of thigh or deltoid - **Gluteal muscle not appropriate** (too much fat in butt) ~20,000 people received rabies post exposure prophylaxis/year ~18,000 people received preexposure prophylaxis/ yr Rabies vaccine, adsorbed (RVA) Licensed 1988,inactivated virus adsorbed to aluminum phosphate Less expensive Chick Embryo grown vaccine and Vero Cell grown vaccine are now available. Recombinant **vaccinia** vaccine, Controversial vaccine expresses rabies G envelope protein, proposed vaccination of raccoons and other wildlife

Answer 3

**First action:** Flush wound with soap and water and cleans thoroughly **On day 0** inject 1/2 of Human rabies immune globulin ( (HRIG) directly into the wound and inject 1/2 of HRIG IM, **Start vaccine** on day 0, don’t administer HRIG and vaccine at the same site; Remember 4 doses: 0, 3,7,14 HRIG- HYPERAB and (IMOGAM) 1/2 life of ab after administration = 21 days

Answer 4

**Filoviridae family** - Enough differences from Rhabdoviruses to be classified as a separate family, differences in protein size, enveloped, neg. stranded RNA: In structure it resembles a piece of spaghetti and is not bullet shaped like Rhabdovirues **Marburg virus,** African hemorrhagic fever (liver is involved, encephalitis)

Answer 5

**Ebola - _antigenically distinct_ from Marburg, _morphologically similar_** * a. Marburg - found in monkeys and derived tissue culture cells - infects laboratory workers * b. **Marburg and Ebola** - high fever, headache, myalgia, diarrhea --\> conjunctivitis, rash, abdominal pain ---\> hemorrhage skin, nose, GI, GU ---\> shock, death 53-88% mortality * c. Natural route to transmission is through person to person contact via infectious biological fluids; Ebola (2014 caused signicant numbers of fatal disease in West Africal Ebola virus is a potential agent for Bioterrorism. The Japanese cult, Aum Shinrikyo, who released Sarin nerve gas into the Tokyo subways several years ago, sent cult members to Africa during the outbreak of Ebola to obtain biological samples. Since Ebola virus is difficult to grow in tissue culture, it is most likely problematic to grow enough virus to produce WMD. It still provides a subject of movies, however. Ebola outbreak in West Africa (2014). 370 Deaths as of July 1, 2014. Spread by human-human transmission perpetrated by poor public health systems. The Russians researched many of the "**hemorrhagic fever viruses**" and attempted to weaponize them as part of Biopreparat. As discussed in the video "Plague Wars", the lethal nature of Marburg virus was demonstrated by the accidental inoculation of a Russian scientist with the agent. The scientists isolated the virus liver and spleen of the decease individual in hopes of developing a more virulent form of the virus. Remember some other **hemorrhagic fever viruses are Arenaviruses, Bunyaviruses and Flaviviruses.**

Answer 6

Zoonotic diseases are caused by numerous microorganisms including viruses. The **animal is the primary host and humans are considered to serve as accidental** or peripheral hosts. The zoonotic virus can be transmitted to humans via **insect vectors or by excretions of the infected animal** that contaminate the human environment. The outcomes of possible virus infections are varied and these infections can be **targeted to one organ system or be multi-system in scope**. Viruses that are transmitted by insect vectors fall under the general category, **_ar_****thropod **_bo_**rne viruses or arboviruses. Insect vector mediated transmission**of viral diseases is multi- factorial and depends on an**animal host**serving as a reservoir for viral infection. Another important factor is the presence of an**insect vector**(mosquitoes, ticks, sandflies, etc) capable of biting the infected animal and transmitting the virus to other animals or to humans as an accidental host. The insect serves as an**instrument of transmission**, whereby the**virus actually replicates in the insect** to produce increased numbers of infectious virus particles. Greater numbers of infectious particles increase the likelihood of transmission to humans.

Answer 7

A **key factor** in arbovirus transmission is the **availability of** **arthropods in a given geographical area.** Colorado tick fever is found in western United States because the tick is resident in this environment and the species of tick is an essential part of the transmission process. Nicolas County, West Virginia is a “hot-spot” for **LaCrosse encephalitis** because the mosquitoes live in the hardwood trees in that environment and are capable of being infected and transmitting the virus to individuals living in or entering into that geographical region. As **man ventures into environments** once spared from human intervention, such as tropical jungles, in order to harvest trees or clear cut jungles for agricultural use, humans are being exposed to **new constellations of viruses.** Likewise certain environmental factors have allowed **insect vectors to survive outside their original niche**. **Global warming**, for example, allows temperature sensitive insect larvae to now survive winter months in northern climates. It often takes a span of weeks to months of freezing temperatures to kill insect larva located deep in the soil. It has already been noted by the CDC that the mosquito responsible for transmitting **dengue viruses (flaviviruses) has been isolated from as far north as Kentucky.** This will more than likely be a common theme rather than an exception.

Answer 8

In classical **epidemiological terms** the “**jungle” (rural) cycle** refers to a process whereby insects naturally resident in the jungle transmit a viral infection to animals that also live in the same environment, *Aedes hemagogus* being an example. In a similar manner certain insects, *Aedes aegypti* mosquito, for example, are well adapted to living in an **urban environment** and are capable of transmitting arboviruses between animal hosts. It is possible that the rural and urban cycles can intersect if animal/human hosts move from one environment to another or, alternatively, the insects span the two environments.

Answer 9

**Arboviruses are a rather diverse group of viruses** and members of several viral families are transmitted by insect vectors. These include: In **excess of 300 different viral agents** generally designated as **arbo**viruses are members of the Togaviridae, Flaviviridae , Bunyaviridae, and Reoviridae . These viruses are transmitted to man by arthropod vectors, usually mosquitoes. **Arboviruses multiply** **in both the vertebrate host and the insect** vector, often causing disease in the vertebrate host, but no disease in the arthropod. The incidence of arthropod-borne infections is **high, especially in tropical areas and in temperate climates.** Clinical disease in man ranges from an **undifferentiated febrile illness to an encephalitis and multi-organ system disease.**

Answer 10

There are more than 300 known arboviruses. Most are recovered from mosquitoes or ticks. Arboviruses; group of viruses containing several families of **Ar**thropod **Bo**rn and related viruses Approximately 100 infect man. About 40, mostly togaviruses and flaviviruses, produce significant disease, which may include the following: 1. **Encephalitis** 2. **Hemorrhagic** **fever**; tick-borne Russian spring-summer, yellow fever, dengue with shock syndrome 3. **Fever** **_+_** **Rash;** Dengue fever alone without complications associated with the hemorrhagic form Many arboviruses are endemic to tropic but they can also cause sporadic epidemics in temperate zones. **First Arbovirus discovered - Yellow Fever Virus**. The first disease in which it was established that a virus was an agent of human disease **and** that insects could serve as a vector.

Answer 11

Classified into **Alphavirus and Rubivirus (rubella)**. Rubella virus is **NOT** an arbovirus, whereas alphaviruses are arboviruses The **structure of Alphaviruses** include an **icosahedral capsid** surrounded by an **envelope**, which covered with fine glycoprotein spikes. To differentiate it from Flaviviruses (see next section) Togaviruses are **protease sensitive** particles. Togaviruses have a **SSRNA (+) polarity** genome which code for 4-5 viral proteins. Viral multiplication occurs within **cytoplasm and acquire their envelop by budding** at cell membranes. **Replication scheme** that was presented for poliovirus will suffice for all of the + stranded RNA viruses

Answer 12

**_First stage_** of Togavirus (alphavirus) infection: Togavirus infections are all **similar in initial stages**. Virus is **introduced into blood via the insect bite**, removed from circulating blood and **multiples** **in** **RE system (esp. spleen and lymph nodes).** **Viremia** then follows (systemic phase of disease) and is associated with minor illness, chills, fever, vomiting, pain. (**1st stage** **symptoms**) **_Second stage_** of Togavirus (alphavirus) infection which leads to an **encephalitis**. **Virus crosses Blood Brain Barrier** which **causes** **lesions in all parts of brain**. This is accompanied by **neuronophagia** (phagocytic destruction of nerve cells) and **encephalomalacia** (destruction of neurons + support structures). **Symptoms** include neck muscle rigidity, confusion, and convulsions (CNS symptoms).

Answer 13

**Eastern Equine Encephalitis (EEE)** causes severe human illness often with a high mortality (50-70%). It is the **least prevalent** of the various equine encephalitis viruses in the US. It has a higher incidence in certain geographical areas due to heavy spring rains and higher numbers of mosquitoes in a geographical region. **Experimental vaccine** is available to lab workers, but horse vaccine available commercially. Reduction of EEE in horses, which is its natural host, leads to less of a chance of humans being bitten by infected mosquitoes and transfer of the virus to humans who serve as an accidental host. **Western EE** - less severe - 2-3% mortality **Venezuelan EE** - primarily in horses - mild in man - 0.5% mortality Name given to these viruses **does not** necessarily indicate actual **geographic distribution** of the virus. The name reflects the location where it was first isolated and there may have just as high an incidence in other locales.

Answer 14

Chikungunya Virus has symptoms very similar to Dengue Fever Virus (Flavivirus, see below). Symptoms include acute fever, joint pain, maculopapular rash on trunk and possibly limbs, headache, nausea, vomiting, conjunctivitis and retinal lesions Chikungunya is an Arbovirus transmitted by mosquitoes. Chikungunya must be distinguished from Dengue in order to determine treatment with NSAIDs and fluids. Aspirin is not recommended for Dengue because aspirin can enhance hemorrhaging . **Age factors relative to clinical disease**: **_WEE infects children at a rate of 50:1_**( infections/clinical case). In adults the WEE rate of infection is 1000:1 infections./clinical case) and most are asymptomatic. In the case of EEE infections most fatal infections are seen in the elderly, ie \>30 % fatality rate.

Answer 15

Family: _Flaviviridae_ Have many structural and replication **features that are similar to Togaviruses** Flaviviruses are p**rotease resistant** and 20-50 nm in diameter **Transmitted by mosquito and ticks** depending on the virus under discussion Key members of the Flaviviridae include a number of **encephalitis viruses, hemorrhagic fever viruses and rash/fever viruses**. Clinical Manifestations **First Stage** of infection by Flaviviruses: Infected insect bites animal or human and inject virus into blood stream. Replication in RE system and a viremia is established. Fever, chills, malaise, vomiting are possible **Second Stage** **Virus invades various tissues during the second stage** of infection which follows first stage viremia. For Flaviviruses that cause **encephalitis** (St. Louis encephalitis, Japanese encephalitis, West Nile encephalitis and many others) virus crosses the BBB and infects the CNS **Other Flaviviruses cause infections that involve multiple systems.** These viruses infect the skin and endothelial cells of the blood vessels as well as various visceral organs. The two **primary viruses of this type** are **Yellow** **Fever** **Virus** and **Dengue** **virus,** the latter having 4 serotypes. In the category of **hemorrhagic fever causing viruses**, **yellow fever virus or dengue fever viruses cause clinical disease that can be severe.** Other hemorrhagic fever viruses are part of other virus families (see Bunya, Arena and Filoviruses) In certain situations **Dengue virus can produce a less severe disease without hemorrhagic fever**. In the latter case after the Dengue induced viremia, the virus infects cells of the skin, muscle and viscera.

Answer 16

YELLOW FEVER VIRUS: Yellow fever is mosquito transmitted. **Clinical disease** **(second stage)** includes a very severe, saddle back (diphasic) fever. Infection of the liver causes necrosis of liver (jaundice) and kidney. Hemorrhages occur in stomach which causes the hemoglobin of the RBCs to react with the acid of the stomach to cause a black colored product. **Black** **vomit** is characteristic of yellow fever. DENGUE FEVER VIRUS **Dengue (breakbone) fever** is caused by primary infection by **one** **of four serotypes** of Dengue virus. The immunity against one serotype does **not** **protect** against the other three serotypes. Dengue is endemic in the tropics but can be imported into the US. Dengue fever in its **less severe** **form** appears as a **maculopapular rash, pain in joints and muscles.** Other symptoms include **ocular** **pain in association with a saddle back fever**. Under certain scenarios the initial disease **can** **progress** to **hemorrhagic fever** **(DHF)** and even further into a **shock syndrome.** Progression into a shock syndrome occurs most often, if a **primary infection by serotype X (1,3,4)** is followed later by a **second infection by Dengue virus type 2.** An antibody-antigen reaction activates monocytes with the production of cytokines which in turn causes an immunopathology . Concomitant hemoconcentration ( more frequent in females) and thrombocytopenia occur as determined by hematocrit and platelet counts. Acetaminophen is preferred over aspirin, the latter having anticoagulant properties. **Hemoconcentration** should be treated aggressively by **hydration therapy** Increased frequencies and increased severity of dengue has been reported in the Americas and Caribbean. Significant outbreak in Hawaii have also been reported.

Answer 17

**Flavivirus induced encephalitis**; West Nile Virus is just one example **West Nile** virus ( WNV) first identified in the US in New York about 14 years ago, but now it has spread to almost every state. **WNV** **can** **be transmitted** to humans via 1) **insect vector****,**2)**blood****transfusions,**and 3)**organ****transplants**. A viremia is established and the virus crosses BBB to infect the CNS. Birds and horses seem to be primary animal reservoirs, but dog and cats and a variety other animals have been shown to be infected. Laboratory Diagnosis of WNV Viral isolation is not practical Serology test acute and convalescent sera using CF antibodies.

Answer 18

**ZIKA VIRUS** The virus infection has be linked to **encephalitis and Guillain Barre syndrome (rarely).** Zika virus has been in the news over the last several years for its ability to cause congenital infections of the fetus, which can manifest a variety of symptoms in the affected individual (developing child) throughout life. Although the virus was first recognized in the late 1940s, it has not been a major concern of health officials until recently. Zika virus infections of humans appears to particularly prevalent in South America and particularly in Brazil. The 2016 summer Olympic Games was held in Rio de Janeiro and athletes, spectators and support agencies traveled to this destination from throughout the world. Without the implementation of appropriate health measures, these groups were susceptible to infection. Zika virus is an arbovirus that is spread by mosquito vectors, primarily the Aedes aegypti and Aedes albopictus. The virus is a member of the **Flaviviridae** along with dengue fever and yellow fever viruses, several encephalitis viruses and West Nile virus. A key component in controlling any arbovirus infection is to reduce numbers or eliminate the insect vectors that transmit the virus. Brazil and many other countries do not routinely have processes in place to control insects. Lack of screens on windows, failure to use of insect repellants, failure to eliminate standing water as breeding grounds and lack of air conditioning (windows opened) all contribute to the high prevalence of mosquito vectors. Mosquitoes can lay their eggs in dry season which remain dormant for about 4 months. Eggs exposed to rain can than develop into larvae.

Answer 19

Zika virus can also be spread by sexual intercourse and blood transfusions in addition to the mosquito bites. Symptoms include fever, rash, joint pain and inflamed eyes. Muscle pain and headache also reported. Symptoms may last for one week. Most people will have mild symptoms or be asymptomatic. Serological test and RT-PCR tests available * RT-PCR of serum collected in the first two weeks of onset of symptoms * RT-PCR of urine collected within 14 days from onset of symptoms * Trioplex RT-PCR for Zika, Dengue and Chikungunya viruses Serum IgM specific to Zika virus is detectable at about one week after onset of symptoms. Clinician should order serology is RT- PCR is negative Serology (IgM) is also recommended for Dengue and Chikungunya viruses * 80% + Have a limited disease * Infection of pregnant women can lead to birth defects, microcephaly * Guillain Barre Syndrome link being investigate **Vaccine** in development, anticipated to be on market in 1.5 years **Prevention:** Do not travel to areas where Zika is prevalent Insect spray, barrier protection, fumigate modes of transportation (airplanes, ships, etc) to eliminate eggs Eliminate breading areas (standing water)

Answer 20

**Powassan Virus** **Encephalitis** resulting from infected tick bite is rare but if it does occur is often severe with neurological sequelae. Ten % of the severe infections are fatal. Only specialize diagnostic labs have capability to employ serological testing for this infection.

Answer 21

**Eradication of vector population**, eg. Aedes, employing bug spray is a primary method of reducing vector populations. Elimination of insect breeding sites (old tires) and other stagnant water. West Nile encephalitis incidence in New York lead to massive insect spraying (DEET). In the case of yellow fever, **immunization** of the human host has been effective. Yellow fever vaccines, 17DD or 17D 204, are composed of live, attenuated virus. Attenuation of virus is produced by passaging YFV in tissue culture cells. Immunization rarely produces complications. Some indication that YFV may provide protection against WNV infections. The availability of other vaccines for human use is limited. There are **no human vaccines for most encephalitis virus infections**, however, a vaccine is available for **Japanese encephalitis**. No vaccine is currently available in US for Dengue fever virus. NOTE: Degvaxia (CYD-TDV) has be developed in Mexico as a 3 dose series (0,6,12 month schedule). Degvaxia has not been “prequalified “ by WHO. Takeda vaccine (TAK-003) shows promise and has better immune response against all 4 Dengue serotypes than the Degvaxia vaccine **Horse vaccines are available** to immunize horses which has the potential to interrupt the transmission cycle.

Answer 22

**Epidemiology**: Vector restricted to ecological niche ( fly range), which restricts virus dispersion. SLE virus most common in U.S. **Imported Yellow Fever** is possible as a result of global travel. If traveler who is re-entering the US is suspected of having or having been exposed to Yellow Fever, he/she should be **quarantined** and not allowed to come in contact with mosquitoes. ArboNet (Arbovirus network): Human and animal surveillance system to determine the risks of human arbovirus infections. System now monitors continental US. **Bioterrorism Concerns** Many of the encephalitis viruses have been viewed as potential bioweapons. Eastern Equine Encephalitis in particular may be on the "short list " of arboviruses that could be weaponized. These viruses could be introduced into the animal population, eg. wild birds in the case of WNV, which would serve as a constant reservoir from which human and animal infections could originate. Mosquitoes would serve as the vector for dissemination. Surveillance of the mosquito, animal and human populations are therefore essential. Immunization of horses and spraying for mosquitoes would control the spread of infection.

Answer 23

**Structural Characteristics (Bunyaviridae)** Viral dimensions are approximately 90-100 nm diameter. The viral particles have a **helical nucleocapsid**, which is surrounded by an **envelop with glycoprotein spikes** extending outward from it surface. *(any animal with helical nuceocapsid will have an envelop)* The **genome** consists of **single stranded** **RNA which present in 3 segments** (Large, Medium and Small). Like members of the Orthomyxoviridae (model for negative polarity RNA virus replication), Bunyaviruses have a **negative polarity genome** and therefore carries a **viral** **RNA polymerase** within the virus particle itself. Also like the Orthomyxovirus, influenza A virus, members of the Bunyavirus family can undergo **reassortment of** **RNA segments** as a result of mixed infections of cells by different strains of a particular Bunyavirus. The **replication** of the Bunyavirus occurs in the **cytoplasm** and progeny virus particles acquire their envelops by **budding** through the membranes of the **Golgi apparatus**.

Answer 24

Genus _Bunyavirus_ As in the case of the other Arboviruses, a subset of Bunyaviruses can multiply in arthropod vectors and can cause human disease upon being bitten by the infected mosquito. **Some Bunyaviruses** are transmitted by **mosquitoes and others by ticks**. There are **10 serogroups** within the Bunyaviridae and one of these causes encephalitis in humans California serogroup: **California encephalitis virus** is found mainly in the upper Mississippi and Ohio River valleys, where the mosquito vector is most prevalent. The peak incidence of the disease is July through September. Clinical disease: The onset of the disease may take mild course or abrupt onset, which includes bifrontal headache, fever, vomiting, sometimes aseptic meningitis. Systemic and meningeal signs abate gradually within a week. 15% of infected children have sequelae. **LaCrosse encephalitis,** a member of the California serogroup, is seen in **Nicolas County, WV** There are a **number of viruses within the Bunyaviridae** that are also capable of causing **hemorrhagic fevers**.

Answer 25

**Genus: Orthobunyavirus** **Bunyamwera' serogroup**

Answer 26

**Genus: Phlebovirus** **Phlebotomus fever group** are transmitted by sand flies

Answer 27

Genus Hantavirus: **Korean hemorrhagic fever virus** **Hantavirus pulmonary syndrome** Hantavirus infections have also been seen in the **American southwest** particularly among native Americans. Exposure to virus results from **aerosols that originate from mouse feces** contaminated dust. The infection often leads to a **pulmonary syndrome (HPS)** Higher incidence of HPS is associated with more rainfall in southwest, which provides better habitat quality and increased numbers of rodents. 5% of HPS cases have been confirmed east of the Mississippi River. In July 2004 two cases of Hantavirus Pulmonary Syndrome reported in **Randolph County, WV** Ribavirin has shown efficacy in treating HPS if given early in the course of the infection. Terrorists could aerosolize this agent and disseminate it to produce HPS.

Answer 28

**Structural characteristics** of this virus include a rather wide range of sizes from 50-300 nm in diameter Virus particles have a **helical nucleocapsid** which is surrounded by an **envelop having** **a dense lipid bilayer**. Within the **core particles** are seen by EM that resemble ribosomes. The **negative polarity genome of the virus is RNA** consists of multiple segments that appear to be circular Arenaviruses replicate in **cytoplasm** using a viral RNA polymerase that is housed within the virus particles.

Answer 29

Arenaviruses are divided into **two serogroups:** 1) The **Old World Complex and 2) the New World Complex**. The primary **old world viruses** are **Lymphocytic Choriomeningitis Virus (LCM) and Lassa virus** **New world** viruses include the **Tacaribe virus complex** including Junin and Machupo viruses Virus **hosts** **are restricted to rodents** in which persistent infections leads to viremia and/or viruria

Answer 30

**Lymphocytic choriomeningitis virus** (LCM) (Old World Arenavirus) LCM infects man at frequency of 5%, except for those **in close contact with rodents** such as laboratory workers. LCM outbreaks have been reported in humans who purchased hamsters sold as pets. Urine and feces spread the virus. Also found in USA as a result of house mice infections which can transmit the virus to humans and rodent pets The **clinical disease** is usually mild with **influenza like** symptoms or infrequently **aseptic meningitis**. Fatal disease was reported in **organ transplant** recipients who received organs from an LCMV infected donor. Three of 4 organs recipients died. Infection of **pregnant women** during first and second trimester can be vertically transmitted to fetus causing severe disease of fetus. Severe disease could result from immune complex formation based on studies with a mouse model

Answer 31

LFV causes severe febrile illness in humans with 20% mortality rate. Infection involves many organs, but rarely a benign febrile illness has been documented. **Clinical Symptoms**: Seen mostly in Africa, patients develop **skin hemorrhages, high fever (hemorrhagic fever) mouth ulcers and severe muscle** **ache.** Virus spreads from human to human and rodent to human. Rats in Africa are chronically infected throughout their lives and shed high levels of virus in the urine

Answer 32

**Tacaribe complex** (New World Arenavirues) These are a group of viruses causing hemorrhagic fever in South America, Trinidad, Florida Everglades, **Argentina (Junin)**and **Bolivia (Machupo)**. Hemorrhagic fevers often result. Mosquitoes and mites may transmit virus, but rodent urine and feces are the primary means of transmission of animals Clinical Symptoms: Hemorrhagic fever is characterized by petechiae, bleeding in the GI tract, uterus, nasal cavity and GU tract 15 New world arenaviruses are recognized Many of the hemorrhagic fever viruses are candidates for weaponization into bioweapons. One possible mode of dissemination of arbovirus caused hemorrhagic fevers is to raise large populations of infected mosquitoes and release them into a human population. The vectors would do the work of the terrorist in transmitting viral agents. This same principle pertains to Toga and Flavivirures that are also transmitted by mosquitoes or other insect vectors.

Answer 33

➤Rostral defects: anencephaly, encephalocele ➤Caudal defects: spina bifida and related conditions ➤Regulators of closure : retinoic acid (teratogen known to lead to neural tube defects in animal models) and folate (inadequate levels significantly increase risk for neural tube defects)

Answer 34

Spina Bifida Occulta

Answer 35

Occult spinal dysraphism

Answer 36

Meningocele

Answer 37

Myelomeningocele

Answer 38

Hydrocephalus

Answer 39

➤most patients have normal intelligence, but specific cognitive disabilities, and language difficulties are common. ➤Head circumference should be followed, if shunt placed at risk for malfunction or infection. ➤Seizures in 17%, almost always if shunted hydrocephalus ➤Bowel and bladder dysfunction, may have hydronephrosis at birth ➤Orthopedic problems, include foot deformities, hip subluxation

Answer 40

* ➤midline septum divides cord into 2 portions, usually unequal in size. * ➤2 types: single arachnoid/dural sleeve, or each hemicord in own sleeve (50-50) * ➤present with congenital scoliosis, hydrocephalus, cutaneous lesions * ➤may have progressive myelopathy * ➤removal of septum does not clinically improve, remove if progressing, otherwise follow clinically

Answer 41

Diplomyelia

Answer 42

SACRAL AGENESIS

Answer 43

Types ➤I. downward displacement of cerebellum and cerebellar tonsils, elongated brainstem/4th ventricle ➤II. downward displacement of tonsils and vermis, elongated medulla, seen in patients with myelomeningocele ➤III. encephalocervical meningocele and protrusion of cerebellum through posterior encephalocele ➤IV. Hypoplasia of cerebellum

Answer 44

ENCEPHALOCELE * ➤cranial meningocele include only meninges and CSF * ➤encephalocele include brain parenchyma * ➤ventriculocele is where herniated contents include portion of ventricle * ➤most commonly occipital (75%) or frontal (25%) * ➤rare transphenoidal encephaloceles extend into upper pharynx. * ➤Folic acid supplementation does not seem to be protective ➤severe intellectual delay ➤microcephaly ➤other malformations including: Dandy-Walker, agenesis of corpus callosum, Klippel-Feil, porencephaly, optic nerve dysplasia, and others

Answer 45

ANENCEPHALY

Answer 46

**SCHIZENCEPHALY** ➤can be **unilateral or bilateral**. Bilateral often associated with mental retardation and spasticity, unilateral frequently associated with epilepsy, but not as often with significant other neurologic deficits.

Answer 47

* **➤agenesis/dysgenesis of corpus callosum** frequent anomaly, wide variety of clinical symptoms. * ➤complete or partial. Partial can be thinning of entire structure or absence caudal portion. Rostral portion usually retained unless complete agenesis present * ➤can be associated with chiari II, disorders of neuronal migration

Answer 48

➤Septum verum, which contains nerve cells, and septum pellucidum thin translucent plate forming medial wall of lateral ventricle. Development associated with corpus callous ➤**Cavum septum pellucidum** 20% of normals *(BENIGN VARIANT)* ➤**absence of the septum pellucidum** - primary agenesis, or secondary due to damage (hydrocephalus) Frequently associated with other abnormalities - septooptic dysplasia, agenesis of corpus callous, schizencephaly, hydrocephalus or encephaloceles.

Answer 49

Septo-optic Dysplasia

Answer 50

* Chiari I * Cerebellar hypoplasia * Dandy-walker * Holoprosencephaly

Answer 51

CEREBELLAR HYPOPLASIA

Answer 52

DANDY-WALKER ➤core criteria: cerebellar vermis hypoplasia/aplasia, cystic enlargement of 4th ventricle, elevation of roof of posterior fossa. ➤associated malformations include occipital encephalocele, polymicrogyria, heterotopias. 10 - 17% have agenesis or dysgenesis of corpus callosum

Answer 53

➤core criteria: cerebellar vermis hypoplasia/aplasia, cystic enlargement of 4th ventricle, elevation of roof of posterior fossa. ➤associated malformations include occipital encephalocele, polymicrogyria, heterotopias. 10 - 17% have agenesis or dysgenesis of corpus callosum

Answer 54

HOLOPROSENCEPHALY * ➤about day 22 of gestation single prosencephalic vesicle forms at end of neural tube. By day 32 the telencephalon and diencephalon separate and the telencephalon divides into 2 separate hemispheres * ➤Holoprosencephaly is characterized by failure of complete separation of the prosencephalon into distinct cerebral hemispheres and also separation of telencephalon from diencephalon. * ➤incidence in live birth 1:10,000, but incidence in aborti is 1:250.

Answer 55

* ➤alobar holoprosencephaly nearly complete lack of separation into hemispheres with single midline ventricle, often communicating with dorsal cyst. Interhemispheric fissure and corpus callosum are not present. * ➤semilobar holoprosencephaly, anterior hemispheres not separated, but some degree of separation of posterior hemispheres. Splenium of corpus callosum is present. Frontal horns of lateral ventricles not developed but posterior horns are. * ➤mildest form - lobar holoprosencephaly lacke of separation of most rostral and ventral components of hemispheres. Splenium and body of corpus callosum present, but genu absent. Rudimentary frontal horns may be present * ➤middle hemispheric variant - midportion of cerebellar hemispheres is continuous, with absence of corpus callosum in this region, but separation of anterior frontal lobes, basal forebrain and occipital lobes.

Answer 56

➤multiple genetic and environmental factors implicated ➤maternal diabetes, exposure to alcohol and retinoic acid have best evidence of association ➤has been associated with trisomy 13, trisomy 18 and triploidy. 8 genes associated with holoprosencephaly ➤disruption of Shh signaling network in animal models produces similar malformations (sonic hedgehog protein)

Answer 57

Holoprosencephaly

Answer 58

* Microcephaly * Macrocephaly * Megalencephaly * Hemimegalencephaly * Focal cortical dysplasia

Answer 59

MICROCEPHALY * ➤microcephaly associated with other disorders, lissencephaly, holoprosencephaly * ➤If only finding then diagnosis is primary microcephaly

Answer 60

* ➤infection - TORCH * ➤drugs * ➤anoxia/ischemia * ➤genetic/hereditary * ➤chromosomal abnormalities * ➤congenital malformations of CNS * ➤postnatal * ➤infections - meningitis * ➤trauma - child abuse * ➤pregnancy issues - nutrition, toxic exposure

Answer 61

**MACROCEPHALY** ➤big head - * ➤hydrocephalus * ➤obstructive * ➤communicating * ➤megalencephaly big brain

Answer 62

**MEGALENCEPHALY** * ➤anatomic without extraneural malformations * ➤asymptomatic (normal neurologic, big head) * ➤symptomatic - doesn’t meet other syndromes * ➤metabolic - lysosomal diseases, mucopolysaccharidoses, Tay-Sachs, generalized gangliosidoses * ➤with gigantism - Beckwith-Wiedemann syndrome, Soto’s, pituitary * ➤with skeletal dysplasia - achrondoplasia, Apert’s * ➤neurocutaneous syndromes * ➤spongy degeneration - Canavan’s, Alexander’s

Answer 63

Criteria for asymptomatic familial megalencephaly * ➤OFC \> 2 sd **(BIG HEAD)** * **➤No evidence of increased ICP** * ➤normal development and neurologic exam * ➤no neurocutaneous signs or other anomalies that suggest syndrome * ➤primary relative with increased OFC and normal neurologically * ➤followup shows leveling of curve, and continued normal development

Answer 64

**Hemimegalencephaly** * ➤some patients no more than half a hemisphere (hemi-hemimegalencephaly) more commonly posterior quadrant * ➤isolate brain lesion but rarely associated with neurocutaneous syndromes * ➤**seizures** usually in first 6 months of life, usually partial onset * ➤can have **infantile spasms**. Some have hemi spasms (one sided spasms)

Answer 65

**FOCAL CORTICAL DYSPLASIA** * ➤area of focal cortical dysplasia * ➤most **common cause of medically intractable focal onset epilepsy** * ➤many are not seen on routine MRI

Answer 66

* ➤lissencephaly *(smooth brain)* * ➤agyria; *no gyri in sulci* * ➤pachygyria; *like elephant skin. big thick folds of gyri* * ➤subcortical band heterotopia (double cortex syndrome); *grey matter - white matter - grey matter - basal ganglia* * ➤cobblestone complex malformations * ➤heterotopias; *not where they suppossed to be*

Answer 67

LISSENCEPHALY - ***Smooth brain*** SUBCORTICAL BAND HETEROTOPIA * ➤most common cause is DCX gene * ➤usually seen in females, due to X-inactivation * ➤males with this gene usually have lissencephaly, although males with band heterotopia are reported

Answer 68

COBBLESTONE COMPLEX LISSENCEPHALY * ➤cobblestone cortex, enlarged ventricles (may have hydrocephalus), abnormal white matter, small brainstem, small dysplastic cerebellum * ➤cortex severely disorganized with no recognizable layers

Answer 69

NEURONAL HETEROTOPIAS

Answer 70

* ➤bilateral frontal polymicrogyria - back to precentral sulcus and frontal operculum. Developmental delay, mild spastic quadraparesis, variable MR, language impairment and epilepsy * ➤bilateral frontoparietal polymicrogyria - involves frontal and parietal lobes, associated with brainstem and cerebellar hypoplasia, patchy white matter signal changes and enlarged ventricles. Global DD, MR, seizures, bilateral pyramidal and cerebellar signs * ➤perisylvian polymicrogyria- prominent psuedobulbar paresis (swallowing difficulties,aspiration), inability to protrude tongue, dysarthria, facial diplegia. Have mild to moderate MR, seizures. * ➤mesial pareito-occipital polymicrogyria, occipital polymicrogyria are also reported.

Answer 71

HYDROCEPHALUS * ➤obstructive, communicating * ➤associated with congenital malformations, infections, neoplasms, bleeds/trauma, vascular malformations (vein of galen), variety of syndromes * ➤X-linked hydrocephalus with aqueductal stenosis * ➤obstructive may need shunt, VP most common

Answer 72

**Hydranencephaly** \*\*\*Most likely Vascular * -Normal spinal cord, some brainstem and basal ganglia * -Cortex is gone?? * -Normal differentiation but something happened in tissues and was lost? **Most likely vascular problem**

Answer 73

History * •Etiology discovered in 1884 by Carle and Rattone * •Passive immunization used for treatment and prophylaxis during World War I * •Tetanus toxoid first widely used during World War II Epidemiology * •overall annual incidence of 0.10 cases per 1 million * •0.23 cases per 1 million persons 65 years or older * •Most reported cases are in patients older than 60 years (immunity and immunization) * •Injection drug abuse places patients at risk for tetanus

Answer 74

**CLOSTRIDIUM TETANI** * •obligately anaerobic bacillus * •gram positive in fresh culture, variable in old culture * •Can be flagellated and sluggish motile during growth * •Produce 2 toxins: * 1)Tetanospasmin (commonly called tetanus toxin) in toxigenic strains * 2)Tetanolysin, uncertain importance * •Mature organisms resemble a squash racquet * **_•Spores are extremely stable,_** retaining the ability to germinate and cause disease indefinitely * •Spores withstand exposure to ethanol, 5% phenol up to 10h, or formalin, heat stable * •Spores rendered noninfectious by iodine, glutaraldehyde, hydrogen peroxide, or autoclaving at 121° C and 103 kPa (15 psi) for 15 minutes * •Growth in culture under strictly anaerobic conditions (no diagnostic value) * Spores of tetanus bacteria are everywhere in the environment, including soil, dust, and manure * In general, the further the injury site is from the central nervous system, the longer the incubation period * A shorter incubation period is associated with more severe disease, complications, and a higher chance of death (worse prognosis) * In neonatal tetanus, symptoms usually appear from 4 to 14 days after birth, averaging about 7 days * Common ways of entry: wounds contaminated, puncture wounds, burns, crush injury * Rare ways of entry: surgeries, dental, IM or IV injections

Answer 75

* •Spores enter the body (wound, needle, stump infection, etc.) * •Anaerobic conditions, the spores germinate producing toxin during stationary phase which released when cell lysis * •Toxin disseminated via blood stream and lymphatic system * •Toxin acts at several sites CNS, sympathetic nervous system * •Toxin blocks inhibitory transmitters release * •Unopposed muscle contraction and **_spasm_** * •Seizure, autonomic nervous system * **_•Death from respiratory failure_** * •The estimated minimum human lethal dose is 2.5 nanograms per kilogram of body weight.

Answer 76

**Generalized Tetanus** * •most common form, accounting for more than 80% of cases * •1st signs: trismus (“lockjaw”; masseter rigidity) and/or risus sardonicus (increased tone in the orbicularis oris) * •The generalized spasm resembles decorticate posturing painful spasms in other muscle groups seizure-like activity or convulsions in severe cases, no loss of consciousness * •clinical course of generalized tetanus is variable and depends on the degree of prior immunity, the amount of toxin present, and the age and general health of the patient * •associated with death rates of 10% to 20% * •The illness can progress for about 2 weeks **Localized Tetanus** * •muscle spasms in a confined area close to the site of the injury * • occurs in people with partial immunity and is usually mild, progression to generalized tetanus can occur **Cephalic Tetanus** * •associated with lesions of the head or face ex: otitis media or head wound * •Extreme rare * •The incubation period is short, usually 1 to 2 days * •results in flaccid cranial nerve palsies rather than spasm * •Spasm of the jaw muscles may also be present * •Extraocular muscle involvement is occasionally noted * •can progress to the generalized form * •Thought is poor prognosis, recent studies revealed many mild cases

Answer 77

* •Tetanus is diagnosed by clinical observation * •Culture C. tetani from wounds are not useful in diagnosis * •Toxicologic studies of serum and urine should be performed when tetanus is suspected * •Differential diagnosis: Strychnine poisoning, **dystonic reactions to neuroleptic drugs (turn head to right or left)** or other central dopamine antagonists

Answer 78

* •Monitor airway and to ventilation * •passive immunization, must be pursued as soon as the respiratory system is secure * •Administer a benzodiazepine IV to control spasm and decrease rigidity * •Administer human tetanus immunoglobulin * •At a different site, administer adsorbed tetanus toxoid such as tetanus-diphtheria vaccine (0.5 mL) or diphtheria-pertussis-tetanus vaccine (0.5 mL) * •Begin metronidazole, 500 mg, IV, q6h, for 7-10 days * •Débride any wounds * •Administer benzodiazepines as required to control spasms and produce sedation * •Treat sympathetic hyperactivity with labetalol or morphine * •Monitor BP and HR * **_•When spasms are no longer present, begin physical therapy_** * **•Before discharge, administer another dose of _tetanus-diphtheria vaccine or diphtheria-pertussis-tetanus vaccine_** * **•Schedule a third dose of toxoid to be given 4 wk after the second**

Answer 79

* **•Tetanus toxoid (TT)**, a heat-inactivated toxin, was developed in 1924 * •Vitamin A deficiency interferes with the response to tetanus toxoid * •Primary tetanus vaccination in combination with **diphtheria and pertussis (DTaP)** at 2 months, 4 months, 6 months, 12 to 18 months, and 4 to 6 years * •2005, the U.S. (FDA) approved the use of a new vaccine formulation: tetanus, reduced diphtheria toxoid, and acellular pertussis (Tdap) * •Tdap should be administered once to all adolescents at age 11 to 18 years * •Tetanus immunity wanes with age * •Adults receive a tetanus diphtheria toxoid (Td) booster every 10 years * •Between the ages of 19 and 64 years, one of these Td boosters should be replaced with a single dose of Tdap * •Tdap should also be given to adults older than 65 years who have not previously received Tdap and who anticipate close contact with infants aged younger than 1 year * •All pregnant women receive Tdap during each pregnancy, regardless of prior vaccination status * •Patients who have undergone bone marrow or stem cell transplantation require revaccination after the procedure, three Td boosters be given, the first of which should be administered 6 to 12 months after transplantation * •No association with Guillain-Barré syndrome

Answer 80

* •**aduls aged \>19** and have not previously received a dose of Tdap: * -single dose of Tdap should replace a single dose of Td for booster even if given Td recently * -subsequent q10 years booster should be Td * •**wound:** Tdap is preferred over Td * •**adolescents and adults in close contact with infant \<12 months old:** * -single dose of Tdap for pertussis prevention if not previously Tdap immunized * •a dose of Tdap **during each pregnancy** irrespective of prior history of receiving Tdap (even same calender year) optimal timing 27-36 weeks * **•grandmother take care of newborne** should have Tdap few weeks before

Answer 81

Td and Tdap are inactivated component vaccines -primary series: * 2 doses of 0.5mL IM at least 4 weeks apart 91st dose Tdap, 2nd dose Td) * 3rd dose Td of 0.5mL IM 6-12 weeks after 2nd dose boosters: * -every 10 y. ***(every patieent should get a booster from the age of 65)*** * -should give all adolescent/adults one Tdap booster * side effect mild local reactions and fever

Answer 82

**Clostridium Botulinum** History of Botulism * •The term botulism derives from the Latin word botulus, or sausage * •Justinus Kerner, connection between sausage and the paralytic illnesses in 1820 * •van Ermengen published the first description of C. botulinum in 1897 * •type A toxin; type B was discovered in 1904 * •Wound botulism was described in 1943 * •Type A toxin was isolated and purified in 1946 * •infant botulism in 1976 * •gastrointestinal colonization, was first reported in 1986 * •In 2014, a possible new toxin was discovered in association with a case of infant botulism

Answer 83

* •large, gram-positive, strictly anaerobic bacillus * •forms a subterminal spore * •found throughout the world in soil samples and marine sediments * •spores are able to tolerate 100° C at 1 atm for several hours (boiling renders solution more anaerobic) * •Proper preparation of food in a pressure cooker will render spores inert * **•Four physiologic groups** * 1.Group I: toxin types A, B, and F * 2.Group II: toxin types B, E, and F * 3.Group III: toxin types C and D * 4.Group IV: Toxin type G * •Group II organisms grow optimally between 25° and 30° C, and the other groups grow best between 30° and 37° C * •Only type G toxin is encoded on a plasmid

Answer 84

* •Foodborne botulism: ingests botulinum toxin, few hours to days, outbreaks, home canned food * •Infant botulism: harbor C. botulinum in their intestinal tract, ingests spores, colonization * •Wound botulism: rare, IVDA, traumatic injury, surgeries * •Adult intestinal colonization = adult intestinal toxemia: very rare, GI colonization, GI surgery, achlohydria, use antibiotics or IBD * •Iatrogenic botulism: overdose of injected botulinum toxin for cosmetic or medical purposes * •Alaskan Natives or fish fermentation = Foodborne botulism * •Consumption of peyote = Foodborne botulism * •Absorption of toxin produced by C. botulinum in situ = Infant botulism * •use of “black-tar” heroin or skin-popping = Wound botulism * •intranasal use of contaminated cocaine = inhalational botulism (rare) * •bioterrorist attack with botulinum toxin = ingestion or as an aerosol

Answer 85

**Clinical Manifestations** * **•acute, _bilateral_ cranial neuropathies** associated with symmetrical descending weakness * •Foodborne botulism usually develops between 12 and 36 hours after toxin ingestion, Nausea, dry mouth * •Diarrhea?: botulinum toxin itself affects parasympathetic autonomic ganglia causing constipation * •Weakness then spreads to the upper extremities, the trunk, and the lower extremities * •Respiratory dysfunction *(main cause of death)*: obstruction or diaphragmatic dysfunction **Cardinal features** * **_1.fever is absent_** * **2.neurologic manifestations are _symmetrical_** * 3.the patient remains responsive * 4.the heart rate is normal or slow in the absence of hypotension * 5.sensory deficits do not occur (except for blurred vision)

Answer 86

* •If MV needed: mean periods of 58 days (type A) and 26 days (type B) for ventilatory weaning * •Recovery may not begin for up to 100 days * •Autonomic problems: GI, Heart, BP, body temperature, GU * **•Infants with botulism** present with c**onstipation, which may be followed by feeding difficulties, hypotonia, increased drooling, and a weak cry** * •Upper airway obstruction may be the initial sign and is the major indication for intubation * •The condition progresses for 1 to 2 weeks and then stabilizes for another 2 to 3 weeks before recovery starts. * •Relapses of infant botulism may occur * •Wound botulism lacks the prodromal gastrointestinal disorder of the foodborne form but is otherwise similar in presentation

Answer 87

* •Diagnosis mainly clinical and by history * •DDx: Myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), Tick paralysis, Guillain-Barré syndrome (acute inflammatory demyelinating polyneuropathy), polio, Magnesium intoxication * •myasthenia lacks autonomic features * •Edrophonium test * •GBS: sensory complaints, rapidly produces areflexia, CN dysfunction extremely rare * •Conventional diagnosis of botulism relies on the demonstration of toxin in serum, gastric secretions, stool, or food samples * •Anaerobic cultures of serum, stool, and the implicated food, if available, may assist in making the diagnosis * •Enzyme-linked immunosorbent assay * •Electrophysiologic studies reveal normal nerve conduction velocities * •amplitude of compound muscle action potentials is reduced in 85% of cases * •Repetitive nerve stimulation at high rates may reveal a small increment in the motor response * •This test is very uncomfortable and should not be requested unless botulism or LEMS is a serious consideration

Answer 88

* •heptavalent botulinum antitoxin (HBAT) * •HBAT is not approved for administration in infants younger than 1 year * •Human botulinum immune globulin (BabyBIG) younger than 1 year * •Use of BabyBIG has resulted in decreased length of intensive care unit stay, length of mechanical ventilation, and overall length of hospital stay * •The decision to intubate should be based: * 1.bedside assessment of upper airway competency * 2.changes in vital capacity * 3.Do not wait for (Paco2) to rise or the oxygen saturation fall before intubating the patient * •wound botulism should also undergo débridement, even if the wound appears to be healing well * •penicillin G (10 to 20 million units daily) is recommended, can use Metronidazole * •Lysis of C. botulinum in the gut by antibiotics may also increase the toxin available in infant botulism

Answer 89

**Prevention** * •The most important aspect of botulism prevention is **proper food handling and preparation** * •Immunity to botulinum toxin does not develop even with severe disease * •vaccine: recombinant toxin A/B vaccines and inhalational vaccines, are currently being investigated

Answer 90

Differential * •Stroke * •Delirium; drug intoxication * •Vascular process – **Anton Syndrome** * Wernicke encephalopahty; opthalmoplegia, ataxia, confusion (TRIAD). Thiamine deficiency * Hypoxia * PRES (posterior reversible encephalopathy syndrme?); elevated blood pressure **Final DIagnosis; PCA stroke - ANTON SYNDORME**

Answer 91

Stroke Statistics * •Effect \> 700,000 persons per year * •Causes 200,000 deaths annually * •Third leading cause of death overall * •Leading cause of long-term disability * •Costs \> $40 billion per year Stroke Belt * •Area of U.S. with highest death rate due to stroke * •Cause is unknown * •Traditional risk factors do not explain it

Answer 92

* •Think **“brain attack”** * –Much like a heart attack, strokes are when the brain is acutely deprived of oxygenated blood * •It is a Medical Emergency * –If stroke is assessed early enough it can be treated

Answer 93

**–Ischemic** * •Block blood vessel (if transient is defined a TIA) * •Accounts for 80-85% of strokes **–Hemorrhagic** * •Ruptured blood vessel * •Accounts for 15-20% of strokes * •May _have previously been ischemic_ * –Vessels become leaky when they are ischemic, which can result in hemorrhage. * ***_Mostly from HTN or ruptured aneurysm_***

Answer 94

* •Advanced age (the risk doubles every decade), * •Diabetic * •Hypertensive * •Hypercholesterolemia * •Tobacco Abusers * •Obesity * •Heart Disease * –CAD, CHF, Atrial Fibrillation * •Blood Dyscrasias

Answer 95

Transient Ischemic Attack (TIA) * •Ischemic (low blood-flow) stroke without permanent damage * •“Angina” of the brain * •\<24 h by definition, but usually 2-20 min * •Important warning of impending stroke * •Prompt evaluation urgent to prevent future stroke–find out the cause!

Answer 96

•The most common cause of intracranial hemorrhages are: –Children: AV malformation. –Adults: * •Aneurysm rupture * –Small Vessel (Charcot Bouchard Aneurysms) * Caused by chronic HTN and involve the same small penetrating arterioles as lacunar strokes, however aneurysm rupture leads to intraparenchymal hemorrhage * –Large Vessel * •**_Cerebral amyloid angiopathy is the most common cause of lobar/cortical parenchymal hemorrhage._** * –Cerebral amyloid angiopathy (CAA) refers to the deposition of β-amyloid in the media and adventitia of small and mid-sized arteries of the cerebral cortex and the leptomeninges. * –It is a component of any disorder in which amyloid is deposited in the brain, and it is not associated with systemic amyloidosis.

Answer 97

Global aphasia – CORTICAL DEFECT **MCA** most likely affected * ED calls “code stroke” to hasten work-up in order to possibly provide emergent intervention for patients appearing to have stroke symptoms * What does a code stroke actually accomplish for the patient? Code Stroke * •NIH Stroke Scale Obtained * •Neurologist “on call” paged and patient history and exam is presented. * •Labs including Finger Stick Glucose, CBC, Basic Metabolic Profile (BMP), PT/PTT/INR * •Imaging is performed. * –CT vs MRI. * –Should you do an MRI now? (*MRI takes longer - 20 to 30 minutes)*

Answer 98

MRI showing low signal foci in cerebral **amyloid angiopathy.** Conventional gradient echo T2\*-weighted image and susceptibility weighted image (SWI)

Answer 99

**Left MCA Stroke** Hyperdensity on left side

Answer 100

**•Left hemisphere;** Cortical symptoms (MCA); visual defects, hemiparesis •If it is **right hemisphere** (subcortical stroke); pure sensory or pure motor and NO CORTICAL LOCALIZATION AT ALL

Answer 101

**IV TPA** EXCLUSIONS * Patient's symptoms are minor or rapidly improving. * Patient had seizure at onset of stroke. * Patient has had another stroke or serious head trauma within the past 3 months. * Patient had major surgery within the last 14 days. * Patient has known history of intracranial hemorrhage. * Patient has sustained systolic blood pressure \>185 mmHg. * Patient has sustained diastolic blood pressure \>110 mmHg. * Aggressive treatment is necessary to lower the patient's blood pressure. * Patient has symptoms suggestive of subarachnoid hemorrhage. * Patient has had gastrointestinal or urinary tract hemorrhage within the last 21 days. * Patient has had arterial puncture at noncompressible site within the last 7 days. * Patient has received heparin with the last 48 hours and has elevated PTT. * Patient's prothrombin time (PT) is \>15 seconds. * Patient's platelet count is \<100,000 uL. * Patient's serum glucose is \<50 mg/dL or \>400 mg/dL.

Answer 102

* •Does TPA immediately reverse the symptoms? * TPA works by initiating local fibrinolysis by binding to fibrin in a thrombus (clot) and converts the entrapped plasminogen to plasmin. Simply stated its hastens clot degradation * •Actually all that has been proven is that it decreases the amount of disability seen three months post stroke. * –There are lots of anecdotal cases of people improving dramatically though * •It has its consequences * –Increases symptomatic hemorrhage rate by approximately 6-7% above those who do not get TPA * –It costs approximately $2-3K per dose, though it has been proven cost effective.

Answer 103

**HEMORRHAGE** * **L**eft side hemorrhage not much you can do * If it was right side hemoorage; can do craniotomy

Answer 104

Wallenburg INFARCT – MEDULLAR INFARCT

Answer 105

VERTEBRAL DISSECTION

Answer 106

**•Cortical strokes** * –Imply large-vessel, often embolic events * –At risk for recurrence if embolic * –At risk for swelling, increased intracranial pressure and herniation syndromes * –Signs * •language abnormalities (aphasias) * •gaze preferences * •neglect syndromes * •cortical sensory findings * •personality changes **•Subcortical Strokes** * –hemibody motor or sensory symptoms without cortical involvement * –the so-called “lacunar” syndromes **•Brainstem Strokes** * –May present with consciousness ranging from completely comatose to fully awake * –Hallmark is crossed findings * –Think of brainstem longitudinally and cross-sectionally

Answer 107

Acute ischemic stroke

Answer 108

* •Do NOT ASSUME etiology * •Identify cause based upon stroke syndrome and laboratory confirmation * –Clinical stroke syndrome * –Imaging characteristics * –Risk Factors * –Laboratory Correlates

Answer 109

TO **SAVE THE PENUMBRA** * •Noninvasive Testing First * –MRI scan * –Transthoracic Echocardiogram * –Carotid Ultrasound * •Invasive Testing if no answer * –Transesophageal echocardiogram * –Traditional Angiogram * •Hypercoag testing and drug screen * –younger patients

Answer 110

* •Identify and treat risk factors * –Hypertension, Hyperlipidemia, Diabetes, Tobacco Abuse, Cardiac Disease, Obesity * •Initiate antiplatelet or anticoagulant therapy * **–Anticoagulation** is indicated for atrial fibrillation, many blood dyscrasias, and dissections (at least temporarily) * **–Antiplatelet therapy** for everyone else (unless contraindicated) * •Best to start with full dose aspirin and advance if necessary to clopidogril or aspirin/dipyridamole combination therapy. * •Tons of articles written about this **Aspirin** dosed at 325mg is generally considered the gold standard following non-embolic stroke **Clopidogrel (Plavix)** is also effective to reduce the risk of a second stroke and is generally offered if the patient has already suffered a stroke while taking full dose aspirin **Combination Aspirin and Clopidogrel** may be effective at reducing stroke risk in patients with atrial fibrillation who cannot take anticoagulation. However the combination therapy carries a little higher risk of hemorrhage when compared to using either medication alone.

Answer 111

**WATER SHED INFARCT** (like between ACA and MCA or MCA and PCA) •Patients that have an MI which leads to cardiogenic shock are more likely to develop areas and necrosis in the brain due to hypoxic-ischemic encephalopathy. * –This is due to the decrease in BP associated with the cardiogenic shock. Profound hypotension causes global cerebral ischemia. * –The areas of the brain that are most susceptible to ischemia are the pyramidal cells of the hippocampus and the Purkinje cells of the cerebellum. I * –If ischemia is profound enough, the watershed areas are susceptible to infarction as well. These zones are the borders between areas perfused by the ACA, MCA, and PCA.

Answer 112

**Apraxia** *  Apraxia is a disorder of the brain and nervous system in which a person is unable to perform tasks or movements when asked, **Alexia** (inability to read) and **Agraphia** (inability to write) * Alexia with Agraphia; o Alexia with agraphia most commonly occurs as part of an aphasia syndrome, but may rarely occur without aphasia. **Agnosia** o Agnosia is a loss of ability to recognize an entity for what it is- a percept stripped of its meanings o Examples:  Finger agnosia: can’t recognize individual fingers  Anosognosia: can’t recognize that something is malfunctioning or is deficient (seen with hemi-neglect)  Asomatognosia: can’t recognize part of your body as part of you (seen with hemi-neglect)  Prosopagnosia: can’t recognize faces  Color agnosia: can’t recognize colors  Pure word deafness (verbal auditory agnosia): can’t recognize words

Answer 113

TO **SAVE THE PENUMBRA** Emergent evaluation of stroke includes: * o Initial assessment by EMS which activates the “code stroke” process * o Once in the ED patient undergoes bedside evaluation and stroke is scored for severity based on the NIH Stroke Scale * o Blood is obtained and sent to lab for CBC, Complete Metabolic Profile, Prothrombin Time and INR. * o Initial brain imaging with a non-contrast CT is performed to assess for hemorrhage or early signs of stroke. * o If the initial non-contrast brain CT is not diagnostic for a hemorrhage then the patient will get a CT-angiogram (with contrast) of the head and neck to assess for stenosis or acute arterial vessel cut-off that may be the cause for the patient’s abrupt onset of neurologic deficit.

Neuro exam 1 part 2 Flashcards

Hematology (145 cards)