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203 Cards in this Set
- Front
- Back
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1. Four major functions of respiration
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1. Pulmonary ventilation
2. Diffusion of O2 and CO2 btwn aveoli and blood 3. Transport of O2 and CO2 in the blood and body fluids 4. Regulation of ventilation and other facets of respiration |
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2. Two ways of expanding and contracting the chest cavity
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1. Downward and upward movement of the diaphragm to lengthen or shorten the chest cavity
-normal quiet breathing 2. Elevation and depression of the ribs to increase or decrease the anteroposterior chest diameter |
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3. Contraction of the diaphragm
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Pulls lower surface of lungs downward for inspiration, relaxation of diaphragm allows for expiration
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4. Heavy breathing
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Elastic forces are not powerful enough to cause necessary rapid expiration so extra force is achieved mainly by contraction of the abdominal muscles, the abdominal contents push upward against the diaphragm compressing the lungs
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5. Muscles of inspiration
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Muscles that elevate the chest cage
1. External intercostals 2. Serratus anterior 3. SCM and scalenes |
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6. Muscles of expiration
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Muscles that depress the chest cage
1. Internal intercostals 2. Abdominal recti |
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7. Ribs angle in which direction during expiration and inspiration?
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Angle downward during expiration
Pulled upward and forward during inspiration to expand the chest cavity |
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8. What are lungs?
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An elastic structure that collapses like a balloon and expel air thru the trachea when there is no force to keep it inflated
They float in the thoracic cavity surrounded by a thin layer of pleural fluid that lubricates their movement in the pleural cavity Continual suction of excess fluid into lymphatic channels maintains a slight suction between the visceral surface of the lung pleural and parietal surface of the thoracic cavity; this holds lungs to the wall |
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9. Pleural pressure
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The pressure of the fluid in the thin space between the lung pleura and the chest wall
Normally slightly negative; approx -5 cm of H2O During normal inspiration, expansion of the chest cage pulls outward on the lungs with greater force and creates more negative pressure to an avg of -7.5 cm of H2O Events are reversed during expiration |
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10. Alveolar pressure
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The pressure of the air inside the lung alveoli when glottis is open and no inflow or outflow occurs, the pressure is equal to that of the atm; approx 0 cm H2O
To cause inward flow of air into alveoli during inspiration, pressure in the alveoli must fall to slightly below atm pressure; approx -1 cm H2O During expiration, opposite pressure occurs; approx +1 cm H2O |
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11. What is transpulmonary pressure?
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The difference btwn the alveolar pressure and pleural pressure; the pressure difference btwn that and the alveoli and that on the outer surface of the lungs.
It is a measure of the elastic forces in the lungs that tend to collapse the lungs at each instant of respiration, called the recoil pressure. |
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12. What is lung compliance?
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The extent to which the lungs will expand for each unit increase in transpulmonary pressure if allowed enough time to reach equilibrium
Avgs about 200 mL of air for each cm of water transpulmonary pressure Thus, every time the transpulmonary pressure increases 1 cm of H2O, the lung volume after 10 to 20 secs will expand to 200 mL |
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13. Compliance of the lungs thorax system compared to the lungs?
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Almost exactly 1/2 that of the lungs alone; when the lungs are expanded to high vol or compressed to low vol, limitations of the chest become extreme
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14. What determines the elastic forces of lung tissue?
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Determined by elastin and collagen fibers interwoven in the lung parenchyma
They stretch and exert force during lung expansion |
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15. What about the elastic forces caused by surface tension?
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More complex than those caused by lung tissue
When lungs are filled w/air, there's an interface btwn alveolar fluid and the air in the alveoli |
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16. Tissue forces and total lung elasticity - how do they compare?
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Tissue forces only represent 1/3 of total lung elasticity.
Transpleural pressures required to expand air filled lungs are 3x as great as those required to expand saline solution filled lungs in which surface tension effect is not present* |
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17. How does the inner surface of alveoli affect the surface tension?
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Water surface is attempting to contract, results in an attempt to force the air out of the alveoli thru the bronchi and causes the alveoli to collapse.
Net effect is to cause an elastic contractile force of the entire lungs, which is called the surface tension elastic force. |
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18. What is surfactant, and what is its purpose?
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Greatly reduces the surface tension of H2O; secreted by Type II alveolar epithelial cells which constitutes 10% of the alveoli.
Cells are granular containing lipid inclusions and surfactant is a complex mixture of several phospholipids, proteins and ions. |
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19. What is the most important phospholipid of surfactant?
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Dipalmitoylphosphatidylcholine.
Along w/several less important phospholipids, it's responsible for reducing surface tension; part of the molecule dissolves while the remainder spreads over the surface of the water in the alveoli. |
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20. Surface tension pressure in the alveoli - what is their relationship to the radius of the alveoli?
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Inversely affected by the radius of the alveolus
*The smaller the alveolus the greater the alveolar pressure caused by surface tension* Esp significant in small premature babies, many of whom have alveoli with a radius less than one quarter of an adult person. Additionally, surfactant does not begin to be secreted until the sixth and seventh month of gestation, and sometimes even later than that. |
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21. Three types of work performed by inspiratory muscles under resting conditions...
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1. That required to expand the lungs against lung and chest elastic forces (compliance work)
2. That required to overcome the viscosity of the lung and chest wall structures (tissue resistance work) 3. That required to overcome airway resistance to movement of air into the lungs (airway resistance work) |
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22. What is spirometry?
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Record of the volume movement of air into and out of the lungs. Consists of a drum inverted over a chamber of H2O with the drum counterbalanced by a weight.
In the drum is a breathing gas and a tube connects the mouth with the gas chamber. Drum rises and falls with inspiration/expiration and records levels. |
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23. What are the pulmonary volumes?
What are the four important ones to know? |
When added together, they equal the max volume to which the lungs can be expanded.
1. Tidal volume 2. Inspiratory reserve volume 3. Expiratory reserve volume 4. Residual volume |
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24. What is the tidal volume?
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The volume of air inspired or expired with each normal breath.
It amounts to about 500 mL in the adult male. |
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25. What is the inspiratory reserve volume?
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The inspiratory reserve volume is the extra volume of air that can be inspired over and above the normal tidal volume when the person inspires w/FULL FORCE.
It amounts to about 3,000 mL |
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26. What is the expiratory reserve volume?
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The expiratory reserve volume is the maximum extra volume of air that can be expired by forceful expiration after the end of a normal tidal expiration.
It amounts to about 1,100 mL |
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27. What is the residual volume?
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The residual volume is the volume of air remaining in the lungs after the most forceful expiration.
It amounts to about 1,200 mL |
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28. What are the pulmonary capacities?
What are the 4 important pulmonary capacities? |
Pulmonary capacities combine two or more of the pulmonary volumes to describe events in the pulmonary cycle.
These are: 1. Inspiratory capacity 2. Functional residual capacity 3. Vital capacity 4. Total lung capacity |
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29. What is the inspiratory capacity?
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The inspiratory capacity is the (tidal volume + inspiratory reserve volume).
This is the amount of air a person can breathe in the beginning at the normal expiratory level and distends the lungs to the maximum amount. It amounts to about 3,500 mL |
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30. What is the functional residual capacity?
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The functional residual capacity equals the (expiratory reserve volume + residual volume).
The amount of air that remains in the lungs at the end of normal expiration. It amounts to about 2,300 mL |
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31. What is the vital capacity?
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The vital capacity = (inspiratory reserve volume + tidal volume + expiratory reserve volume).
This is the maximum amount of air a person can expel from the lungs after first filling the lungs to the maximum extent and then expiring to the maximum extent. It is approx equal to 4,600 mL |
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32. What is the total lung capacity?
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Total lung capacity = (vital capacity + residual volume)
Maximum volume to which the lungs can be expanded with the greatest possible effort . Approx equal to 5,800 mL |
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33. Men vs. women pulmonary volumes and capacities
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20-25% less in women for pulmonary volumes and capacities
Greater in large and athletic people than in small and asthenic people |
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34. What is the minute respiratory volume?
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The minute respiratory volume is the total amount of new air moved into the respiratory passages each minute
Minute respiratory volume = (tidal volume x respiratory rate/min) |
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35. What is the importance of pulmonary ventilation?
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To continually renew air in the gas exchange areas of the lungs, where air is in the proximity to the pulmonary blood.
NO SHIT. |
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36. What is dead space?
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Air a person breathes in that never reaches the gas exchange sites but simply fills respiratory passages where gas exchange does not occur such as the nose, pharynx and trachea
It is expired first before any of the air from the alveoli reaches the atm. Normal dead space air in a young adult male is about 150 mL and increases slightly w/age. |
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37. What is anatomic dead space?
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The anatomic dead space is the volume of all the space of the respiratory system OTHER than the alveoli and their other closely related gas exchange areas.
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38. What is physiologic dead space?
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Physiologic dead space = anatomic dead space BUT INCLUDES the alveolar dead space in the total measurement of dead space.
In a normal person, anatomic and physiologic dead spaces are nearly equal; this is not the case with partially functional alveoli; the physiological dead space may be 10x that of the anatomic dead space |
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39. What is the alveolar ventilation per minute?
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The alveolar ventilation per minute is the total volume of new air entering the alveoli and adjacent gas exchange areas each minute.
It is equal to the respiratory rate times the amount of new air that enters these areas with each breath. Approx 4,200 mL/min ***One of the major factors determining the concentrations of O2 and CO2 in the alveoli*** |
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40. How is the composition of the bronchioles vs. respiratory bronchioles different?
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Wall of bronchioles are almost entirely made of smooth muscle.
The respiratory bronchioles function in gas exchange and are composed of mainly pulmonary epithelium and underlying fibrous tissue. |
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41. The greatest amt of air resistance flow occurs where?
How does this change under diseased states? |
In the larger bronchioles and bronchi near the trachea.
This is because there are relatively fewer larger bronchi in comparison to the many terminal bronchioles, so greater quantities of air have to pass thru the larger vs. smaller ones (under normal conditions). In disease conditions, the smaller bronchioles play a larger role in airway resistance b/c they are easily occluded. |
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42. What is the nervous control of bronchiolar musculature?
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Norepinephrine and epinephrine released in the blood thru sympathetic stimulation stimulate beta receptors and cause dilation of the bronchiole tree.
Parasympathetic nerves secrete ACh which causes mild to moderate constriction of the bronchioles. |
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43. What are 3 respiratory functions performed by the nasal cavities?
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1. Warm the air by the conchae, septum
2. Almost complete humidification 3. Partially filter particles Air conditioning function is the combined result |
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44. What is turbulent precipitation?
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The turbulent precipitation occurs when the air passing thru the nasal passageways hits many obstructing vanes, the conchae, septum, and the pharyngeal wall.
Each time air hits one of these obstructions, it must change direction; particles suspended in the air have more mass and cannot change direction as rapidly causing them to be entrapped in the mucus coating and then is transported by the cilia to be excreted. |
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45. What is gravitational precipitation?
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Particles between 1 and 5 micrometers settle in the small bronchioles due to inability to be removed by the turbulence mechanism.
These particles become entrapped in the alveoli and are removed by alveolar macrophages |
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46. Speech involves not only the respiratory system but also...?
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1. Specific speech nervous control centers in cerebral cortex
2. Respiratory control centers of the brain 3. Articulation and resonance structures of the mouth and nasal cavities |
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47. Speech is composed of what two mechanical functions?
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1. Phonation achieved by larynx
2. Articulation achieved by structures of the mouth |
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48. What are the major organs of articulation?
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The lips, tongue, and soft palate.
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49. What are the major organs of resonation?
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The mouth, nose and associated nasal sinuses, the pharynx, and even the chest cavity.
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50. Blood-borne invasion takes place across what two places to get into the CNS?
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1. The BBB to cause encephalitis
2. The blood-CSF barrier to cause meningitis |
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51. What is the BBB? What is the blood-CSF barrier?
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The BBB consists of tightly joined endothelial cells surrounded by glial processes, while the brain-CSF barrier at the choroid plexus consists of endothelium with fenestrations, and tightly joined choroid plexus epithelial cells.
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52. What are three ways in which microbes can traverse these barriers?
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1. Growing across, infecting the cells that comprise the barrier
2. Being passively transported across in intracellular vacuoles 3. Being carried across by infected WBCs |
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53. Why is CNS invasion rare?
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Because most microorganisms fail to pass from blood to the CNS across the natural barriers. A large variety of viruses can grow and cause disease if introduced directly into the brain, but circulating viruses generally fail to invade, and CNS involvement by polio, mumps, rubella, or measles viruses is seen in only a very small proportion of infected individuals.
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54. What about invasion of the CNS via peripheral nerves?
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Invasion of the CNS via peripheral nerves is a feature of herpes simplex, varicella-zoster and rabies virus infections.
HSV and VZV infections travel up axons using the normal retrograde transport mechanisms that can move virus particles at a rate of about 200 mm/day, to reach the dorsal root ganglia. Rabies virus infects muscle fibers and muscle spindles after the virus binds to the nicotinic ACh receptor. It then enters peripheral nerves and travels to the CNS to reach glial ells and neuronsm where it multiplies. |
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55. What is the body's response to invasion of the CNS?
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CSF cell counts increase in response to infection.
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56. What is aseptic meningitis?
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This is reflected by an increase in lymphocytes, mostly T cells, and monocytes in the CSF. A slight increase in protein also occurs, the CSF remaining clear. This is called aseptic meningitis.
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57. What is septic meningitis?
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The response to pyogenic bacteria shows a more spectacular and more rapid increase in polymorphonuclear leukocytes and proteins, so that the CSF becomes visibly turbid. This condition is termed septic meningitis.
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58. What is the preference of viruses for neural cells?
What about bacteria? |
Polio and rabies viruses, for instance, invade neurons, whereas JC virus invades olidodendrocytes.
B/c there is very little extracellular paces, spread is mostly direct from cell to cell along established nervous pathways. Invading bacteria and protozoa generally induce more dramatic inflammatory events, which limit local spread so that infection is soon localized to form abscesses. |
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59. What is postvaccinial encephalitis?
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Infiltrating B cells produce antibody to the invading microorganism, and T cells react with microbial antigens to release cytokines that attract and activate other T cells and macrophages.
The pathologic condition evolves over the course of several days and occasionally, when partly controlled by host defenses, over the course of years, e.g., subacute sclerosing panencephalitis (SSPE) caused by measles, which has both a virological and immunological pathogenesis. |
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60. Does CNS invasion facilitate the spread of infection?
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Only rarely does CNS invasion assist in the transmission of infection.
The only time when it does are: 1. When dorsal root ganglion neurons are invaded as an essential step in establishing latency (HSV and VZV). 2. In the case of rabies,w here CNS invasion in the animal host is necessary. |
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61. What are two reasons for why rabies requires CNS invasion in the animal host?
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1. It enables spread of the virus from the CNS down peripheral nerves to the salivary glands, from which transmission takes place.
2. Invasion of the limbic system of the brain causes a change in behavior of the infected animal so that it becomes less retiring, more aggressive, and more likely to bite, thus transmitting the infection. Invasion of the limbic system can be regarded as a fiendish strategy on the part of rabies virus to promote its own transmission and survival. |
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62. What is acute bacterial meningitis?
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Acute bacterial meningitis is a life-threatening infection, needing urgent specific treatment.
Bacterial meningitis is more severe but less common than viral meningitis. Prior to the '90's, H. influenzae type b (Hib) was responsible for most cases. However, the intro of new vaccines into childhood immunization regimens has lowered overall Hib incidence in favor of N. meningitidis and S. pneumoniae, which are now responsible for most bacterial meningitis. |
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63. What is meningococcal meningitis?
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Neisseria meningitidis is a Gram-negative diplococcus, which has an additional polysaccharide capsule that is antigenic and by which the serotype of N. meningitidis can be recognized.
The bacteria are carried asymptomatically in the population, up to 20% dependent on geographic location, and are attached by their pili to the epithelial cells in the nasopharynx. |
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64. Who is susceptible to N. meningitidis infection?
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People possessing specific complement-dependent bacterial antibodies to capsular antigens are protected against invasion.
Those with C5-C9 complement deficiencies show increased susceptibility to bacteremia. Young children who have lost the antibodies acquired from their mother, and adolescents who have not previously encountered the infecting serotype, and therefore have no type-specific immunity, are those most often infected. |
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65. How is N. meningitidis spread?
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Person to person spread takes place by droplet infection, and is facilitated by other respiratory infections, often viral, that cause increased respiratory secretions. Thus, conditions of overcrowding and confinement such as prisons, military barracks, and colleges contribute to the frequency of infection in populations.
During outbreaks of meningococcal meningitis, which most freq occur in late winter and early spring, the carrier rate may reach 60-80%. |
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66. What serotypes of N. meningitidis dominate in more resource rich countries?
What serotypes are targeted by vaccines? |
Serotyeps B, C, and Y tend to predominate in more resource-rich countries, whereas serotypes A and W-135 are more common in less developed regions.
Available vaccines target serotypes A, C, Y, and W-135 but not B. |
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67. What are the clinical features of meningococcal meningitis?
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After an incubation period of 1-3 days, the onset of emningococcal meningitis is sudden with a sore throat, headache, drowsiness, and signs of meningitis which include fever, irritability, neck stiffness and photophobia.
*There is often a hemorrhagic skin rash with petechiae, reflecting the associated septicemia.* In about 35% of pts, this septicemia is fulminating, with complications due to DIC, endotoxemia and shock, and renal failure. Mortality from meningococcal meningitis reaches 100% if untreated, but remains around 10% even if treated. In addition, serious sequelae such as permanent hearing loss may occur in some survivors. |
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68. What is the Waterhouse-Friedrichsen syndrome?
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In the most severe cases of meningococcal meningitis, there is an acute Addisonian crisis, with bleeding into the brain and adrenal glands referred to as Waterhouse-Friedrichsen syndrome.
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69. How is a diagnosis of acute meningitis made?
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A Dx is usually suspected on clinical exam. Preliminary microscopy results involving white cell counts and Gram-staining for bacteria should be available within an hour of receipt of the CSF sample. Laboratory identification of the bacterial cause of acute meningitis is essential so that appropriate antibiotic therapy can be given and prophylaxis of contacts initiated.
Serology is not helpful in the Dx b/c the infection is too acute for an antibody response to be detectable. Bacterial meningitis is a medical emergency and antibiotic therapy (penicillin or ampicillin) should be instigated if the Dx is suspected. |
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70. Close contacts of a family member with bacterial meningitis should be given what for prophylaxis?
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Close contacts should be given rifampin for 2 days.
Penicillin is not used for prophylaxis b/c it does not eliminate nasopharyngeal carriage of meningococci. |
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71. What is haemophilus meningitis?
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Type b H. influenzae causes meningitis in infants and young children.
H. influenzae is a Gram-negative coccobacillus. There are six types (a-f), distinguishable by their capsular polysaccharides. |
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72. What strains of H. influenzae are most common?
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Unencapsulated strains are common and are present in the throat of most healthy people.
The capuslated type b, a common inhabitant of the respiratory tract of infants and young children, very occasionally invades the blood and reaches the meninges. |
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73. How does H. influenzae infect?
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Maternal antibody protects the infant up to 3-4 mos of age, but as it wanes, there is a window of susceptibility until the child produces his/her own antibody.
Anticapsular antibodies are good opsonins, which allow the bacteria to be phagocytosed and killed, but children do not generally produce them until 2-3 years of age, possibly b/c these antibodies are T independent. In addition to the capsule, H. influence has several other virulence factors. |
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74. What are the clinical signs and symptoms of acute H. influenza meningitis?
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The incubation period of H. influenzae meningitis is 5-6 days, and the onset is often more insidious than that of meningococcal or pneumococcal meningitis. The condition is less freq fatal, but, as with meningococcal infection, serious sequelae such as hearing loss, delayed language development, and mental retardation and seizures may occur.
General diagnostic features are the same as for meningococcal meningitis. It is important to note that the organisms may be difficult to see in Gram-stained smears of CSF, particularly if they are present in small numbers. |
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75. What types of H. influenzae vaccines are effective?
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H. influenzae type b (Hib) vaccine is effective for children from 2 mos of age and upwards. Close contacts of pts are sometimes given rifampicin prophylaxis.
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76. What is pneumococcal meningitis?
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Streptococcus penumoniae is a common cause of bacterial meningitis, particularly in children and the elderly.
Strep. pneumonia is a capsulate Gram-positive coccus carried in the throats of many healthy individuals. Little is known about its virulence attributes apart from its polysaccharide capsule, and the pneumococcus remains a major cause of morbidity and mortality. |
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77. What type of people are infected with pneumococcal meningitis?
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Invasion of the blood and meninges is a rare event, but is more common in the very young (<2 years of age), in the elderly, in those with sickle cell disease, in debilitated or splenectomized pts and following head trauma.
Susceptibility to infection is associated with low levels of antibodies to capsular polysaccharide antigens: antibody opsonizes the organism and promotes phagocytosis, thereby protecting the host from invasion. However, this protection is type-specific and there are more than 85 different capsular types. |
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78. How is pneumococcal meningitis treated?
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Treatment is with penicillin (or ceftriaxone or chloramphenicol).
*Since penicillin-resistant pneumococci have been observed worldwide, attention must be paid to the antibiotic susceptibility of the infecting strain, and empiric chemotherapy usually involves a combo of vancomycin and either cefotaxime or ceftriaxone. |
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79. What is listeria monocytogenes meningitis?
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Listeria monocytogenes is a Gram-positive coccobacillus and an important cause of meningitis in immunocompromised adults, especially in renal transplant and CA pts.
It also causes intrauterine infections and infections of the newborn. L. monocytogenes is less susceptible than Strep. pneumoniae to penicillin, and the recommended Tx is with a combo of penicillin or ampicillin with gentamicin. |
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80. What types of newborns are at risk of neonatal meningitis?
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In general, neonates, especially those with low birth weight, are at increased risk for meningitis b/c of their immature immunological status.
Although mortality rates due to neonatal meningitis in resource-rich countries are declining, the problem is still serious. |
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81. What causes neonatal meningitis?
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Neonatal meningitis can be caused by a wide range of bacteria, but the most frequent are group B hemolytic streptococci, and E. coli.
This may occur by routes such as nosocomial infection. However, the infant may also be infected from the mother. |
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82. What are the consequences of neonatal meningitis?
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Neonatal meningitis often leads to permanent neurologic sequelae such as cerebral or cranial nerve palsy, epilepsy, mental retardation or hydrocephalus. This is partly b/c the clinical Dx of meningitis in the neonate is difficult, perhaps with no more specific signs than fever, poor feeding, vomiting, respiratory distress or diarrhea.
In addition, due to the possible range of etiological agents, 'blind' antibiotic therapy in the absence of susceptibility tests may not be optimal, and adequate penetration of the antibiotic into the CSF is also an issue. |
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83. What are the characteristics of group B streptococci neonatal meningitis at or soon after birth (< 7 days)?
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1. Generalized infection including bacteremia, pneumonia, and meningitis
2. Can be all serotypes but meningitis mostly due to type III 3. Approx 60% fatal 4. Caused by PPROM, heavily colonized mother lacking specific antibody, pre-term delivery, prolonged labor, obstetric complications |
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84. What are the characteristics of group B streptococci neonatal meningitis with later onset (1 week to 3 months)?
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1. Predominantly meningitis
2. 90% are type III serotype 3. Approx 20% are fatal 4. Caused by lack of maternal antibody, exposure to cross-infection from heavily colonized babies, and poor hygiene in nursery. |
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85. What is the morphology of bacterial meningitis?
1/2 |
The normally clear CSF is cloudy and sometimes frankly purulent. In acute meningitis, an exudate is evident within the leptomeninges over the surface of the brain. The meningeal vessels are engorged and stand out prominently. The location of the exudate varies depending on the microorganisms.
H. influenzae meningitis for example, is usually basal, whereas in pneumococcal meningitis, it is often densest over the cerebral convexities near the sagittal sinus. From the areas of greatest accumulation, tracts of pus can be followed along blood vessels on the surface of the brain. When the meningitis is fulminant, the inflammation may extend to eh ventricles, producing ventriculitis. |
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86. What is the morphology of bacterial meningitis?
2/2 |
On microscopic exam, neutrophils fill the entire subarachnoid space in severely affected areas and are found predominantly around the leptomeningeal blood vessels in less severe cases.
In untreated meningitis, Gram stain reveals varying numbers of the causative organism, although they are frequently not demonstrable in treated cases. |
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87. What is the morphology of fulminant meningitis?
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In fulminant meningitis, the inflammatory cells infiltrate the walls of the leptomeningeal veins with potential extension of the inflammatory infiltrate into the substance of the brain (focal cerebritis). Phlebitis may also lead to venous occlusion and hemorrhagic infarction of the underlying brain.
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88. What may follow pyogenic meningitis?
What is chronic adhesive arachnoiditis? |
Leptomeningeal fibrosis and consequent hydrocephalus may follow pyogenic meningitis, although if it is treated early, there may be little remaining evidence of the infection.
In some infections, particularly in pneumococcal meningitis, large quantities of the capsular polysaccharide of the organism produce a particularly gelatinous exudate that encourages arachnoid fibrosis, called chronic adhesive arachnoiditis. |
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89. What would the spinal tap reveal in septic meningitis?
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A spinal tap yields cloudy or frankly purulent CSF, under increased pressure, with as many as 90,000 neutrophils/mm^3, a raised protein level, and a markedly reduced glucose content.
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90. What is tuberculous meningitis?
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Pts with tuberculous meningitis always have a focus of infection elsewhere, but approximately 25% may have no clinical or historic evidence of such an infection.
In >50% of cases, meningitis is associated with acute miliary tuberculosis. In areas w/a high prevalence of tuberculosis, meningitis tends to be most commonly seen in children from 0-4 years of age. However, in areas where tuberculosis is less frequent, most meningitis cases are in adults. |
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91. What are the signs and symptoms of tuberculous meningitis?
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Tuberculous meningitis usually presents with a gradual onset over a few weeks.
There is a gradual onset of generalized illness beginning with malaise, apathy and anorexia and proceeding within a few weeks to vomiting, photophobia, neck stiffness and impairment of consciousness. Occasionally, the onset is more rapid and may be mistaken for a subarachnoid hemorrhage. |
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92. What are the CSF findings in tuberculous meningitis?
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There is only a moderate CSF pleocytosis made up of mononuclear cells or a mixture of polymorphonuclear and mononuclear cells.
The protein level is elevated, often strikingly so, and the glucose content typically is moderately reduced or normal |
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93. What is the morphology of tuberculous meningitis?
1/2 |
On macroscopic exam, the subarachnoid space contains a gelatinous or fibrinous exudate, most often at the base of the brain, obliteratin the cisterns and encasing cranial nerves. There may be discrete, white granules scattered over the leptomeninges.
*The most common pattern of involvement is a diffuse meningoencephalitis. On microscopic exam, there are mixtures of lymphocytes, plasma cells, and macrophages. Florid cases show well-formed granulomas, often with caseous necrosis and giant cells. |
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94. What is the morphology of tuberculous meningitis?
2/2 |
Arteries running thru the subarachnoid space may show obliterative endarteritis with inflammatory infiltrates in their walls and marked intimal thickening.
Organisms can often be seen with acid-fast stains. The infectious process may spread to the choroid plexuses and ependymal surface, traveling thru the CSF. |
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95. What is a tuberculoma?
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Another manifestation of tuberculous meningitis is the development of a single (or often multiple) well-circumscribed intraparenchymal mass (tuberculoma) which may be associated with meningitis.
A tuberculoma may be up to several cm in diameter, causing significant mass effect. On microscopic exam, there is usually a central core of caseous necrosis surrounded by a typical tuberculous granulomatous reaction; calcification may occur in inactive lesions. |
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96. What are the most serous complications of chronic tuberculous meningitis?
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The most serious complications are arachnoid fibrosis, which may produce hydrocephalus, and obliterative endarteritis, which may produce arterial occlusion and infarction of underlying brain. B/c the process involves the spinal cord subarachnoid space, spinal roots may also be affected.
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97. What about infection by mycobacterium tuberculosis in pts with AIDS?
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Tuberculous infection in pts with AIDS is often similar to those of non-AIDS pts, but there may be less host reaction.
HIV-positive pts are also at risk for infection by M. avium-intracellulare, usually in the setting of disseminated infection. When this occurs, the lesions may consist of confluent sheets of macrophages filled with organisms, and minimal granulomatous reaction. |
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98. What is fungal meningitis?
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Cryptococcus neoformans and Coccidiodes immitis can invade the blood from a primary site of infection in the lungs and thence to the brain to cause meningitis.
Cryptococcus has a marked tropism for the CNS and is the major cause of fungal meningitis. C. neoformans occurs as two varieties, each with two serotypes. |
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99. What is cryptococcus neoformans meningitis?
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C. neoformans meningitis is seen in pts with depressed cell-mediated immunity. It therefore occurs in individuals with AIDS and other immunosuppressive conditions.
The onset is usually slow, over days or weeks. The capsulate yeasts can be seen in India-ink stained preparations of CSF and can be cultured. The CSF may have few cells but a high concentration of protein. |
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100. What is the morphology of cryptococcal meningitis?
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With cryptococcal infection, the brain shows a chronic meningitis affecting the basal leptomeninges, which are opaque and thickened by reactive connective tissue and may obstruct the outflow of CSF and give rise to hydrocephalus.
*Sections of the brain disclose a gelatinous material w/in the subarachnoid space and small cysts w/in the parenchyma ("soap bubbles"), which are essentially prominent in the basal ganglia in the distribution of the lenticulostriate arteries. Parenchyma lesions consist of aggregates of organisms w/in expanded perivascular (Virchow-Robin) spaces associated with minimal or absent inflammation or gliosis. |
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101. What is coccidioides immitis meningitis?
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C. immitis infection is common in particular geographic locations. These locations are notably Southwest, USA, Mexico, and South America. CNS infection occurs in < 1% of infected individuals, but is fatal unless treated. It may be part of the generalized disease or may represent the only extrapulmonary site.
The organisms are rarely visible in the CSF, and cultures are positive in < 50% of cases, but the Dx can be made by demonstrating complement-fixing antibodies in the serum. Tx with amphotericin B, fluconazole, or miconzole is recommended. |
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102. What are the three main patterns of fungal infection in the CNS?
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1. Chronic meningitis
2. Vasculitis 3. Parenchymal invasion |
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103. Which fungi commonly produce vasculitis?
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Vasculitis is most frequently seen with Mucor and Aspergillus, both of which have a marked predilection for invasion of blood vessel walls, but it occasionally occurs with other organisms, such as Candida.
The resultant vascular thrombosis produces infarction that is often strikingly hemorrhagic and that subsequently becomes septic from ingrowth of the causative fungus. |
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104. Which fungi commonly produce parenchymal invasion?
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Parenchymal invasion, usually in the form of granulomas or abscesses, can occur w/most of the fungi and often coexists with meningitis.
The most commonly encountered fungi invading the brain are Candida and Cryptococcus. Candida usually produces multiple microabscesses, with or without granuloma formation. |
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105. What is the protozoa Naegleria - meningitis?
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The free-living amoeba Naegleria can multiply in stagnant fresh water in warm countries, especially in the sludge at the bottom of lakes and swimming pools. If inhaled, they can reach the meninges via the olfactory tract and cribiform plate.
Primary amebic meningoencephalitis cause by Naegleria affects healthy individuals with no obvious defect in immunity. The disease shows a rapid onset, and the mortality rate is high due to a rapidly fatal necrotizing encephalitis. |
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106. What does Naegleria look like under the microscope?
How is it treated? |
Under the microscope, Naegleria appear as slowly motile amoebae on careful exam of a fresh wet sample of CSF.
Amphotericin B, with micanozole and rifampin is the treatment. |
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107. What about Acanthamoeba meningitis?
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Acanthamoeba spp. are widespread in the environment. They more commonly affect those who are already unwell or immunocompromised and are thought to enter via the skin or the respiratory tract.
Acanthamoeba causes a chronic condition (granulomatous amebic encephalitis). Acanthamoeba are rarely seen in the VSF but can be visualized in brain biopsies via staining with methenamine silver or PAS stains. They also grow well in cultures prepared from tissue biopsies. |
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108. What is viral meningitis?
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Viral meningitis is the most common type of meningitis. It is a milder disease than bacterial meningitis, with headache, fever and photophobia, but less neck stiffness.
The CSF is clear in the absence of bacteria, and the cells are mainly lymphocytes, although polymorphonuclear leukocytes may be present in the early stages. |
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109. What viruses causes meningitis?
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There are five groups of human enteroviruses which include the echoviruses, coxsackie Group A and B viruses, and the three polioviruses.
Infection is commonly asymptomatic, and therefore and enterovirus isolated from the throat or stool of a child w/mild meningitis may be of no help. However, the enteroviruses are common causes of seasonal aseptic meningitis. In contrast to bacterial meningitis, viral meningitis usually has a benign course, and complete recovery is the rule. |
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110. What is acute aseptic viral meningitis?
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The clinical course is less fulminant than that of pyogenic meningitis, and the CSF findings also differ between the two conditions.
*In aseptic meningitis, there is a lymphocytic pleocytosis, the protein elevation is only moderate, and the sugar content is nearly always normal. |
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111. What is drug-induced aseptic meningitis?
What about other causes of aseptic meningitis? |
A true noninfectious process has been associated with some classes of medications, including NSAIDs and antibiotics; this entity is has been termed drug-induced aseptic meningitis.
An aseptic meningitis-like picture may also develop subsequent to rupture of an epidermoid cyst into the subarachnoid space or the introduction of a chemical irritant. In these cases, the CSF is sterile, there is pleocytosis with neutrophils and a raised protein level, but the sugar content is usually normal. |
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112. What is encephalitis?
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Encephalitis is usually caused by viruses, but there are many cases where the infectious etiology is not identified. Characteristically, there are signs of cerebral dysfunction, as the substance of the brain is affected, unlike meningitis where the lining of the brain is inflamed.
Someone with encephalitic illness will present with abnormal behavior, seizures, and altered consciousness, often with nausea, vomiting, and fever. |
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113. What are the non-viral causes of encephalitis?
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Toxoplasma gondii and C. neoformans can also cause life-threatening encephalitis or meningoencephalitis. This is particularly likely in those with defective cell-mediated immunity, and cerebral malaria as a complication of Plasmodium falciparum infection is frequently fatal.
Encephalitis may occur in Lyme disease and Legionnaire's disease, but the relative importance of bacterial invasion, bacterial toxins and immunopathology is unknown. |
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114. What are the most characteristic histologic features of viral encephalitis?
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***The most characteristic histologic features of viral encephalitis are perivascular and parenchymal mononuclear cell infiltrates (lymphocytes, plasma cells, and macrophages), glial cell reactions (including the formation of microglial nodules), and neuronophagia.***
Direct indications of viral infection are the presence of viral inclusion bodies and, most important, the identification of viral pathogens by ultrastructural immunocytochemical, and molecular methods. |
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115. What is HSV encephalitis (HSE)?
How are HSV infections of the CNS different from those in older children and adults? |
HSE is the most common form of severe sporadic acute focal encephalitis. It is thought that the incidence of HSE in the USA is about 1/250,000 - 1/500,000 per year.
A distinction is made between HSV infections of the CNS during the neonatal period and those in older children and adults. Neonates may acquire a primary and disseminated infection with diffuse encephalitis after vaginal delivery from a mother shedding HSV-2 in the genital tract. Most HSE seen in older children and adults is due to HSV-1, of which are due to virus reactivation in the trigeminal ganglia, the infection then passing back to the temporal lobes of the brain, and the minority are due to a primary infection. |
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116. What is HSV-1 encephalitis?
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HSV-1 produces an encephalitis that occurs in any age group but is most common in children and young adults.
Only about 10% of the pts have a history of prior herpes. The most commonly observed clinical presenting symptoms in HSE are alterations in mood, memory, and behavior. Herpetic skin or mucosal lesions may be present. The Dx is indicated by finding temporal lobe enhancement using CT and MRI scan. HSV DNA detection should be carried out on a CSF sample using PCR. |
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117. What is the morphology of HSV-1 encephalitis?
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HSV-1 encephalitis starts in, and most severely involves, the inferior and medial regions of the temporal lobes and the orbital gyri of the frontal lobes. The infection is necrotizing and often hemorrhagic in the most severely affected regions.
*Perivascular inflmmatory infiltrates are usually present, and Cowdry type A intranuclear viral inclusion bodies may be found in both neurons and glia.* In pts with slowly evolving HSV-1 encephalitis, there is more diffuse involvement of the brain. |
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118. What is the clinical course of HSV-1 encephalitis?
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The 70% mortality rate in untreated pts is greatly reduced by early and prolonged treatment with IV aciclovir. The 21 day treatment course is important as relapse can occur.
In some individuals, HSV-1 encephalitis follows a subacute course with clinical manifestations (weakness, lethargy, ataxia, seizures) that evolve during a more protracted period. |
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119. What about HSV-2 encephalitis?
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HSV-2 also infects the nervous system and usually manifests in adults as a meningitis.
A generalized and severe encephalitis develops in as many as 50% of neonates born by vaginal delivery to women with active primary HSV genital infections. The dependence on route of delivery indicates that the infection is acquired during passage thru the birth canal rather than transplacentally. In AIDS pts, HSV-2 may cause an acute, hemorrhagic, necrotizing encephalitis. |
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120. What other herpesviruses less commonly cause encephalitis?
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With VZV, encephalitis generally occurs as a sequel to reactivation, and with CMV either during primary infection in utero or reactivation as a complication of immunodeficiency, for example in AIDS.
HHV6 encephalitis has also been reported in immunosuppressed pts. Finally, B virus is a Cercopicthecine herpesvirus of macaque monkeys that does not really affect the animal but can cause a severe and fatal encephalitis in humans when bitten or scratched by an infected monkey. The wound should be cleaned immediately and antiviral prophylaxis is recommended. |
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121. What are the features of VZV encephalitis?
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Herpes zoster reactivation is usually a self-limited process, but there may be a persistent postherpetic neuralgia syndrome n up to 10% of pts. Overt CNS involvement with herpes zoster is much rarer but can be more severe.
Herpes zoster has been associated with a granulomatous arteritis. In immunosuppressed pts, it may cause an acute encephalittis with numerous sharply circumscribed lesions characterized by demyelination followed by necrosis. Inclusion bodies can be found in glia and neurons. |
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122. What is the most common opportunistic viral pathogen in pts with AIDS, affecting the CNS in 15-20% of cases?
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CMV
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123. What is the morphology of CMV encephalitis?
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In the immunosuppressed individual, the most common pattern of involvement is that of a subacute encephalitis, which may be associated with CMV inclusion-bearing cells. *Although any type of cell within the CNS (neurons, glia, ependyma, endothelium) can be infected by CMV, there is a tendency for the virus to localize in the paraventricular subependymal regionsof the brain.* This results in a severe hemorrhagic necrotizing ventriculoencephalitis and a choroid plexitis. The virus can also attack the lower spinal cord and roots, producing a painful radiculoneuritis.
Prominent cytomegalic cells with intranuclear and intracytoplasmic inclusion can be readily identified on microscopic exam. |
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124. What is poliomyelitis?
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Poliovirus used to be a common cause of encephalitis. Poliovirus is a member of the picorna group of enteroviruses. In nonimmunized individuals, poliovirus infection causes a subclinical or mild gastroenteritis. In a small fraction of the vulnerable population, however, it secondarily invades the nervous system.
After an initial 1-4 days of fever, sore throat and malaise, meningeal signs and symptoms appear, followed by involvement of motor neurons and paralysis. |
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125. What is the paralysis like in poliomyelitis?
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When the disease affects the spinal cord with loss of motor neurons, it produces a flaccid paralysis with muscle wasting and hyporeflexia in the corresponding region of the body- the permanent neurologic residue of poliomyelitis.
In the acute disease, death can occur from paralysis of the respiratory muscles, and a myocarditis sometimes complicates the clinical course. Permanent cranial nerve (bulbar) weakness is rare, as is any evidence of encephalitis, but severe respiratory compromise and an important cause of long-term morbidity. At least 75% of paralytic cases are due to type 1 polioviruses. |
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126. What is postpolio syndrome?
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A late neurologic syndrome can develop in pts affected by poliomyelitis who had been stable during intervening years (postpolio syndrome).
This syndrome, which typically develops 25-35 years after the resolution of the initial illness, is characterized by progressive weakness associated with decreased muscle mass and pain, and has an unclear pathogenesis. |
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127. What is the morphology of poliomyelitis?
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Acute cases show mononuclear cell perivascular cuffs and neuronophagia of the anterior horn motor neurons of the spinal cord. In situ reverse transcriptase PCR has shown poliovirus RNA in anterior horn cell motor neurons.
The inflammatory reaction is usually confined to the anterior horns but may extend into the posterior horns, and the damage is occasionally severe enough to produce cavitation. The motor cranial nuclei are sometimes involved. |
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128. What is enterovirus-71?
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Enterovirus-71-associated hand, foot and mouth epidemic resulted in a high rate of neurologic complications.
In 1998, there was a large outbreak of enterovirus 71 hand, foot and mouth infection in Taiwan, in which most of the 405 pts were children under 5 years of age, with a mortality rate of 19%. The most severely affected children had brainstem involvement, and many were left with permanent neurologic sequelae. |
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129. What about paramyxoviral infections, such as mumps?
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Mumps virus is a common cause of mild encephalitis.
Asymptomatic CNS invasion may be common b/c there are increased numbers of cells in the CSF in about 50% of pts with parotitis; on the other hand, meningitis and encephalitis are often seen without parotitis. |
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130. What is Nipah virus encephalitis?
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Nipah virus encephalitis is an emerging zoonotic paramyxovirus infection. There was a serious outbreak in Malaysia among pig farm workers in 1998. The virus was transmitted to humans by close contact with infected pigs, probably by aerosol.
The Island flying fox, Pteropus hypomelanus, a fruit bat, was the likely reservoir as virus could be found in the urine and saliva of infected bats. The pigs were infected having eaten food contaminated by fruit bat secretions. |
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131. What causes rabies encephalitis?
What are the 7 different genotypes? |
The causative agent of rabies is rabdovirus, a bullet-shaped single-stranded RNA virus.
The Lyssavirus genus sits within the Rhabdoviridae family and there are seven genotypes. A: *Type 1 occurs worldwide and is the classical rabies virus B: Types 2, 3, and 4 are the African Lagos, Mokola and Duvenhage bat viruses respectively C: Types 5 and 6 are the European bat Lyssaviruses (EBLV) 1 and 2, respectively D: Type 7 is the Australian bat Lyssavirus. |
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132. How is rabies virus spread?
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The virus is excreted in the saliva of infected dogs, foxes, jackals, wolves, skunks, racoons and vampire and other bats, and transmission to humans follows a bite or salivary contamination of other types of skin abrasions or wounds. Some species of animal, suh as foxes, are more infectious than others, b/c larger amts of virus are present in their saliva.
The infection is eventually fatal, although the course of the disease varies considerably between species. |
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133. Who can become infected by rabies?
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The virus can infect all warm-blooded animals. Rabies from vampire bats causes 1 million deaths per year in cattle. Dogs transmit most of the 35,000 cases of human rabies that occur in the world each year.
In the US, the incidence of human rabies has been falling since the 40's and 50's, when most cases followed exposure to infected dogs. Since then, the course has more often been non-domesticated animals such as skunks, raccoons and bats, or exposure to dogs in other countries. |
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134. How does the rabies virus infect humans?
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The incubation period in humans is generally 4-13 weeks, although it may occasionally be as long as 6 mos, possibly due to a delay in virus entry into peripheral nerves. The virus travels up peripheral nerves and, in general, the further the bite is from the CNS, the longer the incubation period.
While the virus is traveling up the axons of motor or sensory neurons, there is no detectable antibody or cell mediated immune response, possibly b/c antigen remains sequestered in infected muscle cells. Hence, passively administered Ig may be given during the incubation period. |
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135. What happens when rabies gets into the brain?
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Once in the brain, the virus spreads from cell to cell until a large proportion of neurons is infected, but there is little cytopathic effect, even when viewed by EM, and almost no cellular infiltration.
The striking symptoms of this disease are largely due to dysfunction rather than visible damage to infected cells. The change in behavior of infected animals results form virus invasion of the limbic system. |
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136. What are the clinical features of rabies?
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After developing a sore throat, headache, fever and discomfort at the site of the bite, the pt becomes excited, with muscle spasms and convulsions. Involvement of the muscles of swallowing when attempting to drink water gave the old name for rabies, hydrophobia, as the symptoms are sometimes precipitated by the mere site of water.
Once rabies have developed it is fatal, death occurring following cardiac or respiratory arrest. Paralysis is often a major feature of the disease. Periods of alternating mania and stupor progress to coma and death from respiratory center failure. |
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137. What is the morphology of rabies?
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On macroscopic exam, the brain shows intense edema and vascular congestion. On microscopic exam, there is widespread neuronal degeneration and an inflammatory reaction that is most severe in the rhombencephalon (mid brain, particularly in the medulla). The basal ganglia, spinal cord, and dorsal root ganglia may also be involved.
***Negri bodies, the pathognomonic microscopic finding, are cytoplasmic, round to oval, eosinophilic inclusions that can be found in pyramidal neurons of the hippocampus and Purkinje cells of the cerebellum.*** |
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138. After exposure to a possibly infected animal, what 4 immediate preventative actions should be taken?
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1. Prompt cleaning of the wound
2. Confirmation of whether or not the animal is rabid 3. Administration of human rabies Ig, to ensure prompt passive immunization. Half of the dose is given into the wound and half intramuscularly 4. If the risk is definite, active immunization with killed diploid cell-derived rabies virus. The changes of preventing the disease are greater when vaccination is started as early as possible after infection. |
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139. What about arthropod-borne togaviruses?
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Numberous arthropod-borne togaviruses can cause meningitis or encephalitis. In different parts of the world, different mammals, birds or even reptiles act as reservoirs and there are a variety of arthropod (mosquito and tick) vectors. Usually < 1% of humans infected develop neurologic disease. There may be a febrile illness, but asymptomatic infection is common.
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140. What are the most important types of arthropod-borne viruses?
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In the Western hemisphere, teh msot improtant yptes are Eastern and Western equine, Venezuelan, St. Louis, and La Cross.
Elsewhere in the world, pathogenic arboviruses include Japanese B (Far east), Murray Valley (austrialia and New Guinea), and tick-borne (Russia and Eastern Europe). All have animal hosts and mosquito vectors, except for the tick born type. |
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141. What is the CSF like in arthropod borne viral encephalitis?
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The CSF is usually colorless but with a slightly elevated pressure and, initially, a neutrophilic pleocytosis that rapidly converts to lymphocytes.
The protein level is elevated, but sugar content is normal. |
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142. What about West Nile virus?
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West Nile virus belongs to the Japanese encephalitis serogroup of flaviviruses that includes SLE. It is primarily an infection of birds and culicine mosquitoes, with humans and horses acting as incidental hosts.
Since 1999, the virus has been successfully dispersed by migratory birds and has spread thru most of the USA. Clinically, affected pts develop generalized neurologic deficits, such as seizures, confusion, delirium, and stupor or coma, and often focal signs, such as reflex asymmetry and ocular palsies. |
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143. What is the morphology of arthropod-borne viral encephalitis?
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Characteristically, there is a lymphocytic meningoencephalitis (sometimes with neutrophils) with a tendency for inflammatory cells to accumulate perivascularly.
Multiple foci of necrosis of gray and white matter are found; in particular, there is evidence of single-cell neuronal necrosis with phagocytosis of the debris (neuronophagia). |
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144. What is retrovirus meningitis and encephalitis?
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HIV can cause subacute encephalitis, often w/dementia. HIV often invades the CNS shortly after initial infection, resulting in an increase in cells in the CSF and a mild meningitic illness.
At a later stage, subacute encephalitis may develop, often with dementia. This is sometimes difficult to distinguish from the neurologic disease caused by microorganisms such as T. gondii, C. neoformans, CMV, and JC virus. In HIV-related dementia, the brain is shrunken, with enlarged ventricles and vacuolization of myelin tracts. HIV mainly infects macrophages and microglia in the CNS. |
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145. When does HIV aseptic meningitis occur?
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HIV aseptic meningitis occurs w/in 1-2 weeks of seroconversion in about 10% of pts; antibodies to HIV can be demonstrated, and the virus can be isolated from the CSF.
HIV invasion of the nervous system have shown a mild lymphocytic meningitis, perivascular inflammation, and some myelin loss in the hemispheres. |
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146. What is AIDS-dementia complex (ADC)?
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The dementia begins insidiously, w/mental slowing, memory loss, and mood disturbances, such as apathy and depression. Motor abnormalities, ataxia, bladder and bowel incontinence, and seizures can also be present.
Radiologic imaging of the brain may be normal or may show some diffuse cortical atrophy, focal abnormalities of the cerebral white matter, and ventricular dilation. |
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147. What is the morphology of HIV encephalitis?
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On macroscopic exam, the meninges are clear and there is some ventricular dilation w/sulcal widening but normal cortical thickness. This process is best described as a chronic inflammatory reaction with widely distributed infiltrates of microglial nodules, sometimes associated with foci of tissue necrosis and reactive gliosis.
The microglial nodules show abnormally prominent endothelial cells and perivascular foamy or pigment-laden macrophages. These changes occur especially in the subcortical white matter, diencephalon, and brainstem. |
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148. What is an important component of the microglial nodule?
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The macrophage-derived multinucleated giant cell.
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149. What is vacuolar myelopathy?
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This disorder of the spinal cord is found in 20-30% of pts with AIDS in the US. THe histopathologic findings resemble those of subacute combined degeneration, though serum levels of vitamin B12 are normal. The pathogenesis of the lesion is unknown; it does not appear to be caused directly by HIV, and the virus is not present within the lesions.
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150. What is tropic spastic paraparesis, or HTLV-1-associated myelopathy (HAM)?
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HAM occurs in several countries in the Caribbean, along the Indian Ocean, in Japan, and in South America.
Some cases show a severe lymphocytic meningomyelitis unlike that seen in vacuolar myelopathy. Virologic studies and polymerase chain reaction data have implicated another retrovirus: human T-cell lymphotrophic virus (HTLV-1). |
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151. What are the symptoms of viral myelopathy?
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Acute myelitis may result in symmetrical symptoms if it transverses the spinal cord. These will include motor weakness and sensory loss, for example. The symptoms will be asymmetrical if only part of the spinal cord is involved.
When the anterior horn cells of the cord are affected by polio, coxsackie, enterovirus 71 and West Nile virus infection, the symptoms are motor and result in acute flaccid paralysis. Chronic myelopathy can be caused by HTLV-1 infection and pts present with HAM. |
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152. What is AIDS- associated myopathy?
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Inflammatory myopathy has been the most often described skeletal muscle disorder in pts with HIV infection. The disease is characterized by the subacute onset of proximal weakness, sometimes pain, and elevated levels of serum CK.
The histologic findings include muscle fiber necrosis and phagocytosis, interstitial infiltration with HIV-positive macrophages, and in a few cases, cytoplasmic bodies and nemaline rods. |
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153. An acute, toxic, reversible myopathy with "ragged red" fibers and myoglobinuria may also develop in what condition...?
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*An acute, toxic, reversible myopathy with "ragged red" fibers and myoglobinuria may also develop in pts treated with zidovudine (AZT).
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154. What about AIDS in children?
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neurologic disease was common in children with congenital AIDS, occurring in 15-30% of infants born to seropositive mothers; the incidence has decreased due to HAART.
*Clinical manifestations of neurologic dysfunction are evident by the first years of life and include microcephaly with mental retardation and motor developmental delay with spasticity of limbs.* |
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155. What is the most frequent neural morphologic abnormality in children with AIDS?
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The most frequent morphologic abnormality is calcification of the large and small vessels and parenchyma within the basal ganglia and deep cerebral white matter.
There is also loss of hemispheric myelin or delay in myelination; multinucleated giant cells and microglial nodules are also observed in many cases. HIV is present in brain tissue. |
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156. What is PML?
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Progressive multifocal leukocencephalopathy (PML) is a viral encephalitis caused by the JC polyomavirus; because the virus preferentially infects oligodendrocytes, demyelination is its principal pathologic effect.
The disease occurs almost invariably in immunocuppressed individuals in various clinical settings, including chronic lymphoproliferative or myeloproliferative diseases, immunosuppressive chemotherapy, granulomatous diseases, and AIDS. Although the incidence of PML appears to be decreasing HIV-infected individuals w/the advent of HAART, there may be direct interaction btwn HIV and JC viruses w/in cells. |
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157. What are the clinical symptoms of PML?
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No clinical disease has been associated with primary infection by the JC virus, but about 65% of normal people have serologic evidence of exposure to the virus by the age of 14 years. It is thought that PML results from the reactivation of virus as a result of immunosuppression.
*Clinically, pts develop focal and relentlessly progressive neurologic symptoms and signs, and both CT and MRI scans show extensive, often multifocal lesions in the hemispheric or cerebellar white matter.* |
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158. What is the morphology of PML?
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The lesions consist of patches of irregular, ill-defined destruction of the white matter ranging in size from mm's to extensive involvement of an entire lobe of the brain. The cerebrum, brainstem, cerebellum, and occasionally the spinal cord can be involved.
*On microscopic exam, the typical lesion consists of a patchy of demyelination, most often in a subcortical location, in the center of which are scattered lipid-laden macrophages and a reduced number of axons.* At the edge of the lesion are greatly enlarged oligodendrocyte nuclei whose chromatin is replaced by glassy amphophilic viral inclusion. Within the lesions, there may be bizarre giant astrocytes with irregular, hyperchromatic, sometimes multiple nuclei. Reactive fibrillary astrocytes are scattered among the bizarre forms. |
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159. What is post-infectious encephalitis?
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Encephalitis very occasionally occurs 1-2 weeks after apparently normal measles, and even less commonly after varicella.
It is also seen after Mycoplasma infection and various influenza-like illnesses. The virus is generally not recoverable from the CNS, and the perivascular infiltration, sometimes with demyelination, suggests an autoimmune pathogenesis. |
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160. What is post-vaccinial encephalitis?
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A similar condition occurs after administration of brain-derived inactivated rabies vaccine, which is now obsolete, and after other immunizations with non-infectious materials.
The clinical picture resembles experimental allergic encephalitis, and is probably due to autoimmune responses triggered by the infection or by the injected material. |
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161. What is subacute sclerosing panencephalitis?
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SSPE is a rare progressive clinical syndrome characterized by cognitive decline, spasticity of limbs, and seizures.
It occurs in children or young adults, months or years after an initial, early-age acute infection with measles. This disease is thought to represent persistent, but nonproductive, infection of the CNS by an altered measles virus; changes in several viral genes have been associated with the disease. With widespread measles vaccination programs, the disease seems to have largely disappeared. |
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162. What is the morphology of SSPE?
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On microscopic exam, there are widespread gliosis and myelin degeneration; viral inclusions, largely within the nuclei, or oligodendrocytes and neurons; variable inflammation of white and gray matter; and neurofibrillary tangles.
Ultrastructural study shows that the inclusions contain nucleocapsids characteristic of measles, and the measles virus antigen is positive. |
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163. What are spongiform encephalopathies caused by scrapie-type agents?
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Scrapie-type agents are closely associated with host-coded prion protein. Scrapie type agents infect a variety of mammals, including humans, and are transmissible to lab rodents or primates.
Disease is characterized by the appearance of a spongiform appearance of nervous tissues, caused by vacuolation and plaque formation. Infections in animals seem to have originated from sheep and goats with scrapie which has been present in Europe for 200-300 years. Affected animals itch and scrape themselves against posts for relief. |
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164. What part of the body is an important target in toxoplasmosis?
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The CNS is an important target in toxoplasmosis. Although congenitally acquired T. gondii is initially generalized, it may become localized in the CNS. Damage to the eye is the most common consequence, but the brain may also be affected, with hydrocephalus and intracerebral calcification.
Before HAART, toxoplasmosis was an important cause of death in AIDS pts, with encephalitis and toxoplasma abscess due to necrosis as contributory causes. It is still one of the most common causes of neurologic symptoms and morbidity in pts with AIDS. |
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165. The abscesses in toxoplasmosis in the CNS appear where?
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In toxoplasmosis of the CNS, the brain shows abscesses, frequently multiple, most involving the cerebral cortex (near the gray-white junction) and deep gray nuclei, less often the cerebellum and brainstem, and rarely the spinal cord.
The blood vessels in the vicinity of these lesions may show marked intimal proliferation or even frank vasculitis with fibrinoid necrosis and thrombosis. |
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166. What is the morphology of toxoplasmosis in the CNS?
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Acute lesions consist of central foci of necrosis with variable petechiae surrounded by acute and chronic inflammation, macrophage infiltration, and vascular proliferation. *Both free tachyzoites and encysted bradyzoites may be found at the periphery of the necrotic foci.*
After treatment, the lesions consist of large, well-demarcated areas of coagulation necrosis surrounded by lipid-laden macrophages. |
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167. What are the symptoms of toxopasmosis in the fetus?
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Primary maternal infection with toxoplasmosis, particularly if it occurs early in the pregnancy, may be followed by a cerebritis in the fetus, with the production of multifocal cerebral necrotizing lesions that may calcify, producing severe damage to the developing brain.
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168. What is cerebral malaria?
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Plasmodium falciparum shows an unusual feature in that RBCs containing the asexual stages adhere to the walls of capillaries. When this occurs in the brain, cerebral malaria may result that is an important cause of mortality in African children.
Fever is followed by a variety of symptoms, including convulsions and coma, and these lead rapidly to death if not treated. Artemisinin combo therapy is replacing quinine as the treatment of choice for severe malaria. Coma is reversible, mostly w/o residual neurologic deficit, when treatment is successful. |
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169. What is Toxocara infection?
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Toxocara infection can result in granuloma formation in the brain and retina. The cat and dog roundworms Toxocara cati and Toxocara canis infect humans, usually children, when Toxocara eggs derived from kitten or puppy feces are ingested. After infection by humans, the eggs hatch and the larvae migrate from the gut to the liver, lung, eye, brain, kidney and muscles.
However, as humans are dead-end hosts for these parasites, they cannot reach full maturity. Granulomas thus form around the larvae, which in the brain may cause convulsions, and in the eye a tumor-like mass can cause retinal detachment and eventually blindness. Peripheral blood eosinophilia is rarely seen in ocular toxocariasis. |
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170. How is Toxocara infection Dx and Tx?
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Serum can be tested by ELISA for antibodies to Toxocara excretory-secretory antigen, but may give false negative results in ocular toxocariasis. Antibody detection in ocular vitreous fluid samples is more sensitive.
The disease is prevented by deworming puppies and kittens, and by reducing the contamination of children's play areas by dog excreta. Anthelmintic therapy is not give in ocular toxocariasis. Corticosteroids and appropriate ophthalmic surgery are the mainstays of therapy. |
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171. Can hydatid disease occur in the brain?
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Hydatid disease is caused by the tapeworm Echinococcus granulosus. The ingested eggs hatch their embryos and migrate thru the gut to the portal blood vessels, and subsequently develop into hydatid cysts, especially in the liver, but also in the lungs, brain and kidney.
Disease is caused by local pressure from the cysts, and sometimes hypersensitivity reactions to hydatid antigens. Neurologic symptoms include nausea and vomiting, seizures and altered mental status. The disease is prevented by interrupting the natural dog-sheep, dog-goat, or other carnivore-herbivore transmission cycle. |
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172. What is cysticercosis?
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Cysticercosis is characterized by cyst formation in the brain and eye. It results from infection with the larval stage of Taenia solium, a human pork tapeworm. The eggs present in human feces infect pigs which develop cysts in muscle tissue and are a source of further human infection.
After passing thru the gut wall, the parasite develops into cysts, usually in skeletal muscle, but also and more importantly in the brain or eye, causing convulsions or cysticerotic encephalopathy. |
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173. What are brain abscesses?
Where do they come from? |
Brain abscesses are usually associated with predisposing factors. They may arise by direct implantation of organisms, local extension from adjacent foci (mastoidits, paranasal sinusitis), or hematogenous spread (usually from a primary site in the heart, lungs, or distal bones or after tooth extraction).
Predisposing conditions include acute bacterial endocarditis, which tends to produce multiple abscesses; cyanotic heart disease, in which there is a right-to-left shunt and loss of pulmonary filtration or organisms, and chronic pulmonary sepsis, as can be seen with bronchiectasis. Acute abscesses are caused by various bacteria, generally of oropharyngeal origin, including anaerobes. Chronic abscesses may be due to M. tuberculosis or C. neoformans. |
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174. What are the most common offending organisms in brain abscesses in the nonimmunosuppresed?
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Streptococci and staphylococci are the most common offending organisms identified in nonimmunosuppressed populations.
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175. What about abscesses in the immunosuppressed population?
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Opportunistic infection may occur with fungi and protozoan etiologic agents.
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176. What are the clinical features of cerebral abscesses?
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Cerebral abscesses are destructive lesions, and pts almost invariably presents clinically with progressive focal deficits in addition to the general signs of raised ICP.
***The CSF is under increased pressure; the white cell count and protein level are raised but the sugar content is normal*** The increased ICP and progressive herniation can be fatal, and abscess rupture can lead to ventriculitis, meningitis, and venous sinus thrombosis. |
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177. What is the morphology of brain abscesses?
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On macroscopic exam, abscesses are discrete lesions with central liquefactive necrosis, a surrounding fibrous capsule, and edema.
On microscopic exam, there is exuberant granulation tissue with neovascularization around the necrosis that is responsible for the marked vasogenic edema. The collagen of the capsule is produced by fibroblasts. Outside the fibrous capsule is a zone of reactive gliosis with numerous gemistocytic astrocytes. |
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178. What are the most common locations for cerebral abscesses, in descending order?
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In descending order:
1. Frontal lobe 2. Parietal lobe 3. Cerebellum |
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179. What is a subdural empyema?
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Bacterial or occasionally fungal infection of the skull bones or air sinuses can spread to the subdural space and produce a subdural empyema. The underlying arachnoid and subarachnoid spaces are usually unaffected, but a large subdural empyema may develop in the bridging veins that cross the subdural space, resulting in venous occlusion and infarction of the brain.
Symptoms include those referable to the source of the infection. In addition, most pts are febrile, with headache and neck stiffness, and if untreated, may develop focal neurologic signs, lethargy, and coma. |
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180. What is an extradural abscess?
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Extradural abscess, commonly associated with osteomyelitis, often arises from an adjacent focus of infection, such as sinusitis or a surgical procedure.
When the process occurs in the spinal epidural space, it may cause spinal cord compression and constitute a medical emergency. |
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181. What is tetanus?
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Tetanus spores are widespread in teh soil and originate from the feces of domestic animals. All strains fo Cl. tetani produce the same toxin.
The toxin is carried in peripheral nerve axons and probably in the blood to the CNS, where it binds to neurons and blocks the release of inhibitory mediators in spinal synapses, causing overactivity of motor neurons. It can also pass up sympathetic nerve axons and lead to overactivity of the sympathetic nervous system. |
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182. What are the clinical features of tetanus?
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After a period of 3-21 days, but sometimes longer, there are exaggerated reflexes, muscle rigidity, and uncontrolled muscle spasms. Lockjaw (trismus) is due to contraction of jaw muscles.
Dysphagia, risus sardonicus (a sneering appearance), neck stiffness and opisthotonos (esp. in neonatal tetanus) are also seen. Muscle spasms may lead to injury and eventually there is respiratory failure. Tachycardia and sweating can result from effects on the sympathetic nervous system. Mortality is up to 50% depending on the severity and quality of treatment. |
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183. How is tetanus Tx?
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Human antitetanus Ig should be given as soon as tetanus is suspected clinically.
The would should be excised if necessary and penicillin given to inhibit bacterial replication. Muscle relaxants are used and if necessary, respiratory support in an ICU. |
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184. What is botulism?
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Spores of Cl. botulinum are widespread in the soil and contaminate vegetables, meat and fish. Cl. botulinum toxin blocks ACh release from peripheral nerves. It is therefore a type of food poisoning that affects the motor and autonomic nervous systems.
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185. What are the clinical features of botulism?
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After an incubation period of 2-72 h, there is descending weakness and paralysis, w/dysphagia, diplopia, vomiting, vertigo, and respiratory muscle failure.
There is no abdominal pain, diarrhea or fever. Infants develop generalized weakness (floppy babies), but usually recover. Botulism is treated with antibodies and respiratory support. The toxin is heat labile and is destroyed by adequate cooking. |
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186. What is neurosyphilis? What are the three types?
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Neurosyphilis is the tertiary stage of syphilis and occurs in about only 10% of pts with untreated infection.
The major forms are meningovascular neurosyphilis, paretic neurosyphilis, and tabes dorsalis. |
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187. What is meningovascular neurosyphilis?
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Meningovascular neurosyphilis is a chronic meningitis involving the base of the brain, and variably, also the cerebral convexities and the spinal leptomeninges. In addition, there may be an associated obliterative endarteritis (Heubner arteritis) accompanied by a distinctive perivascular inflammatory reaction rich in plasma cells and lymphocytes.
Cerebral gumma (plasma cell-rich mass lesions) may also occur in relation to meninges and extending into the cerebral hemispheres, diencephalon, or spinal cord. |
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188. What is paretic neurosyphilis?
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Paretic neurosyphilis is caused by invasion fo teh brain by T. pallidum and is clinically manifested as insidious but progressive loss of mental and physical functions with mood alterations (including delusions of grandeur), terminating in severe dementia called general paresis of the insane.
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189. What is the morphology of paretic neurosyphilis?
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On microscopic exam, inflammatory lesions are associated with parenchymal damage in teh cerebral cortex (particuarly the frontal lobe but also affecting other areas of teh isocortex) chracterized by loss of neurons with proliferation so microglia (rod cells), gliosis, and iron depsoits demonstrable with the Prussian blue stain.
The spirochetes can be, at times, demonstrated in tissue sections. ***There is often an associated hydrocephalus w/damage to the ependymal lining and proliferation of subependymal glia, called granular ependymitis.*** |
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190. What is tabes dorsalis?
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Tabes dorsalis is the result of damage by the spirochete to the sensory nerves in the dorsal roots which produces impaired joint position sense and resultant ataxia (locomotor ataxia); loss of pain sensation leading to skin and joint damage (Charcot joints); other sensory disturbances, particularly the characteristic "lightning pains" ; and absence of deep tendon reflexes.
On microscopic exam, there is loss of both axons and myelin in the dorsal roots, with pallor and atrophy in the dorsal columns of the spinal cord. |
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191. Who is at an increased risk for neurosyphilis?
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Patients with HIV infection are at an increased risk for neurosyphilis, and the rate of progression and severity of the disease appear to be accelerated, presumably related to the impaired cell-mediated immunity.
CNS involvement by T. pallidum in this setting may be manifested as asymptomatic infection, acute syphilitic meningitis, meningovascular syphilis, and rarely, direct parenchymal invasion of the brain. |
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192. What is neuroborreliosis (lyme disease)?
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Lyme disease is caused by the spirochete Borrelia burgdorferi, transmitted by various species of Ixodes tick; invovlement of the nervous sytem is referred to as neuroborreliosis.
Neurologic symptoms are highly variable and include aseptic meningitis, facial nerve palsies, mild encephalopathy, and polyneuropathies. The rare cases that have come to autopsy have shown a focal proliferation of microglial cells in the brain as well as scattered organisms (identified by Dieterle stain) in the extracellular spaces. |
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193. What are transmissible spongiform encephalopathies?
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These diseases are characterized by spongiform changes due to intracellular vacuoles in neural cells. These are associated with abnormal forms of a specific protein, termed prion protein (PrP). Diseases may be sporadic, infectious, and transmissible, and include:
1. Creutzfeldt-Jakob disease, kuru, Gerstmann-Straussler-Scheinker syndrome 2. Scrapie in sheep and goats 3. Mink transmissible encephalopathy 4. Bovine spongiform encephalopathy (mad cow disease) 5. Chronic wasting disease |
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194. What is the pathogenesis of the prion diseases?
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PrP is a normal cellular protein; disease occurs when PrP changes from a native isoform to an abnormally folded isoform, termed PrP scrapie. The infectious nature of PrP scrapie molecules derives from its ability to induce misfolding of native PrP and thus corrupt the integrity of normal cellular PrP.
*Accumulation of PrP scrapie appears to be the cause of the pathologic changes in these diseases, but the pathways by which this material causes the development of cytoplasmic vacuoles and eventual neuronal death are unknown. |
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195. What is protective against vCJD and CJD?
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Heterozygosity at codon 129 is protective against development of vCJD and sporadic CJD.
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196. What is the morphology of spongiform diseases?
1/2 |
The progression of the dementia in CJD is usually so rapid that there is little if any macroscopic evidence of brain atrophy. ***The pathognomonic finding is a spongiform transformation of the cerebral cortex and, often, deep gray matter structures (caudate, putamen); this consists of a multifocal process that results in the uneven formation of small, apparently empty, microscopic vacuoles of varying sizes within the neuropil and sometimes in the perikaryon of neurons.***
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197. What is the morphology of spongiform diseases?
2/2 |
In advanced cases, there is severe neuronal loss, reactive gliosis, and sometimes expansion of the vacuolated areas into cystlike spaces ("status spongiosus"). No inflammatory infiltrate is present.
Kuru plaques are extracellular deposits of aggregated abnormal protein; they are Congo-red positive as well as PAS positive and occur in the cerebellum in cases of GSS; they are present in abundance in the cerebral cortex in cases of variant CJD. *In all forms of prion disease, immunohistochemical staining demonstrates the presence of proteinase-K-resistant PrP scrapie in tissues. |
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198. What is CJD?
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CJD is a rare cause of rapidly progressive dementia. The clinical picture is usually typical, with the initial subtle changes in memory and behavior followed by a rapidly progressive dementia, often with pronounced involuntary jerking muscle contractions on sudden stimulation (startle myoclonus).
It is primarily sporadic but may be familial. There are well-established cases of iatrogenic transmission, notably by corneal transplantation, deep implantation electrodes, and contaminated preparations of human growth hormone. The disease is uniformly fatal with an average duration of only 7 months. There is extensive atrophy of the involved gray matter. |
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199. What is variant CJD (vCJD)?
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This variant is a CJD like illness found in a small number of pts, mostly from the UK and potentially derived from the bovine spongiform encephalopathy agent.
All cases have been found to be Met/Met homozygotes at codon 129. |
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200. How is vCJD different than CJD (4 ways)?
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1. The disease affected young adults
2. Behavioral disorders figured prominently in the early stages of the disease 3. The neurologic syndrome progressed more slowly than what is usually observed in pts with CJD 4. Extensive cortical plaques are present, with a surrounding halo of spongiform disease. |
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201. What is Gerstmann-Straussler-Scheinker syndrome?
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This syndrome is an inherited disease with mutations of the prion protein gene (PRNP); it typically begins with a chronic cerebellar ataxia, followed by a progressive dementia.
The clinical course is usually slower than that of CJD, with progression to death several years after the onset of symptoms. In addition, GSS is often marked by numerous plaques of PrP scrapie as well as neurofibrillary tangles. |
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202. What is fatal familial insomnia?
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Fatal familial insomnia is name in part for the sleep disturbances that characterize its initial stages.
In the course of the illness, which typically lasts fewer than 3 years, pts develop other neurologic signs, such as ataxia, autonomic disturbances, stupor, and finally coma. A noninherited form has also been found. |
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203. What is the morphology of fatal familial insomnia?
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Unlike other prion diseases, fatal familial insomnia does not show spongiform pathology.
Instead, the most striking alteration is neuronal loss and reactive gliosis in the anterior ventral and dorsomedial nuclei of the thalamus; neuronal loss is also prominent in the inferior olivary nuclei. |
