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Flashcards in CNS Infections- Case 1 Deck (60)
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1
Q

It is important to note that the early signs and symptoms of CNS infection are often similar to:

A

–Bacterial meningitis

–Viral meningitis and encephalitis

–Rickettsial disease (Rocky Mountain Spotted Fever)

–Other CNS infections

Furthermore you do not have the luxury of time to watch and observe for the clinical picture to evolve to a clearer diagnosis. By then the disease may have escalated beyond retrieval. You must act without a clear diagnosis, treat early and treat vigorously.

2
Q

Summary: A 10 year old boy is brought to the ED in a stuporous state, febrile, hypotensive, tachycardic and with nuchal rigidity. His skin has a macular-papular rash. So how do you approach such a case.

A

First localize the lesion. The confused state is consistent with a diffuse, global cerebral dysfunction as occurs in metabolic derangements, including those accompanying sepsis.

The depressed level of consciousness means that the ascending arousal system in the upper brainstem is affected by the same diffuse process disrupting the cortical circuits.

The boy is febrile and hypotensive suggesting sepsis.

3
Q

The stiff neck in case 1 points to what?

A

meningeal irritation.

4
Q

The skin lesions in case 1 are caused by what?

A

an inflammation of small blood vessels, an infectious necrotizing vasculitis that is likely to have widespread organ involvement including the brain and meninges.

This boy’s presentation is classic for meningococcal meningitis.

5
Q

Other pathogens to consider for Case 1 include:

A

Haemophilus influenza (H.flu),

pneumococcus and

a rickettsial infection (Rocky Mountain Spotted Fever).

6
Q

What happens if treatment is delayed?

A

Meningococcus can cause a fulminant illness that leave your patient dead in a matter of hours.

Here you can see the brain covered with pus. The veins have thrombosed as part of DIC, and there is hemorrhagic ischemic brain infarction and edema everywhere. Hence, treatment should start as soon as possible, as soon as you suspect the diagnosis.

7
Q

Rules for tx bacterial meningitis

A

Meningococcal meningitis Can kill in 6 - 12 hr

Patient may deteriorate in ER while undergoing diagnostic testing.

Treat empirically and treat as soon as you suspect the diagnosis!

8
Q

How do bacterial pathogens gain entry into the CSF space?

A

Bacterial meningitis can be caused by pathogens that are blood borne (bacteremia, sepsis) and arrive from another infected location, such as the lungs or urinary bladder.

They may enter from a nearby infected structure by retrograde venous blood movement when veins clot as in the case of mastoiditis or otitis media.

There may also be direct entry from the outside due to head trauma, neurosurgery, a myelomeningocele or a congenital spinal epidermal sinus tract.

9
Q

How do bacterial pathogens cause damage to the CNS?

A

They cause a virulent immune response and it is that host response that is actually so damaging.

First of all, the bacteria have surface antigens that are specialized for gaining entrance across the vascular endothelium. Once inside the CSF space, the infection flourishes because there are few immune cells on patrol but plenty of CSF glucose that acts as a nutrient broth. Nonetheless, within hours immune cells arrive in the CSF space and start the battle.

10
Q

There is a vigorous inflammatory response mediated by cytokines such as:

A

interleukin 1 and tumor necrosis factor.

11
Q

What does the extensive inflammatory response with bacterial meningitis result in?

A

This results in a small vessel vasculitis and thrombophlebitis with consequent decrease in cerebral blood flow. The ischemia leads to infarction and further edema.

There is a generalized breakdown of the blood brain barrier.

12
Q

What hormone is characteristically elevated in bacterial meningitis?

A

Non-specific increase in antidiuretic hormone, aka SIADH, causes the blood sodium conc to fall making the blood hypo-osmolar.

The hypo-osmolar blood provides a source of free water that exacerbates the edema. The intracranial pressure rises rapidly at the same time as the peripheral blood pressure falls due to septic shock. All of this produces a vicious feed-forward cycle of accelerating brain swelling, ischemia, infarction, herniation and death.

13
Q

What is this showing?

A

The sad outcome if treatment is started too late.

14
Q

Note that is was not the pathogen itself can caused the catastrophic series of events but the immune response. That also means that treatment itself can be damaging! How?

A

Antibiotics tear the bacterial cell walls apart and the resulting fragments are highly antigenic. They strongly stimulate the immune response and can accelerate the inflammatory cascade. For this reason, corticosteroids are used to suppress the inflammatory reaction while the antibiotics are doing their work

15
Q

What are the pathogens that commonly cause bacterial meningitis?

A

That depends in part on the host’s age and immune status.

In children older than 2 months of age and adults, the most common etiologies are pneumococcus and meningococcus.

Hemophiles influenza or H. flu used to form a triad with pneumococcus and meningococcus as being the most common community acquired causes of meningitis. H. flu, however, has been virtually eliminate by the widespread use of its vaccine.

The introduction of a meningococcal vaccine in recent years has also reduced the incidence of that deadly pathogen, and the hope is that it too will disappear. Unfortunately not all the strains are covered by the vaccine and so, meningococcus may remain a problem for years to come.

16
Q

In neonates, what are the common pathogens of abcterial meningitis?

A

Group B strep, E. coli and Listeria

17
Q

Who else gets Listeria meningitis often?

A

In older individuals and those with compromised immunity, including pregnancy, Listeria is also a problem.

18
Q

When there is direct penetration of the CSF space through trauma or surgery, ________ and ________ are causative organisms.

A

Staphylococcus and gram negative organisms

19
Q

Remarkably, meningococcus (Neisseria meningitis) can be found in the nares of about 5% of healthy individuals. Why it stays dormant is not clear nor why it suddenly starts up. Once a patient is ill, how is infection transmitted to others?

A

infection is spread through respiratory droplets.

Proximity to an infected individual means everything to the spread of disease. A study of meningococcal outbreaks in military barracks found that epidemics occurred only in barracks that had beds placed closer than three feet apart. This is apparently the critical distance for a respiratory droplet to travel without it drying up or otherwise failing to be inhaled.

20
Q

Meningococcal meningitis is accompanied by sepsis with multiple organs affected including:

A

the adrenal glands.

The adrenal glands undergo a hemorrhagic necrosis and can cause an Addisonian crisis due to an acute depletion of corticosteroids. This is called Waterhouse-Friderichsen syndrome, and it presents another reason to treat with corticosteroids early on.

21
Q

Pneumococcus (Strep pneumo) is the most common bacterial pathogen responsible for causing:

A

community acquired meningitis.

22
Q

What are the main risk factors for penumococcal meningitis?

A

alcoholism,

chronic middle ear infection,

infection of the cranial sinuses,

CSF leaks,

pneumonia,

Sickle cell disease and asplenia.

23
Q

Listeria meningitis has replaced H. flu as the third most common bacterial pathogen. It now is responsible for about 10% of cases. Risk factors typically involve:

A

whatever depresses the host’s immunity.

The very young and the very old are at increased risk as are individuals who are pregnant, undergo organ transplant, have autoimmune disease or are treated with immune suppressive therapy.

Chronic illnesses such as renal and liver failure also present a risk.

24
Q

Listeria is relatively common in certain environments such as foods including:

A

meat counters and the surface of hot dogs.

The dosage can also be especially high in unpasteurized dairy products.

25
Q

How do you recognize bacterial meningitis clinically in infants?

A

In infants, the presentation may be non-specific.

There will be fever, irritability and vomiting. It is when mom notices unusual crying or unusual lethargy that she brings the child to the doctor. Seizures and a bulging fontanae indicate an advanced stage of the illness.

A skin rash may or may not be present depending on the organism.

26
Q

How does bacterial meningitis present in older children and adults?

A

In older children and adults, the clinical presentation too is initially like that of an upper respiratory infection or URI. Individuals complains of sore throat, fever, headache, which is common with many viral syndromes.

The stiff neck is unusual and the presence of a rash can be helpful with diagnosis.

There is vomiting, increasing lethargy, confusion and cranial neuropathies appear due to entrapment by the evolving exudate at the base of the brain. Seizures are followed by coma and finally death.

27
Q

What do you look for on your physical exam with bacterial meningitis?

A

Evidence of infection include fever and shock, but remember that n the elderly, the temperature may actually fall by several degrees rather than increase.

Examine the skin carefully for petechiae, purpura, pustules, cutaneous manifestations of bacterial endocarditis, and evidence for some connection between the CSF space and the exterior such as a dermal sinus.

The head needs to be carefully inspected for trauma, presence of an intraventricular shunt, CSF leak through the nose or ear, ear infection, and sinus tenderness to palpation. The neck should be checked for stiffness.

Look hard for any non-CNS sources of infection such as pneumonia, endocarditis and UTI.

28
Q
A
29
Q

What are these?

A

Skin rash in meningococcal meningitis: early petechiae and purpura. The child is not yet in coma and prognosis may be good with timely treatment.

30
Q

What are these?

A

skin rash in meningococcal meningitis: late limb edema and purpura- Within a day or two, the purpura becomes confluent, and there is extensive tissue necrosis. Limbs are likely to be lost if the patient is lucky enough to survive. This is not the stage to recognize the diagnosis and initiate therapy as therapy is often futile at this point.

31
Q

What are two ways to test for meningismus, that is neck stiffness, in patients usually with advanced meningitis (i.e. stiff neck= its late in the disease process)?

A

Kerning’s sign

Brudzinski sign

32
Q

What is a positive Kernig’s sign?

A

The Kerning’s sign is positive if the knee cannot be fully extended when the patient lies supine with the hip flexed at 90 degrees

33
Q

What is a positive Brudzinski sign?

A

Brudzinski sign is positive when passive neck flexion causes reflex flexing of both legs and thighs. In most circumstances, the neck will be obviously rigid and difficult to move, so these tests are not always performed.

34
Q

What causes the neck to be stiff in bacterial meningitis?

A

The stiffness is caused by agonist and antagonist muscles simultaneously contracting but why would irritation of the meninges do that? The dura has sensory innervation and the inflammatory process causes pain. There is a reflex reaction of the body to immobilize and “splint” any hurtful limb and a similar process occurs for the neck.

If you give sufficient opiates to eliminate the pain, the neck becomes supple. No one does that, however, since opiates are sedating and could deepen the depth of stupor and coma.

35
Q

As it turns out, most cases of meningitis are not clinically so severe and are statistically more likely to be what?

A

“aseptic” and caused by a virus.

Unfortunately, in the early stages, before the spinal fluid is examined, it is often hard to tell if the infection is bacterial or viral and self-limited.

36
Q

What else falls under the umbrella of aspetic meningitis can should be on the DDx for bacterial meningitis?

A

The meninges sometimes become inflamed in due to an adverse drug reaction; this is especially true for drugs that modulate immunity such a intravenous immunoglobulin and drugs used in organ transplant.

NSAIDs such as ibuprofen occasionally can cause aseptic meningitis, as can sulfa antibiotics and lead poisoning.

An inflammatory mass on the external side of the dura, such as an epidural abscess, can also cause inflammatory changes on the interior side of the dura that mimic bacterial meningitis.

37
Q

What is a craniopharyngioma?

A

A benign tumor of Rathke’s pouch. Its interior over time breaks down into a fluid that looks like crank-case oil. When these contents leak into the CSF space, there is a terrific chemical meningitis with a proliferation or pleocytosis of polymorphonuclear cells that for the world looks like bacterial meningitis (keep it on the DDx). The CSF glucose, however, remains normal.

38
Q

Other things on the DDx for bacterial meningitis?

A

Viral encephalitis

Fulminant TB or fungal meningitis

Lyme disease, neurosyphilis, Rocky Mountain Spotted Fever

39
Q

What labs should we order when we suspect bacterial meningitis?

A

Bacterial meningitis is virtually always accompanied by sepsis. That means there is a high WBC count on CBC and a marked increase in neutrophils (aka PMNs). This left shift in the cell differential often includes early band forms and toxic granulations in neutrophils.

Serum Na+ may fall due to SIADH and the carbon dioxide may be affected by metabolic acidosis.

40
Q

What happens to the prothrombin time and INR with bacterial meningitis?

A

They become elevated due to a consumption of clotting factors in DIC.

41
Q

Rules about daignosing bacterial meningitis

A

Cultures are taken of blood and of every potential site from which the infection may have originated. The blood can be gram stained for bacteria. The hematocrit tube’s “buffy coat” may disclose neutrophils engulfing bacteria.

Some hospitals now can run PCR on blood for the common meningeal pathogens.

42
Q

Two blood tests help to separate aseptic causes of meningitis from bacterial pathogens, namely:

A
43
Q

What imaging should be done with suspected bacterial meningitis?

A

A cranial CT scan is obtained to check for abscess, empyema, cerebral edema and any other structural abnormality that may make lumbar puncture or LP hazardous. In other words, a cerebral mass effect could produce herniation following an LP.

44
Q

The use of an LP during suscepted bacterial meningitis

A

The lumbar puncture provides very useful information regarding intracranial pressure, type of purulence that is prevalent. Is the CSF profile more consistent with a bacterial or viral etiology? The CSF is sent for specialized testing that permits pathogen identification.

45
Q

How can the meningitis be confirmed as bacterial?

A

A PCR test for the bacterial 16S ribosomal DNA can confirm that the pathogen is bacterial.

PCR testing can be used to identify specific pathogens such as herpes simplex virus and tuberculosis.

46
Q

Note that there are problems with PCR tests for certain pathogens so that you cannot always rely completely on PCR so other tests are prefered. Give an example.

A

In the case of West Nile testing, for example, IgM is perhaps the best test for identification.

You collect CSF and blood and quantify the IgG levels in each that are directed against a specific antigen. You calculate the CSF-blood ratio of IgG levels, or so-called IgG index. You compare the IgG index early in the infection and again 4-6 weeks later. If the IgG in the CSF rises at a much faster rate than in the blood, you conclude that the CSF was the site of IgG production and infected with the target pathogen.

47
Q

What is the normal CSF profile for

a) WBC/mm3
b) Predominant cell type
c) glucose mg/dl
d) protein mg/dl

A

a) 0-5
b) lymphocytes
c) 50-100
d) 20-45

48
Q

How does a bacterial meningitis profile appear on a LP draw for:

a) WBC/mm3
b) Predominant cell type
c) glucose mg/dl
d) protein mg/dl

A

a) 500-5000
b) Neutrophils (pus forming)
c) 0-25 (The glucose level drops not because the bacteria and neutrophils consume the glucose but because the general break down of the blood brain barrier includes a loss of active glucose transport into the CSF)
d) increased from 45+

49
Q

What would a CSF profile of:

a) WBC/mm3: 100-500
b) Predominant cell type: lymphocytes
c) Glucose: 25-50 mg/dl
d) Protein: increased

suggest?

A

Partially treated bacterial meningitis or chronic meningitis

50
Q

What would a CSF profile of:

a) WBC/mm3: 1000-1500
b) Predominant cell type: lymphocytes
c) Glucose: 25-50 mg/dl
d) Protein: increased

suggest?

A

Aseptic meningitis

51
Q

What would a CSF profile of:

a) WBC/mm3: 0-200
b) Predominant cell type: lymphocytes
c) Glucose: 50-100mg/dl
d) Protein: NL or increased

suggest?

A

brain abscess or parameningeal inflammation

52
Q

Remember that normal CSF glucose concentration is about two-thirds that of the peripheral blood glucose, and that it takes about two hours for the CSF glucose to equilibrate with the peripheral blood glucose. Why is this important?

A

This is important to recognize since the peripheral blood sugar may fluctuate dramatically over a few hours in a diabetic, thereby severely complicating the interpretation of the CSF glucose.

53
Q

Here is a specimen of turbid CSF due to meningococcal meningitis. A gram stain of the CSF centrifuged sediment shows the gram negative diplococci being phagocytized by neutrophils.

A
54
Q

What do you do once you suspect bacterial meningitis?

A

First of all, your suspicion hopefully arose within minutes of your patient encounter. You need to start treatment right away, empirically, even though your diagnosis may turn out to be wrong. It is far easier to stop drugs once you realize they are unnecessary than to start drugs once irreversible damage has transpired.

55
Q

How should suscepted bacterial meningitis be tx?

A

Start with steroids first. The standard dose is dexamethasone 10 mg 15 minutes before or at the start of antibiotics. Steroids are continued for 4 days.

The steroids suppress two of the damaging cytokines, interleukin-1 and TNF, that mediate inflammatory injury.

56
Q

What ABX should be used to empirically tx bacterial meningitis?

A

Treatment includes a broad spectrum antibiotic such as ceftriaxone, cefepime or meropenem. Since about half of community pneumococcal strains are severely resistant to penicillin, vancomycin is added.

57
Q

More on bacterial meningitis tx

A

Ampicillin is given to cover Listeria in patients with increased risk for that pathogen.

Doxycycline treats rickettsia and Lyme disease.

Acyclovir covers herpes encephalitis.

You start by giving all of the antibiotics in a shotgun fashion and then you withdraw antibiotics as nature of the pathogen becomes clarified. This usually requires several hours, sometimes a day, and includes results of gram staining.

58
Q

If seizures develop after you start the antibiotics, be aware that _________ can trigger seizures as an adverse effect, and you may want to switch to another antibiotic.

A

meropenem

59
Q

It cannot be emphasized enough that bacterial meningitis be treated as early as possible, even if that means you will unnecessarily treat some patients with viral meningitis. Usually one day’s worth of antibiotics and steroids cause no harm.

Other therapeutic actions should include:

A

Managing fluids and electrolytes. Patients are often hypotensive and dehydrated yet show a low sodium due to SIADH. Their electrolyte and fluid balance needs to be carefully managed in the ICU.

60
Q

With bacterial meningitis, if the intracranial pressure cannot be controlled with mechanical ventilation and osmotic agents, what should be done?

A

A ventriculostomy can drain CSF and help to reduce intracranial pressure.

It is important to remember that close contact is a risk for infection so patients need to be placed in special negative pressured isolation rooms, and those in close contact should receive prophylactic antibiotics, such as rifampin or Cipro.