CNS Infections- Case 1 Flashcards
It is important to note that the early signs and symptoms of CNS infection are often similar to:
–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.
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.
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.
The stiff neck in case 1 points to what?
meningeal irritation.
The skin lesions in case 1 are caused by what?
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.
Other pathogens to consider for Case 1 include:
Haemophilus influenza (H.flu),
pneumococcus and
a rickettsial infection (Rocky Mountain Spotted Fever).
What happens if treatment is delayed?
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.
Rules for tx bacterial meningitis
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!
How do bacterial pathogens gain entry into the CSF space?
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.
How do bacterial pathogens cause damage to the CNS?
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.
There is a vigorous inflammatory response mediated by cytokines such as:
interleukin 1 and tumor necrosis factor.
What does the extensive inflammatory response with bacterial meningitis result in?
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.
What hormone is characteristically elevated in bacterial meningitis?
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.
What is this showing?
The sad outcome if treatment is started too late.
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?
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
What are the pathogens that commonly cause bacterial meningitis?
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.
In neonates, what are the common pathogens of abcterial meningitis?
Group B strep, E. coli and Listeria
Who else gets Listeria meningitis often?
In older individuals and those with compromised immunity, including pregnancy, Listeria is also a problem.
When there is direct penetration of the CSF space through trauma or surgery, ________ and ________ are causative organisms.
Staphylococcus and gram negative organisms
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?
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.
Meningococcal meningitis is accompanied by sepsis with multiple organs affected including:
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.
Pneumococcus (Strep pneumo) is the most common bacterial pathogen responsible for causing:
community acquired meningitis.
What are the main risk factors for penumococcal meningitis?
alcoholism,
chronic middle ear infection,
infection of the cranial sinuses,
CSF leaks,
pneumonia,
Sickle cell disease and asplenia.
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:
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.
Listeria is relatively common in certain environments such as foods including:
meat counters and the surface of hot dogs.
The dosage can also be especially high in unpasteurized dairy products.
What are these?
Skin rash in meningococcal meningitis: early petechiae and purpura. The child is not yet in coma and prognosis may be good with timely treatment.
What are these?
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.
What is a positive Brudzinski sign?
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.
The use of an LP during suscepted bacterial meningitis
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.
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?
brain abscess or parameningeal inflammation
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.
