AssessmentsCentral nervous system infections: Pathology review
USMLE® Step 1 style questions USMLE
A 15-year-old girl is brought to the emergency department by her parents due to a sudden onset of seizure. The parents report that during the past few days, the patient has been feeling lethargic with fevers and constant headaches. Medical history is insignificant other than a progressive aching tooth pain the week before. The patient lives with her parents, 2 brothers, a cat, and a dog. Temperature is 38.6°C (101.48°F), pulse is 102/min, and blood pressure is 135/85 mmHg. On physical examination, the patient is postictal but arousable. She speaks fluently, but the words are incomprehensible. Meningeal signs are negative. MRI of the head reveals a ring-enhancing lesion occupying the frontal lobes. Which of the following pathogens is most likely responsible for this patient’s condition?
Content Reviewers:Yifan Xiao, MD
At the emergency department, 17-year old Mike is brought in by his parents.
He has a fever, headache, and photophobia.
On clinical examination, Mike has neck stiffness and Kernig and Brudzinski signs are positive.
Lumbar puncture reveals a predominantly neutrophilic pleocytosis, elevated protein, and low glucose.
Next to Mike is 27-year old Helen, who came in with a fever, headache, and confusion for the past 72 hours.
Kernig and Brudzinski signs are negative.
Head CT reveals patchy temporal lobe enhancements.
Finally, there’s 60-year Lucia, who is brought by her family because of a seizure.
She also complains of headache and has a mild fever.
There’s no neck stiffness and Kernig and Brudzinski signs are negative.
Two weeks ago Lucia had an episode of otitis media for which she was treated with antipyretics and analgesics.
She has no history of epilepsy.
Head CT reveals a single ring-enhanced lesion in the right temporal lobe.
Okay, so all 3 people suffer from a central nervous system infection.
CNS infections include meningitis, which is when pathogens infect the meningeal layers; encephalitis, when the pathogens infect the brain parenchyma; meningoencephalitis, where the infection starts in the meninges and then spreads into the brain parenchyma; and abscess which is when pathogens wall themselves off in the brain.
Okay, so let’s take a closer look at the various forms of CNS infections, starting with meningitis.
Meningitis can be caused by any pathogen that infects the meninges.
When it’s caused by viruses, mycobacteria, fungi, or parasites, it’s called aseptic meningitis, because routine bacterial cultures of the cerebrospinal fluid are negative.
However, acute bacterial meningitis is far more common.
The bacteria that is most likely to be responsible will depend on the individual’s age.
It’s also important to consider Listeria monocytogenes in adults over the age of 50 or those who are immunocompromised.
Also, Staphylococcus aureus is more common in individuals with a history of neurosurgical procedures or trauma to the head.
These are separated from the other causes because they’re usually associated with a specific risk factor.
For example, tuberculous meningitis’s biggest factor is traveling to an endemic area or working with a high risk population.
Finally, Rocky Mountain Spotted Fever is caused by Rickettsia rickettsii and is carried by the Dermacentor dog tick.
It is endemic to Central and South America as well as the Southeast United States.
Neurosyphilis is rare, but it can arise in individuals with a history of untreated syphilis, especially in immunocompromised individuals.
Alright, now let’s move on to viruses which can cause aseptic meningitis: meningoencephalitis or pure encephalitis.
Herpes simplex virus, or HSV, is a very high yield cause of viral encephalitis.
It can result from a primary infection but more commonly happens during reactivation.
This is when an HSV infection is being suppressed by the immune system and only the latent virus that’s settled in the sensory ganglia survives in the body.
When the immune system is compromised, like when the individual is taking corticosteroids, the latent HSV can escape into the bloodstream and reach the brain, where it will typically affect the temporal lobes.
Okay, now other viruses that can cause CNS infections include arboviruses like West Nile virus, which use a mosquito vector.
However, even after the acute infection has resolved, a form of encephalitis called subacute sclerosing panencephalitis or SSPE can appear up to 10 years later and is typically fatal!
Okay, now when it comes to fungi, remember that they typically cause CNS infections only in immune compromised people.
So first, we have Cryptococcus neoformans which is found in soil and bird droppings.
It is transmitted via the respiratory route where it could colonize the lungs.
Another very similar fungi is Coccidioides immitis, which is also a soil dwelling fungi transmitted via the respiratory route. In HIV+ individuals with a CD4+ T-cell count below 200, it could cause a disseminated infection, resulting in meningitis.
As for parasites, a particularly fatal form of meningoencephalitis is caused by Naegleria fowleri which is an amoeba.
This organism is called the “brain-eating amoeba”, and it’s usually acquired from freshwater.
It makes its way to the brain through the nasal passages like when someone dives into water and it rushes up through the cribriform plate.
Now, another parasite that can cause CNS infection is the protozoan trypanosoma brucei which is transmitted via the Tsetse fly.
Finally, it’s important to remember that the same pathogens that can cause meningitis can also cause meningoencephalitis.
Alright, now in some situations, bacteria, fungi, and parasites can wall off from the rest of the brain parenchyma, forming an abscess.
Bacterial brain abscesses are usually polymicrobial.
Pathogens can also come from a hematogenous source, like dissemination from a lung abscess or endocarditis.
Now, bacteremia typically leads to multiple abscesses, while single lesions are usually caused by infections that spread from a nearby organ.
Other causes include Nocardiosis caused by Nocardia, which is found in soil and usually develops in immunocompromised individuals.
Individuals with Nocardiosis present with tuberculosis-like symptoms including fever, weight loss, night sweats, and pulmonary infiltrates.
Now, when it comes to fungi, Mucor and Rhizopus species are important causes of brain abscesses.
From the sinuses, fungi can spread to the surrounding blood vessels and bones and enter the brain, causing a brain abscess of the frontal lobe.
As for parasites, the tapeworm Taenia solium can cause neurocysticercosis, especially in those who have been exposed to contaminated pork.
Most individuals with neurocysticercosis are either diagnosed incidentally or they present with epileptic seizures.
Alright, now all forms of meningitis present with a triad of fever, neck rigidity or resistance to flexion of the head, and headache.
Other common symptoms include photophobia, nausea, and vomiting.
Helpful signs include the Kernig and Brudzinski signs.
To illicit the Kernig sign, place the individual in a supine position, flex the hip to 90 degrees, and attempt to extend the knee.
If the individual has pain with full extension of the knee, that’s a positive Kernig sign.
To illicit the Brudzinski sign, you have to passively flex the neck, and if there’s involuntary flexion of the hips due to pain, then that’s a positive Brudzinski sign.
Now, these signs aren’t particularly sensitive, so negative Kernig and Brudzinski signs don’t exclude meningitis.
Sometimes, fundoscopy of the eye can reveal papilledema, which indicates an increased intracranial pressure.
There can also be focal neurological deficits like cranial nerve, motor, or sensory deficits.
Okay, now the various forms of meningitis have a difference in the time course.
Acute bacterial meningitis and HSV meningoencephalitis usually present within hours to a few days.
Viral meningitis, Cryptococcal meningitis, Lyme disease, and Rocky Mountain Spotted Fever usually present over the course of days to weeks, while tuberculosis, coccidioides, and syphilis tend to present over the course of months.
Additionally, some clinical clues on physical exam can point towards a specific cause.
For example, petechiae are characteristic of Neisseria meningitidis.
A red maculopapular rash on the wrists and ankles that spreads towards the body may indicate rocky mountain spotted fever.
Flaccid paralysis of the extremities is characteristic of West Nile Virus, which occurs because the virus can also cause a concomitant myelitis, which is inflammation of the spinal cord.
Features of disseminated tuberculosis like pulmonary infiltrates, lymphadenopathy, and a positive tuberculin skin test should prompt consideration of tuberculous meningitis, especially in infants.
Now, features of meningitis along with erythema nodosum or multiform and arthralgias, suggest coccidioides immitis as the cause.
As for the parasites, trypanosoma brucei causes a disease called African trypanosomiasis which presents with lymphadenopathy, fever, and neurological symptoms such as confusion.
It can also cause sleep disturbances, and that’s why it’s also known as African sleeping sickness.
What distinguishes pure encephalitis from meningitis is an abnormal brain function - like a change in behavior and personality - and the absence of meningeal irritation symptoms like neck rigidity and Kernig and Brudzinski signs.
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