In order to properly “osmose” new information, your brain is protected from the rest of the body by three meningeal layers.
From outside to inside they’re the dura mater, arachnoid mater, and pia mater, with cerebrospinal fluid in the space between the arachnoid and pia.
If pathogens make their way into these layers, the inflammatory response results in meningitis.
If they find a way to penetrate into the brain parenchyma itself, the inflammatory response results in encephalitis.
And if a pathogen walls itself off - it’s called a brain abscess.
Meningitis can be caused by viruses, bacteria - including mycobacteria like TB, fungi, and parasites.
When it’s caused by viruses, tuberculosis, fungi or parasites, it’s called aseptic meningitis, because routine bacterial cultures of the cerebrospinal fluid are negative.
Sometimes, the infection may spill over from the meninges into the brain parenchyma, and that’s called meningoencephalitis.
Now, the most common causes of acute bacterial meningitis depend on the individual’s age.
For example, in infants less than 3 months, the most common causes in a descending order are group B streptococci, Escherichia coli, and Listeria monocytogenes.
In adolescents 13 to 17 years old, the most common causes are Neisseria meningitidis, followed by Streptococcus pneumoniae, and Haemophilus influenzae.
In non-adolescent children 3 months to 12 years and in adults, Streptococcus pneumoniae is the most common cause, followed by Neisseria meningitidis and Haemophilus influenzae.
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.
Other less common, but extremely important bacterial causes include Mycobacterium tuberculosis, lyme meningitis, rocky mountain spotted fever, and neurosyphilis. These are separated from the other causes because they’re usually associated with a specific risk factor.
For example, tuberculous meningitis occurs in individuals with a history of exposure to tuberculosis, oftentimes infants living in endemic areas.
Lyme meningitis is caused by the spirochete Borrelia burgdorferi, and individuals may have a history of travel to an endemic region like the Northeast of the United States.
Finally, Rocky Mountain Spotted Fever is caused by Rickettsia rickettsii and is carried by the Dermacentor dog tick and is endemic to central and south America, as well as the southeast United States.
Neurosyphilis is rare, but it can arise in sexually active individuals with a history of untreated syphilis, especially in immunocompromised individuals.
Now, viruses can cause aseptic meningitis, meningoencephalitis or pure encephalitis.
Pure encephalitis without meningitis is usually caused by viruses. The most common cause is a group of viruses called enteroviruses, like echovirus and coxsackie virus. From their name, these viruses make their way into the body through the intestines.
Herpes simplex virus, or HSV, is a very important cause of meningoencephalitis.
Other viruses include arboviruses like West Nile virus, which use a mosquito vector.
Although mumps is quite rare due to vaccination, but in unvaccinated individuals it can cause viral meningitis as well as encephalitis.
Measles can cause encephalitis in the acute phase of the illness. 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!
Varicella zoster virus, or VZV can cause a life-threatening form of encephalitis, particularly in immunocompromised individuals.
When it comes to fungi, cryptococcus is an important cause, particularly in HIV-infected individuals with a CD4-positive T-cell counts below 100.
Additionally, Coccoides immitis is a potential cause of fungal meningitis, especially in the Southwestern United States.
As for parasites, a particularly fatal form of meningoencephalitis is caused by Naegleria fowleri is primary amebic meningoencephalitis. 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.
A dangerous complication of malaria is cerebral malaria - a type of meningoencephalitis.
Finally, it’s important to remember that the same pathogens that can cause meningitis can also cause meningoencephalitis.
Alright, now all forms of meningitis present with a triad of fever, neck rigidity, and headache. Other common symptoms include photophobia, nausea, and vomiting. The difference is 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.
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.
Seizures can occur in both meningitis and encephalitis, and both can eventually lead to an altered mental status and even a coma or death.
Importantly, infants can present more subtly with irritability and poor feeding.
Additionally, some clinical clues on physical exam may 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.
A bull’s eye-appearing rash called erythema chronicum migrans, bilateral facial nerve palsy, or cardiac arrhythmias like atrioventricular node block point towards Lyme meningitis.
Flaccid paralysis of the extremities is characteristic of West Nile Virus, which occurs because the virus may also cause a concomitant myelitis; which is inflammation of the spinal cord.
Parotitis may suggest mumps, and a group of vesicles in a dermatomal distribution suggests VZV.
Features of disseminated tuberculosis like pulmonary infiltrates, lymphadenopathy, and a positive tuberculin skin test should prompt consideration of tuberculous meningitis, especially in infants.
Also on examination, resistance to flexion of the neck indicates neck rigidity, and fundoscopy of the eye can reveal papilledema, which indicates an increased intracranial pressure. Sometimes, there may also be focal neurological deficits like cranial nerve, motor, or sensory deficits.
Helpful signs include the Kernig and Brudzinski signs.
To illicit the Kernig sign, place the individual in a supine position. Then, 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.
A helpful way to remember these signs is: “Kernig” starts with a “K”, like “knee”, and Brudzinski starts with a “B”, like “back of the head”.
Now, these signs aren’t particularly sensitive, so negative Kernig and Brudzinski signs don’t exclude meningitis.
When meningitis or encephalitis is suspected, it’s important to first identify any risk factors for increased intracranial pressure because increased intracranial pressure is a risk factor for cerebral herniation precipitated by a lumbar puncture, and that can be lethal.
The risk factors include papilledema, a focal neurological deficit, prior history of a tumor or stroke, an abnormal level of consciousness, new-onset seizure, or being immunocompromised.
In individuals without any of these risk factors, the lumbar puncture is done right away without needing a CT scan.
After you’ve obtained the cerebrospinal fluid sample, you can obtain blood cultures, and then start IV dexamethasone and empiric antibiotics.
The logic behind giving IV dexamethasone before IV antibiotics is that it reduces that inflammatory response that usually occurs when antibiotics destroy bacterial cells.
Steroids decrease mortality and the risk of complications like hearing loss, cranial nerve palsies and seizures, particularly from Streptococcus pneumoniae as well as Haemophilus influenzae in children. So, if these pathogens are suspected or found based on the gram stain or culture, then dexamethasone is continued for 4 days. If not, the IV dexamethasone is stopped.
In addition to empiric antibiotics, if the individual has features of encephalitis, such as the presence of abnormal brain function in an adult or fussiness or lethargy in an infant, or temporal lobe enhancement on CT scan, then empiric intravenous acyclovir should be added, because it’s crucial to not delay treatment if herpes simplex encephalitis is a possibility.
If the individual does have one of the risk factors of increased intracranial pressure, then blood cultures are obtained, IV dexamethasone is given, and then 15 minutes later IV antibiotics are started, along with IV acyclovir if herpes simplex encephalitis is suspected.
After that a head CT is obtained, which can identify any mass lesions which might cause the symptoms of an increased intracranial pressure. The head CT might also show some helpful clues. For example, herpes simplex encephalitis commonly cause temporal lobe enhancement, and tuberculous meningitis often involves the brainstem. So, if the CT scan is normal, then the lumbar puncture can be done safely.
There are five key things that are looked at in cerebrospinal fluid: opening pressure, white blood cell count and differential, protein level, glucose level, and gram stain and culture. These can help differentiate between normal CSF and a bacterial, viral, fungal or tuberculous cause of meningitis.
Normally, the opening pressure is below 200 millimeters of water, and only up to 5 white blood cells are present per cubic millimeter. 70 percent of those white blood cells are lymphocytes, 30 percent are monocytes, and very few are neutrophils.
Normal cerebrospinal fluid protein levels range between 15 to 50 milligrams per deciliter, and glucose levels are usually between 45 to 100 milligrams per deciliter. The glucose in cerebrospinal fluid is often two-thirds of that in the serum.
Now, the opening pressure is usually over 200 millimeters of water in all forms of meningitis.
There’s also an elevated white blood cell count in the cerebrospinal fluid called pleocytosis, and is usually in the thousands in bacterial meningitis, and in the hundreds in viral, fungal, and tuberculous meningitis.
A predominantly neutrophilic pleocytosis - over 80% neutrophils - indicates bacterial meningitis.