Meningeal Anatomy and CNS Infections

Why do we have meninges?

To wall of the brain from other parts and to house CSF, which cushions the brain.

What are the 3 layers of the meninges?

Dura, arachnoid and pia maters.

Describe the dura mater

Outermost layer. Hardest layer. Very fibrous and acts as a shield, right against the bone of the skull. Has 2 layers: periosteal, which is against the skull and meningeal which is against the arachnoid.

Describe the arachnoid mater

Middle layer. Has many trabeculae in the middle, as well as many cross-bridges that act as another cushion for the brain. Houses CSF, and blood vessels go through here.

Describe the pia mater.

Innermost layer. Adherent right to the brain.

What is CSF?

Acts as a cushion for the brain, a way for nutrients to get to the brain and moves waste products away from the brain.

What is the pathway of CSF circulation?

2 lateral ventricles -> Foramen of Monro -> Third ventricle -> Aqueduct of Sylvius -> Fourth ventricle -> Foramen of Magendie -> spinal cord.

What is the blood brain barrier?

Protection for the brain against foreign invaders and toxicity. Capillaries in the brain do NOT have fenestrations like other capillaries do, so things don't easily get in. They are linked by tight junctions.

Where is CSF produced?

Choroid plexus.

What is responsible for reabsorbing CSF?

Arachnoid villi.

What are the main types of CNS infections?

Meningitis, encephalitis, cerebritis and brain abscess.

How can you differentiate one type of CNS infection from another?

Difficult to do without a CT scan, as symptoms can be very similar (and meningitis can often present with encephalitis)

What is encephalitis?

Widespread brain inflammation or infection.

What causes encephalitis?

Can be infection from a virus, bacteria, parasite or fungus. Usually a virus.

What are common viral causes of encephalitis?

Mostly HSV1 and HSV2, but can also be different arboviruses (from mosquitos) or rabies, tick borne viruses or enteroviruses. Some people might not ever have sores from HSV1/2 and then pop up with encephalitis from it.

What is a common bacterial cause of encephalitis?

Borrealia burgdorferi, TB or STDs.

What is the clinical manifestation of encephalitis?

Can range from mild to catastrophic. Fever, headache, seizures, AMS all possible (AMS often first change noticed) Some people end up in comas, others never realize they have it. Just depends on your luck.

How do you diagnose and treat encephalitis?

MRI and Lumbar puncture essential. Treatment depends on cause (acyclovir for HSV1/2)

What will the MRI and CSF show in viral encephalitis?

MRI will show inflammation primarily affecting temporal and frontal lobes (can also be global inflammation)

CSF will show elevated protein and LYMPHOCYTES.

What is another disease that can cause encephalitis?

Rabies! Once you start getting sx from this, you're done.

What is meningitis?

Infection and inflammation of the meninges and CSF. Can be septic or aseptic. Can be viral or bacterial.

What is the fatality of bacterial meningitis?

Around 25%. You need to act FAST!!!! Try to get abx within 30 minutes of recognition.

What are the risk factors of bacterial meningitis?

Age, epidemics (crowded living environs), neurosurgery and neurologic procedures, pregnancy, contiguous infection (sinus or ear infection), alcoholism.

What are the immune function risk factors for meningitis?

Lack of splenic function, DM, malignancy with or without chemo, HIV, IVDU, chronic glucocorticoid or TNF blocker use.

What are common viral causes of meningitis?

Enterovirus, varicella zoster, West Nile and HSV.

What are common bacterial causes of meningitis?

Strep pneumo (gram positive diplococci)

Neisseria meningitides (gram negative diplococci)

Listeria monocytogenes (gram positive rods)

What is the pathophysiology of meningitis?

Leukocyte-endothelial cell interaction causes breakdown of intercellular adhesions, leading to permeability of BBB. Subarachnoid and parenchymal inflammation leads to cerebral edema.

What does the most serious sequelae of meningitis stem from?

Increases in ICP, changes in cerebral blood flow and neuronal damage.

What is the classic triad of menigitis?

Fever, headache, and neck stiffness. If only 1/3 is present, you should consider this dx. Also, a new, blotchy, purpuric rash is a red flag.

What are 2 physical signs for mengitis?

Kernig sign and Brudzinski's neck sign. Positive results come from patient trying to relieve stress on meninges.

What is the goal of treatment for menigitis?

Get appropriate treatment within 2 hours of entering the ER (optimal is <30 minutes).

When should you do imaging on a patient prior to doing a LP?

If the patient has:

HIV, is otherwise immunocompromised, recent head trauma or neuro procedure, CNS shunt, altered sensorium, focal neuro signs or papilledema, seizure, hx of CNS disease.

Describe the CSF analysis tube breakdown

Tube 1: make sure to get a CBC with differential

Tube 2: protein and glucose

Tube 3: Gram stain and culture and additional studies for antigens

Tube 4: CBC with diff to compare to tube 1

Why do you collect 2 CBC's when collecting CSF?

To see if RBCs in 1st tube is due to infection/inflammation or a "traumatic tap". If it's due to infection/inflammation, the amount of RBCs will go down by tube 4. If not, it'll stay elevated.

Why do you collect a glucose level with tube 2?

Glucose is a substrate for bacteria, and they eat it up. If there is a significantly lower glucose level in CSF than in peripheral glucose, this is a sign for bacterial meningitis.

What will the CSF show in bacterial meningitis?

High number of polys (neutrophils), very low glucose and high WBCs.

What should be given alongside empiric antibiotics for meningitis?

Steroids like dexamethasone to help with inflammation.

Which organisms are highly prevalent in neonates with meningitis?

E.coli, Listeria, GBS and Klebsiella.

Which organisms are highly prevalent in 2-18 year olds with meningitis?

N. meningitidis, strep pneumo and H. flu (now rare).

Which organisms are highly prevalent in adults <60 years old with meningitis?

Strep pneumo and N. meningitidis

Which organisms are highly prevalent in adults >60 or with impaired immunity with meningitis?

Strep pneumo, Listeria, Gram negatives, GBS.

What conditions predispose someone to a brain abscess?

Otitis media, mastoiditis, penetrating head injury, neurosurgery, and immunocompromise.

What is the pathobiology of a brain abscess?

Collection of purulent material, perivascular at first with progressive involvement of the brain parenchyma. Formation of a fibrous capsule.

What are the symptoms of a brain abscess?

Similar to meningitis and encephalitis. Imaging very helpful for diagnosis as it will show a ringed off lesion.

What is prion disease?

A group of rare neurodegenerative disorders. Prions are misfolded proteins that act like infectious particles and infect other proteins, causing them to misfold.

What is the result of a prion disease?

Rapid, progressive dementia associated with gait abnormalities and myoclonus. Deadly disease, death typically in a few months after sx onset.

What are the main types of prion disease to know?

Creutzfeld-Jacob disease (CJD)

Variant Creutzfeld-Jacod disease (vCJD)

Kuru

Mad cow disease

What is the definitive diagnosis of prion disease?

Brain biopsy. MRI is most sensitive non-invasive test. EEG also helps with dx.

Describe CJD

Most common prion disease in humans. Sporadic about 85% of cases. Appears later in life.

Describe vCJD

Variant form of CJD, caused by exposure to mad cow disease. Typically affects individuals <50 yoa. Characteristic lesions called "florid plaques"

Describe mad cow disease

Encephalopathy that affects cattle, can spread to humans via consumption of infected meat (which leads to vCJD)

Cows get mad cow, humans get vCJD.

Describe Kuru

Very rare in the US, once epidemic in Papua New Guinea. Came from eating people who were infected with CJD (probably).