Infections of the Central Nervous System

Medical Neuroscience Course

CNS infections: Meningitis

Michael Fennewald Ph.D.

Some terms

Pleocytosis: increased WBCs(white blood cells) in the CSF

Meningitis: inflammation of meninges, which are the

membranes covering the brain and spinal cord due to

infection (there are also non-infectious causes which are not

covered here)

Encephalitis: inflammation of the brain due to infection (there

are also non-infectious causes not covered here)

Meningoencephalitis: both of the above

MENINGITIS VERSUS ENCEPHALITIS — The presence or absence of normal brain

function is the important distinguishing feature between encephalitis and

meningitis. Patients with meningitis may be uncomfortable, lethargic, or distracted

by headache, but their cerebral function remains normal. In encephalitis, however,

abnormalities in brain function are common, including altered mental status,

motor or sensory deficits, altered behavior and personality changes, and speech

or movement disorders. Seizures and postictal states can be seen with meningitis

alone and should not be construed as definitive evidence of encephalitis. Other

neurologic manifestations of encephalitis can include hemiparesis, flaccid

paralysis, and paresthesias.

However, the distinction between the two entities is frequently blurred since some

patients may have both a parenchymal and meningeal process with clinical

features of both. The patient is usually labeled as having meningitis or

encephalitis based upon which features predominate in the illness although

meningoencephalitis is also a common term which recognizes the overlap.

Meningitis

Types of meningitis: classically bacterial versus

viral(or aseptic) meningitis.

Physical findings can distinguish between these

two and/or encephalitis but almost always more

information is needed.

Examination of the CSF(cerebrospinal fluid) is

very important to distinguish among the

meningitis/encephalitis diagnoses.

Initial Symptoms with meningitis

Bacterial (%)

Viral (%)

Headache

> 90

50 – 90

Fever

> 90

88 – 100

Meningismus ~50-80

~50(less in neonates)

(Kernig’s and Brudzinski’s signs and/or stiff neck)

Seizures

~ 30

14 – 18

Focal neurologic 10 – 20

Papilledema

< 5

>85% have fever, headache, meningismus, or some signs of

brain dysfunction such as coma, confusion, delirium

focal neurological signs common in meningitis/

encephalitis

• especially ocular and/or facial palsies (cranial

nerves 3, 4, 6 and 7)

• Deafness which can be temporary or permanent

• This is often due to inflammation of the basal

surface of the brain in meningitis

Kernig’ sign

(Vladimir Kernig, 1840-1917, Russian physician)

Limitation in passive extension at the knee

due to spasm of the hamstrings

Basis: A protective reaction to prevent the

pain of stretching inflamed sciatic nerve

roots

Brudzinski’s sign

(Josef Brudzinski, 1874-1917, Polish pediatrician)

Flexion at the knees and hips in

response to passive flexion of the neck

Basis: Protective reaction to prevent

stretch of inflamed sciatic roots

(similar to Kernig’s sign)

May be more sensitive if done in the

sitting position

Normal eye exam

Papilledema

Examples of papilledema

Treatment algorithm for meningitis

Symptoms of meningitis

Check for papilledema and/or focal neurologic deficits

Absent

Present

Blood cultures, lumbar puncture

Obtain blood cultures

Empiric antibiotics

CSF consistent with bacterial meningitis

CT scan of head

Give empiric antibiotics

No mass lesion

mass lesion present

Alternative diagnosis

CSF findings in Patients with Meningitis

Type Opening Leukocyte count

Pressure Cells/microliter-type

mmH20

Normal

50-180

<5 Lymphocytes

Bacterial

200-500

1000-5000 Neutrophils

Viral

<250

50-1000 Lymphocytes

CSF findings in Patients with Meningitis

Type

Glucose

Protein

mg/dL

mg/dL

Normal

40-70

20-50

Bacterial

<40

100-500

Viral

>45

<200

CSF findings in Patients with Meningitis

Type

Gram stain

Culture

Normal

Negative

Negative

Bacterial

Positive:60-90%

Positive in

70-85%

Viral

Negative

Negative

CSF characteristics predictive of bacterial

meningitis

Combination of the following CSF values predicts

bacterial meningitis

WBC counts >1000

– Neutrophil predominating

Protein level > 200

Glucose level <40

CSF – serum glucose ratio < 0.4

Symptoms of acute bacterial

meningitis

Fever (bacterial invasion of blood &

CSF)

Stiff neck (nuchal rigidity due to

protective reflexes from inflammation

of the subarachnoid space)

Brain dysfunction (nausea/vomiting,

headache, irritability/excitability;

obtundation)

Sometimes, rash or petechiae

Pathogenesis of meningitis

Mucosal colonization

Mucosal invasion

Bacteremia

Meningeal invasion

Bacterial replication in CSF

Host response to bacterial antigens

Subarachnoid space inflammation

Why is bacterial meningitis so

devastating?

Increased permeability of blood-brain

barrier resulting in inflammatory response

Brain edema from three mechanisms:

vasogenic from increased blood-brain-

barrier permeability; cytotoxic from toxic

products from inflammatory cells or

bacterial products; interstitial from

obstruction of CSF flow

Case 1: 60-year-old woman with fever, headache, and nuchal rigidity

What is the diagnosis?

1. Bacterial meningitis

8

2. Viral meningitis

3. Encephalitis

4. Strep throat

5. Cellulitis

6. Sinusitis

7. Otitis media

Diagnosis: Acute Streptococcus pneumoniae meningitis

Any further diagnostic tests?

1. CT scan of head

10

2. Blood cultures

3. Culture and sensitivities of

CSF fluid

4. All of above

5. 1 and 2

6. 2 and 3

7. 1 and 3

Any further diagnostic tests at this point?

Draw blood cultures, send sample of CSF for culture

Treatment: ceftriaxone and vancomycin until sensitivities are

known for S. pneumoniae

END OF CASE 1

Case 2: A man with headache

History of present illness:

This is a 19 year old man who was in good health until he noticed 9 days ago that

he had muscle aches. Four days ago he developed a fever but he doesn't recall

how high. He developed a severe headache, as well as a little neck aching and

stiffness, so he went to the emergency room. He was given a diagnosis of "flu",

and was treated with ketorolac. This made the headache better for a while, but it

returned. The headache is severe, and he rates it as "10 on a scale of 1 to 10". The

headache is bilateral periorbital, pounding, with photophobia, phonophobia, and

nausea.

Allergies: None

Medications: Hydrocodone for pain.

Past medical history: Asthma

Family history: Mother suffers from migraines. Other family members have had

hypertension and TIA.

Social: Smokes 1 pack of cigarettes per day. Does not use alcohol. Uses marijuana.

Physical examination:

Vital signs: Temperature 100 degrees F, Pulse 80 , Respiratory rate 16 , Blood

pressure 120/82 , Weight 65 kg.

General physical exam: Normal except for moderate neck stiffness. Kernig's and

Brudzinski's signs absent.

Neurological exam: Alert and cooperative. Mental status normal. Fundus

examination normal. Cranial nerve, motor, sensory, reflex, coordination and gait

exams normal.

Initial laboratory studies:

CBC and basic metabolic panel were normal.

Course of illness:

A lumbar puncture was done. Fluid was clear. White blood cell count was 459 cells/

cu. mm, with 97% lymphocytes. Red blood cell count was 1. Glucose was 62,

protein 44. Gram's stain was negative. Bacterial and viral cultures were done.

What would most likely describe this

patient’s condition?

6

1. Meningitis

2. Encephalitis

3. Meningoencephalitis

4. None of the above

MENINGITIS VERSUS ENCEPHALITIS — The presence or absence of normal brain

function is the important distinguishing feature between encephalitis and

meningitis. Patients with meningitis may be uncomfortable, lethargic, or distracted

by headache, but their cerebral function remains normal. In encephalitis, however,

abnormalities in brain function are common, including altered mental status,

motor or sensory deficits, altered behavior and personality changes, and speech

or movement disorders. Seizures and postictal states can be seen with meningitis

alone and should not be construed as definitive evidence of encephalitis. Other

neurologic manifestations include hemiparesis, flaccid paralysis, and

paresthesias.

However, the distinction between the two entities is frequently blurred since some

patients may have both a parenchymal and meningeal process with clinical

features of both. The patient is usually labeled as having meningitis or

encephalitis based upon which features predominate in the illness although

meningoencephalitis is also a common term which recognizes the overlap.

This patient’s condition would best be described as meningitis.

What type of meningitis is this likely to

be?

6

1. Viral or aseptic

2. Bacterial

3. Fungal

4. TB

What is the diagnosis?

The diagnosis is aseptic meningitis . The diagnosis "aseptic" is made from

analysis of the CSF. This patient had 459 white cells/cu. mm, and 97% of them

were lymphocytes, which is typical for aseptic meningitis, but unusually low for

"septic" (i.e. bacterial) meningitis. In addition, the white cells are almost exclusively

lymphocytes, which is common in aseptic meningitis, but uncommon in septic

meningitis, where polymorphonuclear forms predominate. Glucose and protein

levels in this patient were normal, which is also suggestive of aseptic meningitis.

What are some likely agents?

1. Enterovirus

6

2. Rabies

3. West Nile virus

4. Adenovirus

5. Influenza virus

6. Rotavirus

7. HSV

Can you determine the most likely etiology?

Etiology is often difficult to determine in aseptic meningitis.

The usual cause is viral infection, and enteroviruses are the

most common pathogen. Viral cultures are not usually

performed because they are not sensitive and knowing the

pathogen helps little. However, we did culture this patient's

CSF, which grew echovirus. West Nile virus can present with a

meningitis but usually presents as an encephalitis. HSV can

also present as a meningitis but usually presents as an

encephalitis. When HSV presents as a meningitis, it is usually

due to HSV-2 and the patient usually has had a symptomatic

case of genital herpes in the month before.

How would this patient be treated?

1. Acyclovir

6

2. Ribavirin

3. Ceftiaxone and

vancomycin

4. Gancyclovir

5. Symptom support

What should be done for the patient?

This patient's CSF formula clearly showed an "aseptic"

meningitis. Aseptic meningitis is a benign condition and

requires only supportive care. The patient usually improves in a

few days, though in unusual cases symptoms may bother the

patient for weeks. Unfortunately, early or partially-treated

bacterial meningitis can present with an "aseptic" CSF formula,

and they can worsen suddenly. They are treated with

antipyretics and fluids.

END OF CASE 2

Focal neurological deficits

A focal neurologic deficit is a problem in nerve function that affects a

specific location -- such as the left face, right face, left arm, right arm,

left leg, right leg, even just a small area such as just the tongue

A specific function -- for example, speech may be affected, but not the

ability to write. The problem occurs in the brain or nervous system. It

may result in a loss of movement or sensation. The type, location, and

severity of the change can indicate the area of the brain or nervous

system that is affected.

In contrast, a non-focal problem is NOT site-specific -- such as a general

loss of consciousness .

Focal neurologic changes can include any function. Sensation changes

include paresthesia (abnormal sensations), numbness, or decreases in

sensation. Movement changes include paralysis, weakness , loss of muscle

control, increased muscle tone, and loss of muscle tone .

Other types of focal loss of function include:

Speech or language difficulties such as aphasia or dysarthria (impaired

speech and language skills), poor enunciation, poor understanding of speech,

impaired writing, impaired ability to read or to understand writing, inability

to name objects (anomia)

Vision changes such as reduced vision, decreased visual field , sudden vision

loss , double vision (diplopia)

Neglect or inattention to the surroundings on one side of the body

Loss of coordination , or loss of fine motor control (ability to perform

complex movements)

Horner's syndrome : one-sided eyelid drooping , lack of sweating on one side

of the face, and sinking of one eye into the socket

Poor gag reflex, swallowing difficulty , and frequent choking