CNS Infections

Question 1

Most common forms of bacterial meningitis (3)

Answer 1

Pneumococcal, Meningococcal, Haemophilus
(95% of bacterial meningitis cases)

TB is less common but mentioned

Question 2

List the common causes of brain damage involving meningitis (primary cause and other causes)

Answer 2

Primary: inflammation –> vasculitis, tissue injury
Other: septic thrombosis (sepsis, bacterial, pus, etc., accumulation and cause infarcts)
small infarcts
cerebral edema
increased intracranial pressure
hypoxic ischemic encephalopathy

Question 3

Types of meningitis (3)

Answer 3

Bacterial, Viral, Fungal

Question 4

Bacterial meningitis may impact which cranial nerve and is associated with which long-term sequelae in 15-25% of people?

Answer 4

Cranial nerve 8 (vestibulocochlear)

hearing loss, intellectual disabilities, spasticity/paresis, seizures

Question 5

Bacterial meningitis in children:

50% of children with a history of bacterial meningitis have what sequelae more than 5 years after diagnosis? (general)

Answer 5

cognitive/behavioral difficulties:

learning problems, ADHD

Question 6

Prevalence highest in which two age groups?

Answer 6

Children < 5yo (also highest risk of mortality)

Older adults > 60

Question 7

What increased the risk for bacterial meningitis?

General, list some common conditions

Answer 7

Immunosuppression/immunocompromised
Conditions: HIV, autoimmune disorders, diabetes, post-cancer treatment, cystic fibrosis, hypoparathyroidism, renal/adrenal insufficiency

Question 8

Acute (several hours; 3 sx) vs. Gradual (several days; 1 sx) symptoms of bacterial meningitis

Answer 8

Acute:

1. sudden fever
2. severe headaches (inflammation of vessels)
3. nuchal rigidity (stiff neck)*

Gradual:
nonspecific flu-like symptoms

Pediatric:
Lethargy, hypothermia, anorexia/vomiting, respiratory distress, convulsions, irritability, jaundice, bulging fontanelle (infants), diarrhea, and nuchal rigidity

Question 9

Assessment methods (2) of bacterial meningitis:

Answer 9

1. LP - lumbar puncture, look for bacteria, elevations of WBC, protein, low glucose
2. Neuroimaging (e.g., MRI, CT) to observe inflammation, though not very helpful. More helpful to rule out other etiology

Question 10

Treatments for bacterial meningitis (3):

Answer 10

1. Antibiotics
2. Vaccines
3. Corticosteroids: inflammation/swelling

Question 11

Neuropsychological profile for adults and children with bacterial meningitis:

Answer 11

Sensorineural hearing loss the most common sensorimotor symptom (11%)

Adults:
Mainly slowed processing speed; attention problems (decreased Trails B, Stroop; some studies); executive dysfunction, memory problems (mixed studies)

Pediatric:
ADHD symptoms (inattention, hyperactivity); some suggestion of low average IQ; not a lot of evidence of academic problems (more likely due to ADHD symptoms); language may be affected if contracted before age 1; behavioral changes

Question 12

________ forms of meningitis are more common than ________ meningitis
(bacterial, viral, fungal)
or (bacterial, aseptic)

Answer 12

Viral forms; bacterial meningitis

More than 10,000 cases of viral meningitis are reported annually

Question 13

Aseptic forms of meningitis (3)

Answer 13

Caused by viruses, fungi, and parasites.

Enteroviruses are viruses transmitted through intestines (most common cause, >85%)

Question 14

What is the morbidity of viral meningitis? (recovery, residual deficits/sequelae)

Answer 14

Recovery is generally 7-10 days, with no residual deficits. Most do not have sequelae. If there are deficits, they tend to be mild.

Question 15

What are the presenting symptoms of viral meningitis? (Most common, other common, progression)

Answer 15

Most common: Headache and fever.
Other: irritability (esp. children), nausea, vomiting, nuchal rigidity, rash, and fatigue
Progression: nonspecific flu-like symptoms and low-grade fever precede neurologic symptoms by about 2 days.

Question 16

Assessment methods for viral meningitis (2)

Answer 16

Similar to bacterial meningitis:

1. LP/blood work to observe any viral pathogens
2. Neuroimaging/EEG, to rules out encephalitis and subclinical seizures

Question 17

Treatment for viral and fungal meningitis

Answer 17

Viral: mostly supportive (rest, fluids, anti-inflammatory meds), though antiviral meds may be used

Fungal: antifungal medication

Question 18

Neuropsychological deficits seen in viral/fungal meningitis:

Answer 18

Viral: mixed evidence of mild to moderate deficits in attention and speed

Fungal: limited studies. Cryptococcal has been shown to demonstrated broad deficits with improvements within the first year of recovery

Question 19

What are the general causes of encephalitis? (most common, other causes; e.g., bacterial, viral, fungal, etc.)

Answer 19

Most common: viruses
Next common: autoimmune
Other: various bacteria, fungi, and parasites

Question 20

What are the mechanisms of primary and secondary causes of encephalitis?

Answer 20

Primary: (acute viral encephalitis) direct infection of the brain via pathogen

Secondary: (post-infective encephalitis) results from previous viral infection (e.g., mumps, measels, chickenpox)

Question 21

Etiology of viral encephalitis (most common viruses, neuropathology)

Answer 21

> 100 viruses implicated
Most common: herpes simplex virus (HSV), varicella zoster, Epstein-Barr, adenoviruses, enterovirsus, arboviruses (arthropod-borne - ticks/mosquitoes [seasonal]), human parechovirus

Most viruses enter CNS via bloodstream. Viruses enter cells, replicate, and cause damage/death to the cells. Etiology can also be result of immune responses (activated T cells and macrophages) to the infected cells and surrounding areas.

Certain viruses affect certain areas of the brain, including the cerebellum (cerebellitis), brain stem, and ganglia.

Question 22

Herpes simplex virus (HSV)

Type of CNS infection; most common in what age group?

Answer 22

Most common cause of encephalitis in children (0-15yo) and most common severe form, in general.
Children - highest incidence < 1 year old

Question 23

Encephalitis mortality (overall, in elderly, in children)

Answer 23

Overall: 5%
Though this varies based on age group and type of virus.
Elderly: Japanese B, St. Louis, and West Nile Viruses
Children: HSV, 50%, if left untreated
Highest mortality: rabies virus (almost 100%)

Question 24

HSV neuropathology/etiology/outcomes

Answer 24

Dormant in the trigeminal ganglia. When activated, travels along trigeminal nerve (CN V) into the brain.

Temporal lobe pathology and enhancement of orbitofrontal lobes.

Neonates: lesions develop into subcortical white matter lesions

More cognitive and psychiatric impairments (changes in personality) than other etiologies; increased risk of seizures

Children: risk factors for worse outcome include: longer hospital stays, abnormal neuroimaging, younger age

Question 25

Eastern Equine Encephalitis neuropathology (regions affected)

Answer 25

Thalamus, basal ganglia, and midbrain

Question 26

Encephalitis presenting symptoms (acute, subacute, chronic)

Answer 26

Acute: hours to days, influenza-like symptoms, including severe HA and fever, may include disorientation, altered consciousness, behavioral and speech disturbances, and general and focal neurological signs.

Subacute: weeks, presents with seizures and speech disturbance after a few weeks of altered behavior

Chronic: years, occasional acute symptoms , but generally present/progress over years (e.g., HIV, Lyme)

Behavioral: delusions, hallucinations, affective disorders (depression, aggression, euphoria); small number can present symptoms of Kluver-Bucy syndrome due to damage to the amygdala

Question 27

Assessment of encephalitis (3):

Answer 27

1. LP/Bloodwork, isolate pathogen
2. EEG, possibility of seizures (up to 90% in children with encephalitis; temporal lobe focus in HSV)
3. CT/MRI, identify swelling (edema), abscess, mass effect; differentiate from strokes, tumors

Question 28

Treatment of encephalitis (4):

Answer 28

Pharmacological (3):
Antiviral - acyclovir, ganciclovir
Anticonvulsant - prevent seizures
Corticosteroid - inflammation

Surgical:
Hemispherectomy - may be used to treat Rasmussen’s encephalitis; slows down neurological deterioration in pediatric cases

Question 29

What is Rasmussen’s Encephalitis?

Answer 29

A rare infection that affects primarily one hemisphere of the brain; chronic progression

Most often occurs in children < 10 yo.

Symptoms: severe, frequent seizures; progressive loss of neurological function, including motor skills; eventual hemiparesis

Question 30

Neuropsychological functioning in encephalitis

Answer 30

Limited studies.

General: more commonly executive dysfunction (especially HSV), slowed processing speed; some behavioral and psychiatric difficulties (ADHD, OD more often in children); generally good outcome with recovery

IQ: variable, but generally 0.5-1 SD below mean

Achievement: higher rate of LD

Attention: more so in children; subtle in adults

Language: not a lot of evidence, though naming deficits have been found in HSV

Visuospatial: no consistent findings

Memory: anterograde difficulties more commonly in HSV and West Nile Virus

Sensorimotor: variable depending on virus.

Question 31

Chronic HSV and cognitive impairment

Answer 31

potential connection; mainly mild (lower IQ, low average), increased risk for Alzheimer’s disease (suggested due to reactivation of virus)

Question 32

Autoimmune encephalitis classified into 2 groups:

Answer 32

Intracellular antibody disorders: autoimmune reactions, antibodies in response to tumors (PND falls into this category); more common in older adults
E.g., anti-Hu, anti-Yo, anti-Ri, and anti-CV2 antibodies

Synaptic and neuronal surface autoantibody disorders: 16 known disorders based on associated antigen; antibodies disrupt the neuronal receptor or synaptic protein and prevent post-synaptic electrical impulse
E.g., N-methyl-D-aspartate, NMDA, AMPA, GABAb, and glycine receptors

Question 33

When autoimmune encephalitis is associated with cancer (what is this disorder called?)

Answer 33

Paraneoplastic neurologic disorder (PND)

Question 34

Most common causes of autoimmune encephalitis (2)

Answer 34

Acute disseminated encephalomyelitis (ADEM)

Anti-NMDA receptor (anti-NMDARE)

Question 35

Neuropathology of anti-NMDARE

Answer 35

antibodies decreased the number of NMDA receptors in postsynaptic dendrites, which cause the postsynaptic cell to not function as usual. NMDA receptors are highly concentrated in the hippocampus, forebrain, and other limbic system regions.

NMDA receptors play a significant role in synaptic excitatory transmission (glutamate)

Can be associated with tumors (females with ovarian teratomas [more common among African-Americans]; carcinomas in older men and women)

Question 36

Neuropathology of ADEM

Answer 36

autoimmune response that causes damage to the brain and spinal cord white matter; must be differentiated from MS or other autoimmune disorders (usually a single episode vs. multiple episodes); usually associated with a viral infection

Question 37

Gender differences in autoimmune encephalitis

Answer 37

anti-NMDARE, 80% female
AMPAR, 90% female

Others are more equal

Question 38

Mortality rate in autoimmune encephalitis

Answer 38

Higher with paraneoplastic neurologic disorder (associated with cancer)

Variable, otherwise.

Question 39

Morbidity in autoimmune encephalitis

Answer 39

Associated with secondary seizures, infections, and cognitive deficits

Question 40

Neuropsychological functioning in anti-NMDARE

Answer 40

General: core deficit is episodic memory, last to recover is memory consolidation; persistent executive function, attention, and working memory deficits; slowed processing speed at onset; mutism in children at onset; behavioral/personality changes in children at onset, better by follow-up

IQ/Academic: lower IQ and academic functioning at time of symptoms, but otherwise average

Processing speed: slowed processing speed at onset, with minority of patients with persistent slowed processing speed beyond recovery

Language: no consistent findings in adults; mutism with children, with recovery at follow-up, some persistent fluency impairments

Visuospatial: some deficits at onset, but better by follow-up

Memory: impaired episodic memory, poor memory consolidation, which is the last to recover, verbal memory is most common, though visual memory has been found impaired in some

Executive fx: disorganization, poor planning, disinhibition

Emotions and personality: changes more common in children at onset and back to baseline with recovery; some evidence of increased anxiety in adults

Social: some studies suggested impaired social cognition in both adults and children

Question 41

What is paraneoplastic limbic encephalitis?

Answer 41

PLE
One type of intracellular antibody disorder. Involves an inflammatory process related to cancers (most common is small-cell lung cancer) and localized to the limbic system.

Question 42

Anti-NMDARE phases (4)

Answer 42

1. Prodromal: flu-like symptoms, fever, malaise, HA, and fatigue (5-14 days)
2. Psychotic: acute psychosis, may present to psychiatrist office for concerns of schizophrenia
3. Unresponsiveness: patients stop following verbal commands, appear mute/akinetic, perhaps fixed gaze
4. Hyperkinetic: autonomic instability (hypo/hypertension, cardiac arrhythmia, hypoventilation); this is less common in children

Question 43

How long does it take to recovery from anti-NMDARE?

Answer 43

It can take up to 18 months. Persistent deficits in memory and new learning are noted.

Question 44

What are intracranial abscesses and what are they caused by?

Answer 44

Infectious pus collections that occur in the brain or surrounding spaces.

They can originate from nearby structures (e.g., ear infections, sinusitis, dental infections); can spread through the blood from a remote site; can occur after a depressed skull fracture or penetrating brain injury; rare cases, meningitis. Damage occurs by increased ICP and/or due to mass effect on the brain.