CNS Infections Flashcards
Most common forms of bacterial meningitis (3)
Pneumococcal, Meningococcal, Haemophilus
(95% of bacterial meningitis cases)
TB is less common but mentioned
List the common causes of brain damage involving meningitis (primary cause and other causes)
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
Types of meningitis (3)
Bacterial, Viral, Fungal
Bacterial meningitis may impact which cranial nerve and is associated with which long-term sequelae in 15-25% of people?
Cranial nerve 8 (vestibulocochlear)
hearing loss, intellectual disabilities, spasticity/paresis, seizures
Bacterial meningitis in children:
50% of children with a history of bacterial meningitis have what sequelae more than 5 years after diagnosis? (general)
cognitive/behavioral difficulties:
learning problems, ADHD
Prevalence highest in which two age groups?
Children < 5yo (also highest risk of mortality)
Older adults > 60
What increased the risk for bacterial meningitis?
General, list some common conditions
Immunosuppression/immunocompromised
Conditions: HIV, autoimmune disorders, diabetes, post-cancer treatment, cystic fibrosis, hypoparathyroidism, renal/adrenal insufficiency
Acute (several hours; 3 sx) vs. Gradual (several days; 1 sx) symptoms of bacterial meningitis
Acute:
- sudden fever
- severe headaches (inflammation of vessels)
- 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
Assessment methods (2) of bacterial meningitis:
- LP - lumbar puncture, look for bacteria, elevations of WBC, protein, low glucose
- Neuroimaging (e.g., MRI, CT) to observe inflammation, though not very helpful. More helpful to rule out other etiology
Treatments for bacterial meningitis (3):
- Antibiotics
- Vaccines
- Corticosteroids: inflammation/swelling
Neuropsychological profile for adults and children with bacterial meningitis:
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
________ forms of meningitis are more common than ________ meningitis
(bacterial, viral, fungal)
or (bacterial, aseptic)
Viral forms; bacterial meningitis
More than 10,000 cases of viral meningitis are reported annually
Aseptic forms of meningitis (3)
Caused by viruses, fungi, and parasites.
Enteroviruses are viruses transmitted through intestines (most common cause, >85%)
What is the morbidity of viral meningitis? (recovery, residual deficits/sequelae)
Recovery is generally 7-10 days, with no residual deficits. Most do not have sequelae. If there are deficits, they tend to be mild.
What are the presenting symptoms of viral meningitis? (Most common, other common, progression)
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.
Assessment methods for viral meningitis (2)
Similar to bacterial meningitis:
- LP/blood work to observe any viral pathogens
- Neuroimaging/EEG, to rules out encephalitis and subclinical seizures
Treatment for viral and fungal meningitis
Viral: mostly supportive (rest, fluids, anti-inflammatory meds), though antiviral meds may be used
Fungal: antifungal medication
Neuropsychological deficits seen in viral/fungal meningitis:
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
What are the general causes of encephalitis? (most common, other causes; e.g., bacterial, viral, fungal, etc.)
Most common: viruses
Next common: autoimmune
Other: various bacteria, fungi, and parasites
What are the mechanisms of primary and secondary causes of encephalitis?
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)
Etiology of viral encephalitis (most common viruses, neuropathology)
> 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.
Herpes simplex virus (HSV)
Type of CNS infection; most common in what age group?
Most common cause of encephalitis in children (0-15yo) and most common severe form, in general.
Children - highest incidence < 1 year old
Encephalitis mortality (overall, in elderly, in children)
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%)
HSV neuropathology/etiology/outcomes
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
Eastern Equine Encephalitis neuropathology (regions affected)
Thalamus, basal ganglia, and midbrain
Encephalitis presenting symptoms (acute, subacute, chronic)
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
Assessment of encephalitis (3):
- LP/Bloodwork, isolate pathogen
- EEG, possibility of seizures (up to 90% in children with encephalitis; temporal lobe focus in HSV)
- CT/MRI, identify swelling (edema), abscess, mass effect; differentiate from strokes, tumors
Treatment of encephalitis (4):
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
What is Rasmussen’s Encephalitis?
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
Neuropsychological functioning in encephalitis
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.
Chronic HSV and cognitive impairment
potential connection; mainly mild (lower IQ, low average), increased risk for Alzheimer’s disease (suggested due to reactivation of virus)
Autoimmune encephalitis classified into 2 groups:
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
When autoimmune encephalitis is associated with cancer (what is this disorder called?)
Paraneoplastic neurologic disorder (PND)
Most common causes of autoimmune encephalitis (2)
Acute disseminated encephalomyelitis (ADEM)
Anti-NMDA receptor (anti-NMDARE)
Neuropathology of anti-NMDARE
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)
Neuropathology of ADEM
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
Gender differences in autoimmune encephalitis
anti-NMDARE, 80% female
AMPAR, 90% female
Others are more equal
Mortality rate in autoimmune encephalitis
Higher with paraneoplastic neurologic disorder (associated with cancer)
Variable, otherwise.
Morbidity in autoimmune encephalitis
Associated with secondary seizures, infections, and cognitive deficits
Neuropsychological functioning in anti-NMDARE
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
What is paraneoplastic limbic encephalitis?
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.
Anti-NMDARE phases (4)
- Prodromal: flu-like symptoms, fever, malaise, HA, and fatigue (5-14 days)
- Psychotic: acute psychosis, may present to psychiatrist office for concerns of schizophrenia
- Unresponsiveness: patients stop following verbal commands, appear mute/akinetic, perhaps fixed gaze
- Hyperkinetic: autonomic instability (hypo/hypertension, cardiac arrhythmia, hypoventilation); this is less common in children
How long does it take to recovery from anti-NMDARE?
It can take up to 18 months. Persistent deficits in memory and new learning are noted.
What are intracranial abscesses and what are they caused by?
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.
