2. Central nervous system disease
Definition
• Diseases of any component of the brain or the
spinal cord.
http://www.hon.ch/HONselect/Selection/C10.228.html
7. Meningitis
• อาการคลายกันทั้ง bacterial and viral meningitis
ได ้แก่
• acute onset of fever,
• headache,
• neck stiffness
• photophobia,
• confusion.
• Bacteria significant morbidity (neurologic sequelae,
particularly sensorineural hearing loss) and mortality
• immediate antibiotic therapy.
• only supportive care with analgesics is necessary for
viral meningitis.
Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e
10. Bacterial meningitis
Pathology
• Acute purulent infection within the sub-
arachnoid space.
• CNS inflammatory reaction
• decreased consciousness, seizures, raised
intracranial pressure (ICP), and stroke.
• meninges, the subarachnoid space, and the
brain parenchyma are all frequently involved
(meningoencephalitis).
Harrison's Principles of Internal Medicine, 18e
11. Risk Factors
• Age
• Infants are at higher risk for bacterial meningitis than people
in other age.
• Community setting
• larger groups of people gather together. College freshmen
halls and military personnel are at increased risk for
meningococcal meningitis (caused by Neisseria meningitidis).
• Certain medical conditions
• There are certain diseases, medications, and surgical
procedures ncrease risk.
• Working with meningitis-causing pathogens
• Microbiologists who are increased risk.
• Travel
• Travelers to the meningitis belt in sub-Saharan Africa may be
at risk for meningococcal meningitis
http://www.cdc.gov/meningitis/bacterial.html
12. Common causes of bacterial meningitis vary by age group:
Age Group Causes
Newborns
Group B Streptococcus, Escherichia
coli, Listeria monocytogenes
Infants and Children
Streptococcus pneumoniae,
Neisseria meningitidis,
Haemophilus influenzae type b
Adolescents and Young Adults
Neisseria meningitidis,
Streptococcus pneumoniae
Older Adults
Streptococcus pneumoniae,
Neisseria meningitidis, Listeria
monocytogenes
http://www.cdc.gov/meningitis/bacterial.html
13. Predisposing factor Common organisms
Immunocompromised
L. monocytogenes, aerobic gram-negative rods
(Pseudomonas and Klebsiella)
Pregnant women L. monocytogenes
Csf leak; splenectomy; sickle cell anemia S. pneumoniae
Deficiency of late-acting complement
components; military recruits
N. meningitidis
After neurosurgery S. aureus
Ventriculoperitoneal shunt S. epidermidis
Immunocompromised (HIV/AIDS) C. neoformans
Living in or traveling in Central Valley of
California (Sonoran life zone)
Coccidioides immitis
Swimming/diving in fresh water Naegleria fowleri
Mosquito bite West Nile virus; other arboviruses
Tick bite Borrelia burgdorferi
Sexually transmitted disease (secondary
syphilis)
T. pallidum
Review of Medical Microbiology and Immunology, 13e
14. Proportion of cases of bacterial meningitis
in the United States by host age, 2003–2007
Age
Pathogen <2 Months
2 Months–17
Years
18–50 Years >50 Years
Group B
streptococci
>85% ~5% <5% <5%
H influenzae <5% <5% <5%
Listeria
monocytogene
s
<5% <5% <5% ~10%
N meningitidis ~40% ~20% ~5%
S pneumoniae <5% ~50% ~65% ~75%
Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e
15. Mechanism to infection
• colonization of the nasopharynx: most of bacterial
meningitis .
• exception is Listeria :ingestion of contaminated food
to bloodstream.
• IgA protease:inactivates host antibody: S pneumoniae
and N meningitidis secrete an
• Pili: binds to nonciliated epithelial cells for colonized:
meningitidis
Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e
16. (A). pneumococcus adheres to and
colonizes the nasopharynx. IgA1
protease protects from Ab.
(B) in the bloodstream, the
bacterial capsule helps the
pneumococcus to evade
opsonization.
(C)The pneumococcus accesses the
cerebrospinal fluid through
receptors on the endothelial
surface of the blood-brain barrier.
Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e
17. Pathogenetic of bacterial infection
Neurotropic Stage Host Defense Strategy of Pathogen
1. Colonization or mucosal
invasion
Respiratory mucous Enzymatic degradation
Secretory IgA IgA protease secretion
Ciliary activity Ciliostasic enzymes
Mucosal epithelium
Binding molecules and
adhesive pili
2. Intravascular survival Complement
Production of polysaccharide
capsule and enzymatic
degradation
3. Crossing of blood-brain
barrier
Cerebral endothelium
Binding to endothelial
receptors and adhesive pili
4. Survival within CSF
Complement and antibodies
(low levels in uninfected
patients)
Rapid bacterial replication
prior to complement
production and recruitment of
neutrophils
Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e
18. Viral meningitis
Common symptoms in adults
• Fever
• Headache
• Stiff neck
• Sensitivity to bright light
• Sleepiness or trouble
waking up from sleep
• Nausea
• Vomiting
• Lack of appetite
• Lethargy (a lack of energy)
Common symptoms in
infants
• Fever
• Irritability
• Poor eating
• Sleepiness or trouble
waking up from sleep
• Lethargy (a lack of energy)
Most people with viral meningitis usually get
better on their own within 7 to 10 days.
Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e
19. Viral meningitis
Virus
Season or
Geography
Vector Features
Meningitis
Enterovirus Echo, coxsackie Summer, fall Human Rash, gastroenteritis, carditis
Herpesvirus
Herpes simplex type 2
(HSV2)
— Human Neonates
Varicella-zoster virus
(VZV)
— Human Immunosuppression; rash
Epstein-Barr virus
(EBV)
— Human
Teenagers; infectious
mononucleosis syndrome
Other
Human
immunodeficiency virus
(HIV)
— Human Immunosuppression
Mumps Winter, spring Human
Especially boys; parotitis,
orchitis, oophoritis, pancreatitis
Lymphocytic
choriomeningitis
Fall, winter Mouse
Pharyngitis, pneumonia; marked
CSF pleocytosis, low CSF
glucose; transmissible by organ
transplantation
Pathophysiology of Disease: An Introduction to Clinical Medicine, 7e
23. Lumbar puncture
indications:
• Suspicion of meningitis
• Suspicion of subarachnoid hemorrhage (SAH)
• Suspicion of central nervous system (CNS)
diseases such as Guillain-Barré syndrome and
carcinomatous meningitis
• Therapeutic relief of pseudotumor cerebri
http://emedicine.medscape.com/article/80773-overview#aw2aab6b2b3
24. Lumbar puncture: contraindication
Absolute:puncture on CT of the brain:
• Midline shift
• Loss of suprachiasmatic and basilar cisterns
• Posterior fossa mass
• Loss of the superior cerebellar cistern
• Loss of the quadrigeminal plate cistern
Relative
• Increased intracranial pressure (ICP)
• Coagulopathy
• Brain abscess
http://emedicine.medscape.com/article/80773-overview#aw2aab6b2b3
25. Indication CT previous LP
Abnormal level of consciousness New onset seizure
Focal neurological deficit Immunocompromised state
Papilledema Poorly visualized fundi
http://accessmedicine.mhmedical.com/conten
t.aspx?bookid=496§ionid=41304186&Res
ultclick=2
26. Safe CSF volume to take at LP
- Thwaites G, Fisher M, Hemngwas C, et al. Britrish infection society for diagnosis and treatment of
tuberculosis of the central nervous system in adult and children. Journal of infection (2009). 59: 167-87.
27. CSF diagnostic test
Stain and culture
• Gram's stain and culture
• India ink and fungal culture
• AFB: M. tuberculosis culture
Antibody
• Coccidioides immitis complement
fixation
• West Nile virus CSF-IgM
• Borrelia burgdorferi
Antigen
• Histoplasma polysaccharide Ag
• Cryptococcal polysaccharide Ag
Polymerase chain reaction
• Broad-range bacterial 16S rDNA
• S. pneumoniae
• Hsv types 1 and 2
• EBV
• M. tuberculosis
• N. meningitidis
• Reverse transcriptase for
enteroviruses
• West Nile virus
• Varicella zoster virus
• HIV RNA
Principles and Practice of Hospital Medicine > Chapter 199. Meningitis and Encephalitis
28. CSF analysis
Etiology
Pressure (mm
H2O)
Cells (μL)
Proteins
(mg/100 cc)
Glucose
(CSF/blood)
Normal <200
0–5 Lymphs, 0
Polys
<45 >0.6
Acute bacterial Increased
200–5000;
mostly (>90%)
Polys
>100 <0.6
Acute viral Slight increase
100–700
Lymphs
Slight increase Normal
Subacute/chro
nic (TB,
fungus)
Increased
25–500
Lymphs
>100 <0.6
Review of Medical Microbiology and Immunology, 13e
29. Treatment: Bacterial meningitis
Patient Population Empiric Treatment
Neonate
Ampicillin plus cefotaxime or an
aminoglycoside
Healthy children and adults with
community-acquired disease
3rd - or 4th -generation cephalosporin +
vancomycin [+metronidazole if otitis,
mastoiditis, sinusitis are predisposing
conditions]
≥ 55 year or with chronic illness or
immunosuppressed patients
3rd - or 4th -generation cephalosporin +
vancomycin + ampicillin
Postneurosurgical Vancomycin + meropenem
Principles and Practice of Hospital Medicine > Chapter 199. Meningitis and Encephalitis
30. Microorganism Antibiotic Dose
S. pneumoniae
Penicillin susceptible
(MIC < 0.1 mg/L)
Penicillin G
•Neonates: 0.15–0.2 mU/kg/d (every 8–12 hours)
•Infants and children: 0.3 mU/kg/d (every 4–6 hours)
•Adult: 24 million units/d (every 4–6 hours)
or ceftriaxone
•Infant or child: 80–100 mg/kg/d (every 12 hours)
•Adult: 4 g/d (every 12 hours)
or cefepime
•Infants and children: 150 mg/kg/d (every 8 hours)
•Adult: 6 g/d (every 8 hours)
or cefotaxime
•Neonate: 100–150 mg/kg/d (every 8–12 hours)
•Infant or child: 225–300 mg/kg/d (every 6–8 hours)
•Adult: 8–12 g/d (every 4–6 hours)
Penicillin tolerant (MIC
0.1–1.0 mg/L)
Ceftriaxone or
cefepime or
cefotaxime
As above
Penicillin resistant (MIC
> 1 mg/L or
Cefotaxime/ceftriaxone
MIC ≥ 1 mg/L
Cefepime (or
cefotaxime or
ceftriaxone)
As above
plus vancomycin
•Neonates: 20–30 mg/kg/d (every 8–12 hours)
•Infant and child: 60 mg/kg/d (every 6 hours)
•Adults: 45–60 mg/kg/d (every 6–12 hours)
N. meningitidis Penicillin G as above
or ampicillin
•Neonate: 150 mg/kg/d (every 8 hours)
•Infant and child: 300 mg/kg/d (every 6 hours)
•Adult: 12 g/d (every 4–6 hours)
Principles and Practice of Hospital Medicine > Chapter 199. Meningitis and Encephalitis
31. Microorganism Antibiotic Dose
L. monocytogenes Ampicillin As above
Critically ill patients plus gentamicin
•Neonate: 5 mg/kg/d (every 12 hours)
•Infant and child: 7.5 mg/kg/d (every 8 hours)
•Adult: 5 mg/kg/d (every 8 hours)
S. agalactiae
Ampicillin or penicillin G
or cefotaxime
As above
E. coli or other
Enterobacteriaceae
Ceftriaxone or cefepime or
cefotaxime
As above
P. aeruginosa
•Meropenem
•or
•Infant and child:120 mg/kg/day (every 8 hours)
•Adult: 6 g/d (every 8 hours)
ceftazidime
S. aureus
Methicillin susceptible
•Nafcillin
•or oxacillin
•Neonates: 75 mg/kg/d (every 8–12 hours)
•Infants and children: 200 mg/kg/d (every 6
hours)
•Adult: 9–12 g/d (every 4 hours)
Methicillin resistant Vancomycin As above
S. epidermidis Vancomycin As above
or linezolid
•Neonates: 20 mg/kg/d (every 8–12 hours)
•Infant and child: 30 mg/kg/d (every 8 hours)
•Adult: 600 mg (every 12 hours)
H. influenzae
Ceftriaxone or cefepime
or cefotaxime
As above
Principles and Practice of Hospital Medicine > Chapter 199. Meningitis and Encephalitis
32. Treatment acute viral meningitis
• Viral meningitis is treated symptomatically
• antipyretics, antiemetics, and analgesics.
• Amytriptyline and NSAIDs are often required for months
to treat headache from viral meningitis.
• Patients with HSV-2 meningitis can be treated with
• acyclovir 800 mg 5 times daily, or
• famciclovir 500 mg 3 times daily, or
• Valacyclovir 1000 mg 3 times daily for 7 to 14 days.
Principles and Practice of Hospital Medicine > Chapter 199. Meningitis and Encephalitis
33. Treatment Subacute meningitis
Tuberculous meningitis:
• Empirical therapy of tuberculous meningitis is often
initiated on the basis of a high index of suspicion without
adequate laboratory support.
• Initial therapy is a combination
• isoniazid (300 mg/d)
• rifampin (10 mg/kg per day)
• pyrazinamide (30 mg/kg per day)
• ethambutol (15–25 mg/kg per day)
• pyridoxine (50 mg/d) for 8 weeks
• isoniazid and rifampin continued alone for 9–12 months.
• Dexamethasone therapy is recommended for HIV-
negative patients with tuberculous meningitis. The dose
is 12–16 mg per day for 3 weeks, then tapered over 3
weeks.
Principles and Practice of Hospital Medicine > Chapter 199. Meningitis and Encephalitis
34. Treatment Subacute meningitis
C. neoformans
• intravenous amphotericin B (0.7–1.0 mg/kg/d) or
amBisome 4 mg/kg/day or abelcet 5 mg/kg/day
plus
• oral flucytosine (25 mg/kg four times a day). This
combination is typically used for two weeks or until
the CSF culture is sterile.
then
• followed by fluconazole 400 to 800 mg/day, which
is continued for 8 to 10 weeks.
35. Treatment Subacute meningitis
H. capsulatum
• Amphotericin B (0.7–1.0 mg/kg per day) for 4–
12 weeks. A total dose of 30 mg/kg is
recommended. Therapy with Amphotericin B is
not discontinued until fungal cultures are
sterile.
then
• itraconazole 200 mg twice daily is initiated and
continued for at least 6 months to a year
Principles and Practice of Hospital Medicine > Chapter 199. Meningitis and Encephalitis
36. Meningococcal prophylaxis
Rifampicin
• Adults: 600 mg twice daily for two days
• Children: 10 mg/kg twice daily for two days
• Neonates: 5 mg/kg twice daily for two days
Ceftriaxone (pregnant women or contraindication to rifampicin)
• < 12yo: 125mg IM once only
• > 12yo: 250 mg IM once only
• Reconstitute 1 g vial with 3.2 ml lignocaine 1% (250
mg/ml)
The Royal Children's Hospital Melbourne. Meningococcal Prophylaxis. 2012.
38. Encephalitis
Definition
• Encephalitis is an infection of the brain parenchyma
predominantly caused by viruses. Sometimes both
the brain and the meninges are involved, a
condition called meningoencephalitis
Review of Medical Microbiology and Immunology, 13e
40. Encephalitis
• A virus directly infects the brain.
• A virus that caused an infection in the past
becomes reactivated and directly damages the
brain.
• A virus or vaccine triggers a reaction that
makes the immune system attack brain tissue
(an autoimmune reaction).
http://www.merckmanuals.com/home/brain_spinal_cord_and_nerve_diso
rders/brain_infections/encephalitis.html
41. Viruses Commonly Causing Encephalitis with Various Predisposing Factors
Predisposing Factor Common Viruses Comment
Neonate HSV-2 Acquired at time of birth
Child over age of 1 year and
adult
HSV-1
Primarily affects temporal
lobe. Probably reach the brain
by traveling down sensory
neuron following activation of
latent infection in trigeminal
ganglion
Animal bite (e.g., dog, cat,
bat, skunk, raccoon)
Rabies
In United States, dogs and
cats are uncommon
reservoirs. Bats are the most
common reservoir; raccoons
are common reservoirs east of
the Mississippi
Mosquito bite
West Nile virus, Eastern and
Western equine encephalitis
viruses, St. Louis encephalitis
virus, jE
West Nile virus is the most
common arboviral infection in
the United States
Review of Medical Microbiology and Immunology, 13e > Central Nervous System Infections
42. Japanese encephalitis
• โรคไข ้สมองอักเสบ เกิดจากไวรัสหลายชนิดแต่ที่มักเจอ
ในไทยคือ Japanese encephalitis
สาเหตุ
• ติดเชื้อ Japanese encephalitis
การติดต่อ
• มีหมูเป็นรังโรค และมียุงราคาญ (Culex
triaeniorhynchus) เป็นพาหะ
-คณะเวชศาสตร์เขตร้อน โรงพยาบาลเวชศาสตร์เขตร้อน. ไข ้สมองอักเสบ. มหาวิทยาลัยมหิดล. จาก
http://www.tm.mahidol.ac.th/hospital/hospital-japanese-encephalitis-th.php
43. Japanese encephalitis
• endemic area for Japanese B encephalitis
spreads across Asia from Pakistan to the coast of
Siberia and includes Japan. Around 3 billion
people live in this endemic area.
• There are around 68,000 cases of Japanese B
encephalitis each year
• overall incidence of JE among people from
nonendemic countries traveling to Asia is
estimated to be <1 case per 1 million travelers
-http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3-infectious-diseases-related-to-travel/japanese-encephalitis
-http://www.patient.co.uk/doctor/japanese-b-encephalitis
50. Herpes simplex encephalitis
Pathology
• HSV type 1 encephalitis is an acute, necrotizing,
asymmetric hemorrhagic process with
lymphocytic and plasma cell reaction and usually
involves the medial temporal and inferior frontal
lobes. Intranuclear inclusions may be seen in
neurons and glia. Patients who recover may show
cystic necrosis of the involved regions.
Clinical Neurology, 8e
51. Herpes simplex encephalitis
• HSV-1:
• children > 3 months and in adults
• localized to the temporal and frontal lobes
• HSV-2:
• neonates
• brain involvement is generalized, and the usual
cause is acquired at the time of delivery
• Incidence is 2 cases per million population per
year. HSE may occur year-round. HSV-1 is
ubiquitous, and HSV-2 is also common.
International incidence is similar to that in the
United States
http://emedicine.medscape.com/article/1165183-overview#a0156
52. Herpes simplex encephalitis
• Viral infections can affect the CNS in three ways
• hematogenous dissemination of a systemic viral
infection (eg, arthropod-borne viruses),
• neuronal spread of the virus by axonal transport (eg,
herpes simplex, rabies),
• autoimmune postinfectious demyelination (eg, varicella,
influenza).
Clinical Neurology, 8e
55. Herpes simplex encephalitis
Management
• Initial Management
• supportive management: airway, breathing, and
circulation (ABCs)
• General nutritional and fluid support
• Monitor for ICP and seizures.
• Antiviral
• Adults should receive a dose of 10 mg/kg of
acyclovir intravenously every 8 h (30 mg/kg per day
total dose) for 14–21 days.
• neonates with HSV encephalitis receive 20 mg/kg of
acyclovir every 8 h (60 mg/kg per day total dose)
for a minimum of 21 days
Harrison's Principles of Internal Medicine, 18e
64. CDC classification of Reye syndrome are as follows
• Stage 0 - Alert, abnormal history and laboratory findings
consistent with Reye syndrome, and no clinical manifestations
• Stage 1 - Vomiting, sleepiness, and lethargy
• Stage 2 - Restlessness, irritability, combativeness, disorientation,
delirium, tachycardia, hyperventilation, dilated pupils with
sluggish response, hyperreflexia, positive Babinski sign, and
appropriate response to noxious stimuli
• Stage 3 - Obtunded, comatose, decorticate rigidity, and
inappropriate response to noxious stimuli
• Stage 4 - Deep coma, decerebrate rigidity, fixed and dilated
pupils, loss of oculovestibular reflexes, and dysconjugate gaze
with caloric stimulation
• Stage 5 - Seizures, flaccid paralysis, absent deep tendon reflexes
(DTRs), no pupillary response, and respiratory arrest
• Stage 6 - Patients who cannot be classified because they have
been treated with curare or another medication that alters the
level of consciousness
Debra L Weiner. Reye Syndrome . Available from. http://emedicine.medscape.com/article/803683-treatment#a1156
65. Reye’s syndrome: Diagnostic criteria
• Acute noninflammatory encephalopathy with an altered
level of consciousness
• Hepatic dysfunction with a liver biopsy showing fatty
metamorphosis without inflammation or necrosis or a
greater than 3-fold increase in ALT, AST, or ammonia levels
• No other explanation for cerebral edema or hepatic
abnormality
• CSFwith WBC count of 8 cells/µL or fewer (usually
lymphocytes
• Brain biopsy with findings of cerebral edema without
inflammation or necrosis
Debra L Weiner. Reye Syndrome . Available from. http://emedicine.medscape.com/article/803683-treatment#a1156
66. Reye’s syndrome: treatment
• chemicals and fluids – to correct blood chemistry
and supply nutrients, such as glucose (sugar)
• diuretics – reduce excess fluid and swelling in the
brain
• ammonia detoxicants – reduces ammonia
• antiemetic medication – reduce vomiting
Reye's syndrome. NHS. Avalable from:http://www.nhs.uk/conditions/Reyes-syndrome/Pages/Introduction.aspx
67. Reye’s syndrome: treatment
Prevention
• avoidance of aspirin in children with febrile illness
• The risks and benefits of influenza and varicella
vaccines should be weighed up in children taking
long-term salicylates
Reye's Syndrome. Avalable from:http://www.patient.co.uk/doctor/reyes-syndrome
69. Brain abscess
Definition
• A brain abscess is a focal, suppurative infection
within the brain parenchyma, typically
surrounded by a vascularized capsule. The
term cerebritis is often employed to describe a
nonencapsulated brain abscess.
Harrison's Principles of Internal Medicine, 18e
70. Brain abscess
• incidence of 0.3–1.3:100,000 persons per year
• Male: female = 1.5:3.1
การเกิด
• direct spread: paranasal sinusitis, otitis media,
mastoiditis, or dental infection;
• head trauma or a neurosurgical procedure
• hematogenous spread from a remote site of
infection
Harrison's Principles of Internal Medicine, 18e
72. Brain abscess
The most common pathogenic
• aerobic, anaerobic, and microaerophilic
streptococci, and gram-negative anaerobes
such as bacteroides, Fusobacterium, and
Prevotella. Staphylococcus aureus, Proteus,
• and other gram-negative bacilli are less
common.
• Actinomyces, Nocardia, and Candida are also
found. Multiple organisms are present in the
majority of abscesses.
Clinical Neurology, 8e
79. in adults with normal renal and hepatic function
• cefotaxime, 2 g every 4 to 6 hours
• ceftriaxone, 2 gevery 12 hours
• metronidazole 500 mg every 6 to 8 hours
• meropenem, 2 g every 8 hours
• vancomycin, 15 mg per kilogramof body weight every 8 to 12
hours
• penicillin G,2–4 million units every 4 hours
• ampicillin, 2 g every 4 hours
• isoniazid,300 mg; rifampin, 600 mg, pyrazinamide, 15 to 30
mg/kg/day, ethambutol, 15 mg/kg/day every 24 hours
• TMP/SMZ;, 10 to20 mg TMP plus 50 to 100 mg of SMZ per
kilogram per day, two divide doses
• ceftazidime, 2 g every 8 hours;
• cefepime 2 g every 8 hours;
• voriconazole, 4 mg /kg every 12 hours after a loading dose of
6 mg /kg every 12 hours for two doses
• amphotericin B deoxycholate, 0.6 to 1.0 mg/kg every 24 hours
with doses of up to 1.5 mg/kg
Brouwer MC et al. N Engl J Med 2014;371:447-456.
Pathophysiological alterations leading to neuronal injury during bacterial meningitis. BBB, blood-brain barrier; CBV, cerebral blood volume. (Redrawn, with permission, from Koedel U et al. Pathogenesis and pathophysiology of pneumococcal meningitis