Cns infectious disease

1. CNS Infections

2. Meningitis

3. Variable causes and outcome
• Acute Benign Forms of Viral Meningoencephalitis
• Rapidly Fatal Bacterial Meningitis with Local
• Progressive mental deterioration and death
• Different etiological organisms
• Time of starting appropriate therapy

4. Definitions
• Meningitis – inflammation of the meninges
• Encephalitis – infection of the brain parenchyma
• Meningoencephalitis – inflammation of brain +
meninges
• Aseptic meningitis – inflammation of meninges with
sterile CSF

5. Meninges
• Meningitis: inflammation of the pia mater and the arachnoid mater,
with suppuration of the cerebrospinal fluid

6. CAUSES OF MENINGITIS
INFECTIOUS NON-INFECTIOUS
Viral Aseptic Meningitis
Bacteria Malignancy
Mycobacterial Sarcoid
Brucella behcet disease
Fungal SLE

7. Encephalitis/Encephalopathy
• Herpes simplex: PCR, Acyclovir
• Arboviruses: e.g dengue
• Rabies
• Rare: Listeria, cat scratch
disease, amebic

8. Aseptic Meningitis
• CSF: pleocytosis 100s, Norm G &P, Neg Culture
• Enteroviruses: most common cause 80%
• HSV-2, and other viruses
• HIV
• Partial Rx Bacteria
• Drugs: MTZ, TMP-SMX, NSAIDs, carbamazapine, IVIG
• Rare: leptospirosis

9. Viral Meningitis

10. Viral meningitis
• Causes
• Non-polio enteroviruses are most common cause of viral
meningitis
• Common in summer to fall
• Only small number of peo0ple with an enterovirus develops
meningitis
• Other Viruses that can cause meningitis are:
• Mumps, Measles, Influenza, West Nile Virus

11. Viral Meningitis

12. Viral meningitis
• Symptoms
• In Infants: Fever, Irritability, poor eating
• In Adults: Fever, Headache, Stiff neck, Sensitivity to bright light
• Diagnosis
• Naso-oropharyngeal swabs, stool, cerebrospinal fluid, blood, and serum
• Treatment
• Most cases have no specific treatment
• Prevention
• Wash hands, avoid touching your face with unwashed hands, stay home when
sick, Vaccinate against viral infections that can lead to viral meningitis

13. Bacterial meningitis
• Usually severe
• Most people can recover, but it can cause serious complications
• Brain damage, hearing loss, learning disabilities
• Several pathogens can cause bacterial meningitis
• Leading causes includes:
• Haemophilus influenzae (most often caused by type b, Hib), Streptococcus
pneumoniae, group B Streptococcus, Listeria monocytogenes, and Neisseria
meningitidis.

14. Symptoms of Bacterial Meningitis
• High grade sudden fever
• Severe Headache
• Altered level consciousness, irritability, photophobia
• Vomiting
• Seizures
• Stiff neck
• Bulging fontanel in infants

15. Signs
• Vital signs: Fever
• Nuchal rigidity
• Kerning's sign: while patient is lying supine, with the hip and knee flexed to 90
degrees pain limits passive extension of the knee
• Brudzinski's sign: flexion of the neck causes involuntary flexion of the knee and
hip
• Papilledema
• Neurological defecit
• Don’t forget source of infection: ears, sinsuses, chest..etc
• Petechiae, ecchymosis

16. KEkFv2hfgPRSi3P05h9PGw.webp

17. Signs
• Absence of all 3 signs of the classic triad of fever, neck stiffness, and
an altered mental status virtually eliminates a diagnosis of meningitis
• Changes in mental status are more common in bacterial than viral
meningitis
• Kernig and Brudzinski signs have low sensitivity but high specificity

18. Meningitis Symptoms

19. Complications
• Hydrocephalus
• Seizures
• SIADH
• Subdural effusions & empyema
• Septic sinus or cortical vein thrombosis
• Arterial ischemia / infarction (inflammatory vasculitis)
• CN Palsies (esp deafness)
• Septic shock / multi-organ failure from bacteremia (esp meningococcus &
pneumococcus)
• Risk of adrenal hemorrhage with hypo-adrenalism (Waterhouse-Friderichsen
syndrome)

20. Investigations
• CBC, Creat, lytes: Na
• Blood Culture
• CXR
• CT Head
• CSF analysis
Remember to be careful:
–  ICP may increase risk of herniation
– Cellulitis at area of lumbar puncture
– Bleeding disorder

21. CSF analysis
• Appearance, opening pressure
• Cell count with differential
• Glucose, protein
• CSF appearance
• Gram stain
• Culture
• TB AFB smear PCR and culture
• Brucella serology and PCR
• HSV PCR
• Cryptococcus antigen

22. Bacterial Meningitis

24. Bacterial Pathogens
Neonates
• Group B Streptococci 49%, E coli, enterococci, Klebsiella,
Enterobacter, Samonella, Serratia, Listeria
Older infants and children
– Neisseria meningitidis, S. pneumoniae, M.tuberculosis, H.
influenzae

25. Causes of Bacterial meningitis in Adults
Streptococcus pneumonia………….37%
Neisseria meningitides…..13%
Listeria monocytogenes….10%
Other strept.species……….7%
Gram negative……………….4%
Haemophillus influenza……4%
TB, Brucella

26. Keep in mind
• Global emergence and prevalence of Penicillin- Resistant
Streptococcus pneumonia
• Dramatic Reduction in invasive Hemophillus influenza disease
secondary to use of conjugate Haemophillus Type B- vaccine.
• Group B – Streptococci: previously in neonate, now
emerging as disease of elderly

27. Bacterial Meningitis - Empiric Treatment (Gram stain
Neg)
• Remember MENINGEAL DOSES
• Ceftriaxone 2gm IV Q12h
– High CSF levels
• Vancomycin 500-750mg IV Q6h (highly penicillin resistant
pneumococcus)
• Dexamethasone (0.15mg/kg IV Q6h) for 2-4 days : 1st dose
15-20 min prior to or con-comitant with 1st dose Abx to
block TNF production
• Ampicillin (for Listeria)

28. Management Algorithm for Adults
Suspicion of bacterial meningitis
YES
new onset seizure, papilledema, altered level of consciousness, or focal neurological deficit or delay in
performance of diagnostic L.P
NO YES
Blood c/s & Lumbar puncture B/C stat
Dexamethasone + empirical Abx
Dexamethasone + empirical Abx
-ve CT-scan of the head
CSF is abnormal
NO YES
YES
Perform L.P
+ve CSF gram stain
Dexamethasone +
empirical Abx
Dexamethasone +
targeted Abx

30. Treatment & prevention of Pnemococcus
meningitis
• Penicillin G (MIC< 0.1mcg/ml)
• Ceftriaxone 14 days
• Vancomycin if Highly penicillin resistance (MIC>=2mcg/ml)
• Steroids (pre Abx)
• Vaccination:
• Pneumococcal conjugate vaccine (Prevnar 13): Valent
conjugate vaccine for children
• Pneumococcal polysaccharide vaccine (Pneumovax): 23
purified capsular polysaccharide antigens (serotypes 1, 2,
3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C,
19A, 19F, 20, 22F, 23F, and 33F)

31. Treatment of Pneumococcus meningitis
• Steroids (pre 1st dose Abx) for 4 days
• Pen G MIC less than 0.1mcg/mL: Pen G 4 million U Q 4h or
Ampicillin 2gm IV Q4h
• Pen G MIC 0.1-1: Ceftriaxone 2gm IV Q12h
• Pen G Equal to or more than 2: vanco 500-750mg IV Q6h and
ceftriaxone

32. S. Pneumonia Prevention
• Pneumococcal conjugate vaccine (PCV) is a vaccine used to protect infants
and young children
• 13 serotypes of Streptococcus
• Prevnar 13® is a vaccine approved for children 6 weeks
through 17 years of age for the prevention of invasive
disease caused by 13 Streptococcus pneumoniae strains (1,
3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F), and for
children 6 weeks through 5 years for the prevention of
otitis media caused by 7 of the 13 strains (4, 6B, 9V, 14,
18C, 19F, and 23F) Based upon immune responses to the
vaccine, Prevnar 13® is also approved for adults 50 years of
age and older for the prevention of pneumococcal
pneumonia and invasive disease caused by the 13 vaccine
strains Prevnar 13® is not 100% effective and will only help
protect against the 13 strains included in the vaccine

33. S. Pneumonia Prevention
• Pneumococcal polysaccharide vaccine (PPSV)
• 23 serotypes of Streptococcus
• PPSV is recommended (routine vaccination)
• For both children and adults in special risk categories:
• Serious pulmonary problems, eg. Asthma, COPD
• Serious cardiac conditions, eg., CHF
• Severe Renal problems
• Long term liver disease
• DM requiring medication
• Immunosuppression due to disease (e.g. HIV or SLE) or treatment (e.g. chemotherapy or radio therapy,
long-term steroid use
• Asplenia

34. Listeria Monocytogenes Meningitis Treatment
• Ampicillin 2gm IV Q4h +/- Gentamicin 2mg/kg loading dose then
1.7mg/kg Q8h
• 21 day duration
• Penicillin allergy patients: TMP-SMX or Meropenem

41. VIRAL Encephalitis

42. Introduction
• Encephalitis is irritation, swelling, or acute inflammation of the brain
most often due to viral infection or when the body’s own immune
system attacks brain tissue.
• Rare condition that occurs most often in the first year of life and
decreases with age.
• Around 20,000 cases occur each year in the US

43. Figure 1 is computed tomography (CT) scan of a normal brain.
Figure 2 is a CT scan that shows an accumulation of contrast
material in infected areas and around the brain from encephalitis.

44. Causes of Encephalitis
• The exact cause of encephalitis is often unknown, but the most
commonly diagnosed cause is a viral infection.
• Primary encephalitis – occurs when a virus or other infectious agent
directly infects the brain.
• Secondary encephalitis –occurs when a virus first infects another part
of your body and secondarily enters your brain.

45. Common Viral Causes
• Virus causes inflammation of the brain tissue, brain tissue swells
causing cerebral edema, which may destroy the nerve cells causing
intracranial hemorrhage, thus, causing brain damage.
• Exposure to viruses can occur through:
• Breathing in respiratory droplets from infected person
• From contaminated food or drinks
• Mosquito, tick, or other insect bites.
• Skin contact with the virus

46. Herpes Simplex Virus (HSV)
• HSV is the most common cause of encephalitis in people of all ages,
including infants.
• There are two types of herpes simplex virus (HSV). Either type can cause
encephalitis:
• HSV type 1 (HSV-1) is usually responsible for cold sores or fever blisters
around your mouth.
• HSV type 2 (HSV-2) commonly causes genital herpes.
• Encephalitis caused by HSV-1 is rare, but it has the potential to cause
significant brain damage or death.

47. Other herpes viruses
• Other herpes viruses that may cause encephalitis:
• Epstein-Barr virus, which commonly causes infectious mononucleosis.
• Varicella-zoster virus, which commonly causes chickenpox and shingles.

48. Enteroviruses
• Include the poliovirus and the coxsackievirus, which usually cause an
illness with flu-like symptoms, eye inflammation and abdominal pain.

49. Mosquito-borne viruses
• Arboviruses, or arthropod-borne viruses, are transmitted by mosquitoes or
other blood-sucking insects.
• They can cause infections that include West Nile, La Crosse, St. Louis,
western equine and eastern equine encephalitis.
• Mosquitoes transfer the virus from a nonhuman host — such as a bird,
chipmunk or horse — to humans.
• Symptoms of an infection may appear within a few days to a couple of
weeks after exposure to an arbovirus.

50. Tick-borne viruses
• The Powassan virus is a well-known tick-transmitted virus that causes
encephalitis in the U.S. and Canada.
• Symptoms usually appear about a week after exposure to the virus.

51. Rabies virus
• Infection with the rabies virus is transmitted by a bite from an
infected animal.
• Causes a rapid progression to encephalitis once symptoms begin.
• Rabies is a rare cause of encephalitis in the U.S.

52. Childhood Infections
• Common childhood infections — such as measles (rubeola), mumps,
and rubella (German measles) — used to be fairly common causes of
secondary encephalitis.
• These causes are now rare because of the availability of vaccinations
for these diseases.

53. Other Causes of Encephalitis
• Allergic reaction to vaccination
• Autoimmune disease – attack of the brain by the body’s immune
system.
• Acute Disseminated Encephalitis (ADEM)
• NMDA-Receptor Antibody Encephalitis
• Voltage Gated Potassium Channel-Complex Antibody Associated
Limbic
• Hashimotos Encephalitis
• Rasmussen Encephalitis
• Bacteria – Borrelia burgdorferi (Lyme disease), treponema pallidum
(syphillis), and mycobacterium tuberculosis
• Parasites - roundworms, taenia solium (cysticercosis), and
toxoplasmosis in AIDs patients
• Cancer and its effects on the body can cause encephalitis

54. Risk Factors
• Anyone can develop encephalitis, however, there are factors that may increase the risk of
the condition.
• Age – young children and older adults are at a greater risk for viral encephalitis.
Whereas, encephalitis from the herpes simplex virus tends to be more common in
people 20 to 40 years of age.
• Weakened immune system - People who have HIV/AIDS, take immune-suppressing
drugs, or have another condition causing a compromised or weakened immune system
are at increased risk of encephalitis.
• Geographic regions - Mosquito-borne or tick-borne viruses are common in particular
geographic regions.

55. Signs & Symptoms
• Some patients may have symptoms of a cold or stomach infection
before the encephalitis symptoms begin.
• Most people with encephalitis have mild flu-like symptoms such as:
headache, fever, aches in muscles or joints, fatigue or weakness.

56. Emergency presentation of encephalitis:
• Confusion, agitation, or hallucinations
• Poor responsiveness
• Stupor
• Coma
• Muscle weakness or paralysis
• Seizures
• Severe headaches
• Double vision
• Problems with speech & hearing
• Sudden change in mental function like, flat mood, change in mood, or mood that is inappropriate
for the situation.

57. Signs & symptoms in infants & young children:
• Bulging in soft spots (fontanels) of skull
• Nausea and vomiting
• Body stiffness
• Inconsolable crying
• Poor feeding or not waking for a feeding
• Irritability

58. Complications
• Complications that may occur for months or be permanent include:
• Persistent fatigue
• Weakness or lack of muscle coordination
• Personality changes
• Memory problems - especially among those who had herpes simplex virus
encephalitis.
• Paralysis
• Hearing or vision defects
• Speech impairments - aphasia
• Epilepsy
• The most severe cases can result in coma or death.

59. Tests & Diagnoses
• Brain imaging - May reveal swelling of the brain.
• Magnetic resonance imaging (MRI)
• Computerized tomography (CT)
• Spinal tap (lumbar puncture) - cerebrospinal fluid (CSF) is extracted through spinal tap.
Changes in this fluid can indicate infection and inflammation in the brain. The CSF is
analyzed for elevated white blood cell counts, blood, and the presence of virus.
• Other lab tests - Samples of blood or urine, or of excretions from the back of the throat
can be tested for viruses or other infectious agents.
• Electroencephalogram (EEG) - EEG can record the electrical activity of the brain.
Abnormal patterns may be consistent with a diagnosis of encephalitis.
• Brain biopsy - a procedure to remove a small sample of brain tissue (brain biopsy) is used
if symptoms are worsening and treatments are having no effect.

60. Treatment
• Mild cases:
• Bed rest
• Plenty of fluids
• Anti-inflammatory drugs— such as acetaminophen ibuprofen, and naproxen sodium — to
relieve headaches and fever.
• Severe encephalitis:
• Breathing assistance and careful monitoring of breathing and heart function
• Intravenous fluids to ensure proper hydration and appropriate levels of essential minerals
• Anti-inflammatory drugs, such as corticosteroids, to help reduce swelling and pressure
within the skull
• Anticonvulsant medications, such as phenytoin (Dilantin), to stop or prevent seizures.

61. Treatment (cont’d)
• Antiviral drugs:
• Acyclovir (Zovirax)
• Ganciclovir (Cytovene)
• Foscarnet (Foscavir).
• Follow-up therapy:
• Physical therapy to improve strength, flexibility, balance, motor coordination and mobility
• Occupational therapy to develop everyday skills and to use adaptive products that help with
everyday activities
• Speech therapy to relearn muscle control and coordination to produce speech
• Psychotherapy to learn coping strategies and new behavioral skills to improve mood
disorders or address personality changes — with medication management if necessary

62. Prevention
• Vaccines - keeping up-to-date with vaccines is the most effective way of reducing
the risk of developing encephalitis. These include vaccines for measles, mumps,
rubella, and if the virus exists in those areas, Japanese encephalitis and tick-
borne encephalitis.
• Protection from Mosquitoes- In areas known to have mosquitoes that carry
encephalitis causing viruses, take measures to reduce the risk of being bitten.
• Wear appropriate clothing
• Avoid mosquito-infested areas
• Avoid going outside at specific times during the day when there are lots of mosquitoes about
• Keep homes mosquito free and make sure there is no stagnant water about your house.
• Use mosquito repellant

63. Case Study
• A 65-year-old man of eastern European background was transferred to a
hospital with decreased conscious state and behavioral changes. His past
history included depression (without prior psychotic episodes), alcohol
abuse, and hypertension. He had no family history of psychiatric illness. His
only regular medications were Citalopram and Olmesartan. At this facility,
the patient became increasingly aggressive, requiring sedation and
restraint. Following the oral administration of olanzapine and clonazepam,
the patient became drowsy and was transferred to another hospital for a
second opinion. Biochemistry and chest x-ray were normal, and computed
tomography (CT) scan of the brain with contrast showed multiple old small
basal ganglia infarcts. Delusions of misidentification of staff were present,
as were visual hallucinations.

64. Case Study (cont’d)
• A lumbar puncture was performed which demonstrated a protein of 0.4 g/L
(RR, <0.45 g/L), glucose of 3.9 mmol/L (RR, 2.2–5.5 mmol/L), erythrocytes
of 11, no leukocytes, and a negative gram stain. C Reactive Protein (CRP)
rose from normal to 54 mg/L (RR, <20 mg/L). The patient was treated with
IV acyclovir. HSV-1 PCR performed was positive. After commencing
treatment, the patient showed significant improvement in behavior and
cognition. CRP also dropped from a peak of 54 mg/L to normal. In total, he
received twelve days of IV acyclovir and two days of oral acyclovir and was
transferred back to prison on completion of treatment.