CNS infections

1
Infections of the CNS/Brain Abscesses

• Dr Ngemera Johannes A
• MD, Mmed (Int. Medicine)
• August 24th , 2023

2
Introduction

• The Nervous system
• Complex and sophisticated system
• Regulates and coordinates body activities
• Two major divisions
• Central nervous system
• Brain
• Spinal cord
• Peripheral nervous system
• Sensory
• Motor
• Autonomic

3
Meninges

• Three layers of membranes that cover the brain
  and spinal cord
• Dura mater
• outer, tough fibrous membrane
• Arachnoid mater
• middle web-like membrane containing the CSF
• Pia mater
• innermost layer containing several blood vessels

4
Meninges
5
CNS Infections - Introduction

• CNS infections divided into
• Meningitis
• Primarily involve the Meninges
• Encephalitis
• primarily confined to the Brain parenchyma
• Meningoencephalitis
• involve both Meninges and Brain

6
CNS infections causes

• Viral
• HIV, Cytomegalovirus, Rabies virus, etc
• Bacterial
• S.pneumoniae, N.meningitidis,
• Mycobacterium tuberculosis, Trepanema pallidum,
  etc
• Fungi
• Cryptococcus neoformans, Candida albicans
• Protozoa
• Toxoplasmosis, Malaria
• Helminthes
• Taenia solium (cysticercosis)

7
Overview of CNS infections

• CNS infections are life-threatening
• Associated with high mortality and morbidity
• Based on severity, onset of clinical presentation
  may be
• Acute symptoms manifest within 24 hours,
• Sub-acute symptoms last 1-7 days,
• Chronic symptoms last over 7 days.

8
Overview of CNS infections

• Clinical findings are determined by
• anatomic site of involvement
• infecting pathogen
• host response
• Vulnerability of CNS to the effects of
  inflammation edema mandates prompt diagnosis
  with appropriate therapy if consequences to be
  minimized.

9
Pathogenesis

• Four routes which infectious agents can enter
  the CNS
• Hematogenous spread - most common
• usually via arterial route
• can enter retrograde via veins
• Direct implantation - most often is traumatic
• iatrogenic (rare) via lumbar puncture
• Local extension (secondary to established
  infections)
• most often from mastoid, frontal sinuses,
  infected tooth, etc.
• PNS into CNS
• viruses (e.g. Rabies, Herpes zoster)

10
Meningitis

• Clinical syndrome characterized by inflammation
  of the meninges
• Meningoencephalitis
• Inflammation to meninges and brain parenchyma
• Meningitis classified as
• acute pyogenic - usually bacterial meningitis
• Aseptic - usually acute viral meningitis
• Chronic - usually TB, spirochetes, Cryptococcus.

11
Risk Factors

• Lack of immunization
• against S. pneumoniae, H.influenzae type B in
  children
• Hematogenous spread after invasion from a mucosal
  surface (nasopharynx)
• Parameningeal focus
• Otitis media
• Sinusitis
• Extremes of age (lt5 or gt 60 years)
• Penetrating head trauma, Previous neurosurgical
  procedures, shunts

12
Risk Factors

• immunodeficiency
• corticosteroids
• HIV/AIDS
• Diabetes Mellitus
• asplenia
• hypogammaglobulinemia
• complement deficiency
• Over crowding
• contact with colonized or infected persons e.g.
  meningococcal meningitis
• anatomical meningeal defects CSF leaks

13
Bacterial meningitis pathogens based on
patients age
Age Common Bacterial pathogens
0 - 4 weeks Strep. agalactiae, E.coli, Salmonella spp. Listeria monocytogenes, Enterococcus spp., Klebsiella pneumoniae,
4-12 week S.agalactiae, E.coli, L.monocytogenes, Haemophilus influenzae, Strept. pneumoniae, Neisseria meningitidis
3 mo - 18yr H.influenzae, N.meningitidis, S.pneumoniae
18 - 50 yr S.pneumoniae, N.meningitidis
gt50 yr S.pneumoniae, N.meningitidis, L.monocytogenes, aerobic gram-negative bacilli
14
Clinical Features

• About two third of patients present with triad
  of
• Fever rapid onset
• Neck stiffness
• Altered mental status
• Other symptoms include
• Headache
• Photophobia
• Lethargy
• Malaise
• Seizure/convulsions
• Vomiting

15
Physical examination

• Neurological examination to evaluate for
• Focal neurological deficits
• increased intracranial pressure (ICP)
• Level of consciousness - GCS
• Features of meningeal irritation
• Neck stiffness
• Brudzinskis sign
• Kernings sign
• Dermatological manifestation
• Purpura or petechia ?meningococcemia

16
Glasgow Coma Scale
Score Best Score 15 Comatose
8 Unresponsive - 3
17
Signs of meningeal irritation

• Neck stiffness
• The neck resists gentle passive flexion of the
  neck to bring the chin on to the chest and the
  patient experience pain
• Kerning's sign
• the patient experiences pain and hamstring muscle
  spasms on extending the flexed knee
• Brudzinskis sign
• a forward flexing of the neck elicits involuntary
  hip and knee flexion( found in infants and
  children)

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Testing for meningeal irritation
Kernings sign When the patient is lying with
the thigh flexed on the abdomen, the leg cant be
completely extended.
19
Testing for meningeal irritation
Brudziniskis sign When the patients neck is
flexed, involuntary flexion of the knees and hips
is produced.
20
Meningococcal petechial rashes
21
Investigations
22
Investigations

• Lumbar Puncture ? CSF analysis
• Single most important diagnostic test
• Mandatory, especially if bacterial meningitis
  suspected.
• The desired insertion point of the needle is the
  L3-L4 or L4-L5 interspace thus, the needle is
  inserted below the level of the spinal cord.

23
Investigations

• CSF analysis
• Tube 1 Biochemistry ?Glucose, Protein and ADA
• Tube 2 Cytology ? cell count and differential
• Tube 3 Bacteriology ?Gram stain, AFB stain,
  Indian ink Culture and Sensitivity, Cryptococcal
  antigen, gene Xpert,
• Tube 4 VDRL test, or viral studies (PCR)

24
CSF Characteristics
Bacterial Viral Fungal TB
Opening Pressure Elevated Slight elevated Normal or High Usually high
Glucose Low Normal Low Low
Protein Very high Normal High High
RBCs Few None None None
WBCs/mm3) gt200 lt200 lt50 20-30
Diff PMNs Mono Mono Mono
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Other Investigations

• ??

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BACTERIAL MENINGITIS

• Managements

27
Management

• Overall Goals
• Promptly recognize the patient with acute CNS
  infection
• Rapidly initiate appropriate empirical therapy
• Rapidly and specifically identify the etiologic
  agent, adjusting therapies as indicated
• Optimize management of complications

28
Approach to the patient with suspected meningitis
Decision-Making Within the First 30 Minutes
Quick Clinical Assessment
Mode of presentation Less than 24 hours ?
Acute Less than 7 days ? Subacute More
than 1 week ? Chronic
History/physical examination clues
Clinical status of the patient (ABCD)
Integrity of host defenses
29
Treatment - Bacterial Meningitis

• Antimicrobial Rx
• Recommended route Intravenous
• High dose and bolus
• Dosing intervals should be appropriate for drug
  being administered.
• Utilize cidal therapy whenever possible.
• Initiate therapy promptly (i.e. within 30 mins)

30
Treatment - Bacterial Meningitis

• CNS Penetration
• Good Diffusion
• Penicillins
• 3rd and 4th generation Cephalosporins
• E.g. Ceftriaxone, Cefotaxime, Cefepime
• Chloramphenicol
• Rifampin
• TSX
• Poor Diffusion
• Early Gen Cephalosporins, Clindamycin,
  Aminoglycosides, Tetracycline and Macrolides

31
Empiric therapy of Meningitis in adults

• Community-acquired Meningitis
• Likely pathogens
• S.Pneumoniae
• N.meningitidis
• Listeria and H.influenzae
• Therapy
• Ceftriaxone 2g 12hourly
• Vancomycin 1-2g 12hourly
• Ampicillin 2g 4hourly

32
Empiric therapy of Meningitis in adults

• Closed head trauma
• Likely pathogens
• S. Pneumoniae
• Streptococci
• Therapy
• Penicillin G 3-4 mU 4hourly AND
• Vancomycin 1-2 g 12hourly

33
Specific therapy for known pathogens

• S. pneumoniae, N. meningitidis or Streptococci
• Pen G 18-24 mU/day, OR Ampicillin ?12 gm/day
  Plus
• Chloramphenicol ? 75-100 mg/kg/day OR
• Ceftriaxone ?2-4 gm/day
• H. influenzae
• Cefotaxime 12 gm/d
• Ceftriaxone 2-4 gm/d
• Group B streptococci
• Pen G 18-24 mU/d OR
• Ampicillin 12 gm/day (plus aminoglycoside)

34
Specific therapy for known pathogens

• S. Aureus
• Nafcillin 12 gm/d or Vancomycin 2-3 gm/d
• Listeria
• Ampicillin 12 gm/d or
• Pen G 18-24 mu/d plus aminoglycoside
• Gram negative bacilli
• Cefotaxime 12 gm/d Ceftriaxone 2-4 gm/d
• Pseudomonas
• Ceftazidime 6-8 gm/d or
• Cefepime 6 gm/d plus aminoglycoside

35
Duration of Antibiotic treatment

• Depends on causative agent

Organism Duration of treatment
H. influenzae 7 days
N. meningitidis 7 days
S. pneumoniae 10-14 days
L. monocytogenes 14-21 days
Group B streptococci 14-21 days
Gram Negative Rods 21 days
36
Role of corticosteroids in Meningitis

• Role of steroids still somewhat uncertain
• Recent studies suggested that Dexamethasone is
  associated with
• ? in risk of unfavorable outcome (25?15, RR
  0.59) and
• ? in mortality (15?7, RR for death 0.48)
• Benefit primarily ? patients with S. pneumoniae
• Dose of Dexamethasone
• 10mg IV q6h for 4days per protocol,
• Given concurrent with or 15-20 minutes before 1st
  dose of Antibiotics
• Almost all pts with presumed bacterial meningitis
  are candidates for at least single dose of
  Dexamethasone

37
Aseptic Meningitis
38
Aseptic Meningitis

• All non-bacterial causes of meningitis
• Typically less ill appearing than bacterial
  meningitis
• Most common cause is viral
• HSV
• Consider especially in infants presenting with
  seizure
• Usually HSV type II
• Treat with acyclovir
• Enterovirus (coxsackie, echovirus)
• Typically occurs during late summer and fall
• Spread via respiratory secretions and fecal-oral
• Affects all ages
• Generally self-limited illness

39
Aseptic Meningitis - Other Viruses

• HIV
• Arbovirus
• Mumps
• Cytomegalovirus
• Influenza and parainfluenza
• Lymphocytic choriomeningitis virus

• VZV
• Adenovirus
• Measles
• Rubella
• Rotavirus
• EBV

40
Aseptic Meningitis

• Other infectious
• Borrelia burgdorferi
• Mycobacterium tuberculosis
• Treponema pallidum - Syphilis
• Mycoplasma pneumoniae, Chlamydia
• Fungal
• Cryptococcus, Coccidiodes, Histoplasmosis
• Parasitic
• Toxoplasmosis

41
Aseptic Meningitis

• Malignancies
• Lymphoma and leukemia
• Metastatic carcinoma
• Autoimmune disorders
• Sarcoid
• Behcets
• SLE

42
Meningitis in HIV/AIDS

• AIDS defining illness
• Infections commonly found in association with HIV
  and AIDS include
• Cryptococcus neoformans
• Pneumocystic jiroveci
• Candida species and
• Histoplasma capsulatum
• TB meningitis

43
Cryptococcal Meningitis

• AIDS defining illness
• Causative agent
• Cryptococcus neoformans
• Major cause of meningitis in HIV /AIDS

44
Cryptococcal Meningitis Clinical features

• Contrary to bacterial meningitis, the patient may
  not suffer from fever in this case.
• However, the common presenting features are
• severe headache with or without meningism
• altered level of consciousness
• Diagnosis CSF Analysis
• Indian Ink preparation
• Cryptococcal Antigen (CRAg test)

45
Cryptococcal Meningitis - Treatment

• The preferred regimen - 3 phases
• Phase 1 Induction phase
• Amphotericin B 0.7mg/kg/day IV, and
• 5 Flucytosine 100mg/kg/day orally for 14 days
• Phase 2 Consolidation phase
• Fluconazole 400mg/ day for 8 weeks or until CSF
  is sterile.
• Phase 3 Suppressive phase
• Maintenance therapy with Fluconazole 200mg/day

46
Cryptococcal Meningitis - Treatment

• Alternatively regimen
• Inj. Fluconazole IV 1.2g daily for 10 days or
  until the drug can be administered orally then
  continue with the same dose for 10 weeks.
• Thereafter maintain 200 mg daily on alternate
  days as secondary chemoprophylaxis.
• Serial lumbar puncture ? ?intracranial pressure ?
  ?mortality

47
Tuberculous meningitis

• more frequently secondary infection in HIV/AIDS
• The usual local source of infection is a caseous
  focus in the meninges or brain substance adjacent
  to the CSF pathway.
• The brain is covered by a greenish, gelatinous
  exudate, especially around the base, and numerous
  scattered tubercles are found on the meninges.

48
Tuberculous meningitis Clinical features

• Symptoms

• Signs

• Headache
• Vomiting
• Low-grade fever
• Depression
• Confusion
• Behavior changes

• Meningism
• Neck stiffness
• Kernings sign
• Occulomotor palsies
• Papilloedema
• Altered Conscious level
• Focal neurological deficit

49
Tuberculous meningitis

• Untreated TB meningitis is fatal in few weeks
• Complete recovery if treatment is started before
  the appearance of focal signs or stupor
• When treatment is started at a later stage,
• recovery rate is 60 or less and
• survivors show permanent neurological deficit.

50
Investigations

• Lumbar puncture ? CSF analysis
• ?Opening Pressure
• Clear but, when allowed to stand, a fine clot
  (spider web) may form
• WBC up to 500 106 cells/L, predominantly
  Lymphocytes
• ?? Protein and ??glucose.
• Positive AFBs, BUT Negative smear does not
  exclude the diagnosis
• Culture (results up to 6 weeks) treatment must
  be started without waiting for confirmation.

51
Investigations

• Brain CT-Scan
• hydrocephalus
• brisk meningeal enhancement on enhanced CT and/or
  
• intracranial tuberculoma
• Other Investigations
• Sputum for AFBs and Gene Xpert
• Mantoux test
• FBP ESR
• Chest radiography

52
Management

• Anti-TB therapy - HRZE
• Corticosteroids ?controversial
• If given early ? improve mortality but NOT focal
  neurological damage
• For Obstructive hydrocephalus ? Surgical
  ventricular drainage
• Supportive Treatment
• Adequate hydration
• Analgesics/antipyretics
• Anticonvulsants
• Nutrition

53
TOXOPLASMOSIS
54
Toxoplasmosis

• Causative Organism
• Toxoplasma gondii intracellular protozoan
  parasite.
• Cat is a definitive host,
• human and other animal are infected accidentally
  from ingestion of food or water containing cat
  faeces and by ingestion of undercooked meat of
  infected animal.
• Nearly all cases are associated with HIV related
  immuno-suppression. mainly with CD4 count
  lt100cell/mm3

55
Clinical features

• Headache
• Sub acute onset - days to weeks
• Fever
• Neurological sign - Pattern depend on brain
  affected area
• hemiparesis,
• cranial nerve palsies
• ataxia,
• cofusion,
• altered level of consciousness,
• seizures

56
Diagnosis

• Positive serological screening test
• usually indicates previous exposure rather than
  active disease.
• Cerebrospinal fluid analysis
• non diagnostic
• Brain CT-Scan
• shows ring enhancing lesions with surrounding
  edema usually in basal ganglia or at the junction
  of grey white matter in the cortex

57
Brain CT-Scan
ring enhancing lesions with surrounding edema
58
Management

• High dose Trimethoprim/Sulphamethoxazole
• 1920mg twice a day for 4 weeks
• Then 960mg twice a day for 8 weeks
• Secondary prophylaxis
• 960mg daily if CD4 Count is lt350 cell/mm3

59
Management

• The 6-week regimen is as follows
• Pyrimethamine (100mg Stat, 25-50 mg/day) plus
  Sulfadiazine (2-4 g/day divided 4 times daily) OR
• Pyrimethamine (100stat, then 25-50 mg/day) plus
  Clindamycin (300 mg orally 4 times daily)
• Folinic acid (leucovorin) (10-25 mg/day) should
  be given to all patients to prevent hematologic
  toxicity of pyrimethamine
• alternative
• Trimethoprim (10 mg/kg/day) sulfamethoxazole (50
  mg/kg/day) for 4 weeks

60
Neurocysticercosis

• arises from the larvae of the pork tapeworm,
  Tinea solium.
• most common parasitic causing CNS disease.
• develops when humans ingest ova from human
  faeces-larval migrate and develop to cysts in
  human brain or other organs.(intermediate host)
• If human eat undercooked and measly pork
  containing the viable larvae.
• larvae develop to adult tapeworm in small
  intestine. (Definitive host)

61
Clinical features

• Single or repeated seizures, in gt 90 of cases
• May also cause focal neurological disorders
• hemiparesis,
• hydrocephalus.

62
Diagnosis

• Brain CT-scan or MRI
• Serology

63
Neurocysticercosis - Brain CT Scan
Calcifications appear as hyperdense lesions
without surrounding inflammation, edema nor
enhancement
64
Treatment

• Albendazole
• 15mg/kg 2-4 weeks or
• Praziquantel
• 25mg/kg tds 2-3 weeks
• AND
• Steroids
• Dexamethasone 8mg TDS gt 7days or
• Prednisolone 60mg OD gt7 days

65
Prevention

• personal hygiene
• mass Rx
• safe, faeces disposal,
• pig husbandry meat inspection

66
Brain Abscess
67
Brain Abscess

• Focal collection within brain parenchyma
• Intracranial abscesses are uncommon, serious,
  life-threatening infections.
• Classified according to the anatomical location
  or the etiologic agent

68
Pathogenesis

• Direct (45-50 of cases)
• Usually causes a single (Focal) abscess
• may occur from necrotic areas of osteomyelitis
• more commonly associated with subacute and
  chronic otitis infection and mastoiditis
• May extend to various sites in the CNS, causing
• Cavernous sinus thrombosis
• Retrograde meningitis and
• epidural, subdural, and brain abscess.

69
Pathogenesis

• Hematogenous ( 25)
• From a distant focus
• Commonly cause multiple and multiloculated
  abscesses
• No identifiable sources in 20-40 of the cases
• The most common effected lobes (in descending
  frequency) are the fontal, temporal, parietal,
  cerebellar, and occipital.

70
Pathogenesis

• Trauma
• Open skull fracture allows organisms to seed
  directly in the brain.
• Brain abscess can also occur as a complication
  of
• intracranial surgery, and
• foreign body, such as bullets
• Occasionally brain abscess can develop after
  trauma to the face.
• Cryptogenic (at least 15 of cases)
• Unknown source of the infection

71
Primary sources in direct spread and distribution
of abscess

• Otitis media inferior temporal lobe and
  cerebellum
• Frontal or ethmoid sinuses frontal lobe
• Dental caries frontal lobe
• Foreign bodies - bullet

72
Primary sources of hematogenous spread

• Chronic pulmonary infections
• Lung abscess and empyema
• Skin infection
• Intrabdominal and pelvic infection
• Bacterial endocarditis
• Cyanotic congenital heart disease most common
  in children

73
Causative organisms

• Anaerobics
• Usually mouth flora
• May be from pelvic or intraabdominal infections
  multiple abscesses
• E.g. anaerobic streptococci, bacteroides species,
  fusobacterium

74
Causative organisms

• Aerobics
• Gram positive
• Staphylococcus aureus neurosurgery and trauma
• Streptococcus milleri proteolytic enzymes that
  cause necrosis
• Others viridans streptococci, microaerophilic
  streptocci
• Gram negative
• Usually from trauma or neurosurgery
• Klebsiella pneumoniae, Pseudodomonas species,
  E.coli, and Proteus species

75
Immunocompromised hosts

• Opportunistic infections
• Toxoplasma gondii
• Listeria
• Fungi
• Aspergillus,
• cryptococcus neoformans,
• coccidiodidides immitis,
• Candida albicans

76
Immigrants

• Parasites
• Cysticercosis
• 85 of brain infection in Mexico city

77
Symptoms

• Headache most common
• Neck stiffness
• Associated with occipital abscess
• Abscess leaks into lateral ventricle
• Altered mental status cerebral edema
• Vomiting increased intracranial pressure

78
Physical finding

• Fever not very reliable, since only 45-50
  present
• Focal neurological deficit days or weeks after
  onset of headache
• Seizure
• 25 of the cases
• May be first manifestation of brain abscess
• Grand mal in frontal infection
• Third or sixth cranial palsy increased
  intracranial pressure
• Papilledema cerebral edema

79
Investigations

• CT scan with contrast
• MRI with gadolinium diethylenetriamine
• Lumbar puncture
• Contraindicated
• Analysis
• WBC lt 500/mm3 with predominately lymphocytes
• WBC gt 1,000/mm3 consistent with meningitis but
  not improved with antibiotics, consider MRI for
  ruptured abscess

80
Treatment options

• Antibiotics 6 to 8 weeks
• Surgical drainage

81
Antibiotics for Brain abscess

• Penicillin G
• Aerobic and anaerobic streptococci from mouth
  flora
• Metronidazole
• against anaerobes but not aerobes, good
  intralesional penetration
• Ceftriaxone or cefotaxime
• Enterobacteraciae, particular chronic ear
  infection
• Ceftazidime
• neurosurgery and p. aeruginosa
• Oxacillin or nafcillin
• head trauma or neurosurgery, mainly staph. aureus
  coverage
• Vancomycin
• MRSA
• Aminoglycosides
• poor blood brain barrier, not use

82
Surgical drainage

• Indications
• No clinical improvement within a week
• Depressed sensorium
• Increased intracranial pressure
• Progressive increase in the ring diameter of the
  abscess

83
Surgical approach

• Needle aspiration
• Prefer approach because of less neurological
  deficit
• Under ultrasound or CT guided
• Surgical excision
• More neurological deficit
• Prefer in traumatic abscess, particularly with
  foreign body,and encapsulated fungal abscess
• Advantages shorten antibiotics to 2 to 4 weeks
  and less relapse

84
Steroid use

• Mainly for mass effect
• Disadvantages
• Reduce contrast enhancement on CT scan
• Slow capsule formation
• Increase risk of rupture
• Decrease penetration of antibiotics

85
Complications

• Neurological deficits commonly seizure with
  frontal lesion
• Poor prognosis mortality rate up to 30
• Rapid progression of the infection
• Severe mental changes
• Rupture into ventricle

86
Reference