1. Acute and chronic meningitis, encephalitis III
Prof Dr Meral Sonmezoglu
Yeditepe University Hospital

2. The two major divisions in the nervous system are the central nervous system (CNS), composed of the brain and the spinal cord, and the peripheral nervous system (PNS), composed of afferent (input to CNS) and efferent (output to periphery) neurons.
Within the PNS, major divisions are the somatic nervous system (controls skeletal muscle) and in the autonomic nervous system, which has two branches: the parasympathetic (rest and digest) and the sympathetic (emergency) branches.

3. Protection of the Brain
The brain is protected by bone, meninges, and cerebrospinal fluid (CSF)

4. The CSF circulates through the ventricular system
CSF is produced by the choroid plexus inside the ventricles.
It circulates through the ventricles.
From the fourth ventricle, CSF enters the subarachnoid space, between the arachnoid mater and pia mater.
Reabsorbed from subarachnoid space into venous blood via the arachnoid villi

6. Meninges (s. meninx)
Three connective tissue membranes external to the CNS – dura mater, arachnoid mater, and pia mater
Functions:
Cover and protect the CNS
Protect blood vessels and enclose venous sinuses
Contain cerebrospinal fluid (CSF)
Form partitions within the skull

7. Meninges

8. Dura Mater
Tough meninx composed of two fibrous CT layers. Layers separate in certain areas and form dural sinuses. Dural sinuses collect venous blood from the brain.
3 dural septa limit excessive movement of the brain
Falx cerebri – dural fold that dips into the longitudinal fissure
Falx cerebelli – runs along the vermis of the cerebellum
Tentorium cerebelli – horizontal fold extending into the transverse fissure

9. Dura Mater

10. Arachnoid Mater
Separated from the dura mater by the subdural space (a narrow serous cavity)
Beneath the arachnoid is a wide subarachnoid space filled with CSF and large blood vessels
Arachnoid villi protrude superiorly and permit CSF to be absorbed into venous blood

11. Pia Mater
Deepest meninx – delicate CT that clings tightly to the brain and follows convolutions

12. Cerebrospinal Fluid (CSF)
Watery, similar in composition to blood plasma, but contains less protein and different ion concentrations than plasma
Forms a liquid cushion that gives buoyancy to the CNS organs, prevents the brain from crushing under its own weight
Protects the CNS from blows and other trauma
Nourishes the brain and may carry chemical signals from one part of the brain to another

13. Choroid Plexuses
Clusters of interwoven capillaries in each ventricle between the pia mater and a layer of ependymal cells.
Ion pumps allow them to alter the ion concentrations of the CSF
Help cleanse CSF by removing wastes

14. Circulation of CSF

15. Blood-Brain Barrier
Protective mechanism that helps maintain a stable environment for the brain
Bloodborne substances in brain capillaries are separated from neurons by:
Continuous endothelium of capillary walls
Relatively thick basal lamina
Bulbous feet of astrocytes
Least permeable capillaries in the body due the nature of the tight junctions between endothelial cells

16. Blood-Brain Barrier: Functions
Selective barrier that allows nutrients to pass freely
Is ineffective against substances that can diffuse through plasma membranes (fats, gasses, alcohol)
Absent in some areas (vomiting center and the hypothalamus), allowing these areas to monitor the chemical composition of the blood

17. Meningitis
Meningitis is a clinical syndrome characterized by inflammation of the meninges

18. Classification
Depending on the duration of symptoms, meningitis may be classified as acute or chronic.
Acute meningitis denotes the evolution of symptoms within hours to several days, while chronic meningitis has an onset and duration of weeks to months.
The duration of symptoms of chronic meningitis is characteristically at least 4 weeks.

19. Classification
Meningitis can also be classified according to its etiology.

20. Meningitis Bacterial Viral ( aseptic) TB Fungal Chemical Parasitic
? Carcinomatous

21. Classification of Meningitis
Infectious
Bacterial
Viral
Fungal
Non-infectious
Drug-Induced
Neoplastic
Autoimmune
R1’s: What is the most common cause of bacterial meningitis in the developed world?
R2’s: What is most common viral cause of meningitis?
R3’s: Name a drug that is known to cause meningitis?
Drugs: ibuprofen, erythromycin, amoxicillin, OKT3, azathiprine, INH
Autoimmune – SLE; Behcets (sm vessel vasculitis)

22. Bacterial Meningitis in Adults
Frequency of n. meningitidis is decreasing.
Frequency of s. pneumoniae, group B streptococcal, h. influzena and listeria are constant.
Frequency of staphylococcal meningitis increased (not significant)
Staphylococcal meningitidis is caused by 2 species: S. auerus and s. epidermidis
Streptococcal = GBS + group A strep – not separated in this study.
Staphylococcal associated with instrumentation and hardware.
Deeks SL. Bacterial meningitis in Canada ( ). Canadian Communicable Disease Report. Dec :23.

24. Viral Meningitis
Epidemiology less clear b/c the majority of cases are not reportable and the etiology is often not identified.
Majority of cases occur in children < 1 yr.
Enteroviruses: Strains of echovirus & coxsackie B are the two most common pathogens.
HSV: HSV 2 causes the majority of cases. 30% of patients with primary genital herpes will develop septic meningitis.
Arborviruses: Viruses which cause encephalitis in adults (Western Equine, Eastern Equine, Colardo tick fever, St. Louis encephalitis virus) may cause aseptic meningitis in children. Also includes West Nile virus
Other: mumps (30% of cases will present w/ aseptic meningitis +/- parotitis), HIV
PICNIC Study: Aseptic meningitis in Cdn children –
802 cases
233 had pathogen identified – all enteroviruses

25. Noninfectious.. Metabolic Mitochondrial (Reye’s, MELAS)
NMS (Neuroleptic malignant syndrome)
Nutritional deficiency (Wernicke’s)
Paraneoplastic
PRES or Malignant hypertension
Seizures – (non-convulsive status)
TBI
Toxic
Vascular

26. Meningitis
Aseptic meningitis is a broad term that denotes a non-pyogenic cellular response, which may be caused by many different etiologic agents
Many of these cases are found to have a viral etiology and can then be reclassified as acute viral meningitis (eg, enterovirus meningitis, herpes simplex virus [HSV] meningitis).

27. Bacterial Meningitis Definition Epidemiology
Bacterial meningitis is an inflammatory response to bacterial infection of the pia-arachnoid and CSF of the subarachnoid space
Epidemiology
Incidence is between 3-5 per 100,000
More than 2,000 deaths annually in the U.S.
Relative frequency of bacterial species varies with age.

28. Epidemiology Meningitis Neonates (< 1 Month) Gm (-) bacilli 50-60%
Grp B Strep %
Listeria sp %
H. influenza 0-3%
S. pneumo %

29. Epidemiology Meningitis Children (1 month to 15 years)
H. influenzae 40-60%
Declining dramatically in many geographic regions
N. meningitidis 25-40%
S. pneumo %

30. Meningitis Epidemiology Adults (> 15 years)
S. pneumo %
N. Meningitidis 10-35%
Major cause in epidemics
Gm (-) Bacilli 1-10%
Elderly
S. aureus 5-15%
H. influenzae 1-3%
>60 include Listeria, E. coli, Pseudomonas

31. Pathogenesis Meningitis Majority of cases are hematogenous in origin
Organisms have virulence factors that allow bypassing of normal defenses
Proteases
Polysaccharidases

32. Meningitis Pathology and Pathogenesis
Sequential steps allow the pathogen into the CSF
Nasopharyngeal colonization
Nasopharyngeal epithelial cell invasion
Bloodstream invasion
Bacteremia with intravascular survival
Crossing of the BBB and entry into the CSF
Survival and replication in the subarachnoid space

33. Nasopharynx -> blood -> subarachnoid space

34. Pathophysiology of Bacterial Meningitis
Bacterial colonization within the subarachnoid space
Initiation of inflammatory response which leads to:
Endothelial damage
Disruption of the blood-brain barrier
On a larger scale, this results in:
Cerebral edema
Cytotoxic
Vasogenic
Interstitial
Increased ICP
Cytotoxic: degradation of bacteria & neutrophils -> cell function disruption.
Vasogenic: endothelial damage and BBB leakage
Interstitial: increased CSF viscosity (due to protein leak) and decreased venous drainage

35. Meningitis Pathology and Pathogenesis
Key advances in the pathophysiology of meningitis include the pivotal role of cytokines (eg, tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]–1), chemokines (IL-8), and other proinflammatory molecules in the pathogenesis of pleocytosis and neuronal damage during bacterial meningitis.
Increased CSF concentrations of TNF-alpha, IL-1, IL-6, and IL-8 are characteristic findings in patients with bacterial meningitis

36. Meningitis Pathology Hallmark Exudate in the subarachnoid space
Accumulation of exudate in the dependent areas of the brain
Large numbers of PMN’s
Within 2-3 days inflammation in the walls of the small and medium-sized blood vessels
Blockage of normal CSF pathways and blockage of the normal absorption may lead to obstructive hydrocephalus

38. Meningitis
Overall, the net result is vascular endothelial injury and increased BBB permeability leading to the entry of many blood components into the subarachnoid space.
This contributes to vasogenic edema and elevated CSF protein levels.
In response to the cytokines and chemotactic molecules, neutrophils migrate from the bloodstream and penetrate the damaged BBB, producing the profound neutrophilic pleocytosis characteristic of bacterial meningitis.

39. Pathophysiology of Bacterial Meningitis
Complications:
Seizures
Hydrocephalus
Infarction
Herniation
Seizures: cortical inflammation
Hydrocephalus: basal obstruction of CSF flow
Infarct: Inflammatory occulusion of basal arteries
Herniation: generalized edema
From van de Beek D Community-acquired bacterial meningitis in adults. 354:

40. Clinical Presentation of Meningitis
Classic signs ;
fever, headache, neck stiffness, photophobia, nausea, vomiting, and signs of cerebral dysfunction (eg, lethargy, confusion, decreased level of consciousness coma).
The triad of fever, nuchal rigidity, and change in mental status is found in only two thirds of patients
Atypical presentation may be observed in certain groups (elderly, diabetic, neutropenic, immunocompromised hosts..).

41. Clinical Presentation of Meningitis
Signs of cerebral dysfunction are common, including confusion, irritability, delirium, and coma. These are usually accompanied by fever and photophobia.
Signs of meningeal irritation are observed in only approximately 50% of patients with bacterial meningitis, and their absence certainly does not rule out meningitis

42. Meningitis Clinical Manifestations – Nuchal rigidity Kernig’s
Pt supine with flexed knee has increased pain with passive extension of the same leg
Brudzinski’s
Supine pt with neck flexed will raise knees to take pressure off of the meninges
Present in 50% of acute bacterial meningitis cases
Cranial Nerve Palsies
IV, VI, VII
Seizures

43. Brudzinski’s Sign
Brudzinski’s sign: Passive flexion of the neck leads to hip & knee flexion
Reported sensitivity much higher – 97%
Specificity very low

44. Kernig’s Sign
Kernig’s sign: Patient supine. Flex hip to 90°. Attempt to extend knee. Pain should not occur before 135°.
Probably requires significant meningeal inflammation (as seen with bacterial meningitis), and is less likely to be positive in viral meningitis.
Reported sensitvity of only 57%.

45. Trunk supported by arms
Amos’s Sign
Hips & knees flexed
Back arched
Neck in extension
Trunk supported by arms
Sign of significant meningismus.

46. Meningitis
Focal neurologic signs may develop as a result of ischemia from vascular inflammation and thrombosis
Papilledema and other signs of increased ICP may be present.
Coma, increased blood pressure with bradycardia, and cranial nerve III palsy may be present.
The presence of papilledema also suggests a possible alternate diagnosis (eg, brain abscess).

47. Meningitis
Papilledema

48. Meningitis Clinical Manifestations - Meningococcemia Prominent rash
Diffuse purpuric lesions principally involving the extremities
Fever, hypotension, DIC
History of terminal complement deficiency
Classic findings often absent
Neonates
Elderly

49. Meningitis

50. Diagnosis of Meningitis
Assess for increased ICP
Papilledema
Focal neurologic findings
Defer LP until CT scan or MRI obtained if any of above present
If suspect meningitis and awaiting neuroimaging
Obtain BC’s and start empiric Abx

51. Diagnosis of Meningitis
Obtain CT scan before lumbar puncture in patients with:
Immunucompromised state
History of CNS disease
New onset seizures
Papilledema
Altered level of consciousness
Focal neurologic signs

52. Diagnosis of Meningitis
Obtain blood cultures and give empiric antibiotics if LP is delayed

53. Diagnosing Meningitis
Spinal tap is performed
needle is inserted into an area in the lower back
Identification of the type of bacteria
is important for selection of correct antibiotics.

54. Lumbar puncture

56. LP-CSF Tube # 1 Protein & Glucose Tube # 2 Gram stain & Culture
Tube # 3 Cell count & differential
Tube # 4 Store ( PCR, viral studies etc)

57. Diagnosis of Meningitis
CSF Findings :
Opening pressure
Appearance
Cell count & differential
Glucose
Protein
Gram stain & culture

59. Bacterial Meningitis Opening pressure: high, > 200 mmH20 Cloudy
cells/mm3 with a neutrophil predominance of about 80-95%
<40mg/dl and less than 2/3 of the serum glucose
Protein elevated

60. Tuberculous meningitis 180-300
Agent
Opening Pressure
WBC count per µL
Glucose (mg/dL)
Protein (mg/dL)
Microbiology
Bacterial meningitis
; >80% PMNs*
<40
>100
Specific pathogen demonstrated in 60% of Gram stains and 80% of cultures
Viral meningitis
90-200
10-300; lymphocytes
Normal, reduced in LCM and mumps
Normal but may be slightly elevated
Viral isolation, PCR† assays
Tuberculous meningitis
; lymphocytes
Reduced, <40
Elevated, >100
Acid-fast bacillus stain, culture, PCR
Cryptococcal meningitis
10-200; lymphocytes
Reduced
50-200
India ink, cryptococcal antigen, culture
Aseptic meningitis
Normal
Negative findings on workup
Normal values
80-200
0-5; lymphocytes
50-75
15-40

61. Diagnosis Meningitis Rapid Tests CT/MRI
CIE (Counter immunoelectrophoresis/ latex agglut.)
PCR
CT/MRI
Little role in DIAGNOSIS of menigitis
Obtain if suspect increased ICP

62. Diagnosis Additional Tests Meningitis CBC w/ diff Blood cultures CXR
Electrolytes and renal function

63. Bacterial Cultures “Gold standard”
Positive in 75-85% who have not been treated with antibiotics

64. Differential Diagnosis
Meningitis
Differential Diagnosis
CNS infections (abscess, encephalitis)
Viral/ Tb/ Lyme meningitis
Ricketsial infections
Cerebral vasculitis
Subarachnoid hemorrhage
Neurosyphilis

65. Risk and/or Predisposing Factor Bacterial Pathogen Age 0-4 weeks
S agalactiae (group B streptococci) E coli K1 L monocytogenes
Age 4-12 weeks
S agalactiae E coli H influenzae S pneumoniae N meningitidis
Age 3 months to 18 years
N meningitidis S pneumoniae H influenzae
Age years
S pneumoniae N meningitidis H influenzae
Age older than 50 years
S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli
Immunocompromised state
Intracranial manipulation, including neurosurgery
Staphylococcus aureus Coagulase-negative staphylococci Aerobic gram-negative bacilli, including Pseudomonas aeruginosa
Basilar skull fracture
S pneumoniae H influenzae Group A streptococci
CSF shunts
Coagulase-negative staphylococci S aureus Aerobic gram-negative bacilli Propionibacterium acnes

66. Fungi
Cryptococcus neoformans C immitis B dermatitidis H capsulatum Candida species Aspergillus species
Viruses
Enterovirus PoliovirusEchovirusCoxsackievirus ACoxsackievirus BEnterovirus 68-71
Herpesvirus HSV-1 and HSV-2Varicella-zoster virusEBVCMVHHV*-6HHV-7
Paramyxovirus Mumps virusMeasles virus
Togavirus Rubella virus
Flavivirus Japanese encephalitis virusSt. Louis encephalitis virus
Bunyavirus California encephalitis virusLa Crosse encephalitis virus
Alphavirus Eastern equine encephalitis virusWestern equine encephalitis virusVenezuelan encephalitis virus
Reovirus Colorado tick fever virus
Arenavirus LCM virus
Rhabdovirus Rabies virus
Retrovirus HIV

67. Meningitis Treatment Neonates (<3 months)
Emergent empirical antimicrobial therapy
Based on age and underlying disease status
Empiric antibiotic regimines
Neonates (<3 months)
Ampicillin plus a third generation cephalosporin
Children
Third generation cephalosporin ( alternative -ampicillin and chloramphenicol)
Young adults
Third generation cephalosporin (Ceftriaxone) + Vancomycin

68. Treatment Meningitis Empiric Antibiotic Regimines Older adults
Ampicillin in combination with third generation ceph.
Postneurosurgical Pt’s
Vancomycin plus ceftazidime until cultures are available

69. Treatment Meningitis N. Meningitidis S. pneumoniae High dose Pen G
Ceftriaxone
For areas with high level resistance
Vancomycin plus third generation cephalosporin or rifampin

70. Meningitis Treatment Gm (-) Enterics L. monocytogenes S. aureus
Third generation cephalosporins
L. monocytogenes
Ampicillin
S. aureus
Vancomycin or Nafcillin
S. epidermidis
Vancomycin

71. Treatment Predisposing Feature Antibiotic(s) Age 0-4 weeks
Ampicillin plus cefotaxime or an aminoglycoside
Age 1-3 months
Ampicillin plus cefotaxime plus vancomycin*
Age 3 months to 50 years
Ceftriaxone or cefotaxime plus vancomycin*
Older than 50 years
Ampicillin plus ceftriaxone or cefotaxime plus vancomycin*
Impaired cellular immunity
Ampicillin plus ceftazidime plus vancomycin*
Neurosurgery, head trauma, or CSF shunt
Vancomycin plus ceftazidime

73. Treatment Duration of Treatment Meningitis
Dependent on infecting organism
Average of days
Gm (-) bacilli for 3 weeks

74. Treatment Meningitis Steroids
Shortly before or along with antibiotics. Do not give steroids after antibiotic treatment.
de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347:

75. Corticosteroids in Children
Despite the conclusion of the Cochrane review, use is still controversial
CPS statement:
No recommendations for routine use
If used, should only be given to children > 6 wks and before or within 1 hr of antibiotics
Current Capital Health practice is to limit the use of steroids to children presenting with severe sepsis
Most evidence for benefit of dexamethasone in children is in those infected with h. influenzae – since this is now rarely a cause, feeling is that the evidence cannot be generalized to other types of meningitis.
Canadian Paediatric Society Statement. Therapy of suspected bacterial meningitis in Canadian children six weeks of age and older. Ped & Child Health. 6:3. March Reaffirmed February 2006.

76. Complications
The long-term neurologic sequelae can be grouped into 3 categories as follows:
Hearing impairment
Obstructive hydrocephalus
Brain parenchymal damage: Most important feared complication of bacterial meningitis. It could lead to sensory and motor deficits, cerebral palsy, learning disabilities, mental retardation, cortical blindness, and seizures.

77. Mortality of meningitis
Overall mortality rate from bacterial meningitis has decreased but remains alarmingly high. It is reported to be approximately 25%.
Among the common causes of acute bacterial meningitis, the highest mortality rate is observed with pneumococcus.
19-26% for S pneumoniae meningitis,
3-6% for H influenzae meningitis,
3-13% for N meningitidis meningitis,
15-29% for L monocytogenes meningitis.

78. Meningitis Pneumococcal Meningitis Prognosis
Associated with the highest mortality rate
19-26%
Permanent neurologic sequelae
1/3 of pts
Hearing loss
Mental retardation
Seizures
Cerebral Palsy

79. Vaccination
The use of the HIB vaccination is strongly recommended in susceptible individuals.
Vaccination against S pneumoniae is strongly encouraged in susceptible individuals, (older than 65 years and with chronic cardiopulmonary illnesses).
Vaccinations against encapsulated bacterial organisms (eg, S pneumoniae, N meningitidis) are encouraged for those with functional or structural asplenia.
Offer vaccination with quadrivalent meningococcal polysaccharide vaccine to all high-risk populations, including those with underlying immune deficiencies, those who travel to hyperendemic areas and epidemic areas, and those involved with laboratory work that deals with routine exposure to N meningitidis. College students who live in dormitories or residence halls are at modest risk; inform them about the risk and offer vaccination.
Vaccination against N meningitidis is recommended for all adolescents aged years. 
Vaccination against measles and mumps effectively eliminates aseptic meningitis syndrome caused by these pathogens.

80. Vaccinations Meningitis
Asplenic pts should have had a pneumoccocal vaccine prior to their splenectomy
Vaccines available for H. influenza
Prophylaxis for N. meningitidis contacts
Rifampin

81. Prevention
The widespread use of viral vaccines for polio, measles, mumps, rubella and varicella has almost eliminated CNS complications from these in the US.
Domestic rabies vaccinations have reduced the frequency of rabies encephalitis.

82. Prevention II
Control of encephalitis from arboviruses has been less successful without specific vaccines.
Control of insect vectors by spraying methods and eradication of insect breeding sites hasreduced incidence of these infections.

83. Meningococcal vaccine

84. Chemoprophylaxis

85. Conclusion Meningitis Meningitis is an infectious disease emergency
Mortality is often high but can be prevented with appropriate medical therapy
If you consider meningitis in your differential, you are committed to an LP and empiric antibiotics

86. The characteristic skin rash (purpura) of meningococcal septicemia, caused by Neisseria meningitidis

89. Pneumococcal meningitis in a patient with alcoholism
Pneumococcal meningitis in a patient with alcoholism. Courtesy of the CDC/Dr. Edwin P. Ewing, Jr.

91. Follow-up Close follow-up needed after hospital discharge:
Hearing should be assessed 1-2 mo. after d/c using BEARS testing
Neuromuscular assessment at the time of d/c should be documented and periodically assessed outpatient to detect any deficiencies
Learning disabilities, behavior disorders and speech delay require close monitoring after d/c

92. An Approach to the Adult Patient with Suspected Bacterial Meningitis
Summary:
Shock: Sepsis
Protocol
From supplement to:
Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med ; 354:44-53

93. Summary: An Approach to the Adult Patient with Suspected Bacterial
Meningitis
Indications
Age > 60
Recent seizures
Immunocompromised
Prev CNS disease or hardware
Focal neurological deficits
Papilledema
Altered LOC*
Shock: Sepsis
Protocol
From supplement to:
Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med ; 354:44-53

94. Give dexamethasone IV before or with 1st dose of antibiotics
Summary:
An Approach to the
Adult Patient with
Suspected Bacterial
Meningitis
Corticosteroids
Give dexamethasone IV before or with 1st dose of antibiotics
Contraindications
Antibiotics w/in 48 hrs
Shunt
Head trauma
Shock: Sepsis
Protocol
From supplement to:
Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med ; 354:44-53

95. Contraindications to LP
Summary:
An Approach to the
Adult Patient with
Suspected Bacterial
Meningitis
Shock: Sepsis
Protocol
Contraindications to LP
Recent seizure
Signs of herniation at any time
GCS < 11 or rapidly declining LOC
Focal neurologic deficits
Papilledema *
SOL or brain shift on CT
Coagulopathy
From supplement to:
Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med ; 354:44-53

96. Empiric Antibiotic Therapy
Summary:
An Approach to the
Adult Patient with
Suspected Bacterial
Meningitis
Shock: Sepsis
Protocol
Empiric Antibiotic Therapy
Cefotaxime 2g IV or Ceftriaxone 2g IV
+/- Ampicillin 3g IV
+/- Vancomycin 1g IV
From supplement to:
Van de Beek D. Community-acquired bacterial meningitis in adults. N Engl J Med ; 354:44-53

97. CHRONIC MENINGITIS

98. Chronic meningitis is an inflammation of the meninges with subacute onset and persisting cerebrospinal fluid (CSF) abnormalities lasting for at least one month.
Several non-infectious and infectious etiologies are known to be causative.
The wide range of different etiologies renders the approach to patients with this syndrome particularly difficult

99. Chronic meningitis Bacteria Fungi Parasites Category Agent
M tuberculosis B burgdorferi T pallidum Brucella species Francisella tularensis Nocardia species Actinomyces species
Fungi
C neoformans C immitis B dermatitidis H capsulatum Candida albicans Aspergillus species Sporothrix schenckii
Parasites
Acanthamoeba species N fowleri Angiostrongylus cantonensis G spinigerum B procyonis Schistosoma species S stercoralis Echinococcus granulosus

100. Common infectious causes of chronic meningitis and diagnostic approach

101. Any inflammatory process of the meninges and/or of the brain parenchyma leading to signs and symptoms for more than 4 weeks is termed chronic meningitis and meningoencephalitis, respectively
Criteria of this diagnosis a pleocytosis in the cerebrospinal fluid is obligatory

102. Clinical Picture and Complications
Neurologically, these patients present with an insidious onset of headache, mild neckstiffness, usually low grade fever, and – only as time goes by – with focal neurological signs.
Only in case of vasculitis there may be a sudden onset of neurological focal signs.
A potentially life-threatening complication is the development of hydrocephalus, be it obstructive or malresorptive, eventually leading to qualitative and quantitative impairment of consciousness.
Rarely, a chronic inflammatory process may lead to epileptic seizures, according to the underlying pathology of focal or generalized pattern.

103. ENCEPHALITIS

104. Encephalitis
Encephalitis, an inflammation of the brain parenchyma, presents as diffuse and/or focal neuropsychological dysfunction.
Encephalitis is distinct from meningitis, though on clinical evaluation the 2 often coexist with signs and symptoms of meningeal inflammation, such as photophobia, headache, or a stiff neck.

105. Encephalitis
Acute encephalitis is most commonly a viral infection with parenchymal damage varying from mild to profound
Subacute and chronic encephalopathies, most likely toxoplasmosis in immunocompromised patients

106. Encephalitis
Individuals at the extremes of age are at highest risk, particularly for HSE

107. Encephalitis
The classic presentation is encephalopathy with diffuse or focal neurologic symptoms, including the following:
Behavioral and personality changes, decreased level of consciousness
Stiff neck, photophobia, and lethargy
Generalized or localized seizures (60% of children with California encephalitis [CE])
Acute confusion or amnestic states
Flaccid paralysis (10% with WNE)

108. Infectious etiologies of Encephalitis
Viral agents, such as HSV type 1 and 2 (almost exclusively in neonates),
VZV, EBV,
Measles virus (PIE and SSPE), mumps, and rubella are spread through person-to-person contact.
Human herpesvirus 6 may also be a causative agent.
Bacterial pathogens, such as Mycoplasma species, rickettsial or catscratch disease,
Toxoplasma gondii
West Nile virus can be transmitted by means of an organ transplant and via blood transfusions. 

109. Physical Examination Altered mental status
Personality changes are very common
Focal findings, such as hemiparesis, focal seizures, and autonomic dysfunction
Movement disorders (St Louis encephalitis, eastern equine encephalitis [EEE], western equine encephalitis [WEE])
Ataxia
Cranial nerve defects
Dysphagia, particularly in rabies
Meningismus (less common and less pronounced than in meningitis)
Unilateral sensorimotor dysfunction (postinfectious encephalomyelitis [PIE])
Physical Examination

110. Encephalitis Laboratory tests (biochemical). Viral serology CT scan
EEE
CSF analysis

111. Complications Seizures
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
Increased intracranial pressure (ICP)
Coma

112. Encephalitis-treatment
The goal of treatment for acutely ill patients is administration of the first dose or doses acyclovir with or without antibiotics or steroids as quickly as possible
Look for and treat systemic complications, particularly in HSE, EEE, JE, such as hypotension or shock, hypoxemia, hyponatremia (SIADH), and exacerbation of chronic diseases