1. Central nervous system infections

2. Central nervous system:
The brain and
Spinal cord
They are protected from mechanical pressure or deformation by enclosure in rigid containers:
the skull and
vertebral column, which also act as barriers to the spread of infection.

3. Central nervous system infections
Blood vessels and
Nerves that traverse the walls of the skull and vertebral column are the main routes of invasion.

4. Central nervous system infections
Blood-borne invasion is the most common route of infection:
polioviruses
Neisseria meningitidis.

5. Central nervous system infections
Invasion via peripheral nerves is less common:
herpes simplex,
varicella-zoster and
rabies viruses.

6. Central nervous system infections
Local invasion :
-from infected ears or sinuses,
-local injury
-congenital defects such as spina bifida
-invasion from the olfactory tract :
amebic meningitis: rare.

7. INVASION OF THE CENTRAL NERVOUS SYSTEM
Natural barriers act to prevent blood-borne invasion
Blood-borne invasion takes place across:
the blood-brain barrier: encephalitis
the blood-cerebrospinal fluid (CSF) barrier: meningitis .

8. Structures of the blood-brain and blood-cerebrospinal fluid (CSF) barriers.

9. CNS invasion
rare
most microorganisms fail to pass from blood to the CNS across the natural barriers.
CNS involvement by polio, mumps, rubella or measles viruses is seen in only a very small proportion of infected individuals.
The factors that determine such CNS invasion are unknown.

10. Herpes simplex virus (HSV) Varicella-zoster virus (VZV)
present in skin or mucosal lesions
travel up axons
to reach the dorsal root ganglia

11. Rabies virus
introduced into muscle or subcutaneous tissues by the bite of a rabid animal,
infects muscle fibers and muscle spindles after the virus binds to the nicotinic acetylcholine receptor.
It then enters peripheral nerves and travels to the CNS, to reach glial cells and neurones, where it multiplies

12. The mechanism of central nervous system (CNS) invasion by poliovirus.
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13. THE BODY'S RESPONSE TO INVASION
CSF cell counts increase in response to infection

14. The response to invading viruses
is reflected by an increase in
-lymphocytes,
mostly T cells, and
monocytes in the CSF

15. The response to invading viruses
-A slight increase in protein also occurs, the CSF remaining clear. This condition is termed 'aseptic' meningitis.

16. The response to invading bacteria
more spectacular and more rapid increase in polymorphonuclear leukocytes and proteins
the CSF becomes visibly turbid.
This condition is termed 'septic' meningitis.
Certain slower growing or less pyogenic microorganisms induce less dramatic changes, such as in tuberculous or listerial meningitis.

17. Change in CSF in response to invading microorganism

18. The pathologic consequences of CNS infection depend upon the microorganism
Invading bacteria and protozoa generally induce more dramatic inflammatory events, which limit local spread so that infection is soon localized to form abscesses.

19. occasionally, years ( subacute sclerosing panencephalitis (SSPE)
Pathologic changes
For viruses:
several days
occasionally, years ( subacute sclerosing panencephalitis (SSPE)
Bacteria
Rapid

20. MENINGITIS Bacterial meningitis
Bacterial meningitis
Acute bacterial meningitis is a life-threatening infection, needing urgent specific treatment
Bacterial meningitis is more severe, but less common, than viral meningitis and may be caused by a variety of agents

21. Bacterial MENINGITIS All have a polysaccharide capsule.
Haemophilus influenzae type b (Hib): Prior to the 1990s before the vaccine
Neisseria meningitidis
Streptococcus pneumoniae
All have a polysaccharide capsule.

22. Meningococcal meningitis
Neisseria meningitidis is carried by about 20% of the population, but in epidemics higher rates are seen
Meningococcal septicemia showing a mixed petechial and maculopapular rash on the extremities and exterior surfaces.

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24. Meningococcal meningitis
Neisseria meningitidis
Gram-negative diplococcus
The bacteria are attached by their pili to the epithelial cells in the nasopharynx.
Invasion of the blood and meninges is a rare and poorly understood event.

25. Meningococcal meningitis
Neisseria meningitidis
Person-to-person spread:by droplet infection
Overcrowding such as prisons, military barracks and college dormitories contribute to the frequency of infection in populations
During outbreaks of meningococcal meningitis, which most frequently occur in late winter and early spring, the carrier rate may reach 60-80%.

26. A diagnosis of acute Meningococcal meningitis is usually suspected on clinical examination
Laboratory identification of the bacterial cause of acute meningitis is essential
so that appropriate antibiotic therapy can be given and prophylaxis of contacts initiated.
Preliminary microscopy results involving white cell counts and Gram-staining for bacteria should be available within an hour of receipt of the CSF sample in the laboratory.
Results of culture of CSF and blood should follow after 24 h
Antigen detection
NAT

27. A diagnosis of acute Meningococcal meningitis is usually suspected on clinical examination
Close contacts in the family referred to as 'kissing contacts' should be given rifampin chemoprophylaxis for 2 days.
vaccine

28. Haemophilus meningitis
Type b H. influenzae causes meningitis in infants and young children
H. influenzae is a Gram-negative coccobacillus.
Maternal antibody protects the infant up to 3-4 months of age, but as it wanes, there is a 'window of susceptibility' until the child produces his/her own antibody.

29. Acute H. influenzae meningitis is commonly complicated by severe neurologic sequelae
It is important to note that the organisms may be difficult to see in Gram-stained smears of CSF, particularly if they are present in small numbers.

30. H. influenzae type b (Hib) vaccine is effective for children from 2 months of age
An effective Hib vaccine, suitable for children 2 months of age and upwards, is available.

31. Pneumococcal meningitis
Streptococcus pneumoniae is a common cause of bacterial meningitis, particularly in children and the elderly

32. Pneumococcal meningitis
Strep. pneumoniae
a capsulate Gram-positive diplococcus
carried in the throats of many healthy individuals
Invasion of the blood and meninges is a rare event, but is more common:
in the very young (<2 years of age),
in the elderly, in those with sickle cell disease, in debilitated or splenectomized patients and following head trauma.
The protection is type-specific and there are more than 85 different capsular types of Strep. pneumoniae.

33. Pneumococcal meningitis
Since penicillin-resistant pneumococci have been observed worldwide, attention must be paid to the antibiotic susceptibility of the infecting strain, and empiric chemotherapy usually involves a combination of vancomycin and either cefotaxime or ceftriaxone.

34. Laboratory diagnosis
Microscopy is highly sensitive, as is culture, unless the patient has been treated with antibiotics
Antigen test for pneumococcal C polysaccharide is sensitive with CSF (meningitis) but not with urine (meningitis, pneumonia, other infections)
Nucleic-acid-based tests are not commonly used for diagnosis
Culture requires use of enriched-nutrient media (e.g., sheep blood agar); organism highly susceptible to many antibiotics, so culture can be negative in partially treated patients

35. Pneumococcal meningitis
Immunization with 7-valent conjugated vaccine is recommended for all children younger than 2 years of age; a 23-valent polysaccharide vaccine is recommended for adults at risk for disease (e.g. sickle cell disease, HIV infection, chronic illness or weakened immune systems) for serious pneumococcal infection.

36. Listeria monocytogenes meningitis
Listeria monocytogenes causes meningitis in immunocompromised adults
Gram-positive coccobacillus

37. Neonatal meningitis
especially those with low birth weight

38. the most frequent agents: group B hemolytic streptococci (GBS) E. coli
Although mortality rates due to neonatal meningitis in resource-rich countries are declining, the problem is still serious
the most frequent agents:
group B hemolytic streptococci (GBS)
E. coli
nosocomial infection
from the mother

39. Tuberculous meningitis
always have a focus of infection elsewhere
approximately 25% may have no clinical or historic evidence of such an infection
In >50% of cases, meningitis is associated with acute miliary tuberculosis
In areas with a high prevalence of tuberculosis:
Most common: in children from 0-4 years of age
In areas where tuberculosis is less frequent
Most common: adults

40. Tuberculous meningitis usually presents with a gradual onset over a few week
Spinal tuberculosis is uncommon now except in resource-poor countries; bacteria in the vertebrae destroy the intervertebral disks to form epidural abscesses. These compress the spinal cord and lead to paraplegia.

41. Fungal meningitis Cryptococcus neoformans : major cause
Cryptococcus neoformans : major cause
Coccidioides immitis

42. Cryptococcus neoformans meningitis
Common in patients with depressed cell-mediated immunity
capsulate yeasts: India-ink-stained preparations of CSF and can be cultured .
Antigen
a useful diagnostic tool
a measure of successful therapy.

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44. Protozoal meningitis
Naegleria
the free-living ameba
If inhaled they can reach the meninges via the olfactory tract and cribriform plate.
rapid onset
mortality rate is high.
Under the microscope, Naegleria appear as slowly motile amebae on careful examination of a fresh wet sample of CSF.

45. Protozoal meningitis Acanthamoeba spp. In immunocompromised
Acanthamoeba spp.
In immunocompromised
enter via the skin or the respiratory tract.
Acanthamoeba causes a chronic condition (granulomatous amebic encephalitis).
can be visualized in brain biopsies.

46. Viral meningitis
Viral meningitis is the most common type of meningitis
milder disease than bacterial meningitis
The CSF is clear in the absence of bacteria,
the cells are mainly lymphocytes, although polymorphonuclear leukocytes may be present in the early stages
NAT

47. Viral meningitis
Viral meningitis is the most common type of meningitis
There are five groups of human enteroviruses which include the echoviruses, coxsackie Group A and B viruses, and the three polioviruses.
Enteroviruses are common causes of seasonal aseptic meningitis.
In contrast to bacterial meningitis, viral meningitis usually has a benign course, and complete recovery is the rule.

49. Diagnosis NAT techniques
Spesific antibody index (Serum and CSF antibody and albumin or Immunoglobulin values)in (SSPE)

50. ENCEPHALITIS
Encephalitis is usually caused by viruses, but there are many cases where the infectious etiology is not identified

52. HSV ENCEPHALITIS In neonates: after vaginal delivery: HSV-2
In neonates: after vaginal delivery: HSV-2
In older children and adults: HSV-1, of which most are due to virus reactivation in the trigeminal ganglia

53. HSV ENCEPHALITIS Herpetic skin or mucosal lesions may be present.
HSV DNA in CSF sample using PCR.
In untreated patients : 70% mortality
early and prolonged treatment with intravenous aciclovir

54. Enteroviral infections
Poliovirus used to be a common cause of encephalitis
There are successful vaccines. The disease is completely preventable by vaccination and has been disappearing in resource-rich countries since vaccination programs were first carried out in the 1950s .

55. Enteroviral infections
Enterovirus-71-associated hand, foot and mouth epidemic resulted in a high rate of neurologic complications
Other enteroviruses such as coxsackieviruses and echoviruses occasionally cause meningoencephalitis. Treatment is supportive and there is no vaccine.

56. Paramyxoviral infections
Mumps virus is a common cause of mild encephalitis   
Asymptomatic CNS invasion may be common because there are increased numbers of cells in the CSF in about 50% of patients with parotitis; on the other hand, meningitis and encephalitis are often seen without parotitis.

57. Paramyxoviral infections
Nipah virus encephalitis, an emerging zoonotic paramyxovirus infection
In 1998, an outbreak of encephalitis with a high mortality rate was reported among pig farm workers in Malaysia. In total, there were 105 deaths among 265 patients with Nipah virus encephalitis.

58. Rabies encephalitis
The causative agent of rabies is a rhabdovirus, a bullet-shaped single-stranded RNA virus. The Lyssavirus genus sits within the Rhabdoviridae family.

59. Rabies encephalitis
The virus is excreted in the saliva of infected dogs, foxes, jackals, wolves, skunks, raccoons and vampire and other bats, and transmission to humans follows a bite or salivary contamination of other types of skin abrasions or wounds.
The infection is eventually fatal, although the course of the disease varies considerably between species.
If an apparently healthy dog is still healthy 10 days after biting a human, rabies is extremely unlikely. However, the virus may be excreted in the dog's saliva before the animal shows any clinical signs of disease.

60. Rabies encephalitis
The incubation period in humans is generally 4-13 weeks, although it may occasionally be as long as 6 months, possibly due to a delay in virus entry into peripheral nerves. The virus travels up peripheral nerves and, in general, the further the bite is from the CNS, the longer the incubation period. For instance, a bite on the foot leads to a longer incubation period than a bite on the face.

61. Rabies encephalitis
While the virus is travelling up the axons of motor or sensory neurones, there is no detectable antibody or cell-mediated immune response, possibly because antigen remains sequestered in infected muscle cells. Hence, passively administered immunoglobulin may be given during the incubation period.
Once rabies has developed it is fatal, death occurring following cardiac or respiratory arrest. Paralysis is often a major feature of the disease. One or two patients treated in intensive care units have recovered, but with serious neurologic sequelae.

62. Rabies encephalitis
Rabies can be diagnosed by detecting viral antigen or RNA
Laboratory diagnosis can be made by the detection of viral antigen by immunofluorescence or using PCR to detect rabies viral RNA in skin biopsies, corneal impression smears or brain biopsy. Characteristic intracytoplasmic inclusions called Negri bodies are seen in neurones . There is no treatment except supportive care.
Many countries have developed vaccination programs for domestic dogs, e.g. France, and in Canada and elsewhere, wild foxes have been vaccinated by dropping food baited with live virus vaccine from the air.  

63. Rabies encephalitis
After exposure to a possibly infected animal, immediate preventive action should be taken
This action includes:
Prompt cleaning of the wound (alcoholic iodine, debridement)
Confirmation of whether or not the animal is rabid (clinical observation of suspected dogs, histologic observation of the brain of other suspected species)
Administration of human rabies immunoglobulin(HRIG) to ensure prompt passive immunization. Half of the dose is given into the wound and half intramuscularly
If the risk is definite, active immunization with killed diploid cell-derived rabies virus(HDCV) . The chances of preventing the disease are greater when vaccination is started as early as possible after infection. (0,3,7,28,90)

64. Multiple cytoplasmic Negri bodies in pyramidal neurones of the hippocampus in rabies.

65. Togavirus and Flavivirus(Arboviruses) meningitis and encephalitis
Numerous arthropod-borne togaviruses can cause meningitis or encephalitis
sometimes cause outbreaks of infection
In different parts of the world, different mammals, birds or even reptiles act as reservoirs and there are a variety of arthropod (mosquito and tick) vectors.
Usually, <1% of humans infected develop neurologic disease . There may be a febrile illness, but asymptomatic infection is common.
In California:
Western equine encephalomyelitis (WEE) virus
St Louis encephalitis (SLE) virus : transmitted by the mosquito Culex tarsalis; a WEE vaccine is available, but only for horses.   
Japanese encephalitis virus infection: in India a vaccine for humans has been developed.
West Nile virus, another emerging viral cause of encephalitis

66. Retrovirus meningitis and encephalitis
HIV can cause subacute encephalitis, often with dementia
HIV often invades the CNS
İndistinguishable from the neurologic disease caused by microorganisms such as T. gondii, C. neoformans, cytomegalovirus and JC virus. JC virus, a polyomavirus, occasionally invades oligodendrocytes in immunodeficient people, particularly in AIDS, and eventually gives rise to progressive multifocal leukoencephalopathy (PML).

67. Viral myelopathy inflammation of the spinal cord, a myelitis:
inflammation of the spinal cord, a myelitis:
by polio, coxsackie, enterovirus 71 and West Nile virus infection, a number of herpes viruses including HSV, CMV, EBV and VZV
Chronic myelopathy :HTLV-1 ,HIV-1 infection

68. Post-vaccinial and post-infectious encephalitis
Encephalitis following viral infection or vaccination possibly has an autoimmune basis
An analogous inflammatory demyelinating condition of the peripheral nervous system called Guillain-Barré syndrome has been associated with a variety of viral infections, as well as with immunization with non-infectious material. In 1976, most adults in the USA were given inactivated influenza virus vaccine, which resulted in a small but highly significant number of cases of Guillain-Barré syndrome.

69. NEUROLOGIC DISEASES OF POSSIBLE VIRAL ETIOLOGY ?
neurologic diseases of unknown origin:
multiple sclerosis
amyotrophic lateral sclerosis
Parkinson's disease
Schizophrenia
senile dementia

70. SPONGIFORM ENCEPHALOPATHIES CAUSED BY SCRAPIE-TYPE AGENTS
  prion
spongiform appearance of nervous tissues, caused by vacuolation and plaque formation.
Infections in animals seem to have originated from sheep and goats with scrapie, which has been present in Europe for years.

71. CNS DISEASE CAUSED BY PARASITES
Toxoplasma gondii
Plasmodium falciparum
Toxocara cati
Toxocara canis
Echinococcus granulosus
Taenia solium Cysticercosis

72. BRAIN ABSCESSES
Brain abscesses are usually associated with predisposing factors
Since the development of antibiotics, brain abscesses have become rare and usually follow surgery or trauma, chronic osteomyelitis of neighboring bone, septic embolism or chronic cerebral anoxia. They are also seen in children with congenital cyanotic heart disease in whom the lungs fail to filter off circulating bacteria.
Acute abscesses are caused by various bacteria, generally of oropharyngeal origin, including anaerobes. There is usually a mixed bacterial flora.
Chronic abscesses may be due to Mycobacterium tuberculosis or C. neoformans. In immunosuppressed patients, opportunistic infection may occur with fungi and protozoan etiologic agents.