Parasitic diseases of the central nervous system.pdf

Parasitic causes of CNS infection

1. Parasitic diseases of the central
nervous system
ShahinHameed

2. •There are essentially two broad categories of
parasitic infections, protozoan and metazoan,
and several of these affect the central nervous
system (CNS).
•The protozoalinfections that infect the CNS
include malaria, trypanosomiasis, amebiasis,
toxoplasmosis, leishmaniasis, and
microsporidiosis.

3. PROTOZOAL INFECTIONS

4. 1.Cerebral malaria

5. Epidemiology
•Until recently P. falciparumwas the only species
known to involve the CNS.
•In the past decade, however, there have been two
reports of P. vivaxmanifesting with neurological
disease.
•Cerebral malaria typically occurs in tropical regions
where P. falciparumis rampant, such as, Africa,
South-East Asia, and Central and South America.

6. Life cycle
•The parasite has two life cycles:
–sexual reproduction in the anopheles mosquito
vector and
–asexual reproduction in the intermediate human
host.

7. Clinical manifestations
•Cerebral malaria can occur as early as 1-2 days
after the onset of symptoms.
•Presentation can vary from seizures, confusion
to coma, and even focal neurological deficits.

8. •Although the encephalopathy is potentially
reversible, mortality rates range from 10% to
50%, even in adequately treated cases
•A proportion of patients recover without any
significant sequelae
–10% have residual complications,including
cognitive impairment, seizures, and neurological
deficits.

9. •Several factors contribute to the pathogenesis
of cerebral malaria.
•Parasite sequestration is a specific receptor-
mediated process wherein erythrocytes bind to
host receptors on the endothelial cells.
Pathogenesis

10. •For example, P. falciparumerythrocyte
membrane protein 1 (Pf EMP-1), which is
predominantly expressed on the surface of an
individual erythrocyte, binds to cell adhesion
molecules ICAM-1 and VCAM on endothelial
cell surfaces.

11. •Sequestration of parasitized red blood cells
(RBCs) stimulates the production of
inflammatory cytokines, such as TNF.
•These cytokines upregulateadhesion
molecules, such as ICAM-1, CD36, and VCAM-
1, in the microvasculature, resulting in further
sequestration,activationof astrocytesand
monocytes, as well as causing disruption of
intercellular junctionalprotein complexes,
resulting in abnormal vascular permeability.

12. •Impaired nitric oxide availability is also
thought to contribute to this process.
•Functional obstruction eventually results in
reduced blood flow, hypoxia, and reduced
glucose.

13. Pathology
•Malarial encephalopathy results in petechial
hemorrhages in the cerebral white matter,
particularly in the corpus callosum,
cerebellum, brain stem, and subcorticalregion
•The external surface is usually congested, and
the brain may show swelling with flattening of
the gyriand compression of the ventricles.

15. •Hemazoinpigment lends a slate gray hue to
the brain.
•Histologically, parasitized erythrocytes are
sequestered in the cerebral microvasculature.
Hemazoinpigment is easy to identify within
erythrocytes as brownish—black granular
material .

16. Sequestration of parasitized red blood cells in the cerebral
microvasculature

17. Haemazoinpigment within erythrocytes

18. •Foci of hemorrhage, especially ring-like
hemorrhages, are characteristic .These contain
a central necrosedblood vessel surrounded by
concentric zones of parasitized and
nonparasitizederythrocytes, free pigment,
and few monocytesand lymphocytes.
•Also seen are punctiformhemorrhages due to
rupture of a blood vessel

19. Ring hemorrhages in the white matter

20. •“Dürckgranuloma” is a focus of reactive
astrocytosisadmixed with microglialcells and
lymphocytes surrounding a focus of ischemic
necrosis or hemorrhage.

21. Diagnosis
•The diagnosis of cerebral malaria is based on the
clinical picture and demonstration of the parasite
in blood rather than a biopsy diagnosis..
•In acute untreated cases or cases with active
cerebral malaria, diagnosis is simple, as
numerous parasitized erythrocytes are seen
within capillaries.
•In treated cases ,hemorrhages, Dürck
granulomas, and pigment deposits may be the
only residual signs of an infection.

22. 2.Toxoplasmosis

23. Epidemiology
•Toxoplasmosis is caused by the intracellular
coccidian parasite Toxoplasmagondii.
•T. gondiiis found worldwide and the
prevalence varies widely.
•Nearly 25%-50% of patients with HIV infection
have latent T. gondiiinfection

24. Life cycle
•T. gondiiexists in three forms: oocysts,
tachyzoites, and bradyzoites.
•The definitive hosts are members of the family
Felidae(cat), and oocystsof T gondiiare only
produced in them.

25. •Humans get infected either by ingesting food
or water contaminated with infected feline
feces or by eating undercooked or raw meat
containing tissue cysts

26. Clinical picture
•The clinicopathologicalsyndromes associated
with toxoplasmosis fall into the following three
categories:
•1.Primary toxoplasmosis in immunocompetent
individuals.
•Clinical manifestations in this set of
individuals are rare

27. •2.Toxoplasmosis in immunosuppressed
patients.
•Most common opportunistic infection in
HIV patients.
•Patients present with headache, seizures,
and cranial nerve and neurological deficits

28. •3.Congenital toxoplasmosis.
•Primary infection during pregnancy could
be clinically silent, or, in those who
become seropositive, could have fever,
headache, and lymphadenopathy.
•The risk of transmission rises with
gestational age; however, the severity of
manifestations are less with advancing
pregnancy.

29. Pathogenesis
•Natural killer cells induced by T helper type I
cells are cytotoxicto infected cells.
•Extracellular tachyzoitesare destroyed by
antibodies and by TNF-and interleukin-2 (IL-2)
secreted by activated macrophages.
•Tissue necrosis is thought to be cytokine-
induced.
•Infection also induces vasculitiswith resultant
obliteration of vessels and infarction

30. Pathology
In congenital toxoplasmosis, hydrocephalus and foci of calcification are
seen

31. •Gross changes may not be apparent in the
diffuse encephalitic form in adults.
•Once necrosis sets in, the necrotic foci may
enlarge to form abscesses with or without
hemorrhage.
•The infection may also manifest as a
ventriculitiswith periventricularnecrosis, or
as a space-occupying lesion.

32. Mass lesions with necrosis,
hemorrhage, and cerebral edema

33. Bilateral thalamic hyperintenselesions showing mild peripheral ring
enhancement. The location of these granulomasis
highly suggestive of toxoplasmosis

34. •Histologically, in the congenital form of
toxoplasmosis, intracellular Toxoplasmaare
seen in ependymaland glialcells in a
periventricularlocation associated with an
acute inflammatory response to cell death and
necrosis.
•Periaqueductaland leptomeningeal
involvement results in hydrocephalus

35. Leptomeningealinflammation involving vasculature

36. •In adults, in the encephalitic form, microglialnodules
are diffusely scattered throughout the parenchyma

37. •The necrotic foci contain infected cells, tachyzoites, and karyorrhectic
debris surrounded by microglia, inflammatory cells, and astrocytes

38. •Bradyzoitesmay be present at the periphery
of the lesion

39. •Blood vessel involvement can result in vasculitis, hemorrhage,
and thrombotic occlusion

40. •In chronic lesions, organisms are reduced in number, and with
treatment, the lesions undergo cystic change.
Immunopositivityfor Toxoplasmatachyzoiteswithin cerebral lesion

41. Diagnosis
•Cerebral spinal fluid (CSF) examination may
demonstrate the presence of antibodies and
ToxoplasmaDNA.
•Biopsies are usually submitted from stereotactic
procedures for deep-seated lesions or following
surgical drainage of an abscess.
•Histopathology shows necrotic material admixed
with tachyzoites.

42. 4.Trypanosomiasis
•Human African trypanosomiasis(African
sleeping sickness)
•American trypanosomiasis(Chagas’ disease)

43. Human African trypanosomiasis
•Epidemiology
•T.b. rhodesienseisfound in in East and South
Africa whereas T.b. gambienseis found in
West Africa.
•T.b. rhodesienseis a zoonosiswith cattle being
the reservoir, whereas T.b. gambienseuses
humans as its host.
•The vector involved in transmission of the
parasite is of the Glossinaspecies, the tsetse
fly.

44. Life cycle
•The tsetse fly is infected on ingestion of blood
from mammalian hosts containing
trypomastigotes.
•In the fly, the trypomastigotesgo through many
cycles of multiplication and their procyclicforms
migrate to the salivary glands.
•The cycle is complete when the injected
metacyclicform becomes a trypomastigotethat
multiplies in blood.

45. Clinical features
•CNS involvement occur weeks to months after
an infected bite.
•T.b. rhodesiensehas a more rapid and acute
course
•Somnolence, irritability, headache, and
extrapyramidalsigns after a long symptom-
free period leading to coma and death in
untreated cases is typical of T.b. gambiense.

46. •In T.b. rhodesiense, the hemolymphaticstage
overlaps with the meningo-encephalitic stage
–Death is from carditis, secondary bacterial
infection and encephalitis
–usually develop within 6months if untreated.

47. Pathology and pathogenesis
•The meningesare cloudy and the brain
appears swollen
•Histologically, chronic meningitis with
lymphoplasmacytic infiltrates and arteritisare
seen.
•The cerebral parenchyma shows perivascular
chronic inflammation, microglialnodules, and
reactive astrocytosis.
•Parasites are usually not demonstrable.

48. •Although polyclonal activation of B cells in the
CSF and blood is observed, the surface
glycoprotein undergoes variations continually and
thereby cannot be neutralized by the antibodies
•Activation of CD8 T cells results in secretion of
IFN-and IL-2, which activates macrophages that
in turn produce nitric oxide and TNF-which
induces the astroglialreaction.

49. •Antigen–antibody complexes trigger complement
activation causing endarteritis.
•Vasogenicedema results from breakdown of the
blood–brain barrier
•Diagnosis is made by finding parasites and
antibodies in blood and CSF.

50. American trypanosomiasis(Chagas’
disease)
•Epidemiology
•Chagas’ disease is caused by T. cruzi.
•T. cruziis a zoonosisand is transmitted by the
insect vector, T. infestans, where humans are
accidental hosts.

51. Life cycle
•The triatomineinsects suck blood from humans
and mammals containing the trypomastigotesof
T. cruzi.
•The parasites enter through breaks in the mucosa
or skin and enter the host cells, where they
multiply and transform into amastigotes, multiply
and differentiate into trypomastigotes, which
when released during cell rupture spread
hematogenouslyand by invading tissues

52. Clinical features
•In the acute phase, encephalitis can develop,
particularly in children.
•Clinical manifestations in the chronic phase
include mental dysfunction, neurological
deficits, and ataxia.

53. Chagas’ encephalitis: Zone of inflammation with
parasitized macrophages, lymphocytes, and astrocytes.

54. Chagas’ encephalitis: Trypomastigotein CSF.

55. Pathology and pathogenesis
•In the acute stage, the encephalitic picture
includes perivascularcuffing by lymphocytes
and formation of microglialnodules.
•Congestion, edema, and petechial
hemorrhages are seen within the brain
parenchyma. The parasite in its amastigote
form is seen within macrophages, endothelial
cells, microglia, and astrocytes

56. •The pathogenesis of Chagas’ disease in the CNS is
not well understood.
•The parasite probably invades the endothelium
and passes into astrocytesor enters through the
CSF.
•In the chronic phase, neuronal destruction is
thought to be the main pathogeneticmechanism.

57. •Peripheral neuropathy results from
autoimmunity.
•Antibodies to flagellarproteins have been
found to cross-react with host tissues,
particularly myelin sheaths and neurons

58. Diagnosis
•A diagnosis of trypanosomiasisrequires the
–finding of parasites and antibodies in blood and
CSF or
–demonstration of amastigoteforms by histology,
in situ hybridization, and PCR

59. 5.Amebiasis
•The various clinicopathologicentities that
comprise amebic infections of the CNS include
the following:
•1. Amebic abscess due to Entamoebahistolytica
•2. Primary amebic meningoencephalitisdue to
Naegleriafowleri
•3. Granulomatousamebic encephalitis due to
Acanthamoebaand Balamuthiaspp.
•4. Encephalitis due to Sappiniadiploidea

60. Cerebral amebiasis
•Epidemiology
•This is due to human colonic infection with
Entamoebahistolytica.
•Global disease, although most cases are seen
in Central and South America, Africa, and India

61. •Life cycle
•The organisms are ingested as cysts that are
present in infected feces.
•Hematogenousspread from the liver to the
brain results in brain abscesses

62. •Clinical manifestations
•The disease has an abrupt onset and a rapid
course with death within 72 hours if left
untreated.
•Symptoms are of meningismuswith focal
neurological deficits

63. Pathology and pathogenesis
•Abscesses are usually at the junction of gray and
white matter.
•The abscess consists of a central area of necrosis
that contains amebic trophozoites
•The parasites are typically 10-60 m in size and
have a round nucleus with a central karyosome
and periodic acid-Schiff (PAS) positive cytoplasm
that contains phagocytosederythrocytes

64. Necrotic center of abscess with trophozoites.

65. •Pathogenesis involves primarily a process of
host cell destruction through stages of
adherence to host cells, contact-dependent
lysis, and phagocytosisfollowing death of the
host cell

66. •Diagnosis
•A combination of serology and examination of
stool or pus to demonstrate the parasite aids
in diagnosis of amebiasis.

67. Primary amebic meningoencephalitis
(PAM)
•Epidemiology
•This is a global disease and N. fowleriare
found in soil, river, and lake water.
•It enters via the nasal mucosa and travels
along olfactory nerves to enter the brain

68. •Clinical manifestations
•The disease has a fulminantcourse and is
usually fatal.
•The incubation period is 1-14 days. There is
fever, headache, vomiting, seizures, coma, and
death

69. Pathology and pathogenesis
•Hemorrhagic necrosis is seen involving the
inferior frontal lobe along the olfactory nerve.
•The inflammatory infiltrate seen in the
leptomeningesand in the Virchow–Robin
spaces consists of neutrophils and
lymphocytes admixed with trophozoites.

70. •The trophozoitesmeasure 10-20 m in
diameter and have a round nucleus with a
prominent nucleolus. There is hemorrhagic
necrosis of the gray and white matter

71. Primary amebic meningoencephalitis: Inflammatory
infiltrate in the leptomeningesadmixed with trophozoites

72. Virchow Robin spaces with amebic
trophozoitesand a dense inflammatory
infiltrate.
Primary amebic meningoencephalitis:
Hemorrhagic necrosis of gray and white
matter.

73. •Diagnosis
•The trophozoitecan be seen on wet mounts of
CSF, which shows pleocytosis

74. Granulomatousamebic encephalitis

75. Epidemiology
•This is a global disease caused by free-living
amebaeAcanthamoebacastellaniiand
polyphagaand Balamuthiamandrillaris.
•The CNS is affected in immunocompromised
individuals. The infection reaches the CNS via
the bloodstream from a site of skin injury.

76. Clinical manifestations
•The disease manifests as headache,
meningism, seizures, and focal neurological
deficits.
•The clinical course is more prolonged than
that caused by Naegleriaand varies from 1
week to several months, with death being the
inevitable outcome in untreated patients.

77. Pathology and pathogenesis
•Necrotizing hemorrhagic lesions associated
with cerebral edema are seen.
•The brain shows reactive gliosis, acute and
chronic inflammation, and areas of necrosis
containing blood vessels with fibrinoid
necrosis surrounded by trophozoites and
cysts
•Several multinucleated giant cells of the
foreign body and Langhans’ type are seen.

78. •The pathogenesis is poorly understood and
involves the release of toxic enzymes,
apoptosis, and phagocytosisof host cells,
resulting in tissue damage.

79. Granulomatousamebic encephalitis: Fibrinoidnecrosis of blood vessel walls
surrounded by trophozoitesand cy

80. Diagnosis
•Skin biopsy with granulomatousinfection and
demonstration of trophozoites would aid in
diagnosis.
•The diagnosis can be confirmed by culture.

81. 6.Microsporidiosis
•Zoonoticdisease seen primarily in immunosuppressed
individuals.
•Manifests as nodular encephalitis
•Parasites are seen as small hematoxyphilicdots within
foci of necrosis and inflammation that are associated
with reactive astrocytosisand microglialproliferation.
•Acid-fast and Gram-positive.

82. 7.Leishmaniasis
•CNS involvement is rare with one case report
from India of meningitis due to L. donovaniin
a child with drug-resistant visceral
leishmaniasis.

83. METAZOAL INFECTIONS

84. Metazoalinfections
•Trematodeinfections
•Cestodeinfections
•Nematode infections

85. TREMATODE INFECTIONS

86. Schistosomiasis
•Epidemiology
•Schistosomiasisis endemic in certain parts of
the world.
•Schistosomajaponicumis the most common
species affecting the brain.
•S. haematobiumand S. mansonicause spinal
cord lesions.

87. Life cycle
•Humans are the definitive hosts of S. mansoni
and S. haematobium.
•Humans are infected when cercariaepenetrate
the skin and enter dermal veins, lose their tail
to become developing worms or
schistosomulae, and then migrate to the lung.

88. •The schistosomulaethen migrate to the liver,
where they undergo sexually maturation, pair
and migrate either to the portal venous
system or the urinary tract.
•The adult parasites could migrate in the
vasculature to other locations where they lay
eggs.

89. Clinical manifestations
•Seizures, focal neurological deficits,
paraplegia, and radiculopathyare seen
depending on whether the parasite lodges in
the brain or spinal cord.

90. Pathology and pathogenesis
•The brain and spinal cord may show foci
of necrosis or hemorrhage.
–In the acute phase, live eggs are surrounded
by eosinophils, lymphocytes, plasma cells,
and rimmed by a zone of reactive gliosis.
–After the egg dies, circumscribed
granulomas are seen around the
degenerating eggs .

91. (A, B) Schistosomiasis: Multiple circumovalgranulomasin the cerebral parenchyma. (C)
The granulomashave Schistosomaeggs surrounded by an inflammatory reaction
comprising numerous eosinophilsand fibrosis..

92. (D) Schistosomiasis: Some of the eggs are seen within giant cells. (E) Schistosomiasis: Zone
of reactive astrocytosissurrounding the granulomatousreaction

93. •Schistosomiasisarises from an initial immune
complex-based reaction to egg antigens
followed by a cell-mediated granulomatous
process in which cytokines determine the size
of thegranulomaand the extent of fibrosis.

94. Diagnosis
•Correlation of clinical and epidemiologic
information together with demonstration of
eggs in the urine or feces and positive
serology is useful in diagnosis.
•Biopsies, when performed, can offer a
definitive diagnosis

95. Paragonimiasis
•Epidemiology
•Paragonimiasisis infection by trematodesof
the genus Paragonimuswith P. westermani
being the most prominent of this species.
•These are endemic in Asia, the Americas, and
Central and Western Africa.

96. Life cycle
•Human infection is acquired by eating crustaceans that are
the second intermediate hosts.
•Paragonimusneeds three hosts to complete its life cycle.
Carnivorous mammals are definitive hosts
•First intermediate host, a mollusk, where mircidiamultiply
and develop into sporocysts, rediae, and cercariae.
•The latter now invade the second intermediate host, a
crustacean, where they develop into encysted
metacercaria.

97. •Definitive hosts, such as man, are infected by
ingesting metacercariae.
•If the larvae migrate via blood or through skull
foramina, they reach the brain, where they
develop into adults that produce eggs

98. Clinical manifestations
•The clinical manifestations are insidious in
onset and include fever, headache, nausea,
vomiting, seizures, meningism, and focal
neurological deficits.
•Spinal cord lesions cause paraplegia, sensory
loss, and bladder and bowel incontinence.

99. Pathology and pathogenesis
•Cerebral and spinal cord paragonimiasiscause
arachnoiditis, abscesses, and granulomas.
•Necrotizing abscesses can be up to 10 cm in
size and have a thin capsule.
•Granulomasare seen as firm fibrotic lesions.

100. •The space occupying lesions are seen more
frequently in the temporal and occipital lobes
and in the spinal cord.
•The leptomeningealinflammation is
composed of polymorphonuclearleukocytes
and eosinophilsin the acute phase and
lymphocytes and fibrosis in more chronic
stages.

101. CESTODE INFECTIONS

102. Cysticercosis
•Epidemiology
•Infection occurs with larvae of tapeworm
Taeniasolium.
•Globally endemic, this infection is usually seen
in impoverished regions

103. Life cycle
•Cysticercosisoccurs when man, who is
normally the definitive host, accidentally
ingests eggs and becomes the intermediate
host.
•The adult worm resides in the human gut,
and excreted eggs are eaten by pigs.

104. •In cysticercosis, man ingests eggs that hatch
into oncospheres. These penetrate the gut
wall and disseminate hematogenouslyto
organs where they encyst.
•The encysted form is called a cysticercusand
survives for a few years.

105. Clinical manifestations
•The clinical features vary depending on the
location of the cyst and include seizures,
headache, neurological deficits, and
transverse myelitis.
•However, the vast majority of cases are
asymptomatic.

106. Pathology and pathogenesis
•The cysts vary in size from 0.5 to 2.0 cm in
diameter and can be seen in the meninges,
ventricles or parenchyma
•The number of cysts varies and range from a
solitary cysticercusto several hundred.
•When present in the subarachnoid space and in
the ventricle, the morphology of the cysticercus
changes to form grape-like clusters.
–known as the “racemose” form of cysticercus.

107. (A)Numerous cysticerciwithin cerebral parenchyma.
(B)T2 weighted image of multiple NCC in vesicular and colloid stages many showing
eccentric scoliceswithin. Also seen is a racemosecyst in the left sylvianfissure.
(C) Neurocysticercosis: T1 with contrast of image seen in Fig 6B with multiple NCC in
vesicular and colloid stages many showing eccentric scoliceswithin.

108. (D) Neurocysticercosis: The bladder wall of the cysticercuslarva with microvillion the
outer tegument. The parenchyma is loose and contains haphazardly arranged smooth
muscle fibers, fluid filled spaces and excretory vacuoles which calcify with time to form
calcareous bodies. (E, F) Neurocysticercosis: The proto-scolexhas four suckers and a
rostellumwith a double row of 22-36 large and small
hookletsthat are birefringent. (G) Neurocysticercosis: Cysticercuswith cavitaryspace

109. (H) Neurocysticercosis: Cysticercuswith cavitaryspace bordered by dense inflammation.
(I)Neurocysticercosis: Cavitaryspace without a cysticercuslined by inflammatory
granulation tissue containing palisadedhistiocytes, giant cells, lymphocytes, plasma
cells and eosinophils.
(J) Neurocysticercosis: Cerebral parenchyma surrounding cysticercuslarva with reactive
gliosisand chronic inflammation.

110. •Sometimes the only tell-tale signs of the
parasite are the calcareous corpuscles.
•In infection with cysticercus, both humoral
and cell-mediated immune mechanisms are
activated.
•The T helper-2 cell-mediated response is the
most significant reaction

111. Diagnosis
•The diagnosis is usually made on radiological
imaging
•In cases of solitary cysticercusgranulomas, the
lesion is seen as a single, small (1 cm)
contrast-enhancing lesion.
•A biopsy, if done, yields evidence of the
parasite, especially if the cyst is submitted
intact

112. Coenurosis
•Epidemiology
•This is a rare infection by Taeniamulticeps.
The disease is seen in Europe, North and
South America, and Africa

113. Life cycle
•The definitive host is a carnivore.
•Infection in humans occurs by inadvertent
ingestion of eggs in feces.

114. •Clinical features
•Meningism, nausea and vomiting, headache,
and neurological deficits are seen depending
on the location of the parasite

115. Pathology and pathogenesis
•A parasitic yellowish-white cyst surrounded by
a capsule formed by host tissues is seen.
•The cyst contains numerous protoscolicesand
is surrounded by a foreign body giant cell
reaction, chronic inflammatory cells, fibrosis,
and reactive gliosis.
•Meningitis and endarteritis may be seen.
•Chronic lesions exhibit calcification

116. •Diagnosis
•Demonstration of the parasite is required for
definitive diagnosis

117. Hydatidosis
•Epidemiology
•Hydatidinfections can be caused by two
different species:
•Echinococcusgranulosusand E. multilocularis.
–E.granulosusis endemic worldwide.
–E. multilocularisis seen in North and South
America, Australia, Europe, China, Japan, Russian
Federation, and Turkey

118. Life cycle
•The definitive hosts of E. granulosusare
canines.
•In humans, the disease is caused by accidental
ingestion of eggs
•The definitive host of E. multilocularisis the
fox, and this infection, although rare, is more
aggressive.

119. (A) Echinococcosisamultiloculatedcyst with calcified margins in the left
temporal lobe
(B) Echinococcosis:Postcontrast CT sections of the same case seen in (A).
(C) Echincococcosis: T2W images showing a multiloculatedcystic lesion in the right side of
the posterior fossawithin the subarachnoid spaces with a T2W hypointenserim indenting the
medulla and cerebellum focally

120. (E) Echinococcosis: Section of metacestodeshowing the thin germinal membrane with
brood capsules and protoscolices
(F) Echinococcosis: Section of metacestodeshowing the brood capsules and
protoscolices.
(G) Echinococcosis: Section showing an invaginatedprotoscolexof E.granulosus
containing one of 4 suckers and hooklets

121. (H, I) Echinococcosis: Granulomatousreaction surrounding the parasite.
(J) Echinococcosis: Collapsed laminated cyst wall of metacestodeof E. granulosus.

122. •Clinical features
•Patients present with symptoms based on the
location of the cysts and include symptoms
like headache, seizures, focal neurological
deficits, chorea, and signs of spinal cord
compression

123. Pathology and pathogenesis
•Cysts can reach up to 10 cm in diameter
•The wall is white and jelly-like, and the
appearance is likened to that of tender
coconut flesh.
–These cysts could be unilocularor contain several
daughter cysts and are surrounded by a fibrous
wall formed by host tissues

124. •In E. granulosusthe hydatidcyst has three layers.
1.The endocystis the germinal membrane that is
lined by flattened cells and gives rise to brood
capsules and protoscolices
2.The ectocystthat surrounds this layer is
composed of a laminated acellularmembrane
3.This, in turn, is surrounded by a pericystthat
consists of an inflammatory reaction consisting
of neutrophils, eosinophils, and histiocyteswith
formation of granulomas, This is surrounded by
a zone of fibrosis and reactive astrocytosis.

125. •Following infection, the host develops an
immunologic response that is protective
against reinfection, but does not protect the
host from the lodged parasite as the parasite
evades host immune attack.
•Spilling of cyst fluid due to trauma or surgery
may trigger anaphylaxis as well as
disseminated infection

126. •Host reaction is minimal in the brain; however, a foreign giant cell
reaction develops when the cyst contents spill
•A wide range of evasion mechanisms have been proposed,
including
–a barrier for host cells due to the hydatidcyst’s laminated cuticle,
–polyclonal activation of lymphocytes by parasite soluble antigens, and
–depression of host cell immune responses.
•Chronic stimulation of the host by the parasitic antigens leads to
increased specific IgG4 production, which might act as blocking
antibodies to protect the host against anaphylaxis

127. •Diagnosis
•This is based on radiological or histologic
demonstration of hydatidstructure from any
site, positive CSF serology, and rarely biopsy.

128. Sparganosis
•Epidemiology
•This is a zoonoticlarval infection by
Sparganumspecies.
•Reported primarily from South-East Asia,
America, and Africa

129. Life cycle
•The adult worm is found in cat and dog
intestine.
•Humans are infected by drinking water
containing copepods or by eating
undercooked meat of the intermediate hosts
•The larvae migrate in tissues in humans
without maturing

130. Sparganosis: An abscess surrounds the parasite larva
that has a cuticle and contains excretory ducts, smooth muscle, and
calcareous corpuscles.

131. •Clinical manifestations
•Focal neurological deficits, seizures, and
hemorrhageare seen depending on the
location of the parasite

132. Pathology and pathogenesis
•The parasite burrows into the CNS and being
long, forms multiple cavitarylesions.
•The lesions are in the form of abscesses or cysts.
•An abscess with a wall of inflammation surrounds
the parasite larva, which has a cuticle and
contains excretory ducts, smooth muscle, and
calcareous corpuscles
•Granulomatousinflammation can also occur
surrounding the parasite.

133. •The sparganummigrates by secreting
proteases that degrade extracellular matrix
proteins.
•The parasite releases an allergenic protease
and prostaglandin E, which cleave
immunoglobulin molecules in the host,
thereby escaping detection.
•Dead and dying sparganumelicit an
inflammatory reaction

134. •Diagnosis
•This is based on history of consuming raw
meat, radiological evidence, positive CSF
serology, and rarely a biopsy.

135. Nematode infections

136. Strongyloidiasis
•Strongyloidesstercoralisis an intestinal
infection with man as the definitive host.

137. •Epidemiology
•Strongyloidiasisis globally distributed but is
more common in the tropics and subtropics,
which have a warm, wet climate.

138. Life cycle
•S. stercoralishas three life cycles: direct, indirect,
and autoinfection.
•In the direct cycle, rhabditiformlarvae in the
fecesbecome filariformlarvae in the soil and
infect humans by penetrating the skin.
•In the indirect cycle, rhabditiformlarvae molt
several times in soil and mature into male and
female adult worms, which go through the life
cycle as eggs, rhabditiformlarvae, and adult
worms under favorableconditions.

139. •In autoinfection, rhabditiformlarvae become infective filariform
larvae while in the intestine or in the perianalskin.
•Once in the skin, they enter dermal vessels and reach the lungs and
enter the alveolar spaces.
•These larvae then migrate up the bronchial tree and are swallowed.
•The larvae mature in the proximal gut into adult female worms that
produce eggs by parthenogenesis.
•The autoinfection cycle is particularly accelerated in
immunosuppressedpatients, which leads to hyperinfectionand
CNS lesions

140. Strongyloidiasis: Rhabditiformlarvae in feces.

141. •Clinical manifestations
•Patients manifest with headache, fever, and
focal neurological syndromes

142. Pathology and pathogenesis
•Meningitis with purulent exudates on the
surface of the brain is seen with
strongyloidiasis. Foci of cerebral infarction
may also occur.
•Histologically, the leptomeningescontains
dense infiltrates of polymorphonuclear
leukocytes and filariformlarvae of S.
stercoralis.

143. •Obstruction of microvasculature by filariform
larvae causes a thrombotic microangiopathy
and resultant microinfarction.
•Granulomatousinflammatory reaction has
also been reported.
•Patients with hyperinfectionoften develop
Gram-negative septicemia, and, in such cases,
small cerebral abscesses caused by bacteria
have been reported

144. •Diagnosis
•Microscopic examination of fecesthat yield
rhabditiformlarvae is the best diagnostic test .
•Enzymelinkedimmunosorbentassay (ELISA)
for IgGantibodies to antigens of filariform
larvae of S. stercoralisis a sensitive test, with
low specificity as other nematodalinfections
result in cross-reactions.

145. Gnathostomiasis
•Epidemiology
•This disease is caused by nematodes of the
Gnathostomagenus.
•Initially endemic in Mexico, Spain, South-East
Asia, and Japan
•It is part of a viscera larva migranssyndrome

146. Life cycle
•Humans are accidental hosts in whom the
larvae cannot reach sexual maturity and
causes a viscera larva migranssyndrome

147. •Clinical manifestations
•The patients develop meningitis or
neurological deficits, including radiculitisand
cranial nerve palsies

148. Pathology and pathogenesis
•Hemorrhagesin the subarachnoid and
cerebral cortex are characteristic.
•Histologically, eosinophilic
meningoencephalitiswith hemorrhagic
necrosis and edemain the brain and spinal
cord.
•If the larval form is present, they have a
cuticle that is covered with short spine

149. Diagnosis
•In the appropriate epidemiologic setting,
eosinophiliain the CSF should raise suspicion
of this infection.
•Specific antibody tests are available for
diagnosis
•A biopsy is rarely undertaken

150. Trichinosis
•Epidemiology
•Consumption of raw or undercooked meat containing
encysted larval forms of Trichinellacauses trichinosis.
•T.spiralisis the most common species that affects
humans,andinfection in the brain occurs very rarely.
The parasite is seen globally except in Australia.
•The adult worm lives in the intestine of carnivores, and
the larvae enter the portal system and spread
throughout the body, particularly into skeletal muscle.

151. Trichinosis: Longitudinal and cross-sections of T.
spiralis larvae in skeletal muscle.

152. •Clinical features
•Involvement of the CNS is extremely rare and
causes headache, irritability, and seizures

153. Pathology and pathogenesis
•An eosinophilicmeningoencephalitis, glial
hyperplasia,hemorrhagicfoci, vascular necrosis,
arteriolar and small capillary thrombosis, and
ischemic lesions have been described.
•The lesions in the CNS are attributed to trauma
secondary to larval migration, vascular
obstruction, and toxemiasecondary to larva or to
eosinophilinfiltration

154. •Diagnosis
•Serology and muscle biopsy help in confirming
the diagnosis

155. Toxocariaisis
•Toxocaracanusis a zoonoticworm infection.
•The definitive host is dog and in humans it is a
paratenicinfection
•Headache, meningism, mental confusion, focal
or generalized seizures, neurological deficits,
and ataxia are the presenting symptoms.

156. •Eosinophiliaoccurs in both the peripheral blood
and cerebrospinal fluid.
•Lesions occur in the leptomeninges, brain, or
spinal cord.
•Histologically, a granulomatousreaction around
fragmented larva, surrounded by fibrosis, and an
infiltrate of eosinophilsis seen as an allergic
reaction to the larva

157. Diagnosis
•Serology is useful, although cross-reactions
with other nematode species may give false-
positive reactions.
•Prior absorption of serum or CSF with larval
antigens from other nematodes would,
however, improve specificity.

158. Filariasis
•The main filariasesof humans are lymphatic filariasis,
onchocerciasis, loiasis, mansonelliasis, and
dirofilariasis.
•The brain and spinal cord are not affected by most
filarial infections.
•Chemotherapy with diethylcarbamazine(DEC) or
ivermectinfor Loa loacan cause an encephalopathy in
those who have high microfilaremia, where death of
the microfilaria results in an immunopathological
reaction

159. •Histologically, microvasculature within the brain
contains thrombi with enmeshed microfilariaeof
L. loa, which is surrounded by reactive
astrocytosisand microglia proliferation.
•The CSF may contain the parasite in cases with
Mansonellaperstansand meningonema
infection, the patient however remains
asymptomatic

160. Conclusions
•The vast range of parasites that infect the
brain and spinal cord stands testimony to the
fact that, although seemingly protected within
bony and membranous coverings, the CNS is
as vulnerable as all other sites to infection.
•Whereas some parasites cause disease by
direct effects, others manifest with clinical
disease owing to immune responses against
the parasite.

161. •The global pandemic of HIV has further changed
the epidemiology of these infections with
relatively unknown and rare parasites infecting
the CNS.
•Accurate diagnosis involves an understanding of
the prevalence, risk factors, clinical syndromes,
and pathology associated with each parasite and
above all the protean manifestations of parasitic
diseases in the CNS.