parasitic diseases of the central nervous system

Parasitic diseases of the central nervous system

Shahin Hameed

• There are essentially two broad categories of parasitic infections, protozoan and metazoan, and several of these affect the central nervous system (CNS).

• The protozoal infections that infect the CNS include malaria, trypanosomiasis, amebiasis, toxoplasmosis, leishmaniasis, and microsporidiosis.

PROTOZOAL INFECTIONS

1.Cerebral malaria

Epidemiology

• Until recently P. falciparum was the only species known to involve the CNS.

• In the past decade, however, there have been two reports of P. vivax manifesting with neurological disease.

• Cerebral malaria typically occurs in tropical regions where P. falciparum is rampant, such as, Africa, South-East Asia, and Central and South America.

Life cycle

• The parasite has two life cycles:

– sexual reproduction in the anopheles mosquito vector and

– asexual reproduction in the intermediate human host.

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.

• 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.

• 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

• For example, P. falciparum erythrocyte 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.

• Sequestration of parasitized red blood cells (RBCs) stimulates the production of inflammatory cytokines, such as TNF.

• These cytokines upregulate adhesion molecules, such as ICAM-1, CD36, and VCAM-1, in the microvasculature, resulting in further sequestration,activation of astrocytes and monocytes, as well as causing disruption of intercellular junctional protein complexes, resulting in abnormal vascular permeability.

• Impaired nitric oxide availability is also thought to contribute to this process.

• Functional obstruction eventually results in reduced blood flow, hypoxia, and reduced glucose.

Pathology

• Malarial encephalopathy results in petechialhemorrhages in the cerebral white matter, particularly in the corpus callosum, cerebellum, brain stem, and subcortical region

• The external surface is usually congested, and the brain may show swelling with flattening of the gyri and compression of the ventricles.

• Hemazoin pigment lends a slate gray hue to the brain.

• Histologically, parasitized erythrocytes are sequestered in the cerebral microvasculature. Hemazoin pigment is easy to identify within erythrocytes as brownish— black granular material .

Sequestration of parasitized red blood cells in the cerebral microvasculature

Haemazoin pigment within erythrocytes

• Foci of hemorrhage, especially ring-like hemorrhages, are characteristic .These contain a central necrosed blood vessel surrounded by concentric zones of parasitized and nonparasitized erythrocytes, free pigment, and few monocytes and lymphocytes.

• Also seen are punctiform hemorrhages due to rupture of a blood vessel

Ring hemorrhages in the white matter

• “Dürck granuloma” is a focus of reactive astrocytosis admixed with microglial cells and lymphocytes surrounding a focus of ischemic necrosis or hemorrhage.

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, Dürckgranulomas, and pigment deposits may be the only residual signs of an infection.

2.Toxoplasmosis

Epidemiology

• Toxoplasmosis is caused by the intracellular coccidian parasite Toxoplasma gondii.

• T. gondii is found worldwide and the prevalence varies widely.

• Nearly 25%-50% of patients with HIV infection have latent T. gondii infection

Life cycle

• T. gondii exists in three forms: oocysts, tachyzoites, and bradyzoites.

• The definitive hosts are members of the family Felidae (cat), and oocysts of T gondii are only produced in them.

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

Clinical picture

• The clinicopathological syndromes associated with toxoplasmosis fall into the following three categories:

• 1.Primary toxoplasmosis in immunocompetentindividuals.

• Clinical manifestations in this set of individuals are rare

• 2.Toxoplasmosis in immunosuppressedpatients.

• Most common opportunistic infection in HIV patients.

• Patients present with headache, seizures, and cranial nerve and neurological deficits

• 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.

Pathogenesis

• Natural killer cells induced by T helper type I cells are cytotoxic to infected cells.

• Extracellular tachyzoites are 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 vasculitis with resultant obliteration of vessels and infarction

Pathology

In congenital toxoplasmosis, hydrocephalus and foci of calcification are seen

• 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 ventriculitis with periventricular necrosis, or as a space-occupying lesion.

Mass lesions with necrosis,hemorrhage, and cerebral edema

Bilateral thalamic hyperintense lesions showing mild peripheral ring enhancement. The location of these granulomas is

highly suggestive of toxoplasmosis

• Histologically, in the congenital form of toxoplasmosis, intracellular Toxoplasma are seen in ependymal and glial cells in a periventricular location associated with an acute inflammatory response to cell death and necrosis.

• Periaqueductal and leptomeningealinvolvement results in hydrocephalus

Leptomeningeal inflammation involving vasculature

• In adults, in the encephalitic form, microglial nodules are diffusely scattered throughout the parenchyma

• The necrotic foci contain infected cells, tachyzoites, and karyorrhecticdebris surrounded by microglia, inflammatory cells, and astrocytes

• Bradyzoites may be present at the periphery of the lesion

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

• In chronic lesions, organisms are reduced in number, and with treatment, the lesions undergo cystic change.

Immunopositivity for Toxoplasma tachyzoites within cerebral lesion

Diagnosis

• Cerebral spinal fluid (CSF) examination may demonstrate the presence of antibodies and Toxoplasma DNA.

• 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.

4.Trypanosomiasis

• Human African trypanosomiasis (African sleeping sickness)

• American trypanosomiasis (Chagas’ disease)

Human African trypanosomiasis

• Epidemiology

• T.b. rhodesiense is found in in East and South Africa whereas T.b. gambiense is found in West Africa.

• T.b. rhodesiense is a zoonosis with cattle being the reservoir, whereas T.b. gambiense uses humans as its host.

• The vector involved in transmission of the parasite is of the Glossina species, the tsetse fly.

Life cycle

• The tsetse fly is infected on ingestion of blood from mammalian hosts containing trypomastigotes.

• In the fly, the trypomastigotes go through many cycles of multiplication and their procyclic forms migrate to the salivary glands.

• The cycle is complete when the injected metacyclic form becomes a trypomastigote that multiplies in blood.

Clinical features

• CNS involvement occur weeks to months after an infected bite.

• T.b. rhodesiense has a more rapid and acute course

• Somnolence, irritability, headache, and extrapyramidal signs after a long symptom-free period leading to coma and death in untreated cases is typical of T.b. gambiense.

• In T.b. rhodesiense, the hemolymphatic stage overlaps with the meningo-encephalitic stage

– Death is from carditis, secondary bacterial infection and encephalitis

– usually develop within 6months if untreated.

Pathology and pathogenesis

• The meninges are cloudy and the brain appears swollen

• Histologically, chronic meningitis with lymphoplasmacytic infiltrates and arteritis are seen.

• The cerebral parenchyma shows perivascularchronic inflammation, microglial nodules, and reactive astrocytosis.

• Parasites are usually not demonstrable.

• 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 astroglial reaction.

• Antigen–antibody complexes trigger complement activation causing endarteritis.

• Vasogenic edema results from breakdown of the blood– brain barrier

• Diagnosis is made by finding parasites and antibodies in blood and CSF.

American trypanosomiasis (Chagas’ disease)

• Epidemiology

• Chagas’ disease is caused by T. cruzi.

• T. cruzi is a zoonosis and is transmitted by the insect vector, T. infestans, where humans are accidental hosts.

Life cycle

• The triatomine insects suck blood from humans and mammals containing the trypomastigotes of 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 hematogenously and by invading tissues

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.

Chagas’ encephalitis: Zone of inflammation withparasitized macrophages, lymphocytes, and astrocytes.

Chagas’ encephalitis: Trypomastigote in CSF.


• In the acute stage, the encephalitic picture includes perivascular cuffing by lymphocytes and formation of microglial nodules.

• Congestion, edema, and petechialhemorrhages are seen within the brain parenchyma. The parasite in its amastigoteform is seen within macrophages, endothelial cells, microglia, and astrocytes

• The pathogenesis of Chagas’ disease in the CNS is not well understood.

• The parasite probably invades the endothelium and passes into astrocytes or enters through the CSF.

• In the chronic phase, neuronal destruction is thought to be the main pathogenetic mechanism.

• Peripheral neuropathy results from autoimmunity.

• Antibodies to flagellar proteins have been found to cross-react with host tissues, particularly myelin sheaths and neurons

Diagnosis

• A diagnosis of trypanosomiasis requires the

– finding of parasites and antibodies in blood and CSF or

– demonstration of amastigote forms by histology, in situ hybridization, and PCR

5.Amebiasis

• The various clinicopathologic entities that comprise amebic infections of the CNS include the following:

• 1. Amebic abscess due to Entamoeba histolytica

• 2. Primary amebic meningoencephalitis due to Naegleria fowleri

• 3. Granulomatous amebic encephalitis due to Acanthamoeba and Balamuthia spp.

• 4. Encephalitis due to Sappinia diploidea

Cerebral amebiasis

• Epidemiology

• This is due to human colonic infection with Entamoeba histolytica.

• Global disease, although most cases are seen in Central and South America, Africa, and India

• Life cycle

• The organisms are ingested as cysts that are present in infected feces.

• Hematogenous spread from the liver to the brain results in brain abscesses

• Clinical manifestations

• The disease has an abrupt onset and a rapid course with death within 72 hours if left untreated.

• Symptoms are of meningismus with focal neurological deficits


• 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 karyosomeand periodic acid-Schiff (PAS) positive cytoplasm that contains phagocytosed erythrocytes

Necrotic center of abscess with trophozoites.

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

• Diagnosis

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

Primary amebic meningoencephalitis(PAM)

• Epidemiology

• This is a global disease and N. fowleri are found in soil, river, and lake water.

• It enters via the nasal mucosa and travels along olfactory nerves to enter the brain


• The disease has a fulminant course and is usually fatal.

• The incubation period is 1-14 days. There is fever, headache, vomiting, seizures, coma, and death


• Hemorrhagic necrosis is seen involving the inferior frontal lobe along the olfactory nerve.

• The inflammatory infiltrate seen in the leptomeninges and in the Virchow–Robin spaces consists of neutrophils and lymphocytes admixed with trophozoites.

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

Primary amebic meningoencephalitis: Inflammatoryinfiltrate in the leptomeninges admixed with trophozoites

Virchow Robin spaces with amebictrophozoites and a dense inflammatory infiltrate.

Primary amebic meningoencephalitis: Hemorrhagic necrosis of gray and white matter.

• Diagnosis

• The trophozoite can be seen on wet mounts of CSF, which shows pleocytosis

Granulomatous amebic encephalitis

Epidemiology

• This is a global disease caused by free-living amebae Acanthamoeba castellanii and polyphaga and Balamuthia mandrillaris.

• The CNS is affected in immunocompromisedindividuals. The infection reaches the CNS via the bloodstream from a site of skin injury.


• The disease manifests as headache, meningism, seizures, and focal neurological deficits.

• The clinical course is more prolonged than that caused by Naegleria and varies from 1 week to several months, with death being the inevitable outcome in untreated patients.


• 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 fibrinoidnecrosis surrounded by trophozoites and cysts

• Several multinucleated giant cells of the foreign body and Langhans’ type are seen.

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

Granulomatous amebic encephalitis: Fibrinoid necrosis of blood vessel walls surrounded by trophozoites and cy

Diagnosis

• Skin biopsy with granulomatous infection and demonstration of trophozoites would aid in diagnosis.

• The diagnosis can be confirmed by culture.

6.Microsporidiosis

• Zoonotic disease seen primarily in immunosuppressedindividuals.

• Manifests as nodular encephalitis

• Parasites are seen as small hematoxyphilic dots within foci of necrosis and inflammation that are associated with reactive astrocytosis and microglial proliferation.

• Acid-fast and Gram-positive.

7.Leishmaniasis

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

METAZOAL INFECTIONS

Metazoal infections

• Trematode infections

• Cestode infections

• Nematode infections

TREMATODE INFECTIONS

Schistosomiasis

• Epidemiology

• Schistosomiasis is endemic in certain parts of the world.

• Schistosoma japonicum is the most common species affecting the brain.

• S. haematobium and S. mansoni cause spinal cord lesions.

Life cycle

• Humans are the definitive hosts of S. mansoniand S. haematobium.

• Humans are infected when cercariae penetrate the skin and enter dermal veins, lose their tail to become developing worms or schistosomulae, and then migrate to the lung.

• The schistosomulae then 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.


• Seizures, focal neurological deficits, paraplegia, and radiculopathy are seen depending on whether the parasite lodges in the brain or spinal cord.


• 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 .

(A, B) Schistosomiasis: Multiple circumoval granulomas in the cerebral parenchyma. (C) The granulomas have Schistosoma eggs surrounded by an inflammatory reaction comprising numerous eosinophils and fibrosis..

(D) Schistosomiasis: Some of the eggs are seen within giant cells. (E) Schistosomiasis: Zone of reactive astrocytosis surrounding the granulomatous reaction

• Schistosomiasis arises from an initial immune complex-based reaction to egg antigens followed by a cell-mediated granulomatousprocess in which cytokines determine the size of thegranuloma and the extent of fibrosis.

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

Paragonimiasis

• Epidemiology

• Paragonimiasis is infection by trematodes of the genus Paragonimus with P. westermanibeing the most prominent of this species.

• These are endemic in Asia, the Americas, and Central and Western Africa.

Life cycle

• Human infection is acquired by eating crustaceans that are the second intermediate hosts.

• Paragonimus needs three hosts to complete its life cycle. Carnivorous mammals are definitive hosts

• First intermediate host, a mollusk, where mircidia multiply and develop into sporocysts, rediae, and cercariae.

• The latter now invade the second intermediate host, a crustacean, where they develop into encysted metacercaria.

• 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


• 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.


• Cerebral and spinal cord paragonimiasis cause arachnoiditis, abscesses, and granulomas.

• Necrotizing abscesses can be up to 10 cm in size and have a thin capsule.

• Granulomas are seen as firm fibrotic lesions.

• The space occupying lesions are seen more frequently in the temporal and occipital lobes and in the spinal cord.

• The leptomeningeal inflammation is composed of polymorphonuclear leukocytes and eosinophils in the acute phase and lymphocytes and fibrosis in more chronic stages.

CESTODE INFECTIONS

Cysticercosis

• Epidemiology

• Infection occurs with larvae of tapeworm Taenia solium.

• Globally endemic, this infection is usually seen in impoverished regions

Life cycle

• Cysticercosis occurs 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.

• In cysticercosis, man ingests eggs that hatch into oncospheres. These penetrate the gut wall and disseminate hematogenously to organs where they encyst.

• The encysted form is called a cysticercus and survives for a few years.


• 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.


• 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 cysticercus to several hundred.

• When present in the subarachnoid space and in the ventricle, the morphology of the cysticercuschanges to form grape-like clusters.

– known as the “racemose” form of cysticercus .

(A) Numerous cysticerci within cerebral parenchyma.(B) T2 weighted image of multiple NCC in vesicular and colloid stages many showing

eccentric scolices within. Also seen is a racemose cyst in the left sylvian fissure.(C) Neurocysticercosis: T1 with contrast of image seen in Fig 6B with multiple NCC in vesicular and colloid stages many showing eccentric scolices within.

(D) Neurocysticercosis: The bladder wall of the cysticercus larva with microvilli on 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 formcalcareous bodies. (E, F) Neurocysticercosis: The proto-scolex has four suckers and a rostellum with a double row of 22-36 large and smallhooklets that are birefringent. (G) Neurocysticercosis: Cysticercus with cavitary space

(H) Neurocysticercosis: Cysticercus with cavitary space bordered by dense inflammation.

(I) Neurocysticercosis: Cavitary space without a cysticercus lined by inflammatory granulation tissue containing palisaded histiocytes, giant cells, lymphocytes, plasma cells and eosinophils.

(J) Neurocysticercosis: Cerebral parenchyma surrounding cysticercus larva with reactive gliosis and chronic inflammation.

• Sometimes the only tell-tale signs of the parasite are the calcareous corpuscles.

• In infection with cysticercus, both humoraland cell-mediated immune mechanisms are activated.

• The T helper-2 cell-mediated response is the most significant reaction

Diagnosis

• The diagnosis is usually made on radiological imaging

• In cases of solitary cysticercus granulomas, 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

Coenurosis

• Epidemiology

• This is a rare infection by Taenia multiceps. The disease is seen in Europe, North and South America, and Africa

Life cycle

• The definitive host is a carnivore.

• Infection in humans occurs by inadvertent ingestion of eggs in feces.

• Clinical features

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


• A parasitic yellowish-white cyst surrounded by a capsule formed by host tissues is seen.

• The cyst contains numerous protoscolices and 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

• Diagnosis

• Demonstration of the parasite is required for definitive diagnosis

Hydatidosis

• Epidemiology

• Hydatid infections can be caused by two different species:

• Echinococcus granulosus and E. multilocularis.

– E.granulosus is endemic worldwide.

– E. multilocularis is seen in North and South America, Australia, Europe, China, Japan, Russian Federation, and Turkey

Life cycle

• The definitive hosts of E. granulosus are canines.

• In humans, the disease is caused by accidental ingestion of eggs

• The definitive host of E. multilocularis is the fox, and this infection, although rare, is more aggressive.

(A) Echinococcosisa multiloculated cyst with calcified margins in the lefttemporal lobe(B) Echinococcosis:Post contrast CT sections of the same case seen in (A). (C) Echincococcosis: T2W images showing a multiloculated cystic lesion in the right side ofthe posterior fossa within the subarachnoid spaces with a T2W hypointense rim indenting the medulla and cerebellum focally

(E) Echinococcosis: Section of metacestode showing the thin germinal membrane with brood capsules and protoscolices(F) Echinococcosis: Section of metacestode showing the brood capsules and protoscolices.(G) Echinococcosis: Section showing an invaginated protoscolex of E.granulosus

containing one of 4 suckers and hooklets

(H, I) Echinococcosis: Granulomatous reaction surrounding the parasite. (J) Echinococcosis: Collapsed laminated cyst wall of metacestode of E. granulosus.


• 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


• 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 unilocular or contain several daughter cysts and are surrounded by a fibrous wall formed by host tissues

• In E. granulosus the hydatid cyst has three layers.1. The endocyst is the germinal membrane that is

lined by flattened cells and gives rise to brood capsules and protoscolices

2. The ectocyst that surrounds this layer is composed of a laminated acellular membrane

3. This, in turn, is surrounded by a pericyst that consists of an inflammatory reaction consisting of neutrophils, eosinophils, and histiocytes with formation of granulomas, This is surrounded by a zone of fibrosis and reactive astrocytosis.

• 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

• 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 hydatid cyst’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

• Diagnosis

• This is based on radiological or histologicdemonstration of hydatid structure from any site, positive CSF serology, and rarely biopsy.

Sparganosis

• Epidemiology

• This is a zoonotic larval infection by Sparganum species.

• Reported primarily from South-East Asia, America, and Africa

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

Sparganosis: An abscess surrounds the parasite larvathat has a cuticle and contains excretory ducts, smooth muscle, andcalcareous corpuscles.


• Focal neurological deficits, seizures, and hemorrhage are seen depending on the location of the parasite


• The parasite burrows into the CNS and being long, forms multiple cavitary lesions.

• 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

• Granulomatous inflammation can also occur surrounding the parasite.

• The sparganum migrates 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 sparganum elicit an inflammatory reaction

• Diagnosis

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

Nematode infections

Strongyloidiasis

• Strongyloides stercoralis is an intestinal infection with man as the definitive host.

• Epidemiology

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

Life cycle

• S. stercoralis has three life cycles: direct, indirect, and autoinfection.

• In the direct cycle, rhabditiform larvae in the feces become filariform larvae in the soil and infect humans by penetrating the skin.

• In the indirect cycle, rhabditiform larvae moltseveral times in soil and mature into male and female adult worms, which go through the life cycle as eggs, rhabditiform larvae, and adult worms under favorable conditions.

• In autoinfection, rhabditiform larvae become infective filariformlarvae while in the intestine or in the perianal skin.

• 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 immunosuppressed patients, which leads to hyperinfection and CNS lesions

Strongyloidiasis: Rhabditiform larvae in feces.


• Patients manifest with headache, fever, and focal neurological syndromes


• Meningitis with purulent exudates on the surface of the brain is seen with strongyloidiasis. Foci of cerebral infarction may also occur.

• Histologically, the leptomeninges contains dense infiltrates of polymorphonuclearleukocytes and filariform larvae of S. stercoralis.

• Obstruction of microvasculature by filariformlarvae causes a thrombotic microangiopathyand resultant microinfarction.

• Granulomatous inflammatory reaction has also been reported.

• Patients with hyperinfection often develop Gram-negative septicemia, and, in such cases, small cerebral abscesses caused by bacteria have been reported

• Diagnosis

• Microscopic examination of feces that yield rhabditiform larvae is the best diagnostic test .

• Enzymelinked immunosorbent assay (ELISA) for IgG antibodies to antigens of filariformlarvae of S. stercoralis is a sensitive test, with low specificity as other nematodal infections result in cross-reactions.

Gnathostomiasis

• Epidemiology

• This disease is caused by nematodes of the Gnathostoma genus.

• Initially endemic in Mexico, Spain, South-East Asia, and Japan

• It is part of a viscera larva migrans syndrome

Life cycle

• Humans are accidental hosts in whom the larvae cannot reach sexual maturity and causes a viscera larva migrans syndrome


• The patients develop meningitis or neurological deficits, including radiculitis and cranial nerve palsies


• Hemorrhages in the subarachnoid and cerebral cortex are characteristic.

• Histologically, eosinophilicmeningoencephalitis with hemorrhagic necrosis and edema in the brain and spinal cord.

• If the larval form is present, they have a cuticle that is covered with short spine

Diagnosis

• In the appropriate epidemiologic setting, eosinophilia in the CSF should raise suspicion of this infection.

• Specific antibody tests are available for diagnosis

• A biopsy is rarely undertaken

Trichinosis

• Epidemiology• Consumption of raw or undercooked meat containing

encysted larval forms of Trichinella causes trichinosis.

• T.spiralis is the most common species that affects humans,and infection 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.

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


• Involvement of the CNS is extremely rare and causes headache, irritability, and seizures


• An eosinophilic meningoencephalitis, glialhyperplasia,hemorrhagic foci, 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 toxemia secondary to larva or to eosinophil infiltration

• Diagnosis

• Serology and muscle biopsy help in confirming the diagnosis

Toxocariaisis

• Toxocara canus is a zoonotic worm infection.

• The definitive host is dog and in humans it is a paratenic infection

• Headache, meningism, mental confusion, focal or generalized seizures, neurological deficits, and ataxia are the presenting symptoms.

• Eosinophilia occurs in both the peripheral blood and cerebrospinal fluid.

• Lesions occur in the leptomeninges, brain, or spinal cord.

• Histologically, a granulomatous reaction around fragmented larva, surrounded by fibrosis, and an infiltrate of eosinophils is seen as an allergic reaction to the larva

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.

Filariasis

• The main filariases of 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 ivermectin for Loa loa can cause an encephalopathy in those who have high microfilaremia, where death of the microfilaria results in an immunopathologicalreaction

• Histologically, microvasculature within the brain contains thrombi with enmeshed microfilariae of L. loa, which is surrounded by reactive astrocytosis and microglia proliferation.

• The CSF may contain the parasite in cases with Mansonella perstans and meningonemainfection, the patient however remains asymptomatic

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.

• 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.

parasitic diseases of the central nervous system

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