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By

Ahmed Abudeif Abdelaal

Assistant Lecturer of Tropical Medicine & Gastroenterology

Sohag Faculty of Medicine2013

Eosinophilic Meningitis

Definition of meningitis- It is inflammation of the arachnoid, pia mater and intervening CSF. The inflammatory process extends throughout the subarachnoid space into the brain and spinal cord and involves the ventricles.

Eosinophilic meningitis is defined as the presence of 10 eosinophils /mL in CSF or at least 10% eosinophils in the total CSF leucocyte count.

- Helminthic infections are the most common cause of eosinophilic meningitis.

- Eosinophilia is classified as one of the following:i. Reactive as in the inflammatory reaction to

helminths.ii. Clonal as in eosinophilic leukemia.iii. Unexplained, as in HES.

- CSF eosinophilia is most frequently associated with reaction to infectious agents.

Causes of Eosinophilic MeningitisA)Parasitic Diseases:

i. More common1) Angiostrongyliasis.2) Gnathostomiasis.3) Baylisascariasis.4) Schistosomiasis.5) Cysticercosis.6) Toxoplasmosis.7) Toxocariasis.8) Paragonimiasis.

ii. Less common1) Trichinellosis.2) Hydatid Disease.

Causes of Eosinophilic Meningitis

3) Coenurosis.4) Myiasis.

B) Fungal Infections• Coccidioides immitus.

C) Neoplastic Disease• Lymphoma, leukaemia, metastatic carcinoma.• Hypereosinophilic syndrome.

D) Inflammatory Processes• Sarcoidosis• Drug hypersensitivity.• Presence of foreign body in the CNS.

Parasitic Diseases

Parasites More Commonly Producing

Eosinophilic Meningitis

Angiostrongyliasis• Causative agent:

- Angiostrongylus cantonensis is the most important aetiological agent of eosinophilic meningitis.

- A. cantonensis is a nematode that normally infect rodents, primarily rats.

- The adult worms inhabit the pulmonary arteries of rodents (rat lung worm).

Angiostrongyliasis- Humans are incidentally infected after eating poorly cooked or raw intermediate mollusk hosts. Fresh vegetables may also serve as a vehicle of human infection if they are contaminated with parts of mollusk containing infective larvae.

- Larvae can migrate to the CNS but can't develop further.

Angiostrongyliasis• Epidemiology:

- Human infections occur mainly in Southeast Asia, the South Pacific and less frequently in Africa and the Caribbean.

Angiostrongyliasis• Disease:

- Clinical manifestations usually occur 1 week to 1 month after exposure and include fever, severe headache, meningismus, nausea, vomiting, seizures, focal neurologic deficits, paresthesias, cranial nerve palsies and visual disturbances.

- The natural course of the disease involves spontaneous resolution of symptoms within few

Angiostrongyliasisweeks, rarely entails sequelae and is rarely fatal.- The mean duration is 20 days (range 6-34 days), although the headache and paresthesia can persist for weeks to months.

Angiostrongyliasis• Diagnosis:

- It is based largely on a history of possible exposure, clinical picture (meningitis with severe headache), peripheral eosinophilia and detection of eosinophils (rarely larvae) in the CSF.

- CSF findings include: cloudy CSF, increased opening pressure, elevated protein level, normal glucose, elevated absolute leucocytic count with eosinophilia.

Angiostrongyliasis- CT and MRI brain: usually there is no focal lesions.

- Immunological diagnosis: under development.

Angiostrongyliasis• Treatment:

- Most patients recover completely after about 2 weeks.

- The use of anthelmintics is controversial, with only a few reports of benefit with albendazole or mebendazole, usually administered in combination with analgesics and steroids to relieve symptoms.

- Periodic removal of CSF can relieve symptoms of raised intracranial pressure.

Gnathostomiasis• Causative agent:

- Gnathostoma spinigerum is an intestinal nematode of dogs and cats.

- Humans are accidentally infected after eating of raw or undercooked intermediate hosts (fish, frogs, pigs) or rarely through direct larval penetration of the skin.

Gnathostomiasis• Epidemiology:

- Gnathostomiasis mainly affect young male adults in the 3rd and 4th decades of life and is known to have a seasonal occurrence corresponding to the rainy season in Thailand.

- The disease is prevalent in Asian countries especially Thailand, Korea, Japan, parts of Mexico and Central and South America.

Gnathostomiasis• Disease:

- Infection with Gnathostoma spp. is typically categorized into cutaneous, visceral and CNS forms.

- Gnathostoma infection can cause symptoms that recur for 10-13 years.

- The cutaneous manifestations include migrating painful and pruritic subcutaneous swellings.

Gnathostomiasis- The organism can invade the eye directly causing pain, uveitis and blindness.

- In the CNS, Gnathostoma infection is more severe than Angiostrongylus infection.

- CNS gnathostomiasis usually presents with radicular pain followed by severe headache, impaired sensorium, neck stiffness, seizures, weakness or paralysis and sometimes urinary incontinence. SAH may occur.

Gnathostomiasis• Diagnosis:

- The diagnosis is challenging.

- The presence of history of travel to regions with high risk of infection, progression of symptomatology and the presence of peripheral and CSF eosinophilia are suggestive of disease.

- CSF findings include: bloody or xanthochromic CSF, increased opening pressure (50 % of cases), normal or elevated protein levels,

Gnathostomiasisnormal glucose levels, increased leucocytic count with eosinophilia.

- CT and MRI: There is nodular lesions, areas of haemorrhage and even hydrocephalus.

- There is no commercially available serologic tests for gnathostomiasis.

Gnathostomiasis• Treatment:

- For cutaneous disease: both albendazole and ivermectin are effective, although multiple courses are needed for some patients.

- For CNS disease: the treatment is mainly supportive. The role of anthelmintics and steroids hasn’t been clearly defined.

Comparison of features of Angiostrongylus and Gnathostoma

Baylisascariasis• Causative agent:

- The disease is a rare zoonosis caused by infection with the ascarid Baylisascaris procyonis, which is primarily a nematode parasite of raccoons and other small carnivores.

- Humans get infection through contact with raccoons or environments contaminated with their feces.

Baylisascariasis• Epidemiology:

- The disease is prevalent in North America, Japan and Germany.

Baylisascariasis• Disease:

- Migration of larvae may be asymptomatic or may produce visceral, cutaneous or ocular larva migrans syndrome.

- Unlike angiostrongyliasis and gnathostomiasis, ocular disease is concomitant with neurological disease in many patients.

- CNS disease is usually very severe and leads to sequelae or death.

Baylisascariasis- The typical clinical presentation of CNS disease is an acute and rapidly progressing meningoencephalitis, characterized by lethargy, ataxia, seizures and paralysis. Fever is usually not prominent.

Baylisascariasis• Diagnosis:

- MRI eventually demonstrates nonspecific diffuse white matter lesions.

- Eosinophilia in the CSF may be extremely high. It varies from 4 to 68%. Protein and glucose levels may be normal.

- Peripheral eosinophilia can vary widely from 5 to 45%.

Baylisascariasis- Antibodies can be detected in serum and CSF, preferably by ELISA or WB.

Baylisascariasis• Treatment:

- Anthelmintics aren’t effective for the treatment of baylisascariasis.

- So, prophylactic treatment with albendazole (20 to 40 mg/kg/day) or thiabendazole (50 mg/kg/day) should be started immediately after exposure to raccoon latrines or cages. Treatment should be maintained for at least 10 days.

Schistosomiasis• Causative agent:

- Schistosoma spp. parasitize the blood vessels of vertebrates.

- Five species are known human parasites: S. mansoni, S. haematobium, S. japonicum, S. mekongi, and S. malayensis.

- The CNS is an ectopic location for eggs of Schistosoma spp. especially S. mansoni and S. japonicum.

Schistosomiasis• Epidemiology:

- Schistosomiasis is endemic in sub-Saharan Africa, Latin America, Egypt and China.

- Neuroschistosomiasis (NSM) is most common in young male adults.

- Humans get infection through contact with water containing cercariae.

Schistosomiasis• Disease:

- In NSM, spinal cord lesions predominate, also it can affect the cerebrum or cerebellum.

- Cerebral schistosomiasis occurs in 1.7-4.5% of hospitalized patients with S. japonicum. It may occur as early as 6 weeks after infection and the most common sign is focal jacksonian epilepsy, headache, optic field lesions or difficulty in speech.

Schistosomiasis- Spinal cord lesions may be:

i. Medullar, when the involvement of the spinal cord predominates.

ii. Myeloradicular, when spinal cord and nerve root lesions occur.

iii. Conus-cauda equina syndrome, when there is a predominant involvement of the terminal spinal cord and cauda equina.

- There is acute or subacute progression.

Schistosomiasis• Diagnosis:

- CSF findings include: mild to moderate increase in cells and protein, glucose levels are slightly low or normal, eosinophilia is evident in 50% of patients.

- ELISA performed with soluble egg antigen (SEA) is the most reliable immunological method for diagnosis of NSM. A value of 1.4 mg/ml IgG anti-SEA in CSF supports the possibility of schistosomiasis.

Schistosomiasis- MRI shows enlargement of the spinal cord and thickening of the spinal roots, including the cauda equina on T1-weighted images.

Schistosomiasis• Treatment:

- Praziquantel and steroids are the drugs of choice for treatment of NSM.

- PZQ should be administered at (50-60 mg/kg) either as a single dose or as a daily dose for 5 days.

- Steroids should be maintained for long periods (3-6 months).

Cysticercosis• Causative agent:

- Cysticercosis is the infection with the larval stage of T.solium (cysticercus).

- Neurocysticercosis (NCC) occurs when cysticerci are present in the CNS.

- The infection is acquired by ingestion of eggs released with feces.

Cysticercosis• Epidemiology:

- Cysticercosis is found in all regions of the world where pigs are raised .

- Countries with the largest prevalence of NCC are Mexico and India. Infections are also prevalent in other countries of Latin America, Africa and Asia.

Cysticercosis• Disease:

- The clinical manifestations of NCC vary with the location of cysticerci and the associated host response.

- In general, parenchymal cysticerci are associated with seizures, whereas ventricular and subarachnoid cysticercosis is associated with hydrocephalus.

- The spinal cord is involved in less than 5% of

CysticercosisNCC cases and this may lead to compression syndromes or meningomyelitis.

- Small number of intraparenchymal cysts are asymptomatic.

Cysticercosis• Diagnosis:

- CT and MRI are sensitive for identification of the lesions.

- CSF findings include: increased leucocytic count with eosinophilia. Cell counts rarely exceed 300/mm3. Proteins are elevated, and glucose levels are usually normal.

- Immunological diagnosis: WB with purified cysticercus glycoprotein antigens is the current

Cysticercosisgold standard antibody detection assay.

- PCR in the CSF.

Cysticercosis• Treatment:

- Albendazole (15 mg/kg/b.i.d. for 8 days) is the drug of choice for the treatment of NCC.

- PZQ is less effective alternative.

- Steroids are necessary in cases of meningitis, vasculitis, large intraventricular cysts and encephalitis.

- Symptomatic treatment as antiepileptics, shunting, surgical removal of large cysts.

Toxocariasis• Causative agent:

- The disease results from accidental ingestion of the embryonated eggs of the dog and cat ascarides Toxocara canis and Toxocara cati, respectively.

- T.canis has migration preference for nervous tissue.

Toxocariasis• Epidemiology:

- Toxocariasis is a cosmopolitan infection.

- Children are most frequently infected.

Toxocariasis• Disease:

- Human toxocariasis manifests as either VLM or ocular larva migrans syndrome.

- CNS infection is rare, and may be manifested as meningitis, myelitis, encephalitis or compination.

Toxocariasis• Diagnosis:

- MRI brain may show multiple or solitary subcortical, cortical or white matter lesions.

- Eosinophilia can reach up to 70% in either blood or CSF. It is possible to have peripheral eosinophilia without CSF eosinophilia and vice versa.

- CSF protein is slightly elevated in about 50% of cases, and glucose levels are usually normal.

Toxocariasis- Immunological methods detecting the 2nd stage larva excretory-secretory (TES) antigens of T. canis are highly sensitive and specific.

Toxocariasis• Treatment:

- There has been no clinical trial evaluating drug treatment for neurotoxocariasis.

- Albendazole is recommended at a dose of (5-15 mg/kg b.i.d. for 2 to 4 weeks).

- Steroids can be used if there is vasculitis.

Paragonimiasis• Causative agent:

- Paragonimiasis is a zoonotic disease caused by Paragonimus spp. the most common is P.westermani.

- Humans get infected through consumption of raw or undercooked crustaceans especially crabs.

Paragonimiasis• Epidemiology:

- The disease is endemic in Asia, South America and Africa.

Paragonimiasis• Disease:

- Paragonimiasis manifests as a pulmonary infection with cough, chest pain, haemoptysis,..

- CNS infection is the most common (50%) non-pulmonary form of the disease.

- Clinical manifestations of cerebral disease are seizures, focal signs, and meningismus. Unlike other forms of meningitis, there is no severe compromise of general condition or mental

Paragonimiasisstatus.

- Spinal involvement may occur.

Paragonimiasis• Diagnosis:

- CNS paragonimiasis can be difficult to be detected.

- CSF eosinophilia is not present in all patients, CSF glucose levels are typically low.

- Immunofluorescence, ELISA, and WB are the main methods for diagnosis.

Paragonimiasis• Treatment:

- PZQ (total dose of 150 mg/kg, divided into three doses over 2 days).

- Triclabendazole is an alternative treatment (10 mg/kg/day for 3 days).

Parasites Less Commonly Producing

Eosinophilic Meningitis

Trichinellosis• Causative agent:

- It is due to infection with Trichinella spiralis.

- Humans get infection through consumption of inadequately cooked pork containing encysted infective larvae.

Trichinellosis• Disease:

- The condition started with acute fever, myalgia, periorbital or facial oedema.

- Up to 17% of patients infected with T.spiralis may present with neurological symptoms, including headache, abnormal deep reflexes, neck stiffness and behavior disturbances. Recovery is usually spontaneous and complete.

Trichinellosis• Diagnosis:

- The condition should be suspected in patients with a compatible clinical presentation, history of eating raw or undercooked pork, peripheral eosinophilia and elevated muscle enzymes (e.g creatine kinase, LDH).

- CSF is normal in most patients.

- Antibodies can be detected using ELISA or WB.

Trichinellosis- Muscle biopsy revealing encysted larvae will confirm the diagnosis.

Trichinellosis• Treatment:

- Mebendazole can be given at 200 mg/day for 5 days. or

- Albendazole can be given at 400 mg/day for 3 days.

- Steroids must be given in severe cases.

Hydatid Disease• Causative agent:

- It is due to infection with the larval stage of the cestode, Echinococcus granulosus.

- Humans are infected by ingestion of eggs through hands or food contaminated with dog excreta.

Hydatid Disease• Epidemiology:

- The disease is common in sheep-raising countries, where dogs have access to infected offal. These include South Australia, New Zealand, Africa, South America, southern Europe and the Middle and Far East.

- The disease is more common during childhood.

Hydatid Disease• Disease:

- Typical locations of hydatid cysts are the liver and lungs.

- CNS lesions occur in 2-8% of patients.

- All hydatid cysts grow slowly, and depending on their location can cause a variety of effects, such as headache, vomiting, weakness in extremities, seizures, visual disturbances and cranial nerve palsies.

Hydatid Disease- Eosinophilic meningitis may occur as a complication of surgical resection, but this is rare.

Hydatid Disease• Diagnosis:

- CT and MRI can reveal the cysts.

- Antibodies can be detected by indirect hemagglutination, indirect fluorescence tests, and ELISA.

Hydatid Disease• Treatment:

- Long term administration of albendazole.

- PAIR technique.

- Complete surgical resection of the cyst.

Coenurosis- Infection with larval stages of the dog tapeworm Taenia multiceps.

- CNS disease is very rare and manifests as increased ICP. CSF eosinophilia is not the rule.

Myiasis- Myiasis is the invasion of animal tissues with larval stages of flies.

- The larvae may parasitize the skin of vertebrates.

- Facial lesions, especially next to the eyes and in the paranasal sinuses, may result in bone erosion and migration of the larvae to the CNS, where eosinophilic meningitis may occur.

Myiasis- The efficacy of anthelmintics is not yet established, and surgical resection may be necessary.

Fungal Infections

Coccidioidomycosis kok-sid-ee-oy-doh-my-KOH-sis

- Coccidioides immitis is the most prevalent fungal cause of eosinophilic meningitis.

- Infection occurs by inhalation of conidia.

- The disease is endemic to desert areas in the southwestern United States and northwestern Mexico.

- About 2/3 of cases are asymptomatic.

Coccidioidomycosis- In symptomatic cases it affect the lungs, LNs, skin or may disseminate by blood to various organs including meninges.

- According to records from endemic areas, about 30% of patients with CNS infections caused by C. immitis present with significant CSF eosinophilia, 40% have lower counts and the remaining 30% have no eosinophils detected. Other reports describe eosinophilic meningitis as a very rare manifestation of C. immitis infection.

Coccidioidomycosis- CSF glucose levels are decreased and protein levels are usually high. CSF cultures are positive for only a small number of cases.

- Detection of IgG and IgM is best performed by CF test. However, this test is negative in 30% of cases of coccidioidal meningitis, so their absence shouldn’t rule out diagnosis.

- Without treatment, coccidioidal meningitis is universally fatal.

Coccidioidomycosis- Fluconazole in high doses (up to 1200 mg/day) is the best option for treatment.

- Itraconazole, voriconazole, and intrathecal amphotericin B are also options.

- Treatment should be sustained for years, since therapy is not curative, and the fungus remains latent in tissue even after successful clinical remission.

- Meningeal eosinophilic reaction may be concomitant with other infections, these include:

1. Allergic aspergillus sinusitis.

2. Streptococcal newborn infection.

3. Coxsackie viral meningitis.

4. Lymphocytic choriomeningitis virus.

5. Rickettsial disease and Rocky Mountain spotted fever.

6. Few cases of neurosyphilis and tuberculous meningitis.

Neoplastic Diseases

A) Neoplastic Diseases- CSF eosinophilia have been documented with:

1) Acute lymphoblastic leukemia.

2) Acute myeloid leukemia.

3) Chronic eosinophilic leukemia.

4) Chronic myeloid leukemia.

5) Systemic mastocytosis.

6) Chronic myelomonocytic leukemia.

7) Juvenile myelomonocytic leukemia.

8) Myelodysplastic syndrome.

9) Hodgkin‘s disease.

10) Non-Hodgkin's lymphoma.

11) Disseminated glioblastoma and carcinomatosis .

B) Hypereosinophilic Syndrome (HES)- HES is a disorder characterized by eosinophilia of unknown origin lasting longer than 6 months.

- The signs of HES are cell counts exceeding 1500/ml of blood in the absence of known causes of eosinophilia, accompanied by organ damage or dysfunction due to release of the toxic components of eosinophil granules.

- Although nervous tissues are reported to be

B) Hypereosinophilic Syndrome (HES)affected in 54% of HES patients, neurological disturbances and specific eosinophilic meningitis are not a common finding.

Inflammatory Processes

A) Drug Hypersensitivity- There are a few reports of CSF eosinophilia associated with use of drugs.

- Associations with ibuprofen, ciprofloxacin, trimethoprim/sulfamethoxazole and intraventricular vancomycin and gentamicin have been found.

- Drug-induced meningitis can mimic the clinical features of infectious meningitis.

A) Drug Hypersensitivity- Signs and symptoms generally develop within 24 hours of drug ingestion, although it may sometimes take days.

- CSF usually reveals an elevated opening pressure, increased leucocytic count (ranging from hundreds to several thousands), glucose levels are usually normal or decreased, and protein levels are usually elevated. All cultures, must be negative for any bacterial, viral, or fungal etiologies.

A) Drug Hypersensitivity- Treatment consists of discontinuing the suspected medication and supportive measures. Most meningeal signs and symptoms resolve within 24 to 48 hours of stopping the offending drug.

- In-hospital observation and treatment with IV antibiotics is appropriate until bacterial meningitis has been ruled out.

A) Drug Hypersensitivity- The prognosis is excellent, typically with complete reversal of symptoms and no evidence of residual effects.

- There have been no documented fatalities to date.

B) Foreign Body in the CNS- CSF eosinophilia may indicate malfunction of a plastic implant or any nonorganic materials coming in contact with the meninges.

- CSF eosinophilia is present in up to 30% of children with an intraventricular shunt.

Thank you