Dive into the realm of parasitic infections affecting the nervous system, covering cases like cerebral malaria and neurocysticercosis. Gain insights into diagnostics and treatments, unravelling the impact on neurological health.

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In the central nervous system (CNS), they may remain asymptomatic, cause some acute manifestations, or develop into a chronic disease.

This article highlights the most common parasitic nervous system infections seen in routine clinical practice, along with salient features of some rare ones.

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Cerebral malaria

Malaria is the most common cause of parasitic mortality and morbidity worldwide, affecting not only the inhabitants of tropical countries but also travellers. Out of the four species, only Plasmodium falciparum is seen to affect the CNS and cause severe disease.[1]

P. falciparum is transmitted through the bite of Anopheles species mosquito. The life cycle involves various stages involving the liver, RBCs in humans and the GI tract of mosquitoes.

Besides the usual systemic symptoms of malaria (fever, malaise, etc.), patients present with seizures (focal onset or generalised), behavioural abnormalities, and alteration of the sensorium, subsequently resulting in coma.

Adults have fewer complications and neurologic sequelae compared to children. Neurological symptoms can also occur from high fever, adverse effects of antimalarials, metabolic derangements and severe anaemia.

Fig. 1: Typical changes seen in Malarial Retinopathy.

The presence of retinopathy (Fig. 1) is both sensitive and specific for malaria and is associated with a poorer prognosis.[3] Neuroimaging (mainly MRI) may reveal the presence of focal infarcts, and cerebral and cerebellar oedema, while CSF study is largely normal.

Malaria treatment:

Initiation: Early use of antimalarials

• Intravenous Artesunate (I/V Artesunate)

Supportive measures:

• Control of seizures
• Other supportive interventions as needed

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Neurocysticercosis

Humans acquire NCC by ingesting the tapeworm eggs via faecal/oral transmission.

Clinical manifestations

1. Clinical manifestations of NCC depend on the location of the lesion, its size, number, and stage as well as the inflammatory response of the host.
2. Seizures & headaches are the main features of intraparenchymal NCC, whereas the extraparenchymal (subarachnoid and intraventricular) forms present with intracranial hypertension, arachnoiditis and hydrocephalus.
3. The various evolutive stages of NCC can be well visualised on neuroimaging. Initially, it begins with a viable cyst (Vesicular Stage) which later degenerates (Colloidal Stage) and is associated with inflammation.
4. Subsequently, it transforms into an inflammatory nodule (Granulo-nodular Stage) and then disappears.
5. In a few cases, it may reappear as a calcified scar (Calcified Stage). Sometimes, uncontrolled parasite growth in the subarachnoid space leads to the formation of large parasite clusters resembling a bunch of grapes (racemose neurocysticercosis) (Fig. 2)
6. Hence, NCC has a long latent period in which the brain cysts evade the immune mechanisms of the host. It is the death of the cyst which brings about the inflammatory reaction and subsequent clinical features of NCC.

Recent guidelines recommend the usage of both CT and MRI for the diagnosis of NCC5. Detection of antibodies against T. solium can be done by the enzyme-linked immunoelectrotransfer blot (EITB) assay using lentil-lectin purified glycoprotein parasitic antigens in serum. Antigen detection confirms the presence of living parasites and helps in monitoring treatment.[6]

Fig 2: Racemose form of NCC. Multiple CT and MR images demonstrate multilobulated and multiseptated CSF signal/density structures within the suprasellar cistern, associated with localised mass effect and a few linear areas of peripheral enhancement.

Management of NCC:

1. Therapy for NCC included management of seizures, raised intracranial pressure and the use of antiparasitic drugs (with/without corticosteroids).
2. Both viable and degenerating cysts contain live parasitic tissue and antiparasitic drug usage is beneficial in both cases.
3. However, the use of antiparasitic drugs may initially worsen neurological symptoms because of an increase in inflammation around the cyst.

Albendazole treatment
Single cyst	Multiple cysts
Dose: 15mg/kg/d	Combination therapy: Albendazole plus praziquantel
Duration: 7 to 15 days	Albendazole dose: 15mg/kg/d
	Praziquantel dose: 50mg/kg/d
	Duration: 10 days
Surgical intervention
Indications
1. Hydrocephalus management
2. Removal of large intraventricular cysts

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Toxoplasmosis

It is caused by the protozoan Toxoplasma gondii, which infects humans by:

• Consumption of infected meat containing tissue cysts
• Ingesting infective oocysts in soil
• Organ transplantation
• Blood transfusion or mother-to-foetus transplacental infection

It is a frequent cause of neurological disease in HIV-infected immunocompromised patients.

Congenital infection during pregnancy may lead to abnormalities and parenchymal brain tissue calcification. Retinal scars can be seen in early childhood infection.

In adults who are immunocompromised, tissue cysts may reactivate, resulting in clinical symptoms (fever, headache, focal neurological deficits, raised intracranial pressure, seizure, etc.)

Neuroimaging reveals the presence of ring-enhancing lesions mostly seen in the basal ganglia and subcortical white matter (Fig 3). The eccentric-target and concentric-target signs are highly specific for the diagnosis of CNS Toxoplasma infection.

Serology helps in confirming the diagnosis: a positive IgM test or rising IgG antibody titres are indicative of acute infection.[7] 

Negative serology results may be found in HIV-infected patients. PCR of CSF is helpful in neurological disease. 

Fig 3: Patient with CNS toxoplasmosis. A. Axial FLAIR exhibiting hypointense lesion in the nuclei of the base with hyperintense peripheral halo (arrow). B. Axial T1 exhibiting the same hypointense lesion with peripheral ring enhancement. Mural nodule (eccentric target signal).

Treatment includes early initiation of a combination of pyrimethamine and sulfadiazine for 6 weeks or more with Leucovorin added to reduce haematological toxicity.

Patients with a sulfa allergy can be given-

• Clindamycin or
• Atovaquone

Alternatively, Trimethoprim-Sulfamethoxazole can be given resulting in a lower pill burden, less frequent dosing, and lower cost of therapy. Treatment efficacy is assessed by imaging follow-up. Non-responders should be evaluated for the presence of Primary CNS Lymphoma which is a close differential diagnosis. 

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Other parasitic infections of the central nervous system (CNS)

1. Free-living amoebae:

Types: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri

Modes of invasion: Through the skin, respiratory tract, or directly through olfactory mucosae

Diseases caused:

• Naegleria: Primary amoebic meningoencephalitis
• Acanthamoeba and Balamuthia: Granulomatous amoebic encephalitis (more chronic)

Trypanosomiasis
Subdivisions	Caused by
Sleeping Sickness (African Trypanosomiasis)	T. brucei
Chagas Disease (American Trypanosomiasis)	T. cruzi

• Insect vectors:

1. Tsetse fly for Sleeping Sickness
2. Bugs of the genus Triatoma for Chagas Disease

Other rare parasitic human infections
Infection	Caused by
Toxocariasis	Toxocara canis, Toxocara cati
Angiostrongyliasis	Angiostrongylus cantonensis
Strongyloidiasis	Strongyloides stercoralis
Gnathostomiasis	Gnathostoma spinigerum
Trichinosis	Trichinella spiralis
Paragonimiasis	Paragonimus westermani, Paragonimus mexicanus, Paragonimus skrjabini
Schistosomiasis	Schistosoma japonicum, Schistosoma mansoni, Schistosoma haematobium
Echinococcosis/Hydatid Disease	Echinococcus granulosus, Echinococcus multilocularis
Sparganosis	Spirometra sp.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr. Annesh Bhattacharjee is a Consultant Neurologist, Dept. of Neurology GNRC Hospital, Guwahati.