Neurocysticercosis: A Review on Global Neurological Disease

Abstract

The most prominent parasitic disease of the human central nervous system is neurocysticercosis, a neurologic parasite disease brought on by the engorged larva of the tapeworm Taenia solium. It is the most frequent cause of acquired epilepsy in endemic areas and a problem for the bulk of the developing world’s public health systems. However, because of globalisation, neurocysticercosis cases are now also increasing in wealthy nations. With two intermediate hosts (i.e., pigs and humans) and one final host, neurocysticercosis has a complicated disease path, through faecal-oral contamination, one contracts it. Neurocysticercosis is the most significant CNS parasite that causes severe illness. Based on the location of the disease, it has historically been classified into active and inactive types. Radiologists must be aware of the differential diagnosis because of the wide variety of its imaging appearances. Imaging results are influenced by the number and distribution of parasites as well as any related consequences such as vascular involvement, an inflammatory response, and, in the case of ventricular forms, the degree of blockage. As a result, the diagnosis, treatment, and prognosis of neurocysticercosis vary widely depending on the type of infection.

1. Introduction

Initially recognised in ancient Greece as a pig disease, neurocysticercosis is the most prevalent helminthic disease of the human CNS. The majority of the developing world is affected by the disease, which thrives in environments with a warm climate, extreme deprivation, and widespread illiteracy. The disease is a health concern in metropolitan areas of developing countries because neurocysticercosis is a significant contributor [1, 2, 3]. In the industrialised world, the prevalence of neurocysticercosis has grown along with the number of immigrants coming from endemic countries. Latin American immigrants account for approximately 90% of neurocysticercosis patients in the United States and Europe [4, 5, 6]. However, neurocysticercosis has also been seen in people who have never travelled to a location where it is endemic. The majority of these people become ill after being exposed to an adult T. solium in their bowel [7]. The host’s immunological response to the cysticerci pleomorphic lesions that parasites generate in the body is sporadic, and the condition is intriguing because it affects the CNS. Neurocysticercosis has sparked a great deal of interest due to medications. Here, we’ll go over the key elements of this emphasis on the pathogenesis of parasitic diseases, and on current developments in diagnosis and treatment.

2. Etiopathogenesis

The life cycle of T. solium completes within two hosts (Figure 1). Pigs and humans can both act as intermediate hosts for the tapeworm metacestode stage called cysticercus larvae, but humans are the permanent host. During the typical cycle of transmission, the adult Theridion solium resides in the human small intestine, where it is affixed to the intestinal wall by its powerful suckers and hooks. The gravid proglottids, which are connected to the worm’s distal end, are separated and passed with the faeces, release thousands of viable eggs into the environment. In places with inadequate faeces disposal, pork is fed with human faeces bearing T. solium eggs. The eggs shed their outer covers once they are within the pig’s digestive tract, releasing oncospheres that go through the intestinal wall and into the circulation before being transported to the tissues, where they develop into cysticercus. Cysticerci are produced in the small intestine, after people consume tainted hog meat, where the action of digestive enzymes leads their scolices to evaginate and adhere to the intestinal wall.

Figure 1.

Life cycle of Neurocysticercosis (Source: [8]).

Once the scolex is attached, the proglottids proliferate until they reach maturity 4 months after infection [9]. Humans can act as intermediate hosts for T. solium after eating its eggs. Under these circumstances, human cysticercosis can occur. Cysticercosis can be contracted from faeces by people who consume food contaminated with T. solium eggs or by those who already have the adult parasite in their intestines. Previous hypotheses that claimed that environmental contamination with T. solium eggs was the main cause of human contamination with the parasite have been disproved by recent epidemiological research that shows the clustering of cysticercosis patients near taeniasis patients. Human cysticercosis is considered to be an illness that primarily spreads from person to person, with infected pigs acting as the vehicle for the parasites [10].

The two main parts of cysticerci are the scolex and the vesicular wall [11]. After entering the central nervous system, cysticerci are in the vesicular (viable) stage, when the parasites have a transparent membrane, clear vesicular fluid, and a characteristically invaginated scolex. Cysticerci may last for years or undergo a degenerative process that causes them to turn into calcifications as a result of the host’s immune response. The vesicular fluid becomes murky during the colloidal stage of cysticercal involution, and the scolex shows signs of hyaline degeneration. During the next stage, known as the granular stage, the cyst wall hardens and the scolex changes into mineralised granules. The cysticercus is no longer alive at this moment. Finally, the parasite remains are visible as a mineralised nodule [12]. The tissue around vesicular cysticerci does not experience considerable inflammation. In contrast, the parasite is typically wrapped in a collagen capsule, with a mononuclear inflammatory response surrounding colloidal cysticerci.

The surrounding brain parenchyma exhibits astrocyte gliosis, microglial proliferation, oedema, neuronal degenerative changes, and lymphocyte perivascular cuffing. When the parasites reach the granular and calcified phases, the oedema disappears; however, the astrocytic changes around the lesions may worsen. Epithelioid cells also begin to grow and assemble into multinucleated big cells at this time. Meningeal cysticerci often cause a strong inflammatory response in the subarachnoid space and aberrant thickening of the leptomeninges. This exudate contains collagen fibres, lymphocytes, multinucleated giant cells, eosinophils, and hyalinized parasite membranes [13]. Widespread inflammation may cause damage to cranial nerves, the optic chiasm, and small penetrating arteries that arise from the circle of Willis.

The latter might result in a blockage of the vessel’s lumen, which would cause a cerebral infarction to form [14]. Ventricular cysticerci may potentially trigger an inflammatory response if they are linked to the choroid plexus or the ventricular wall.

While certain cysticerci antigens aid in the evasion of the immune system’s defences against cysticerci, other cysticerci antigens, including (especially antigen B), cause the production of particular antibodies that constitute the cornerstone of the cysticercosis immunological diagnosis [15]. Furthermore, it has been postulated that increased subpopulations of CD8 T-lymphocytes, poor lymphocyte proliferation, and aberrant cytokine concentrations in neurocysticercosis patients lead to cellular immunological dysfunction. According to the studies, immunodeficiency conditions and the growth of gliomas are associated with neurocysticercosis [16].

According to a notion, the immune system may find it challenging to detect malignancy in these circumstances due to the high levels of glial proliferation around the parasites and the inhibition of cellular immune responses, resulting in the malignant transformation of astrocytes (Figure 2) [17].

Figure 2.

Transmission of Neurocysticercosis. Source: https://journals.plos.org/plosntds/article/figures?id=10.1371/journal.pntd.0 008005

3. Clinical manifestations

Individual variability in the number and location of lesions within the CNS, as well as variations in the intensity of disease activity, accounts for the clinical pleomorphism of neurocysticercosis. The most frequent symptom of neurocysticercosis is seizures, which may be the only or major symptom in over 70% of individuals [18]. Patients with parenchymal neurocysticercosis experience seizures more frequently than those with subarachnoid or ventricular illnesses [19].

4. Diagnosis

Modern neuroimaging techniques have significantly improved our ability to diagnose neurocysticercosis. The quantity and topography of lesions as well as their stage of involution may be objectively determined using computed tomography and magnetic resonance (Figure 3) [21, 22]. On computed tomography and magnetic resonance, vesicular cysticerci show up as tiny, spherical cysts that are clearly separated from the surrounding brain parenchyma. Physicians may now use a set of diagnostic criteria based on an unbiased assessment of clinical, radiological, immunological, and epidemiological data to help them identify individuals who may have neurocysticercosis (Table 1) [23]. Absolute, major, minor, and epidemiologic are the four types of criteria in this collection, which are ranked according to each diagnostic category’s strengths.

Figure 3.

Imaging with parenchymal brain cysticercosis: (a) viable cysts showing the scolex (b) colloidal cyst appearing as a ring-enhancing lesion [20].

Diagnostic criteria
Absolute	Major	Minor	Epidemiologic
Histologic evidence of the parasite.	Neuroimaging investigations diagnosed the abnormalities	Neuroimaging studies	Household contact with suffering people
In neuroimaging studies, there is evidence of cystic lesions displaying the scolex.	Treatment of cerebral cystic lesions with albendazole or praziquantel.	Clinical symptoms of neurocysticercosis are seen.	where cysticercosis is endemic
The fundoscopic examination allows for the direct visualisation of subretinal parasites.	Anti cysticercal antibodies were detected in a positive serum immunoblot.	Presence of cysticercosis outside of the central nervous system.

Table 1.

Table showing differential diagnostic criteria.

The introduction of three-dimensional MRI sequences, such as Fast Imaging Employing Steady-State (FIESTA) and 3D constructive interferences steady state (3D CISS), has recently enhanced MRI sensitivity and specificity, particularly for subarachnoid and ventricular cysticerci [24, 25, 26]. Several approaches for detecting antigens and anti-cysticerci antibodies in CSF have been established. Although enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immuno electro transfer blot assay (EITB) in CSF have good sensitivity and specificity, their complexity, length of execution, and cost are significant barriers to their use [27, 28]. Taenia antigens, which are more sensitive than eosinophils, can also be identified in CSF, particularly in clinically active kinds of NCC [28].

5. Treatment

There are four stages of neurocysticercosis completion (Figure 4). Based on which stage of neurocysticercosis is identified as are necessary for treatment, not every patient with neurocysticercosis is expected to respond favourably to a certain course of therapy. A well-informed treatment plan depends on accurately describing the illness in terms of the health of the cysts, the strength of the host’s immune response to the worm, and the place and number of lesions [30]. Typically, treatment involves taking both symptomatic and cestocidal/cysticidal drugs. Additionally, surgery is used to treat certain individuals [31].

Figure 4.

Representing Stages of Neurocysticercosis [29].

The prognosis for the majority of patients with neurocysticercosis has been considerably influenced by the widespread use of two potent cestocidal/cysticidal drugs (praziquantel and albendazole) [32]. Initial dosages of praziquantel were given for 15 days at a rate of 50 mg/kg/day (given every 8 hours) [33]. Then it was suggested that eliminating the parasites could only require three different doses of 25 to 30 mg/kg given at intervals of 2 hours, exposing cysticerci to high drug concentrations sustained for up to 6 hours. It seems that patients with a single parenchymal brain cyst respond better to praziquantel’s one-day therapy, but those with numerous cysts should utilise the 15-day trial, despite the early data with this unique regimen being encouraging.

Albendazole, the other cestocidal/cysticidal drug, was originally administered at dosages of 15 mg/kg/day for a month [34]. According to additional studies, if a patient just has a single brain cyst, the period of treatment might be shortened to just 1 week or perhaps just 3 days. In trials comparing the effectiveness of the two drugs, albendazole has outperformed by praziquantel. Another advantage of albendazole is that it removes ventricular and subarachnoid cysts. In some of these circumstances, especially in people with significant subarachnoid cysts, higher doses of albendazole (up to 30 mg/kg/day) or longer or even repeated courses may be necessary.

The use of cestocial/cysticidal medications has come under investigation due to the mild nature of some cases of neurocysticercosis, which has caused patient uncertainty and poor treatment choices. Cestocidal/Cysticidal medications are allegedly only effective at removing cysts; they have no impact on the clinical course of the disease. Recent studies, however, have shown that the majority of patients who use cestocidal/cysticidal drugs also see improvements in their clinical conditions. In a placebo-controlled study, albendazole was effective in treating viable parenchymal brain cysticerci [35, 36, 37].

Other well-conducted trials demonstrated that, in contrast to non-treatment, therapy improves the prognosis of individuals with colloidal parenchymal brain cysts. A recent meta-analysis of randomised controlled trials investigated the effects of cestocidal/cysticidal drugs on neuroimaging and clinical outcomes in patients with neurocysticercosis. According to that meta-analysis of published data, cestocidal/cysticidal drug therapy results in a lower risk of seizure recurrence in patients with colloidal cysticerci, a decrease in the frequency of generalised seizures in patients with vesicular cysticerci, and better resolution of both colloidal and vesicular cysticerci. Remember that not all neurocysticercosis patients should be treated with cestocidal/cysticidal drugs. These drugs may exacerbate the symptoms of intracranial hypertension found in cysticercotic encephalitis patients [36].

To avoid further therapy-related increases in intracranial pressure, cestocidal/cystocidal medicines should only be administered to patients with parenchymal brain cysts and hydrocephalus. Concurrent steroid administration is necessary to reduce the risk of a cerebral infarct. Individuals with ventricular cysts should refrain from taking cestocidal/cysticidal drugs. Last but not least, cestocidal/cysticidal drugs should not be administered to individuals who merely have calcifications because these lesions simply reveal parasites that are already dead. Patients with epilepsy brought on by neurocysticercosis often get seizure control after using just one first-line antiepileptic drug. According to some research, in order to effectively manage their seizures, patients with live intracranial cysts should first receive cestocidal/cysticidal medication before receiving antiepileptic medication [38].

It is unknown how long patients with neurocysticercosis should take antiepileptic medication. Prospective research found that up to 50% of patients with parenchymal brain cysticercosis who were successfully handled with cestocidal/cysticidal drugs later lost consciousness after quitting their antiepileptic drugs [39].

6. Control measures

T. solium transmission factors include inadequate faecal waste management practices, a lack of education, pig slaughter houses with no veterinary control, and the presence of wild pigs close to households, which are common causes of neurocysticercosis. The parasite condition could be fully eliminated. However, in order for eradication efforts to be effective, they must concentrate on complete control, such as with human adult tapeworm carriers, infected pigs, and environmental eggs. Inadequate focus on one of these targets might result in a subsequent increase in the prevalence of taeniasis and cysticercosis since these targets correspond to related phases in the life cycle of T. solium [36, 37].

7. Conclusion

The morbidity and mortality of the NCC are strongly impacted by accurate diagnosis together with appropriate symptomatic assessment, followed by a well-designed therapeutic intervention by the healthcare professional. Potential research avenues include the creation of novel cestocidal/cysticidal medications and drug delivery technologies for both the human and swine populations [8].

8. Future prospects

With an understanding of these immunological and genetic pathways, more modern drugs like tamoxifen and cutting-edge drug delivery techniques like lactic acid-conjugated solid lipid nanoparticles carrying albendazole and prednisolone will be created to successfully treat NCC. Preclinical animal studies on the pharmacokinetics, safety, and toxicity of oxfendazole for humans have yielded encouraging findings. For the management of swine cysticercosis, another promising area of study is the development of potent antiparasitic drugs, particularly in combination therapy, [40].

9. Preventive measures

There are many issues, including a lack of adequate epidemiological data on infection, control, and elimination. Suspected cases can be avoided through community health and education efforts, as well as a comprehensive healthcare approach involving [41, 42, 43, 44].

• Pig vaccination and anthelmintic medication to prevent T. solium cysticercosis infection.

• Updated pig management procedures to keep pigs away from human excrement.

• Inspection and adequate cooking of pigs to limit the danger of human infection.

• Healthcare promoting hand cleanliness, food hygiene, sanitation, and pig management.

Acknowledgments

The authors are grateful for the facilities provided by the Department of Zoology, Chaudhary Charan Singh University, Meerut, India.

Conflict of interest

None