**2.1 Clinical diagnosis**

Although clinical history alone is insufficient for NCC diagnosis, healthcare professionals should become familiar with some of the nonspecific clinical manifestations, particularly in endemic regions [13]. NCC symptoms vary depending on the location, number, and size of the infecting worm(s), the duration of the infection, the evolutionary stage of the lesions, and the presence or absence of a cephalic budding cysticercus [14].

Patients with symptomatic NCC frequently appear with nonspecific signs that may not allow diagnosis. Seizures are the most prevalent manifestation, accounting for 70% of symptomatic cases, and can happen at any age [15]. Headaches, focal neurologic impairments, intracranial pressure, and cognitive deterioration are other clinical signs of the illness [13]. Focal neurological signs are uncommon and depend on where parasites are located in the nervous system or when a cysticercosis-related stroke occurs. Intracranial hypertension is mainly limited to people with hydrocephalus, cysticercotic encephalitis, and large subarachnoid or ventricular cysts [16].

Health professionals must gather epidemiological information about patients, such as travel history, birthplace, address, and awareness of past or present intestinal tapeworm infection in oneself or household members, in addition to clinical assessments [13, 17]. Based on clinical suspicion, neuroimaging and serological tests will be required to confirm or rule out a diagnosis. The target sites for cysticercosis detection are illustrated in **Figure 1**.

#### **Figure 1.**

*Taeniasis/cysticercosis diagnostic tests (dx). Human: Adult tapeworm (taeniasis detection), larval cysts ([neuro] cysticercosis detection); pigs: Cysticerci in live pig or pork (cysticercosis detection).*

#### **2.2 Neuroimaging methods**

Imaging techniques, such as CT and MRI, are essential because they can reveal the parasite's presence, number, location, size and stage, and the host's immune response, which manifests as diffuse or perilesional inflammation and blood-brain barrier dysfunction visible by focal contrast enhancement. Additionally, those techniques might indicate additional related diseases, such as hydrocephalus or a stroke [3, 18].

Both CT and MRI should be performed in patients with suspected NCC. MRI offers better imaging of tiny lesions, particularly those close to the skull and in the posterior fossa and provides more information on parenchymal inflammation or periventricular effusion in hydrocephalus [15, 19]. However, CT is considerably better at detecting calcifications and quantifying lesions and is more available in hospitals in endemic regions [20]. In addition to imaging studies, electroencephalography is useful in diagnosing NCC. It can provide a helpful map and the source of abnormal brain activity consistent with the regional distribution of lesions observed on CT scans [21, 22].

#### **2.3 Laboratory diagnosis**

#### *2.3.1 Serologic diagnosis*

Immunodiagnostic techniques are essential to support clinical results and help with diagnosis. Two immunological assays are available: antibody detection of past and current infections and antigen detection of recent infections. *T. solium* infection triggers the formation of a specific immunoglobulin G antibody that can be detected in serum and cerebrospinal fluid (CSF) [23].

Lentil lectin-purified glycoproteins are used in an enzyme-linked immunoelectrotransfer blot format in the serodiagnostic assay for cysticercosis and neurocysticercosis. They are approved by the World Health Organization and the Pan-American Health Organization [24]. Despite this assay's excellent sensitivity and specificity, antigen purification requires advanced techniques and specialized knowledge. It is not a quantitative assay and is challenging to apply in field research [25]. In addition, multiple types of antigens have been used for the immunodiagnosis of cysticercosis, including low molecular mass antigens, excretory/secretory antigens, crude soluble extract, total saline extract, antigen B, vesicular fluid, membrane and scolex extracts, somatic antigens, recombinant proteins, and synthetic peptides [26].

The major drawback of this approach is the possibility of false positives because antibodies do not always indicate an active infection with viable metacestodes but a resolved infection or exposure to the parasite [27]. Another disadvantage is the possibility of cross-reactivity with other parasitic diseases, such as the one caused by *Echinococcus granulosus*. However, cross-reactivity has also been reported with other diseases, including hymenolepiasis, fascioliasis, toxocariasis [28], toxoplasmosis, malaria, amoebiasis, cerebral tuberculosis [29], syphilis, and hepatitis [30].

There has been an increased interest in diagnosing NCC using new alternative antigenic sources because the presence or absence of antibodies cannot distinguish between different stages of the disease. A 2017 study by Nunes et al. used protein purification and gel filtration chromatography to identify potential heterologous antigens in a *T. solium* metacestode [31]. The study sought to discover specific polypeptides of interest and B cell epitopes for diagnosing NCC using gel filtration fractions and mass spectroscopy. Precursors of enolase and the calcium-binding protein

#### *Advances in the Diagnosis of Cysticercosis DOI: http://dx.doi.org/10.5772/intechopen.112372*

calreticulin unique to the metacestode were discovered to have particular B cell epitopes indicative of NCC patients. Identifying these markers in serological samples is crucial and could be a reliable diagnostic tool for identifying NCC patients.

Detecting the specific circulating parasitic antigens can confirm the presence of viable parasites and overcome potential limitations. Several antigen detection techniques utilizing polyclonal or monoclonal antibodies have been studied. Two monoclonal antibody-based tests are standardized: B158/B60 Ag-ELISA and HP10. Antigen detection assays can also be used to monitor the efficacy of anthelminthic drugs and differentiate between viable parasites and locate them in the central nervous system [32]. A 2020 study by Kabululu et al. observed that the B158/B60 monoclonal-based sandwich enzyme-linked immunosorbent assay (Ag-ELISA) was more reliable in ruling out *T. solium* cysticercosis in pigs [33].
