The most common clinical manifestation of parenchymal NC is epileptic seizure, which occurs in 60–90 % of cases. The symptomatology of altered mental state and psychiatric manifestations remains poorly described in the literature (Carabin et al. 2011). In two studies (Forlenza et al. 1997; Carpio et al. 2008) which provided definitions of clinical manifestations, depression was reported in about 53 % and 15 % of the patients, respectively. A recent study reports a spectrum of cognitive abnormalities, including dementia (Rodrigues et al. 2012).

At these locations (around 15–30 % of cases) headache and signs of elevated intracranial pressure due to the obstruction of CSF circulation are the most frequent symptoms. These occur in 88 % of the cases, in comparison with 10 % of cases with parenchymal location (Carpio et al. 1994). Inflammation of meninges can also generate cranial nerve dysfunction, chiasmatic syndrome, and cerebral infarcts secondary to vasculitis (Agapejev et al. 2007; Cárdenas et al. 2010a, b). When hydrocephalus is present (Fig. 5a), the mortality rate is high (50 %), and most patients die within 2 years after CSF shunting (Cárdenas et al. 2010a, b; Sotelo et al. 1988). This is why ventricular and basal cisternal locations are considered to be malignant forms of NC (Estañol et al. 1986).

Spinal cord cysticercosis is rare. Patients experience nonspecific clinical manifestations, such as nerve root pain or spinal cord compression syndromes, according to the level of the lesion (Alsina et al. 2002). Severe forms of NC may exceptionally occur, including cysticercotic encephalitis, and result in permanent neurological sequels, such as amaurosis.

In addition to being less common in children, NC clinical manifestations clearly vary in different age groups (Kelvin et al. 2009a, b; Rosenfeld et al. 1996). Most cases of childhood NC present mild to moderate symptomatology and single lesions (Ruiz-Garcia et al. 1997; Kelvin et al. 2011). A study specifically carried out to compare the clinical manifestations between pediatric and adult NC patients (Sáenz et al. 2006) has reported statistically significant differences: seizures were more frequent in children (80.4 % vs. 56.1 %) and intracranial hypertension and headaches were more frequent in adults (27.2 % vs. 15.2 % and 35.1 % vs. 21.7 %, respectively). Although these age-related differences seem clear, a single effect of age is difficult to demonstrate, since various confounding factors are probably involved (Kelvin et al. 2009a, b).

Most paediatric cases show a single enhancing lesion, also named solitary cysticercus granuloma (Singh et al. 2010). This lesion is a common finding in patients with newly identified seizures in developing countries. These patients have some benign and transitory clinical manifestations, predominantly partial or partial secondary generalized seizures. Single enhancing lesions tend to resolve spontaneously, without anticysticercal treatment or surgery, since the parasite is already in the degenerative phase and will eventually disappear or become calcified.

Inflammation surrounding parenchymal cysticerci is more intense in women (Kelvin et al. 2009a, b), and multiple degenerating parasites localized in the CNS parenchyma are also more frequently reported in young women. Regardless of the localization of the parasite, the inflammatory response, as expressed by CSF cellularity, is more intense in women (Fleury et al. 2010). There are significant gender and age differences in the local immune response (Kelvin et al. 2009a, b). It has been suggested that both age and gender influence the strength of the host’s immune response. The odds of having transitional cysts are higher for female patients than for males (Kelvin et al. 2011).

Clinical heterogeneity across geographical areas is well documented. Most cases from the Indian subcontinent present single degenerative lesions, whereas those from Latin America present few viable cysts (Singh et al. 2010). These differences are probably due to complex interactions between the host, parasite, and environmental factors (Singh 1997; Fleury et al. 2010). Genetic differences in T. solium cysticerci have been reported from different countries (Maravilla et al. 2008; Vega et al. 2003) and may contribute to clinical variations among countries. Genetic susceptibility to NC has been suggested on the basis of positive association of HLA-DRBII 13 with single, contrast-enhancing CT lesions (Jain et al. 1999). However, neither familial aggregation of seizures in first degree relatives of NC patients with seizures (Kelvin et al. 2009a, b) nor significant aggregation of NC cases in families have been found (Fleury et al. 2006), arguing in favor of the involvement of multiple genes.

Diagnosis of NC is mainly made by neuroimaging. MRI is more sensitive than CT for the diagnosis of viable and degenerating cysticerci, since it improves recognition of the perilesional edema and degenerative changes of the parasite, as well as of cysts located inside the ventricles or the subarachnoid space. However, CT is more sensitive than MRI for the detection of calcifications.

CT or MRI can identify the four developmental phases of cysticerci when located in the brain parenchyma. In the vesicular phase, the CT scan depicts circumscribed, round, hypodense areas, varying in size and number, without enhancement by contrast media (Zee et al. 2000). In the MRI, the vesicular larva appears with a CSF-like intensity signal on all sequences, with no surrounding high signal on T2-weighted images (Lucato et al. 2007; Mont’Alverne Filho et al. 2011). Both MRI and CT may show a high intensity or hyperdense, 2–3 mm mural nodule depicting the scolex, within some vesicular cysts (Fig. 4a). MRI sequences such as axial fluid attenuated inversion recovery (FLAIR) detect a significantly higher number of scolices than other sequences, which is helpful for improving the diagnosis of NC (Lucato et al. 2007). As the cyst degenerates, the contrast-enhanced CT scan shows an annular (colloidal phase) or nodular (nodular phase) enhancement surrounded by irregular perilesional edema (Fig. 4b). In this phase, the fluid content gives a slightly higher signal than CSF and is sometimes isodense with the parenchyma on MRI-T1 and/or proton density-weighted, and high signal on T2 images. The capsule shows a higher signal than the adjacent brain tissue, with thick ring enhancement on T1 images, while on T2 images there is a low ring signal surrounded by high signal lesion, due mostly to edema (Dumas et al. 1997; Zee et al. 2000). When the cyst dies it may disappear or become an inactive calcified nodule with homogeneous high density on CT or low intensity on proton-weighted MRI (Fig. 5b).

When the parasites are located in the subarachnoid space or within the ventricular system, recognition of parasites with MRI is more difficult, as parasites emit an intensity signal similar to that of the CSF, generally do not enhance after intravenous administration of contrast, and commonly lack a scolex. Thus, often only indirect signs of the presence of the parasite are available, such as the unilateral enlargement of the basal cistern (Lucato et al. 2007) (Fig. 6). Specific MRI sequences including diffusion-weighted MRI magnetization transfer ratio (MTR), 3D constructive interference in steady state (3DCISS), fast imaging employing steady state acquisition sequences (FIESTA; Fig. 6a), and FLAIR sequences have proven to be more sensitive tools to visualize the cyst wall (Braga et al. 2004; Fleury et al. 2011). In case of meningeal inflammatory process, gadolinium enhancement of MRI or contrast-enhanced CT may depict leptomeningeal thickening (Kioumehr et al. 1995) and hydrocephalus (Fig. 5a).

No optimal immunological test for NC diagnosis is yet available. The difficulties of developing a sensitive and specific immunological test for NC diagnosis are mainly the result of the proper characteristics of the disease. An immunological test useful for medical practice must be specific in terms of CNS localization and should differentiate between viable and non-viable forms of the parasite.

Different immunological tests have been developed. The most widely used tests aim at the detection of specific antibodies. In these cases, different types of antigens have been used: crude antigens or partially purified antigenic extracts of T. solium or of the related parasites T. crassiceps or T. saginata, and recombinant or synthetic proteins. Techniques have also evolved, from complement fixation test, indirect hemagglutination, to the enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunoelectrotransfer blot (EITB) assay (Tsang et al. 1989; Brandt et al. 1992), which are the two main techniques currently in use. Also, detection of antigens by monoclonal or polyclonal antibodies using the ELISA technique has been developed (Brandt et al. 1992).

Comparisons of these tests have given divergent results, in part due to differences in methodology between studies. Despite these sources of variations, it seems that EITB in sera has higher sensibility and specificity than ELISA to detect antibodies, at least when carried out in non-endemic areas (Ramos-Kuri et al. 1992). It is also clear that sensitivity of both tests falls in cases with a single parasite, when parasites are located in the brain parenchyma or are calcified (Wilson et al. 1991; Singh et al. 1999). In CSF, performance of Ab-ELISA and EITB seems to be quite similar (Proaño-Narvaez et al. 2002; Michelet et al. 2011). Antigen detection in sera or CSF is highly specific for detecting viable extra-parenchymal parasites (Fleury et al. 2007). Another important point is the feasibility of carrying out ELISA and EITB techniques in endemic countries. In fact, while ELISA can be accomplished in 20 h and costs around $2.00 per sample, EITB assay requires almost 2 weeks, sophisticated equipment, highly skilled personnel, and its cost is up to ten times greater than ELISA (Proaño-Narvaez et al. 2002).

Despite the current immunological and imaging advances, the diagnosis of NC is still a challenge in many patients. Del Brutto et al. (2001) proposed diagnostic criteria for NC based on clinical, imaging, immunological and epidemiological features. This proposal, though not validated so far, may be useful to identify patients with parenchymal, but not extraparenchymal, forms of NC (Machado 2010). Such diagnostic criteria should be revised to incorporate current scientific knowledge, in order to achieve a new consensus on the diagnosis of NC.