From January 1995 to September 2024, 518 new cysticercosis cases were reported in this high-incidence region, including 197 residents from the study area, 132 from other Regional Health Department XIII municipalities, and 189 from other locations. Of these reported cases, 465 patients with confirmed NCC diagnosis were included for clinical form analysis, with 136 (29.2%) presented IHS and 329 (70.8%) other clinical presentations. The absolute risk of developing severe disease was 29.2% (95% CI: 25.1%-33.6%) among all confirmed NCC cases in this endemic region.

A significant decline in NCC incidence rates occurred from 1995 to 2024, with the decline more pronounced in the primary study region compared to surrounding municipalities, suggesting success of the Prevention Program implemented in this endemic area (Table 1; Fig. 1). Concurrently, a progressive increase in the proportion of patients with IHS occurred over three decades, from 13.4% in the first decade (1991–2000; 35/262) to 65.4% in the last decade (2011–2020; 51/78) (Cochran-Armitage trend test; chi-square 30.99; p < 0.0001), with significant trends observed throughout the period and rate convergence in 2011–2020.

Temporal evolution of neurocysticercosis incidence in Ribeirão Preto. Annual incidence rates of neurocysticercosis cases per 100,000 inhabitants in Ribeirão Preto from 1995 to 2024, demonstrating significant decline over three decades following implementation of the Taeniasis/Cysticercosis prevention program. The graph shows more pronounced reduction compared to surrounding municipalities in regional health department XIII, supporting the effectiveness of mandatory notification and prevention measures implemented exclusively in Ribeirão Preto

For detailed clinical manifestations analysis, 443 patients were considered (465 minus 22 patients diagnosed through necropsy). In initial evaluation, 181 patients were categorized as ISH forms; however, through proposed reclassification allocating only intracranial hypertension syndrome patients to ISH form, 45 patients were reclassified, leaving 136 in the final ISH form group. Clinical manifestations presented significant differences between groups (Table 2).

The severe group showed higher frequency of meningeal manifestations (47.7% vs. 15.9%) and lower occurrence of epileptic manifestations (44.9% vs. 77.8%), with some cases presenting overlap of multiple clinical manifestations. Asymptomatic manifestation occurred in 14.0% of the non-severe group. Multivariable analysis identified independent protective factors against IHS: epileptic manifestations (OR = 0.295; 95%CI: 0.182–0.477; p < 0.001) and asymptomatic presentation (OR = 0.212; 95%CI: 0.111–0.404; p < 0.001), while meningeal manifestations were associated with higher severity probability (OR = 2.992; 95%CI: 1.811–4.943; p < 0.001) (Fig. 2).

Neurosurgical procedures by disease severity. Distribution of patients who underwent neurosurgery for cyst removal according to the presence of IHS. Of the 34 patients (7.6% of the sample) who underwent neurosurgical procedures, 27 (79.4%) presented with IHS, demonstrating a strong association between this specific clinical phenotype and the need for surgical intervention. This pattern reflects the predominance of extraparenchymal cysts and hydrocephalus in IHS presentations requiring surgical management

Magnetic resonance imaging access increased progressively in the study region (42.0% in 1991–2000 to 75.0% in 2011–2020), particularly in ISH forms (46.7% to 90.0%), while surrounding areas showed peak utilization in the intermediate period (87.5% in 2001–2010) with subsequent stabilization. Magnetic resonance imaging predominated in severe cases (77.2%) versus computed tomography (23.5%), with higher frequency of viable cysts in ISH forms (77.2% versus 32.2%) and calcifications in other clinical presentations (61.2% versus 27.2%) (Fig. 3A and B).

Radiological presentations of neurocysticercosis. (A) Brain MRI in FLAIR (fluid-attenuated inversion recovery) sequence demonstrating multiple viable cysticerci with visible scolex diffusely distributed throughout the cerebral parenchyma. (B) Contrast-enhanced cranial computed tomography showing the chronic phase of neurocysticercosis with multiple calcified cysticerci. (C) Cranial MRI in T1-weighted sequence demonstrating giant neurocysticercosis cysts. (D) Lumbosacral spine MRI showing an extraparenchymal cyst located within the cauda equina. (E) Thoracic spine MRI in T1-weighted sequence demonstrating an intramedullary cyst in the thoracic spinal cord

In 24 individuals (5.4%), NCC diagnosis was made through incidental neuroimaging findings, with giant cysts identified in 2 cases requiring neurosurgical resection (Fig. 3C). Hydrocephalus was identified in 75 patients (100% in ISH), representing 16.9% of the total sample. Spinal cysts were found in 8 patients, with 3 from other clinical presentations and 5 from ISH forms, described as 7 cysts in the spinal canal and 1 intramedullary cyst (Fig. 3D and F).

Cyst location analysis revealed 362 patients (81.7%) with isolated locations without overlap: 274 cases with purely intraparenchymal location and 88 cases with exclusively extraparenchymal location. There was frequent association of cysts in different locations in the same individual, corresponding to 81 cases (18.3%). In other clinical presentations, there was predominance of non-viable intraparenchymal cysts (74.8% of 258 analyzed), with only 2 cases having extraparenchymal subarachnoid location. As expected, our findings corroborated a strong association between severe disease and extraparenchymal cyst location, whereas intraparenchymal location predominated in the non-severe, predominantly epileptic, group.

Eighty-two patients (18.5%) presented pleocytosis, with 49 (59.7%) from the ISH form group and 33 (40.3%) from the other clinical presentations group. Cell counts ranged from 10.0 to 4,560.0/mm³, all with lymphomonocytic predominance. Significant association between pleocytosis and disease severity occurred in all analyzed regions, with stronger association in the primary study area and distant referrals (p < 0.001) compared to surrounding Regional Health Department XIII municipalities (p ≈ 0.035).

Positive cerebrospinal fluid ELISA results were obtained in 33 patients (7.4%), with 21 (63.6%) from the ISH form group and 13 (36.4%) from other clinical presentations group. In 4 cases (12.1%), titers exceeded 1/4000.

Antiparasitic treatment was performed for patients with viable intraparenchymal cysts and extraparenchymal forms when surgical approach was not indicated. Of treated intraparenchymal NCC cases, 90% received albendazole and dexamethasone in single-course treatment lasting 8 days, at albendazole dose of 15 mg/kg/day and dexamethasone dose of 10-16 mg daily. Some patients (6%) received 2 treatment courses, and 4% received 3 or more courses. For extraparenchymal cases with surgical contraindication, treatment with albendazole and dexamethasone was indicated in 62%, generally with treatment courses of 15–30 days at 15 or 30 mg/kg/day albendazole dose. Only 2 cases of extraparenchymal NCC underwent retreatment with praziquantel at 50 mg/kg/day, also associated with dexamethasone at 16 mg daily.

Therapeutic management differed significantly between groups, with greater corticosteroid use (5.1% vs. 0.6%) and methotrexate use (3.7% vs. 0%) in ISH forms, reflecting the need for more intensive interventions. The corticosteroid use specified refers to controlling symptoms secondary to chronic meningitis and refractory epileptic seizures, distinct from association with antiparasitic treatment mentioned above.

Thirty-four patients (7.6%) underwent neurosurgery for cyst removal, with 27 (79.4%) in the ISH group, while 75 patients (16.9%) underwent ventriculoperitoneal shunt placement (Figs. 4 and 5). Notably, 16 cases underwent neurosurgical approach for cyst removal and ventriculoperitoneal shunt placement simultaneously. Surgical procedures occurred predominantly in patients from the primary study region (73.5% of surgical cases, p < 0.01).

Distribution of ventriculoperitoneal shunt (DVP) procedures according to the presence of intracranial hypertension syndrome (IHS). Among 75 patients (16.9% of the total sample) who underwent DVP placement, there was an almost exclusive association with IHS, with 74 cases in the IHS group versus only 1 case in the group of other clinical presentations. This finding underscores the strong relationship between IHS (the defining criterion for the group previously labeled as severe) and the need for cerebrospinal fluid diversion

Multivariable logistic regression analysis - factors associated with severe disease. Forest plot showing odds ratios (OR) and 95% confidence intervals (CI) from multivariable logistic regression analysis identifying factors independently associated with severe neurocysticercosis. Protective factors against IHS included epileptic manifestations (OR = 0.295; 95%CI: 0.182–0.477; p < 0.001) and asymptomatic presentation (OR = 0.212; 95%CI: 0.111–0.404; p < 0.001). Meningeal manifestations were associated with increased risk of severe disease (OR = 2.992; 95%CI: 1.811–4.943; p < 0.001). Age groups 21–40 and 41–60 years showed increased probability of ISH forms compared to reference categories

Regarding hospitalizations, 160 patients (36.1%) required hospitalization, with proportional increase from 19.4% to 34.2% throughout the years despite overall case reduction. The most significant complication in the ISH group was vasculitis (2.9%), indicating strong association with disease severity, while myelitis and encephalitis complications showed no significant differences between groups. Additionally, 7 patients presented muscular forms concomitant with CNS involvement (3 other clinical presentations, 4 ISH), 2 cases of optic neuritis, and 4 cases of ventriculitis (all associated with surgical manipulation).

Among 443 patients included in detailed analysis, 63 (14.2%) died, though reliable information about death causes was unavailable, preventing definitive conclusions about NCC-death relationships. Of the total patients, 38 (8.5%) remain under follow-up, 44 (10%) were lost to follow-up, and 57 (12.8%) were discharged for secondary-level care. Nine patients (2%) had definitive diagnosis through brain biopsy for diagnostic confirmation and exclusion of differential diagnoses.

Age groups demonstrated significant impact on severe disease development, with individuals aged 21–40 years showing increased ISH form probability (β = 1.55345; p = 0.02031) and those between 41 and 60 years similarly affected (β = 1.50821; p = 0.02456). For individuals over 60 years, the effect was positive but with lower statistical significance. Sex showed no statistically significant association, suggesting men and women have similar risks for severe disease.

Meningitis presence was a significant predictor, substantially increasing severe disease probability (β = 1.30861; p = 2.00e-07), while epilepsy presence showed a protective negative effect, significantly reducing severe disease occurrence probability (β = -1.28491; p = 1.02e-07).