This study is the first systematic review of clinical manifestations associated with NCC, which can have a wide spectrum of neurologic and psychiatric manifestations including seizures, epilepsy, headache, cerebrovascular disorders, motor deficits and depression 
More than three-quarters of symptomatic NCC patients seen in neurological clinics present with seizures or epilepsy. Although definitions of these conditions were very rarely provided, the estimate was surprisingly consistent across studies as a result of including only studies of a certain quality, making them more comparable to one another and the results more valid. Several recent review papers have reported percentages of NCC cases presenting with seizures and epilepsy varying from 70% to 90% 
The proportion of NCC cases seen in neurological clinics with seizures/epilepsy was higher in children than adults. In a review paper of NCC in childhood from India, the authors reported that from 70% to 90% of children with NCC present with seizures 
, which agrees very well with our finding. However, these results may also reflect the fact that more children with seizures/epilepsy are referred to facilities with CT as compared to adults. In addition, if adults tend to be referred to neurology clinics for a larger spectrum of neurological disorders, this would reduce the proportion of seizure/epilepsy observed.
The next most common manifestation was headaches, at a frequency of approximately one-third of symptomatic NCC patients. The between-study estimates were more variable than what was seen for seizures/epilepsy, but were still reasonably consistent. This is surprising, since no study provided a definition for headaches. The proportion of pediatric patients with headaches was similar to that in adults but lower than the estimate for all ages combined. Measuring headaches in toddlers and young children is especially challenging since most of them cannot communicate their symptoms 
The effect of NCC on altered mental state and psychiatric symptoms remains poorly described. However, in the studies that were included here, they were the presenting manifestations in about 5% of cases of NCC, except for one study 
, where 52% were found to have depression at presentation. Had the studies also included psychiatry clinics, these estimates may have been higher. The proportion of NCC cases with symptoms of or increased intracranial pressure was similar between children and adults. This could be due to the fact that papilledema, which is more common among children, was included in this category of symptoms.
All of the publications found in this review reported on patients with symptomatic NCC seen in neurology clinics where imaging was available. Therefore, the distribution of manifestations over-estimates the true frequency of NCC-associated disease, since patients who are asymptomatic or with only mild symptoms are unlikely to be seen in neurology clinics. Indeed, in two studies which were conducted in neuroimaging departments, about 35% of all NCC cases were asymptomatic 
. In an autopsy study, nearly 50% of cases of NCC did not have symptoms noted in their medical charts 
. There is a lack of knowledge on the proportion of NCC cases who will develop symptoms, when in the course of disease specific symptoms occur, and the frequency with which the manifestations change over time. In a study conducted in Mexico, 9.1% of randomly-selected residents without neurological symptoms were found to have NCC based on CT-scan examinations 
. In another study conducted in Honduras with sampling based on EITB results, 31 of 148 participants (21%) had lesions of NCC. Of these, 26 (18%) showed no manifestations, two had headaches, two had epilepsy, and one had dizziness 
. The authors demonstrated that EITB had very poor accuracy in detecting NCC, which would suggest that sampling based on EITB may not introduce any important selection bias. If this is the case, then we could conclude that 16.1% (5/31) of people in that community had prevalent NCC symptoms. Unfortunately, in none of those studies was the history of manifestations reported.
Assessing the distribution of manifestations among people with active and inactive lesions can inform us somewhat about the natural history of NCC. Seizures and epilepsy were more frequent among patients with calcified lesions. Those with active lesions were more likely to present with increased intracranial pressure, hydrocephalus or meningitis. If properly defined, the term “epilepsy” would be used to include only persons with unprovoked, recurrent seizures 
. Thus, any cases of epilepsy that were a result of NCC would, by definition, have to occur in persons with inactive lesions, otherwise they would be acute symptomatic seizures. The higher proportion of seizures/epilepsy in those with inactive lesions may also reflect that NCC and epilepsy may be co-occurring conditions rather than be causally linked.
The duration of NCC-associated disease remains unknown. This review of the literature only allowed the estimation of the time between the first recorded or reported symptom and medical care. Some patients will never seek care and the duration of disease will remain unknown since NCC can only be accurately diagnosed with imaging. Once patients are in care, in case of active disease, cysticercosis will be treated and the symptoms will most likely disappear, although in the case of seizures, they may persist beyond the period of active disease.
Death was reported in only a few studies. It has been reported that neurologic deterioration in patients with NCC may be a life-threatening event with numerous causes and diverse clinical presentations 
. In one study, the principal concurrent conditions listed as contributing to death included hydrocephalus, cerebral edema, cerebral compression, and epilepsy/convulsions 
. The methods to estimate death rates were so heterogeneous that they could not be combined. In order to estimate the global burden of NCC, using a country-specific case fatality rate would be more helpful.
Various uncommon clinical manifestations have been reported in numerous case reports, illustrating that clinical manifestations associated with NCC are non-specific and pleomorphic 
. However, in this review, only case series that had more than 20 participants were included meaning that rarer manifestations are not included. Another important limitation is the lack of definitions of the outcomes of interest. In addition, it is possible that some researchers chose to report on only a certain set of symptoms and not on others.
Alertness of medical staff is needed to better recognize and diagnose NCC, including providing symptoms' definitions to improve our knowledge of its clinical spectrum. Other limitations are inherent to NCC itself and result from the difficulty of diagnosing NCC even with neuro-imaging 
. Brain calcifications or granulomas which represent the most frequently observed feature in NCC are also common in tuberculosis, sarcoidosis and toxoplasmosis 
. These lesions may lead to false positive NCC diagnoses and biased estimates of symptoms' distribution 
This systematic review of the literature shows that NCC imposes a heavy burden in endemic communities causing a wide range of neurological, neuropsychological and psychiatric manifestations and even premature death. Some clinical manifestations have an insidious onset and a slow progression, making their diagnosis difficult and often delayed. Hence, NCC should be kept in mind when confronted with any neurological manifestation in patients with histories of residing in endemic areas. When the clinical presentation suggests NCC infection, it is critical to perform a neuroimaging examination. The development of modern, affordable, valid diagnostic procedures and tests is needed to improve understanding of all the clinical manifestations of NCC and its epidemiology. A highly sensitive, specific and inexpensive diagnostic tool will represent a big step in gaining insight into the morbidity and mortality caused by NCC and will help to accurately estimate its global burden.