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Infectious Disease and Neurocognition
of cysts and corticosteroid treatment was the most common (79.7 percent) initial
surgical approach to address the cysts, and a high percentage (60.6 percent) had
endoscopic third ventriculostomy for treatment of the hydrocephalus followed by
septostomy (14.3 percent) and ventricular shunt (14.0 percent) (Yamaki et al., 2023).
Associations between neurocysticercosis and
neuropsychiatric function
Psychosis
Numerous case reports support associations between neurocysticercosis and psychosis (Ahmed et al., 2022). In one case report, a 37- year- old immigrant woman
from El Salvador presented to an emergency department with paranoia, auditory
hallucinations, and depression but with intact orientation. e neurological examination was non focal. Her score on the Mini- Mental State Examination (MMSE)
was 27 (range 0– 30) (Ahmed et al., 2022). In another case report, a 25- year- old
man from India presented with behavioral changes, delusions, and a recent seizure.
Provisionally diagnosed with schizophrenia and a generalized tonic– clonic seizure, he was later diagnosed with neurocysticercosis aer computed tomography
imaging showed numerous brain lesions, which on pathological evaluation were
found to be neurocysticercosis (Bhatia et al., 1994). In another case (Bourgeois et al.,
2002), a woman with a 20- year history of hydrocephalus reported depression and
was later diagnosed with neurocysticercosis. Aer the diagnosis and treatment of
neurocysticercosis, she reported audio and visual hallucinations.
Singh et al. (2004) reported a case of a previously healthy 23- year- old man who
presented with auditory hallucinations, social withdrawal, and cognitive problems.
Facial and neck subcutaneous nodules were positive for T. solium, and brain computed tomography imaging showed disseminated cystic lesions. e cerebral spinal
uid also was positive for T. solium. e patient was treated with albendazole, pred-
nisolone, and antihistamines. By the time of follow- up, he had improved although
he “had not quite reached his premorbid lucidity” (p. 1522).
Verma and Kumar (2013b) described a 25- year- old male with recent onset of
visual and auditory hallucinations and cognitive impairment with a MMSE score
of 14. MRI was signicant for multiple cortical and subcortical cysts and areas of
both hypointensities and hyperintensities. Other potential contributing diagnoses
were ruled out. e patient tested positive for T. solium and aer treatment with the
steroid prednisone, acetazolamide, an antipsychotic (olanzapine), and a benzodiazepine (clonazepam), he improved substantially. Psychosis at 2 weeks was improved,
and his posttreatment MMSE score was 24 at 2 months. Aer 6 months, he returned
to work (Verma & Kumar, 2013a).
In a case series, Forlenza et al. (1997) evaluated 38 consecutive admissions to
a neuroinfectious disease hospital in Brazil and found that 76 percent had active
Neurocysticercosis 269
neurocysticercosis. Although semi- structured interviews and specific diagnostic psychiatric criteria (Diagnostic and Statistical Manual of Mental Disorders
(DSM), third edition) were used, patients with neurological conditions were included as well as those with a history of psychiatric illness making it difficult to
know which of those with active neurocysticercosis also had psychotic symptoms. Overall, the authors reported that 10– 15 percent of the cases were identified as having psychotic symptoms, which included depression with psychotic
features. Despite the psychotic features, most patients had relatively normal
MMSE scores based on level of education. However, using a measure other than
the MMSE, the authors reported that almost 72 percent of the patients presented
with mild to moderate cognitive difficulties including impairment in memory,
attention, and executive function, although no specific pattern of cognitive impairment was observed.
Not all studies, however, have found an association between T. solium and psy-
chosis. Similar to their not nding an association between T. solium and seizures and
epilepsy, Langa et al. (2022) did not nd an association between T. solium seroposi-
tivity and psychosis in a district in Mozambique.
As a group, though, these case studies and series, and others (Da Silva Miranda
et al., 2020; Shah & Chakrabarti, 2013; Shriqui & Milette, 1992; Signore &
Lahmeyer, 1988), suggest that neurocysticercosis can present with psychosis.
As much of the evidence suggesting associations between neurocysticercosis
and psychosis is based on case studies or a small series, additional research is
clearly needed to better characterize the associations between cysticercosis and
psychosis. Nonetheless, the available evidence looking at associations between
neurocysticercosis and psychosis suggest that neurocysticercosis should be considered in the dierential diagnosis of psychosis, particularly in regions where
cysticercosis is endemic.
Depression
Some studies have observed a high prevalence of depression in those diagnosed with
neurocysticercosis. In one study from Brazil investigating the association between
neurocysticercosis characterized by calcication and depression, the authors found
that in the sample of neurocysticercosis with epilepsy, 83 percent of the patients also
had depression. In the sample without epilepsy, 88 percent had depression. However,
in the sample of epilepsy without neurocysticercosis, 92 percent had depression, and
in a sample with headaches but no epilepsy or cysticercosis, 100 percent had depression. e authors noted that although the prevalence of depression in these four
samples was higher than the reported prevalence of depression in Brazil, the prevalence estimates in the four samples did not dier from each other, suggesting that the
association between neurocysticercosis and depression could be due to nonspecic
eects of neurologic diseases and not due to a specic eect of neurocysticercosis.
Infectious Disease and Neurocognition
An important limitation of this study was that depression was diagnosed by questionnaire and not by a clinician (De Almeida & Gurjao, 2010), possibly leading to
diagnostic misclassication. In another study based on self- report of psychiatric
symptoms in patients with epilepsy (n = 160), those with calcied parenchymal lesions from past neurocysticercosis infection had the highest prevalence (14.3 percent) of depression (Leon et al., 2015).
In a meta- analysis investigating associations between the neurotropic parasitic
diseases Chagas disease, cysticercosis, human African trypanosomiasis, malaria,
toxocariasis, and toxoplasmosis and anxiety, bipolar disorder, depression, and
schizophrenia in what the authors dened as developing and emerging nations,
the prevalence of anxiety or depression, or both, in people with Chagas diseases or
cysticercosis, or both, was 44.9 percent (Dare et al., 2019), a nding suggesting an
association between neurocysticercosis and depression.
In their study of 38 consecutive patients and in those that met diagnostic criteria for neurocysticercosis, Forlenza et al. (1997) found 12 of 23, or 52 percent,
met criteria for depression. Another study found depression in 18 of 50 (36 percent) patients with neurocysticercosis and epilepsy compared to 15 of 50 (30 percent) without neurocysticercosis but with epilepsy (Srivastava et al., 2013). ey
also found mixed anxiety and depression in nine of 50 (18 percent) in the positive
group compared to the comparison (control) group which had ve of 50 (10 percent) presenting with mixed anxiety and depression (Srivastava et al., 2013).
However, as described in the epilepsy section of this chapter, epilepsy by itself is
associated with depression, and not only did this study nd a similar prevalence
of depression between those with and without neurocysticercosis, the presence
of epilepsy in both groups is likely confounding the association between depression and neurocysticercosis. Overall, some have suggested that the prevalence
of depression in neurocysticercosis is approximately 53– 85 percent (De Almeida
& Gurjao, 2011). However, this estimate is based on very few studies, and an attempt to determine if markers of active versus inactive neurocysticercosis (e.g.,
presence of calcications or cysts, cerebrospinal uid inammatory markers,
etc.) were associated with depression scores on the Hamilton Rating Scale for
Depression was not supported (De Almeida & Gurjao, 2011). Still, as described
by these authors, depression has been associated with inammatory markers and
with various pathogens, and there is a need for additional studies investigating
the potential eects of neurocysticercosis and risk for depression (De Almeida &
Gurjao, 2011).
Twelve percent of children aged 1– 11 years with neurocysticercosis in one small
study had changes in their behavior (Morales et al., 2000). An observational study
of 500 children initially diagnosed with neurocysticercosis at ages 1– 14 and then
followed up 7 years later found 7.6 percent had parent- reported behavior problems
(Singhi et al., 2018). As stated by Singhi et al. (2018), the number of studies evaluating
academic and behavioral outcomes in children diagnosed with neurocysticercosis
appears to be quite small.
Neurocysticercosis 271
Bipolar disorder
Although uncommonly associated with neurocysticercosis, bipolar disorder has
been described in cases of neurocysticercosis. In one case report, a 23- year- old
woman presented with a history of neurocysticercosis and epilepsy presented rst
with depression near the end of a pregnancy and then aer antidepressant treatment
and the birth of her child with features of mania, including psychosis. MRI showed
cysts in the le cerebellar hemisphere, right temporal lobe, le and right thalami, le
insular cortex, and the le occipital cortex. Follow- up imaging showed multiple calcied lesions (Batra et al., 2021). While confounded by the perinatal and postpartum
periods (Batra et al., 2021), as well as by the history of epilepsy, neurocysticercosis
could have been an etiological factor in this patient’s bipolar aective disorder.
Another case of bipolar disorder was observed in a 69- year- old woman with a history of neurocysticercosis (Gournellis et al., 2019). She rst presented with bipolar
symptoms at age 47 and at that time was found to have evidence of calcied cerebral
lesions but not active infection. At the time of the episode at age 69, computed tomography demonstrated calcied intraparenchymal lesions and enlarged third and
lateral ventricles and MRI was signicant for periventricular white matter changes.
e neurologic exam was negative, and intellectual function was below average. She
was successfully treated with olanzapine.
In another case, a 20- year- old woman presented during a manic episode and was
treated and released but failed to continue with medications (carbamazepine and
haloperidol) and returned in a similar clinical state 12 weeks later (Mishra & Swain,
2004). At follow- up, neuroimaging was positive for cysticercosis and edema in the
right frontal lobe, which improved with treatment. ough less common than other
neuropsychiatric conditions, bipolar disorder has been observed in some cases with
acute or chronic neurocysticercosis.
Associations between neurocysticercosis and
cognitive function
Neurocysticercosis has been associated with decits in a variety of cognitive domains including executive function, attention, memory, verbal uency, visual perception, and spatial ability (Ciampi de Andrade et al., 2010; El- Kady et al., 2021).
ere is evidence that one or more neurocognitive domains may be aected in
neurocysticercosis and that the level of cognitive impairment is associated with the
phase of the disease (Rodrigues et al., 2012). In a cross- sectional study, two- thirds
of patients with neurocysticercosis had some type of cognitive impairment. To control for cognitive eects of seizures and epilepsy, the authors compared cognitive
function in the group with neurocysticercosis to a group without neurocysticercosis
but with cryptogenic epilepsy. is analysis showed that compared to cryptogenic
epilepsy, neurocysticercosis was associated with decreased constructional praxis,
Infectious Disease and Neurocognition
executive function, naming, verbal episodic memory, verbal uency, visual- spatial
orientation, and working memory function, thus controlling for confounding
from cognitive decits associated with epilepsy (Ciampi de Andrade et al., 2010).
Neurocysticercosis appears to aect cognitive function in children also. In the small
study from Brazil of pediatric neurocysticercosis (ages 1– 11 years) mentioned
above, learning disorders were found in 24 percent of the children, and 8 percent of
the children in this study had developmental regression (Morales et al., 2000).
In addition to its associations with cognitive dysfunction, neurocysticercosis
also has been associated with dementia (Ciampi de Andrade et al., 2010). In an
early report, neurocysticercosis was associated with dementia in 20 percent of
neurocysticercosis cases (Torrealba et al., 1984). Another early report found that
17 percent of patients with neurocysticercosis had dementia (Ramirez- Bermudez
et al., 2005). More recently, Ciampi de Andrade et al. (2010) found in their crosssectional study that approximately 12 percent of patients with neurocysticercosis
met DSM- IV criteria for dementia. e study design accounted for comorbid conditions such as epilepsy and antiepileptic drug use (Ciampi de Andrade et al., 2010).
e authors indicated that lesion number or location on MRI did not correlate with
cognitive impairment.
While the mechanism for cognitive impairment in neurocysticercosis is unclear,
some have suggested that neurocysticercosis may directly damage neurons or that
neuroinammation may be the cause, while others have posited that additional
mechanisms may be involved, including central nervous system gene expression
(Bianchin et al., 2010).
Neuroimaging studies have demonstrated that neurocysticercosis lesions may be
found within the parenchyma, ventricles, or subarachnoid space (Santos et al., 2013).
Furthermore, diusion- weighted imaging may provide a way to identify infection
stages as well as increasing diagnostic accuracy of the presence of neurocysticercosis
(Santos et al., 2013).
e dementia associated with neurocysticercosis could in fact be at least partially
reversible with treatment (El- Kady et al., 2021; Ramirez- Bermudez et al., 2005),
making neurocysticercosis an important consideration in the dierential diagnosis
of dementia particularly in endemic regions and in in immigrants from endemic
regions.
Conclusion
Despite infecting an estimated 50 million people worldwide, being the most
common neuroparasitosis, and the numerous reports associating it with adverse neurological, neuropsychiatric, and neurocognitive outcomes, the central
nervous system eects of neurocysticercosis remain surprising poorly studied
(El- Kady et al., 2021). Nonetheless, neurocysticercosis has been associated with a
range of neurological, neuropsychiatric, and cognitive decits, including epilepsy,
Neurocysticercosis 273
psychosis, depression, bipolar disorder, cognitive dysfunction, dementia, hydrocephalus, headache, focal neurological decits (El- Kady et al., 2021), and movement disorders (Alarcón et al., 2017). Although the neurological, neuropsychiatric,
and neurocognitive associations with neurocysticercosis are comparatively poorly
studied, upwards of two- thirds of patients with neurocysticercosis might show
neurocognitive impairment. Available data suggest that neurocysticercosis is
an important contributor to the global neuropsychiatric and cognitive burden,
and, as such, better characterization of the neuropsychiatric and cognitive effects of neurocysticercosis is required not only because of the personal and public
health consequences but also because at least some of the neuropsychiatric and
neurocognitive burden of neurocysticercosis may be avoidable through symptomatic and antiparasitic treatment and through public health measures such as sanitation, keeping pigs away from human sewage, and proper cooking of pork. All
told, considerable potential exists to substantially reduce or even eliminate the considerable eects of neurocysticercosis on human neurological, neuropsychiatric,
and cognitive function (Millogo et al., 2019).
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PART IV
INFECTIOUS DISEASES AND CLINICAL
CONDITIONS AND SYNDROMES