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Del Brutto et al. Neurocysticercosis and hippocampal damage

rates of epilepsy secondary to NCC in developed Most patients with hippocampal sclerosis and
countries of North America and Western Europe. [4] epilepsy -- particularly mesial temporal lobe epilepsy
(MTLE) have history of perinatal trauma, recurrent
For a better understanding of mechanisms involved febrile seizures, status epilepticus, or traumatic brain
in the pathogenesis of epilepsy secondary to NCC, injury. Such initial precipitating injuries often lead to
a review of the stages of involution of parenchymal the development of neuronal loss in CA1 and CA3
brain cysticerci is mandatory. After lodging in the brain hippocampal layers. The increasingly recognized
[10]
parenchyma, cysticerci establish as vesicular (viable) association between granular or calcified lesions
cysts, which provoke little or no inflammatory changes NCC lesions located within the hippocampus or in
in neighboring tissues. In most cases, vesicular the adjacent cerebral tissue, points to this parasitic
cysts degenerate and are transformed into calcified disease as the initial precipitating injury causing
nodules due to the attack of the host’s immune hippocampal atrophy and sclerosis. [11-13] In addition,
system. Intermediate involutive stages during which pathological reports have shown neuronal loss in the
cysticerci experience such degeneration have been CA1 layer and gliosis, as well as the presence of a
called “colloidal” (cysticerci showing degenerative severe inflammatory reaction in the brain parenchyma
signs but still with liquid contents) and “granular” surrounding calcified cysticerci. In this view, it
[14]
(compact lesions with more advanced degenerative has been postulated that calcified cysticerci could
changes) stages, respectively. [5] generate the development of both seizures and late
hippocampal atrophy that will perpetuates the seizure
Parenchymal brain cysticerci in any of the disorder.
aforementioned stages may be associated with
reactive seizures. Compressive effect on the brain Hippocampal atrophy has also been documented
parenchyma is the most likely explanation for in patients with calcified cysticerci located outside
seizures occurring in patients with vesicular cysts. hippocampal areas. Different studies from Brazil and
Degenerating cysticerci may be associated with the Indian subcontinent, have revealed a significantly
seizures due to the inflammatory reaction induced higher than expected prevalence of cysticercotic
by the host’s immune attack. In cases of calcified lesions among patients with MTLE undergoing surgery
cysticerci, the gliosis that develops around dead for medically intractable epilepsy. [11-15] This, together
parasites or the exposure of remaining parasitic with the finding that patients with NCC and MTLS/
antigens (trapped in the interior of calcifications) hippocampal sclerosis have less often history of other
to the brain parenchyma could be the cause of types of initial precipitating injuries (febrile seizures)
recurrent seizures. [6] than those with MTLS/hippocampal sclerosis alone,
led to the concept that a causal relationship between
Semiology of seizures related to NCC is varied. Patients NCC and MTLE with hippocampal sclerosis exists.
with multiple parasites may present with focal seizures In addition, a population-based study conducted
and those with a single lesion develop generalized in an Ecuadorian rural population showed a strong
seizures. The lack of anatomic-semiologic correlation association between NCC and HS in community-
[7]
between cysticerci location and seizure semiology in a dwelling adults. In the same population, it was
[16]
sizable proportion of patients with epilepsy and NCC demonstrated that this association is strongly related
has long been a cause of debate and concern. This to age, suggesting that NCC-related hippocampal
has even led to the hypothesis that both epilepsy and atrophy takes a long time to develop. Interestingly,
[17]
NCC might simply occur by chance in areas where many of the studied individuals do not had epilepsy
NCC is endemic. While this is theoretically possible, or electroencephalography evidence of paroxysmal
MRI findings of inflammatory changes surrounding abnormalities, showing that the association between
calcified cysticerci after a seizure in about 50% of NCC and hippocampal atrophy may occur irrespective
cases, provides strong evidence favoring a cause-and- of seizure activity (unpublished data).
effect relationship between NCC and seizures. In
[8]
other cases, particularly in NCC patients with medically In NCC patients, the relationship between epilepsy
refractory epilepsy, chronic seizures have been shown and hippocampal atrophy/sclerosis is most likely
to come from an associated atrophic or sclerotic bidirectional. According to a current hypothesis,
hippocampus and not from the parasites themselves. parasite-induced inflammation is the trigger for
[9]
In these cases, the damaged hippocampus is for sure repetitive seizures, which may cause hippocampal
not an innocent bystander, but the result of signals or atrophy, which is the pathological substrate for the
forces -- epileptogenic or inflammatory -- coming from subsequent development of MTLE. Parasites may be
the parasites. located outside the hippocampal region, suggesting
Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ August 08, 2017 153