Edema surrounding calcified intracranial cysticerci: clinical manifestations, natural history, and treatment

Abstract

Calcified granulomas are the most common radiological finding in neurocysticercosis (10-20% of endemic populations). A small proportion serves as foci of seizure activity, which results in large numbers of persons with epilepsy. Calcified granulomas are not all the same. Some demonstrate blood-brain barrier dysfunction (magnetic resonance imaging enhancement) most likely due to the presence of inflammation, visualizable scolices, and/or gliosis. About half the patients with a recent history of seizures, positive serology, and only calcified lesions develop perilesional edema at the time of a seizure recurrence. The natural history, treatment, and pathophysiology of this phenomenon are not well studied. Episodes are usually associated with seizures or other neurological manifestations, resolve by 4-6 weeks, sometimes occur repeatedly, and usually involve a subset of the same calcifications. Treatment is supportive. Histopathological examination of one calcification associated with multiple perilesional edema episodes revealed significant inflammation and supports the concept that perilesional edema is inflammatory in nature. This most likely is due to host responses to released or newly recognized parasite antigen and/or upregulation of the host immune response. Immunosuppressive and anti-inflammatory agents may be useful in prevention and/or treatment of this phenomenon.

Inflammation is a key risk factor for persistent seizures in neurocysticercosis

“…Many studies have shown an association between the formation of calcified lesions and seizures,1, 2, 6, 33, 34 both of which may be more likely in subjects with a strong inflammatory response. Although the process by which calcifications form is not completely understood, a breakdown in the blood–brain barrier due to inflammation could allow calcium from the bloodstream to be deposited into the brain parenchyma 35, 36…”

“…The role of inflammation as a contributing factor to seizures in subjects with calcified lesions has not been well studied, as these lesions have traditionally been thought to be immunologically inert. However, recent studies have provided evidence that calcifications may experience periodic remodeling that can expose parasite antigen and thus provoke a host immune response 1, 35, 37. Perilesional edema has been seen surrounding calcified lesions in symptomatic NCC patients,1, 2, 6 and PET scans evaluating this perilesional edema showed increased markers of neuroinflammation 29.…”

“…As evidence for this, calcified lesions from subjects in the persistent seizure group were more likely than those in subjects without seizures to demonstrate perilesional edema. Why some calcifications provoke an inflammatory response while others do not is not well understood,35 and merits further study.…”

Corticosteroid Withdrawal Precipitates Perilesional Edema around Calcified Taenia solium Cysts

“…Recent studies indicate calcifications are important foci of seizure activation. 3,4 The presence of enhancement around a subset of calcifications [5][6][7][8][9] the episodic occurrence of perilesional edema and seizure activity localized to some calcifications, 3,4,10 and the presence of significant inflammation in two excised lesions 11 (Nash and others, in preparation), strongly suggest the continued presence of inflammation associated with a subset of calcifications. This hypothesis implies that immune responses are periodically induced, perhaps by intermittent antigen release 10 or after episodic loss of suppressive immune inhibition, or some combination of both.…”

Calcified Neurocysticercus, Perilesional Edema, and Histologic Inflammation

“…The most favored hypothesis is that perilesional edema is caused by inflammation, perhaps as a result of intermittent release and/or recognition of enmeshed parasite antigen. 13 However, others hypothesize perilesional edema is a result of seizure activity or release of ionic calcium. 13 This is an important distinction, as therapies could differ, with immunosuppressive medications or antiepileptic drugs alone, respectively.…”