Migrainous headaches, calcified cysticercosis and breakthrough seizures

To the Editor, Neurocysticercosis is the infection of the central nervous system and its coverings by the larval stage (cysticercus) of Taenia solium, the pork tapeworm. Parasites may lodge in brain parenchyma, subarachnoid space, ventricular system or spinal cord, causing a myriad of pathological changes that are responsible for the clinical pleomorphism of this disease. While epilepsy is the most common clinical presentation of neurocysticercosis, more than one-third of patients present with headache as the single or most important manifestation of the disease. Neurocysticercosis-related headaches have been mostly associated with intracranial hypertension related to either hydrocephalus, giant extraparenchymal cysts, or cysticercotic encephalitis. These forms of neurocysticercosis clearly represent the minority of cases. Most patients with calcified cysticerci in the brain parenchyma develop headache without the presence of any additional evidence of intracranial hypertension or focal neurological deficits. Mechanisms involved in the association between headache and parenchymal brain calcified cysticerci are elusive. A door-to-door epidemiological survey conducted in a community where cysticercosis is endemic, disclosed that 19 out of 57 (33%) migrainous individuals receiving head CT had calcified cysticercosis. In addition, a case-control study nested to a population-based cohort disclosed that lifetime headache prevalence, current headaches, intense headaches and, in particular, migrainous (but not tensiontype) headaches, were almost five times more frequent among patients with calcified neurocysticercosis than in their matched controls without neurocysticercosis. These studies provide grounds for the further evaluation of the association between headache and calcified neurocysticercosis, particularly with the aim to better understand pathogenetic mechanisms involved in its occurrence and potential therapeutic interventions. The pathogenesis of migrainous headaches related to calcified cysticerci is not completely understood. Calcifications represent the end stage of previously viable cysticerci that have been destroyed by either the host immune system or as the result of cysticidal drug therapy. Calcified cysticerci have been considered inert lesions. However, recent evidence strongly suggest that these lesions contain trapped antigenic parasitic membranes, which may be intermittently presented to the host immune system when structural changes in the calcifications related to remodeling mechanisms allow antigenic remnants to be in contact with neighboring cerebral tissues. This exposure induces inflammatory changes in the brain parenchyma with the subsequent breakdown in the blood-brain barrier, edema formation and oxidative stress resulting from liberation of nitric oxide and other free radicals. These events may be the pathogenetic substrate for the occurrence of seizures, which often take the form of breakthrough seizures, since they ensue unexpectedly after a seizure-free interval and occur despite the regular use of antiseizure medications. In addition, the above-mentioned oxidative stress upregulates the liberation of the calcitonin gene-related peptide (CGRP) by perivascular sensory fibers, which is a key