Neurocysticercosis Oscar H. Del Brutto, MD, FAAN

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1 Review Article Address correspondence to Dr Oscar H. Del Brutto, Air Center 3542, PO Box , Miami, FL , Relationship Disclosure: Dr Del Brutto has received travel expenses for serving on the Safe Implementation of Treatment of Stroke steering committee. Unlabeled Use of Products/Investigational Use Disclosure: Dr Del Brutto reports no disclosure. * 2012, American Academy of Neurology. Neurocysticercosis Oscar H. Del Brutto, MD, FAAN ABSTRACT Purpose of Review: Neurocysticercosis occurs when humans become intermediate hosts in the life cycle of Taenia solium by ingesting its eggs directly from a taenia carrier or, less often, by contaminated food. Within the nervous system, cysticerci may lodge in the brain parenchyma, subarachnoid space, ventricular system, or spinal cord, causing a number of pathologic changes that are responsible for the pleomorphism of neurocysticercosis. This article discusses the clinical manifestations, diagnosis, and treatment of neurocysticercosis. Recent Findings: Formerly endemic in the developing world, mass immigration of people from disease-endemic to nonendemic areas has caused a recent increase in the prevalence of neurocysticercosis in developed countries, where this condition should no longer be considered exotic. Recent advances in neuroimaging and immune diagnostic methods, and the introduction of a set of diagnostic criteria, have enhanced the diagnostic accuracy for neurocysticercosis. Likewise, introduction of potent cysticidal drugs has radically changed its prognosis. Summary: Neurocysticercosis is the most common helminthic infection of the CNS and a major cause of acquired epilepsy worldwide. Diagnosis of neurocysticercosis is possible after interpretation of clinical data together with findings of neuroimaging studies and results of immunologic tests in a proper epidemiologic context. The use of cysticidal drugs reduces the burden of infection in the brain and improves the clinical course of most patients. Further efforts must be directed to eradicate the disease through the implementation of control programs against all interrelated steps in the life cycle of T. solium, including human carriers of the adult tapeworm, infected pigs, and eggs in the environment. Continuum Lifelong Learning Neurol 2012;18(6): INTRODUCTION Neurocysticercosis, defined as infection of the CNS by the larval stage of the pork tapeworm Taenia solium, is currently considered the most common helminthic disease of the CNS in humans and a major public health challenge for most of the developing world. In rural areas of endemic countries, almost all conditions favoring the transmission of the disease, including warm climate, poverty, and illiteracy, are combined. The complex and unpredictable nature of the immunologic reaction of the host against cysticerci, as well as the myriad pathologic lesions that parasites may induce in the CNS, make neurocysticercosis a fascinating disease. Basic and clinical aspects of neurocysticercosis with emphasis on recent advances on diagnosis and therapy will be discussed in this review. EPIDEMIOLOGY The exact prevalence of neurocysticercosis is unknown; however, it is estimated that millions of people living in the developing world are infected by the larval form of T. solium, andthat many of them will experience the clinical consequences of this infection at any point of their lives. 1 In broad terms, neurocysticercosis is endemic in most Latin American countries, sub-saharan Africa, and some regions of Asia, including the Indian subcontinent, Indonesia, Vietnam, Korea, and China. Cysticercosis is rare in Northern Europe, Canada, December 2012

2 Australia, Japan, and New Zealand, except among immigrants, and is only occasionally reported from Israel and Muslim countries of Africa and Asia (Figure 8-1). Neurocysticercosis was rare in the United States and Western European countries up to 30 years ago. With the growing number of immigrants from endemic areas, an increased numberofpatientsinthesecountriesare estimated to have neurocysticercosis. These outbreaks, followed by an endemic nature of cysticercosis in the affected region, together with the appearance of indigenous cases, are examples of the difficulties that exist to control a zoonotic disease once it has been established. In the United States, most cases have been reported from the southwestern states, where more than 20 million Mexican Americans live. Almost 90% of patients with neurocysticercosis diagnosed in the United States are immigrants from Mexico or South America. 2,3 A similar scenario has been observed in Spain, where mass immigration of people from South America has caused a recent increase in the prevalence of this parasitic disease. 4 These and other major cysticercosis outbreaks have resulted from mass movement of people (or infected swine) from endemic to nonendemic areas (Figure 8-2). While neurocysticercosis is still an important cause of admission to neurologic hospitals and a major cause of acquired epilepsy, some recent evidence suggests that its prevalence is decreasing in developing countries, not only in urban centers but also at the rural level. It has been considered that widespread use of cysticidal drugs, improved sanitation, and increased public awareness of the disease may be responsible for the recently recognized drop in the number of patients with symptomatic neurocysticercosis in endemic areas. 5,6 KEY POINTS h In broad terms, neurocysticercosis is endemic in most Latin American countries, sub-saharan Africa, and some regions of Asia, including the Indian subcontinent, Indonesia, Vietnam, Korea, and China. h In the United States, most cases of neurocysticercosis have been reported from the southwestern states, where more than 20 million Mexican Americans live. Almost 90% of patients with neurocysticercosis diagnosed in the United States are immigrants from Mexico or South America. FIGURE 8-1 World map showing regions where neurocysticercosis is endemic. Continuum Lifelong Learning Neurol 2012;18(6):

3 Neurocysticercosis KEY POINT h The life cycle of Taenia solium involves two hosts: humans and pigs. Humans are the only definitive hosts for the adult cestode, whereas both pigs and humans may act as intermediate hosts for the larval form called cysticercus. FIGURE 8-2 World map showing major outbreaks of human cysticercosis related to mass movement of people or infected swine from endemic to nonendemic areas. (1) Return of British soldiers from India to England; (2) gift of infected swine from Bali to Irian Jaya; (3) mass return of Portuguese living in African colonies after wars in Angola and Mozambique; (4) migratory movements of people from Mexico and South America to the United States (mainly to the southwestern and the New York City areas); (5) mass migration of people from Ecuador, Perú, and Bolivia to Spain; (6) migration of people from India to countries of the Arabian Peninsula (mainly Kuwait, Saudi Arabia, and Qatar). ETIOPATHOGENESIS Life Cycle of Taenia Solium The life cycle of T. solium involves two hosts: humans and pigs. Humans are the only definitive hosts for the adult cestode, whereas both pigs and humans may act as intermediate hosts for the larval form called cysticercus (Figure 8-3). FIGURE 8-3 Diagram of major steps in the life cycle of Taenia solium December 2012

4 FIGURE 8-4 Pigs roaming free in rural villages of developing countries. In this way, pigs have access to human feces, become infected with Taenia solium eggs, and develop cysticercosis. The head (scolex) of the adult T. solium consists of four suckers and a double crown of hooks, a narrow neck, and a body formed by hundreds of proglottids. The adult parasite is attached to the intestinal wall by its potent suckers and hooks. Every few days, some gravid proglottids are detached from the distal end of the worm and passed with the feces. Each proglottid liberates thousands of fertile eggs that are resistant to the environment. In places with deficient disposal of human feces, free-roaming pigs have access to human feces containing T. solium eggs (Figure 8-4). Once in the intestinal tract of the pig, the eggs liberate embryos (oncospheres), which cross the intestinal wall, enter the bloodstream, and are carried to the tissues, where they evolve to form metacestodes, which, in turn, evolve into larvae (cysticerci). The larvae are small vesicles that consist of two parts, the vesicular wall and the scolex. 7 Under these circumstances, pigs develop cysticercosis and become intermediate hosts in the life cycle of T. solium. The normal life cycle of T. Continuum Lifelong Learning Neurol 2012;18(6): solium is completed when humans consume improperly stored and cooked pork meat infected with cysticerci (Figure 8-5). This process results in release of cysticerci in the small intestine where, by the action of digestive enzymes, scolices evaginate and attach to the intestinal wall, and proglottids FIGURE 8-5 Consumption of undercooked pork meat under poor sanitary conditions is a threat to thousands of people living in rural villages of developing countries

5 Neurocysticercosis KEY POINTS h Human cysticercosis should now be considered as a disease mostly transmitted from person to person; the role of infected pigs is to perpetuate the infection. h It is common to find cysticerci in different involutive stages in the same person. It is unknown whether this represents cysts of different ages from recurrent infections or a single infection in which only some parasites have been attacked by the host s immune system. FIGURE 8-6 Anatomopathologic findings in neurocysticercosis. A, Vesicular cysts in brain parenchyma. B, Subarachnoid parasitic membranes surrounded by dense mononuclear inflammatory reaction. C, Dense exudate surrounding the brainstem and the engulfing basilar artery. begin to multiply and become mature approximately 4 months after the infection. Humans can also act as intermediate hosts for T. solium after ingesting its eggs, thereby allowing human cysticercosis to develop. The mechanisms by which eggs cross the intestinal wall and lodge in human tissues are the same as those described in the pig. Humans most often acquire cysticercosis by the fecal-oral route from a close contact harboring the adult parasite in the intestine. Recent epidemiologic data showing clustering of people with cysticercosis around taeniasic individuals have changed previous concepts crediting the environment as the main source of human contamination with T. solium eggs. 8 Human cysticercosis should now be considered as a disease mostly transmitted from person to person; the role of infected pigs is to perpetuate the infection. Morphology and Stages of Involution of Cysticerci After entering the CNS, cysticerci are in a vesicular (viable) stage in which the parasites have a transparent membrane, a clear vesicular fluid, and a normal invaginated scolex (Figure 8-6A). Cysticerci may remain viable for years or, as the result of the host s immunologic attack, enter into a process of degeneration that ends with their transformation into inert nodules. It is also possible that the immune attack can occur even before the transformation of metacestodes into vesicular cysticerci. Independently, if the metacestode or the vesicular cyst undergoes the immunologic attack from the host, the first stage of involution of cysticerci is the colloidal stage, in which the vesicular fluid becomes turbid and the scolex shows signs of hyaline degeneration. Thereafter, the wall of the cyst thickens and the scolex is transformed into mineralized granules; this stage, in which the cysticercus is no longer viable, is called the granular stage. Finally, the parasite remnants appear as a calcified nodule. It is common to find cysticerci in different involutive stages in the same individual. It is unknown whether this represents cysts of different ages from recurrent infections or a single infection in which only some parasites have been attacked by the host s immune system. In some cysticercus, the scolex cannot be identified. These parasites are composed of several membranes attached to each other that tend to group in clusters resembling a bunch of grapes. This form is called the racemose form of cysticerci, and is usually observed in parasites located within the CSF cisterns at thebaseofthebrain,wheretheymay attain a large size. 9 While the mechanisms responsible for the transformation of cysticerci from single vesicles to the racemose form are not totally understood, it is likely that scolices disappear December 2012

6 and parasites grow as the result of a degenerative process called hydropic degeneration, caused by the continuous entrance of CSF into the vesicles. Tissue Reaction Around Cysticerci Parenchymal brain cysticerci in the vesicular stage elicit a scarce perilesional inflammatory reaction that is mainly composed of plasma cells, lymphocytes, and eosinophils. Colloidal cysticerci are surrounded by a thick collagen capsule and a mononuclear inflammatory reaction that usually includes the parasite itself. The surrounding brain parenchyma shows an astrocytic gliosis associated with microglial proliferation, edema, neuronal degenerative changes, and perivascular cuffing of lymphocytes. When parasites enter into the granular and calcified stages, the edema subsides but the astrocytic changes in the vicinity of the lesions may become more intense, and epithelioid cells appear and coalesce to form multinucleated giant cells (Table 8-1). Meningeal cysticerci usually elicit a severe inflammatory reaction in the subarachnoid space with formation of an exudate composed of collagen fibers, lymphocytes, multinucleated giant cells, eosinophils, and hyalinized parasitic membranes leading to abnormal thickening of the leptomeninges (Figure 8-6B). This inflammation may be disseminated, inducing damage in structures distant to the site where the parasites lodge. The optic chiasm and cranial nerves arising from the brainstem are encased in this leptomeningeal thickening. The foramina of Luschka and Magendie may also be occluded by the thickened leptomeninges and parasitic membranes, with the subsequent development of obstructive hydrocephalus. Intracranial vessels may also be affected by the subarachnoid inflammatory reaction (Figure 8-6C) and cause occlusion of the lumen of the vessel TABLE 8-1 Correlation Between Appearance of Parasites and Pathologic Changes in CNS According to Stage of Involution of Parenchymal Brain Cysticerci Stage of Involution Vesicular stage Colloidal stage Granular stage Calcified stage Appearance of the Parasite Translucent vesicular wall Transparent vesicular fluid Viable invaginated scolex Thick vesicular wall Turbid vesicular fluid Scolex showing signs of hyaline degeneration Thick vesicular wall Degenerated scolex Transformation of the parasite in coarse calcified nodules Pathologic Changes in the Brain Parenchyma Scarce inflammatory reaction Formation of a thin collagen capsule around the parasite Intense inflammatory reaction that includes the parasite Thick collagen capsule around the parasite Astrocytic gliosis around the cyst Microglial proliferation Intense gliosis Multinucleated giant cells Continuum Lifelong Learning Neurol 2012;18(6):

7 Neurocysticercosis KEY POINT h Defining a typical syndrome of neurocysticercosis is unrealistic. In endemic areas this parasitic disease has traditionally been considered the great imitator, as it may mimic almost any neurologic disorder. with the subsequent development of a cerebral infarction. 10 Ventricular cysticerci may also elicit an inflammatory reaction if they are attached to the choroid plexus or to the ventricular wall. The ependymal lining is disrupted, and proliferating subependymal glial cells protrude toward the ventricular cavities, blocking the transit of CSF, particularly when the site of protrusion is at or near the foramina of Monro or the cerebral aqueduct. 9 Immune Response Against Cysticerci Some cysticercal antigens play a role in the evasion of the immune surveillance against the parasite. One of them, antigen B, is a paramyosin with affinity for collagen that may bind to C1q, inhibiting the classic pathway of complement activation. Since destruction of cysticerci seems to be mediated by activation of the complement cascade, antigen B could play a role in the protection of cysticerci against the host s immunologic attack. Host immunoglobulins have been found around living intracranial cysts, suggesting that cysticerci use these molecules as a screen to avoid recognition from the immune system. Some reports suggest the occurrence of cellular immune dysfunction in patients with neurocysticercosis. This impairment results from an increase in the subpopulations of CD8 T lymphocytes, impaired proliferation of lymphocytes, and abnormal concentration of cytokines. The depressed cellular immunity may be responsible for the association of neurocysticercosis with conditions resulting from immunodeficiency states and glial tumors. In the latter, the intense glial proliferation around the parasites, along with the suppression of the cellular immune responses, may cause inhibition of the immunologic surveillance against cancer, leading to malignant transformation of astrocytes. 11 CLINICAL MANIFESTATIONS Neurocysticercosis may produce no clinical manifestations at all or may be severe enough to cause the death of the patient. This pleomorphism is related to individual differences in the number and location of the lesions as well as in the severity of the host s immune response to the parasite. Therefore, defining a typical syndrome of neurocysticercosisisunrealistic.inendemicareasthis parasitic disease has traditionally been considered the great imitator, as it may mimic almost any neurologic disorder. 12 A recent systematic review showed that recurrent seizures occur in approximately 80% of symptomatic neurocysticercosis cases, confirming previous findings that epilepsy is the most common clinical manifestation of the disease. 13 Other manifestations of neurocysticercosis include focal neurologic deficits (16%), increased intracranial pressure (12%), and cognitive decline (5%). Cysticercosis outside the CNS is not associated with clinical manifestations, with the exception of ocular cysticercosis and some cases with massive muscular involvement. 12 Cysticercosis affects males and females equally from infancy to old age, with a peak incidence among middle-aged adults. The course of the disease is somewhat different in infants and children compared to adults, and neurocysticercosis tends to be more severe in women. The reasons for these findings are incompletely understood; however, it is possible that the interaction of several factors, including increased reactivity of the immune system in children and women, could be responsible for the age- and gender-related observed differences in the pattern of disease expression. Geographic differences in the clinical spectrum of the disease have also been noted. For unclear reasons, subcutaneous and muscular cysticercosis is observed far more frequently in Asia and Africa than in the Americas. Moreover, almost December 2012

8 all reported patients with massive and symptomatic infection of skeletal muscles came from China and the Indian subcontinent. 14 Such geographic differences have led to the suggestion of possible strain differences of cysticerci; however, other factors such as a more severe burden of infection due to environmental, cultural, dietary, and nutritional differences, as well as genetic variations between populations, could more suitably explain clinical differences among African, Asian, and American patients with the disease. Seizures/Epilepsy Recurrent seizures usually represent the primary or sole manifestation of parenchymal brain cysticercosis. 1,15 Neurocysticercosis is a leading cause of acquired epilepsy in endemic areas and partly responsible for the increased prevalence of epilepsy in the developing world. 16Y18 Whilesomeseries have shown that most patients with neurocysticercosis-related epilepsy have generalized seizures, it is most likely that those patients actually had partial seizures with rapid secondary generalization. Epileptogenesis in neurocysticercosis has been a subject of debate. While it has been suggested that seizures occur when the parasites begin to degenerate, large series have shown that seizures may also occur in patients who only have vesicular (viable) cysts at the time of diagnosis. 15 There has also been debate about the risk of recurrent seizures in patients with calcified parenchymal brain cysticerci. 19 While calcifications have been considered inert lesions, recent data suggest that calcified cysticerci may cause recurrent seizures when parasitic antigens trapped in the calcium matrix are exposed to the host immune system because of a process of calcification remodeling, inducing inflammatory changes in the brain parenchyma. 20,21 Recurrent seizures may Continuum Lifelong Learning Neurol 2012;18(6): also be the cause of hippocampal sclerosis, thus perpetuating the risk of seizures. 22 Focal Neurologic Deficits Neurocysticercosis has been associated with almost any known focal deficit of central origin, including motor and sensory deficits, language disturbances, involuntary movements, parkinsonian rigidity, gait disturbances, incoordination, and signs of brainstem dysfunction. 13 Such deficits may be related to strategically located parenchymal brain cysts or, most often, to compressive effects of large subarachnoid cysticerci. Other patients present with focal signs of acute onset related to the occurrence of a cerebral infarct due to cysticercotic angiitis. Ischemic cerebrovascular complications of neurocysticercosis include lacunar infarcts and large cerebral infarcts. Lacunar infarcts occur as the result of inflammatory occlusion of small perforating arteries at the base of the brain and may be located at the posterior limb of the internal capsule, the corona radiata, or the brainstem; they produce typical lacunar syndromes, clinically indistinguishable from those caused by hypertensive arteriolopathy. Large cerebral infarcts may be caused by occlusion of major intracranial arteries; patients present with profound focal neurologic deficits secondary to an infarct involving basal ganglia and cerebral cortex, or may develop subacute dementia when both anterior cerebral arteries are occluded. 10 Cysticercotic arachnoiditis may also cause entrapment of cranial nerves arising from the ventral aspect of the brainstem. This may cause extraocular muscle paralysis due to damage of oculomotor nerves, as well as sensorineural hearing loss, facial palsy, or even trigeminal neuralgia due to involvement of lower cranial nerves. Neurocysticercosis of the spinal canal also occurs with focal neurologic signs, including weakness and sensory KEY POINTS h Neurocysticercosis is a leading cause of acquired epilepsy in endemic areas and is partly responsible for the increased prevalence of epilepsy in the developing world. h While calcifications have been considered inert lesions, recent data suggest that calcified cysticerci may cause recurrent seizures when parasitic antigens trapped in the calcium matrix are exposed to the host immune system because of a process of calcification remodeling, inducing inflammatory changes in the brain parenchyma

9 Neurocysticercosis KEY POINT h The frequency of positive stool examinations for T. solium eggs has varied from one series to another and seems to be related to the severity of infection. Patients with heavy infections have a greater chance of also having taeniasis. disturbances below the level of the lesion that may be associated with radicular pain when cysts are located in the spinal subarachnoid space. 23 Intracranial Hypertension Various mechanisms explain the occurrence of increased intracranial pressure in patients with neurocysticercosis. The most common is hydrocephalus, which, in turn, is most often related to inflammatory occlusion of the Luschka and Magendie foramina, although some patients develop hydrocephalus because of blockage of CSF circulation by ventricular cysts or ependymitis occluding Monro foramina or the cerebral aqueduct. 24 The clinical course of increased intracranial hypertension in patients with hydrocephalus due to basal arachnoiditis is subacute or chronic, while that of patients with hydrocephalus related to fourth ventricle cysts may be punctuated by episodes of sudden loss of consciousness related to movements of the head (Bruns syndrome), and that of cerebral aqueduct stenosis may be associated with paroxysmal headache and Parinaud syndrome (Case 8-1). Irrespective of their pathogenetic mechanism, hydrocephalus is an ominous sign associated with high mortality rates. Intracranial hypertension may also be related to the occurrence of the socalled cysticercotic encephalitis, which is a severe form of parenchymal neurocysticercosis that usually affects children and young women (Case 8-2). Patients with cysticercotic encephalitis present with cloudiness of consciousness of acute or subacute onset associated with seizures, decreased visual acuity, headache, vomiting, and papilledema. 12 Cognitive Decline Cognitive decline, ranging from poor performance on neuropsychological testing to severe dementia, may occur in some patients with neurocysticercosis, particularly in those with chronic normal pressure hydrocephalus. 12 Before the introduction of CT, these patients were admitted to psychiatric hospitals for years until the correct diagnosis was suspected because of the occurrence of seizures or focal neurologic signs. Some patients with parenchymal brain lesions develop psychotic episodes characterized by confusion, paranoid ideation, psychomotor agitation, violent behavior, and visual hallucinations; some of these episodes could represent attacks of psychomotor epilepsy or postictal psychosis. DIAGNOSIS Peripheral eosinophilia is a common, albeit nonspecific, hematologic abnormality in patients with neurocysticercosis. The frequency of positive stool examinations for T. solium eggs among these patients has varied from one series to another and seems to be related to the severity of infection. Patients with heavy infections have a greater chance of also having taeniasis. 25,26 Recognition of Taenia eggs is not easy, and many patients may escape detection when coproparasitologic studies are performed. Specific coproantigen detection by ELISA and PCR has improved the screening for T. solium carriers. 27 Nonspecific abnormalities in the cytochemical composition of CSF are common in patients with neurocysticercosis. These abnormalities directly correlate with the activity of the disease and with whether or not the parasites are located in the subarachnoid space. The most common finding is a moderate mononuclear pleocytosis, with cell counts rarely exceeding 300/2L. Mild increase in CSF protein counts, usually in the range of 50 mg/dl to 300 mg/dl, is also common. CSF glucose levels are December 2012

10 Case 8-1 A 60-year-old woman was evaluated because of progressive headache and vomiting. She had been admitted 2 months before at another hospital because of hydrocephalus with asymmetric dilatation of the lateral ventricles, as well as dilatation of the third and fourth ventricles. A right ventricular shunt was placed with isolated reduction in the size of the right lateral ventricle, and 15 days later, she underwent the placement of another ventricular shunt, this time on the left side, with reduction in the size of left lateral and third ventricles. However, because the fourth ventricle remained dilated she was transferred to the present institution for further evaluation. On admission, neurologic examination revealed abnormal downward gaze and generalized increased muscle stretch reflexes with bilateral Babinski signs. CT of the head showed collapse of both lateral ventricles resulting from shunt placement and an abnormally dilated fourth ventricle (Figure 8-7). MRI showed no evidence of a cystic lesion in the fourth ventricle. A serum immunoblot test for the detection of anticysticercal antibodies was positive. She underwent the placement of another shunt device for drainage of the fourth ventricle, with progressive clinical improvement and further reduction in the size of that ventricle. Comment. This woman had double compartment hydrocephalus related to simultaneous occlusion of the cerebral aqueduct and the Luschka and Magendie foramina. She also had FIGURE 8-7 CT scans of a patient with double compartment hydrocephalus due to simultaneous occurrence of aqueductal stenosis and occlusion of Luschka and Magendie foramina. ependymitis at the level of the right Monro foramen, which explains the fact that the first ventricular shunt only reduced the size of the right lateral ventricle, and it was only after the second derivative procedure that the size of the left lateral and third ventricle returned to normal. Double compartment hydrocephalus in neurocysticercosis may also be related to a fourth ventricle cyst occluding the CSF transit at both the cerebral aqueduct and the Luschka and Magendie foramina levels. In this patient, the absence of a fourth ventricle cyst on MRI and the finding of an incomplete Parinaud syndrome favored the diagnosis of aqueductal stenosis, since fourth ventricle cysts have rarely, if ever, been associated with Parinaud syndrome. Differential diagnosis between these two pathogenetic mechanisms causing an isolated fourth ventricle in patients with neurocysticercosis is important, as the therapeutic approaches are completely different. For patients with a fourth ventricle cyst, endoscopic resection of the lesion is advised. In contrast, multiple shunts are needed for patients with segmental occlusion of the CSF transit at different levels because of the simultaneous occurrence of ependymitis and basal arachnoiditis. Continuum Lifelong Learning Neurol 2012;18(6):

11 Neurocysticercosis Case 8-2 A 20-year-old woman presented with a 1-week history of progressive headache, vomiting, and somnolence. On admission, neurologic examination showed obtundation, bilateral papilledema (Figure 8-8), increased muscle stretch reflexes, and bilateral Babinski signs. MRI showed diffuse brain swelling with collapse of the ventricular system, and multiple small cysticerci disseminated through the brain parenchyma with predominance of the cerebral cortex. Lesions showed a ringlike pattern of enhancement after contrast medium administration (Figure 8-9). Serum immunoblot for the detection of anticysticercal antibodies was strongly positive. ELISA and Western blot for the detection of antibodies against HIV were negative. High doses of dexamethasone (8 mg IV every 8 hours) and mannitol (100 ml of a 20% solution every 6 hours) were started. Standard doses of sodium phenytoin were also added to the regimen. The patient improved over the next few days. Mannitol was discontinued after 3 days, and IV dexamethasone was switched to oral prednisone after 1 week. She was discharged asymptomatic 2 weeks after admission. FIGURE 8-8 Comment. This young woman had cysticercotic encephalitis, a severe form of neurocysticercosis related to an intense inflammatory reaction from the host in response to massive cysticerci infestation of the brain parenchyma. Diagnosis is suspected on clinical and imaging grounds and must be confirmed by the practice of a serum immunoblot test. It is also prudent to evaluate the HIV status of the patient, since Toxoplasma encephalitis or other HIV-related opportunistic infections of the nervous system may occur with similar clinical and neuroimaging findings. Cysticidal drugs are formally contraindicated in patients with cysticercotic encephalitis, as therapy may exacerbate the inflammatory reaction within the brain parenchyma, causing further increase in the intracranial pressure and death. In Funduscopic examination showing papilledema. FIGURE 8-9 MRI of patient with cysticercotic encephalitis. A, T1-weighted imaging showing diffuse brain edema with collapse of the ventricular system. B, T2-weighted imaging showing multiple colloidal parenchymal brain cysts surrounded by edema. C, Aftercontrast administration, cysticerci appear as ring-enhancing lesions. contrast, prompt administration of corticosteroid and osmotic diuretics usually result in marked clinical improvement. Decompressive craniotomies have been suggested for patients who do not respond to this initial therapeutic approach. Patients who survive recover without sequelae, and further neuroimaging studies from 3 to 6 months after the acute episode usually show complete resolution of lesions. usually normal despite active meningeal disease. Hypoglycorrhachia, observed in a few patients, is associated with a poor prognosis. Immunologic Diagnosis Immune diagnostic tests have been used to assess the prevalence of cysticercosis in populations and to exclude or confirm December 2012

12 the diagnosis of neurocysticercosis in neurologic patients with inconclusive neuroimaging findings. The complement fixation test and the serum ELISA are time-honored tests used for decades to diagnose cysticercosis. These tests, however, have been faced with problems related to poor sensitivity or specificity. False-negative results are due to local production of antibodies within the CNS, without a parallel increase of antibodies in peripheral blood, or to immune tolerance to the parasite without production of anticysticercal antibodies at all. False-positive results are due to previous contact with the adult T. solium or to crossreactivity with other helminths. 28 Enzyme-linked immunoelectrotransfer blot assay for detection of antibodies to T. solium glycoprotein antigen in serum. The only reliable serologic test for the detection of antibodies specific for T. solium antigens is the enzyme-linked immunoelectrotransfer blot (EITB) using partially purified antigenic extracts. The EITB has been extensively evaluated in different hospitalbased and population-based studies. This assay has a documented specificity approaching 100% and a sensitivity of up to 98% for patients with two or more parasites in the nervous system. A major weakness of the EITB is the high rate of false-negative results (up to 50%) observed in patients with a single intracranial cysticercus. 29 Sensitivity of the EITB is also poor in patients with calcified cysticerci. Since antibody assays reflect cysticercus infection in any tissue, not only patients with neurocysticercosis but also those with muscular or subcutaneous cysticercosis may test positive. Consequently, results of the EITB must be evaluated with caution, since extraneural cysticercosis or even exposure without infection may result in antibody development. Paradoxically, the sensitivity and specificity of antibody Continuum Lifelong Learning Neurol 2012;18(6): detection by EITB performed in CSF is lower than that performed in serum, even in patients with evidence of CNS involvement. ELISA for detection of anticysticercal antibodies or cysticercal antigens in CSF. Detection of anticysticercal antibodies by ELISA using CSF is 87% sensitive and 95% specific, and remains a relatively useful tool for the diagnosis of neurocysticercosis in areas with limited access to the EITB assay. ELISA may be falsely negative in patients with only parenchymal brain lesions or in those with inactive disease, and it may be falsely positive in patients with other helminthic infections. 28 Detection of cysticercal antigens. Detection of circulating parasitic antigens using monoclonal antibodies is another immune diagnostic technique that has been used in some field studies. However, detection of circulating antigens is possible only in patients with active disease. While the sensitivity of this test as a screening tool for the diagnosis of neurocysticercosis is poor, it may be of value to monitor the response to cysticidal drug therapy. 27 Some studies have also suggested that this test may be useful for the demonstration of excretory-secretory cysticercal antigens in CSF, as it has sensitivity ranging from 72% to 86%, with falsenegative cases restricted to patients with a single intracranial cysticercus and inactive disease. However, the specificity of this assay has not been assessed in patients with other infections of the CNS. Neuroimaging The advent of modern neuroimaging techniques has drastically improved diagnostic accuracy for neurocysticercosis. Both CT and MRI provide objective evidence on the topography of lesions, the burden of infection, the stage of involution of cysticerci, and the KEY POINTS h The only reliable serologic test for the detection of antibodies specific for T. solium antigens is the enzyme-linked immunoelectrotransfer blot using partially purified antigenic extracts. h A major weakness of the enzyme-linked immunoelectrotransfer blot is the high rate of false-negative results (up to 50%) observed in patients with a single intracranial cysticercus. Sensitivity of the enzyme-linked immunoelectrotransfer blot is also poor in patients with calcified cysticerci

13 Neurocysticercosis KEY POINTS h CT remains the best screening neuroimaging procedure for patients with suspected neurocysticercosis, since many patients have parenchymal brain calcifications as the sole evidence of the disease, and many of these lesions may escape detection if only an MRI is performed. h Many vesicular cysts have in their interior an eccentric hyperdense nodule representing the scolex, giving the lesions a pathognomonic hole-with-dot appearance. FIGURE 8-10 Imaging findings in parenchymal brain cysticercosis. A, T1-weighted MRI of vesicular cysticerci showing scolices. B, Contrast-enhanced MRI showing single colloidal cysticercus. C, Plain CT showing parenchymal brain calcifications. severity of the host s inflammatory reaction against the parasites. While MRI is the preferred method for evaluating patients with cystic lesions located in the ventricular system, the brainstem, and the subarachnoid space, CT remains the best screening neuroimaging procedure for patients with suspected neurocysticercosis, since many patients have parenchymal brain calcifications as the sole evidence of the disease, and many of these lesions may escape detection if only an MRI is performed. 30 Parenchymal neurocysticercosis. The stage of involution of parenchymal brain cysticerci determines their appearance on neuroimaging studies (Figure 8-10). Vesicular cysticerci appear as small and rounded cystic lesions that are well demarcated from the surrounding brain parenchyma. Imaging shows little or no perilesional edema and no abnormal enhancement after contrast-medium administration. Many vesicular cysts have in their interior an eccentric hyperdense nodule representing the scolex, giving the lesions a pathognomonic hole-with-dot appearance. When the infection is massive, as in the so-called heavy nonencephalitic form of neurocysticercosis, 25 the brain looks like a Swiss cheese, another imaging finding that is pathognomonic of neurocysticercosis (Figure 8-11). FIGURE 8-11 A, B, C, Contrast CT of patient with heavy nonencephalitic parenchymal brain cysticercosis showing more than 100 vesicular cysts with no evidence of abnormal enhancement or perilesional edema December 2012

14 Colloidal cysticerci appear as illdefined lesions surrounded by edema, and most of them show an abnormal ring pattern of enhancement after contrast medium administration. Since the scolex is rarely visualized in colloidal cysticerci using CT or conventional MRI sequences, the presence of one or two ring-enhancing lesions in the brain parenchyma has generated much debate in the literature and may represent a diagnostic challenge, as other conditionsvtuberculomas, Toxoplasma brain abscesses, primary or metastatic brain tumorsvmay course with similar neuroimaging findings. 29 In doubtful cases, the practice of diffusion-weighted images and apparent diffusion coefficient maps facilitates the diagnosis by allowing the recognition of the scolex (Figure 8-12). 31 Another particular neuroimaging pattern of parenchymal neurocysticercosis in the colloidal stage is observed in patients with cysticercotic encephalitis (Case 8-2). In this severe form of the disease, both CT and MRI show diffuse or multifocal brain edema and collapse of the ventricular system without midline shift. After contrast administration, multiple small nodular or ring-enhancing lesions appear disseminated through the brain parenchyma. Parenchymal brain cysticerci may also appear on CT as discretely hyperdense nodular-enhancing lesions surrounded or not by edema. This pattern corresponds to the granular stage of cysticerci, which on MRI are often visualized as areas of signal void on both T1- and T2-weighted images, surrounded by hyperintense rims representing gliosis. Calcified cysticerci appear on CT as small, hyperdense nodules without perilesional edema or abnormal enhancement after contrast-medium administration. As noted before, the sensitivity of conventional MRI sequences for the detection of calcified lesions is poor. Recent evidence, however, suggests that the use of susceptibility-weighted images may enhance the identification of calcifications by MRI. 32 Subarachnoid neurocysticercosis. Subarachnoid cysts are most often small when located within cortical sulci and may present with similar neuroimaging findings to those described for parenchymal brain cysts, ie, cystic lesions showing the scolex, ring-enhancing lesions, or calcifications. On the other hand, cystic lesions located within the sylvian fissures or at the CSF cisterns at the base of the brain usually attain a large size and have a multilobulated appearance (the racemose form of FIGURE 8-12 A, Contrast-enhanced imaging; B, diffusion-weighted imaging; and C, apparent diffusion coefficient map of patient with colloidal parenchymal cysticerci. Scolices are visualized only on the last two sequences. Continuum Lifelong Learning Neurol 2012;18(6):

15 Neurocysticercosis KEY POINTS h Cystic lesions located within the sylvian fissures or at the CSF cisterns at the base of the brain usually attain a large size and have a multilobulated appearance (the racemose form of neurocysticercosis), displacing neighboring structures and behaving as space-occupying mass lesions. h Cyst mobility within the ventricular cavities in response to movements of the head, the ventricular migration sign, facilitates the diagnosis of ventricular cysticercosis in some cases. FIGURE 8-14 FIGURE 8-13 Imaging findings in subarachnoid cysticercosis. A, Contrast-enhanced CT showing large cyst in sylvian fissure. B, Contrast-enhanced CT showing hydrocephalus associated with cysts in CSF cisterns. C, T1-weighted MRI showing huge cyst compressing brainstem. Cysticercotic angiitis. A, Plain CT showing infarct in territory of left anterior cerebral artery. B, Angiogram showing segmental narrowing of A 1 segment of left anterior cerebral artery. neurocysticercosis), displacing neighboring structures and behaving as spaceoccupying mass lesions (Figure 8-13). Another common finding in patients with subarachnoid neurocysticercosis is hydrocephalus caused by inflammatory occlusion of the Luschka and Magendie foramina. The fibrous arachnoiditis responsible for the development of hydrocephalus is seen on CT or MRI as areas of abnormal leptomeningeal enhancement at the base of the brain. 24,30 Cerebrovascular complications of neurocysticercosis are well visualized with CT or MRI. In patients with cysticercosisrelated infarcts, the association of subarachnoid cystic lesions (particularly at the suprasellar cistern) or abnormal enhancement of basal leptomeninges suggests the correct diagnosis. 10 Angiographic findings in subarachnoid neurocysticercosis include segmental narrowing or occlusion of the major intracranial arteries in patients with infarcts (Figure 8-14) or even in those lacking clinical or neuroimaging evidence of a cerebral infarct. Magnetic resonance angiography is a valuable noninvasive imaging modality to demonstrate narrowing or occlusion of intracranial arteries in patients with subarachnoid neurocysticercosis. Ventricular neurocysticercosis. Ventricular cysticerci appear on CT as hypodense lesions that distort the ventricular system, causing asymmetric obstructive hydrocephalus. Ventricular cysts are isodense with CSF; therefore, they cannot be directly visualized (Figure 8-15). In contrast, most ventricular cysts are readily visualized on MRI because the signal properties of the cystic fluid or the scolex differ from those of the CSF. 30 Cyst mobility within the ventricular cavities in response to movements of the head, the ventricular migration sign, facilitates the diagnosis of ventricular cysticercosis in some cases. In other patients, December 2012

16 is not identified, however, it may be difficult to differentiate this condition from spinal tumors. Leptomeningeal cysts are easily identified with MRI (Figure 8-16). These lesions may be freely mobile within the spinal subarachnoid space and change their position during the examination according to movements of the patient on the exploration table. FIGURE 8-15 Plain CT showing ventricular cysticercus causing asymmetric dilatation of right lateral ventricle. parasitic membranes or ventriculitis occlude the Monro foramina. In such cases, it is common to observe asymmetric internal hydrocephalus, most often noticed after the placement of a ventricular shunt, as the lateral ventricle contralateral to the shunt remains dilated after the derivative procedure. A particular finding in ventricular cysticercosis is the so-called double compartment hydrocephalus, in which the fourth ventricle is isolated from the rest of ventricular cavities because of simultaneous occlusion of the cerebral aqueduct and the foramina of Luschka and Magendie (Case 8-1). Spinal cord neurocysticercosis. While myelography and CT were used for years for the diagnosis of spinal cysticercosis, they are now of historical significance since MRI has become the imaging modality of choice for the evaluation of patients with suspected cysticercosis of the spinal cord or the spinal subarachnoid space. On MRI, intramedullary cysticerci appear as rounded or septated lesions that may have an eccentric hyperintense nodule representing the scolex. 30 If the scolex Continuum Lifelong Learning Neurol 2012;18(6): Unification of Diagnostic Criteria Despite the introduction of the abovedescribed immune diagnostic tests and neuroimaging methods, the diagnosis of neurocysticercosis can still be a challenge because clinical manifestations are nonspecific, neuroimaging findings are often not pathognomonic, and immune diagnostic tests are faced with problems related to poor sensitivity or specificity. Moreover, histologic demonstration of the parasite is not possible in most cases. During the second half of the 20th century, it was common in field studies to diagnose neurocysticercosis in patients presenting with seizures and a positive immunologic test for the detection of anticysticercal antibodies FIGURE 8-16 T1-weighted gadolinium contrast-enhanced MRI of patient with spinal cysticercosis showing multiple hypointense cystic lesions in the spinal canal

17 Neurocysticercosis KEY POINTS h Revised criteria for the diagnosis of neurocysticercosis include four categoriesvabsolute, major, minor, and epidemiologicvstratified on the basis of their individual diagnostic strength. Absolute criteria allow unequivocal diagnosis; major criteria strongly suggest the diagnosis but cannot be used alone to confirm the diagnosis; minor criteria are frequent but nonspecific manifestations of the disease; and epidemiologic criteria refer to circumstantial evidence favoring the diagnosis. h Accurate characterization of neurocysticercosis in terms of viability of cysts, degree of the host s immune response to the parasites, and location of the lesions is important for a rational therapy. in serum. Such practice could have resulted in the inclusion of many patients who actually had cryptogenic epilepsy and false-positive results on immunologic testing. On the other hand, some infected persons escaped detection just because they had negative immunologic study results. In the hospital setting, diagnosis of neurocysticercosis usually rested only on neuroimaging findings. Using this approach, neurocysticercosis could be overdiagnosed in endemic areas. In contrast, this disease used to be overlooked in other regions of the world simply because it was rare. Such diagnostic pitfalls could lead either to the progression of other diseases requiring urgent therapy or to the practice of unnecessary and invasive diagnostic procedures. In 1996, the first attempt to settle a chart of diagnostic criteria for human cysticercosis was published, based on the objective evaluation of clinical, radiologic, immunologic, and epidemiologic data of patients. 33 After some years of experience, the same group of investigators considered that chart to be somewhat confusing and complex, since it was developed for the diagnosis of patients with neurocysticercosis as well as those with systemic cysticercosis. With few exceptions, cysticercosis outside the CNS is not clinically relevant. Therefore, it was considered that a more accurate and stringent set of diagnostic criteria exclusively devoted to the diagnosis of neurocysticercosis would be more comprehensible than those initially identified. 34 As in the 1996 publication, revised criteria included four categoriesvabsolute, major, minor, and epidemiologicvstratified on the basis of their individual diagnostic strength. Absolute criteria allowed unequivocal diagnosis of neurocysticercosis; major criteria strongly suggested the diagnosis but could not be used alone to confirm the diagnosis; minor criteria were frequent but nonspecific manifestations of the disease; and epidemiologic criteria referred to circumstantial evidence favoring the diagnosis. Interpretation of these criteria permitted two degrees of diagnostic certainty: (1) definitive diagnosis in patients who had one absolute criterion or in those who had two major plus one minor and one epidemiologic criteria; and (2) probable diagnosis in patients who had one major plus two minor criteria, in those who had one major plus one minor and one epidemiologic criteria, and in those who had three minor plus one epidemiologic criteria (Table 8-2). 34 This set of diagnostic criteria was promptly adopted by the medical community and is now considered by many as the gold standard for the diagnosis of neurocysticercosis. Advances in neuroimaging from the time of that publication should be incorporated in the subheading of highly suggestive lesions to enhance the diagnostic accuracy of MRI. These include the use of diffusion-weighted imaging to visualize the scolex in doubtful cases, the use of susceptibility-weighted images to enhance the identification of calcifications, and the practice of spectroscopy to differentiate neurocysticercosis from neurotuberculosis in selected cases. 30Y32 THERAPY Accurate characterization of neurocysticercosis in terms of viability of cysts, degree of the host s immune response to the parasites, and location of the lesions is important for a rational therapy. 35 Therapeutic approaches may include a combination of symptomatic therapy, cysticidal drugs, surgical resection of lesions, and placement of ventricular shunts. General strategies of therapy described in Table 8-3 may need some adjustment in the individual patient, particularly in those who have mixed forms of the disease December 2012

18 TABLE 8-2 Diagnostic Criteria for Neurocysticercosisa b Diagnostic Criteria & Absolute Criteria Histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion Evidence of cystic lesions showing the scolex on neuroimaging studies Direct visualization of subretinal parasites by funduscopic examination & Major Criteria Evidence of lesions highly suggestive of neurocysticercosis on neuroimaging studies Positive serum immunoblot for the detection of anticysticercal antibodies Resolution of intracranial cystic lesions after therapy with albendazole or praziquantel Spontaneous resolution of small single-enhancing lesions & Minor Criteria Evidence of lesions suggestive of neurocysticercosis on neuroimaging studies Presence of clinical manifestations suggestive of neurocysticercosis Positive CSF ELISA for detection of anticysticercal antibodies or cysticercal antigens Evidence of cysticercosis outside the CNS & Epidemiologic Criteria Individuals coming from or living in an area where cysticercosis is endemic History of frequent travel to disease-endemic areas Evidence of a household contact with Taenia solium infection b Degrees of Diagnostic Certainty & Definitive Diagnosis Presence of one absolute criterion Presence of two major plus one minor or one epidemiologic criteria & Probable Diagnosis Presence of one major plus two minor criteria Presence of one major plus one minor and one epidemiologic criteria Presence of three minor plus one epidemiologic criteria a Reprinted from Del Brutto OH, et al, Neurology. 34 B 2001, with permission from American Academy of Neurology. Continuum Lifelong Learning Neurol 2012;18(6): Parenchymal Neurocysticercosis Parenchymal brain calcifications. Calcifications represent sequelae of previous infections and should not be treated with cysticidal drugs. In cysticercosisendemic areas, parenchymal brain

19 Neurocysticercosis TABLE 8-3 General Guidelines for Therapy of Neurocysticercosisa b Parenchymal Neurocysticercosis & Vesicular Cysts Single cyst: Use albendazole 15 mg/kg/d for 3 days or praziquantel 30 mg/kg in three divided doses every 2 hours. Corticosteroids are rarely needed. Use antiepileptic drugs (AEDs) for seizures. Mild to moderate infections: Use albendazole 15 mg/kg/d for 1 week or praziquantel 50 mg/kg/d for 15 days. Corticosteroids may be used when necessary. Use AEDs for seizures. Heavy infections: Use albendazole 15 mg/kg/d for 1 week (repeated cycles of albendazole may be needed). Corticosteroids are mandatory before, during, and after therapy. Use AEDs for seizures. & Colloidal Cysts Single cyst: Use albendazole 15 mg/kg/d for 3 days or praziquantel 30 mg/kg in three divided doses every 2 hours. Corticosteroids may be used when necessary. Use AEDs for seizures. Mild to moderate infections: Use albendazole 15 mg/kg/d for 1 week. Corticosteroids are usually needed before and during therapy. Use AEDs for seizures. Cysticercotic encephalitis: Cysticidal drugs are contraindicated. Use corticosteroids and osmotic diuretics to reduce brain swelling. Use AEDs for seizures. Perform decompressive craniotomies in refractory cases. & Granular and Calcified Cysticerci Single or multiple: Cysticidal drug therapy is unnecessary. Use AEDs for seizures. Use corticosteroids in patients with recurrent seizures and perilesional edema surrounding calcifications. b Extraparenchymal Neurocysticercosis & Small Cysts Over Convexity of Cerebral Hemispheres Single or multiple: Use albendazole 15 mg/kg/d for 1 week. Corticosteroids may be used when necessary. Use AEDs for seizures. & Large Cysts in Sylvian Fissures or Basal CSF Cisterns Racemose cysticercus: Use albendazole 15 mg/kg/d to 30 mg/kg/d for 15 to 30 days (repeated cycles of albendazole may be needed). Corticosteroids are mandatory before, during, and after therapy. & Other Forms of Extraparenchymal Neurocysticercosis Hydrocephalus: Cysticidal drug therapy is unnecessary. Insert a ventricular shunt. Continual corticosteroid administration (50 mg 3 times a week for up to 2 years) may be needed to reduce the rate of shunt dysfunction. Ventricular cysts: Perform endoscopic resection of cysts. Albendazole may be used only in small lesions located in lateral ventricles. Ventricular shunt only needed in patients with associated ependymitis. Angiitis, chronic arachnoiditis: Cysticidal drug therapy is unnecessary. Corticosteroids are mandatory. Cysticercosis of the spine: Perform surgical resection of lesions. Anecdotal use of albendazole with good results has been reported. a Level 1 evidence favors the use of cysticidal drugs in patients with parenchymal brain vesicular and colloidal cysts. For other forms of the disease, guidelines are based on Level 2 and Level 3 evidence. calcifications may be an incidental finding on neuroimaging studies. Since the actual risk of epilepsy in these patients is unknown, prophylactic antiepileptic drug (AED) therapy is not justified in such cases. In contrast, December 2012

20 treatment with AEDs is advised when parenchymal brain calcifications are associated with seizures. In these cases, the administration of a single AED usually produces adequate seizure control. 15 Length of AED therapy in patients with epilepsy due to parenchymal brain calcifications remains undefined as some studies have shown that the risk of seizure recurrence after AED withdrawal is high, even in patients who had been seizure-free for 2 years. 36 Neuroimaging studies performed immediately after seizure relapse have shown focal edema and abnormal contrast enhancement around previously inert calcifications. 19,20,36 As previously noted, these observations suggest that parenchymal brain calcifications represent permanent epileptogenic foci susceptible to reactivation when the host immune system is exposed to antigenic material located in the interior of the lesion. 19 While epilepsy due to parenchymal brain calcifications is easily controlled with AEDs, a seizure-free state without medication seems to be difficult to achieve in many patients. These patients should receive corticosteroids to relieve the inflammatory reaction that is causing recurrent seizures. 19 Viable parenchymal brain (vesicular) cysts. Vesicular cysts have reached a state of immune tolerance with the host and may remain for years in the brain parenchyma. Therefore, the only way to destroy these cysts is by the use of a cysticidal drug (Figure 8-17). Level 1 evidence favors the use of cysticidal drugsinsuchcases,asthisapproach provides clinical improvement and resolution of lesions in most patients when compared with placebo or no therapy. 37,38 The optimal therapeutic regimen in such patients, however, is somewhat uncertain. 39 Current evidence seems to favor the use of albendazole over praziquantel; however, the latter is also a potent drug that may be needed in Continuum Lifelong Learning Neurol 2012;18(6): some cases, particularly in albendazole failures. The initial regimen of therapy for patients with parenchyma brain vesicular cysts mainly depends on the burden of infection. Levels 2 and 3 evidence favor the use of albendazole for 3 days or a single-day course of praziquantel therapy for patients with a single cyst, albendazole for 1 week or praziquantel for 15 days for patients with mild to moderate infections, and albendazole for 1 week for patients with heavy infections (Table 8-3). Repeated courses of therapy may be needed as control neuroimaging studies, performed 3 months after the trial, showed persistence of some lesions. In such cases, it is advised to give a different cysticidal drug than the one used in the first attempt. 12 During the trial with cysticidal drugs, some patients develop headache, vomiting, or seizures. These manifestations are related to the inflammatory reaction developed by the host in response to destruction of the parasites and may be anticipated in patients with more than a few cysts in the brain parenchyma. Simultaneous use of corticosteroids usually results in control of these adverse reactions. 35 Likewise, patients with epilepsy due to vesicular cysts FIGURE 8-17 Contrast-enhanced CT of patient with heavy infection of the brain parenchyma by multiple vesicular cysticerci, before (A) and 3 months after (B) a trial with albendazole. Note the resolution of most lesions as a result of therapy. KEY POINTS h Calcifications represent sequelae of previous infections and should not be treated with cysticidal drugs. h While epilepsy due to parenchymal brain calcifications is easily controlled with antiepileptic drugs, a seizure-free state without medication seems to be difficult to achieve in many patients. h Vesicular cysts have reached a state of immune tolerance with the host and may remain for years in the brain parenchyma. Therefore, the only way to destroy these cysts is by the use of a cysticidal drug