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Neurocysticercosis: a review
Surgical Neurology 63 (2005) 123 – 132 www.surgicalneurology-online.com
Infection
Neurocysticercosis: a review Mark W. Hawk, MDa, Kiarash Shahlaie, MDa, Kee D. Kim, MDa,*, J.H. Theis, DVM, PhDb a
Department of Neurological Surgery, University of California-Davis Medical Center, Sacramento, CA 95817, USA b Department of Medical Microbiology, University of California-Davis Medical Center, Davis, CA 95616, USA Received 15 December 2003; accepted 12 February 2004
Abstract
Background: In North America, the largest number of neurosurgical cases stemming from parasitic infections involves the larval form of Taenia solium, the infectious organism causing neurocysticercosis. This infection of the central nervous system (CNS) is most commonly seen in areas with significant immigrant populations and can often present particular challenges to treating physicians. Methods: A review of the literature was performed, highlighting the epidemiology, parasitology, and clinical manifestations of neurocysticercosis. Particular attention was paid to 4 locations of neurocysticercosis lesions: parenchymal, subarachnoid/cisternal, intraventricular, and spinal. Results: Both medical and surgical interventions may be necessary for adequate treatment of neurocysticercosis, depending on various factors, including location of lesion. Conclusions: A review of neurocysticercosis, with particular attention paid to location of disease involvement in the CNS, provides important information to the clinical management of this disease. D 2005 Elsevier Inc. All rights reserved.
Keywords:
Neurocysticercosis; CNS infections; Parasite
1. Introduction Between 380 and 375 bc, Aristophanes referred to the bladders of cysticerci and described how to search for them in a pig’s tongue [6,58]. Aristotle described a disease in pigs defined by the presence of btender meat which have bladders which are like hailstones in the region of the thigh, neck, and loin; these are the regions in which they generally appear Q [7,58]. In 1550, Parnolus described neurocysticercosis in a priest who died of a stroke and was found to have a cysticercal cyst involving the corpus callosum [42,58]. The causal relationship of Taenia solium to the parasitic disease was first recognized by Kqchenmeister in 1855 when a condemned murderer developed the adult tapeworm in his intestine after ingesting cysticercal cysts [58]. In North America, Walter Dandy first described the disease in 1927 [21,22,44,58]. Clinical, pathological, and epidemiologic studies in the 20th century better defined the nature,
* Corresponding author. Tel.: +1 916 734 3658; fax: +1 916 734 3658. E-mail address: [email protected] (K.D. Kim). 0090-3019/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2004.02.033
incidence, and global distribution of the disease [28,87]. From the 1980s through the 1990s, a greater understanding of the disease was gained through improvements in immunochemistry and innovations in neuroimaging. 2. Epidemiology Worldwide, particularly in Central and South America, India, Africa, East Asia, Eastern Europe, and other developing countries, cysticercosis is the most common parasitic disease and continues to be an important health problem [36,87]. Poor sanitation and hygiene play a key role in perpetuation of this parasitic disease. In 1976, the World Health Organization estimated that 2.5 million people worldwide harbor the T solium tapeworm and that many more are infected with the larval stage. It is the larval stage of the disease that causes cysticercosis [8,89]. Neurocysticercosis is quite prevalent in Latin America and India [1]. For example, in endemic villages in Latin America, the seroprevalence has been estimated to be between 4.9% and 24% [72]. In 1979, a 1% incidence of
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neurocysticercosis was reported in Mexico [34]. In 1983, neurocysticercosis accounted for 0.16% of all admissions to a major hospital in Mexico and over 10% of all surgical procedures performed by its neurosurgeons [49]. Neurocysticercosis is a common etiology of epilepsy in endemic regions. In one recent study of 100 consecutive patients with adult-onset epilepsy from Mexico City, 50 had computed tomography (CT) evidence of neurocysticercosis [54,87]. In India, up to 50% of patients with seizure disorders have serological evidence of cysticercosis [50,81,86]. More recently, cysticercosis has become an important parasitic disease in the United States, particularly in California and other states with a large immigrant population [84]. The number of cases diagnosed in Los Angeles increased 4-fold between 1977 and 1981 [87]. Between 1973 and 1983, over 500 cases were reported from just 4 general hospitals in Los Angeles [36,47]. In 1998, it was estimated that 1000 new cases of neurocysticercosis will be diagnosed each year in the United States alone [72,87]. The increasing prevalence in this country has been attributed to the migration of large numbers of rural immigrants from developing countries to the United
States, along with improvements in neuroimaging leading to better diagnosis [66]. 3. Parasitology The life cycle of T solium involves the pig as the more common intermediate host and the human as the only definitive host (Fig. 1). The definitive host, by definition, is the organism in which the sexually mature parasite develops. The tapeworm, characterized by a head (scolex) with 4 suckers and a double crown of hooks (Fig. 2A) and a large body composed of hundreds of proglottids (segmental units containing thousands of eggs) (Fig. 2B), lives within the small intestine of the human and can measure several meters in length (Fig. 2C). The pig acts as an intermediate host by ingesting food contaminated with eggs or proglottids shed from the human feces. Once the eggs (embryophores) are in the stomach or small intestine of the pig, they hatch, liberating the hexacanth embryo known as the oncosphere. Oncospheres have an enzymatic system that is activated by the acids and
Fig. 1. Life cycle of Taenia solium.
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Fig. 2. A, Photograph of a scolex, consisting of a head and neck with 4 suckers and a double crown of hooks. B, Photograph of a sectioned proglottid containing eggs. C, Photograph of the adult tapeworm measuring over 1 m in length.
enzymes of the stomach. The hexacanth embryo then penetrates the mucosa of the stomach or small intestine and is spread hematogenously to the somatic muscles, eyes, and the central nervous system (CNS) of the pig. The hexacanth embryo develops to the cysticercus in 9 to 14 weeks and is comprised of a fluid-filled bladder and an invaginated scolex (Fig. 3). If infected pork is undercooked or eaten raw, the scolex evaginates and attaches to the mucosa of the small intestine. In 3 to 4 months, the adult tapeworm reaches maturity resulting in taeniasis. Human beings may become an intermediate host and acquire cysticercosis by ano-oral contamination or by ingesting food contaminated with T solium eggs. Alternatively, those with the adult tapeworm may become auto-
infected by reverse peristalsis as the eggs or proglottids regurgitate into the stomach and are thus stimulated to hatch. Just as in the pig, the hexacanth embryo penetrates the intestinal mucosa and is hematogenously transported to the muscles, subcutaneous tissues, eyes, or CNS of human beings [36]. Cysticercosis, therefore, is not acquired by eating infected pork as is commonly thought, but usually from T solium eggs passed by human beings carrying the adult tapeworm. Involvement of the CNS is seen in 60% to 90% of patients with cysticercosis [9,11,13,46,47,62,77]. Brain parenchyma is most likely seeded through hematogeneous dissemination [5,19,35,36]. The ventricular system, subarachnoid space, and basilar cisterns are then seeded via the choroid plexus [4]. Spinal cysticercosis most commonly involves the subarachnoid space by the extension of cerebral subarachnoid disease, but intramedullary involvement may also occur hematogenously [63,75]. 4. Clinical manifestations
Fig. 3. Noncontrast head CT showing multiple, punctate, calcified parenchymal cysts and a right frontal ventriculostomy placed for hydrocephalus.
The clinical presentation of neurocysticercosis is varied and depends on the stage, number, size, and locations of the cysticercal cysts within the CNS and the host’s immune response to the parasite. Seizures occur in 50% to 80% of patients with parenchymal disease [24,26,37,38,54,87]. Due to this high incidence of seizures, neurocysticercosis must always be considered as a part of the differential diagnosis for a new-onset seizure in endemic areas [24,54]. Seizures are thought to occur either from parenchymal irritation because of active inflammation or from gliosis associated with end-stage calcified lesions [87]. Focal mass effect by parenchymal cysts or reactive edema as the result of an immunologic response to the cyst may give rise to the symptoms of elevated intracranial pressure, most notably headaches, nausea, and vomiting.
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Depending on the location of the pathology, pyramidal tract signs, sensory deficits, movement disorders, cerebellar or brainstem signs, and even dementia may develop [8,13]. When located in the subarachnoid space, cysts can give rise to focal mass effect or to an inflammatory response manifested as basilar meningitis [20,30,45,73]. Communicating hydrocephalus and signs of elevated intracranial pressure, such as nausea, vomiting, headache, and papilledema may follow. Cranial neuropathy or vasculitis may result from the inflammatory changes. Vasculitis can lead to small- or large-vessel infarcts [8]. Thus, a lacunar or lobar infarct, particularly in a young patient from an endemic region, should raise the suspicion for vasculitis due to neurocysticercosis. In children, meningoencephalitis may result from an intense immune response to the parasite [12]. These patients present clinically with confusion, seizures, headaches, nausea, and vomiting [65]. Intraventricular cysts can be found in any ventricular compartment but tend to migrate to the fourth ventricle because of gravity and cerebrospinal fluid (CSF) flow patterns [48,76]. By physically obstructing the CSF pathway, intraventricular cysts may cause a noncommunicating hydrocephalus. Alternatively, the death of an intraventricular cyst may lead to ependymitis resulting in a communicating hydrocephalus [4,18,19]. Acute intermittent hydrocephalus or sudden loss of consciousness (Bruns’ syndrome) may result if a mobile ventricular cyst is present [69]. A case of sudden death due to migration of a cyst from the wall of the lateral ventricle to the foramina of Monro has been reported [90]. Spinal cysticercosis is rare, with spinal cord involvement reported to occur in only about 1% to 5% of neurocysticercosis [2,38,85]. Spinal intramedullary, intradural extramedullary, and extradural cysticercosis may present with radiculopathy or myelopathy. In 4 cases of spinal extradural cysticercosis reported in 1998, 2 presented with spastic paraparesis, 1 presented with radiculopathy, and 1 presented with a partial Brown Sequard syndrome [57].
5. Diagnosis Given the wide range of clinical presentations, diagnosis is seldom made by history and physical examination alone. Although patients commonly present with a recent history of travel to endemic areas or are immigrants from endemic regions, mere exposure to an infected food handler or a housekeeper, for example, may be all that is necessary to become infected [70]. Consumption of pork may not even be part of the patient’s dietary history as exemplified by cases reported among the Orthodox Jewish community in New York [36,70]. This population presumably developed cysticercosis from food handlers who carried the worm T solium. Accurate diagnosis is based on the combination of clinical, epidemiologic, radiographic, and immunologic information. Peripheral blood smears, eosinophilia, and
CSF assessment is neither sensitive nor specific. Examination of the stool for ova and parasite or co-proantigen, although seldom diagnostic, should always be included in the event that the patient is carrying an adult tapeworm [3]. 6. Immunologic studies Immunologic studies used to detect anticysticercal antibodies to T solium antigens in the serum and CSF include indirect hemagglutination, complement fixation, immunoelectrophoresis, indirect immunofluorescence, enzymelinked immunosorbent assay (ELISA), and enzyme-linked immunoelectrotransfer blot (EITB). Of these, ELISA and EITB are the 2 most useful tests. Enzyme-linked immunosorbent assay measures specific IgG to partially purified antigen from cysticercal fluid. Serum sensitivity of 65% to 87% and a specificity of 63% to 100% and the CSF sensitivity of 62% to 90% and specificity of 98% to 100% have been reported [17,27,32,67]. Most studies examining the sensitivity and specificity of ELISA are limited, however, because of the lack of biopsy-proven diagnosis [15,17,32,33,61,94]. Enzyme-linked immunoelectrotransfer blot detects anticysticercal antibodies to as many as 7 glycoprotein bands specific to T solium and allows nonspecific bands to be ignored, leading to increased specificity with this test [41,80]. However, in one study, decreased sensitivity of the EITB assay was seen when fewer intracranial lesions were present or when calcified lesions were primarily present [71,88]. Nevertheless, some studies with pathologic confirmation have reported serum and CSF sensitivities of 94% to 100% [27,33,80,88]. Both the ELISA and EITB have a higher false-negative rate when parenchymal disease alone is present, suggesting immunologic tolerance to the parasite and a lack of antibody production [15,55,94]. In addition, it is unknown whether ELISA or EITB can distinguish between the intestinal infestation and neurocysticercosis [8]. The only definitive diagnosis, therefore, is made by direct pathological examination of excised cysts. 7. Imaging studies Neurocysticercosis may be found in multiple CNS locations, and cysticerci may occur at different stages of development within the same patient. Depending on factors such as host immune response, this process may take several months to years to evolve. Although plain films of the limbs may show multiple calcified cysts, their presence does not necessarily imply the presence of intracranial lesions or even cysticercosis [29,36]. Magnetic resonance imaging (MRI) is the imaging study of choice, because it is more sensitive than CT for all phases of the disease process, with the exception of end-stage calcified disease [16,51,78,93]. Computed tomography and MRI findings differ depending on the parasite’s location and
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on its stage of development [14,30,59]. Therefore, neurocysticercosis involving different intracranial compartment is discussed separately. 7.1. Parenchymal cysticercosis The cerebral parenchyma is the most frequently affected CNS site. In 1983, Escobar [30] published a classification system that divides parenchymal cysticercosis cysts into 4 pathologic stages. The initial stage, called the vesicular stage, is characterized by noncystic hexacanth embryos that tend to lodge at the gray-white junction and in the basal ganglia or cerebellum. Initially, little to no local tissue response occurs and minimal abnormality is seen on CT and MRI. As the hexacanth embryo develops into a cystic larva, a local tissue reaction occurs, which is manifested as edema. At this stage, CT shows areas of decreased density surrounding the lesion, and MRI shows subtle surrounding hypointensity on T1-weighted images and hyperintensity on T2-weighted images [59]. As the host immune response mounts, homogeneous contrast enhancement may be observed [14,21,91]. Over the next several weeks, the larvae develops into a cyst measuring 1 to 2 cm in diameter, as its bladder becomes engorged with clear fluid. The cyst wall is initially thin and not yet visible with current imaging modalities. A mural nodule within the cyst cavity becomes apparent as the invaginated scolex develops. It appears isointense to brain on all MRI pulse sequences and enhances with contrast. Tissue edema dissipates and the previous surrounding hypodensity seen on CT and hyperintensity on T2-weighted images tends to resolve [59]. At this stage, the cystic fluid appears identical to CSF on all MRI pulse sequences [14,21,91]. After 5 to 7 years, the larvae enters the colloid vesicular stage and begins to degenerate, eliciting an immune response. The cyst wall thickens and becomes fibrotic, and the cystic fluid becomes proteinaceous. As a result, the cystic fluid appears slightly hyperintense relative to CSF on T1-weighted sequences and markedly hyperintense on T2weighted sequences. The scolex appears isointense to hypointense on T2-weighted sequences and provides good contrast relative to the surrounding hyperintense cystic fluid. Contrast studies may show cyst wall enhancement [14,21,91]. In the granular nodular stage, cyst fluid absorption begins and the capsule thickens further. The lesion may appear more solid and isointense on T1-weighted sequences and isointense to hypointense with or without a central area of hyperintensity on T2-weighted sequences. Homogeneous enhancement with surrounding edema is seen. In the final stage, termed the nodular calcified stage, the dead larvae calcify and are best identified on CT as multiple calcified nodules [59] (Fig. 3). Children may present with an encephalitic form of the disease characterized by multiple small enhancing lesion and diffuse cerebral edema [77]. Medical therapy with
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praziquantel or albendazole accelerates cyst death. Initially, an intense inflammatory response characterized by an exacerbation in neurological symptoms and an increased edema, cyst size, and contrast enhancement may occur. As a result, the various MRI features just discussed may be seen over a much shorter period. 7.2. Subarachnoid/cisternal cysticercosis Imaging characteristics of cisternal cysticercosis differ from the parenchymal form as the result of 2 different presentations of the larvae. In the first form, cysticercus cellulosae, the parasite is characterized by a single bladder measuring 3 to 18 mm in diameter with an invaginated scolex. The cyst contents tend to follow CSF on all pulse sequences and can be easily overlooked. Enlargement of a cisternal space or hydrocephalus may be the only clue to abnormality [21]. The second form, cysticercus racemosus, presents as large multiloculated cystic lesions lacking scolices. Both forms may be found in any of the cisterns, the sylvian fissure, or within the sulci over the cerebral hemispheres. The septae seen in multiloculated, racemose cysts can be seen on T1- and T2-weighted sequences, but the cyst contents tend to blend with CSF (Fig. 4). Usually, minimal to no enhancement of the cyst wall is seen. Alternatively, a basilar cistern inflammatory reaction leading to profound enhancement of the cisterns and meninges at the skull base may occur [30,45,53,73]. This inflammatory reaction may subsequently evolve into chronic granulomatous meningitis resulting in chronic hydrocephalus. 7.3. Intraventricular cysticercosis Intraventricular cysticercosis is seen in 10% to 20% of neurocysticercosis. Although the cysts may be found anywhere within the ventricles, the fourth ventricle is most
Fig. 4. Gadolinium-enhanced coronal T1-weighted brain MRI showing suprasellar and bilateral sylvian cisternal cysts with third ventricular enlargement.
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Fig. 5. Combined cisternal and intraventricular cyst. A, Gadolinium-enhanced axial T1-weighted MRI shows a racemose cyst without scolices in the prepontine cistern with multiple septae and fourth ventricular cystic enlargement. B, Axial T2-weighted image shows minimal perilesional edema.
commonly involved [14,48,91]. Intraventricular cysts (Fig. 5A and B) tend to be single, but multiple cysts do occur. The cyst wall and its contents are not typically seen on CT or MRI pulse sequences. If the cystic fluid becomes turbid, proton density images may show subtle differences between the cyst contents and CSF. In patients with
ventriculoperitoneal shunts, intraventricular metrizamide applied through the shunt may help delineate the cyst [49]. However, the scolex is usually seen on gadolinium-enhanced T1-weighted images obviating the need for intraventricular metrizamide injection in most cases. An inflammatory reaction manifested as ependymal and subependymal hyperintensity on T2-weighted images and contrast enhancement of the cyst wall on T1-weighted images may be seen. These findings have been associated with a high probability that a permanent shunt will be required, even if the cyst is completely removed [92]. 7.4. Spinal cysticercosis Spinal cysticercosis most commonly involves the subarachnoid space and results in intradural cysts or arachnoiditis. Cysts appear as filling defects on myelography and may be mobile (Fig. 6). T1, T2, and proton density MRI
Fig. 6. Spinal myelogram showing a cluster of subarachnoid cysts in the lower lumbar region manifested as multiple round filling defects.
Fig. 7. Spinal subarachnoid cysticercal cyst. Gadolinium-enhanced sagittal T1-weighted image shows an enhancing lesion anterior to the cord at the upper cervical levels.
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sequences reveal findings similar to those seen in cerebral cisternal disease. Intramedullary cysts (Fig. 7) are even more rare and have similar MRI characteristics compared with cerebral parenchymal cysts. 8. Treatment The treatment approach and response depends on the location of the pathology. In general, parenchymal cysticercosis in a patient with a stable neurological examination should be treated with a trial of antihelmintic medical therapy. Medical failures often necessitate surgical treatment. Subarachnoid/cisternal, intraventricular, and spinal cysticercosis require individualized approaches, and combined medical and surgical treatments are often used. 8.1. Parenchymal cysticercosis Both praziquantel, a heterocyclic isoquinolone, and albendazole, an imidazole, have been shown to be effective in the treatment of parenchymal cysticercosis. In a prospective study of 26 patients with the parenchymal form of the disease, CT improvement was demonstrated in 25 of 26 patients (96%) treated with 50 mg/kg of praziquantel for 15 days [74]. All treated patients improved clinically and 67% of patients had total remission of cystic lesions by CT, whereas most controls worsened without spontaneous remission. This same study suggested that a second treatment 3 months later might be beneficial for those with only partial resolution of their cysts. Albendazole was demonstrated to be superior to praziquantel in one study based on CT resolution of parenchymal cysts [31,76]. Sixty-seven percent of brain parenchymal cysticerci disappeared on a 2-week course of praziquantel compared with 86% on a 30-day course of albendazole [31]. Subsequent studies demonstrated similar efficacy with an 8day course of albendazole [76]. Albendazole has the added advantage of lower cost compared with praziquantel, an important advantage in developing countries. Side effects are usually mild and include elevations in serum transaminases, abdominal pain, headaches, leukopenia, alopecia, and allergic reactions. Seizures due to neurocysticercosis, although often controlled with first-line antiepileptic drugs such as phenytoin and carbamazepine, may be further improved upon after treatment with praziquantel and albendazole. In a study involving 122 patients with neurocysticercosis and epilepsy, 95 patients were treated with antiepileptic drugs and either praziquantel or albendazole and the remaining 27 were treated with antiepileptic drugs alone [25]. Among those treated with both antiepileptic drugs and anticysticercal therapy, 83% remained seizure-free compared with only 26% of those treated with antiepileptic drugs alone over a 28-month follow-up. Despite improved seizure control, praziquantel and albendazole may not be a definitive cure for epilepsy, and antiseizure medication may need to be continued indefinitely [25,82].
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Larval death is associated with an intense host immune response, and patients may worsen clinically while on medical treatment with antihelmintic agents. In fact, 92% of patients in one study experienced short-term exacerbation of seizures, worsening of headaches, or developed intracranial hypertension [23,74]. Treatment-related adverse reactions may be lessened and life-threatening inflammatory response may be averted with the use of glucocorticoids. Incidence of adverse reaction has been reported to be between 92% and 100% among those not receiving steroids as opposed to 11% to 16% among patients receiving steroids while being treated with praziquantel [40]. Thus, the use of steroids should be strongly considered in the medical treatment of parenchymal cysticercosis. Steroids may, however, reduce serum levels of praziquantel by 50% and increase serum levels of albendazole [43,83]. In addition, administration of praziquantel with cimetidine significantly increases the bioavailability of praziquantel [60]. Given the efficacy of medical treatment, surgical treatment is reserved as second-line therapy for parenchymal disease. In parenchymal cysticercosis, surgery is primarily aimed at relieving local mass effect and treating hydrocephalus. Surgical treatments include craniotomy, cyst extraction, or stereotactic aspiration of the cyst and shunt placement. If the cyst is causing significant mass effect in noneloquent regions of the brain or if the patient has failed medical therapy, direct craniotomy and removal of the cyst is appropriate. Since cysts commonly adhere to adjacent neural and vascular structures, surgical resection, in some cases, may lead to a worsening of symptoms. To minimize the risk of additional injury to the brain, stereotactic aspiration of parenchymal cysts with placement of an indwelling cyst catheter-reservoir for repeated cyst aspirations is a viable alternative [20]. Unlike pyogenic abscesses, penetration of the cyst wall with a blunt tip is easily accomplished [19]. 8.2. Subarachnoid/cisternal cysticercosis Based on the available literature, the efficacy of medical therapy with praziquantel and albendazole for subarachnoid/ cisternal cysticercosis is less clear, and prognosis is poor in comparison with parenchymal cysticercosis. The racemose form, which is frequently accompanied by basilar arachnoiditis, hydrocephalus, cranial neuropathies, and vasculitis, complicates treatment of cisternal disease. Although some advocate surgery as the best treatment for this form of the disease [52,64,79], others recommend an initial trial of medical treatment in clinically stable patients [20]. In one retrospective study of 20 patients with neurocysticercosis that included 12 cases primarily involving the cisterns, open craniotomy was successful in removing the cysts in all 12 [20]. Two of the cases underwent craniotomy after unsuccessful attempted stereotactic aspiration. Although results were reported for the group as a whole (parenchymal, cisternal, or combined disease), 15 of 20 (75%) showed neurological or symptomatic improvement over a follow-up
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period of 36 months, and no deaths occurred [20]. The authors concluded that large parenchymal cysticercal cysts and cisternal lesions may be amenable to surgery if the patient presents with neurological decline or if medical therapy fails. They also suggested that multiloculated lesions should be treated by open craniotomy rather than stereotactic aspiration secondary to difficulty in achieving adequate decompression with this technique. Cyst marsupialization has been suggested for ringenhancing cisternal lesions. These lesions tend to be tenacious and are prone to rupture [46,64]. In any event, when the surgical option is selected, every care should be taken to avoid spillage of cyst contents to avoid the possibility of severe meningitis. 8.3. Intraventricular cysticercosis Similar to cisternal cysticercosis, the reported efficacy of medical therapy with praziquantel and albendazole for intraventricular cysticercosis is limited. Intraventricular cysticercosis is complicated by the potential for cyst migration, with the possibility for the development of acute life-threatening hydrocephalus. In addition, ependymitis may be present, which may lead to hydrocephalus with intraventricular loculations or cyst adherence to the ependyma. Although reports of successful treatment with antihelmintics have been published, surgical treatment is recommended by most in an effort to avoid the possibility of acute neurological deterioration [5,49]. Furthermore, medical treatment alone may lead to severe ependymitis [4]. Complete surgical excision may avoid this complication. Most cases of intraventricular cysticercosis involve a single cyst and ependymitis is usually not present. Direct surgical extirpation with low morbidity can frequently be achieved in these patients [5]. Unless limited by adhesions as the result of ventriculitis, cysts can move within the ventricular space. Therefore, reimaging just before the surgical procedure for precise cyst localization may be prudent [91]. Transcortical or transcallosal approach for cysts in the lateral ventricle or transcallosal approach for third ventricle may be used. Alternatively, endoscopic excision with or without image guidance may be attempted [19], although cyst rupture may be more frequent with this technique. Intraventricular cyst rupture may result in death, as reported in 2 of 21 cases of intraventricular cysticercosis studies by Madrazo et al [49]. Although some advocate shunting procedures as the sole treatment of fourth ventricular lesions, others recommend direct cyst excision via suboccipital approach secondary to concerns of continued parasitic growth without excision [48,49,64]. Fenestration of the septum pellucidum should be considered in cases in which loculations or ependymitis is present. High-potency glucocorticoids with vigorous intraventricular lavage is recommended in the event of cyst rupture [5]. Although ventriculostomies are commonly required in the treatment of intraventricular cysticercosis uncomplicated by ependymitis, permanent CSF diversionary procedures may not be neces-
sary. For example, in a series of 45 surgically treated patients with intraventricular cysticercosis, only 7 required a permanent ventriculoperitoneal shunt [5]. Ependymitis is associated with cystic lesions that are more difficult to remove surgically, have greater likelihood of need for permanent CSF diversionary procedures, and a high incidence of shunt malfunction [19]. Therefore, in cases of intraventricular cysticercosis associated with ependymitis, primary CSF diversion and medical therapy without removal of the cysts should be considered [19]. Frequently, in the face of ependymitis, intraventricular loculations are present, and multiple conduits may be required with attendant complications such as shunt failures [5]. 8.4. Spinal cysticercosis Because of a limited number of spinal cysticercosis, true efficacy of medical or surgical treatment is unknown. One case report described an excellent outcome for 2 patients with spinal intramedullary cysticercosis who presented with paraparesis and bladder dysfunction [39]. After treatment with 15 mg/kg of albendazole for 4 weeks, both patients improved and became ambulatory. Results of laminectomy and cyst extirpation for spinal subarachnoid cysticercosis have been variable [10,56,68], although more rare extradural cysticercosis has been treated with laminectomy, decompression, and stabilization [57]. Acknowledgments The authors thank James Boggan, MD, James Brunberg, MD, and Jalal Abbaszadeh, MD, for providing some of the figures and Dorie DeCosta for her assistance with the preparation of this manuscript. References [1] Acha PN, Aguilar FJ. Studies on cysticercosis in Central America and Panama. Am J Trop Med Hyg 1964;13:48 - 53. [2] Akiguchi T, Fujiwara T, Matsuyama H, et al. Intramedullary spinal cysticercosis. Neurology 1979;29:1531 - 4. [3] Allan JC, Velasquez-Tohom M, Torres-Alvarez R, et al. Field trial of the coproantigen-based diagnosis of Taenia solium taeniasis by enzyme-linked immunosorbent assay. Am J Trop Med Hyg 1996; 54:352 - 6. [4] Amar AP, Ghosh S, Apuzzo ML. Treatment of central nervous system infections: a neurological perspective. Neuroimaging Clin N Am 2000;10(2):445 - 59. [5] Apuzzo MLJ, Dobkin WR, Zee CS, et al. Surgical considerations in treatment of intraventricular cysticercosis: an analysis of 45 cases. J Neurosurg 1984;60:400 - 7. [6] Aristophanes. Las once comedias. Mexico City7 Editorial Porru´a; 1976. [7] Aristotle. Les belles lettres. Histoire des animaux, Socie´te´ d’Edition, vol. III. 1969. p. 48 - 9 [book VIII, paragraph XXI, Paris]. [8] Barry M, Kaldjian LC. Neurocysticercosis. Semin Neurol 1993;13(2):131 - 43. [9] Brown WJ, Voge M. Neuropathology of parasitic infections. New York7 Oxford Univ. Press; 1985. [10] Cabieses FM, Vallenas M, Landa R. Cysticercosis of the spinal cord. J Neurosurg 1959;16:337.
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[84] Warren KS. Helminthic diseases endemic in the United States. Am J Trop Med Hyg 1974;23:723 - 30. [85] Webbe G. Human cysticercosis: parasitology, pathology, clinical manifestations and available treatment. Pharmacol Ther 1994;64: 175 - 200. [86] White Jr AC. Neurocysticercosis: a major cause of neurologic disease worldwide. Clin Infect Dis 1997;24:101 - 13. [87] White Jr AC. Neurocysticercosis: updates on epidemiology, pathogenesis, diagnosis, and management. Annu Rev Med 2000;51: 187 - 206. [88] Wilson M, Bryan RT, Fried JA, et al. Clinical evaluation of the cysticercosis enzyme-linked immunoelectrotransfer blot in patients with neurocysticercosis. J Infect Dis 1991;164:1007 - 9. [89] World Health Organization. Research needs in taeniasis: cysticercosis. Bull World Health Organ, Suppl 1976;53:67 - 93. [90] Yang S, Wing M, Xue Q. Cerebral cysticercosis. Surg Neurol 1990; 34:286 - 93. [91] Zee CS, Go JL, Kim PE, DiGiorgio CM. Imaging of neurocyticercosis. Neuroimaging Clin N Am 2000;10(2):386 - 407. [92] Zee CS, Segall HD, Apuzzo MLJ, et al. Intraventricular cysticercal cysts: further neuroradiologic observations and neurosurgical implications. AJNR Am J Neuroradiol 1984;5:727 - 30. [93] Zee CS, Segall HD, Boswell W, et al. MR imaging of neurocyticercosis. J Comput Assist Tomogr 1988;12:927 - 34. [94] Zini D, Farrell VJR, Wadee AA. The relationship of antibody levels to the clinical spectrum of human neurocysticercosis. J Neurol Neurosurg Psychiatry 1990;53:656 - 61.
Commentary Neurocysticercosis is one of the pathologies most frequently seen by neurosurgeons from developing countries. With the exception of Muslim countries, brain cysticercosis is endemic in Latin America, Asia, and Africa. Some figures show its importance in neurological departments; neurocysticercosis accounts for more than 50% of all cases of lateonset epilepsy and more than 40% of hydrocephalus in adults, as well as 20% of all surgical procedures. Although the last cipher is going down with the recent introduction of effective cysticidal drugs, in the United States, when studying patients who migrated from endemic countries, it is important to entertain the potential diagnosis of neurocysticercosis in cases of parenchymal calcifications, cystic lesions, or chronic meningitis. Hawk et al made a timely review on the subject that presents, in a didactic form, practical hints on diagnosis and treatment. The separation that Hawk et al made according to the localization of parasites has practical significance, because clinical manifestations, imaging studies, and therapeutic options have substantial differences depending on whether the parasites are lodged in the brain parenchyma, the ventricles, the meninges, or the spinal area. The authors are to be congratulated for this well-summarized and updated review of a very complex disease. Julio Sotelo, MD (General Director) Instituto Nacional de Neurologı´a y Neurocirugı´a C.P. 14269 Mexico City, Mexico
Infection
Neurocysticercosis: a review Mark W. Hawk, MDa, Kiarash Shahlaie, MDa, Kee D. Kim, MDa,*, J.H. Theis, DVM, PhDb a
Department of Neurological Surgery, University of California-Davis Medical Center, Sacramento, CA 95817, USA b Department of Medical Microbiology, University of California-Davis Medical Center, Davis, CA 95616, USA Received 15 December 2003; accepted 12 February 2004
Abstract
Background: In North America, the largest number of neurosurgical cases stemming from parasitic infections involves the larval form of Taenia solium, the infectious organism causing neurocysticercosis. This infection of the central nervous system (CNS) is most commonly seen in areas with significant immigrant populations and can often present particular challenges to treating physicians. Methods: A review of the literature was performed, highlighting the epidemiology, parasitology, and clinical manifestations of neurocysticercosis. Particular attention was paid to 4 locations of neurocysticercosis lesions: parenchymal, subarachnoid/cisternal, intraventricular, and spinal. Results: Both medical and surgical interventions may be necessary for adequate treatment of neurocysticercosis, depending on various factors, including location of lesion. Conclusions: A review of neurocysticercosis, with particular attention paid to location of disease involvement in the CNS, provides important information to the clinical management of this disease. D 2005 Elsevier Inc. All rights reserved.
Keywords:
Neurocysticercosis; CNS infections; Parasite
1. Introduction Between 380 and 375 bc, Aristophanes referred to the bladders of cysticerci and described how to search for them in a pig’s tongue [6,58]. Aristotle described a disease in pigs defined by the presence of btender meat which have bladders which are like hailstones in the region of the thigh, neck, and loin; these are the regions in which they generally appear Q [7,58]. In 1550, Parnolus described neurocysticercosis in a priest who died of a stroke and was found to have a cysticercal cyst involving the corpus callosum [42,58]. The causal relationship of Taenia solium to the parasitic disease was first recognized by Kqchenmeister in 1855 when a condemned murderer developed the adult tapeworm in his intestine after ingesting cysticercal cysts [58]. In North America, Walter Dandy first described the disease in 1927 [21,22,44,58]. Clinical, pathological, and epidemiologic studies in the 20th century better defined the nature,
* Corresponding author. Tel.: +1 916 734 3658; fax: +1 916 734 3658. E-mail address: [email protected] (K.D. Kim). 0090-3019/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2004.02.033
incidence, and global distribution of the disease [28,87]. From the 1980s through the 1990s, a greater understanding of the disease was gained through improvements in immunochemistry and innovations in neuroimaging. 2. Epidemiology Worldwide, particularly in Central and South America, India, Africa, East Asia, Eastern Europe, and other developing countries, cysticercosis is the most common parasitic disease and continues to be an important health problem [36,87]. Poor sanitation and hygiene play a key role in perpetuation of this parasitic disease. In 1976, the World Health Organization estimated that 2.5 million people worldwide harbor the T solium tapeworm and that many more are infected with the larval stage. It is the larval stage of the disease that causes cysticercosis [8,89]. Neurocysticercosis is quite prevalent in Latin America and India [1]. For example, in endemic villages in Latin America, the seroprevalence has been estimated to be between 4.9% and 24% [72]. In 1979, a 1% incidence of
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neurocysticercosis was reported in Mexico [34]. In 1983, neurocysticercosis accounted for 0.16% of all admissions to a major hospital in Mexico and over 10% of all surgical procedures performed by its neurosurgeons [49]. Neurocysticercosis is a common etiology of epilepsy in endemic regions. In one recent study of 100 consecutive patients with adult-onset epilepsy from Mexico City, 50 had computed tomography (CT) evidence of neurocysticercosis [54,87]. In India, up to 50% of patients with seizure disorders have serological evidence of cysticercosis [50,81,86]. More recently, cysticercosis has become an important parasitic disease in the United States, particularly in California and other states with a large immigrant population [84]. The number of cases diagnosed in Los Angeles increased 4-fold between 1977 and 1981 [87]. Between 1973 and 1983, over 500 cases were reported from just 4 general hospitals in Los Angeles [36,47]. In 1998, it was estimated that 1000 new cases of neurocysticercosis will be diagnosed each year in the United States alone [72,87]. The increasing prevalence in this country has been attributed to the migration of large numbers of rural immigrants from developing countries to the United
States, along with improvements in neuroimaging leading to better diagnosis [66]. 3. Parasitology The life cycle of T solium involves the pig as the more common intermediate host and the human as the only definitive host (Fig. 1). The definitive host, by definition, is the organism in which the sexually mature parasite develops. The tapeworm, characterized by a head (scolex) with 4 suckers and a double crown of hooks (Fig. 2A) and a large body composed of hundreds of proglottids (segmental units containing thousands of eggs) (Fig. 2B), lives within the small intestine of the human and can measure several meters in length (Fig. 2C). The pig acts as an intermediate host by ingesting food contaminated with eggs or proglottids shed from the human feces. Once the eggs (embryophores) are in the stomach or small intestine of the pig, they hatch, liberating the hexacanth embryo known as the oncosphere. Oncospheres have an enzymatic system that is activated by the acids and
Fig. 1. Life cycle of Taenia solium.
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Fig. 2. A, Photograph of a scolex, consisting of a head and neck with 4 suckers and a double crown of hooks. B, Photograph of a sectioned proglottid containing eggs. C, Photograph of the adult tapeworm measuring over 1 m in length.
enzymes of the stomach. The hexacanth embryo then penetrates the mucosa of the stomach or small intestine and is spread hematogenously to the somatic muscles, eyes, and the central nervous system (CNS) of the pig. The hexacanth embryo develops to the cysticercus in 9 to 14 weeks and is comprised of a fluid-filled bladder and an invaginated scolex (Fig. 3). If infected pork is undercooked or eaten raw, the scolex evaginates and attaches to the mucosa of the small intestine. In 3 to 4 months, the adult tapeworm reaches maturity resulting in taeniasis. Human beings may become an intermediate host and acquire cysticercosis by ano-oral contamination or by ingesting food contaminated with T solium eggs. Alternatively, those with the adult tapeworm may become auto-
infected by reverse peristalsis as the eggs or proglottids regurgitate into the stomach and are thus stimulated to hatch. Just as in the pig, the hexacanth embryo penetrates the intestinal mucosa and is hematogenously transported to the muscles, subcutaneous tissues, eyes, or CNS of human beings [36]. Cysticercosis, therefore, is not acquired by eating infected pork as is commonly thought, but usually from T solium eggs passed by human beings carrying the adult tapeworm. Involvement of the CNS is seen in 60% to 90% of patients with cysticercosis [9,11,13,46,47,62,77]. Brain parenchyma is most likely seeded through hematogeneous dissemination [5,19,35,36]. The ventricular system, subarachnoid space, and basilar cisterns are then seeded via the choroid plexus [4]. Spinal cysticercosis most commonly involves the subarachnoid space by the extension of cerebral subarachnoid disease, but intramedullary involvement may also occur hematogenously [63,75]. 4. Clinical manifestations
Fig. 3. Noncontrast head CT showing multiple, punctate, calcified parenchymal cysts and a right frontal ventriculostomy placed for hydrocephalus.
The clinical presentation of neurocysticercosis is varied and depends on the stage, number, size, and locations of the cysticercal cysts within the CNS and the host’s immune response to the parasite. Seizures occur in 50% to 80% of patients with parenchymal disease [24,26,37,38,54,87]. Due to this high incidence of seizures, neurocysticercosis must always be considered as a part of the differential diagnosis for a new-onset seizure in endemic areas [24,54]. Seizures are thought to occur either from parenchymal irritation because of active inflammation or from gliosis associated with end-stage calcified lesions [87]. Focal mass effect by parenchymal cysts or reactive edema as the result of an immunologic response to the cyst may give rise to the symptoms of elevated intracranial pressure, most notably headaches, nausea, and vomiting.
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Depending on the location of the pathology, pyramidal tract signs, sensory deficits, movement disorders, cerebellar or brainstem signs, and even dementia may develop [8,13]. When located in the subarachnoid space, cysts can give rise to focal mass effect or to an inflammatory response manifested as basilar meningitis [20,30,45,73]. Communicating hydrocephalus and signs of elevated intracranial pressure, such as nausea, vomiting, headache, and papilledema may follow. Cranial neuropathy or vasculitis may result from the inflammatory changes. Vasculitis can lead to small- or large-vessel infarcts [8]. Thus, a lacunar or lobar infarct, particularly in a young patient from an endemic region, should raise the suspicion for vasculitis due to neurocysticercosis. In children, meningoencephalitis may result from an intense immune response to the parasite [12]. These patients present clinically with confusion, seizures, headaches, nausea, and vomiting [65]. Intraventricular cysts can be found in any ventricular compartment but tend to migrate to the fourth ventricle because of gravity and cerebrospinal fluid (CSF) flow patterns [48,76]. By physically obstructing the CSF pathway, intraventricular cysts may cause a noncommunicating hydrocephalus. Alternatively, the death of an intraventricular cyst may lead to ependymitis resulting in a communicating hydrocephalus [4,18,19]. Acute intermittent hydrocephalus or sudden loss of consciousness (Bruns’ syndrome) may result if a mobile ventricular cyst is present [69]. A case of sudden death due to migration of a cyst from the wall of the lateral ventricle to the foramina of Monro has been reported [90]. Spinal cysticercosis is rare, with spinal cord involvement reported to occur in only about 1% to 5% of neurocysticercosis [2,38,85]. Spinal intramedullary, intradural extramedullary, and extradural cysticercosis may present with radiculopathy or myelopathy. In 4 cases of spinal extradural cysticercosis reported in 1998, 2 presented with spastic paraparesis, 1 presented with radiculopathy, and 1 presented with a partial Brown Sequard syndrome [57].
5. Diagnosis Given the wide range of clinical presentations, diagnosis is seldom made by history and physical examination alone. Although patients commonly present with a recent history of travel to endemic areas or are immigrants from endemic regions, mere exposure to an infected food handler or a housekeeper, for example, may be all that is necessary to become infected [70]. Consumption of pork may not even be part of the patient’s dietary history as exemplified by cases reported among the Orthodox Jewish community in New York [36,70]. This population presumably developed cysticercosis from food handlers who carried the worm T solium. Accurate diagnosis is based on the combination of clinical, epidemiologic, radiographic, and immunologic information. Peripheral blood smears, eosinophilia, and
CSF assessment is neither sensitive nor specific. Examination of the stool for ova and parasite or co-proantigen, although seldom diagnostic, should always be included in the event that the patient is carrying an adult tapeworm [3]. 6. Immunologic studies Immunologic studies used to detect anticysticercal antibodies to T solium antigens in the serum and CSF include indirect hemagglutination, complement fixation, immunoelectrophoresis, indirect immunofluorescence, enzymelinked immunosorbent assay (ELISA), and enzyme-linked immunoelectrotransfer blot (EITB). Of these, ELISA and EITB are the 2 most useful tests. Enzyme-linked immunosorbent assay measures specific IgG to partially purified antigen from cysticercal fluid. Serum sensitivity of 65% to 87% and a specificity of 63% to 100% and the CSF sensitivity of 62% to 90% and specificity of 98% to 100% have been reported [17,27,32,67]. Most studies examining the sensitivity and specificity of ELISA are limited, however, because of the lack of biopsy-proven diagnosis [15,17,32,33,61,94]. Enzyme-linked immunoelectrotransfer blot detects anticysticercal antibodies to as many as 7 glycoprotein bands specific to T solium and allows nonspecific bands to be ignored, leading to increased specificity with this test [41,80]. However, in one study, decreased sensitivity of the EITB assay was seen when fewer intracranial lesions were present or when calcified lesions were primarily present [71,88]. Nevertheless, some studies with pathologic confirmation have reported serum and CSF sensitivities of 94% to 100% [27,33,80,88]. Both the ELISA and EITB have a higher false-negative rate when parenchymal disease alone is present, suggesting immunologic tolerance to the parasite and a lack of antibody production [15,55,94]. In addition, it is unknown whether ELISA or EITB can distinguish between the intestinal infestation and neurocysticercosis [8]. The only definitive diagnosis, therefore, is made by direct pathological examination of excised cysts. 7. Imaging studies Neurocysticercosis may be found in multiple CNS locations, and cysticerci may occur at different stages of development within the same patient. Depending on factors such as host immune response, this process may take several months to years to evolve. Although plain films of the limbs may show multiple calcified cysts, their presence does not necessarily imply the presence of intracranial lesions or even cysticercosis [29,36]. Magnetic resonance imaging (MRI) is the imaging study of choice, because it is more sensitive than CT for all phases of the disease process, with the exception of end-stage calcified disease [16,51,78,93]. Computed tomography and MRI findings differ depending on the parasite’s location and
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on its stage of development [14,30,59]. Therefore, neurocysticercosis involving different intracranial compartment is discussed separately. 7.1. Parenchymal cysticercosis The cerebral parenchyma is the most frequently affected CNS site. In 1983, Escobar [30] published a classification system that divides parenchymal cysticercosis cysts into 4 pathologic stages. The initial stage, called the vesicular stage, is characterized by noncystic hexacanth embryos that tend to lodge at the gray-white junction and in the basal ganglia or cerebellum. Initially, little to no local tissue response occurs and minimal abnormality is seen on CT and MRI. As the hexacanth embryo develops into a cystic larva, a local tissue reaction occurs, which is manifested as edema. At this stage, CT shows areas of decreased density surrounding the lesion, and MRI shows subtle surrounding hypointensity on T1-weighted images and hyperintensity on T2-weighted images [59]. As the host immune response mounts, homogeneous contrast enhancement may be observed [14,21,91]. Over the next several weeks, the larvae develops into a cyst measuring 1 to 2 cm in diameter, as its bladder becomes engorged with clear fluid. The cyst wall is initially thin and not yet visible with current imaging modalities. A mural nodule within the cyst cavity becomes apparent as the invaginated scolex develops. It appears isointense to brain on all MRI pulse sequences and enhances with contrast. Tissue edema dissipates and the previous surrounding hypodensity seen on CT and hyperintensity on T2-weighted images tends to resolve [59]. At this stage, the cystic fluid appears identical to CSF on all MRI pulse sequences [14,21,91]. After 5 to 7 years, the larvae enters the colloid vesicular stage and begins to degenerate, eliciting an immune response. The cyst wall thickens and becomes fibrotic, and the cystic fluid becomes proteinaceous. As a result, the cystic fluid appears slightly hyperintense relative to CSF on T1-weighted sequences and markedly hyperintense on T2weighted sequences. The scolex appears isointense to hypointense on T2-weighted sequences and provides good contrast relative to the surrounding hyperintense cystic fluid. Contrast studies may show cyst wall enhancement [14,21,91]. In the granular nodular stage, cyst fluid absorption begins and the capsule thickens further. The lesion may appear more solid and isointense on T1-weighted sequences and isointense to hypointense with or without a central area of hyperintensity on T2-weighted sequences. Homogeneous enhancement with surrounding edema is seen. In the final stage, termed the nodular calcified stage, the dead larvae calcify and are best identified on CT as multiple calcified nodules [59] (Fig. 3). Children may present with an encephalitic form of the disease characterized by multiple small enhancing lesion and diffuse cerebral edema [77]. Medical therapy with
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praziquantel or albendazole accelerates cyst death. Initially, an intense inflammatory response characterized by an exacerbation in neurological symptoms and an increased edema, cyst size, and contrast enhancement may occur. As a result, the various MRI features just discussed may be seen over a much shorter period. 7.2. Subarachnoid/cisternal cysticercosis Imaging characteristics of cisternal cysticercosis differ from the parenchymal form as the result of 2 different presentations of the larvae. In the first form, cysticercus cellulosae, the parasite is characterized by a single bladder measuring 3 to 18 mm in diameter with an invaginated scolex. The cyst contents tend to follow CSF on all pulse sequences and can be easily overlooked. Enlargement of a cisternal space or hydrocephalus may be the only clue to abnormality [21]. The second form, cysticercus racemosus, presents as large multiloculated cystic lesions lacking scolices. Both forms may be found in any of the cisterns, the sylvian fissure, or within the sulci over the cerebral hemispheres. The septae seen in multiloculated, racemose cysts can be seen on T1- and T2-weighted sequences, but the cyst contents tend to blend with CSF (Fig. 4). Usually, minimal to no enhancement of the cyst wall is seen. Alternatively, a basilar cistern inflammatory reaction leading to profound enhancement of the cisterns and meninges at the skull base may occur [30,45,53,73]. This inflammatory reaction may subsequently evolve into chronic granulomatous meningitis resulting in chronic hydrocephalus. 7.3. Intraventricular cysticercosis Intraventricular cysticercosis is seen in 10% to 20% of neurocysticercosis. Although the cysts may be found anywhere within the ventricles, the fourth ventricle is most
Fig. 4. Gadolinium-enhanced coronal T1-weighted brain MRI showing suprasellar and bilateral sylvian cisternal cysts with third ventricular enlargement.
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Fig. 5. Combined cisternal and intraventricular cyst. A, Gadolinium-enhanced axial T1-weighted MRI shows a racemose cyst without scolices in the prepontine cistern with multiple septae and fourth ventricular cystic enlargement. B, Axial T2-weighted image shows minimal perilesional edema.
commonly involved [14,48,91]. Intraventricular cysts (Fig. 5A and B) tend to be single, but multiple cysts do occur. The cyst wall and its contents are not typically seen on CT or MRI pulse sequences. If the cystic fluid becomes turbid, proton density images may show subtle differences between the cyst contents and CSF. In patients with
ventriculoperitoneal shunts, intraventricular metrizamide applied through the shunt may help delineate the cyst [49]. However, the scolex is usually seen on gadolinium-enhanced T1-weighted images obviating the need for intraventricular metrizamide injection in most cases. An inflammatory reaction manifested as ependymal and subependymal hyperintensity on T2-weighted images and contrast enhancement of the cyst wall on T1-weighted images may be seen. These findings have been associated with a high probability that a permanent shunt will be required, even if the cyst is completely removed [92]. 7.4. Spinal cysticercosis Spinal cysticercosis most commonly involves the subarachnoid space and results in intradural cysts or arachnoiditis. Cysts appear as filling defects on myelography and may be mobile (Fig. 6). T1, T2, and proton density MRI
Fig. 6. Spinal myelogram showing a cluster of subarachnoid cysts in the lower lumbar region manifested as multiple round filling defects.
Fig. 7. Spinal subarachnoid cysticercal cyst. Gadolinium-enhanced sagittal T1-weighted image shows an enhancing lesion anterior to the cord at the upper cervical levels.
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sequences reveal findings similar to those seen in cerebral cisternal disease. Intramedullary cysts (Fig. 7) are even more rare and have similar MRI characteristics compared with cerebral parenchymal cysts. 8. Treatment The treatment approach and response depends on the location of the pathology. In general, parenchymal cysticercosis in a patient with a stable neurological examination should be treated with a trial of antihelmintic medical therapy. Medical failures often necessitate surgical treatment. Subarachnoid/cisternal, intraventricular, and spinal cysticercosis require individualized approaches, and combined medical and surgical treatments are often used. 8.1. Parenchymal cysticercosis Both praziquantel, a heterocyclic isoquinolone, and albendazole, an imidazole, have been shown to be effective in the treatment of parenchymal cysticercosis. In a prospective study of 26 patients with the parenchymal form of the disease, CT improvement was demonstrated in 25 of 26 patients (96%) treated with 50 mg/kg of praziquantel for 15 days [74]. All treated patients improved clinically and 67% of patients had total remission of cystic lesions by CT, whereas most controls worsened without spontaneous remission. This same study suggested that a second treatment 3 months later might be beneficial for those with only partial resolution of their cysts. Albendazole was demonstrated to be superior to praziquantel in one study based on CT resolution of parenchymal cysts [31,76]. Sixty-seven percent of brain parenchymal cysticerci disappeared on a 2-week course of praziquantel compared with 86% on a 30-day course of albendazole [31]. Subsequent studies demonstrated similar efficacy with an 8day course of albendazole [76]. Albendazole has the added advantage of lower cost compared with praziquantel, an important advantage in developing countries. Side effects are usually mild and include elevations in serum transaminases, abdominal pain, headaches, leukopenia, alopecia, and allergic reactions. Seizures due to neurocysticercosis, although often controlled with first-line antiepileptic drugs such as phenytoin and carbamazepine, may be further improved upon after treatment with praziquantel and albendazole. In a study involving 122 patients with neurocysticercosis and epilepsy, 95 patients were treated with antiepileptic drugs and either praziquantel or albendazole and the remaining 27 were treated with antiepileptic drugs alone [25]. Among those treated with both antiepileptic drugs and anticysticercal therapy, 83% remained seizure-free compared with only 26% of those treated with antiepileptic drugs alone over a 28-month follow-up. Despite improved seizure control, praziquantel and albendazole may not be a definitive cure for epilepsy, and antiseizure medication may need to be continued indefinitely [25,82].
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Larval death is associated with an intense host immune response, and patients may worsen clinically while on medical treatment with antihelmintic agents. In fact, 92% of patients in one study experienced short-term exacerbation of seizures, worsening of headaches, or developed intracranial hypertension [23,74]. Treatment-related adverse reactions may be lessened and life-threatening inflammatory response may be averted with the use of glucocorticoids. Incidence of adverse reaction has been reported to be between 92% and 100% among those not receiving steroids as opposed to 11% to 16% among patients receiving steroids while being treated with praziquantel [40]. Thus, the use of steroids should be strongly considered in the medical treatment of parenchymal cysticercosis. Steroids may, however, reduce serum levels of praziquantel by 50% and increase serum levels of albendazole [43,83]. In addition, administration of praziquantel with cimetidine significantly increases the bioavailability of praziquantel [60]. Given the efficacy of medical treatment, surgical treatment is reserved as second-line therapy for parenchymal disease. In parenchymal cysticercosis, surgery is primarily aimed at relieving local mass effect and treating hydrocephalus. Surgical treatments include craniotomy, cyst extraction, or stereotactic aspiration of the cyst and shunt placement. If the cyst is causing significant mass effect in noneloquent regions of the brain or if the patient has failed medical therapy, direct craniotomy and removal of the cyst is appropriate. Since cysts commonly adhere to adjacent neural and vascular structures, surgical resection, in some cases, may lead to a worsening of symptoms. To minimize the risk of additional injury to the brain, stereotactic aspiration of parenchymal cysts with placement of an indwelling cyst catheter-reservoir for repeated cyst aspirations is a viable alternative [20]. Unlike pyogenic abscesses, penetration of the cyst wall with a blunt tip is easily accomplished [19]. 8.2. Subarachnoid/cisternal cysticercosis Based on the available literature, the efficacy of medical therapy with praziquantel and albendazole for subarachnoid/ cisternal cysticercosis is less clear, and prognosis is poor in comparison with parenchymal cysticercosis. The racemose form, which is frequently accompanied by basilar arachnoiditis, hydrocephalus, cranial neuropathies, and vasculitis, complicates treatment of cisternal disease. Although some advocate surgery as the best treatment for this form of the disease [52,64,79], others recommend an initial trial of medical treatment in clinically stable patients [20]. In one retrospective study of 20 patients with neurocysticercosis that included 12 cases primarily involving the cisterns, open craniotomy was successful in removing the cysts in all 12 [20]. Two of the cases underwent craniotomy after unsuccessful attempted stereotactic aspiration. Although results were reported for the group as a whole (parenchymal, cisternal, or combined disease), 15 of 20 (75%) showed neurological or symptomatic improvement over a follow-up
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period of 36 months, and no deaths occurred [20]. The authors concluded that large parenchymal cysticercal cysts and cisternal lesions may be amenable to surgery if the patient presents with neurological decline or if medical therapy fails. They also suggested that multiloculated lesions should be treated by open craniotomy rather than stereotactic aspiration secondary to difficulty in achieving adequate decompression with this technique. Cyst marsupialization has been suggested for ringenhancing cisternal lesions. These lesions tend to be tenacious and are prone to rupture [46,64]. In any event, when the surgical option is selected, every care should be taken to avoid spillage of cyst contents to avoid the possibility of severe meningitis. 8.3. Intraventricular cysticercosis Similar to cisternal cysticercosis, the reported efficacy of medical therapy with praziquantel and albendazole for intraventricular cysticercosis is limited. Intraventricular cysticercosis is complicated by the potential for cyst migration, with the possibility for the development of acute life-threatening hydrocephalus. In addition, ependymitis may be present, which may lead to hydrocephalus with intraventricular loculations or cyst adherence to the ependyma. Although reports of successful treatment with antihelmintics have been published, surgical treatment is recommended by most in an effort to avoid the possibility of acute neurological deterioration [5,49]. Furthermore, medical treatment alone may lead to severe ependymitis [4]. Complete surgical excision may avoid this complication. Most cases of intraventricular cysticercosis involve a single cyst and ependymitis is usually not present. Direct surgical extirpation with low morbidity can frequently be achieved in these patients [5]. Unless limited by adhesions as the result of ventriculitis, cysts can move within the ventricular space. Therefore, reimaging just before the surgical procedure for precise cyst localization may be prudent [91]. Transcortical or transcallosal approach for cysts in the lateral ventricle or transcallosal approach for third ventricle may be used. Alternatively, endoscopic excision with or without image guidance may be attempted [19], although cyst rupture may be more frequent with this technique. Intraventricular cyst rupture may result in death, as reported in 2 of 21 cases of intraventricular cysticercosis studies by Madrazo et al [49]. Although some advocate shunting procedures as the sole treatment of fourth ventricular lesions, others recommend direct cyst excision via suboccipital approach secondary to concerns of continued parasitic growth without excision [48,49,64]. Fenestration of the septum pellucidum should be considered in cases in which loculations or ependymitis is present. High-potency glucocorticoids with vigorous intraventricular lavage is recommended in the event of cyst rupture [5]. Although ventriculostomies are commonly required in the treatment of intraventricular cysticercosis uncomplicated by ependymitis, permanent CSF diversionary procedures may not be neces-
sary. For example, in a series of 45 surgically treated patients with intraventricular cysticercosis, only 7 required a permanent ventriculoperitoneal shunt [5]. Ependymitis is associated with cystic lesions that are more difficult to remove surgically, have greater likelihood of need for permanent CSF diversionary procedures, and a high incidence of shunt malfunction [19]. Therefore, in cases of intraventricular cysticercosis associated with ependymitis, primary CSF diversion and medical therapy without removal of the cysts should be considered [19]. Frequently, in the face of ependymitis, intraventricular loculations are present, and multiple conduits may be required with attendant complications such as shunt failures [5]. 8.4. Spinal cysticercosis Because of a limited number of spinal cysticercosis, true efficacy of medical or surgical treatment is unknown. One case report described an excellent outcome for 2 patients with spinal intramedullary cysticercosis who presented with paraparesis and bladder dysfunction [39]. After treatment with 15 mg/kg of albendazole for 4 weeks, both patients improved and became ambulatory. Results of laminectomy and cyst extirpation for spinal subarachnoid cysticercosis have been variable [10,56,68], although more rare extradural cysticercosis has been treated with laminectomy, decompression, and stabilization [57]. Acknowledgments The authors thank James Boggan, MD, James Brunberg, MD, and Jalal Abbaszadeh, MD, for providing some of the figures and Dorie DeCosta for her assistance with the preparation of this manuscript. References [1] Acha PN, Aguilar FJ. Studies on cysticercosis in Central America and Panama. Am J Trop Med Hyg 1964;13:48 - 53. [2] Akiguchi T, Fujiwara T, Matsuyama H, et al. Intramedullary spinal cysticercosis. Neurology 1979;29:1531 - 4. [3] Allan JC, Velasquez-Tohom M, Torres-Alvarez R, et al. Field trial of the coproantigen-based diagnosis of Taenia solium taeniasis by enzyme-linked immunosorbent assay. Am J Trop Med Hyg 1996; 54:352 - 6. [4] Amar AP, Ghosh S, Apuzzo ML. Treatment of central nervous system infections: a neurological perspective. Neuroimaging Clin N Am 2000;10(2):445 - 59. [5] Apuzzo MLJ, Dobkin WR, Zee CS, et al. Surgical considerations in treatment of intraventricular cysticercosis: an analysis of 45 cases. J Neurosurg 1984;60:400 - 7. [6] Aristophanes. Las once comedias. Mexico City7 Editorial Porru´a; 1976. [7] Aristotle. Les belles lettres. Histoire des animaux, Socie´te´ d’Edition, vol. III. 1969. p. 48 - 9 [book VIII, paragraph XXI, Paris]. [8] Barry M, Kaldjian LC. Neurocysticercosis. Semin Neurol 1993;13(2):131 - 43. [9] Brown WJ, Voge M. Neuropathology of parasitic infections. New York7 Oxford Univ. Press; 1985. [10] Cabieses FM, Vallenas M, Landa R. Cysticercosis of the spinal cord. J Neurosurg 1959;16:337.
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Commentary Neurocysticercosis is one of the pathologies most frequently seen by neurosurgeons from developing countries. With the exception of Muslim countries, brain cysticercosis is endemic in Latin America, Asia, and Africa. Some figures show its importance in neurological departments; neurocysticercosis accounts for more than 50% of all cases of lateonset epilepsy and more than 40% of hydrocephalus in adults, as well as 20% of all surgical procedures. Although the last cipher is going down with the recent introduction of effective cysticidal drugs, in the United States, when studying patients who migrated from endemic countries, it is important to entertain the potential diagnosis of neurocysticercosis in cases of parenchymal calcifications, cystic lesions, or chronic meningitis. Hawk et al made a timely review on the subject that presents, in a didactic form, practical hints on diagnosis and treatment. The separation that Hawk et al made according to the localization of parasites has practical significance, because clinical manifestations, imaging studies, and therapeutic options have substantial differences depending on whether the parasites are lodged in the brain parenchyma, the ventricles, the meninges, or the spinal area. The authors are to be congratulated for this well-summarized and updated review of a very complex disease. Julio Sotelo, MD (General Director) Instituto Nacional de Neurologı´a y Neurocirugı´a C.P. 14269 Mexico City, Mexico