Neurocysticercosis: a neurosurgical perspective.

Key Words: antihelminthic, cysticercosis, intraventricular, shunting

Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system (CNS) worldwide. An estimated 50 million people are infected and 50,000 people die annually as a result of this disease. (1) It accounts for 11% of hospital admissions and 35 to 45% of all neurosurgical procedures in certain endemic areas. (2) The incidence in the United States is increasing and involvement by neurosurgical services is increasing.

Life Cycle

Humans are the definitive host for the adult tapeworm Taenia solium, which harbors in the small intestine without consequence. (3) Fecal shedding of eggs usually leads to ingestion of eggs in contaminated water or food by an intermediate host, typically human or pig. (3,4) Once inside the intestine, the eggs are released and produce primary larvae that enter the circulatory system. Hematogenous spread to muscular, ocular, and neural tissue then occurs. Once inside the brain, the primary larvae develop into secondary larvae, the cysticerci. (3,4)

Clinical Manifestations

Clinical manifestations of the neural form of the disease are varied and nonspecific. This pleomorphism is related to the number, size, and topography of the lesions. Parenchymal disease is most common and frequently presents with seizures in 50 to 80% of patients. (5-7) The colonization of the ventricular system often presents with rapid clinical deterioration due to increased intracranial pressure from obstructive hydrocephalus. (8-11) Subarachnoid disease is usually more difficult to manage because the cysts are usually multiple, attain larger sizes, and produce severe basal meningitis. (4,12-15)

Laboratory Studies

Complete blood count, peripheral eosinophil level, and serum anticysticercal antibody levels should be obtained in all patients suspected of having NCC. (3) Patients requiring ventriculostomy placement should have cerebrospinal fluid (CSF) analyzed for eosinophil and anticysticercal antibody levels. (3) Stool for ova and parasites is helpful in patients with simultaneous intestinal tapeworm infection, but is insensitive and nonspecific for T. solium species and is found in less than 33% of cases. Several laboratory methods have been developed to detect host antibodies against circulating cysticercal antigens. From the many tests performed, current data indicate that enzyme-linked immunosorbent assay (ELISA) and immunoblot tests are the most effective. ELISA, based on the use of a crude antigenic extract of the parasite, is relatively inexpensive, can be accomplished within 24 hours, and is sensitive when testing CSF but insensitive for serum antibodies. (16,17) Conversely, electroimmunotransfer blot (EITB) has a higher sensitivity for serum samples compared with CSF samples (17,18) but is considerably more expensive and may require weeks for processing. Overall, serum EITB is more sensitive for cysticercal infection than ELISA, but neither test is specific for central nervous system involvement, especially in areas where the parasite is endemic. False-positive ELISA results can occur in patients with other helminth infections such as Echinococcus, (19) but a positive EITB is specific for T. solium. Therefore, a positive CSF ELISA or positive serum or CSF EITB with suggestive neuroimaging is diagnostic. (20)

Imaging Studies

High-resolution computed tomographic (CT) scanning and magnetic resonance imaging (MRI) systems are most commonly used for diagnosing NCC. (3,4) MRI testing allows for better visualization of the scolex, which is diagnostic. (3) If MRI is not available, a CT scan with contrast is useful. However, the presence of ventricular cysts may not be visible on CT scan, often requiring positive-contrast ventriculography to confirm the diagnosis.

The radiologic appearance of NCC changes according to the host immune response and viability of the larval cyst. Viable cysts tend not to contrast-enhance along their periphery and are thought to evade the host's immune detection by active modulation. (21)

Larval viability has been estimated to average 4 to 5 years, (22) after which larval death or loss of host-immune modulation results in an immune response. Inflammation becomes apparent as contrast-enhancement and pericystic edema. (23) Finally, when the larva dies, the cysticercus becomes calcified, edema lessens, and contrast-enhancement resolves, (24) although there are rare reports of recurrent pericystic edema after calcification (Fig. 1). (25,26)

Parenchymal Disease

Antihelminthic therapy has been the mainstay of treatment for this form of disease. The two drugs most commonly used are praziquantel (50 mg/kg/d in divided doses for 14 days) and albendazole (15 mg/kg/d for 1 month). Albendazole has a greater parasiticidal effect and better CSF penetration, and is cheaper than praziquantel. (4,27) Praziquantel interacts with steroids and may lower serum levels of both phenytoin and carbamazepine. (28,29) There is controversy as to what role antiparasitic treatment should have for parenchymal neurocysticercosis. In patients with single lesions, one randomized controlled trial of albendazole found more rapid radiologic resolution of cysts with medical therapy, (30) whereas three other trials found no difference. (31,33) In contrast to patients with solitary parenchymal cysts, antiparasitic therapy is more likely to completely treat cysts in patients harboring multiple cysts than no medical therapy. (31) Seizure control also appears to be improved in patients receiving antihelminthic agents. (6,34) Current consensus guidelines suggest that antiparasitic therapy may be used with solitary viable or degenerating cysts, and are strongly indicated for multiple viable or degenerating cysts. (27) A temporary increase in pericystic inflammation is often observed during treatment, as the dying parasite can no longer escape host defenses. For this reason, most physicians prescribe glucocorticoids concomitantly (dexamethasone 4 mg every 6 hours by mouth or intravenously).

[FIGURE 1 OMITTED]

If medical therapy fails, surgery has a role in select cases. Surgical intervention may take the form of CT scan-guided stereotactic drainage, placement of a catheter-reservoir system for repeat aspiration, (35) and craniotomy. These cysts are in various stages of degeneration and tend to incite a diffuse pericystic inflammatory response, sometimes precluding complete drainage or resection. Once the cysts are removed either partially or in whole, an antihelminthic medication should be started with a short course of steroids.

Subarachnoid/Cisternal Disease

Cysts in the subarachnoid spaces are harbored by 27 to 56% of patients with NCC. These cysts are usually multiple and attain larger sizes than their parenchymal counterparts. Some argue that large subarachnoid cysts, which have not yet induced an inflammatory reaction, can be safely managed surgically. (36-38) Cysts that have induced an inflammatory reaction pose a challenge due to their size and adherence to eloquent anatomy. In these cases, some have advocated marsupialization, (37,39) but increasingly antiparasitic therapy is used solely or in conjunction with surgery for this form of disease. Smaller cysts in the subarachnoid space have been shown to respond to antihelminthic therapy (12) and even dramatic remission has been described for giant (>50 mm) cysts. (13,14,40) Patients with basilar arachnoiditis and communicating hydrocephalus have a protracted course despite aggressive therapy. One study showed that mortality in patients with basal arachnoiditis and hydrocephalus was 50%, with most patients dying within 24 months of a shunting procedure. (41)

Intraventricular Disease

Intraventricular involvement occurs in 15 to 20% of patients with neurocysticercosis (27) and is associated with high rates of mortality and morbidity. (8-11)

Medical Management

Medical management is not advocated for patients with symptomatic hydrocephalus; however, controversy exists for patients harboring asymptomatic ventricular cysts. There are reports of successful treatment of ventricular cysts with antihelminthic medication (39,42,43) and other reports that are not as promising. (44) Even if effective agents were available, their use should be contraindicated because death of the larvae within the ventricular system should be avoided. If medical therapy is attempted, worsening clinical or radiographic findings would be immediate indicators for shunting or surgical removal.

Shunting

Shunting has been advocated by some as the definitive method of treating intracranial hypertension in patients with obstructive hydrocephalus and ventricular NCC for several reasons. (9,41,45) First, because NCC is a chronic inflammatory disease, seeding of the subarachnoid cisterns results in communicating hydrocephalus, which can be relieved only by shunting. Second, ventricular shunting is faster, less damaging to the brain, uses smaller incisions with faster recovery times, and carries less morbidity than open surgical procedures. Third, some argue that open surgical resection can be avoided with shunting and antihelminthics. Although these arguments are valid, there are compelling reasons for surgical resection. Apuzzo et al (8) reported the cases of seven patients who underwent ventriculoperitoneal shunting as the primary mode of therapy. Three patients needed a reoperation for cyst expansion at 8, 11, and 48 months. Furthermore, by 6 years, 50% of patients with shunts required at least one revision, (46) and shunts associated with hydrocephalus secondary to neurocysticercosis had higher failure rates. (35) A recent retrospective review of shunt malfunctions among patients with neurocysticercosis found that shunts placed during the vesicular stage of cysticercal infection were twice as likely to malfunction compared with shunts placed during the degenerative or calcified stages of the disease. (47) The same study also found that concurrent administration of antiparasitics after shunt placement during the vesicular stage greatly reduced the rate of shunt failure. Because it is difficult to predict which patients with ventricular cysticercosis will develop ventriculitis, CSF channel obstruction, and/or cyst expansion with antihelminthic therapy or shunting, some have advocated a more aggressive surgical strategy. (8,11,47-51)

Surgery

Transcortical resection of lateral ventricular cysts, transcallosal or transcortical approaches for third ventricular cysts, and a suboccipital approach for fourth ventricular cysts are established microsurgical techniques for cyst excision. More recently, neuroendoscopy has become the primary treatment modality for ventricular cysticercosis at many institutions. (48-52) It allows for internal CSF diversion in conjunction with cyst removal and avoids shunting. In addition, neuroendoscopy prevents the need for multiple craniotomies, gives access to the ventricular system in a matter of minutes, and allows for physiologic internal CSF drainage.

Conclusion

Increasing immigration from endemic areas has caused a greater incidence of neurocysticercosis in the United States. This review outlines the current understanding of the pathophysiology, clinical manifestations, diagnostic and radiologic findings, and therapeutic options available to physicians who manage such patients.

The more we depend on God, The more dependable we find God is.

--Cliff Richards

Acknowledgment

We extend special thanks to Suzanne Truex for assistance in preparing the photographs reproduced in this article.

From the Department of Neurosurgery, University of Texas Southwestern School of Medicine, and the Children's Medical Center, Dallas, TX.

Reprint requests to Thomas G. Psarros, MD, Department of Neurosurgery, University of Texas Southwestern School of Medicine, 5323 Harry Hines Boulevard, Dallas, TX 75390-8855. Email: [e-mail]

Accepted February 15, 2003.

Copyright [c] 2003 by The Southern Medical Association 0038-4348/03/9610-1019

References

1. Shandera WX, White AC Jr, Chen JC, et al. Neurocysticercosis in Houston, Texas: A report of 112 cases. Medicine (Baltimore) 1994;73:37-52.

2. Lombardo L, Mateos JH. Cerebral cysticercosis in Mexico. Neurology 1961;11:824-828.

3. Breeze R. Neurocysticercosis. Contemp Neurosurg 1990;23:1-5.

4. Garcia HH, Del Brutto OH. Taenia solium cysticercosis. Infect Dis Clin North Am 2000;14:97-119, ix.

5. Del Brutto OH, Noboa CA. Late onset epilepsy in Ecuador: Aetiology and clinical features in 225 patients. J Trop Geogr Neurol 1991;1:31-34.

6. Del Brutto OH, Santibanez R, Noboa CA, et al. Epilepsy due to neurocysticercosis: Analysis of 203 patients. Neurology 1992;42:389-392.

7. Del Brutto OH, Sotelo J, Roman GC. Neurocysticercosis: A Clinical Handbook. Exton, PA, Swets & Zeitliger, 1998.

8. Apuzzo MLJ, Dobkin WR, Zee CS, et al. Surgical considerations in treatment of intraventricular cysticercosis: An analysis of 45 cases. J Neurosurg 1984;60:400-407.

9. Bandres JC, White AC Jr, Samo T, et al. Extraparenchymal neurocysticercosis: Report of five cases and review of management. Clin Infect Dis 1992;15:799-811.

10. Cuetter AC, Garcia-Bobadilla J, Guerra LG, et al. Neurocysticercosis: Focus on intraventricular disease. Clin Infect Dis 1997;24:157-164.

11. Zee CS, Segall HD, Apuzzo MLJ, et al. Intraventricular cysticercal cysts: Further neuroradiologic observations and neurosurgical implications. AJNR Am J Neuroradiol 1984;5:727-730.

12. Del Brutto OH, Sotelo J. Albendazole therapy for subarachnoid and ventricular cysticercosis: Case report. J Neurosurg 1990;72:816-817.

13. Del Brutto OH, Sotelo J, Aguirre R, et al. Albendazole therapy for giant subarachnoid cysticerci. Arch Neurol 1992;49:535-538.

14. Noboa C. Albendazole therapy for giant subarachnoid cysticerci. Arch Neurol 1993;50:347-348 (letter).

15. Sotelo J, Marin C. Hydrocephalus secondary to cysticercotic arachnoiditis: A long-term follow-up review of 92 cases. J Neurosurg 1987;66:686-689.

16. Espinoza B, Ruiz-Palacios G, Tovar A, et al. Characterization by enzyme-linked immunosorbent assay of the humoral immune response in patients with neurocysticercosis and its application in immunodiagnosis. J Clin Microbiol 1986;24:536-541.

17. Proano-Narvaez JV, Meza-Lucas A, Mata-Ruiz O, et al. Laboratory diagnosis of human neurocysticercosis: Double-blind comparison of enzyme-linked immunosorbent assay and electroimmunotransfer blot assay, J Clin Microbiol 2002;40:2115-2118.

18. 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;164:1007-1009.

19. Gekeler F, Eichenlaub S, Mendoza EG, et al. Sensitivity and specificity of ELISA and immunoblot for diagnosing neurocysticercosis. Eur J Clin Microbiol Infect Dis 2002;21:227-229.

20. Del Brutto OH, Rajshekhar V, White AC Jr, et al. Proposed diagnostic criteria for neurocysticercosis. Neurology 2001;57:177-183.

21. White AC Jr, Robinson P, Kuhn R. Taenia solium cysticercosis: Hostparasite interactions and the immune response. Chem Immunol 1997;66:209-230.

22. Pittella JE. Neurocysticercosis. Brain Pathol 1997;7:681-693.

23. White AC Jr, Shandera WX. Seizures and treatment for cerebral cysticercosis. N Engl J Med 1992;327:1955-1956 (letter).

24. Dumas JL, Visy JM, Belin C, et al. Parenchymal neurocysticercosis: Follow-up and staging by MRI. Neuroradiology 1997;39:12-18.

25. Park SY, Barkovich AJ, Weintrub PS. Clinical implications of calcified lesions of neurocysticercosis. Pediatr Infect Dis J 2000;19:581-583.

26. Sheth TN, Pillon L, Keystone J, et al. Persistent MR contrast enhancement of calcified neurocysticercosis lesions. AJNR Am J Neuroradiol 1998;19:79-82.

27. Garcia HH, Evans CA, Nash TE, et al. Current consensus guidelines for treatment of neurocysticercosis. Clin Microbiol Rev 2002;15:747-756.

28. Bittencourt PR, Gracia CM, Martins R, et al. Phenytoin and carbamazepine decreased oral bioavailability of praziquantel. Neurology 1992;42:492-496.

29. Vazquez ML, Jung H, Sotelo J. Plasma levels of praziquantel decrease when dexamethasone is given simultaneously. Neurology 1987;37:1561-1562.

30. Baranwal AK, Singhi PD, Khandelwal N, et al. Albendazole therapy in children with focal seizures and single small enhancing computerized tomographic lesions: A randomized, placebo-controlled, double blind trial. Pediatr Infect Dis J 1998;17:696-700.

31. Carpio A, Santillan F, Leon P, et al. Is the course of neurocysticercosis modified by treatment with antihelminthic agents? Arch Intern Med 1995;155:1982-1988.

32. Padma MV, Behari M, Misra NK, et al. Albendazole in single CT ring lesions in epilepsy. Neurology 1994;44:1344-1346.

33. Singhi P, Ray M, Singhi S, et al. Clinical spectrum of 500 children with neurocysticercosis and response to albendazole therapy. J Child Neurol 2000;15:207-213.

34. Vazquez V, Sotelo J. The course of seizures after treatment for cerebral cysticercosis. N Engl J Med 1992;327:696-701.

35. Couldwell WT, Zee CS, Apuzzo MLJ. Definition of the role of contemporary surgical management in cisternal and parenchymatous cysticercosis cerebri. Neurosurgery 1991;28:231-237.

36. Martinez-Lopez M, Quiroz y Ferrari F. Cysticercosis. J Clin Neuroophthalmol 1985;5:127-143.

37. Ramina R, Hunhevicz SC. Cerebral cysticercosis presenting as mass lesion. Surg Neurol 1986;25:89-93.

38. Torrealba G, Del Villar S, Tagle P, et al. Cysticercosis of the central nervous system: Clinical and therapeutic considerations. J Neurol Neurosurg Psychiatry 1984;47:784-790.

39. Leblanc R, Knowles KF, Melanson D, et al. Neurocysticercosis: Surgical and medical management with praziquantel. Neurosurgery 1986;18:419-427.

40. Proano JV, Madrazo I, Avelar F, et al. Medical treatment for neurocysticercosis characterized by giant subarachnoid cysts. N Engl J Med 2001;345:879-885.

41. Colli BO, Martelli N, Assirati JA Jr, et al. Results of surgical treatment of neurocysticercosis in 69 cases. J Neurosurg 1986;65:309-315.

42. Madrazo I, Garcia-Renteria JA, Sandoval M, et al. Intraventricular cysticercosis. Neurosurgery 1983;12:148-152.

43. Proano JV, Madrazo I, Garcia L, et al. Albendazole and praziquantel treatment in neurocysticercosis of the fourth ventricle. J Neurosurg 1997;87:29-33.

44. Robles C, Chavarria M. A case of successfully treated cerebral cysticercosis [in Spanish]. Gac Med Mex 1980;116:65-71.

45. McCormick GF. Cysticercosis: Review of 230 patients. Bull Clin Neurosci 1985;50:76-101.

46. Sainte-Rose C, Hoffman HJ, Hirsch JF. Shunt failure, in Marlin AE (ed): Concepts in Pediatric Neurosurgery. Basel, S. Karger, 1989, vol 9. PP 7-20.

47. Kelley R, Duong DH, Locke GE. Characteristics of ventricular shunt malfunctions among patients with neurocysticercosis. Neurosurgery 2002;50:757-762.

48. Anandh B, Mohanty A, Sampath S, et al. Endoscopic approach to intraventricular cysticercal lesions. Minim Invasive Neurosurg 2001;44:194-196.

49. Bergsneider M. Endoscopic removal of cysticercal cysts within the fourth ventricle: Technical note. J Neurosurg 1999;91:340-345.

50. Bergsneider M, Holly LT, Lee JH, et al. Endoscopic management of cysticercal cysts within the lateral and third ventricles. J Neurosurg 2000;92:14-23.

51. Cudlip SA, Wilkins PR, Marsh HT, Endoscopic removal of a third ventricular cysticercal cyst, Br J Neurosurg 1998;12:452-454.

52. King JS, Hosobuchi Y. Cysticercus cyst of the lateral ventricle. Surg Neurol 1977;7:125-129.

RELATED ARTICLE: Key Points

* Clinical manifestations of neurocysticercosis are varied and nonspecific and are related to the number, size, and topography of the lesions.

* Several laboratory methods have been developed to detect host antibodies against circulating cysticercal antigens, but current data indicate that enzyme-linked immunosorbent assay and electroimmunotransfer blot tests are the most effective.

* Antihelminthic therapy including praziquantel (50 mg/kg/d in divided doses for 14 days) and albendazole (15 mg/kg/d for 1 month) has been the mainstay of treatment for parenchymal neurocysticercosis.

* Cysts in the subarachnoid spaces usually attain larger sizes than their parenchymal counterparts, but most are responsive to antiparasitic therapy.

* Management options for ventricular cysticercosis include antihelminthic therapy, cerebrospinal fluid shunting, and/or surgical removal of cysts.

Thomas G. Psarros, MD, Alexander Zouros, MD, and Caetano Coimbra, MD