Neurocysticercosis: A Review.
One should consider the diagnosis of neurocysticercosis when a patient has new-onset seizures, common causes of seizures have been ruled out, and the patient is an immigrant from or a recent visitor to an area where T. solium is endemic such as Mexico, most other Latin American countries, Korea, Cambodia, Laos, and many African countries (St. Geme et al., 1993). Imaging tests play a crucial role in the diagnosis of neurocysticercosis. The imaging study most appropriate for detection of neurocysticercosis depends on both the stage of disease and the type of involvement. Both computed tomography (CT) and magnetic resonance (MR) are capable of detecting the findings that are either characteristic or highly suggestive of neurocysticercosis. In general, CT and MR scans are equivalent for the detection of the cyst and granuloma stage of the parenchymal form of neurocysticercosis (St. Geme et al., 1993). The CT scan is superior to the MR scan for detecting calcification, whereas MR has been found to be 4 times more sensitive than CT in the detection of active cysts (Dumois et al., 1993; St. Geme et al., 1993). As a general consideration, MR is a more expensive examination than CT and requires longer scanning times, which is an important issue with children.
Immunologic testing for antibodies to T. solium antigens can provide valuable diagnostic information (Dumois et al., 1993; St. Geme et al., 1993). The enzyme-linked immuno-transfer blot (EITB) assay is the serologic test of choice for confirming a clinical and radiographic presumptive diagnosis (Tsang, Brand, & Boyer, 1989; Wilson et al., 1991). In patients with multiple ([is greater than] 2) lesions, the test has more than 90% sensitivity (Wilson et al., 1991). Unfortunately, it is often negative in patients with a solitary lesion, and 75% of children fall into this category (Mitchell & Crawford, 1988).
Neurocysticercosis causes a variety of neurologic symptoms. The most common is seizures due to cysts in the brain parenchyma (Garcia et al., 1997). However, the clinical presentation is variable and usually depends on the number and location of cysts, the extent of the inflammatory reaction, and if the infection is active or inactive (Mehta et al., 1998). The neurologic manifestations at the time of clinical presentation, which may include seizures, headaches, focal neurological deficits, and manifestations of increased intracranial pressure, dictate the therapy selected (Kramer, 1995). Antihelminthic therapy is clearly indicated if the patient has arachnoiditis, hydrocephalus, or radiographic evidence of noncalcified, nonenhancing cystic lesions of the brain parenchyma (Dumois et al., 1993). Lesions that do not show significant contrast enhancement usually resolve within a few months with no drug therapy administered (Dumois et al., 1993; Mitchell & Crawford, 1988). Calcified cysts would not be affected by antihelminthic therapy, since these lesions signify already dead parasites.
There appears to be widespread controversy in the literature concerning treatment for neurocysticercosis. The first controversy is whether or not to treat neurocysticercosis. Secondly, if a decision is made to treat, then with what agent(s) and for how long. There are a couple of reasons why some believe that treatment of the active form of neurocysticercosis is not warranted. Both Carpio and colleagues (1995) and Kramer (1995) believe that previous reports of favorable response to treatment of neurocysticercosis with antihelminthic therapy are by no means definitive and may be a reflection of the natural history of the condition. In addition, both feel that rigorously conducted long-term, placebo-controlled trials with clinical endpoints, proper randomization, and predetermined statistical analysis and sample size calculations had not been performed at the time of their respective publications. However, Del Brutto (1995) sums up the pro-treatment point of view best when he states, "Some authors still claim that a double-blind, placebo-controlled trial is needed to measure the efficacy of the antihelminthic therapy. It should be remembered that the evaluation of a given therapeutic approach must be individualized according to the characteristics of the disease. In the case of neurocysticercosis, the objective evidence of disappearance of brain cysts (documented by CT) after a course with anticysticercal drugs and the obvious clinical improvement that such disappearance produces, provide reliable evidence of their efficacy. A double-blind, placebo-controlled trial would undoubtedly reinforce our knowledge on this subject but, pending such results, I consider that there is no reason to leave neurocysticercosis untreated when an effective, harmless, and inexpensive treatment exists." In addition, Vazquez and Sotelo (1992) found that the greatest reduction in seizure frequency occurred in the patients that were treated with antithelminthics versus those patients that were not treated at all. After 3 years of follow-up, 54% were seizure-free without anticonvulsants. Of the group that were not treated with cysticidal medications, none was seizure-free.
For many years, therapeutic approaches to neurocysticercosis were limited to steroids and surgery for intracranial hypertension (Alarcon, Escalante, Duenas, Montalvo, & Roman, 1989; Garcia et al., 1997; Nash & Neva, 1984). In 1978, praziquantel was introduced as the first effective antiparasitic drug for neurocysticercosis (Garcia et al., 1997). Praziquantel is an isoquinolone with a broad antihelminthic activity (Sotelo et al., 1990). Praziquantel selectively increases the permeability of the parasite cell membrane, which causes loss of intracellular calcium and leads to contractions, paralysis, and eventual death of the parasite (Mehta et al., 1998). The dosage most commonly cited for treating neurocysticercosis is 50 mg/kg/day orally, in three divided doses, with meals for at least 15 days (Sotelo, Escobedo, & Penagos, 1988; Takayanagui & Jardim, 1992). Some of the adverse effects of praziquantel include drowsiness, headache, mild abdominal pain, dizziness, nausea, and diarrhea (Carpio, Santillan, Leon, Flores, & Hauser, 1995; Mehta et al., 1998).
Albendazole, the [5-(propylthio)- 1H-benzimidazole-2-y1] carbamic acid methyl ester (Sotelo, Escobedo, et al., 1988), was first used for neurocysticercosis in 1987 (Garcia et al., 1997). Its discovery was due to the motivated search to find new anticysticercal drugs because of the high cost of praziquantel and its numerous drug interactions (Del Brutto, 1995). Albendazole selectively causes degeneration of parasite cytoplasmic microtubules, which eventually leads to decreased adenosine triphosphate levels and energy depletion (Mehta et al., 1998). A big debate surrounding neurocysticercosis is if one decides to treat using albendazole, which dosing regimen is optimal? Reports in the literature use 3-day (Alarcon et al., 1989), 7-day (Garcia et al., 1997), 8-day (Cruz, Cruz, Carrasco, & Horton, 1995; Sotelo, Penagos, Escobedo, & Del Brutto, 1988; Sotelo et al., 1990), 14-day (Garcia et al., 1997), 15-day (Cruz et al., 1995; Rajshekhar, 1993), 21-day (Takayanagui & Jardim, 1992), and 30-day (Alarcon et al., 1989; Cruz et al., 1995; Garcia et al., 1997; Sotelo, Penagos, et al., 1988; Sotelo et al., 1990) courses of therapy. The most recent literature uniformly demonstrate that a 7 to 8-day regimen appears to be the most favorable. Regardless of length of treatment, most published studies recommend a dose of 400 mg orally, twice daily with meals. In lighter patients ([is less than] 60 kg), 15 mg/kg/day (to a maximum of 800 mg/day), also in two divided doses, is recommended. Albendazole, whose oral absorption is ordinarily poor, should be taken with meals (Mehta et al., 1998). A fatty meal may increase albendazole concentration fivefold on average, but is not required. Headache, nausea, and vomiting, which occur in 6%-11% of patients, are the most common adverse effects of albendazole (Garcia et al., 1997; Mehta et al., 1998).
Studies that have compared the efficacy of praziquantel and albendazole have shown that most cases (80%-90%) respond well to both drugs. However, the efficacy of albendazole in terms of parenchymal brain cyst eradication, achieving higher concentrations in the cerebrospinal fluid, less likely to interact with other drugs, clinical improvement of patients, and cost savings is superior to that of praziquantel (Cruz et al., 1995; Sotelo, Escobedo, et al., 1988; Sotelo et al., 1990; Takayanagui & Jardim, 1992).
The decision of whether or not to give dexamethasone concomitantly with antihelminthic therapy is also somewhat controversial in the literature. Because antihelminthics are larvicidal, varying degrees of inflammation and surrounding edema should be anticipated (St. Geme et al., 1993). However, there is a general consensus that such reactions are usually mild, transient, and may be ameliorated with common analgesics or antiemetics, avoiding the routine use of corticosteroids in every case (Del Brutto, 1995). Thus, dexamethasone therapy should be reserved only for those patients who develop neurologic symptoms and secondary reactions (headache, vomiting, seizures) attributed to the acute inflammation triggered by the destruction of the cysticerci (Del Brutto, 1995; St. Geme et al., 1993; Sotelo, Escobedo, et al., 1988; Sotelo et al., 1990). If dexamethasone is used, short term therapy is initiated on the second or third day of cysticidal therapy and stopped 2 or 3 days later. The acute symptoms of cerebral edema usually present within the first 24 to 48 hours of antihelminthic therapy (St. Geme et al., 1993), so hospitalization is recommended for the first 72 hours of treatment, and then therapy can be completed at home.
If dexamethasone is used, it affects the serum concentrations of the antihelminthic therapy when albendazole is given concomitantly with dexamethasone, the serum and CSF metabolite concentrations are increased by up to 50% (Jung, Hurtado, Medina, Sanchez, & Sotelo, 1990), whereas the plasma levels of praziquantel decrease 50% when given dexamethasone simultaneously (Vazquez, Jung, & Sotelo, 1987).
Another drug therapy that should be considered in neurocysticercosis is anticonvulsants. Since seizures occur in 50%-87% of patients, anticonvulsants are almost always used (Del Brutto et al., 1992; Sotelo et al., 1985; Vazquez & Sotelo, 1992). Most patients have seizures as the sole manifestation of the disease. Anticonvulsant therapy with either phenytoin or carbamazepine is usually started on the first day of treatment (Del Brutto et al., 1992). The anticonvulsants are then titrated to a therapeutic level. The anticonvulsant duration of therapy depends on the seizure symptomology of the patient.
In a patient with new-onset seizures from an area where T. solium is endemic and whose CT scan reveals high density or cystic lesions, the diagnosis of neurocysticercosis should be considered. Considerations on deciding whether to initiate antihelminthic therapy once a diagnosis of neurocysticercosis has been established should include the number of cysts present, whether the cysts are viable or calcified, and whether the patient is symptomatic or asymptomatic. Patients who have multiple cysts (3) are commonly associated with severe disease and are likely to benefit from antihelminthic therapy. Cysts that are degenerating or have died, generally do not require cysticidal medication. Treatment with dexamethasone should be considered in patients whose symptoms are attributed to acute inflammation. And finally, anticonvulsants should be used for the patients who present with seizures.
* Albendazole should be given with food.
* Absorption of phenytoin is impaired when given concurrently to patients who are receiving continuous nasogastric feedings. A method to resolve this is to withhold the administration of nutritional supplements for 1-2 hours before and after each phenytoin dose.
* Monitoring parameters of phenytoin:
-- blood pressure and vital signs (for intravenous infusion)
-- plasma level monitoring
-- CBC with platelet count (at baseline, then every 2 weeks until stabilized, then every month for 12 months, then every 3 months)
-- liver function tests (at baseline)
* Shake phenytoin oral suspension well prior to each dose.
* Phenytoin IV infusion rate: 1 mg/kg/min or a maximum of 50 mg/minute.
* Do not give phenytoin IM.
* Observe patient taking carbamazepine for excessive sedation.
* Monitoring parameters of carbamazepine:
-- CBC with platelet count (at baseline, then monthly for 2 months, then yearly thereafter)
-- liver function tests (at baseline)
-- serum drug concentration
* In general, when checking therapeutic drug levels, a trough concentration is usually preferred due to its being more consistent versus the peak.
Alarcon, F., Escalante, L., Duenas, G., Montalvo, M., & Roman, M. (1989). Neurocysticercosis: Short course of treatment with albendazole. Archives of Neurology, 46, 1231-1236.
Carpio, A., Santillan, F., Leon, R, Flores, C., & Hauser, W.A. (1995). Is the course of neurocysticercosis modified by treatment with antihelminthic agents? Archives of Internal Medicine, 155, 1982-1988.
Cruz, I., Cruz, M.E., Carrasco, F., & Horton, J. (1995). Neurocysticercosis: Optimal dose treatment with albendazole. Journal of the Neurological Sciences, 133, 152-154.
Del Brutto, O.H., Santibanez, R., Noboa, C.A., Aguirre, R., Diaz, E., & Alarcon, T.A. (1992). Epilepsy due to neurocysticercosis: Analysis of 203 patients. Neurology, 42, 389-392.
Del Brutto, O.H. (1995). Medical treatment of cysticercosis - Effective. Archives of Neurology, 52, 102-104.
Dumois, J.A., Whitman, B.W., & Vezina, L.G. (1993). Profuse neurocysticercosis with minimal signs and a favorable outcome. The Pediatric Infectious Disease Journal, 12, 885-887.
Garcia, H.H., Gilman, R.H., Horton, J., Martinez, M., Herrera, G., Altamirano, J., Cuba, J.M., Rio-Saavedra, N., Verastegui, M., Boero, J., & Gonzalez, A.E. (1997). Albendazole therapy for neurocysticercosis: A prospective double-blind trial comparing 7 versus 14 days of treatment. Neurology, 48, 1421-1427.
Jung, H., Hurtado, M., Medina, M.T., Sanchez, M., & Sotelo, J. (1990). Dexamethasone increases plasma levels of albendazole. Journal of Neurology, 237, 279-280.
Kramer, D. (1995). Medical treatment of cysticercosis - Ineffective. Archives of Neurology, 52, 101-102.
Mehta, S.S., Hatfield, S., Jessen, L., & Vogel, D. (1998). Albendazole versus praziquantel for neurocysticercosis. American Journal of Health-System Pharmacy, 55, 598-600.
Mitchell, W.G., & Crawford, T.O. (1988). Intraparenchymal cerebral cysticercosis in children: Diagnosis and treatment. Pediatrics, 82, 76-82.
Nash, T.E., & Neva, F.A. (1984). Recent advances in the diagnosis and treatment of cerebral cysticercosis. The New England Journal of Medicine, 311, 1492-1496.
Rajshekhar, V. (1993). Albendazole therapy for resistant solitary cysticercosis granulomas in patients with seizures. Neurology, 43, 1238-1240.
Sotelo, J., Escobedo, F., & Penagos, R (1988). Albendazole vs. praziquantel therapy of neurocysticercosis: A controlled trial. Archives of Neurology, 45, 532-534.
Sotelo, J., Guerrero, V., & Rubio, F. (1985). Neurocysticercosis: A new classification based on active and inactive forms. A study of 753 cases. Archives of Internal Medicine, 145, 442-445.
Sotelo, J., Penagos, R, Escobedo, F., & Del Brutto, O.H. (1988). Short course of albendazole therapy for neurocysticercosis. Archives of Neurology, 45, 1130-1133.
Sotelo, J., Del Brutto, O.H., Penagos, P., Escobedo, F., Torres, B., Rodriguez-Carbajal, J., & Rubio-Donnadieu, F. (1990). Comparison of therapeutic regimen of anticysticercal drugs for parenchymal brain cysticercosis. Journal of Neurology, 237, 69-72.
St. Geme, J.W., Maldonado, Y.A., Enzmann, D., Hotez, P.J., Overturf, G.D., & Schantz, P.M. (1993). Consensus: Diagnosis and management of neurocysticercosis in children. The Pediatric Infectious Disease Journal, 12, 455-461.
Takayanagui, O.M., & Jardim, E. (1992). Therapy for neurocysticercosis: comparison between albendazole and praziquantel. Archives of Neurology, 49, 290-294.
Tsang, V.C.W., Brand, J.A., & Boyer, A.E. (1989). An enzyme-linked immunoelectrotransfer blot assay and glycoprotein antigens for diagnosing human cysticercosis (Taenia solium). The Journal of Infectious Diseases, 159, 50-59.
Vazquez, M.L., Jung, H., & Sotelo, J. (1987). Plasma levels of praziquantel decrease when dexamethasone is give simultaneously. Neurology, 37, 1561-1562.
Vazquez, V., & Sotelo, J. (1992). The course of seizures after treatment for cerebral cysticercosis. The New England Journal of Medicine, 327, 696-701.
Wilson, M., Bryan, R.T., Fried, J.A., Ware, D.A., Schantz, P.M., Pilcher, J.B., & Tsang, V.C.W. (1991). Clinical evaluation of the cysticercosis enzyme-linked immunoelectrotransfer blot in patients with neurocysticercosis. The Journal of Infectious Diseases, 164, 1007-1009.
The Pediatric Drug Information column publishes drug information, questions, reviews of new drugs or new indications for drugs, drug interactions, drug administration issues, and pharmacotherapy reviews of diseases. Suggestions for future columns or submissions should be sent to: Elizabeth Farrington, PharmD, BCPS; Clinical Specialist-Pediatrics; Department of Pharmacy; UNC Hospitals; 101 Manning Drive; Chapel Hill, NC 27514.
Greg A. Dunsworth, MS, BS, is a PharmD candidate and lab technician, University of North Carolina, Chapel Hill, NC.
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||infection by intestinal tapeworm|
|Author:||Dunsworth, Greg A.|
|Date:||May 1, 1999|
|Previous Article:||Understanding Alcohol Abuse in American Indian/Alaskan Native Youth.|
|Next Article:||PEDIATRIC MANAGEMENT PROBLEMS.|