Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 58, Num. 4, 2010, pp. 507-508

Neurology India, Vol. 58, No. 4, July-August, 2010, pp. 507-508

Editorial

Solitary cysticercus granuloma-treatment with albendazole: What is the optimal duration?

Singh Gagandeep, Murthy J.M.K

Department of Neurology, Dayanand Medical College, Ludhiana
Correspondence Address:Professor and Head, Department of Neurology, Dayanand Medical College, Ludhiana, 141001, gagandeep_si@yahoo.co.uk

Date of Acceptance: 21-Jul-2010

Code Number: ni10138

PMID: 20739782

DOI: 10.4103/0028-3886.68656

NI_485_10The era of antihelminthic treatment in neurocysticercosis (NCC) began in 1978 with the first use of praziquantel.^[1] Later in 1987, albendazole was introduced in the treatment of NCC. Treatment with albendazole for 1 month in 7 patients, who also served as historical controls, resulted in reduction of the cyst load by 25% at 1 month; and by another 14%, at 3 months. ^[2] Albendazole was found to be as effective as praziquantel, but more economical and convenient to administer. Initially, the dose and duration of albendazole (15 mg/kg/d for 30 days) in NCC was based on the experience of a related parasitic disorder, human echinococcosis. Subsequent small controlled and uncontrolled trials have shown that shorter duration of treatment (15 days and 7 days) results in reduced active cyst burden by 3% to 25% at 3 months. ^[3],[4] A randomized, double-blind trial of albendazole, 7 versus 14 days, found no difference in the efficacy as measured by the reduction in cyst load on computed tomography (CT) at 3 months after intervention. Subsequent to this study, 1 week of treatment has been purported to be effective, well tolerated and cost effective and the preferred duration of treatment in active parenchymal NCC (multiple lesions).

Intuitively, the argument in favor of longer duration of albendazole therapy in active parenchymal NCC is that sustained action over an extended period of time may lead to eradication of a greater number of lesions and thus higher cure-rates. The counter-intuitive argument against longer duration of albendazole therapy is that drug-related adverse events may be more and certainly cost would be four times greater.

Subsequent to the earlier small trials of albendazole, more trials have been undertaken and there is now Class I evidence for the effectiveness of short-duration albendazole therapy for active parenchymal NCC. ^[5] However, its efficacy in solitary cysticercus granuloma (degenerating forms) is uncertain. ^{[6],[7],[8],[9],[10]} In a meta-analysis of antihelminthic treatment in cysticercus granuloma (1-2 in number), which included 5 controlled clinical trials, the pooled odds ratio was 1.18, with wide confidence intervals (CIs) (95% CI, 0.82 to 1.71) on either side of unity. ^[11] This might imply a mild beneficial effect or lack thereof. Thus the efficacy of albendazole in cysticercus granuloma remains to be established. There is need for a well-designed study with sufficient sample size to prove or disprove the efficacy of albendazole in cysticercus granuloma (1-2 in number).

In this issue of the journal, Kaur et al.[12] report results of a randomized, open-labeled prospective trial of 7 versus 28 days of albendazole treatment in solitary cysticercus granuloma. The authors found no difference in the efficacy between the two regimens in terms of the proportion of subjects demonstrating complete resolution of the lesion on follow-up CT at 3 and 6 months, as well as the proportion of subjects with seizure recurrence in the follow-up at 6 months. The results of this study should be interpreted with caution. From the previously available controlled trials, it appears that the clinical benefit in terms of lesion resolution with albendazole is small. ^{[6],[7],[8],[9],[10]} This requires a large sample size to demonstrate any significant differences in the efficacy between the 1-week (short duration) and 4-week (long duration) treatments. It is possible that the sample size was small and this might have accounted for the lack of benefit of the longer duration of treatment, if any, and that the comparative trial was not adequately powered to detect the differences in the efficacy of the antihelminthic agent given for different periods of time.

The authors of this study did not report any side effects in either group. ^[12] In a previous comparative trial of 7 days versus 1 month of albendazole therapy in active parenchymal NCC, 92% of the subjects complained of headache, 24% had seizures in addition to rare complications like significant deterioration in neurological condition. ^[13] The absence of side effects in this study may be related to the fact that all the patients included had a single lesion. ^[12]

In view of the purported advantages of shorter duration of treatment, novel regimens have been proposed and tried in clinical trials, albeit small. A single-day praziquantel-based regimen has been evaluated in both active parenchymal NCC and solitary cysticercus granuloma. ^{[14],[15],[16],[17]} The rationale for this regimen is that praziquantel has a half-life of 2 hours. Furthermore, the antihelminthic agent has on interaction with dexamethasone, which reduces praziquantel levels by about 50%. By administering 3 doses of praziquantel (25 mg/kg, q8) 2 hours apart, it was argued that a high drug level can be maintained for a longer time sufficient to initiate destruction of the cysts. Dexamethasone was administered on the following day to avoid any interactions with praziquantel and at the same time to be able to limit the inflammatory exacerbations associated with praziquantel administration. The regimen unfortunately did not show any dramatic results in the solitary cysticercus granuloma group. ^[16]

Of the available randomized controlled trials of albendazole in solitary cysticercus granuloma, 4 trials followed a 28-day protocol; and only 1 trial used a 1-week protocol. ^{[7],[8],[9],[10]} The 1-week treatment trial failed to show efficacy of albendazole treatment; while of the 4 trials that followed 28-day protocol, 2 trials demonstrated significantly improved lesion resolution rates on follow-up imaging studies. ^[7],[8] These differences should not be attributed purely to the difference in the duration of albendazole treatment and might well be due to the difference in the study population or the trial methodology. The evidence thus is in favor of 28-day albendazole treatment in solitary cysticercus granuloma (Class II). From the available evidence, till we have an adequately clear picture based on sufficiently powered trials, we recommend longer-duration albendazole treatment in patients with solitary cysticercus granuloma and also in patients with two granulomas.

References

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13.	Garcia HH, Gilman RH, Horton J, Martinez M, Herrera G, Altamirano J, et al. Albendazole therapy for neurocysticercosis: A prospective double-blind trial comparing 7 versus 14 days of treatment. Cysticercosis Working Group in Peru. Neurology 1997;48:1421-7.  Back to cited text no. 13  [PUBMED]
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