Definitions of the levels of the recommendations (A, B, C, U) and classification of the evidence (Class I-IV) are provided at the end of the "Major Recommendations" field.
In Patients with Symptomatic Intraparenchymal Neurocysticercosis, is Cysticidal Therapy More Effective Than No Therapy, and Does it Affect Long-term Seizure Outcome?
Based on imaging findings in 4 Class I studies (3 concordant, 1 underpowered study failing to show an effect) and a meta-analysis of 2 Class I and 4 Class II studies, albendazole (400 mg twice daily [BID] for adults or weight-based dosing for either adults or children) is probably safe and effective in reducing both the number of cysts and long-term seizure frequency in adults and children with neurocysticercosis. In most studies, corticosteroids were coadministered, in varying dosages, and this combination appears effective. Data are insufficient to indicate whether corticosteroids are necessary in this setting.
The available studies have used different stratification methods for seizure analysis and different criteria for judging improvement in imaging. On the basis of the 3 Class I studies it appears albendazole plus corticosteroids decreases the number of active brain lesions relative to placebo and, on the basis of a meta-analysis of available data, decreases the number of patients with seizures, at modest cost. These findings appear to be consistent in adults and children.
Albendazole plus either dexamethasone or prednisolone should be considered for adults and children with neurocysticercosis, both to decrease the number of active lesions on brain imaging studies (Level B) and to reduce long-term seizure frequency (Level B).
In Patients with Symptomatic Intraparenchymal Neurocysticercosis, is Treatment with Corticosteroids More Effective Than No Treatment?
On the basis of one Class I study showing no benefit radiologically and ambiguous benefit clinically and one Class II/IV study showing benefit, there is insufficient evidence to recommend steroid treatment alone for patients with solitary intraparenchymal neurocysticercosis granulomata.
The effect of corticosteroid treatment alone in neurocysticercosis has not been widely studied. Most trials include a combination of cysticidal therapy and steroid treatment.
The evidence is insufficient to support or refute the use of steroid treatment alone in patients with intraparenchymal neurocysticercosis (Level U).
When During the Course of Antiparasitic Treatment Should Steroids be Started?
The Subcommittee found no studies to answer this question.
What is the Efficacy of Antiepileptic Drugs (AEDs) in Treating or Decreasing Occurrence of Subsequent Seizures Secondary to Intraparenchymal Neurocysticercosis, and What is the Optimal Time Course of AED Treatment for Seizures Secondary to Intraparenchymal Neurocysticercosis?
The Subcommittee found no studies to answer this question.
Given the well-established efficacy and safety of a broad range of AEDs and the frequency with which neurocysticercosis causes seizures, it is reasonable to treat these patients with AEDs at least until the active lesions have subsided.
Classification of Evidence for Therapeutic Intervention
Class I: A randomized, controlled clinical trial of the intervention of interest with masked or objective outcome assessment, in a representative population. Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences. The following are also required:
- Concealed allocation
- Primary outcome(s) clearly defined
- Exclusion/inclusion criteria clearly defined
- Adequate accounting for dropouts (with at least 80% of enrolled subjects completing the study) and crossovers with numbers sufficiently low to have minimal potential for bias.
- For noninferiority or equivalence trials claiming to prove efficacy for one or both drugs, the following are also required*
- The authors explicitly state the clinically meaningful difference to be excluded by defining the threshold for equivalence or noninferiority.
- The standard treatment used in the study is substantially similar to that used in previous studies establishing efficacy of the standard treatment (e.g., for a drug, the mode of administration, dose and dosage adjustments are similar to those previously shown to be effective).
- The inclusion and exclusion criteria for patient selection and the outcomes of patients on the standard treatment are comparable to those of previous studies establishing efficacy of the standard treatment.
- The interpretation of the results of the study is based upon a per protocol analysis that takes into account dropouts or crossovers.
Class II: A randomized controlled clinical trial of the intervention of interest in a representative population with masked or objective outcome assessment that lacks one criteria a–e above or a prospective matched cohort study with masked or objective outcome assessment in a representative population that meets b–e above. Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome is independently assessed, or independently derived by objective outcome measurement.**
Class IV: Studies not meeting Class I, II, or III criteria including consensus or expert opinion.
*Note that numbers 1-3 in Class Ie are required for Class II in equivalence trials. If any one of the three is missing, the class is automatically downgraded to Class III.
**Objective outcome measurement: an outcome measure that is unlikely to be affected by an observer's (patient, treating physician, investigator) expectation or bias (e.g., blood tests, administrative outcome data).
Classification of Recommendations
Level A = Established as effective, ineffective or harmful (or established as useful/predictive or not useful/predictive) for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.*)
Level B = Probably effective, ineffective or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population. (Level B rating requires at least one Class I study or two consistent Class II studies.)
Level C = Possibly effective, ineffective or harmful (or possibly useful/predictive or not useful/predictive) for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies.)
Level U = Data inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven.
* In exceptional cases, one convincing Class I study may suffice for an "A" recommendation if 1) all criteria are met, 2) the magnitude of effect is large (relative rate improved outcome >5 and the lower limit of the confidence interval is >2).