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Antiepileptic drugs for seizure control in people with neurocysticercosis
and Cochrane Epilepsy GroupAbstract
Background
Neurocysticercosis is the most common parasitic infection of the brain. Epilepsy is the most common clinical presentation, though it may also present with headache, symptoms of raised intracranial pressure, hydrocephalus and ocular symptoms depending upon the localisation of the parasitic cysts. Anthelmintic drugs, anti‐oedema drugs, such as steroids, and antiepileptic drugs (AEDs) form the mainstay of treatment.
This is an updated version of the original Cochrane Review published in 2015, Issue 10.
Objectives
To assess the effects (benefits and harms) of AEDs for the primary and secondary prevention of seizures in people with neurocysticercosis.
For the question of primary prevention, we examined whether AEDs reduce the likelihood of seizures in patients who have neurocysticercosis but have not had a seizure.
For the question of secondary prevention, we examined whether AEDs reduce the likelihood of further seizures in patients who have had at least one seizure due to neurocysticercosis.
As part of primary prevention studies, we also aimed to examine which AED has been found to be beneficial in people with neurocysticercosis in terms of duration, dose and side‐effect profile.
Search methods
For the latest update of this review, we searched the following databases on 8 July 2019: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to July 05, 2019) and LILACS (1982‐ ). CRS Web includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised or quasi‐randomised, controlled trials from Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We also checked the references lists of identified studies, and contacted experts in the field and colleagues to search for additional studies and for information about ongoing studies.
Selection criteria
Randomised and quasi‐randomised controlled trials.
Single‐blind, double‐blind or unblinded studies were eligible for inclusion.
Data collection and analysis
Two review authors screened all citations for eligibility (MS screened the initially identified 180 citations, MF and BDM screened the 48 citations identified for the purpose of this update).Two review authors independently extracted data and evaluated each study for risk of bias.
Main results
We did not find any trials that investigated the role of AEDs in preventing seizures among people with neurocysticercosis, presenting with symptoms other than seizures.
We did not find any trials that evaluated evaluating individual AEDs in people with neurocysticercosis.
We found one trial, comparing two AEDs in people with solitary neurocysticercosis with seizures. However, we excluded this study from the review as it was of poor quality.
We found four trials that compared the efficacy of short term versus longer term AED treatment for people with solitary neurocysticercosis (identified on computed tomography (CT) scan) presenting with seizures. In total, 466 people were enrolled. These studies compared various AED treatment durations, six, 12 and 24 months. The risk of seizure recurrence with six months treatment compared with 12 to 24 months treatment was not statistically significant (odds ratio (OR) 1.34 (95% confidence interval (CI) 0.73 to 2.47; three studies, 360 participants; low‐certainty evidence)). The risk of seizure recurrence with six to 12 months compared with 24 months treatment was not statistically significant (OR 1.36 (95% CI 0.72 to 2.57; three studies, 385 participants; low‐certainty evidence)).
Two studies co‐related seizure recurrence with CT findings and suggested that persistent and calcified lesions had a higher recurrence risk and suggest longer duration of treatment with AEDs. One study reported no side effects, while the rest did not comment on side effects of drugs. None of the studies addressed the quality of life of the participants.These studies had certain methodological deficiencies such as a small sample size and a possibility of bias due to lack of blinding, which affect the results of this review.
Authors' conclusions
Despite neurocysticercosis being the most common cause of epilepsy worldwide, there is currently no evidence available regarding the use of AEDs as seizure prophylaxis among people presenting with symptoms other than seizures. For those presenting with seizures, there is no reliable evidence regarding the duration of treatment required. There is therefore a need for large scale randomised controlled trials to address these questions.
Plain language summary
Treatment of epilepsy in people with neurocysticercosis
Background
Neurocysticercosis is a common infection of the brain caused by the larvae of the pork tapeworm, migrating to the brain. Seizures are the most common symptom, although some people may present with headache, vomiting or other symptoms of brain swelling.
This review investigates the usefulness of antiepileptic drugs (AEDs) in preventing seizures in people who did not have seizures but presented with these other symptoms. We also examined the usefulness of the AEDs in people with epilepsy due to neurocysticercosis in terms of choice of drug, dosage, duration of treatment, cost, side effects and the quality of life.
Study characteristics
Four trials with a total of 466 participants were reviewed, focusing on the comparison of 'short duration' and 'long duration' of AEDs drugs in people with a single cerebral lesion. These trials compared various durations of AED therapy: six to 12 months as short duration and 12 to 24 months as long‐duration therapy.
Key results
No statistically significant benefit of one duration of AED over the other (six, 12 or 24 months) could be demonstrated. In people with calcified cysts, longer duration of therapy may be preferable.
All four included trials, enrolled people with a single brain lesion. The findings of our review cannot be extrapolated to people with multiple cysts or with cysts in unusual parts of the brain.
The evidence is current to July 2019.
Summary of findings
Background
This review is an update of a previously published review in The Cochrane Database of Systematic Reviews (2015, Issue 10; Sharma 2015) on Antiepileptic drugs for seizure control in people with neurocysticercosis.
Description of the condition
Neurocysticercosis is an infection of the central nervous system by Taenia solium cysticerci. Taenia solium is an intestinal parasite that infests animals such as pigs and has a secondary life cycle in human beings. Ingestion of the parasite eggs, excreted in the faeces of the pig or an infested human host, can result in cysticercosis. After ingestion, the eggs can migrate from the gut to lodge in various tissues of the body, where they form cysts. Cysticercosis is usually asymptomatic. When symptoms of cysticercosis do develop it is usually due to cysticercal invasion of the central nervous system and eyes.
Neurocysticercosis is the most common parasitic infection of the brain. The prevalence of neurocysticercosis is high in low‐ and middle‐income countries where there is close proximity between humans and pigs. It is common in much of South and Central America, China, the Indian subcontinent, South‐East Asia, and sub‐Saharan Africa. It affects around 50 million people worldwide (Dhawan 2011), with men and women equally affected, and has a peak incidence at ages 30 to 40 years (Zafar 2013). However, migration of populations has changed the epidemiology of the disease and the prevalence of the disease in developed countries is now increasing.
The presentation of neurocysticercosis is related to the site of invasion by the cyst, the stage of the parasite and the host immune response. Cysts in the cerebral parenchyma are noted to have four stages ‐ vesicular stage, colloidal stage, granulomatous stage and calcified stage (DeGiorgio 2004; García 2002). The vesicular stage is the viable cyst which is associated with a minimal immune response and hence shows limited enhancement after intravenous contrast in neuroimaging. Although an eccentric scolex may be seen with magnetic resonance imaging (MRI) within the cyst at this stage. The second stage is where the viable cyst ruptures to release its fluid in the surrounding parenchyma. This fluid stimulates an intense immune response in the host and results in perilesional oedema which is associated with contrast enhancement on MRI. This is the most common clinically evident stage of neurocysticercosis. Cellular response to this stage results in the next granulomatous (or nodular) stage during which some perilesional oedema may still be visible. The final stage of destruction and calcification may result in permanent calcific lesions in the parenchyma. There may also be a conglomeration of cysts in the basal cisterns (termed racemose cysts). Single cysts are usually up to 20 mm in diameter. Giant cysts more than 50 mm in diameter may produce space‐occupying effects. Cysts may also occur within the ventricles or in the spinal cord.
Epilepsy is an important neurological condition characterised by recurrent seizures, and has an estimated annual incidence of 50/100,000 and a prevalence of five to 10/1000 in the developed world (Sander 1996). Approximately three per cent of the population will suffer from seizures at some point in their lives (Hauser 1992). Epilepsy can have several causes, for example, head injury, infections of the brain, tumours, infarcts and haemorrhage. Neurocysticercosis is an important cause of symptomatic seizures or secondary epilepsy among children and adults in many low‐ and middle‐income countries. In some countries neurocysticercosis has been reported to be the cause of 20% to 70% of cases of symptomatic epilepsy (Daniels 2006; Del Brutto 2005; Palacio 1998; Rajshekhar 2006). In some Asian countries, neurocysticercosis causes up to 50% cases of epilepsy Rajshekhar 2003), and up to 90% of cases of symptomatic seizures in children (Singhi 2000).
Seizures are the most common first presenting feature of neurocysticercosis, occurring in nearly 70% to 90% of patients (DeGiorgio 2004). The seizures are usually partial seizures, with or without secondary generalisation (Del Brutto 1992; Singhi 2000). Host immune response (resulting in oedema and/or gliosis surrounding the cysts) and calcification are the reasons for epileptogenesis (the gradual process during which a previously normal brain develops epilepsy) in neurocysticercosis (Pradhan 2000). Multiple parenchymal cysts are associated with more frequent seizures (Ferreira 2002). A smaller but significant number of patients may present with severe and recurrent headaches. Localisation in the ventricles or in the basal cisterns may result in development of hydrocephalus causing severe headache and features of raised intracranial pressure. In addition, cysticercostic encephalitis is a rare clinical presentation of neurocysticercosis (García 2002).
The diagnosis of neurocysticercosis is established on the basis of clinical presentation and computed tomography (CT) scan or MRI. Diagnostic criteria proposed by Rajshekhar and Brutto (Del Brutto 2001; Rajshekhar 2003) includes these features and can be used to define the disease The clinical and radiological diagnosis can be supported by serological tests such as enzyme‐linked immunosorbent assay (ELISA) and enzyme‐linked immuno transfer blot test (ELITB), which have been found to be highly specific for the diagnosis (Dhawan 2011).
Description of the intervention
As seizures are the most common presentation of neurocysticercosis, antiepileptic drugs (AEDs) are often used. The duration of AED therapy has been based on expert opinions or consensus. Most experts recommend that AEDs be continued until the epileptogenic focus, in the form of the oedema or the degenerating cyst, resolves completely. This may be a variable period of up to six months. However, as some of the lesions may resolve as a calcified lesion in the parenchyma, they may continue to be a focus for seizures. The benefit of longer‐term AED therapy on seizure frequency has not been established (Gupta 2002; Thussu 2002; Verma 2006). Seizure recurrence in people with neurocysticercosis is usually associated with the presence of multiple parenchymal cysts, frequent seizures before the start of treatment with AEDs, and persistent calcification (Del Brutto 1996; Gupta 2002; Rajshekhar 2004; Thussu 2002). Monotherapy with carbamazepine or phenytoin is the common choice for seizure control. A small proportion may require polytherapy (Rajshekhar 2004).
How the intervention might work
AEDs are important in the control of seizures, which are the most common presentation of neurocysticercosis. These drugs help to prevent the recurrence of seizures in patients with symptomatic epilepsy secondary to neurocysticercosis and may have a role in primary prevention of seizures in people with neurocysticercosis who present with features other than seizures, such as headache or altered behavior.
Why it is important to do this review
The management of an individual with neurocysticercosis imposes a great burden on the economy of the world, costing an estimated 0.0037% of the gross national product for one treatment of all the neurocysticercosis patients in one country (Murthy 2007; Pal 2000). Solitary neurocysticercosis is essentially self‐limiting and presents clinically when the viable cysts actually start degenerating to produce an immune response. The use of anthelmintic treatment has been a subject of debate and is the topic of another Cochrane Review (Abba 2010). Short courses of steroids (oral prednisolone) are used to control the host response and pericystic oedema.
For people with symptomatic epilepsy secondary to neurocysticercosis, there are no systematic reviews on which AED to use, what dosage to prescribe, or how long to treat for. In addition, for those with neurocysticercosis who present with symptoms other than seizures, there are no systematic reviews on the use of AEDs to prevent seizures occurring. Hence, we undertook a systematic review of the role of AEDs in the treatment of people with neurocysticercosis presenting with or without seizures.
Objectives
To assess the effects (benefits and harms) of antiepileptic drugs (AEDs) for the primary and secondary prevention of seizures in people with neurocysticercosis.
- For the question of primary prevention, we examined whether AEDs reduce the likelihood of seizures in patients who have neurocysticercosis but have not had a seizure.
- For the question of secondary prevention, we examined whether AEDs reduce the likelihood of further seizures in patients who have had at least one seizure due to neurocysticercosis.
- As part of primary prevention studies, we also aimed to examine which AED has been found to be beneficial in people with neurocysticercosis in terms of duration, dose and side‐effect profile.
Methods
Criteria for considering studies for this review
Types of studies
Randomised and quasi‐randomised controlled trials.
Single‐blind, double‐blind or unblinded studies were eligible for inclusion.
For studying primary prevention, we planned to include studies where individuals with neurocysticercosis presented with symptoms other than seizures, such as headache or behavioural changes.
For secondary prevention, we planned to include studies where the participants had neurocysticercosis with seizures prior to randomisation.
Types of participants
We included studies of people with neurocysticercosis, diagnosed on the basis of neuroimaging findings, with or without additional serological or histopathological confirmation.
We excluded studies on neurocysticercosis at extracerebral sites.
The participants were of all age groups (children and adults) and both genders. The participants may have had any type of seizures associated with neurocysticercosis or presented with symptoms other than seizures.
Types of interventions
The intervention group may have received any of the currently marketed AEDs, in addition to the usual treatment for neurocysticercosis (anthelmintics or steroids, or both). The controls may have received placebo or only the usual treatment for neurocysticercosis without AEDs. The AEDs may have been a single drug (monotherapy) or in combination. The duration of treatment may have been short (a few weeks or months) or prolonged (years).
Types of outcome measures
Primary outcomes
- Proportion of individuals experiencing seizures.
- Time to first seizure post randomisation.
Secondary outcomes
- Proportion of individuals who were seizure free for a specific time period (12 or 24 months).
- Proportion of individuals who withdrew from treatment.
- Proportion of individuals who developed drug‐related side effects or complications.
- For studies comparing short versus long duration of treatment, proportion of individuals who were seizure free with each treatment policy.
- Quality of life (measured by validated scales).
- Cost of therapy.
- Requirement for hospitalisation, need for intensive care treatment and length of hospitalisation.
- Mortality.
Search methods for identification of studies
We attempted to identify all relevant trials regardless of language or publication status (published or unpublished, in press, or in progress).
Electronic searches
Searches for the original review were run in April 2014. Subsequent searches were run in May 2015, December 2016, and June 2018. For the latest update, we searched the following databases on 8 July 2019.
- Cochrane Register of Studies (CRS Web), using the search strategy outlined in Appendix 1.
- MEDLINE (Ovid, 1946 to July 05, 2019), using the search strategy outlined in Appendix 2.
- LILACS (1982‐ ), using the search strategy outlined in Appendix 3.
CRS Web includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised or quasi‐randomised, controlled trials from Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP).
Searching other resources
We also checked the references list in the selected studies and tried to contact researchers in the field to look at unpublished data. We contacted experts in the field and colleagues and asked if they were aware of any studies which we may have missed in our searches. We also tried to identify any ongoing studies from registries of clinical trials.
Data collection and analysis
We analysed the data using Cochrane's Review Manager software,RevMan 5.3 (RevMan 2014). The primary analysis was intention‐to‐treat analysis. We calculated odds ratio (OR) for dichotomous data (proportion of individuals experiencing seizures, seizure free for a specific time period (12 or 24 months), withdrew from treatment, developed drug‐related side effects or complications, were seizure‐free with each treatment policy, mortality), and planned to use mean difference (MD) for continuous data, if any continuous data were identified (quality of life, cost of treatment). We intended to evaluate time to first seizure after randomisation by hazard ratios (HRs). We assessed precision using 95% confidence intervals (CIs).
We stratified the analysis by treatment comparison. We also considered the duration of the drugs used, co‐medications used and the length of follow‐up.
Selection of studies
The review authors (MS, MF and BDM) independently screened all citations and abstracts and evaluated the eligibility of each study for the review. MS screened the initially identified 180 citations, MF and BDM screened the 48 citations identified for the purpose of this update. We included studies on the basis of the criteria earlier described in Criteria for considering studies for this review. We excluded studies that were not eligible and documented the reasons for exclusion.
Data extraction and management
Two review authors (MS, AM) independently extracted data using a tailored data extraction form. We summarised and coded data on study design, participant characteristics, interventions, and outcomes and entered them into RevMan (RevMan 2014). We resolved any discrepancies between data extracted by the two authors by discussion and by referring to the third review author.
We extracted the following data.
- Trial factors:
- study setting, country and year of study;
- study design;
- randomisation method;
- blinding;
- duration of study;
- duration of follow‐up.
- Participants:
- number in each group;
- age and sex distribution per randomised group;
- seizure type and frequency per randomised group;
- number of seizures before randomisation in each group;
- other neurologic deficits;
- neuroimaging data: location of lesion; number of lesions‐solitary or multiple, nature of cyst ‐ live or dying or calcified.
- Type of intervention:
- AED studied;
- number of drugs used;
- duration of AED;
- adjunctive medications used in each group.
- Outcome measures (as described earlier).
- Withdrawals from study.
Assessment of risk of bias in included studies
Two review authors (MS, AM) assessed each trial independently. We resolved any disagreements by consensus, or with consultation of a third party (TS) in case of disagreement. We assessed risk of bias using Cochrane's 'Risk of bias' tool (Higgins 2011).
We used the following criteria.
- Was the allocation sequence adequately generated?
- Was the allocation adequately concealed?
- Was knowledge of the allocated intervention adequately prevented during the study?
- Were incomplete outcome data adequately addressed?
- Are reports of the study free of suggestion of selective outcome reporting?
- Was the study apparently free of other problems that could put it at a high risk of bias?
We used individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). A 'Risk of bias' graph figure and 'Risk of bias' summary figure can be accessed here (Figure 1; Figure 2).
We planned to explore the influence of individual 'Risk of bias' criteria in a sensitivity analysis.
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Measures of treatment effect
We measured treatment effect as the proportion of individuals in each group who were seizure free for a specific time period (six,12 or 24 months). We calculated ORs for dichotomous data and planned to use MD for continuous data. We assessed precision using 95% CIs.
We planned to measure the adverse effect of treatment as the proportion of individuals withdrawn from the study due to adverse effects of the drugs. We also planned to try to measure and compare the adverse effects between short and long duration of treatment in studies that compared short and long duration of treatment.
We carried out an analysis of three studies comparing six months AED with 12 to 24 months AED and of three studies comparing six to 12 months versus 24 months AED therapy.
Unit of analysis issues
We intended to take into account the level at which randomisation occurred, such as cross‐over trials, cluster‐randomised trials and multiple observations for the same outcome. However, none of the studies included in the review are cross‐over or cluster‐randomised trials.
Dealing with missing data
We procured the complete article for collection of data. In case of missing data (number of patients excluded, reasons), we contacted the principal investigator of the study by email. Up until the time of writing the review, we had not received any replies.
Assessment of heterogeneity
We assessed heterogeneity between trials by examining the forest plot, and using the I2 statistic for heterogeneity, where an I2 greater than 50% indicates substantial heterogeneity
We assessed clinical heterogeneity by comparing the differences in demographics, type and number of seizures, type of AED used, dosages and duration of treatment and radiological data in the various studies.
Assessment of reporting biases
We assessed the included studies for reporting bias by evaluating the exclusion criteria in the study and also by evaluating the dropout rate and noting the reasons for it. We also assessed the probability of publication bias by examining a funnel plot for asymmetry.
Data synthesis
We combined dichotomous data by the method of Mantel Haenzsel using a fixed‐effect model.
Subgroup analysis and investigation of heterogeneity
We had planned to undertake subgroup analysis for the following subgroups:
- individuals with a single granuloma and those with multiple cerebral granulomas;
- individuals with neurocysticercosis treated with monotherapy and polytherapy;
We did not find any studies comparing treatment in people with single and multiple granulomas or that compared monotherapy versus polytherapy.
Sensitivity analysis
We carried out a sensitivity analysis to test the robustness of meta‐analysis.
Summarising and interpreting results
Two 'Summary of findings' tables have been created; one table for each comparison (six months AED treatment versus 12 to 24 months AED treatment and six to 12 months AED treatment versus 24 months AED treatment), including the primary outcome of proportion of individuals experiencing seizure recurrence (Table 1, Table 2). The other primary outcome of the review, time to first seizure after randomisation was not reported in any of the included studies. If this outcome is reported in included studies in future updates of the review, it will be added to the 'Summary of findings' tables. The certainty of the evidence was determined using the GRADE approach (GRADEPro 2004); where evidence was downgraded in the presence of high risk of bias in at least one trial, indirectness of the evidence, unexplained heterogeneity or inconsistency, imprecision of results, high probability of publication bias. Evidence was downgraded by one level if the limitation was considered serious and two levels if considered very serious; as judged by the review authors.
Summary of findings for the main comparison
| Short duration AEDs (six months) compared with long duration AEDs (12 to 24 months) for seizure control in people with neurocysticercosis | ||||||
| Patient or population: people with neurocysticercosis Settings: outpatients, in India Intervention: short duration AEDs (6 months) Comparison: long duration AEDS (12 to 24 months) | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of Participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Long duration AEDs (12 to 24 months) | Short duration AEDs (6 months) | |||||
| Seizure control Seizure recurrence Follow‐up: median 12 months | Study population | OR 1.34 (95% CI 0.73 to 2.47) | 360 (3 studies) | ⊕⊕⊝⊝ low1 | OR > 1 indicates seizure recurrence is more likely on short duration AEDs (6 months) | |
| 121 per 1000 | 162 per 1000 (88 to 299 per 1000) | |||||
| Assumed Risk: The event rate in the long duration AEDs group multiplied by 1000. The event rate is the proportion of the total, in which the event occurred. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio; | ||||||
| GRADE Working Group grades of evidence High certainty: Further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: We are very uncertain about the estimate. | ||||||
1 Down‐graded twice due to lack of blinding of participants and researchers in all the included studies, unclear risk of bias in patient concealment, and lack of applicability.
Summary of findings 2
| Six to 12 months AED treatment compared with 24 months AED treatment for seizure control in people with neurocysticercosis | ||||||
| Patient or population: people with neurocysticercosis Settings: outpatients, in India Intervention: 6 to 12 months AED treatment Comparison: 24 months AED treatment | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of Participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| 24 months AED treatment | 6 to 12 months AED treatment | |||||
| Seizure control Seizure recurrence Follow‐up: 18 months | Study population | OR 1.36 (95% CI 0.72 to 2.57) | 385 (3 studies) | ⊕⊕⊝⊝ low1,2 | OR > 1 indicates seizure recurrence is more likely on 6 to 12 months AED treatment | |
| 103 per 1000 | 140 per 1000 (74 to 264 per 1000) | |||||
| Assumed Risk: The event rate in the long duration AEDs group multiplied by 1000. The event rate is the proportion of the total, in which the event occurred. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio; | ||||||
| GRADE Working Group grades of evidence High certainty: Further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: We are very uncertain about the estimate. | ||||||
1 Down‐graded twice due to lack of blinding of participants and researchers in all the included studies, unclear risk of bias in patient concealment, and lack of applicability.
2 Inconsistency in report of withdrawals and reasons for them
Results
Description of studies
The review authors (MS, MF, BDM) independently reviewed the results of the electronic search to identify relevant trials for the complete review.
Results of the search
A total of 228 records were identified through database searching, including 48 newly identified trials and a further three records were identified through other sources. We removed duplicate citations and obviously irrelevant items (i.e. not reports of trials), trials studying the use of albendazole, praziquantel and their combinations and trials studying various protocols of steroids for people with neurocysticercosis. Of the 85 remaining records, 78 were excluded as they were studies addressing laboratory diagnosis of neurocysticercosis or trials for which the outcomes reported were an assessment of the impact of non‐AED medicines such as anthelmintics and/or steroids.
We found seven potentially relevant studies for the review. Full published texts of the articles of these seven publications were reviewed. Three were excluded and we finally included four studies. The review authors decided which studies should be included for the review after discussion. The inclusion, exclusion criteria and methodological quality were graded on a pre designed format. The review authors were not blinded to the study authors names, institute of the studies and the journal of publication. The search results are shown in Figure 3.
Included studies
We identified four studies, which together enrolled 466 patients with neurocysticercosis. One study (Singhi 2003) included children between the ages of three and 14 years; one study (Verma 2006) included adults (age not specified); one study (Thussu 2002) included both children and adults, ages varying from four to 52 years; and one study (Gupta 2002) did not clearly mention the age range of patients included in the study. Three studies (Singhi 2003; Thussu 2002; Verma 2006) enrolled patients from outpatient clinics whereas Gupta 2002 did not mention the source of patients.
Of the 466 people involved, the gender of 81 people included in one study (Gupta 2002) was not specified. Of the rest, 237 were male and 148 were female participants. Partial seizures were the commonest form of seizures. Forty‐two people had primary generalised seizures and 343 people had partial seizures. One study (Gupta 2002) did not elaborate on the type of seizures and drugs given. In the other three studies, 299 people were given carbamazepine and 105 people received phenytoin.
All the studies included were single‐centre studies carried out at various centres in India. A total of 466 people were included in the trials. These studies compared efficacy of various durations (six, 12 and 24 months) of AED therapy. Three studies (Gupta 2002; Thussu 2002; Verma 2006) considered six months AED treatment as short duration and one study (Singhi 2003) considered 12 months treatment as short duration. Twelve months was considered as long duration of treatment in Gupta 2002 and three studies (Singhi 2003; Thussu 2002Verma 2006) considered 24 months as long duration of treatment. One hundred and eight‐six people in three studies (Gupta 2002; Thussu 2002; Verma 2006) received six months of AED and 55 people in one study (Singhi 2003) received 12 months AED as short duration. One hundred and eighty‐five people in three studies (Singhi 2003; Thussu 2002Verma 2006) received 24 months AED as long duration and 40 people in one study (Gupta 2002) received 12 months AED as long duration of treatment.
Patients were followed up for a period of 12 months in three studies (Gupta 2002; Singhi 2003; Thussu 2002) and for 18 months in one (Verma 2006) after randomisation. Repeat neuroimaging was performed in three studies; at three or six months in two studies (Gupta 2002; Verma 2006) and at 12 months in one study (Singhi 2003) after an initial scan at randomisation.
The common AEDs used were carbamazepine or phenytoin. Two studies (Singhi 2003; Verma 2006) stated that choice of drug was decided by the treating physician and possibly affected by cost of treatment. One study (Thussu 2002) did not state the reason, if any, for choice of a particular AED. The fourth study (Gupta 2002) focused on the comparison of the duration of AED given and did not state which drug was given. This adds an element of bias in choice of therapy and affects outcome and we judged it as high risk of other bias.
Details of each of the included studies are further described in Characteristics of included studies.
Excluded studies
We excluded three studies. One study (Chang 1998) was a small case series of add‐on treatment with tiagabine in adults with neurocysticercosis receiving AEDs for seizure control. The second study (Kaushal 2006) compared the tolerability and efficacy and safety of clobazam with phenytoin sodium. We excluded this study as the participants in this open‐label pilot study were only observed for six months and the authors do not provide 12 months follow‐up data on the outcome measures required in this review. The third study (Lanchote 2002) investigated the pharmacokinetic interactions between AEDs and serum albendazole enantiomer concentrations.
Risk of bias in included studies
The risk of bias is demonstrated in Figure 1 and Figure 2 and detailed below.
Allocation
The method used for randomisation was stated in three studies (Singhi 2003; Thussu 2002; Verma 2006), whereas Gupta 2002 did not state the method of randomisation. Methods used for randomisation included a lottery system (Thussu 2002), coin toss (Verma 2006) and random number tables (Singhi 2003). We assumed that randomisation was done appropriately and thus there was a low risk of allocation bias.
There is an unclear risk of allocation concealment bias in all four studies (Gupta 2002; Singhi 2003; Thussu 2002; Verma 2006) as concealment has not been mentioned.
Blinding
None of the studies mention blinding of participants or treating physicians to the study arm or to the antiepileptic agent being used. In two studies (Singhi 2003; Verma 2006) the choice of drug used depended upon the physician and affordability of the agent. We report a high risk of performance bias and an unclear risk of detection bias in all four studies (Gupta 2002; Singhi 2003; Thussu 2002; Verma 2006).
Incomplete outcome data
One study (Verma 2006) detailed the number of patients excluded from the study due to loss to follow‐up and fulfilment of exclusion criteria. We judged a low attrition bias in this study. The other three studies (Gupta 2002; Singhi 2003; Thussu 2002), mentioned exclusion criteria but did not detail the number of patients excluded in the final analysis. We judged a unclear attrition bias in these studies.
Selective reporting
The protocols of the selected studies were not available for comparison with the final conduct of the studies. We judged two studies (Singhi 2003, Verma 2006) to have a low risk of reporting bias as evident from the reported results in the studies. We judged two studies (Gupta 2002, Thussu 2002) to have an unclear risk of reporting bias.
Effects of interventions
All four studies included in the review compared the effectiveness of short‐term versus long‐term antiepileptic drugs (AED) treatment in seizure control in people with neurocysticercosis. All included studies recruited patients with seizures prior to AED treatment therefore analyses are of secondary prevention as opposed to primary prevention.
Primary Outcomes
None of the identified studies randomised individuals to specific AEDs and none compared the proportion of individuals experiencing seizures between the AEDs prescribed.
Secondary Outcomes
Three studies (Gupta 2002; Thussu 2002; Verma 2006) considered six months as short‐term treatment, whereas Singhi 2003 considered patients treated for 12 months as the short‐term group. Gupta 2002 considered 12 months as the long‐duration treatment arm and the other three studies (Singhi 2003; Thussu 2002; Verma 2006) considered 24 months treatment as the long‐duration arm. Three studies (Gupta 2002; Singhi 2003; Thussu 2002) followed up patients for 12 months after stopping AED while one study (Verma 2006), followed up patients for 18 months. The outcome seizure recurrence was recorded from patient reports on follow‐up visits every two or three months after randomisation.
We analysed data comparing six months AED treatment versus 12 to 24 months AED treatment (data from three studies (Gupta 2002; Thussu 2002; Verma 2006)) and data comparing six to 12 months AED treatment versus 24 months AED treatment (data from three studies (Singhi 2003; Thussu 2002; Verma 2006)).
The odds ratio (OR) of seizure recurrence with six months AED treatment compared with 12 to 24 months AED treatment was not statistically significant (OR 1.34, 95% CI 0.73 to 2.47; three studies; 360 participants; low‐certainty evidence; (Figure 4, Analysis 1.1)). The risk of seizure recurrence with six to 12 months AED treatment compared with 24 months AED treatment was also not statistically significant (OR 1.36, 95% CI 0.72 to 2.57; three studies, 385 participants; low‐certainty evidence; (Figure 5; Analysis 2.1)).
Forest plot of comparison: 2. 6 months AED treatment versus 12‐24 months AED treatment, outcome: 2.1 Seizure recurrence.
Forest plot of comparison: 2. 6‐12 months AED treatment versus 24 months AED treatment, outcome: 2.1 Seizure recurrence.
Comparison 1 6 months AED treatment versus 12 to 24 months AED treatment, Outcome 1 Seizure recurrence.
Comparison 2 6 to 12 months AED treatment versus 24 months AED treatment, Outcome 1 Seizure recurrence.
Two studies (Singhi 2003; Verma 2006) correlated seizure recurrence with CT findings. Both studies suggest that prolonged AED treatment may be required for patients with persistent lesions or calcification, based on seizure recurrence and follow‐up CT scanning.
Only one study (Verma 2006) mentioned that no side effects occurred in any patient. The other three studies (Gupta 2002; Singhi 2003; Thussu 2002) did not comment on side effects of AEDs in their patients.
The cost of treatment, quality of life, mortality, and requirement for hospitalisations were not evaluated in any of the studies.
The dosage of drug used was mentioned in one study (Verma 2006); no information was provided on drug doses in the other three studies. Therefore, we did not carry out subgrouping of drug given or dosage for this review.
Discussion
We intended to look at trials evaluating the efficacy of various antiepileptic drugs (AEDs) for seizure control in people with neurocysticercosis. For primary prevention, we intended to look at patients with neurocysticercosis presenting with problems other than seizures for example, headache, diplopia (double vision) etc. However, in our electronic search we did not find trials addressing the above. This finding indicates a gap in our knowledge base and the need for randomised controlled trials to address this issue.
For secondary prevention, we aimed to look at studies that considered whether AEDs decrease the likelihood of further seizures in patients who have experienced at least one seizure.
Summary of main results
We found seven trials of apparent relevance. One study (Chang 1998) was excluded as it was a description of four cases. One study (Kaushal 2006) compared the safety and efficacy of clobazam versus phenytoin sodium in seizure control in people with a single neurocysticercosis. This study was excluded as it was of poor quality. The third excluded study (Lanchote 2002) investigated the pharmacokinetic interactions between AEDs and serum albendazole enantiomer concentrations.
The four studies included in the review compared the use of short duration and long duration AED treatment in control of seizures in people with a single cerebral cysticercal cyst.
Four hundred and sixty‐six people with neurocysticercosis participated in the four included studies (Gupta 2002; Singhi 2003; Thussu 2002; Verma 2006). These studies examined seizure recurrence with varying durations of AED treatment (six or 12 or 24 months).
The odds ratio (OR) of seizure recurrence with six months AED treatment compared with 12 to 24 months treatment was not statistically significant (OR 1.34; 95% CI 0.73 to 2.47; three studies, 360 participants (186 participants for six months treatment and 174 participants for 12 to 24 months treatment) (Analysis 1.1)). The risk of seizure recurrence with six to 12 months AED treatment compared with 24 months treatment was also not statistically significant (OR 1.36; 95% CI 0.72 to 2.57; three studies, 385 participants (200 participants randomised to six to 12 months treatment and 185 participants to 24 months treatment) (Analysis 2.1)).
Two studies (Singhi 2003; Verma 2006) indicated that in cases where a persistence of lesion or calcification is found on review computed tomography (CT) scans, prolongation of AED treatment may be effective in optimal seizure control.
Overall completeness and applicability of evidence
A major drawback of the four studies included in the review, comparing short‐duration and long‐duration treatments, is that none of the studies sought to establish the effectiveness of the specific AED being given, with respect to choice of drug, dosage, compliance or side‐effect profiles. All four studies solely focused on comparison of duration of drugs being given. The results thus have limited applicability to choice of AED for physicians.
With the exception of Verma 2006, where exclusions and losses are detailed, none of the included studies mentioned the exact number of people excluded from the trial and why.
Most studies mentioned that neurocysticercosis is a benign and often a self‐limiting condition. Thus patient selection may affect the final outcome of the studies. Two studies (Thussu 2002; Verma 2006) excluded patients who had a persistence of lesion, which is actually a high risk for seizure recurrence, implying that patients selected for the study had a low risk of seizure recurrence in the first place.
Most of the studies included in the review excluded patients with persistent lesions and those needing albendazole therapy, some of whom may have actually been potential candidates for seizure recurrence. As a result, the study inferences prevent generalisation to all patients will neurocysticercosis and rather focuses on patients with inactive parasitic cysts.
Also, all of the included studies focused on people with a solitary cerebral lesion. These factors limit the applicability and generalisation of the study results as evidence for future use in people with neurocysticercosis who may have multiple cysts or the lesion is situated in unusual locations for example, intra ventricular cysts, brainstem cysts etc .
Three of the studies (Gupta 2002; Singhi 2003; Verma 2006) correlated seizure recurrence and the need for prolonged therapy with the presence of a calcified lesion. They suggest that people with calcified lesions would benefit with a longer duration of AEDs and additionally helped by repeated neuroimaging to check the status of the lesion. This suggestion is useful in practice.
Certainty of the evidence
The studies that compared short‐duration and long‐duration AEDs included in this review have methodological deficiencies, such as lack of blinding, small sample sizes, reporting biases, lack of description of withdrawals from the study. We graded the level of evidence as low. All the included studies had an inherent bias in patient allocation and blinding. Though not clearly mentioned, it can be assumed that the treating physicians and patients were not blinded to the study drug and study arm being studied. This also adds a possibility of a reporting bias, all of which together affect the quality of evidence provided by the study results.
We evaluated the included studies for heterogeneity using the I2 statistic (I2 = 0%). The studies included in the meta‐analysis, were homogenous with respect to diagnostic criteria used, method of sampling, method of observation, follow‐up and analysis of results. The forest plot of comparison shows a trend (not statistically significant) in favour of a longer duration of AED treatment over a short duration of treatment for seizure recurrence (OR 1.34; 95% CI 0.73 to 2.47) for six months versus 12 to 24 months AED treatment (Analysis 1.1) and (OR 1.36; 95% CI 0.72 to 2.57) for six to 12 months versus 24 months AED treatment (Analysis 2.1).
An analysis of the findings is shown in the Table 1 and Table 2. We graded the level of evidence as low.
Potential biases in the review process
Potentially, studies may have been missed by the search strategy if smaller studies were presented at clinical conferences, but not in the literature identified through the search engines employed.
None of the identified studies reported the primary outcome measures of the proportion of individuals experiencing seizures or the time to first seizure between AED treatment groups. We contacted the authors to attempt to obtain these data but did not receive these data to undertake these analyses. Nevertheless, had these data been made available, there would potentially be significant bias as the prescription of AEDS was not randomised but rather determined by the clinician, which reflects clinical and potentially financial bias.
Study selection potentially could have introduced bias as in the protocol we limited our inclusion to studies with at least 12 months of data, therefore we are unable to comment on the efficacy of AEDs in the first six months of therapy.
All four included studies were single‐centre studies from various parts of India. The geographic location and disease behaviour outcomes may be different in the subcontinent versus other regions of the world where neurocysticercosis is equally rampant. We cannot rule out a regional bias in this review.
We generated a funnel plot indicating a publication bias in the included studies Figure 6. The quality of the trials included is not uniform, in terms of study design. For example, one study enrolled children only (Singhi 2003), one study included only adults (Verma 2006), while one included people of all age ranges (Thussu 2002). The mean age of people in the latter study (Thussu 2002) was in the adult range. The fourth study (Gupta 2002),did not specify details of the enrolled patients, such as age, gender or type of seizures. This factor affects the result of this review.
Agreements and disagreements with other studies or reviews
So far, there have been reviews on treatment of people with neurocysticercosis, highlighting anthelmintic therapy, anti‐oedema measures such as steroids and various combinations of these measures with respect to seizure control (Abba 2010; García 2002; Zafar 2013). While most of these reviews mention the need for AEDs in patients presenting with seizures, there are no reviews dedicated to the use of AEDs with respect to drug choices, duration of treatment, side‐effect profiles etc.
Authors' conclusions
What's new
| Date | Event | Description |
|---|---|---|
| 8 July 2019 | New search has been performed | Searches updated 8 July 2019; no new trials identified. |
| 8 July 2019 | New citation required but conclusions have not changed | Conclusions are unchanged. |
Acknowledgements
The original review authors wish to acknowledge the constant guidance of our editorial mentor, Dr Sridharan Ramaratnam in the preparation of the review protocol and the final review. We also wish to thank Dr Ravindra Arya for help in procuring full texts of some of the included studies.
This review update was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Epilepsy Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.
Appendices
Appendix 1. CRS Web search strategy
1. MeSH DESCRIPTOR Neurocysticercosis Explode All AND CENTRAL:TARGET
2. neurocysticercosis AND CENTRAL:TARGET
3. MeSH DESCRIPTOR Taenia solium Explode All AND CENTRAL:TARGET
4. "Taenia solium" AND CENTRAL:TARGET
5. tapeworm OR "tape worm" AND CENTRAL:TARGET
6. #1 OR #2 OR #3 OR #4 OR #5 AND CENTRAL:TARGET
7. MeSH DESCRIPTOR Epilepsy Explode All WITH QUALIFIER DT AND CENTRAL:TARGET
8. MESH DESCRIPTOR Seizures EXPLODE ALL WITH QUALIFIER DT AND CENTRAL:TARGET
9. MeSH DESCRIPTOR Anticonvulsants Explode All AND CENTRAL:TARGET
10. MeSH DESCRIPTOR Midazolam Explode All AND CENTRAL:TARGET
11. MeSH DESCRIPTOR Methazolamide Explode All AND CENTRAL:TARGET
12. MeSH DESCRIPTOR Propofol Explode All AND CENTRAL:TARGET
13. MeSH DESCRIPTOR Temazepam Explode All AND CENTRAL:TARGET
14. MeSH DESCRIPTOR Thiopental Explode All AND CENTRAL:TARGET
15. (antiepilep* or anti‐epilep* or anticonvulsant* or anti‐convulsant* or AED or AEDs):AB,KW,MC,MH,TI AND CENTRAL:TARGET
16. (Acetazolamid* or Aedon or Aethosuximide or Alodorm or Amizepin* or Antelepsin or Anxirloc or Arem or Ativan or Atretol or Avugane):AB,KW,MC,MH,TI AND CENTRAL:TARGET
17. (Baceca or Barbexaclon* or Beclamid* or Biston or Bomathal or Brivaracetam or Bromid*):AB,KW,MC,MH,TI AND CENTRAL:TARGET
18. (Calepsin or Carbagen or Carbamazepen* or Carbamazepin* or Carbatrol or Carbazepin* or Carbelan or Carisbamat* or Castilium or CBZ or Celontin or Cerebyx or Chlonazepam or Chloracon or Chlorepin or Clorepin or Chlormethiazole or Clormethiazole or Clarmyl or Cloazepam or Clobam* or Clobator or Clobazam or Clofritis or Clonazepam* or Clonex or Clonopin or Clopax or Clorazepate or Comfyde or Convulex):AB,KW,MC,MH,TI AND CENTRAL:TARGET
19. (Dapaz or Dasuen or Delepsine or Depacon or Depak* or Depamide or Deproic or Desitin or Diacomit or Diamox or Diastat or Diazepam or Difenilhidantoin* or Dihydantoin or Dilantin or Dimethadione or Dimethyloxazolidinedione or Diphenin* or Diphenylan or Diphenylhydantoin* or Distraneurin or Divalpr* or Dormicum):AB,KW,MC,MH,TI AND CENTRAL:TARGET
20. (Ecovia or Emeside or Epanutin or Epiject or Epilepax or Epilex or Epilim or Episenta or Epitol or Epival or Eptoin or Equanil or Equetro or Ergenyl or Erimin or Erlosamide or Eslicarbazepine or Estazolam or Ethadione or Ethosucci* or Ethosuxi* or Ethotoin or Ethylphenacemide or Etosuxi* or Euhypnos or Exalief or Excegran or Ezogabine):AB,KW,MC,MH,TI AND CENTRAL:TARGET
21. (Fanatrex or Felbam* or Felbatol or Fenitoin* or Fenytoin* or Fenobarbit* or Finlepsin or Fosphenytoin or Frisium or Fycompa):AB,KW,MC,MH,TI AND CENTRAL:TARGET
22. (Gabapentin* or Gabapetin* or Gabarone or Gabitril or Gabrene or Ganaxolone or Garene or Gralise or Grifoclobam):AB,KW,MC,MH,TI AND CENTRAL:TARGET
23. (Halogabide or Halogenide or Harkoseride or Hibicon or Hydroxydiazepam or Hypnovel):AB,KW,MC,MH,TI AND CENTRAL:TARGET
24. (Iktorivil or Inovelon or Insoma or Intensl or Karbamazepin or Karidium or Keppra or Klonopin or Kriadex):AB,KW,MC,MH,TI AND CENTRAL:TARGET
25. (Lacosamid* or Lamict* or Lamitor or Lamitrin or Lamogine or Lamotrigin* or Lamotrine or Landsen or Levanxol or Levetiracetam* or Lexin or Liskantin or Loraz or Lorazepam* or Losigamon* or Lucium or Luminal or Lyrica):AB,KW,MC,MH,TI AND CENTRAL:TARGET
26. (Magnesium sulfat* or Magnesium sulphat* or Mebaral or Medazepam or Mephenytoin or Mephobarbit* or Mephyltaletten or Meprobamate or Meprospan or Mesantoin or Mesuximide or Methazolamid* or Methsuximide or Methylacetazolamide or Methyloxazepam or Methylphenobarbit* or Midazolam or Miltown or Mogadon or Mylepsinum or Mylproin or Mysoline or Mystan):AB,KW,MC,MH,TI AND CENTRAL:TARGET
27. (Neogab or Neptazane or Nesdonal or Neurontin or Neurotop or Nimetazepam or Nitrados or Nitrazadon or Nitrazepam or Nobrium or Nocturne or Noiafren or Norkotral or Normison or Normitab or Nortem or Novo‐Clopate or Nuctalon or Nupentin or Nydrane):AB,KW,MC,MH,TI AND CENTRAL:TARGET
28. (OCBZ or Onfi or Orfiril or Orlept or Ormodon or Ospolot or Oxcarbamazepin* or Oxcarbazepin* or Oxydiazepam):AB,KW,MC,MH,TI AND CENTRAL:TARGET
29. (Pacisyn or Paraldehyde or Paramethadione or Paxadorm or Paxam or Peganone or Penthiobarbital or Pentothal or Perampanel or Petinutin or Petril or Phemiton or Phenacemide or Pheneturide or Phenobarbit* or Phensuximide or Phenylethylbarbit* or Phenylethylmalonylurea or Phenytek or Phenytoin* or Planum or Posedrine or Potiga or Pregabalin or Primidone or Prodilantin or Progabide or Prominal or Pronervon or Propofol or Prosom or Prysoline):AB,KW,MC,MH,TI AND CENTRAL:TARGET
30. (Ravotril or Remacemide or Remestan or Remnos or Resimatil or Restoril or Retigabine or Riluzole or Rilutek or Rivotril or Rudotel or Rufinamide or Rusedal or "RWJ‐333369"):AB,KW,MC,MH,TI AND CENTRAL:TARGET
31. (Sabril or Seclar or Sederlona or Selenica or Seletracetam or Sentil or Sertan or Sibelium or Signopam or Sirtal or Sodipental or Somnite or Stavzor or Stazepin* or Stedesa or Stiripentol or Sulthiam* or Sultiam*):AB,KW,MC,MH,TI AND CENTRAL:TARGET
32. (Talampanel or Taloxa or Tasedan or Tegretal or Tegretol or Telesmin or Temaze or Temazep* or Temesta or Temtabs or Tenox or Teril or Thiomebumal or Thionembutal or Thiopent* or Tiagabin* or Tiletamine or Timonil or Tiobarbit* or Tipiram* or Topamax or Topiram* or Tranmep or Tranxene or Trapanal or Tridione or Trileptal or Trimethadione or Trobalt):AB,KW,MC,MH,TI AND CENTRAL:TARGET
33. (Urbadan or Urbanil or Urbanyl):AB,KW,MC,MH,TI AND CENTRAL:TARGET
34. (Valance or Valcote or Valium or Valnoctamide or Valparin or Valpro* or Versed or Vigabatrin* or Vimpat or Visano or VPA):AB,KW,MC,MH,TI AND CENTRAL:TARGET
35. (Xilep or "YKP 509" or Zalkote or Zarontin or Zebinix or Zonegran or Zonisamid*):AB,KW,MC,MH,TI AND CENTRAL:TARGET
36. #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR #34 OR #35 AND CENTRAL:TARGET
37. #6 AND #36
Appendix 2. MEDLINE search strategy
This strategy is based on the Cochrane Highly Sensitive Search Strategy for identifying randomised trials published in Lefebvre 2011.
1. exp NEUROCYSTICERCOSIS/
2. neurocysticercosis.tw.
3. Taenia solium.tw.
4. exp Taenia solium/
5. (tape worm or tapeworm).tw.
6. 1 or 2 or 3 or 4 or 5
7. exp *Epilepsy/dt [Drug Therapy]
8. exp Seizures/dt [Drug Therapy]
9. exp Anticonvulsants/
10. exp Midazolam/
11. exp Methazolamide/
12. exp Propofol/
13. exp Temazepam/
14. exp Thiopental/
15. (antiepilep$ or anti‐epilep$ or anticonvulsant$ or anti‐convulsant$ or AED or AEDs).tw.
16. (Acetazolamid$ or Aedon or Aethosuximide or Alodorm or Amizepin$ or Ant?lepsin or Anxirloc or Arem or Ativan or Atretol or Avugane).tw.
17. (Baceca or Barbexaclon$ or Beclamid$ or Biston or Bomathal or Brivaracetam or Bromid$).tw.
18. (Calepsin or Carbagen or Carbamazepen$ or Carbamazepin$ or Carbatrol or Carbazepin$ or Carbelan or Carisbamat$ or Castilium or CBZ or Celontin or Cerebyx or Chlonazepam or Chloracon or C?lorepin or C?lormethiazole or Clarmyl or Cloazepam or Clobam$ or Clobator or Clobazam or Clofritis or Clonazepam$ or Clonex or Clonopin or Clopax or Clorazepate or Comfyde or Convulex).tw.
19. (Dapaz or Dasuen or Delepsine or Depacon or Depak$ or Depamide or Deproic or Desitin or Diacomit or Diamox or Diastat or Diazepam or Difenilhidantoin$ or Dihydantoin or Dilantin or Dimethadione or Dimethyloxazolidinedione or Diphenin$ or Diphenylan or Diphenylhydantoin$ or Distraneurin or Divalpr$ or Dormicum).tw.
20. (Ecovia or Emeside or Epanutin or Epiject or Epilepax or Epilex or Epilim or Episenta or Epitol or Epival or Eptoin or Equanil or Equetro or Ergenyl or Erimin or Erlosamide or Eslicarbazepine or Estazolam or Ethadione or Ethosucci$ or Ethosuxi$ or Ethotoin or Ethylphenacemide or Etosuxi$ or Euhypnos or Exalief or Excegran or Ezogabine).tw.
21. (Fanatrex or Felbam$ or Felbatol or Fenitoin$ or Fenobarbit$ or Fenytoin$ or Finlepsin or Fosphenytoin or Frisium or Fycompa).tw.
22. (Gabapentin$ or Gabapetin$ or Gabarone or Gabitril or Gabrene or Ganaxolone or Garene or Gralise or Grifoclobam).tw.
23. (Halogabide or Halogenide or Harkoseride or Hibicon or Hydroxydiazepam or Hypnovel).tw.
24. (Iktorivil or Inovelon or Insoma or Intensl or Karbamazepin or Karidium or Keppra or Klonopin or Kriadex).tw.
25. (Lacosamid$ or Lamict$ or Lamitor or Lamitrin or Lamogine or Lamotrigin$ or Lamotrine or Landsen or Levanxol or Levetiracetam$ or Lexin or Liskantin or Loraz or Lorazepam$ or Losigamon$ or Lucium or Luminal or Lyrica).tw.
26. (Magnesium sulfat$ or Magnesium sulphat$ or Mebaral or Medazepam or Mephenytoin or Mephobarbit$ or Mephyltaletten or Meprobamate or Meprospan or Mesantoin or Mesuximide or Methazolamid$ or Methsuximide or Methylacetazolamide or Methyloxazepam or Methylphenobarbit$ or Midazolam or Miltown or Mogadon or Mylepsinum or Mylproin or Mysoline or Mystan).tw.
27. (Neogab or Neptazane or Nesdonal or Neurontin or Neurotop or Nimetazepam or Nitrados or Nitrazadon or Nitrazepam or Nobrium or Nocturne or Noiafren or Norkotral or Normison or Normitab or Nortem or Novo‐Clopate or Nuctalon or Nupentin or Nydrane).tw.
28. (OCBZ or Onfi or Orfiril or Orlept or Ormodon or Ospolot or Oxcarbamazepin$ or Oxcarbazepin$ or Oxydiazepam).tw.
29. (Pacisyn or Paraldehyde or Paramethadione or Paxadorm or Paxam or Peganone or Penthiobarbital or Pentothal or Perampanel or Petinutin or Petril or Phemiton or Phenacemide or Pheneturide or Phenobarbit$ or Phensuximide or Phenylethylbarbit$ or Phenylethylmalonylurea or Phenytek or Phenytoin$ or Planum or Posedrine or Potiga or Pregabalin or Primidone or Prodilantin or Progabide or Prominal or Pronervon or Propofol or Prosom or Prysoline).tw.
30. (Ravotril or Remacemide or Remestan or Remnos or Resimatil or Restoril or Retigabine or Riluzole or Rilutek or Riv?tril or Rudotel or Rufinamide or Rusedal or "RWJ‐333369").tw.
31. (Sabril or Seclar or Sederlona or Selenica or Seletracetam or Sentil or Sertan or Sibelium or Signopam or Sirtal or Sodipental or Somnite or Stavzor or Stazepin$ or Stedesa or Stiripentol or Sulthiam$ or Sultiam$).tw.
32. (Talampanel or Taloxa or Tasedan or Tegret?l or Telesmin or Temaze or Temazep$ or Temesta or Temtabs or Tenox or Teril or Thiomebumal or Thionembutal or Thiopent$ or Tiagabin$ or Tiletamine or Timonil or Tiobarbit$ or Tipiram$ or Topamax or Topiram$ or Tranmep or Tranxene or Trapanal or Tridione or Trileptal or Trimethadione or Trobalt).tw.
33. (Urbadan or Urban?l).tw.
34. (Valance or Valcote or Valium or Valnoctamide or Valparin or Valpro$ or Versed or Vigabatrin$ or Vimpat or Visano or VPA).tw.
35. (Xilep or "YKP 509" or Zalkote or Zarontin or Zebinix or Zonegran or Zonisamid$).tw.
36. or/7‐35
37. 6 and 36
38. (randomized controlled trial or controlled clinical trial or pragmatic clinical trial).pt. or (randomi?ed or placebo or randomly).ab.
39. clinical trials as topic.sh.
40. trial.ti.
41. 38 or 39 or 40
42. exp animals/ not humans.sh.
43. 41 not 42
44. 37 and 43
45. remove duplicates from 44
Appendix 3. LILACS search strategy
(anticonvulsant OR mh:("anticonvulsants")) AND (mh:("NEUROCYSTICERCOSIS" OR "TAENIA") OR neurocysticercosis OR taenia OR (tape AND worm) OR tapeworm)
Notes
New search for studies and content updated (no change to conclusions)
Data and analyses
Comparison 1
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Seizure recurrence | 3 | 360 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.34 [0.73, 2.47] |
Comparison 2
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Seizure recurrence | 3 | 385 | Odds Ratio (M‐H, Fixed, 95% CI) | 1.36 [0.72, 2.57] |
Characteristics of studies
Characteristics of included studies [ordered by study ID]
| Methods | Randomised trial. Method of randomisation not stated. Single centre in New Delhi, India. Total duration of trial 1.5 to 2 years in both study groups. Ethical approval/consents not stated. | |
| Participants | 81 participants, 41 people with NCC treated for 6 months in group A, 40 people with NCC treated for a period of 12 months in group B. Diagnostic criteria based on CT Scan findings. Age and sex distribution not stated. Inclusion criteria: all patients with epilepsy and diagnostic CT findings, only patients with a single lesion. Exclusion criteria: suspected tuberculoma and NCC patients treated with albendazole. Follow‐up: 12 months after drug withdrawal. | |
| Interventions | AED treatment for seizure control for 6 months in group A and 12 months in group B. Details of drug used, dosage in either groups not stated. | |
| Outcomes | Seizure recurrence after stoppage of treatment. | |
| Notes | Single outcome studied. Withdrawls and exact number of excluded patients not stated. Choice of AED not mentioned. Dosage, side effects, cost and impact on quality of life not studied. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Method of randomisation not detailed |
| Allocation concealment (selection bias) | Unclear risk | Exact methodology not detailed in the article |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Not mentioned in article, probably not blinded |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Method of outcome recording not stated |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Withdrawals, exclusions and reasons (if any) not stated |
| Selective reporting (reporting bias) | Unclear risk | Protocol not available. Insufficient information to comment on reporting |
| Other bias | High risk | AED used, formulation and dosage not stated in the article |
| Methods | Randomised controlled trial. Single centre in India. Total duration of trial 2‐3 years in both comparison groups. | |
| Participants | Children with NCC. Diagnostic criteria based on CT Scan findings, only single lesions included. 55 children treated with AEDs for 1 year as group A, 51 children treated for 2 years as group B. Age range: 3 to 14 years, 61 boys, 45 girls. Demographically comparable groups. Inclusion criteria: children with seizures and CT scan diagnosis of NCC. Exclusion criteria: children with multiple or calcified CT lesions, static or progressive neurological disorder, any systemic or chronic illness, any clinical or ancillary evidence of tuberculosis; 55% also received albendazole within 3 months of presentation. Follow‐up: 12 months after drug withdrawal. | |
| Interventions | AEDs for 12 months in group A and 24 months in group B. All children received monotherapy. 80% received carbamazepine, 18% received dilantin. Formulations, dosage, group‐wise distribution not stated. | |
| Outcomes | Seizure recurrence during and after drug withdrawal. Association of seizure recurrence with clinical variables (type and frequency of seizures). Association of seizure recurrence with CT and EEG abnormalities. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random sequence tables used for randomisation Demographic variables of children in both groups comparable Type and frequency of seizures, AEDs given, EEG and CT Scan observations detailed and comparable |
| Allocation concealment (selection bias) | Unclear risk | Not stated |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Participants and personnel were not blinded to the intervention. Hence, we assume here that they were also not blinded to short or long duration treatment arms. |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Not stated |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Withdrawals and reasons not stated |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, all expected outcomes suitably detailed in the results section |
| Other bias | High risk | Dosage of AEDs given not stated |
| Methods | Randomised clinical trial. Single centre in India. Duration of trial 1.5‐3 years in two groups. | |
| Participants | People with seizures and CT scan suggestive of NCC Age range: 4 to 52 years, Mean ages in group A and B 19.5 ± ‐8.79 years and 25.6 ± 12.5 years, respectively. 53% of patients were males. Total: 73 people, 47 in group A treated with AEDs for 6 months, 26 in group B treated for 24 months. Follow‐up: every 2 months for 12 months after withdrawal of drugs. Exclusion criteria: people with persistent lesions requiring albendazole therapy. | |
| Interventions | AEDs for 6 months in group A, 24 months in group B. Group A 25 received carbamazepine, 22 received phenytoin. Group B 13 each received carbamazepine and phenytoin. Exact dosage and formulations not stated. Mentioned to have received quote: "therapeutic dosage according to weight". | |
| Outcomes | Seizure recurrence after withdrawal of AED. Correlation of seizure recurrence with CT Scan findings. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation based on lottery system |
| Allocation concealment (selection bias) | Unclear risk | Not stated |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Not stated |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Not stated |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Number of patients excluded or withdrawing from the study not mentioned |
| Selective reporting (reporting bias) | Unclear risk | Protocol not available. Insufficient information to confirm reporting bias. |
| Other bias | Unclear risk | Seizure recurrence discussed but timing of recurrence, i.e. during or after AED therapy not clear |
| Methods | Randomised clinical trial. Single centre in India. Duration of trial 2 to 3.5 years in two groups. | |
| Participants | 227 people with NCC, 206 randomised. Inclusion criteria: people with epilepsy with CT Scan criteria of Del Brutto et al. Only people with complete resolution of lesion at 3 to 6 months CT scan or presence of calcified residua included. Exclusion criteria: persistent lesions on repeat CT scan at 3 to 6.months interval. Mean age 21.8 ± 6.1 years in group A, 19.5 ± 8.8 years in group B. Gender distribution in two groups comparable. Seizure type, duration at randomisation and frequency comparable in the two groups. Follow‐up for a minimum of 18 months after drug withdrawal. | |
| Interventions | AEDs for 6 months in Group A and 24 months in Group B. 176 people treated with carbamazepine (600 to 1000 mg/day). 51 people treated with phenytoin (300 to 400 mg/day). | |
| Outcomes | Seizure recurrence during and after withdrawal of AED. Severe side effects to AED. Correlation of seizure recurrence with CT scan finding in follow‐up scans. | |
| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Simple random sampling by coin toss method |
| Allocation concealment (selection bias) | Unclear risk | Authors do not detail the conduct of the coin toss and wether result of the coin toss was visible to the researchers or participants |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | Not stated |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Not stated |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Number of people lost to follow‐up in both groups and number of people completing study mentioned in table 1 |
| Selective reporting (reporting bias) | Low risk | Study protocol not available, no differences between planned and reported outcomes evident |
| Other bias | Low risk | Insufficient evidence to suggest risk of bias |
AED: antiepileptic drug
CT: computed tomography
EEG: electroencephalography
NCC: neurocysticercosis
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
|---|---|
| Chang 1998 | Case series study of 4 adult patients with NCC with epilepsy. Tiagabine HCL was used as an add‐on drug in 4 patients (2 on carbamazepine and 2 on phenytoin). |
| Kaushal 2006 | Comparison of clobazam with phenytoin sodium for prevention of seizures in people with single NCC. This is an underpowered study which was prematurely terminated due to relocation of one of the authors. The reason for the difference in numbers between the two comparison groups is not clear. It is not clear whether the two groups were balanced as far as the prognostic variables are concerned. The number of participants randomised to phenytoin and clobazam differ in the text and in the CONSORT flow chart. The study planned to enrol 135 participants in each of the two groups, in order to provide sufficient power to detect 10% difference in the primary outcome measure with 90% confidence. The numbers accrued, however fell short on account of premature termination of the study. |
| Lanchote 2002 | The objective of this study was to determine the interaction between the AEDs and the selective metabolism of albendazole. In this study plasma concentrations of albendazole sulfoxide (ASOX) and albendazole sulphone (ASON) metabolites were measured in 32 adults who received phenytoin, carbamazepine, phenobarbital or no AED. None of the primary or secondary outcome measures in this review were assessed. |
AED: antiepileptic drug
HCL: hydrochloride
NCC: neurocysticercosis
Differences between protocol and review
In the protocol, we planned to analyse seizure control with AEDs over a specified period of time. We had also planned to look at studies comparing duration of treatment with respect to seizure control. A subgroup analysis between patients with single versus multiple cerebral lesions and monotherapy versus polytherapy was planned.
In the final review, we were restricted to comparing short‐duration versus long‐duration therapy according to the studies identified and included in the review. All the included studies were carried out on people with single cerebral lesions and all patients received monotherapy. The intended subgroup analysis was hence not possible.
In the protocol, we had mentioned that we would exclude studies comparing two AEDs. However, we decided to include such studies after this oversight was pointed out in the review process. This was essential to answer our primary question of "which AED is better for seizure control?"
In the protocol, we intended to look at the effect of drugs in seizure control in a population with neurocysticercosis and therefore planned to calculate the risk ratio (RR). As we were able to find studies that compared short duration versus long duration AED treatment, we calculated the odds ratio (OR) to look at the odds of seizure recurrence in long duration of AED treatment against short duration of treatment.
As far as the search methods, data collection and analysis are concerned, we were able to proceed as per the protocol design.
Contributions of authors
MS independently screened all 180 citations and abstracts and evaluated the eligibility of the study for the review. MF and BDM independently screened 48 newly identified citations and abstracts and evaluated the eligibility of the study for the review. MS and AM independently extracted data using a tailored data extraction form. TS supervised data extraction and resolved any discrepancies between MS and AM, if needed. MS prepared the first draft of the review. TS reviewed the final draft.
Sources of support
Internal sources
- No sources of support supplied
External sources
- National Institute of Health Research, UK.
Declarations of interest
MF: none known
MS: none known
TS: none known
AM: none known
BDM has received funding from the NIHR, Wellcome Trust, Academy of Medical Sciences, British Medical Association.
References
References to studies included in this review
Gupta 2002 {published data only}
- Gupta M, Agarwal P, Khwaja GA, Chowdhury D, Sharma B, Bansal J, et al. Randomized prospective study of outcome of short term antiepileptic treatment in small single enhancing CT lesion in brain. Neurology India 2002;50(2):145‐7. [PUBMED: 12134176] [PubMed] [Google Scholar]
Singhi 2003 {published data only}
- Singhi PD, Dinakaran J, Khandelwal N, Singhi SC. One vs. two years of anti‐epileptic therapy in children with single small enhancing CT lesions. Journal of Tropical Pediatrics 2003;49(5):274‐8. [DOI: 10.1093/tropej/49.5.274; PUBMED: 14604159] [PubMed] [CrossRef] [Google Scholar]
Thussu 2002 {published data only}
- Thussu A, Arora A, Prabhakar S, Lal V, Sawhney IM. Acute symptomatic seizures due to single CT lesions: how long to treat with antiepileptic drugs?. Neurology India 2002;50(2):141‐4. [PUBMED: 12134175] [PubMed] [Google Scholar]
Verma 2006 {published data only}
- Verma A, Misra S. Outcome of short‐term antiepileptic treatment in patients with solitary cerebral cysticercus granuloma. Acta Neurologica Scandinavica 2006;113(3):174‐7. [DOI: 10.1111/j.1600-0404.2005.00538.x; PUBMED: 16441247] [PubMed] [CrossRef] [Google Scholar]
References to studies excluded from this review
Chang 1998 {published data only}
- Chang GY. Tiagabine HCl may be effective in complex partial epilepsy due to neurocysticercosis. Neurology 1998;50(4 Suppl 4):A200, Abstract no: P04.003. [Google Scholar]
Kaushal 2006 {published data only}
- Kaushal S, Rani A, Chopra SC, Singh G. Safety and efficacy of clobazam versus phenytoin sodium in the anti‐epileptic drug treatment of solitary cysticercus granulomas. Neurology India June 2006;54(2):157‐60. [PUBMED: 16804259] [PubMed] [Google Scholar]
Lanchote 2002 {published data only}
- Lanchote VL, Garcia FS, Dreossi SA, Takayanagui OM. Pharmocokinetic interaction between albendazole sulfoxide enantiomers and antiepileptic drugs in patients with neurocysticercosis. Therapeutic Drug Monitoring 2002;24(3):338‐45. [PUBMED: 12021623] [PubMed] [Google Scholar]
Additional references
Abba 2010
- Abba K, Ramratnam S, Ranganathan LN. Anthelmintics for people with neurocysticercosis. Cochrane Database of Systematic Reviews 2010, Issue 3. [DOI: 10.1002/14651858.CD000215.pub4] [PMC free article] [PubMed] [CrossRef] [Google Scholar]
Daniels 2006
- Daniels TL, Moore TA. Neurocysticercosis in Kansas. Annals of Internal Medicine 2006;144(2):150‐2. [PubMed] [Google Scholar]
DeGiorgio 2004
- DeGiorgio CM, Medina MT, Duron R, Zee C, Escueta SP. Neurocysticercoisis. Epilepsy Currents 2004;4(3):107‐11. [PMC free article] [PubMed] [Google Scholar]
Del Brutto 1992
- Brutto OH, Santibañez R, Noboa CA, Aguirre R, Díaz E, Alarcón TA. Epilepsy due to neurocysticercosis. Analysis of 203 patients. Neurology 1992;42:389‐92. [PubMed] [Google Scholar]
Del Brutto 1996
- Brutto OH, Campos X. Discontinuation of antiepileptic drugs in patients with calcified neurocysticercosis. Journal of Epilepsy 1996;9(4):231‐3. [Google Scholar]
Del Brutto 2001
- Brutto OH, Rajshekhar V, White AC Jr, Tsang VC, Nash TE, Takayanagui OM, et al. Proposed diagnostic criteria for neurocysticercosis. Neurology 2001;57(2):177‐83. [PMC free article] [PubMed] [Google Scholar]
Del Brutto 2005
- Brutto OH, Santibáñez R, Idrovo L, Rodrìguez S, Díaz‐Calderón E, Navas C, et al. Epilepsy and neurocysticercosis in Atahualpa: a door to door survey in rural coastal Ecuador. Epilepsia 2005;46(4):583‐7. [PubMed] [Google Scholar]
Dhawan 2011
- Dhawan VK. Pediatric Nnurocysticercosis. http://emedicine.medscape.com/article/999053‐overview#a0199 2011 (accessed 22 May 2014).
Ferreira 2002
- Ferreira LS, Li LM, Zanardi VA, Guerreiro MM. Number and viability of parasite influence seizure frequency in children with neurocysticercosis. Arquivos de Neuropsiquiatria 2002;60(4):909‐11. [PubMed] [Google Scholar]
García 2002
- García HH, Evans CA, Nash TE, Takayanagui OM, White AC Jr, Botero D, et al. Current consensus guidelines for treatment of neurocysticercosis. Clinical Microbiology Reviews 2002;15(4):747‐56. [PMC free article] [PubMed] [Google Scholar]
GRADEPro 2004 [Computer program]
- Brozek J, Oxman A, Schunemann H. GRADEpro GDT. Version accessed 6 August 2016. Hamilton (ON): McMaster University (developed by Evidence Prime).. Available at gradepro.org.. GRADE Working Group, 2004.
Hauser 1992
- Hauser WA. Seizure disorders: the changes with age. Epilepsia 1992;33(Suppl 4):6‐14. [DOI: 10.1111/j.1528-1157.1992.tb06222.x] [PubMed] [CrossRef] [Google Scholar]
Higgins 2011
- Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from http://handbook.cochrane.org/.
Lefebvre 2011
- Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from http://handbook.cochrane.org/.
Murthy 2007
- Murthy J, Rajshekhar G. Economic evaluation of seizures associated with solitary cysticercus granuloma. Neurology India 2007;55(1):42‐5. [PubMed] [Google Scholar]
Pal 2000
- Pal DK, Carpio A, Sander JW. Neurocysticercosis and epilepsy in developing countries. Journal of Neurology, Neurosurgery, and Psychiatry 2000;68(2):137‐43. [PMC free article] [PubMed] [Google Scholar]
Palacio 1998
- Palacio LG, Jiménez L Garcia HH, Jiménez ME, Sánchez JL, Noh J, et al. Neurocysticercosis in persons with epilepsy in Medellin, Colombia. Epilepsia 1998;39(12):1334‐9. [PubMed] [Google Scholar]
Pradhan 2000
- Pradhan S, Kathuria MK, Gupta RK. Perilesional gliosis and seizure outcome:a study based on magnetization transfer magnetic resonance imaging in patients with neurocysticercosis. Annals of Neurology 2000;48(2):181‐7. [PubMed] [Google Scholar]
Rajshekhar 2003
- Rajshekhar V. Solitary cerebral cysticercus granuloma. Epilepsia 2003;44(Suppl 1):25‐8. [PubMed] [Google Scholar]
Rajshekhar 2004
- Rajshekhar V, Jeyaseelan L. Seizure outcome in patients with a solitary cerebral cysticercus granuloma. Neurology 2004;62(12):2236‐40. [PubMed] [Google Scholar]
Rajshekhar 2006
- Rajshekhar V, Raghava MV, Prabhakaran V, Oommen A, Muliyil J. Active epilepsy as an index of burden of neurocysticercosis in Vellore district, India. Neurology 2006;67(12):2135‐9. [PubMed] [Google Scholar]
RevMan 2014 [Computer program]
- The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Sander 1996
- Sander JW, Shorvon SD. Epidemiology of the epilepsies. Journal of Neurology, Neurosurgery, and Psychiatry 1996;61(5):433‐43. [PMC free article] [PubMed] [Google Scholar]
Singhi 2000
- Singhi P, Ray M, Singhi S, Khandelwal N. Clinical spectrum of 500 children with neurocysticercosis and response to albendazole therapy. Journal of Child Neurology 2000;15(4):207‐13. [PubMed] [Google Scholar]
Zafar 2013
- Zafar MJ. Neurocysticercosis. http://emedicine.medscape.com/article/1168656‐overview#a0156 2013 (accessed 22 May 2014).
References to other published versions of this review
Sharma 2011
- Sharma M, Singh T, Mathew A. Drugs for seizure control in people with neurocysticercosis. Cochrane Database of Systematic Reviews 2011, Issue 3. [DOI: 10.1002/14651858.CD009027] [PubMed] [CrossRef] [Google Scholar]
Sharma 2015
- Sharma M, Singh T, Mathew A. Antiepileptic drugs for seizure control in people with neurocysticercosis. Cochrane Database of Systematic Reviews 2015, Issue 10. [DOI: 10.1002/14651858.CD009027.pub2] [PubMed] [CrossRef] [Google Scholar]