Correspondence
Unité des Maladies Infectieuses Tropicales et Hygiène, Centre hospitalier Andrée Rosemon, 97300 Cayenne, French Guiana, France, and EA 3595, Université des Antilles et de la Guyane, Cayenne, France (AM, PA, MD, FD); and Service d’Imagerie Médicale, Centre hospitalier Andrée Rosemon, Cayenne, French Guiana, France (DJ) 1
2
3
Del Brutto OH. Clinical management of neurocysticercosis. Expert Rev Neurother 2014; 14: 389–96 White AC Jr. New developments in the management of neurocysticercosis. J Infect Dis 2009; 199: 1261–62. Garcia HH, Gonzales I, Lescano AG, for the Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis 2014; 14: 687–95.
We read the Article by Hector Garcia and colleagues1 reporting the efficacy and safety of combined anthelmintic treatment for parenchymal neurcysticercosis with great interest. The efficacy of albendazole and praziquantel monotherapy has largely been suboptimum, leading to complete disappearance of active cysts in only a minority of patients after initial treatment.2 We celebrate the results of Garcia and colleagues, which showed that the combination of albendazole and praziquantel has greatly improved efficacy compared with albendazole monotherapy in patients with parenchymal neurocysticercosis.1 An important attribute of this trial is the primary endpoint of complete cyst resolution, which allows comparison with previous placebo-controlled trials of anthelmintic monotherapy.3 Nevertheless, this trial shows some important issues in treatment of neurocysticercosis. Patients were included if they had “epilepsy secondary to neurocysticercosis” rather than newonset seizures. Because these patients had prevalent seizures, the causal relation between these events and neurocysticercosis cysts is more difficult to ascertain than with newonset seizures. Inclusion of patients with incident seizures (ie, newonset seizures) would be preferable because one can be more certain that these events are directly related to www.thelancet.com/infection Vol 15 March 2015
degenerating cysts that are seen on imaging. Inclusion of these patients is also more likely to be representative of clinical practice where new-onset symptoms are the reason that patients seek care. Furthermore, a clear distinction should be made between seizures and epilepsy because acute symptomatic seizures and unprovoked seizures are associated with different risks of seizure recurrence.4 This trial also shows that diagnostic criteria for neurocysticercosis remain open to interpretation because validated criteria do not exist.5 Garcia and colleagues state that, to their knowledge, their study provides “the first evidence that complete cyst resolution is associated with fewer seizure relapses”. In a previous prospective cohort study of 77 patients with parenchymal neurocysticercosis and new-onset seizures,6 disappearance of cysts was predictive of seizure recurrence irrespective of anthelmintic treatment. Despite finding a reduction in seizure rate comparing patients with and without cyst resolution, Garcia and colleagues did not find a significant difference in the proportion of patients with at least one seizure during followup in the three treatment groups. Thus, findings from this trial do not show that combined treatment has any effect on seizure recurrence. Many unmet needs of evidencebased treatment of neurocysticercosis remain. Extraparenchymal neurocysticercosis is associated with worse prog nosis than is parenchymal disease, and anthelmintic treatment has not been associated with greater disappearance of active cysts compared with placebo.3 Future trials are needed to see if combination treatment would be efficacious in patients with extraparenchymal disease. We declare no competing interests.
*Arturo Carpio, Matthew L Romo [email protected] School of Medicine, University of Cuenca, PO Box 0101-719, Cuenca, Ecuador, and Gertrude H Sergievsky Center, College of Physicians and
Surgeons, Columbia University, New York, NY, USA (AC); and City University of New York School of Public Health, New York, NY, USA (MLR) 1
2
3
4
5
6
Garcia HH, Gonzales I, Lescano AG, et al, for the Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis 2014; 14: 687–95. Carpio A, Romo ML. Epilepsy and neurocysticercosis: an endless debate. Arq Neuropsiquiatr 2014; 72: 383–90. Carpio A, Kelvin E, Bagiella E, et al, for the Ecuadorian Neurocysticercosis Group. The effects of albendazole treatment on neurocysticercosis: a randomized controlled trial. J Neurol Neurosurg Psychiatry 2008; 79: 1050–55. Hesdorffer DC, Benn EK, Cascino GD, Hauser WA. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia 2009; 50: 1102–08. Machado LR. The diagnosis of neurocysticercosis: a closed question? Arq Neuropsiquiatr 2010; 68: 1–2. Carpio A, Hauser WA. Prognosis for seizure recurrence in patients with newly diagnosed neurocysticercosis. Neurology 2002; 59: 1730–34.
Hector Garcia and colleagues,1 in a double-blind, randomised, controlled trial, reported that combined treat ment with albendazole and praziquantel resulted in an increased antiparasitic efficacy in patients with multiple brain cysticercosis cysts without increased side-effects. This study is a big advance towards treatment of neurocysticercosis. However, Chinese scientists have substantial experience in treatment of cerebral cysticercosis with albendazole plus praziquantel. In a randomised clinical trial recruiting 864 patients with definite diagnosis of cerebral cysticercosis, 2 two albendazole– praziquantel combination regimens (96% and 98% total effective rate) were noted to be more efficacious than was treatment with albendazole (55% total effective rate) or praziquantel (68% total effective rate) alone (p
Unité des Maladies Infectieuses Tropicales et Hygiène, Centre hospitalier Andrée Rosemon, 97300 Cayenne, French Guiana, France, and EA 3595, Université des Antilles et de la Guyane, Cayenne, France (AM, PA, MD, FD); and Service d’Imagerie Médicale, Centre hospitalier Andrée Rosemon, Cayenne, French Guiana, France (DJ) 1
2
3
Del Brutto OH. Clinical management of neurocysticercosis. Expert Rev Neurother 2014; 14: 389–96 White AC Jr. New developments in the management of neurocysticercosis. J Infect Dis 2009; 199: 1261–62. Garcia HH, Gonzales I, Lescano AG, for the Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis 2014; 14: 687–95.
We read the Article by Hector Garcia and colleagues1 reporting the efficacy and safety of combined anthelmintic treatment for parenchymal neurcysticercosis with great interest. The efficacy of albendazole and praziquantel monotherapy has largely been suboptimum, leading to complete disappearance of active cysts in only a minority of patients after initial treatment.2 We celebrate the results of Garcia and colleagues, which showed that the combination of albendazole and praziquantel has greatly improved efficacy compared with albendazole monotherapy in patients with parenchymal neurocysticercosis.1 An important attribute of this trial is the primary endpoint of complete cyst resolution, which allows comparison with previous placebo-controlled trials of anthelmintic monotherapy.3 Nevertheless, this trial shows some important issues in treatment of neurocysticercosis. Patients were included if they had “epilepsy secondary to neurocysticercosis” rather than newonset seizures. Because these patients had prevalent seizures, the causal relation between these events and neurocysticercosis cysts is more difficult to ascertain than with newonset seizures. Inclusion of patients with incident seizures (ie, newonset seizures) would be preferable because one can be more certain that these events are directly related to www.thelancet.com/infection Vol 15 March 2015
degenerating cysts that are seen on imaging. Inclusion of these patients is also more likely to be representative of clinical practice where new-onset symptoms are the reason that patients seek care. Furthermore, a clear distinction should be made between seizures and epilepsy because acute symptomatic seizures and unprovoked seizures are associated with different risks of seizure recurrence.4 This trial also shows that diagnostic criteria for neurocysticercosis remain open to interpretation because validated criteria do not exist.5 Garcia and colleagues state that, to their knowledge, their study provides “the first evidence that complete cyst resolution is associated with fewer seizure relapses”. In a previous prospective cohort study of 77 patients with parenchymal neurocysticercosis and new-onset seizures,6 disappearance of cysts was predictive of seizure recurrence irrespective of anthelmintic treatment. Despite finding a reduction in seizure rate comparing patients with and without cyst resolution, Garcia and colleagues did not find a significant difference in the proportion of patients with at least one seizure during followup in the three treatment groups. Thus, findings from this trial do not show that combined treatment has any effect on seizure recurrence. Many unmet needs of evidencebased treatment of neurocysticercosis remain. Extraparenchymal neurocysticercosis is associated with worse prog nosis than is parenchymal disease, and anthelmintic treatment has not been associated with greater disappearance of active cysts compared with placebo.3 Future trials are needed to see if combination treatment would be efficacious in patients with extraparenchymal disease. We declare no competing interests.
*Arturo Carpio, Matthew L Romo [email protected] School of Medicine, University of Cuenca, PO Box 0101-719, Cuenca, Ecuador, and Gertrude H Sergievsky Center, College of Physicians and
Surgeons, Columbia University, New York, NY, USA (AC); and City University of New York School of Public Health, New York, NY, USA (MLR) 1
2
3
4
5
6
Garcia HH, Gonzales I, Lescano AG, et al, for the Cysticercosis Working Group in Peru. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial. Lancet Infect Dis 2014; 14: 687–95. Carpio A, Romo ML. Epilepsy and neurocysticercosis: an endless debate. Arq Neuropsiquiatr 2014; 72: 383–90. Carpio A, Kelvin E, Bagiella E, et al, for the Ecuadorian Neurocysticercosis Group. The effects of albendazole treatment on neurocysticercosis: a randomized controlled trial. J Neurol Neurosurg Psychiatry 2008; 79: 1050–55. Hesdorffer DC, Benn EK, Cascino GD, Hauser WA. Is a first acute symptomatic seizure epilepsy? Mortality and risk for recurrent seizure. Epilepsia 2009; 50: 1102–08. Machado LR. The diagnosis of neurocysticercosis: a closed question? Arq Neuropsiquiatr 2010; 68: 1–2. Carpio A, Hauser WA. Prognosis for seizure recurrence in patients with newly diagnosed neurocysticercosis. Neurology 2002; 59: 1730–34.
Hector Garcia and colleagues,1 in a double-blind, randomised, controlled trial, reported that combined treat ment with albendazole and praziquantel resulted in an increased antiparasitic efficacy in patients with multiple brain cysticercosis cysts without increased side-effects. This study is a big advance towards treatment of neurocysticercosis. However, Chinese scientists have substantial experience in treatment of cerebral cysticercosis with albendazole plus praziquantel. In a randomised clinical trial recruiting 864 patients with definite diagnosis of cerebral cysticercosis, 2 two albendazole– praziquantel combination regimens (96% and 98% total effective rate) were noted to be more efficacious than was treatment with albendazole (55% total effective rate) or praziquantel (68% total effective rate) alone (p
