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Background Infection with the larval form of the pork tapeworm, Taenia solium, can lead to the development of cysts in the brain. Surgical removal of cysts has been the accepted treatment for neurocysticercosis characterized by giant cysts when there is associated intracranial hypertension.
Methods We describe 33 patients whom we treated medically for malignant forms of neurocysticercosis. All patients had evidence of intracranial hypertension and subarachnoid cysts at least 50 mm in diameter. All patients received 15 mg of albendazole per kilogram of body weight per day for four weeks. Ten patients were also treated with 100 mg of praziquantel per kilogram per day for four weeks. Seventeen patients received a second course of albendazole, three received a third course, and one received a fourth course. During the first cycle of treatment, all patients also received dexamethasone. Five patients had previously undergone neurosurgery for giant cysts.
Results After a median of 59 months of follow-up (range, 7 to 102), the condition of all 33 patients had improved, and the cysts had disappeared or become calcified. Of the 22 patients with a history of seizures, only 11 continued to receive antiseizure medications. The median quality-of-life score on the Karnofsky scale improved from 40 to 100. Fifteen patients received a ventriculoperitoneal shunt because of hydrocephalus. Four patients had persistent sequelae (bilateral partial optic atrophy, stroke, or diplopia) of the cysts.
Conclusions Intensive medical treatment can be effective in patients with neurocysticercosis characterized by giant cysts. Neurosurgery may be required only when there is an imminent risk of death.
The clinical picture of neurocysticercosis ranges from asymptomatic infections to severe, life-threatening disease.4 Cysticercosis is highly prevalent in developing countries, where it constitutes a serious public health problem.3,4 Treatment of the severe forms of neurocysticercosis can be very expensive.5 Among the forms of the infection, neurocysticercosis characterized by giant cysts is relatively uncommon,6 although in our referral hospital this form accounts for nearly 10 percent of all cases of neurocysticercosis.
The subarachnoid space is the most frequent site of neurocysticercosis.6 Neurocysticercosis with giant cysts has generally been defined by the presence of a cyst more than 50 mm in diameter.7 Because of the prognostic and therapeutic implications, we also included in the definition clinical manifestations that suggest an expansile mass and intracranial hypertension. Perilesional cerebral edema responds well to corticosteroids, which raises the possibility of medical instead of surgical treatment for neurocysticercosis.
Giant cysts do not always cause intracranial hypertension, possibly because the cysts grow slowly. The development of intracranial hypertension is an ominous sign, and surgery has been considered the treatment of choice for patients with neurocysticercosis with intracranial hypertension.5,8,9,10
We report on a series of patients with neurocysticercosis with giant cysts and intracranial hypertension whom we treated with corticosteroids and the cesticidal drugs albendazole and praziquantel.
Methods
Patients
A total of 320 patients with different forms of neurocysticercosis were seen between November 1991 and May 2000 at the neurocysticercosis clinic in the Hospital de Especialidades, Centro Médico Nacional Siglo XXI, in Mexico City. Thirty-three had a subarachnoid cyst with a diameter of more than 50 mm, which is currently accepted as the standard definition of neurocysticercosis with giant cysts,7,10,11 and evidence of intracranial hypertension. The group consisted of 17 men and 16 women 18 to 81 years of age (mean, 48.6) who were studied prospectively.
At admission, most patients presented with headache, nausea, and vomiting. A total of 15 patients had papilledema, 5 had hemiparesis, 1 had paraparesis, 3 had cerebellar dysfunction, 3 had visual impairment, 15 had hydrocephalus, and in 4 an acute confusional state developed that lasted several days. A total of 7 patients had a history of surgical removal of cysts, which were giant in 5.
The quality of life of patients was measured by the Karnofsky scale, with scores from 0 (which indicates death) to 100 (which indicates functional independence and lack of symptoms).
The current study complies with the Declaration of Helsinki and was approved by the hospital ethics committee. Before entry into the study, patients received detailed information concerning the surgical procedures available for this type of neurocysticercosis. Each patient provided written informed consent.
Imaging Studies and Laboratory Tests
Diagnosis was made by computed tomography (CT) in all 33 patients. Magnetic resonance imaging (MRI) was performed in 31 patients at the onset of treatment. The presence of antibodies against T. solium in serum was determined by Western blot analysis in all patients. Follow-up scanning with CT and MRI was performed every six months until the lesions disappeared or became calcified. MRI or CT was then performed at least once a year. The criterion for treatment success was evidence of the disappearance or calcification of the lesions on imaging studies.
Treatment
Ten of the 15 patients in whom hydrocephalus developed were admitted to the hospital and treated with a ventriculoperitoneal shunt before the initiation of cesticidal treatment; the other 5 patients received shunts after the initiation of treatment. All 33 patients initially received 8 mg of intravenous dexamethasone every eight hours. After the first three doses of dexamethasone, most patients no longer had symptoms related to intracranial hypertension, which we considered a necessary condition for the initiation of cesticidal treatment. The 33 patients received a total of 59 courses of albendazole at a dose of 15 mg per kilogram of body weight per day, administered in three divided doses, for four weeks. Intravenous dexamethasone was initiated at a dose of 8 mg every eight hours, as noted above, and then reduced to 4 mg every eight hours on day 3, after which it was replaced by 0.4 mg of prednisone per kilogram per day in three divided doses, with the dose tapered after albendazole treatment was stopped. Twelve patients received one cycle, 17 received two cycles, 3 received three cycles, and 1 received four cycles. The criterion for giving a patient an additional course of albendazole was a partial or incomplete response. Ten patients who did not have a response to albendazole received one course of 100 mg of praziquantel per kilogram per day, in two divided doses administered two hours apart, accompanied by the same type of treatment with dexamethasone as was given with albendazole. Three of these patients had previously received only a single course of albendazole.
Results
Adverse Effects
Headache was the most frequent adverse effect and was reported after day 3 during 20 of the 59 courses of albendazole and in 5 of the 10 patients treated with praziquantel from day 1 of the regimen. Headache was relieved by nonprescription analgesics. Other adverse effects included a transient loss of seizure control despite medical therapy in four patients receiving albendazole and in one receiving praziquantel; seizure control improved after an increase in the dose of antiepileptic drugs.
Clinical Follow-up
The follow-up period ranged from 7 to 102 months (median, 59). One patient died because of aplastic anemia, which was present well before the diagnosis of neurocysticercosis was made. Of the 22 patients with seizures, only 11 continued to receive antiepileptic treatment. The mental status of all four patients with confusional states returned to normal after the first day of treatment with dexamethasone. The condition of all patients with focal, motor, or sensory deficits returned to normal during the first cycle of treatment. Two of the 15 patients with ventriculoperitoneal shunts had shunt malfunctions during one of the treatment cycles and required a new device.
One patient had bilateral partial optic atrophy due to nerve entrapment by basal arachnoiditis at admission, with a slight improvement of visual function after cesticidal treatment. Two patients had strokes that were considered possible complications of treatment, one in the territory of the left middle cerebral artery and the other a lacunar infarction in the left thalamus; both patients had additional risk factors for stroke. These complications occurred months after the cesticidal treatment, and in both cases the giant cysts and strokes were on opposite sides of the brain. Diplopia (due to paresis of cranial nerve VI) persisted in one patient who had intracranial hypertension due to hydrocephalus.
Two other patients with persistent headache had a partial response to analgesics and beta-blockers. No patient required neurosurgical removal of cysts at any time after the medical treatment began.
The quality of life was evaluated with the Karnofsky scale before treatment and after lesions disappeared or calcified.12 At the beginning, the median was 40 (interquartile range, 30 to 60); at the end, the median was 100 (interquartile range, 90 to 100; P<0.001 by the Wilcoxon signed-rank test).
Imaging Follow-up
A total of 50 giant cysts were initially present in all 33 patients (range, 1 to 3 cysts per patient). The most frequent location was the sylvian fissure. In 23 patients, additional smaller cysts were also present, with 1 to 18 cysts per patient in 17 patients (mean, 4) and too many to count in 6 patients. Fourteen of the patients with additional lesions could have been classified as having severe forms of neurocysticercosis even without the giant cysts. In 11, the cysts were located in the basal cisterns, whereas in the other 4 patients they were located in the ventricles (Table 1). All patients had several degrees of edema surrounding the giant cysts, ranging from mild to severe, which enhanced the mass effect and increased the displacement of adjacent structures. All patients with supratentorial giant cysts had evidence of displacement of midline structures at admission.
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Although the efficacy of praziquantel and albendazole in parenchymal forms of neurocysticercosis has been clear for many years,13,14 surgical removal of cysts has been considered the treatment of choice for neurocysticercosis characterized by giant cysts.3,4,8,9,10 Some authors suggest that surgery should be performed as soon as possible after the diagnosis to minimize the risk of sequelae or death.8,9,10
The definition of neurocysticercosis with giant cysts in the medical literature is far from precise. Joubert and Van As11 and Castellanos et al.10 adopted their criteria from the single case report by Berman et al., who described the pathological characteristics of a surgically removed cyst approximately 50 mm in diameter and 60 ml in volume.7 Other authors do not provide criteria for defining neurocysticercosis with giant cysts. Because of the therapeutic and prognostic implications, we propose that the size of the cyst should not be the sole criterion for defining this form of neurocysticercosis. In addition to a 50-mm or larger cyst, intracranial hypertension must be present. We included only patients with intracranial hypertension and with imaging studies that documented severe compression and displacement of adjacent brain structures.
Joubert and Van As11 described the first four patients with neurocysticercosis with large cysts who were treated with praziquantel and whose disease completely resolved. Del Brutto et al. reported on four patients successfully treated with albendazole and dexamethasone.15 However, intracranial hypertension was not described in any of these eight patients. Noboa reported on one patient without intracranial hypertension who was treated with albendazole and dexamethasone, with poor results and severe neurologic deficits.16 Soto Hernández et al. reported on two patients with neurocysticercosis associated with human immunodeficiency virus infection; one was treated with albendazole and the other with surgery because of intracranial hypertension. On the basis of this limited experience, they concluded that surgery is lifesaving in patients with intracranial hypertension.9 Castellanos et al. reported on two patients who were successfully treated, one with albendazole and the other, who had intracranial hypertension, with surgical removal of the parasite.10 Bandres et al. reported a poor response to cesticidal treatment in patients with extraparenchymal forms of neurocysticercosis and therefore discouraged the use of this treatment for subarachnoid cysts.17 Finally, Agapejev et al. reported a poor prognosis for patients with intracranial hypertension who were treated with albendazole or praziquantel. In their series, only 10 of 22 patients treated had satisfactory results. Eight patients died, three during treatment with albendazole; four had severe sequelae; and only one of the patients with a large cyst had a good outcome.18
In the current study, we report the results of 33 patients with neurocysticercosis characterized by giant cysts, all of whom had intracranial hypertension as the principal feature. All patients were treated with 15 mg of albendazole per kilogram per day. Ten patients also received 100 mg of praziquantel per kilogram per day, twice the usual dose,19 since corticosteroids reduce serum levels of praziquantel by approximately 50 percent20 and these levels are further decreased by the concomitant use of antiepileptic drugs.21 We used a sustained dose of albendazole for four weeks because, in comparison with parenchymal forms, subarachnoid neurocysticercosis usually requires more than one cycle of treatment. Moreover, albendazole is the drug of choice because it reaches higher levels in the subarachnoid space, drug levels are not affected by corticosteroids, and it has fewer adverse effects than praziquantel.20
The fact that, in patients with neurocysticercosis with giant cysts, corticosteroids induce an early improvement in intracranial hypertension, which in patients with hydrocephalus also requires shunting, led us to reason that these patients could receive pharmacologic treatment in an attempt to eliminate the need for the surgical removal of giant cysts. This hypothesis was further supported by the presence of multiple coexisting cysts in 23 of the patients, including intraventricular cysts in 4, which would have been nearly impossible to remove simultaneously with the giant cysts. Moreover, seven of the patients we describe had had a relapse after the earlier surgical removal of cysticerci (which were giant in five). Thus, most of our patients would have been obvious candidates for cesticidal treatment even after the removal of giant cysts.
Symptoms resolved in most of our patients during the first cycle of treatment, regardless of the need for additional cycles of therapy and long before the disappearance of lesions in imaging studies. Both praziquantel and albendazole were well tolerated, without severe adverse effects or complications. These results differ from those of Bandres et al.17 and Agapejev et al.18 Two patients required replacement of a ventricular peritoneal shunt during treatment. Shunt dysfunction is a common complication of hydrocephalus due to neurocysticercosis,8,22 but it cannot be ruled out as a complication of the medical treatment.
We could not confirm the previously reported response to a single cycle of treatment with albendazole for neurocysticercosis with giant cysts,10,11,15,16 since in many of our patients more than one cycle was required. We have observed in MRI studies that, despite an initial clinical improvement, the lesions of neurocysticercosis with giant cysts need considerable time and more than one treatment cycle to disappear. Associated nongiant cysts usually disappear more quickly, which could account for the initial improvement. In all but one of the reported cases, patients were followed up only by CT. Although in our study follow-up included both CT and MRI, the latter was a better method for monitoring the remaining lesions, because of its higher resolution.
Our results demonstrate that patients with neurocysticercosis with giant cysts that responds to corticosteroids or shunting should be given cesticidal treatment. Surgical removal of cysts should be considered only in patients who have life-threatening intracranial hypertension despite treatment with corticosteroids. Surgical procedures and their potential complications can be avoided in most patients with neurocysticercosis with giant subarachnoid cysts, a condition previously considered to be an absolute indication for surgery.
We are indebted to Dr. José Moreno for his critical reading of the manuscript, to Antonio Sánchez for creating the figures, and to Margarita Jiménez for her invaluable assistance in the statistical analysis of the data.
Source Information
From the Medical Research Unit for Neurologic Diseases (J.V.P., I.M., I.G.) and the Departments of Imaging (F.A., G.D.) and Neurosurgery (B.L.-F.), Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Mexican Institute of Social Security, Mexico City, Mexico.
Address reprint requests to Dr. Proaño at Santiago Valverde No. 68, Col. Presidentes Ejidales, C.P. 04470, México D.F., Mexico, or at proanio_00{at}yahoo.com.
References
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