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Subarachnoidal Neurocysticercosis non-responsive to cysticidal drugs: a case series
© Cárdenas et al; licensee BioMed Central Ltd. 2010
Received: 8 October 2009
Accepted: 4 March 2010
Published: 4 March 2010
Neurocysticercosis (NC) is one of the most frequent parasitic diseases of the central nervous system. Cysticidal drugs, albendazole and praziquantel, are generally effective when parasites localize in the parenchyma. In contrast, parasites lodged in the subarachnoid basal cisterns are less responsive to treatment.
The clinical and radiological pictures of six Mexican patients non-respondent to cysticidal treatment are presented.
The possible factors involved in the cysticidal non-response are discussed and hints are provided of potentially useful changes to therapeutic protocols.
Taenia solium is a parasite which larvae (cysticercus) may localize in the central nervous system of humans causing neurocysticercosis (NC). Most NC cases occur with little or no neurological symptoms but others may present a variety of non-specific mild clinical symptoms (headache, partial seizures) or severe neurological syndromes with intracraneal hypertension and generalized seizures .
The introduction of cysticidal drugs, albendazole (ABZ) and praziquantel (PZQ), for the treatment of NC have dramatically improved its prognosis . In Mexico, ABZ is becoming the drug of choice due to its low costs and availability. Parasite localization is one of the main factors involved in the success of the treatment. When cysticerci are lodged in the parenchyma, the use of these drugs allows generally a prompt radiological and clinical improvement in most of the patients although only a modest effect is reported in some cases [3, 4]. When the parasites are located in the subarachnoid basal cisterns (SA-NC), the prognosis is more uncertain. Several case series have reported the effectiveness of these drugs in SA-NC treatment [5–7]. However, in our experience and that of others , it is a frequent finding that the parasites persist after treatment, even when a high dose of ABZ has been used .
In this report, six cases NC-SA patients who are non-respondent to conventional pharmacological treatment and a brief review of literature are described.
Patient B (Figure 1, B0 to 1B3). A 60 year old man with chronic headache. Nine months before hospital admission, headache frequency increased and lower limb motor dysfunction appeared. Neurological examination revealed only papilledema. On MRI, vesicular subarachnoidal NC in posterior fossa was observed. CSF analysis showed an inflammatory profile with abundant lymphocytes and eosinophils. During the year following the diagnosis, he received two courses of ABZ at 30 mg/kg/day during 8 days and one course of ABZ at the same dose, associated with PZQ at 50 mg/kg plus corticosteroids. However, radiological evidence of vesicular parasites was still observed and CSF inflammatory profile and clinical complaints persisted.
Patient C (Figure 1, C0 to 1C5). A 29-year old man with new onset generalized seizures. CT scan showed vesicular NC and he received ABZ plus steroids in the United States of America. Post treatment, progressive motor dysphasia, right sided weakness and intracranial hypertension signs appeared. The patient returned to Mexico. MRI showed vesicular racemose cysticercosis on left Sylvian fissure with displacement of midline anatomical structures. A second ABZ cycle was administered and although the racemose cyst evinced a substantial reduction, other SA vesicular parasites appeared. During two years this patient received four other courses of ABZ (30 mg/kg/day during eight days) and two combined courses of ABZ and PZQ. These treatments were delivered at the same doses as with the other patients and showed no evidence of parasite eradication.
Patient D (Figure 1, D4 to 1D7). A 65-year-old woman with vomiting, papilledema, gait disturbances, and urinary incontinency. The patient had a 6-year history of chronic headache. On admission, CT scan showed multiple vesicular parasites in the Sylvian fissure with mass effect. A surgical removal of parasites located in the right Sylvian fissure and opto-chiasmatic cistern was performed. Three months after surgical procedure, a CT scan showed persistence of subarachnoid vesicular parasites in the chiasma and pontocerebellar cistern. CSF analysis revealed an inflammatory profile (20 cells/mm3) with presence of anti-cysticercal Abs. During four years, patient completed seven courses of ABZ (30 mg/kg/day during 8 days) associated to corticosteroids without complete clinical and radiological improvement.
Patient F (Figure 2, F2 to 2F6). A 26-year old man with new onset partial motor epilepsy. His CT scan showed perimesencephalic vesicular parasites and CSF was inflammatory (75 cells/mm3) with specific anticysticercal Abs. During the following five years, the patient received 7 courses of ABZ (30 mg/kg/day during eight days with corticosteroids) and he required the placement of a VPS for hydrocephalus during the fourth year. In spite of the received treatment, vesicular parasites persisted on the last MRI, and CSF was still inflammatory.
Previous published cases of non-responder patients to cysticidal drugs.
PZQ, PZQ + ABZ
SA (Sylvian fissure)
Intracranial hypertension and ataxia
ABZ, ABZ + ivermectine
ABZ, PZQ + ABZ, ivermectine
SAb and SA sulci
Seizures, hydrocephalus and motor deficit
Whatever are the reasons, this scenario clearly points out to the relevance of developing new therapeutic strategies. One approach could be the elaboration of new albendazole formulations in order to improve its bioavailability and therapeutic efficacy . Another approach is the search of new pharmacological alternatives as ivermectine, which seems to destroy cysticerci in patients resistant to cysticercidal drugs . Nitazoxanide and tizoxanide combined with ABZ have also shown promising results albeit in vitro and using another related cestode .
Finally, although these non-respondent cases are not the most frequent, their severity should encourage controlled studies to evaluate new forms of medical intervention and management. In particular, fuller understanding of the key elements that participate in controlling the inflammatory response would greatly help in devising new, potent and less harmful ways to prevent severe disease.
Written informed consent was obtained from the patients for publication of these cases report and any accompanying images. A copy of the written consents is available for review by the Editor-in-Chief of this journal.
This work was partially supported by Consejo Nacional de Ciencia y Tecnología, México (grant number S0008- 86527).
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