Anticysticercal Drugs Research Articles

Neurocysticercosis presenting as Meningoencephalitis

Human neurocysticercosis, the infection of the nervous system by the larvae of Taenia solium , is a cause of epileptic seizures and other neurologic morbidity worldwide. The disease occurs when humans become intermediate hosts of Taenia solium by ingesting its eggs from contaminated food or, most often, directly from a taenia carrier by the fecal-to-oral route. Cysticerci may be located in brain parenchyma, subarachnoid space, ventricular system, or spinal cord, causing pathological changes that are responsible for the pleomorphism of neurocysticercosis. The most common clinical manifestation being the seizures (70-90%), but many patients present with focal deficits, intracranial hypertension, or cognitive decline. The accurate diagnosis of neurocysticercosis is possible after interpretation of clinical data together with findings of neuroimaging studies and/ or results of immunological tests. Encephalitis is the inflammation of brain parenchyma presenting as acute febrile illness with altered level of consciousness, confused behavioral abnormality and depressed level of consciousness ranging from mild lethargy to coma and evidence of either focal or diffused neurological sign and symptoms. Parenchymal brain cysticerci in the acute encephalitic phase have been recognized since the first reports of CT in patients with neurocysticercosis. These lesions were described as focal low densities surrounded by oedema and ring-like enhancement after giving contrast medium. The abnormal enhancement of these lesions were related to the breakdown in the blood-brain barrier caused by the inflammatory reaction around dying cysticerci. We report a case of 10-year-old female child presenting with fever, headache and altered sensorium. This case report may help the practitioners to identify this disease with different presentations, some with fatal presentation, so that needful imaging and management would be instituted at the earliest keeping in mind that Anticysticercal drugs are contraindicated in patients with cysticercotic encephalitis because they may exacerbate the inflammatory response within the brain parenchyma.

Cerebrovascular Complications of Neurocysticercosis

It is well established that several infectious diseases can directly lead to ischemic or hemorrhagic stroke. Neurocysticercosis (NCC), caused by infection of the human central nervous system with the parasite Taenia solium, is recognized as an important public health problem in developing countries. The clinical manifestations of NCC are nonspecific and varied depending on the number and topography of lesions. Cerebrovascular disease is a relatively common but underrecognized complication of NCC; published data indicate that the incidence of stroke is between 4% and 12% in patients with NCC, depicting a clear relationship among these 2 pathologies. We review the cerebrovascular complications of NCC including the possible role of NCC as a cerebrovascular risk factor, including epidemiology, pathogenesis, diagnosis, and management of the cerebrovascular complications derived from cysticercal infarction and those associated with the use of anticysticercal drugs. Common and uncommon clinical manifestations, localization of stroke, and associated syndromes are discussed along with their prognostic significance. Although an underrecognized cause of stroke, present preponderantly in undeveloped countries, NCC still causes significant incapacity and even death in young patients suffering from stroke in the absence of cerebrovascular risk factors; hence, neurologists should become familiar with this potential complication.

Treatment of neurocysticercosis: is it beneficial?

Evaluation of: Carpio A, Kelvin EA, Bagiella E et al.; Neurocysticercosis Group TE. The effects of albendazole treatment on neurocysticercosis: a randomized controlled trial. J. Neurol. Neurosurg. Psychiatry DOI: 10.1136/jnnp.2008.144899 (2008) (Epub ahead of print).Neurocysticercosis is the most common parasitic disease of the CNS. Intracranial neurocysticercosis is classified into cerebral parenchymal and extraparenchymal forms (subarachnoidal and intraventricular). Current medical therapy for parenchymal and extraparenchymal neurocysticercosis invovles the use of anticysticercal drugs. Albendazole and praziquantel are two commonly used drugs. Most experts prefer to always use oral or parenteral corticosteroids along with anticysticercal drugs. The role of anticysticercal drugs in the treatment of parenchymal neurocysticercosis has always been a subject of intense controversy. Whether therapy with anticysticercal drugs results in improved seizure-related prognosis remains a major concern. A recent meta-analysis evaluating six controlled trials suggests that treatment with anticysticercal drugs results in better resolution of colloidal and vesicular cysticerci; in patients taking anticysticercal drugs, there was a lower risk of seizure reccurence in patients with colloidal cysticerci and a significant reduction in the rate of generalized seizures in patients with vesicular cysticerci. However, the findings of the study by Carpio et al. have revived the controversy regarding this treatment. These authors noted that the effect of a single dose of albendazole is, at best, only modest. Only a minority of patients with parenchymal neurocysticercosis benefitted and became cyst free and there was a lack of effectiveness toward the associated seizure disorders. No response was seen in patients with degenerative parenchymal or extraparenchymal forms of neurocysticercosis. Carpio et al. suggest that there is a need for further studies that employ different approaches, such as the use of high initial doses of albendazole, the use of two anticysticercal drugs or repeated prolonged courses of albendazole.

Surgical treatment of cerebral cysticercosis: long-term results and prognostic factors

Cysticercosis is the most frequent parasitosis of the central nervous system. Although anticysticercal drugs have proven efficient in some cases, many patients with NCC require palliative, occasionally curative, surgical procedures. The authors analyzed the data and prognostic factors obtained during the follow-up period (range 1-255 months, median 38 months) in 160 patients with cerebral cysticercosis who underwent surgical treatment. Different surgical approaches were indicated to control increased intracranial pressure (ICP) in most patients, and some patients had undergone decompressive surgery for local brain lesions. Most patients required more than one surgical procedure. Statistical analysis was performed using the Fisher exact, the log-rank, and the Kruskall-Wallis tests. Survival curves were calculated according the Kaplan-Meier method. The removal of a giant cyst from the parenchyma or cisterns for relief of increased ICP and for chiasm/optic nerve decompression improved most symptoms in patients. The removal of ventricular cysts was effective in the control of increased ICP in most patients. Patients with a ventricular cyst and ependymitis/arachnoiditis required placement of a ventriculoperitoneal (VP) shunt after the cyst was removed. This therapy effectively controlled increased ICP. Patients younger than 40 years of age at the time of treatment and male patients had worse outcomes. The outcome in patients who underwent VP shunt surgery or shunt surgery combined with reservoir implantation was worse than that in those who underwent cyst removal alone. Shunt-related infection was the most frequent complication, and the global mortality rate during the follow-up period was 21.2%. Although both complications were more frequent in the first 2 postoperative years, they occurred at any time. Long-term prognosis in patients with cerebral cysticercosis who required surgery was not good. Cysts located in the basal cisterns and patient age younger than 40 years were poor prognostic factors.

Single enhancing computerized tomography–detected lesion in immunocompetent patients

Single enhancing computerized tomography (CT)-documented lesions may occur in several infectious and neoplastic diseases of the central nervous system and are the most common radiological abnormality seen in patients with acute-onset seizures in India and many other developing countries. Similar CT-documented lesions have also been reported in the developed world where these lesions are often considered to be caused by neoplasms or tuberculoma. Histopathological studies in India and even in some developed countries revealed that neurocysticercosis (NCC) is the most likely cause of these lesions provided they fulfill a rigid set of clinical and radiological criteria. Single cysticercus granuloma measures less than 20 mm in diameter, may be associated with cerebral edema not severe enough to produce midline shift, and occur in patients with seizures, normal neurological status, and no evidence of active systemic disease. When these lesions resolve spontaneously, either disappearing or changing into a calcified nodule, the diagnosis of NCC is very likely. The second most common cause of these CT-detected lesions is tuberculoma; in patients with these lesions similar clinical and neuroimaging features are also present. Few authors believe that in poor and developing countries, where both tuberculosis and NCC are common, it is difficult to differentiate between tuberculoma and a single cysticercal granuloma. The most interesting feature of these solitary enhancing lesions is their spontaneous disappearance within weeks or months. Some lesions "heal" by becoming calcified. These patients require only antiepileptic therapy, and this medication may be withdrawn safely after the lesion has resolved on CT scanning. In several studies provision of anticysticercal drugs has been attempted, but because of conflicting results, their role in the management of these single lesions is uncertain. Neurosurgeons have a very limited role to play. In very rare situations, if the lesion increases in size and if focal neurological deficits manifest or seizures are uncontrolled, a brain biopsy sample may be required and histopathological evaluation performed to establish the correct diagnosis.

Pharmacokinetic optimisation of the treatment of neurocysticercosis.

Neurocysticercosis is the most important parasitic infection of the nervous system. It is common in communities living in conditions with poor hygiene. Until the last 2 decades, there was no specific pharmacological treatment: surgery and corticosteroids were the only medical alternatives. The recent introduction of anticysticercal drugs, an isoquinoline (praziquantel) and a benzimidazole (albendazole), has dramatically changed the medical management of neurocysticercosis. Praziquantel is taken orally and undergoes extensive first pass hepatic biotransformation. Peak concentration in serum is reached after 1 to 2 hours and the elimination half-life is between 1 and 3 hours. Praziquantel permeates the blood-brain barrier, thus explaining its effectiveness on parenchymal brain cysticercosis. Plasma concentrations of the drug are increased when a high carbohydrate diet is administered. Cimetidine also increases the plasma concentration of praziquantel by inhibition of cytochrome P450. Bioavailability of the drug is markedly reduced when given jointly with antiepileptics or corticosteroids, specially carbamazepine, phenytoin or dexamethasone. The current schedule for neurocysticercosis treatment lasts 2 weeks at daily doses of 50 mg/kg. Recently, a new therapeutic scheme has been proposed that considers the pharmacokinetics of the drug. This regime lasts only 1 day and includes 3 dosages of 25 mg/kg at 2-hour intervals. This increases the time that the parasite is exposed to high drug concentrations. This therapeutic scheme has produced similar results to longer schemes, with the additional advantages of cost, length of usual treatments and reduction in total dose received (being one-tenth of the total dosage). Albendazole is considered by many as the drug of choice for treatment of neurocysticercosis. It is given orally and is rapidly and extensively metabolised to albendazole sulfoxide (ALBSO), which is considered to be the metabolite directly or indirectly responsible for both toxicity and efficacy outside the gastrointestinal tract. Concentrations of ALBSO are highly variable between individuals and it has a half-life of between 6 and 15 hours. It also crosses the blood-brain barrier. In patients with extrahepatic obstruction, the elimination process is prolonged and plasma concentration is increased. Fatty meals improve absorption. Concomitant administration of albendazole with dexamethasone or with praziquantel increases plasma concentration of ALBSO. Albendazole is administered in an 8 day course of 15 mg/kg per day in 2 divided doses 12 hours apart. This scheme, based on drug pharmacokinetics, has proven to be highly effective. Inflammation is a common accompaniment of neurocysticercosis; in many cases it is the aetiopathogen responsible for histological damage. Corticosteroid therapy is useful for preventing further tissue injury. Long term corticosteroid therapy can be accomplished with 50 mg of oral prednisone 3 times a week. Acute corticosteroid therapy includes brief courses with high dosages of intramuscular dexamethasone or intravenous methylprednisolone. Clinical decisions on cysticidal and anti-inflammatory treatments must be made with the information gathered by neuroimaging studies, either computed tomography or magnetic resonance, and by the analysis of cerebrospinal fluid.

Is the Course of Neurocysticercosis Modified by Treatment With Anthelmintic Agents?

It is with great surprise that I read the article on anticysticercal drug therapy by Carpio et al.¹In that study, anticysticercal drugs were not better than symptomatic therapy for the resolution of parenchymal brain cysticerci and did not modify the clinical course of the disease. These results differ from those reported in most studies about praziquantel or albendazole therapy for parenchymal neurocysticercosis (NC)^2-10and did not match with those previously reported by the same authors in the same population of patients with NC. In 1988, Carpio et al¹¹described 20 patients with parenchymal NC in whom albendazole was highly effective and caused a 84% reduction in the number of brain cysts. Because albendazole has been used to treat human NC since 1986,³it must be assumed that those 20 patients had to be included in their 1995 study, because, according to the authors, "Between July

Surgical Treatment of Cysticercosis of the Central Nervous System

Summary: Cysticercosis is the most frequent parasitosis of the central nervous system. Because anticysticercal drugs do not prevent complications such as hydrocephalus, many patients with cysticercosis require surgical intervention. A review of the pathophysiology and surgical treatment of this disease is presented. Free spinal cysts may need surgical removal, generally with transient good results. Cysts compressing cranial nerves or the brainstem may be removed, generally with good results. Frequently patients with cysticercosis need surgery to control increased intracranial pressure. Based on the pathophysiological mechanisms of intracranial hypertension, different surgical approaches may be indicated. Giant cysts are removed with good results. Patients with the pseudotumoral form of cyst whose clinical treatment has failed generally have poor outcomes when subjected to decompressive craniectomies. Removal of cysts and/or ventriculoperitoneal shunting are performed in patients with hydrocephalus. Removal of free ventricular cysts generally produces a good outcome. Patients with adherent cysts need ventriculoperitoneal shunting posteriorly. Patients with inflammatory hydrocephalus require ventriculoperitoneal shunting. Despite many complications, ventriculoperitoneal shunting is effective to control increased intracranial pressure. Generally, patients with intraparenchymal forms of cysticercosis (normal size or giant cysts) have a better prognosis than do patients with the extraparenchymal form (cisternal, ventricular, and spinal), except for cases of free intraventricular cysts. We present our recent policy for management of patients with this disease.

Medical Treatment of Cysticercosis--Ineffective

The firststudies on specific drug therapy for neurocysticercosis (NCC) appeared more than one decade ago. 1-5 As usually occurs with pioneer work with many other drugs, such studies only included anecdotal case reports or small series of patients with different forms of the disease. Therefore, the efficacy of anticysticercal drugs was difficult to evaluate. A new age of knowledge on medical treatment for NCC began when Sotelo and coworkers 6,7 published the first controlled trials of praziquantel therapy in patients with parenchymal brain cysts. The authors used historical controls to demonstrate that viable cysticerci may live unchanged for several years within the brain parenchyma and that a course with praziquantel at daily doses of 50 mg per kilogram of body weight for 15 days destroys more than 60% of these cysts in less than 3 months. Using a similar design, several articles from different areas of the world further

Cysticercosis of the central nervous system. I. Surgical treatment of cerebral cysticercosis: a 23 years experience in the Hospital das Clínicas of Ribeirão Preto Medical School.

Cysticercosis is the most frequent parasitosis of the nervous system and nowadays it is widespread through the world. Despite the development of anticysticercal drugs (praziquantel and albendazole), their efficacy is more marked in cases with parenchymal active cysts and they do not prevent complications such as hydrocephalus. Thus, many patients with neurocysticercosis require surgical intervention, generally of palliative nature, but that may occasionally produce a cure. The clinical outcome of 180 patients with cerebral cysticercosis who underwent surgical treatment form 1970 to 1993 was analyzed. Surgical treatment was performed to control increased ICP in 177 patients and due to local compression of cranial nerves or brainstem in five. Some patients had more than one surgical procedure, totalizing 287 interventions. Increased intracranial pressure (ICP) was caused by hydrocephalus in 91%, by intracranial mass lesion (tumoral form) in 6.2% and by pseudotumor cerebri (pseudotumoral form) in 2.8% of the case. Based on the pathophysiological mechanisms of intracranial hypertension identified through conventional CT-scan, ventriculography, cysternotomography, ventriculotomography and MRI, different surgical approaches were indicated. Patients with tumoral form were submitted to direct approach and cyst removal and generally they had benefits from this procedure. Patients with pseudotumoral form whose clinical treatment failure underwent decompressive craniectomies and had a poor outcome (40% of good results). Direct removal of ventricular/cisternal cysts and/or ventriculoatrial/peritoneal shunting (VA/VPS) was performed in patients with hydrocephalus. Removal of free ventricular cysts in patients who had no ependimitis/arachnoiditis generally allowed a good outcome. Patients with adherent cysts and inflammatory process needed a VA/VPS posteriorly and the outcome was not so good. One hundred thirty-two patients were submitted to VA/VPS (109 as the first procedure and 23 after another surgical treatment). The VA/VPS was effective to control increased ICP, despite many complications observed mainly during the two first postoperative years. After this period the surviving patients generally had a better outcome. The patients submitted to cyst removal due to local compression of cranial nerves/brainstem generally had good results. Based on the experience acquired with the management of these patients we present our recent policy for the treatment of patients with neurocisticercosis.

Therapy for Neurocysticercosis: A Reappraisal

Accepted approaches to therapy for the different forms of neurocysticercosis are reviewed. Therapy must be individualized according to the level of disease activity and the location of the parasite. Patients with inactive disease should receive only symptomatic treatment. In contrast, patients with parenchymal brain cysts must receive a course of anticysticercal drugs. Both albendazole and praziquantel are useful; however, recent evidence favors the former as the drug of choice for this form of the disease. Albendazole (but not praziquantel) is also effective in the treatment of giant subarachnoid cysts; such medical treatment obviates surgery in some cases. Patients with ventricular cysts may also benefit from medical therapy; however, surgery is the current approach to this type of lesion, as it is to spinal cysticercosis. Although intraocular cysts have classically been resected by surgery, a recent study indicates that albendazole is equally effective. For patients with mixed forms of neurocysticercosis, therapeutic measures related to--but not directly targeting--the disease (i.e., steroid administration for brain edema or shunt placement for hydrocephalus) should be contemplated before therapy with anticysticercal drugs is instituted.

Epilepsy due to neurocysticercosis

We reviewed clinical, EEG, and CT findings of 203 patients with epilepsy due to neurocysticercosis. Seizures were generalized in 121 patients and partial in 82. Thirty-two patients had focal signs and eight had papilledema. Eighty-one had generalized and 16 had focal EEG abnormalities. CT showed parenchymal brain calcifications in 53 patients and cysts in 150. There was an increased rate of focal signs in patients with single cysts as compared with patients with multiple cysts, and focal EEG abnormalities were present only in patients with single cysts. Fifty patients were lost to follow-up. The remaining 153 patients were followed for 28 +/- 6 months; of these, 31 had calcifications and 122 had cysts. Anticonvulsants were started after the first visit in every patient. The 31 patients with calcifications remained free of seizures. Ninety-five of the 122 patients with cysts were also treated with anticysticercal drugs; of these, 79 (83%) had control of seizures. In contrast, only seven (26%) of 27 patients who did not receive anticysticercal drugs had control of seizures, indicating a strong correlation between the use of anticysticercal drugs and seizure control. Finally, of the 21 patients in whom anticonvulsants were withdrawn, 16 had relapses.

Cysticercosis Mimicking Brain Neoplasm

The clinical and radiologic manifestation of neurocysticercosis are varied. Since the introduction of anticysticercal drugs, surgery is only rarely needed in treatment. During the last 2 years, we have encountered two patients with minimal symptomatology whose cerebral CT and magnetic resonance studies demonstrated single lesions consisting of an enhancing nodule surrounded by edema. There was ring enhancement of the nodule in one case and homogeneous enhancement in the other. Surgery was performed in both cases, because the primary consideration was brain tumor.

Comparison of therapeutic regimen of anticysticercal drugs for parenchymal brain cysticercosis

The efficacy of different regimens of therapy for parenchymal brain cysticercosis either with praziquantel (PZQ) or with albendazole (ALB) was compared in 114 patients. Four schemes of treatment were used: PZQ 50 mg/kg per day for 15 days, PZQ 50 mg/kg per day for 8 days, ALB 15 mg/kg per day for 30 days, and ALB 15 mg/kg per day for 8 days. Three months after therapy, it was apparent that both PZQ and ALB were effective, as shown by the disappearance of cystic lesions in computed tomographic scans. Thirty-three control patients followed for a mean of 11 months had no spontaneous remission of lesions. When comparing PZQ with ALB, the latter was found to be more effective than the former for both the full and the short course of treatment: 85% vs 60% and 85% vs 48% disappearance of lesions, respectively (P less than 0.001). Comparison of the full vs the short course of PZQ showed that the short course had a further 12% reduction in drug effectiveness. In contrast, the length of ALB therapy could be shortened without lessening its efficacy. Based on these results, an 8-day course of ALB is recommended as treatment for parenchymal brain cysticercosis; a 15-day course of PZQ could be subsequently used in those patients who show only partial response to ALB.