Osvaldo Massaiti Takayanagui

Proposed diagnostic criteria for neurocysticercosis.

Neurocysticercosis is the most common helminthic infection of the CNS but its diagnosis remains difficult. Clinical manifestations are nonspecific, most neuroimaging findings are not pathognomonic, and some serologic tests have low sensitivity and specificity. The authors provide diagnostic criteria for neurocysticercosis based on objective clinical, imaging, immunologic, and epidemiologic data. These include four categories of criteria stratified on the basis of their diagnostic strength, including the following: 1) absolute—histologic demonstration of the parasite from biopsy of a brain or spinal cord lesion, cystic lesions showing the scolex on CT or MRI, and direct visualization of subretinal parasites by funduscopic examination; 2) major—lesions highly suggestive of neurocysticercosis on neuroimaging studies, positive serum enzyme-linked immunoelectrotransfer blot for the detection of anticysticercal antibodies, resolution of intracranial cystic lesions after therapy with albendazole or praziquantel, and spontaneous resolution of small single enhancing lesions; 3) minor—lesions compatible with neurocysticercosis on neuroimaging studies, clinical manifestations suggestive of neurocysticercosis, positive CSF enzyme-linked immunosorbent assay for detection of anticysticercal antibodies or cysticercal antigens, and cysticercosis outside the CNS; and 4) epidemiologic—evidence of a household contact with Taenia solium infection, individuals coming from or living in an area where cysticercosis is endemic, and history of frequent travel to disease-endemic areas. Interpretation of these criteria permits two degrees of diagnostic certainty: 1) definitive diagnosis, in patients who have one absolute criterion or in those who have two major plus one minor and one epidemiologic criterion; and 2) probable diagnosis, in patients who have one major plus two minor criteria, in those who have one major plus one minor and one epidemiologic criterion, and in those who have three minor plus one epidemiologic criterion.

Current Consensus Guidelines for Treatment of Neurocysticercosis

SUMMARY Taenia solium neurocysticercosis is a common cause of epileptic seizures and other neurological morbidity in most developing countries. It is also an increasingly common diagnosis in industrialized countries because of immigration from areas where it is endemic. Its clinical manifestations are highly variable and depend on the number, stage, and size of the lesions and the hosts immune response. In part due to this variability, major discrepancies exist in the treatment of neurocysticercosis. A panel of experts in taeniasis/cysticercosis discussed the evidence on treatment of neurocysticercosis for each clinical presentation, and we present the panels consensus and areas of disagreement. Overall, four general recommendations were made: (i) individualize therapeutic decisions, including whether to use antiparasitic drugs, based on the number, location, and viability of the parasites within the nervous system; (ii) actively manage growing cysticerci either with antiparasitic drugs or surgical excision; (iii) prioritize the management of intracranial hypertension secondary to neurocysticercosis before considering any other form of therapy; and (iv) manage seizures as done for seizures due to other causes of secondary seizures (remote symptomatic seizures) because they are due to an organic focus that has been present for a long time.

Calcific neurocysticercosis and epileptogenesis

Neurocysticercosis is responsible for increased rates of seizures and epilepsy in endemic regions. The most common form of the disease, chronic calcific neurocysticercosis, is the end result of the host’s inflammatory response to the larval cysticercus of Taenia solium. There is increasing evidence indicating that calcific cysticercosis is not clinically inactive but a cause of seizures or focal symptoms in this population. Perilesional edema is at times also present around implicated calcified foci. A better understanding of the natural history, frequency, epidemiology, and pathophysiology of calcific cysticercosis and associated disease manifestations is needed to define its importance, treatment, and prevention.

Treatment of neurocysticercosis: Current status and future research needs

Here we put forward a roadmap that summarizes important questions that need to be answered to determine more effective and safer treatments. A key concept in management of neurocysticercosis is the understanding that infection and disease due to neurocysticercosis are variable and thus different clinical approaches and treatments are required. Despite recent advances, treatments remain either suboptimal or based on poorly controlled or anecdotal experience. A better understanding of basic pathophysiologic mechanisms including parasite survival and evolution, nature of the inflammatory response, and the genesis of seizures, epilepsy, and mechanisms of anthelmintic action should lead to improved therapies.

Aspectos clinicos da neurocisticercose: análise de 500 casos

This was a retrospective study, made at the Hospital das Clinicas University of São Paulo Medical School--Ribeirão Preto from 1956 to 1979 in 500 patients with neurocysticercosis. To our knowledge, this represented the largest sample analysed so far. Clinical manifestations and complemmentary tests were studied. The neurocysticercosis is a serious endemic disease in our region and represented 2.7% of all clinical evaluations by the Neurology Department and 7.5% of all hospital admissions. The most frequent clinical presentations were the epileptic (64.8%), the intracranial hypertension (35.6%), and the meningitic (29%). Radiological study of the skull showed intracranial calcifications suggestive of cysticercosis in 47.6%. The cerebrospinal fluid was abnormal in 81.3%: pleocytosis in 60.9%, increased protein in 49.1% and increased pressure in 29%. The presence of eosinophils occurred in 41.9%, and the Weinberg test was positive in 62,6% of all the cases. It was discussed the utility of the different drugs and the results of the surgical treatment in neurocysticercosis drawing the conclusion that they show no efficacy when analysed at the end of a long follow-up. Since none of the drugs seems to be really efficient, only the sanitary education will be able to control this endemic disease that grasses among us with so somber perspectives.This was a retrospective study, made at the Hospital das Clinicas University of Sao Paulo Medical School - Ribeirao Preto from 1956 to 1979 in 500 patients with neurocysticercosis. To our knowledge, this represented the largest sample analysed so far. Clinical manifestations and complemmentary tests were studied. The neurocysticercosis is a serious endemic disease in our region and represented 2.7% of all clinical evaluations by the Neurology Department and 7.5% of all hospital admissions. The most frequent clinical presentations were the epileptic (64.8%), the intracranial hypertension (35.6%), and the meningitic (29%). Radiological study of the skull showed intracranial calcifications suggestive of cysticercosis in 47.6%. The cerebrospinal fluid was abnormal in 81.3%: pleocytosis in 60.9%, increased protein in 49.1% and increased pressure in 29%. The presence of eosinophils occurred in 41.9%, and the Weinberg test was positive in 62,6% of all the cases. It was discussed the utility of the different drugs and the results of the surgical treatment in neurocysticercosis drawing the conclusion that they show no efficacy when analysed at the end of a long follow-up. Since none of the drugs seems to be really efficient, only the sanitary education will be able to control this endemic disease that grasses among us with so somber perspectives.

Calcified neurocysticercotic lesions and postsurgery seizure control in temporal lobe epilepsy

Background: Several studies suggest that neurocysticercosis is the main cause of symptomatic epilepsy in developing countries. In such areas, calcified cysticercotic lesions (CCL) are frequently found in patients with complex partial seizures associated with hippocampal sclerosis (HS). The authors studied whether there are clinical and pathologic differences between HS patients with and without CCL. Methods: The authors determined the clinical and pathologic findings of 30 patients with HS and compared them with 32 patients with HS + CCL. Hippocampi from both groups were measured for fascia dentata Timm staining and cell density in hippocampal subfields. Results: In the HS + CCL group, single or multiple CCL were found in all lobes with no lobar predominance. An initial precipitating event occurred in 83.3% of HS and in 62.5% of HS + CCL. First complex partial seizure occurred at 10.1 years in HS and at 11.9 years in HS + CCL. No significant differences were found for fascia dentata Timm staining and hippocampal cell densities. Good postsurgery outcome (Engel I classification) did not differ between groups, with this result occurring in 76.6% of patients with HS and 81.2% of patients with HS + CCL. Conclusions: The presence of CCL does not influence the clinical and pathologic profile of patients with hippocampal atrophy. Clinical histories and postsurgical outcomes were similar to those of patients with classic HS, suggesting that the CCL is probably, in this set of patients, a coincidental pathology and does not have a role in epileptogenesis.–1491

Taenia solium DNA is present in the cerebrospinal fluid of neurocysticercosis patients and can be used for diagnosis

Neurocysticercosis is the most frequent parasitic infection of the CNS and the main cause of acquired epilepsy worldwide. Seizures are the most common symptoms of the disease, together with headache, involuntary movements, psychosis and a global mental deterioration. Absolute diagnostic criteria include the identification of cysticerci, with scolex, in the brain by MRI imaging. We demonstrate here, for the first time, that T. solium DNA is present in the cerebrospinal fluid of patients. The PCR amplification of the parasite DNA in the CSF enabled the correct identification of 29/30 cases (96.7 %). The PCR diagnosis of parasite DNA in the CSF may be a strong support for the diagnosis of neurocysticercosis.

Use of neuron-specific enolase for assessing the severity and outcome of neurological disorders in patients

Neuron-specific enolase (NSE) is a glycolytic enzyme present almost exclusively in neurons and neuroendocrine cells. NSE levels in cerebrospinal fluid (CSF) are assumed to be useful to estimate neuronal injury and clinical outcome of patients with serious clinical manifestations such as those observed in stroke, head injury, anoxic encephalopathy, encephalitis, brain metastasis, and status epilepticus. We compared levels of NSE in serum (sNSE) and in CSF (cNSE) among four groups: patients with meningitis (N=11), patients with encephalic injuries associated with impairment of consciousness (ENC, N=7), patients with neurocysticercosis (N=25), and normal subjects (N=8). Albumin was determined in serum and CSF samples, and the albumin quotient was used to estimate blood-brain barrier permeability. The Glasgow Coma Scale score was calculated at the time of lumbar puncture and the Glasgow Outcome Scale (GOS) score was calculated at the time of patient discharge or death. The ENC group had significantly higher cNSE (P=0.01) and albumin quotient (P=0.005), but not sNSE (P=0.14), levels than the other groups (Kruskal-Wallis test). Patients with lower GOS scores had higher cNSE levels (P=0.035) than patients with favorable outcomes. Our findings indicate that sNSE is not sensitive enough to detect neuronal damage, but cNSE seems to be reliable for assessing patients with considerable neurological insult and cases with adverse outcome. However, one should be cautious about estimating the severity of neurological status as well as outcome based exclusively on cNSE in a single patient.

Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis

AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect.

Therapy for neurocysticercosis

Therapy for neurocysticercosis has advanced during the last 20 years with the advent of albendazole (Zentel®) and praziquantel (Cysticide®). Albendazole is the current medication of choice for the treatment of neurocysticercosis and is recommended for symptomatic patients with multiple viable cysts in the brain parenchyma. Albendazole may also be useful in extraparenchymal cysticercosis, especially in the subarachnoid racemose form, when complete surgical resection of the cysts is usually impracticable. Currently, there is an intense debate over the value and safety of anticysticercal therapy. Causes for failure of anticysticercal therapy include high inter-individual variability in plasma concentration of albendazole sulfoxide and the complex interactions of several drugs with the albendazole metabolite. Furthermore, albendazole sulfoxide is an enantiomeric mixture of (+)- and (−)-albendazole sulfoxide with accumulation of the (+)-enantiomer in the cerebrospinal fluid. However, the question over which enantiomer is effective against cysticerci remains to be clarified.