Dolores Correa

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.

Laboratory Diagnosis of Human Neurocysticercosis: Double-Blind Comparison of Enzyme-Linked Immunosorbent Assay and Electroimmunotransfer Blot Assay

ABSTRACT Neurocysticercosis is a common disease in underdeveloped countries. Its diagnosis is based on clinical, imaging (tomography or magnetic resonance), epidemiological, and laboratory data. Several methods based on the detection of antibodies against cysticerci in cerebrospinal fluid or serum have been tested. Among them, an enzyme-linked immunosorbent assay (ELISA) based on the use of a crude parasite antigen has been used by the laboratory network of cysticercosis in Mexico, which has given support to clinicians for up to 7 years. A Taenia solium-specific glycoprotein-based electroimmunotransfer blot (EITB) assay was reported to be highly sensitive and specific for this purpose. In order to compare both techniques, we studied 100 neurocysticercosis patients and 70 neurological noncysticercosis controls and searched for specific antibodies in paired samples of serum and cerebrospinal fluid using both techniques. We found that the EITB assay is more sensitive than the ELISA, especially when serum is being tested. Both techniques are more sensitive in cases with multiple living cysts than in cases with single cysts or calcified lesions. No global differences among cases with parasites located in different parts of the central nervous system were found. In the patients with cysts within the parenchyma, the sensitivity of the EITB assay was higher with serum than with cerebrospinal fluid. The immunodominant bands were found to be the same as those previously reported, i.e., GP-39 to -42, GP-24, and GP-13. Based on these results, we suggest the use of the EITB assay in routine diagnosis of cysticercosis for clinical cases.

Cyclosporin-A inhibits lipid peroxidation after spinal cord injury in rats

Besides its immunosuppressive/anti-inflammatory activity, cyclosporin-A (CsA) may protect damaged tissues from lipid peroxidation (LP) by free radicals. To determine the effect of CsA on LP spinal cord (SC) injury, Wistar rats were treated with either vehicle or CsA (2.5 mg/kg per 12 h i.p.) 1, 2, 6 or 12 h after SC trauma by T8-T9 spinal cord contusion, analyzing LP 24 h after injury at the lesion site by the lipid fluorescent products formation method. CsA significantly diminished LP to levels below control values after contusion (P < 0.05). The greater inhibition was observed when CsA was given during the first 6 h after injury, furthermore, animals showed a significant clinical improvement. Results show that CsA may be beneficial to injured tissue by inhibiting the levels of LP.

Effects of cyclosporin-A on immune response, tissue protection and motor function of rats subjected to spinal cord injury

The aim of this work was to test the effect of cyclosporin-A (CsA) on some immunological, morphological and functional aspects developed after spinal cord injury. The specific cellular immune response against spinal cord constituents, the amount of spared tissue and myelination at the site of injury, and the motor function outcome were assessed in a first series of experiments. Rats were subjected to spinal cord compression and treated with cyclosporin-A before lesion and during the entire study. A specific lymphocyte response against spinal cord antigens was found in untreated spinal cord injured rats but not in cyclosporine-A treated injured rats. A significantly better myelination index was also found in injured cyclosporin-A-treated rats, as compared to untreated animals. The amount of spared spinal cord tissue at the epicenter was not significantly different comparing CsA-treated with vehicle-treated rats. Looking for a potential therapeutic use of CsA, in a second series of experiments, rats were subjected to spinal cord contusion and treated with cyclosporin-A from 1 to 72 h after lesion. Motor recovery and red nuclei neurons survival, were evaluated, and found to be significantly better in spinal cord injured rats treated with cyclosporin-A than in injured-untreated rats. This work confirms the existence of an autoimmune cellular reaction after injury that can be inhibited by cyclosporin-A treatment. Furthermore, cyclosporin-A promotes neuroprotection by diminishing both demyelination and neuronal cell death, resulting in a better motor outcome after spinal cord injury.

Lipid peroxidation inhibition in spinal cord injury: cyclosporin-A vs methylprednisolone.

To compare the effectiveness of cyclosporin-A (CsA) with methylprednisolone (MP) or a combination of both upon inhibition of lipid peroxidation (LP) after spinal cord (SC) injury, rats were treated with either CsA, MP, CSA+MP or vehicle starting 1 h after SC contusion at T9 level. LP was assessed 24 h after injury by the lipid fluorescent product formation method. The survival rate was also evaluated in other series of rats by the Kaplan–Meier curves. Lipid peroxidation was similarly inhibited in rats treated with CsA, MP, or CSA+MP (p >0.05). Animals receiving MP (alone or combined with CsA) showed the poorest surviving rate. LP was inhibited by CsA to the same extent as by MP but without the lethal effect of the latter.

Congenital and acquired toxoplasmosis: diversity and role of antibodies in different compartments of the host.

The apicomplexan parasite Toxoplasma gondii is remarkable in several aspects, since it is a protozoan that infects most nucleated cells in many warm‐blooded animals, worldwide. Although the cellular immune response against T. gondii is critical for infection control, antibodies may either enhance or block protective mechanisms, and even mediate immunological damage, directly or indirectly. Since cytokines regulate the class/subclass switch, antibodies may also be the biomarkers of protective or pathological cellular immune events. There is a scientific and clinical interest in the presence of natural and autoreactive antibodies, as well as in the ‘chronic’ immunoglobulin M (IgM) response and the post‐treatment ‘rebound’. Another interesting aspect is compartmentalization; certain immunoglobulins may uniquely be found in specific host fluids. Local synthesis has been demonstrated, but antibodies may also traverse several cell layers, like the blood–brain and haemato‐ocular barriers, and the placenta. In some instances, Fc receptors (FcRs) facilitate transport and may even have a concentrator effect, which can be related to resistance or pathology. These aspects of the humoral response against T. gondii are reviewed in the present paper.

Human neurocysticercosis: comparison of enzyme immunoassay capture techniques based on monoclonal and polyclonal antibodies for the detection of parasite products in cerebrospinal fluid

Current diagnosis of neurocysticercosis relies mostly on computerized tomography and nuclear magnetic resonance, with detection of antibodies being confirmatory rather than decisive. An assay which detects parasite products in cerebrospinal fluid would conclusively demonstrate a current infection and could be important when decisions regarding treatment must be made. Cerebrospinal fluid from patients with neurocysticercosis was used in 4 enzyme immunoassay capture tests designed to detect parasite products. Of the systems tested, one, based on the use of a monoclonal antibody reactive with a surface and secretion component of the metacestode, was particularly promising, giving a sensitivity of 72%. The assay has the double advantage of a very low background and a proved specificity for the products of living cysticerci. The other 3 systems (monoclonal anti-vesicular fluid antibody, polyclonal antibody against a saline extract and polyclonal anti-antigen B antibody) were less sensitive. Results with the anti-antigen B system support the proposal that products of low immunogenicity are the most appropriate targets for the serological detection of the parasite.

Praziquantel treatment of porcine brain and muscle Taenia solium cysticercosis. 1. Radiological, physiological and histopathological studies.

PorcineTaenia solium cysticercosis, recognized as a model of the human disease, was used to analyze the effect of the anthelminthic drug praziquantel on hosts and parasites. The drug (50 mg/kg daily) was given over 15 days in the feed of 13 cysticercotic and 9 control pigs. Changes in the number, size and appearance of brain parasites were seen by computerized tomography immediately after the last dose of praziquantel, although not all cysticerci had disappeared by day 47 following the end of the treatment. Muscle parasites became small and hyperdense shortly after treatment and disappeared from tomographic images afterwards. No alterations were found in EEGs or in brain-stem auditory and somatosensory evoked potentials. Muscle cysticerci showed increasing degrees of degeneration with time after treatment, and an augmented inflammatory reaction was concomitantly observed. In contrast, more heterogeneous results were obtained in parasites lodged in the brain, since viable cysts and less intense inflammatory reactions were found in the brain at different times after treatment. Physiological evaluation of the parasites showed that evagination was inhibited immediately after treatment and that oxygen consumption decreased with time. The results of this investigation suggest that praziquantel damages cysticerci and that the inflammatory reaction destroys and eliminates them.Porcine Taenia solium cysticercosis, recognized as a model of the human disease, was used to analyze the effect of the anthelminthic drug praziquantel on hosts and parasites. The drug (50 mg/kg daily) was given over 15 days in the feed of 13 cysticercotic and 9 control pigs. Changes in the number, size and appearance of brain parasites were seen by computerized tomography immediately after the last dose of praziquantel, although not all cysticerci had disappeared by day 47 following the end of the treatment. Muscle parasites became small and hyperdense shortly after treatment and disappeared from tomographic images afterwards. No alterations were found in EEGs or in brain-stem auditory and somatosensory evoked potentials. Muscle cysticerci showed increasing degrees of degeneration with time after treatment, and an augmented inflammatory reaction was concomitantly observed. In contrast, more heterogeneous results were obtained in parasites lodged in the brain, since viable cysts and less intense inflammatory reactions were found in the brain at different times after treatment. Physiological evaluation of the parasites showed that evagination was inhibited immediately after treatment and that oxygen consumption decreased with time. The results of this investigation suggest that praziquantel damages cysticerci and that the inflammatory reaction destroys and eliminates them.

Host--parasite relationship in cysticercosis: immunologic study in different compartments of the host.

Cysticerci parasitize several mammalian species, including man, in which the parasitic disease shows unique characteristics since cysticerci are established mainly in immunologically privileged sites and can survive for many years. The study of the human immune response to cysticerci is helpful in diagnosis and could perhaps also aid in preventing or curing the disease. Anti-cysticercus IgG can be detected in serum and cerebrospinal fluid (CSF) of almost all patients with neurocysticercosis, by the enzyme-linked immunosorbent assay (ELISA); antibodies of the other classes are found less frequently. Antibodies react with up to eight Taenia solium cysticercus antigens, mainly with antigen B. This antigen has an affinity for collagen and is not commonly found in the CSF. It could therefore be participating in vasculitic processes spotted in the brain of neurocysticercotic patients. Immunoglobulins are also identified on the surface of the parasites: IgG is detected on parasites obtained from various tissues; IgM, IgA and IgE mostly on extracerebral cysticerci. We discuss the possibility of extraneural cysticerci being destroyed by the immune response of the host whereas natural aging may cause brain cysticerci death.