Tropical Neurology - part 6 pptx

264 Tropical Neurology 15 Laboratory Findings Hematological Abnormalities Mild eosinophilia, usually below 10%, is the most common hematological abnormality in patients with NCC and may be found in 6-37% of cases. 10 Some patients also have moderate leukocytosis (up to 17,000 per mm 3 ) as well as an erythrocyte sedimentation rate above 30 mm. These findings appear to be more common in patients with massive cysticercal infestation. Stool Examination for Taenia solium Eggs Eggs of T. solium are detected in the stool of 3-27% patients with NCC. It is more important to search for T. solium carriers in the patients’ close environment than to determine the prevalence of taeniasis. 2 Recognition of Taenia eggs is not easy and many patients may remain undiagnosed if a single sample study is performed. Serial stool specimens, therefore, must be examined before the patient is considered negative. Two recent advances have been made for the diagnosis of human taeniasis: ELISA for coproantigen detection and DNA hybridization for egg identification. These new tests will greatly improve the screening for T. solium carriers among healthy individuals in the endemic areas. Cytochemical Analysis of CSF CSF abnormalities have been reported in about 80% of patients with NCC (Table 15.2). These abnormalities correlate with the activity of the disease and subarachnoid location of the parasite. 9,10 A normal CSF examination, therefore, does not rule out the diagnosis of NCC. The most consistent CSF finding is a moderate mononuclear pleocytosis, with an increase in the number of eosinophils. The cell count rarely exceeds 300 per mm 3 ; however, in severe cysticercus meningitis CSF cell count may rise up to 5000/mm 3 . CSF glucose levels are usually within the normal range despite active meningeal disease. Hypoglycorrhachia (<40 mg/dl) has been associated with poor prognosis. Elevated CSF protein is common in patients with pleocytosis. Protein usually ranges from 50 to 300 mg/dl, although it may be as high as 1,600 mg/dl. Immunologic Diagnosis Immunologic diagnostic tests have been used to assess the prevalence of cysticercosis in a population and to exclude or confirm the diagnosis of NCC. 2 As the accuracy of these tests depends on the complex humoral immune response of the host against cysticerci, these tests have limitation of suboptimal sensitivity and specificity. False-negative results are related to local production of antibodies within the CNS without a parallel increase of antibodies in peripheral blood, or to immune tolerance to the parasite without production of anticysticercal antibodies. The false-positive results are due to previous contact with adult T. solium or to cross-reactivity with other helminths. We are still far from a reliable test that serves as a “gold standard” for the diagnosis of human cysticercosis. Complement Fixation Test Complement fixation test has been used for the diagnosis of cysticercosis for more than 80 years. Initially this test was developed to determine the presence of anticysticercal antibodies in serum but later it has been found to be more useful 265 Neurocysticerosis 15 when used in CSF. The complement fixation test is positive in 83% of patients with NCC who also had inflammatory changes in the CSF but only in 22% of patients with normal CSF. The complement fixation test is less sensitive in ventricular than subarachnoid CSF; therefore, a negative result in a CSF sample obtained at the time of shunt surgery does not exclude the diagnosis of NCC. Enzyme-Linked Immunosorbent Assay (ELISA) ELISA has been one of the most widely evaluated immunologic diagnostic tests for human cysticercosis. Preliminary experience with the ELISA postulated that a positive result “strongly suggests” cysticercosis and a negative result indicates that the diagnosis is “highly unlikely”. Subsequent studies, however, showed that up to 30% of patients with NCC may have a false-negative ELISA, particularly if the test is performed in serum. A similar percentage of individuals may have a false-positive result due to cross-reactivity with other infectious diseases. Detection of anticysticercal antibodies in CSF by ELISA is more accurate than in serum. Some authors have found 87% sensitivity and 95% specificity of ELISA in CSF. These results, however, depend on the presence of active disease, since many patients with parenchymal brain calcifications or granulomas have a negative ELISA, even if the test is performed in CSF. 12 Enzyme-Linked Immunoelectrotransfer Blot (EITB) Assay The demonstration that antibodies to species-specific antigens of T. solium can be detected by EITB stimulated investigators to develop highly purified antigens of cysticercus to be used in a new immunologic diagnostic test for cysticercosis. Seven antigenic bands are usually recognized by antibodies of patients with cysticercosis. Among these GP13, GP14, GP24 and GP39-42 are the most fre- quently recognized antigens. The EITB has been extensively evaluated. Some re- ports suggest that serum EITB is 94-98% sensitive and 100% specific for the diagnosis of human cysticercosis, while results from other studies have been disappointing. In patients with a single cyst, a high frequency of false negative results has been Table 15.2. Cerebrospinal fluid findings in neurocysticercosis Finding Range of Abnormality Prevalence Pleocytosis 10-300 x mm 3 π 50-70%+ Eosinophils in sediment —— 4-60% Increased proteins 100-300 mg/dl β 50-70%+ Hypoglycorrhachia <40 mg/dl ξ 12-18% Increased IgG >15% of protein count —————— Oligoclonal bands ——- Unknown Increased neopterin ——- Unknown Increased alcohol ——- Unknown π Pleocytosis may be up to 5,000 per mm 3 . β Protein count may be as high as 6,000 mg/dl. ξ Glucose levels<10 mg/dl carry a poor prognosis. + The percentage is higher when only patients with arachnoiditis are considered. 266 Tropical Neurology 15 reported, reducing the sensitivity of EITB to 30%. Patients with calcified lesions are less likely to have positive EITB compared to those with active disease. Another limitation is that EITB assay may be positive in patients with taeniasis, which is especially important in endemic areas since many patients who had been exposed to the adult parasite without developing cysticercosis may test positive. The EITB results, therefore, must be interpreted with caution in light of the clinical manifestations, neuroimaging findings and, more importantly, the habitat of the patient. A positive EITB in serum is of lesser value in patients coming from areas where cysticercosis is endemic than in those living in areas where it is rare. A negative EITB does not exclude NCC in patients with a single cerebral lesion or in those with parenchymal brain calcifications. 13 Computed Tomography With computed tomography (CT) cysticerci can be easily visualized. Computed tomography also allows assessment of the topography, number and stage of cysticerci. In addition, CT studies are important for determining the rational thera- peutic approach. Parenchymal Neurocysticercosis CT findings in parenchymal NCC depend on the stage of development of the parasites (Fig. 15.5). Vesicular cysticerci appear as small and rounded low-density areas that are well demarcated from the surrounding brain parenchyma. These cysts lack perilesional edema and do not enhance after contrast administration. Most of these lesions contain an eccentric hyperdense nodule representing the scolex. Some- times cysts are so numerous that the brain resembles “Swiss cheese”. 11 Colloidal cysticerci appear on CT scan as ill-defined hypodense or isodense lesions surrounded by edema. Most of these show a ring pattern of enhancement after contrast administration. Colloidal cysticerci represent the so-called “acute encephalitic phase” of NCC in which the host’s immune system is actively reacting against the parasite. Parenchymal brain cysticerci may also appear on CT scan as hyperdense lesions surrounded by edema with nodular enhancement after contrast administration. This CT scan picture corresponds to the granular stage of cysticerci and is commonly referred as to “cysticercus granuloma.” Finally, calcified cysticerci appear as small hyperdense nodules without perilesional edema or enhancement after contrast administration. Another CT scan pattern of parenchymal NCC is observed in patients with cysticercous encephalitis. In these patients, CT shows diffuse brain edema and sinking of the ventricular system without midline shift. Following contrast administration, multiple small ring-like or nodular lesions appear disseminated within the brain parenchyma (Fig. 15.6). Most of the described CT patterns are characteristic of parenchymal NCC. The differential diagnosis, however, with other infectious or neoplastic diseases of the CNS may be difficult in some cases. The main problem arises with single or multiple ring enhancing lesions, since pyogenic brain abscess, toxoplasma, tuberculoma, mycotic granuloma and primary or metastatic brain tumors may present with similar findings on CT scan. In such situations, the presence of different stages of the cyst on CT, clinical findings, immunodiagnostic tests and epidemiological data, as well as the empirical administration of anticysticercal drugs, help in the diagnosis. 13 267 Neurocysticerosis 15 Fig. 15.5a. Computed tomographic appearance of parenchymal brain cysticercus: cystic vesicular lesion showing scolex. Subarachnoid Neurocysticercosis Hydrocephalus, caused by inflammatory occlusion of the foramina of Luschka and Magendie, is the most common CT finding in patients with subarachnoid NCC. The fibrous arachnoiditis responsible for the development of hydrocephalus is seen on CT scan as areas of abnormal leptomeningeal enhancement at the base of the brain after contrast administration. Some patients with hydrocephalus due to 268 Tropical Neurology 15 cysticercus arachnoiditis also have single or multiple subarachnoid and parenchymal brain cysts or calcifications, a finding that facilitates the diagnosis of NCC (Fig. 15.7). Cystic subarachnoid lesion may be small when located within the corti- cal sulci or may reach a large size if these are located in the Sylvian fissure or within the basal CSF cisterns. The latter usually have a multilobulated appearance, displace neighboring structures and behave like space occupying lesions. Fig. 15.5b. Computed tomographic appearance of parenchymal brain cysticercus: colloidal cyst appearing as ring-enhancing lesion surrounded by edema. 269 Neurocysticerosis 15 Ischemic stroke in subarachnoid NCC can be seen on CT scan. These findings are nonspecific since the CT appearance of cysticercus-related cerebral infarctions are similar to cerebral infarctions from other causes. In some patients, the association of subarachnoid cysts or the presence of abnormal enhancement of basal leptomeninges in the opticochiasmatic region suggests the correct diagnosis. The differential diagnosis should include fungal, tuberculous and carcinomatous meningitis since these conditions are also associated with cerebral infarctions and abnormal enhancement of the leptomeninges. Fig. 15.5c. Computed tomographic appearance of parenchymal brain cysticercus: granular cysticercus appearing as nodular lesion. 270 Tropical Neurology 15 Ventricular Neurocysticercosis Ventricular cysticerci appear on CT scan as hypodense lesions that cause asym- metric or obstructive hydrocephalus. Ventricular cysts are usually isodense with the CSF; therefore, these can only be inferred on the basis of distortion of the ventricular system (Fig. 15.8). The administration of positive intraventricular contrast allows precise localization of intraventricular cysticerci. This is usually performed by Fig. 15.5d. Computed tomographic appearance of parenchymal brain cysticercus: calcified cysticerci. 271 Neurocysticerosis 15 Fig.15.6. Computed tomography of a patient with cysticercus encephalitis. There is diffuse brain edema, collapse of the ventricular system and multiple small areas of nodular enhancement disseminated throughout the brain parenchyma (with permission from Del Brutto OH, Sotelo J, Roman GC. Neurocysticercosis: A Clinical Handbook. © Lisse: Swets & Zeitlinger). transcutaneous puncture of the antechamber of a ventricular shunt previously placed for the hydrocephalus or through a ventriculostomy tube. The contrast may also be administered through a lumbar puncture; however, this procedure should be con- ducted cautiously since this may result in brain herniation in patients with hydrocephalus or intraventricular cysts. Magnetic Resonance Imaging Magnetic resonance imaging (MRI) has the advantage of multiplanar (axial, coro- nal and sagittal) reconstruction of images and the capacity to visualize the posterior fossa without bone artifacts and high contrast resolution. By MRI it is possible to recognize forms of cysticerci that were not seen on CT scan. The main shortcoming of MRI, however, is failure to detect small calcifications. Parenchymal brain calcifications are the most common CT finding in patients with NCC and, in many patients, these may be the only radiological evidence. Because of this limitation of MRI, CT still remains the best screening neuroimaging procedure for patients with suspected NCC. 1 Parenchymal Neurocysticercosis MRI appearance of parenchymal brain cysticerci depends on their stage of development. Vesicular cysts appear as rounded lesions with signal properties similar to that of CSF in both T1- and T2- weighted images. The scolex is usually seen within the cyst as a high intensity nodule giving the lesion a “hole-with-dot” image which is pathognomonic of vesicular cysts (Fig. 15.9). The appearance of colloidal cysts is 272 Tropical Neurology 15 quite different because as the parasite begins to degenerate, proteins from the scolex combine with the vesicular fluid, and the whole cysticercus becomes discretely hypointense with the surrounding brain parenchyma. The wall of the cyst becomes thick and hypointense and there is marked perilesional edema; these findings are better visualized on T2-weighted images. Administration of gadolinium results in a ring-like pattern of enhancement (Fig. 15.10). Granular cysticerci are visualized as areas of signal void on both T1- and T2-weighted images surrounded by edema or gliosis with hyperintense rims around the area of signal void. MRI findings in cysticercus encephalitis consist of multiple small rounded areas of decreased signal intensity on a T1-weighted sequence; these lesions become hyperintense on T2 and Fig. 15.7. Computed tomography showing hydrocephalus, subarachnoid cysticercus in Sylvian fissure and lacunar infarction in genu of internal capsule. 273 Neurocysticerosis 15 most of these are surrounded by edema. Due to the small size of the cysts and their stage of development, some cysts are only discernible on proton-density and T2-weighted sequences. Fig.15.8. Computed tomography showing distortion of ventricular system caused by ventricular cysticercus. [...]... ( 16. 7 mg/kg delivered over four hours) plasma quinine 16 294 Tropical Neurology Table 16. 3 Characteristics of human plasmodium species P falciparum Exoerythrocytic cycle (days) Prepatent period (days) Hypnozoites Asexual cycle (hours) Earliest appearance of peripheral gametocytes (days) P malariae P vivax P ovale 5-7 5-3 0 > 180 days in P falciparum CQR malaria None 48 8 –15 1 4-1 5 1 8 -6 0 8 8-2 7 9 1 2-2 0... Parasitol 1992; 31:8 3-1 73 Pouvelle B, Fusai T, Lepolard C, Gysin J Biological and biochemical characteristics of Plasmodium-falciparum-infected erythrocyte cytoadherence on chondroitin-4-sulfate Infect Immunol 1998; 66 :495 0-4 9 56 Kwiatowski D, Hill AVS, Sambou I et al TNF concentrations in fatal cerebral, nonfatal cerebral and uncomplicated falciparum malaria Lancet 1990; 3 36: 120 1-1 204 Grau GE, Taylor... sequelae of cerebral malaria in children Lancet 1990; 3 36: 103 9-1 043 Bondi FS The incidence and outcome of neurological abnormalities in childhood cerebral malaria: A long-term follow-up of 62 survivors Trans R Soc Trop Med Hyg 1992; 86: 1 7-1 9 Newton CRJC, Warrell DA Neurological manifestations of falciparum malaria Ann Neurol 1998; 43 :69 5-7 02 16 ... Rodriguez-Carbajal J, Taveras JM, eds Cysticercosis of the Central Nervous System Springfield: Charles C Thomas Publisher, 1983:2 7-5 4 Pittella JEH Neurocysticercosis Brain Pathol 1997; 7 :68 1 -6 93 Sotelo J, Del Brutto OH, Roman GC Cysticercosis In: Remington JS, Swartz MN, eds Current Clinical Topics in Infectious Diseases, 16 Cambridge: Blackwell Science, 19 96: 24 0-2 59 White Jr AC, Tato P, Molinari JL Host-parasite... protein-1(PfEMP-1) These proteins show clonal variation allowing them to evade host immune responses Knobs are essential for cytoadherence and facilitate the attachment of the red cells to the vascular endothelial cell The third component implicated in cytoadherence is a number of specific endothelial receptors: ICAM-1, CD- 36 protein, VCAM-1, E-selectin, thrombospondin and chondroitin-sulfate-A (CSA)... distinguished from black water fever and hemolysis induced by glucose -6 - phosphate dehydrogenase (G -6 - PD) deficiency In the former, sensitization of red cells has been observed after intermittent use of aminoalcohol drugs such as quinine, quinidine, halofantrine and mefloquine In the latter group hemoglobinuria occurs in patients with G -6 - PD deficiency who take oxidant drugs such as primaquine or certain... malaria New Engl J Med 19 96; 335:7 6- 8 3 Barennes H, Pissard E, MaHAMan Sani A et al Efficacy and pharmacokinetics of Cerebral Malaria 12 13 14 15 299 a new intrarectal quinine formulation in children with Plasmodium falciparum malaria Br J Clin Pharmacol 19 96; 41:38 9-3 95 Nguyen Thi Hoang Mai, Day NPJ, Van Chuong L, Waller D et al Post-malaria neurological syndrome Lancet 19 96; 348:917 9-2 1 Brewster D, Kwiatowski... (PRBCs) sequester in the maternal compartment of the placenta, binding to CSA Preliminary studies have shown that antibodies developed after multiple pregnancies are associated with reduced number of parasitized RBCs in the placenta and block CSA-binding of parasitized RBCs, suggesting that protection is conferred by a conserved Pf-antigen.4 16 2 86 Tropical Neurology Fig 16. 1 Rosetting phenomenon Agglutination... fever and neurological symptoms Antimalarial 16 16 290 Table 16. 1 Coma score in cerebral malaria Glasgow scale for adults Score Eyes open Total 4 3 2 1 5 4 3 2 1 Score Motor Response Localized painful stimulus 2 Withdrew limb from pain 1 Nonspecific or absent response 0 Verbal Response Appropriate Inappropriate cry None 2 1 0 Total 0–4 6 5 4 2 1 3-1 5 Tropical Neurology Spontaneously To speech To pain Never... 1989; 320:158 6- 1 591 Warrell DA Clinical features of malaria In: Gilles HM, Warrell DA, eds Bruce-Chwatt’s Essential Malarialogy, 3rd ed London: Edward Arnold, 1993:3 5-4 9 Cordoliani YS, Sarrazin JL, Felten D et al MR of cerebral malaria Am J Neuroradiol 1998; 19:87 1-8 74 Marsh K, Forster D, Waruriu C et al Indicators of life-threatening malaria in African children New Engl J Med 1995; 332:139 9-1 404 Hien . Abnormality Prevalence Pleocytosis 1 0-3 00 x mm 3 π 5 0-7 0%+ Eosinophils in sediment —— 4 -6 0% Increased proteins 10 0-3 00 mg/dl β 5 0-7 0%+ Hypoglycorrhachia <40 mg/dl ξ 1 2-1 8% Increased IgG >15% of. Diseases, 16. Cambridge: Blackwell Science, 19 96: 24 0-2 59. 8. White Jr. AC, Tato P, Molinari JL. Host-parasite interactions in Taenia solium cysticercosis. Infect Ag Dis 1992; 1:18 5-1 93. 9. Sotelo. Nervous System. Springfield: Charles C. Thomas Publisher, 1983:2 7-5 4. 6. Pittella JEH. Neurocysticercosis. Brain Pathol 1997; 7 :68 1 -6 93. 7. Sotelo J, Del Brutto OH, Roman GC. Cysticercosis. In: