[The prevalence of cerebrovascular disease in the rural community of Salamá, Honduras, using the capture-recapture epidemiological method]. / Prevalencia de la enfermedad cerebrovascular en la comunidad rural de Salamá, Honduras, utilizando el método epidemiológico de captura-recaptura.

INTRODUCTION: Cerebrovascular disease (CVD) is one of the leading causes of mortality and disability in Honduras. In 2001 the first epidemiological study conducted into stroke or CVD in the urban district of Colonia Kennedy in Tegucigalpa, Honduras, was published; the prevalence rate was found to be 5.7 x 1000 inhabitants. To date few epidemiological studies have been carried out on CVD in rural areas of Central America. AIM: To determine the prevalence of CVD in the rural community of Salama, Olancho, Honduras, using the epidemiological method known as capture-recapture. SUBJECTS AND METHODS: The capture-recapture technique includes three sources of data: door-to-door interviews, research of medical records and interviews held with community leaders. All the residents in the rural community of Salama, Olancho, in north-western Honduras, were evaluated and the prevalence day was 5th May, 2005. The World Health Organisation's definition of CVD and the recommendations of the 'Global stroke initiative' were used. RESULTS: A total of 1121 households were visited, which involved a total population of 5608 inhabitants. The prevalence for CVD was found to be 3.6 x 1000 inhabitants. CONCLUSIONS: The prevalence rate for CVD in the rural community of Salama, Honduras, is similar to that reported for other rural regions of Latin America. The capture-recapture technique is recommended for conducting studies into the prevalence of stroke in rural areas.

Neurocysticercosis as the main cause of late-onset epilepsy in Mexico.

We studied 100 consecutive Mexican patients with epilepsy that started after the age of 25 years. All patients underwent clinical evaluation, computed tomography, and electroencephalography; additionally, cerebrospinal fluid analysis was performed in 82 of them. Neurocysticercosis or its sequelae were diagnosed in 50 patients (50%); 36 of these patients had partial seizures, 41 had parenchymal calcifications, and 15 had two or more lesions. Our results are in contrast with those of most studies from countries with a low incidence of neurocysticercosis, where brain tumors, cerebrovascular disease, trauma, and alcoholism are the main causes of tardive epilepsy.

Continuous focal spikes during REM sleep in a case of acquired aphasia (Landau-Kleffner syndrome).

We report a girl 3 years and 6 months old with onset of aphasia at age 3 years and 3 months. There was no evidence of brain damage and there were no seizures. The neuropsychological evaluation showed that the girl tended to be right-handed, that aphasia was global and that other higher cortical functions seemed to be preserved. Isolated spikes and spikes-and-wave were recorded during wake over the right temporal region with rare independent contralateral abnormalities. During polysomnography (PSG), the physiological patterns of sleep were preserved and right temporal epileptiform discharges were significantly increased in all sleep stages. Maximal activation was obtained at sleep onset and during rapid eye movement (REM) sleep periods, when focal abnormalities became continuous and spread contralaterally. Repeat PSGs showed that the activation profile retained this particular trait, although subclinical discharges tended to increase during slow wave sleep (SWS). This pattern of subclinical temporal status epilepticus during REM sleep differs from the characteristic activation profile found in the syndrome of continuous spikes-and-waves during SWS. However, this profile was transient and all epileptiform changes disappeared during clinical recovery at 18 months of follow-up.

Juvenile myoclonic epilepsy in chromosome 6p12-p11: locus heterogeneity and recombinations.

We recently analyzed under homogeneity a large pedigree from Belize with classic juvenile myoclonic epilepsy (JME). After a genome wide search with 146 microsatellites, we obtained significant linkage between chromosome 6p markers, D6S257 and D6S272, and both convulsive and EEG traits of JME. Recombinations in two affected members defined a 40 cM JME region flanked by D6S313 and D6S258. In the present communication, we explored if the same chromosome 6p11 microsatellites also have a role in JME mixed with pyknoleptic absences. We allowed for heterogeneity during linkage analyses. We tested for heterogeneity by the admixture test and looked for more recombinations. D6S272, D6S466, D6S294, and D6S257 were significantly linked (Zmax > 3.5) to the clinical and EEG traits of 22 families, assuming autosomal dominant inheritance with 70% penetrance. Pairwise Zmax were 4.230 for D6S294 (theta m = f at 0.133) and 4.442 for D6S466 (theta m = f at 0.111). Admixture test (H2 vs. H1) was significant (P = 0.0234 for D6S294 and 0.0128 for D6S272) supporting the hypotheses of linkage with heterogeneity. Estimated proportion of linked families, alpha, was 0.50 (95% confidence interval 0.05-0.99) for D6S294 and D6S272. Multipoint analyses and recombinations in three new families narrowed the JME locus to a 7 cM interval flanked by D6S272 and D6S257.

Intraepithelial and lamina propria leucocyte subsets in inflammatory bowel disease: an immunohistochemical study of colon and rectal biopsy specimens.

AIMS: To gain new insights into the pathogenesis and differential diagnosis of ulcerative colitis and colonic Crohn's disease. METHODS: Immunohistochemistry for different leucocyte subsets was performed in biopsy specimens of the sigmoid colon and rectum from 55 patients with inflammatory bowel disease and 11 healthy controls. RESULTS: Colonic biopsy specimens from patients with active ulcerative colitis had significantly higher numbers of CD45+ and CD3+ leucocytes compared with those from patients with inactive disease, and higher numbers of total leucocytes and macrophages than those from patients with Crohn's disease. Rectal biopsy specimens from patients with Crohn's disease had greater numbers of intraepithelial leucocytes (CD45, CD3 and CD8 cells) than specimens from patients with active or inactive ulcerative colitis, or from healthy controls. CONCLUSIONS: Because of the phenotypic differences in the inflammatory infiltrate in the mucosa from the sigmoid colon and the rectum, the segment of the intestine to be biopsied should be specified. Assessment of the leucocytic component of the intraepithelial infiltrate in rectal biopsy specimens was more useful than examination of colonic biopsy specimens in the differential diagnosis of ulcerative colitis and Crohn's disease.

Clinical pharmacokinetics of albendazole in patients with brain cysticercosis.

Albendazole pharmacokinetics were studied in eight patients who were receiving albendazole in doses of 15 mg/kg per day for 8 days as treatment of brain cysticercosis. Albendazole was not detected in plasma, but its main metabolite albendazole sulphoxide could be measured. Maximum plasma levels for albendazole sulphoxide ranged from 0.45 to 2.96 micrograms/mL. The half-life of albendazole sulphoxide was between 10 and 15 hours. A double peak was found in three patients. Mean residence time values were from 14 to 20 hours. Plasma levels of albendazole sulphoxide at the steady state showed great intraindividual variability. The results suggest that albendazole can be administered twice daily rather than three times as is currently done.

Dexamethasone increases plasma levels of albendazole.

Therapy of neurocysticercosis with cysticidal drugs is frequently complicated by the exacerbation of symptoms that follows the inflammation triggered by the acute destruction of cysticerci. Treatment of such adverse reactions with dexamethasone is highly effective. However, it has been shown that dexamethasone lowers the plasma levels of praziquantel, thus reducing its cysticidal efficacy. We measured plasma levels of albendazole, another strong cysticidal drug, when dexamethasone was given simultaneously. We found that dexamethasone increased the plasma levels of albendazole by about 50% (P less than 0.002); hence, it seems that cysticercosis and the ensuing inflammation can be treated simultaneously with albendazole and dexamethasone without diminishing the efficacy of the cysticidal drug.

Prevalence of taeniasis and cysticercosis in a population of urban residence in Honduras.

To determine the prevalence of antibodies to Taenia solium and taeniasis in a population of urban residence, an epidemiological study was carried out in a military institution located in Tegucigalpa, the capital city of Honduras. A total of 404 persons were interviewed to collect epidemiological data, investigate antibodies to T. solium cysticercus by the enzyme-linked immunoelectrotransfer blot (EITB) assay and taeniasis by Ritchie's concentration technique. A total of 41 persons that were living at the headquarters and were traveling frequently to their rural hometowns were regarded as rural residents, the remaining 363 persons were considered urban residents. The seroprevalence of antibodies was 22% (9/41) in the rural residents and 15% (54/363) in the urban residents. The overall seroprevalence was 15.6% (63/404). Analyses of risk factors for seropositivity in the urban residents showed that seropositivity was statistically associated with poor household conditions such as raising pigs (odds ratio (OR), 5.39; 95% confidence interval (CI), 1.42-19.50), lack of potable water (OR, 3.66; CI, 1.25-9.94), lack of sanitary toilet (OR, 2.92; CI, 1.35-6.05) and earthen floor (OR, 2.48; CI, 1.28-4.73). Also seropositivity was associated with low academic education (OR, 2.5O; CI, 1.33-4.69) and lack of knowledge about the parasite (OR, 2.39; CI, 1.26-4.49). Out of 328 persons examined for intestinal parasites, two soldiers (0.6%) coming from rural areas were identified as Taenia sp. carriers. T. solium was identified in one case. Although T. solium infections originate and are more prevalent in rural villages, the high seroprevalence found in this study indicates that they can also be found at important levels in urban communities. Migration of tapeworm carriers from rural areas to the city grants the transmission of cysticercosis when poor environmental and social conditions are present.

Plasma and CSF levels of albendazole and praziquantel in patients with neurocysticercosis.

Albendazole or praziquantel were measured in plasma and cerebrospinal fluid (CSF) in 29 patients with neurocysticercosis. Mean levels of albendazole in plasma were 0.918 microgram/ml and in CSF were 0.392 microgram/ml and levels of praziquantel were 1.640 micrograms/ml in plasma and 0.398 microgram/ml in CSF, after doses of 15 and 50 mg/kg, respectively. Drug concentrations in CSF were 43% for albendazole and 24% for praziquantel. The drug levels obtained for both drugs showed ample individual variations that were not related to age, sex, presence of inflammation in the subarachnoid space, or therapeutic effectiveness; such variations seem to be due to individual differences in pharmacokinetics. Both drugs were effective and the doses currently used of each drug seem to be optimal for therapy of neurocysticercosis.

Mapping and positional cloning of common idiopathic generalized epilepsies: juvenile myoclonus epilepsy and childhood absence epilepsy.

Among the 40 to 100 million persons with epilepsy worldwide and the 2 to 2.5 million persons with epilepsies in the United States, approximately 50% have generalized epilepsies. Among all epilepsies, the most common are juvenile myoclonus epilepsy (JME) with 10% to 30% of cases, childhood absence epilepsy (CAE) with 5% to 15% of cases, and pure grand mal on awakening with 22% to 37% of cases. In the last decade, six different chromosomal loci for common generalized epilepsies have been identified. These include two separate loci for JME in chromosomes 6p and 15q. The epilepsy locus in chromosome 6p expresses the phenotypes of classic JME, pure grand mal on awakening, and possibly JME mixed with absences. Two separate loci also are present for pyknoleptic CAE, namely, CAE that evolves to JME in chromosome 1p and CAE with grand mal in chromosome 8q24. Pandolfo et al. from the Italian League Against Epilepsy have reported two other putative susceptibility loci for idiopathic generalized epilepsies, namely, grand mal and generalized spike waves 35l in chromosome 3p and generalized epilepsies with febrile convulsions, grand mal, JME, absences, and electroencephalographic spike waves in 8q24. This chapter reports on the debate concerning whether there may be two separate epilepsy loci in chromosome 6p, one in the HLA region and one below HLA. The chapter then discusses the progress made in our laboratories as a result of the Genetic Epilepsy Studies (GENES) International Consortium. We discuss (a) the 2 to 6 cM critical region for classic JME located some 20 cM below HLA in chromosome 6p, (b) the 7-cM area for pyknoleptic CAE that evolves to JME in chromosome 1p, and (c) the 3.2 cM area for pyknoleptic CAE with grand mal and irregular 3 to 4 Hz spike waves in chromosome 8q24. We discusses efforts underway to refine the genetic map of JME in chromosome 6p11 and the advances in physical mapping and positioning of candidate genes, such as the gamma-aminobutyric acid receptor gene, the potassium channel gene of the long-QT family (KvLQT), named KCNQ3, and the human homologue of the mouse jerky gene for CAE in chromosome 8q24 and JME in chromosome 6p11.

Diagnosis of human neurocysticerocosis in endemic countries: a clinical study in Honduras.

With the purpose of evaluating the available methodology for neurocysticercosis (NCC) diagnosis, 60 neurological patients were studied during a 4-year period in Honduras. Neurological evaluation, Computed Tomography (CT), cysticercosis Enzyme-Linked Immunoelectrotransfer blot (EITB) assay, electroencephalographic studies, and collection of epidemiological information were performed to assess a final diagnosis. The presenting clinical manifestations were: epileptic seizures (52%), headache without intracranial pressure (27%) and intracranial hypertension (10%). A protocol for the diagnosis of NCC is suggested. According to this protocol, patients with active (live) cysticercus and/or antibodies in Cerebrospinal fluid (CSF) were diagnosed as definitive cases of NCC, whereas those with only brain calcifications were diagnosed as probable cases. NCC diagnosis was definitive in 14 (23%) patients, probable in 32 (54%) and ruled out in 14 (23%). Of the patients with epileptic seizures, six (19%) had definitive and 20 (65%) had probable NCC. Overall seropositivity was 28%. EITB positivity varied from 14 to 100%, and from 20 to 35% in definitive and probable cases of NCC, respectively. When compared to CT, EITB overall sensitivity for definitive, active cases, was 50% in serum and 63% in CSF. These results suggest that brain images combined with neurological evaluation remains the best approach for neurocysticercosis diagnosis, and that EITB, even though its variable sensitivity, offers valuable information, especially if performed in CSF.

[Juvenile myoclonic epilepsy in chromosome 6p12: clinical and genetic advances]. / Epilepsia mioclónica juvenil del cromosoma 6p12: avances clínicos y genéticos.

Amongst idiopathic generalized epilepsies, juvenile myoclonic epilepsy (JME) is the most common, accounting for 12% to 30% of all epilepsies in the Western world. Classic JME consists of awakening myoclonias, grand mal convulsions and EEG 4 to 6 Hz polyspike waves that appear in adolescence. Probands and affected family members do not have pyknoleptic 3Hz spike and wave absences. However, in 10 to 30% of patients, rare or spanioleptic polyspike wave absences appear. In 1988,1995,1996,we mapped classic JME to a 7 cM locus in chromosome 6p12 11, called EJM1, using families from Los Angeles and Belize. In 2001,we studied one large family from Belize and 21 new families from Los Angeles and Mexico Cities, aided by a BAC/PAC based physical map and 6 new dinucleotide repeats, to narrow EJM1 to an interval between D6S272 and D6S1573. In 2002, we found myoclonin, the putative gene for typical JME in 6p12. At the congress, we will reveal the identity of the myoclonin gene, its putative function and discuss the significance of this discovery in the JME population at large.

[Functional hemispherectomy in adult patients with catastrophic epilepsy: a new therapeutic indication?]. / La hemisferectomía funcional también es eficaz en pacientes adultos con epilepsia catastrófica: ¿una nueva indicación terapéutica?

Functional hemispherectomy was reported in 1983 for the treatment of catastrophic refractory epilepsies in order to reduce the complications derived by the anatomical hemispherectomy. A series of variants of the functional hemisphectomy have been reported. They include peri-insular hemispherectomy, modified lateral hemispherectomy, vertical parasagital hemispherectomy. The functional hemispherectomy has been used mainly in the treatment of catastrophic epilepsies in children, in which extensive hemispheric lesions are associated with pharmacoresistant epileptic seizures and focal neurological deficit such as: Rasmussen's encephalitis, hemimegalencephaly, Sturge-Weber syndrome, and extensive hemispheric cortical dysplasias, etc. Recently, two series of adults patients with catastrophic epilepsies with excellent control of the episodes (above 75 %) and without mortality have been reported. Thus, functional hemispherectomy may be an effective procedure in appropriately selected adult patients, although more studies with larger series are still needed to evaluate the long-term prognosis.

Novel mutations in Myoclonin1/EFHC1 in sporadic and familial juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) accounts for 3 to 12% of all epilepsies. In 2004, the GENESS Consortium demonstrated four missense mutations in Myoclonin1/EFHC1 of chromosome 6p12.1 segregating in 20% of Hispanic families with JME. OBJECTIVE: To examine what percentage of consecutive JME clinic cases have mutations in Myoclonin1/EFHC1. METHODS: We screened 44 consecutive patients from Mexico and Honduras and 67 patients from Japan using heteroduplex analysis and direct sequencing. RESULTS: We found five novel mutations in transcripts A and B of Myoclonin1/EFHC1. Two novel heterozygous missense mutations (c.755C>A and c.1523C>G) in transcript A occurred in both a singleton from Mexico and another singleton from Japan. A deletion/frameshift (C.789del.AV264fsx280) in transcript B was present in a mother and daughter from Mexico. A nonsense mutation (c.829C>T) in transcript B segregated in four clinically and seven epileptiform-EEG affected members of a large Honduran family. The same nonsense mutation (c.829C>T) occurred as a de novo mutation in a sporadic case. Finally, we found a three-base deletion (-364--362del.GAT) in the promoter region in a family from Japan. CONCLUSION: Nine percent of consecutive juvenile myoclonic epilepsy cases from Mexico and Honduras clinics and 3% of clinic patients from Japan carry mutations in Myoclonin1/EFCH1. These results represent the highest number and percentage of mutations found for a juvenile myoclonic epilepsy causing gene of any population group.