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Summary: Purpose: A prospective series of 643 persons with epilepsy attending a reference neurologic center in Medellin, Colombia, was examined by computed tomography (CT scan) or serology or both with the enzyme-linked immunoelectrotransfer blot assay (EITB) to assess the prevalence of Taenia solium cysticercosis. Methods: All presenting patients were consecutively enrolled in the study. Five hundred forty-six persons underwent cerebral CT scans; 376 of them also had serum EITB performed. Results: Prevalence of neurocys@ercosis by CT scan was 13.92%. Overall prevalence of T. solium antibodies with EITB was 9.82%, but for those with late-onset epilepsy (onset after age 30 years), prevalence increased to 17.5% and 19% for those who originated from outside urban Medellin. Seroprevalence in individuals with mixed lesions (cysts and calcifications) was 88.2% and 64.10% in those with live cysts. Conversely, only 2.72% of persons with CT findings not related to neurocysticercosis had positive EITB tests. Conclusions: Our study shows that an important proportion of individuals with epilepsy have radiologic or serologic evidence of T. solium infection, suggesting that neurocysticercosis is an important etiology for epilepsy in Colombia.

Background Chagas disease is a neglected illness, with limited treatments, caused by the parasite Trypanosoma cruzi. Two drugs are prescribed to treat the disease, nifurtimox and benznidazole, which have been previously reported to have limited efficacy and the appearance of resistance by T. cruzi. Acquisition of drug-resistant phenotypes is a complex physiological process based on single or multiple changes of the genes involved, probably in its mechanisms of action. Results The differential genes expression of a sensitive Trypanosoma cruzi strain and its induced in vitro benznidazole-resistant phenotypes was studied. The stepwise increasing concentration of BZ in the parental strain generated five different resistant populations assessed by the IC50 ranging from 10.49 to 93.7 μM. The resistant populations maintained their phenotype when the BZ was depleted from the culture for many passages. Additionally, the benznidazole-resistant phenotypes presented a cross-resistance to nifurtimox but not to G418 sulfate. On the other hand, four of the five phenotypes resistant to different concentrations of drugs had different expression levels for the 12 genes evaluated by real-time PCR. However, in the most resistant phenotype (TcR5x), the levels of mRNA from these 12 genes and seven more were similar to the parental strain but not for NTR and OYE genes, which were down-regulated and over-expressed, respectively. The number of copies for these two genes was evaluated for the parental strain and the TcR5x phenotype, revealing that the NTR gene had lost a copy in this last phenotype. No changes were found in the enzyme activity of CPR and SOD in the most resistant population. Finally, there was no variability of genetic profiles among all the parasite populations evaluated by performing low-stringency single-specific primer PCR (LSSP-PCR) and random amplified polymorphic DNA RAPD techniques, indicating that no clonal selection or drastic genetic changes had occurred for the exposure to BZ. Conclusion Here, we propose NTR as the major marker of the appearance of resistance to BZ.

Individuals affected with multiple sclerosis (MS) from a genetically homogeneous Caucasian population in Antioquia, a tropical region of Colombia, were evaluated in order to observe the clinical behavior of the disease. The frequency of clinical manifestations in 65 patients with definite MS from Antioquia was compared with those reported from temperate regions. The most common manifestations were optic neuritis and motor symptoms with absence of cerebellar symptoms. This presentation is significantly different from the frequency distribution at onset in series from temperate regions. These differences suggest that environmental factors could modify the clinical expression of MS in this population.

Introduction. Myasthenia gravis (MG), considered the commonest of all the illnesses that affect neuromuscular transmission, is a disorder in which the autoimmune system attacks the post-synaptic acetylcholine-receptor proteins in the end plate terminal; it is characterised by weakness and skeletal muscle fatigue, with no anomalies in reflexes, sensitivity or coordination. Epidemiological indicators, such as incidence and prevalence, are not known in Colombia. Aims. To determine the prevalence of MG among the inhabitants of Antioquia, through the use of the capture-recapture method. Patients and methods. The capture-recapture method was used for two sources, the Instituto NeurolOgico de Antioquia and the Hospital Universitario San Vicente de Pa´ul, which are the most important institutions for the diagnosis of neurological diseases in Antioquia. MG prevalence was calculated using the following formula: p=n/N×10 5 . We examined the datafrom the period between 1 July 1995 and 30 June 2000 with the aim of identifying subjects who fitted the profile of MG sufferers. Results. General MG prevalence in Antioquia was 27.7 cases per million inhabitants (CI 95%= 23.2-32.2). The male/female ratio was 1:3.77. Conclusions. The estimated prevalence of MG is lower than that reported in United States and other temperate regions, where it varies between 60 and 150 cases per million. The prevalence ofMG is low in Antioquia, as in other tropical areas.

OBJECTIVE To perform linkage analysis between the Short Tandem Repeats (STR) microsatellite markers D19S923, D19S929, D19S22, which are in strong genetic linkage to Notch3 gene in order to contrast the hypothesis that the vascular hereditary dementia phenotype described in a multigenerational extended pedigree from Colombia correspond to CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). Even we know that using techniques as the Single Strand Conformational Polymorphisms (SSCP) could determine mutations in Notch3, the rationality of this approach is that intronic variations could not be defined and that we are interested in determine if some forms of the clinical presentation and its phenotypic variability make part of CADASIL. INTRODUCTION The CADASIL phenotype is caused by mutations in the Notch3 gene. Clinical features of CADASIL are: 1. Recurrent cerebra-vascular episodes; 2. Migraine history; 3. History of transitory ischemic attack and, 4. Behavior changes and dementia. MATERIAL AND METHODS By using SIMLINK we showed that the extended genealogy had the enough power to detect significant LOD (logarithm of oods) score values when Notch3 was considered the disorder cause. Linkage analysis was carried out by using parametric and non parametrical methods. The Elston-Stewart general method was used as the parametrical analysis and the sib pair method as the non-parametrical one. We perform simulations changing the affection status codification by including as affected or not including those individuals with migraine. Furthermore, in order to detect the stability of the results, we changed the penetrance values, the genetic frequencies on both, the marker loci and the affection locus. RESULTS The maximum pair-wise LOD score was 2.04 which was detected at the marker D19S23 with q= 0.11cM. This distance correspond exactly with the Notch3 location. That is 100 times more probable that there is linkage that there is not. In other words this probability could be explained as if the phenotype correspond to CADASIL than to other vascular dementia. The non parametric results were compatibles with the parametric ones. When the migraine symptom was considered as a part of the affected status, the LOD score values showed not linkage. CONCLUSIONS The results of the linkage analysis to these STR microsatellite markers suggest that the vascular hereditary dementia phenotype described in this family correspond to CADASIL caused by a polymorphism on the Notch3 gene. On the contrary, these same results suggest that the migraine phenotype is not a part of the progressive dementia.

INTRODUCTION There are more than 40 clinical types of epilepsy classified according to aetiology and/or mode of clinical onset. The term idiopathic epilepsy is reserved for cases with convulsions but no detectable structural lesions of the brain or neurological anomalies. DEVELOPMENT AND CONCLUSIONS In spite of many studies confirming the importance of genetic factors in the occurrence of idiopathic epilepsy, these appear to be complex and probably involve a locus of variable expression or several loci with similar phenotype expression (epistaxis). Also, environmental factors have variable effects. In recent years the principal genes involved in susceptibility to develop epilepsy have been mapped. In this way one mitochondrial and three autosomic genes have been cloned as responsible for the development of certain forms of this disorder. Also several studies of genetic linkage have given evidence, sometimes inconsistent, regarding the influence of another five loci in the susceptibility to develop epilepsy (6p21.2, 6q23-25, 8q24, 8p, 10q). On occasions the same locus has been linked with different forms of epilepsy, and on other occasions one form of epilepsy has been shown to be linked to several loci.

INTRODUCTION Multiple sclerosis (MS) is the commonest demyelinating condition of the nervous system. It is characterized by numerous demyelinating areas or plaques of demyelination which are found dispersed throughout the nervous system. It has been shown that MS is less frequent in tropical regions than in subtropical regions. In Latin America particularly, there are some studies which show this phenomenon. However, in Colombia no studies of prevalence of MS have been done. OBJECTIVE To determine the prevalence of multiple sclerosis in five provinces of Colombia (Antioquia, Caldas, Santander, Risaralda and Bolivar). PATIENTS AND METHODS The capture-recapture method was used for two sources to determine the number of cases defined on the criteria of Poser et al seen between July 1995 and June 2000. RESULTS The prevalence (cases of MS per 100,000 inhabitants) varied between 1.48 in Antioquia (95% CI 1.12; 1.78) and 4.98 in Risaralda (95% CI 3.52; 6.43). Seventy two percent were women. The regions included in this study represented 25% of the population of Colombia. CONCLUSIONS There is a low prevalence of MS which is as expected in tropical areas. Persons with MS in these regions may be very useful in the study of other factors involved in the aetiology of MS (genetic). The capture-recapture method is an excellent tool for carrying out prevalence studies since it is cheap and requires little time.

INTRODUCTION In extended and multigenerational pedigrees, the idiopathic epilepsy phenotype shows an extreme variability. OBJECTIVE The range of idiopathic epilepsy onset age in multigenerational pedigrees was studied in order to determine if genetic anticipation play a role in the heredity of Idiopathic Epilepsies. PATIENTS AND METHODS We compare the seizures onset age among relative-pairs of (parents-children, grandfathers-grandsons and nephew uncles). The mean onset age was compared using the Wilcoxon sign-rank paired-sample non-parametrical test to determine whether or not significant differences over > 0 exist, which refutes the null hypothesis of not anticipation. 84 pairs of relatives were taken from 72 extended multigenerational pedigrees. RESULTS The onset age of idiopathic epilepsy of the pairs showed a difference significantly > 0, which confirm the existence of intergenerational differences. This difference has a tendency to decrease in age which each successive generation. This difference occur in all relative pairs and therefore contradicts the ascertainment bias described by Penrose. CONCLUSIONS The results outline the existence of unstable mutations (those produced by a nucleotidic variable number of tandem repeats) as a probable explanation of the susceptibility to develop some forms of idiopathic epilepsy.

In attempt to identify the possible role of mayor genes, multifactorial inheritance, and cohort effects in the susceptibility to idiopathic epilepsy with generalized tonic clonic seizures of the awakening type (GTCS), complex segregation analysis was performed in 196 nuclear families ascertained through affected with probands with idiopathic epilepsy with GTCS belonging to the Paisa community of Antioquia (Colombia). Models postulating no transmission, single mayor locus (dominant and recessive) only, and multifactorial component only, were rejected. The models postulating no polygenic component to transmission, and no transmission of the major effect were also rejected. Thus far, complex segregation analysis suggested that a major autosomal codominant allele together with a multifactorial component (mixed model) best explains clustering of idiopathic epilepsy with GTCS in families of the Paisa community. The deficit of transmission of heterozygotes (0.17) is compatible with the existence of epistasis acting on a major gene whose frequency was estimated to be 0.0211. Its transmission variance accounts for 81% of the susceptibility to idiopathic epilepsy with GTCS. The complementary variance (19%) is due to polygenic component.

INTRODUCTION AND OBJECTIVE In order to elucidate the genetic and environmental components involved in the susceptibility to develop attention deficit hyperactivity disorder (ADHD), a complex segregation analysis on nuclear families (n = 53) ascertained from affected probands belonging to Medellin, in the Antioquian State, Colombia, was performed. METHODS AND RESULTS Models of cohort effect (non-inheritance), multifactorial, recessive major gene, non-major gene component and non-transmission of major gene were rejected. Contrarily, dominant and codominant major gene models and non-multifactorial component could not be rejected. Thus, the better model fitting the data was that of the major gene (dominant/codominant). This major gene explains more than 99.99% of the ADHD phenotypic variance (value of heritability in the mixed model equal to 0.007%), which permit to assume a low aport of the environmental component to the phenotype ADHD. Gene frequency of the major gene was 3% in the general population of Antioquia and its penetrance was closed to 30%. CONCLUSION Some cautions and aspects related to the bias of the interview and diagnosis of the parents are discussed.

Objective and methods An experimental study about the predictions from the multifactorial threshold model created by Falconer is presented, assuming that this model may explain the genetic mechanisms underlying the family aggregation of idiopathic epilepsies. Results We failed to confirm the following predictions from the falconer model: decreased prevalence of disease in relatives, proportional to decreased family links, and the order of birth effect. An heredity greater than 100% was calculated which is concordant with the presence of at least a locus with a major gen affect. Conclusion Our results reject the multifactorial threshold effect and suggest the presence of a major gen or Mendelian effect. An analysis of complex segregation is suggested for future studies.