Pseudodystonic Posture Secondary to Klippel–Feil Syndrome and Diastematomyelia

Background: Dystonic postures possess a great number of differential diagnoses. Phenomenology Shown: We describe a pseudodystonic posture in a 61‐year‐old woman with skeletal and extra‐skeletal abnormalities. Educational Value: Klippel–Feil syndrome represents an unusual cause of pseudodystonic posture to be considered in the differential diagnosis of dystonia

Pantothenate kinase-associated neurodegeneration: Novel mutations in the PANK2 gene in an argentinean young woman

Neurodegeneration with brain iron accumulation (NBIA) refers to a heterogeneous group of disorders.1–3 The pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder caused by defective iron metabolism associated with mutations in the pantothenate kinase 2 (PANK2) gene on chromosome 20p13–p12.3.Fil: Gatto, Emilia Mabel. Instituto de Neurociencias Buenos Aires; ArgentinaFil: Etcheverry, Jose L.. Instituto de Neurociencias Buenos Aires; ArgentinaFil: Converso, Daniela Paola. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bidinost, Carla. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; ArgentinaFil: Rosa, Alberto Luis. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentin

Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)

Parkinson’s disease (PD) represents the second most common neurodegenerative disease and remains incurable. Mutations in multiple genes have been linked to monogenic PD (gPD); these monogenic forms, however, represent a small number of cases while in most instances PD appears as idiopathic (iPD). These findings raise the question of whether genetic and idiopathic parkinsonisms constitute the same disease. Nevertheless, monogenic-PD phenotypes and iPD both fulfill MDS criteria for PD, and show evidence of alpha-synuclein aggregates in both conditions. Distinct genetic loci in rare Mendelian forms have been identified as causal mutations, others as possible disease-causing genes, and genome-wide association studies have reported several risk loci, many of them located in the genes associated with the dominant mutations. Not only single-nucleotide polymorphisms (SNPs), but other kinds of DNA molecular defects as well have been spotted as significant disease-causing mutations, including large chromosomal structural rearrangements and copy number variations (CNVs). As their size varies, and detection methodologies have different sensitivity and resolution, CNVs pose a special challenge in genetic studies, and there currently is a debate on the pathogenetic or susceptibility impact of specific CNVs on PD. In this review, through multiple instances of experimental evidence, we analyze the impact on histopathology of the different mutational mechanisms involved in the genesis and etiology of PD. We believe that increasing our knowledge about the changes and implications at tissue level produced by each of those mechanisms will allow to develop much more suitable and personalized potential therapeutic strategies, biomarker identification, as well as disease modeling, agreeing with the precision medicine concept.Fil: Gatto, Emilia Mabel. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Radrizzani Helguera, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín; ArgentinaFil: González Rojas, Natalia. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Cesarini, Martin Emiliano. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Etcheverry, José Luis. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Perandones, Claudia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentin

Overexpression of neutrophil neuronal nitric oxide synthase in Parkinson's disease

Much evidence supports a role of nitric oxide (·NO) and peroxynitrite (ONOO-) in experimental and idiopathic Parkinson's disease (PD); moreover, an overexpression of neuronal nitric oxide synthase (nNOS) was recently reported in the basal ganglia of PD patients. In accord, we previously found a 50% increased ·NO production rate during the respiratory burst of circulating neutrophils (PMN) from PD patients. As PMN express the nNOS isoform, the objective of the present study was to ascertain whether this increased ·NO production is representative of nNOS gene upregulation. PMN were isolated from blood samples obtained from seven PD patients and seven age- and sex-matched healthy donors; nNOS mRNA was amplified by reverse transcriptase-polymerase chain reaction and the products were hybridized with a probe for nNOS. Nitrotyrosine-containing proteins and nNOS were detected by Western blot and NO production rate was measured spectrophotometrically by the conversion of oxymyoglobin to metmyoglobin. The results showed that both ·NO production and protein tyrosine nitration were significantly increased in PMN isolated from PD patients (PD 0.09 ± 0.01 vs 0.06 ± 0.008 nmol min-1 106 cells-1; P < 0.05). In addition, five of the seven PD patients showed about 10-fold nNOS mRNA overexpression; while two of the seven PD patients showed an expression level similar to that of the controls; detection of nNOS protein was more evident in the former group. In summary, it is likely that overexpression of nNOS and formation of ONOO- in PMN cells from PD patients emphasizes a potential causal role of ·NO in the physiopathology of the illness. (C) 2000 Academic Press.Fil: Gatto, Emilia Mabel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; ArgentinaFil: Riobó, Natalia A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; ArgentinaFil: Carreras, Maria Cecilia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cherñavsky, Alejandra Claudia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Inmunogenética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Rubio, Andrea. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Inmunogenética; ArgentinaFil: Satz, M. Leonardo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Inmunogenética; ArgentinaFil: Poderoso, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín. Laboratorio de Metabolismo del Oxígeno; Argentin

Pharmacovigilance in Neuroscience

Background: Adverse drug reactions (ADRs) have a high impact on morbidity and mortality of the population, becoming a public health issue. Studying and publishing about these is referred as pharmacovigilance.Objective: To describe and compare the adverse reactions produced by drugs of nervous system action (CNS-D) and neurological ADRs produced by drugs of systemic action (Sys-D). To further develop the need of reporting adverse reactions. Methods: An observational, cross-sectional, retrospective study performed on a database of neurological consultations which took place at the Neurology department. Patients meeting the inclusion criteria were selected and divided into two groups: Sys-D and CNS-D. Demographic and neurological variables were analyzed. Parametric and non-parametric statistics were used according to distribution. The Naranjo Algorithm (NA) was used to define causality.Results: 71 ADRs were described, from which 63.38% (n=45) were produced by CNS-D, especially antiepileptics by 47% (n=21) and psycholeptics by 44%. Of the total, 36.62% (n=26) were caused by Sys-D, such as antineoplastics (n=9) and antibiotics (n=9), being Cefepime the most frequent. The diagnosis of ADRs caused by a Sys-D was delayed prolonging hospitalization (p 0.05) due to a lower NA score (p 0.003) compared to the CNS-D group.Conclusion: Multiple frequently used drugs of systemic action, such as antineoplastics and antibiotics, generate neurological adverse effects. From our analysis, it was presumed that the suspicion of a neurological ADR caused by these drugs was scarce, thus causing a higher morbidity for the patient

Intrafamilial variable phenotype including corticobasal syndrome in a family with p.P301L mutation in the MAPT gene: first report in South America

Frontotemporal lobar degeneration is a neuropathological disorder that causes a variety of clinical syndromes including frontotemporal dementia (FTD), progressive supranuclear palsy, and corticobasal syndrome (CBS). FTD associated with parkinsonism occurs frequently as a result of mutations in the C9orf72 gene and also in the genes coding for the protein associated with microtubule tau (MAPT) and progranulin (GRN) on chromosome 17 (FTDP-17). Herein, we report an Argentinean family, of Basque ancestry, with an extensive family history of behavioral variant of FTD. Twenty-one members over 6 generations composed the pedigree. An extensive neurologic and neurocognitive examination was performed on 2 symptomatic individuals and 3 nonsymptomatic individuals. Two different phenotypes were identified among affected members, CBS in the proband and FTD in his brother. DNA was extracted from blood for these 5 individuals and whole-exome sequencing was performed on 3 of them followed by Sanger sequencing of candidate genes on the other 2. In both affected individuals, a missense mutation (p.P301L; rs63751273) in exon 10 of the MAPT gene (chr17q21.3) was identified. Among MAPT mutations, p.P301L is the most frequently associated to different phenotypes: (1) aggressive, symmetrical, and early-onset Parkinsonism; (2) late parkinsonism associated with FTD; and (3) progressive supranuclear palsy but only exceptionally it is reported associated to CBS. This is the first report of the occurrence of the p.P301L-MAPT mutation in South America and supports the marked phenotypic heterogeneity among members of the same family as previously reported

Ataxia plus myoclonus in a 23-year-old patient due to STUB1 mutations

More than 1,000 mutations mapping to 60 different loci have been recognized as the cause of hereditary ataxias. However, almost 50% of the cases are still genetically uncharacterized, with etiology remaining to be identified.1 Diagnosis and research in rare diseases such as ataxia has been significantly improved with the recent availability of next generation sequencing technologies.2 In order to expand the phenotype recently described in ataxia due to STUB1 mutations and to illustrate the utility of clinical genomics in the diagnosis of ataxias, we present a 23-year-old patient who had ataxia plus myoclonus in whom exome sequencing revealed novel compound heterozygous mutations in the STUB1 gene.Fil: Córdoba, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodríguez Quiroga, Sergio. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gatto, Emilia Mabel. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Alurralde, Agustín. Hospital Caleta Olivia; ArgentinaFil: Kauffman, Marcelo Andres. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Holmes Tremor Partially Responsive to Topiramate: A Case Report

Background: Holmes tremor is a rare symptomatic movement disorder, characterized by a combination of resting, postural, and intention tremor. It is usually caused by lesions in the brainstem, thalamus, and cerebellum. Despite pharmacological advances, its treatment remains a challenge; many medications have been used with various degrees of effectiveness. Stereotactic thalamotomy and deep brain stimulation in the ventralis intermedius nucleus have been effective surgical procedures in cases refractory to medical treatment. Case Report: Here we report a young woman with topiramate-responsive Holmes tremor secondary to a brainstem cavernoma. Discussion: Herein we report a Holmes tremor responsive to Topiramate

Juvenile Huntington disease in Argentina

ABSTRACT We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environmental or biological factors