RESUMO
OBJECTIVE: In this study, we determine the incidence and outcomes of Guillain-Barré syndrome (GBS) in Iceland over a 20-year period. METHOD: Cases were identified from the records of both referral hospitals in the country. All cases met the Brighton Criteria for GBS. Disability was assessed at diagnosis, peak of symptoms, discharge, and follow-up using the Guillain-Barré Disability Scale. RESULTS: Sixty-three individuals fulfilled the diagnostic criteria with an average age of onset of 46 years (range 1-89 years) and a male:female ratio of 1. The average annual incidence was 1.1 per 100 000 person-years. Nerve conduction studies were consistent with demyelinating polyneuropathy in 87% of cases, acute motor axonal neuropathy (AMAN) in 4%, and were normal in 9%. Treatment was received by 89% of patients and included IVIG (84%), plasmapheresis (8%), or both treatments (3%). Mechanical ventilation was required by 22% of patients. Long-term follow-up with an average length of 6.5 years was available for 98% of patients, and the average GBS disability score at follow-up was 0.9. Four deaths related to GBS (6%) were observed. CONCLUSION: We believe we have identified all patients diagnosed with GBS in Iceland during the study period, with an incidence comparable to recent studies from well-defined populations around the world. Our reported mortality is similar to or higher than other population-based studies. At follow-up, 13% of patients still required a walking aid, but most survivors (74%) had minor or no symptoms.
Assuntos
Avaliação da Deficiência , Síndrome de Guillain-Barré/epidemiologia , Recuperação de Função Fisiológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Islândia/epidemiologia , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
We previously mapped susceptibility to stroke to chromosome 5q12. Here we finely mapped this locus and tested it for association with stroke. We found the strongest association in the gene encoding phosphodiesterase 4D (PDE4D), especially for carotid and cardiogenic stroke, the forms of stroke related to atherosclerosis. Notably, we found that haplotypes can be classified into three distinct groups: wild-type, at-risk and protective. We also observed a substantial disregulation of multiple PDE4D isoforms in affected individuals. We propose that PDE4D is involved in the pathogenesis of stroke, possibly through atherosclerosis, which is the primary pathological process underlying ischemic stroke.
Assuntos
3',5'-AMP Cíclico Fosfodiesterases/genética , Isquemia Encefálica/enzimologia , Isquemia Encefálica/genética , Cromossomos Humanos Par 5 , Desequilíbrio de Ligação , Regiões 5' não Traduzidas/genética , Sequência de Bases , Mapeamento Cromossômico , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3 , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Predisposição Genética para Doença , Humanos , Isoenzimas/genética , Repetições de Microssatélites , Dados de Sequência Molecular , Polimorfismo Genético , Polimorfismo de Nucleotídeo ÚnicoRESUMO
INTRODUCTION: Upper motor neuron lesions after stroke are a major cause of disability. We aimed to determine whether skeletal muscles from these patients display typical molecular signatures of inflammation, growth arrest, and atrophy. METHODS: Muscle biopsies were analyzed for morphological, histochemical, ultrastructural, and molecular features indicative of changes in gene expression involved in muscle atrophy. RESULTS: Chronic hemiplegia resulted in ~9.5% atrophy, fiber type shifts, and histochemical and ultrastructural signs of impaired remodeling. TNF and TWEAK expressions were unaltered, but MSTN mRNA was lower (-73%, P < 0.05) in paretic tibialis anterior vs. age-matched controls. The expression of autophagy-related genes (BCN-1, LC3, and GABARAPL1) was lower in paretic tibialis anterior (-81%, -48%, and -60%, respectively, P < 0.01) and soleus (-85%, -54%, and -60% respectively, P < 0.01) compared with old controls. CONCLUSIONS: Persistent atrophy in chronic spastic hemiplegia may be associated with impaired remodeling partly due to altered autophagy gene expression.
Assuntos
Autofagia/genética , Hemiplegia/genética , Hemiplegia/patologia , Músculo Esquelético/patologia , Atrofia Muscular/genética , Atrofia Muscular/patologia , Adulto , Idoso , Doença Crônica , Feminino , Regulação da Expressão Gênica , Hemiplegia/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Adulto JovemRESUMO
BACKGROUND/AIM: To determine the prevalence and clinical spectrum of Charcot-Marie-Tooth disease (CMT) in Iceland. METHODS: We identified all individuals with symptomatic CMT, based on information from all practicing neurologists, both neurophysiology laboratories and the only neurology department in the country. The diagnosis was based on clinical features and neurophysiological testing. DNA testing was regarded as confirmatory. RESULTS: We identified 37 individuals in 18 families, which were not linked by identifying 5 generations of ancestors. The point prevalence (January 1, 2007) for all CMT subtypes in Iceland was 12.0/10(5), 10.1/10(5) for CMT1 and 2.0/10(5) for CMT2. The clinical features include lower limb weakness (95%), impaired gait (68%), decreased or absent deep tendon reflexes (86%), pes cavus (70%) and hammer toes (46%). Clinical symptoms were similar for the 2 main CMT subtypes. CONCLUSION: We report the prevalence and clinical spectrum of CMT, which is comparable to the results of other prevalence studies, in a well-defined, total population sample.
Assuntos
Doença de Charcot-Marie-Tooth/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Doença de Charcot-Marie-Tooth/fisiopatologia , Criança , Pré-Escolar , Família , Feminino , Humanos , Islândia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P<5×10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.
Assuntos
Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Transtornos de Enxaqueca/genética , Cerebelo/metabolismo , Biologia Computacional , Lobo Frontal/metabolismo , Humanos , Polimorfismo de Nucleotídeo Único , Locos de Características QuantitativasRESUMO
We identified a marker in LINGO1 showing genome-wide significant association (P = 1.2 x 10(-9), odds ratio = 1.55) with essential tremor. LINGO1 has potent, negative regulatory influences on neuronal survival and is also important in regulating both central-nervous-system axon regeneration and oligodendrocyte maturation. Increased axon integrity observed in Lingo1 mouse [corrected] knockout models highlights the potential role of LINGO1 in the pathophysiology of ET [corrected]
Assuntos
Tremor Essencial/genética , Predisposição Genética para Doença , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Animais , Áustria , Frequência do Gene , Genética Populacional , Estudo de Associação Genômica Ampla , Alemanha , Humanos , Islândia , Desequilíbrio de Ligação , Camundongos , Camundongos Knockout , Polimorfismo de Nucleotídeo Único/fisiologia , Fatores de Risco , Estados UnidosRESUMO
In Iceland, the crude prevalence for all types of primary dystonia was 37.1/10(5) (confidence interval, 30.4-44.9). Focal dystonia had the highest prevalence (31.2/10(5)), followed by segmental (3.1/10(5)), multifocal (2.4/10(5)) and generalized dystonia (0.3/10(5)). Cervical dystonia was the most common focal dystonia (11.5/10(5)), followed by limb dystonia (8.0/10(5)), laryngeal dystonia (5.9/10(5)), blepharospasm (3.1/10(5)), and oromandibular dystonia (2.8/10(5)). The male:female ratio for all patients was 1:1.9 (P=0.0007), and females outnumbered males in all subtypes except oromandibular dystonia. Mean age of onset for all patients was 42.7 years (range, 3-82 years). This prevalence of primary dystonia is higher than in most reported studies, possibly because of more complete ascertainment but the relative frequencies of dystonia subtypes is similar.
Assuntos
Distúrbios Distônicos/epidemiologia , Adulto , Distribuição por Idade , Distúrbios Distônicos/classificação , Distúrbios Distônicos/fisiopatologia , Feminino , Humanos , Islândia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por SexoRESUMO
Previous work has suggested that in many neurological diseases genetic variability in the loci predisposing subjects to autosomal dominant disease contributes to the risk of sporadic disease. Here, using a population-based sample of dystonia cases, we show an association with the torsin A haplotype and sporadic idiopathic dystonia.
Assuntos
Distonia/genética , Chaperonas Moleculares/genética , Alelos , Distonia/epidemiologia , Frequência do Gene , Genótipo , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , PopulaçãoRESUMO
Stroke is one of the most complex diseases, with several subtypes, as well as secondary risk factors, such as hypertension, hyperlipidemia, and diabetes, which, in turn, have genetic and environmental risk factors of their own. Here, we report the results of a genomewide search for susceptibility genes for the common forms of stroke. We cross-matched a population-based list of patients with stroke in Iceland with an extensive computerized genealogy database clustering 476 patients with stroke within 179 extended pedigrees. Linkage to 5q12 was detected, and the LOD score at this locus meets the criteria for genomewide significance (multipoint allele-sharing LOD score of 4.40, P=3.9 x 10(-6)). A 20-cM region on 5q was physically and genetically mapped to obtain accurate marker order and intermarker distances. This locus on 5q12, which we have designated as "STRK1," does not correspond to known susceptibility loci for stroke or for its risk factors and represents the first mapping of a locus for common stroke.