Spinocerebellar ataxia types 2 and 3 segregating simultaneously in a single family.

Spinocerebellar ataxia (SCA) types 2 and 3 are autosomal-dominant neurodegenerative disorders caused by mutations in two different genes. We identified mutations for SCA2 and SCA3 segregating simultaneously in a single Brazilian family. The index patient had SCA2, whereas her two second-degree cousins had SCA3. Disease was more rapidly progressive in the SCA2 patient, who presented severe brainstem and pancerebellar atrophy, as opposed to the two SCA3 patients, who had only mild cerebellar vermian atrophy. In such situations, molecular confirmation of all patients may avoid misdiagnosis of SCA subtypes and eventual errors in predictive testing of unaffected family members.     

Periodic alternating nystagmus and rebound nystagmus in spinocerebellar ataxia type 6.

We report on a family with ataxia type 6 (SCA6) showing peculiar oculomotor symptoms. The proband presented with periodic alternating nystagmus (PAN), and her 2 brothers had rebound nystagmus and gaze-evoked nystagmus. They carried the identical mutation (the number of expanded CAG repeat, 24) in the CACNA1A gene. The intrafamilial variability of oculomotor symptoms may be ascribed to factors other than CAG repeat expansion size in SCA6.     

PRKCG mutation (SCA-14) causing a Ramsay Hunt phenotype.

Progressive myoclonic ataxia, also referred to as Ramsay Hunt syndrome, is characterized by a combination of myoclonus and cerebellar ataxia, infrequently accompanied by tonic-clonic seizures. Its differential diagnosis overlaps with progressive myoclonic epilepsy, a syndrome with myoclonus, tonic-clonic seizures, progressive ataxia and dementia. In patients with progressive myoclonic epilepsy, specific diseases can frequently be recognized, but the diagnostic yield in progressive myoclonic ataxia is much lower. We describe a patient who presented with multifocal myoclonus in his thirties and who later developed cerebellar ataxia and focal dystonia. His father was similarly affected. Genetic studies revealed a mutation in the protein kinase C gamma (PRKCG) gene, known to cause spinocerebellar ataxia type 14 (SCA-14). This case illustrates that both myoclonus and dystonia are part of the clinical spectrum in SCA-14 and that myoclonus can even be the presenting symptom. We suggest that SCA-14 should be considered in the differential diagnosis of progressive myoclonic ataxia.     

A patient homozygous for the SCA6 gene with retinitis pigmentosa

The present authors studied a 55-year-old-patient homozygous for the SCA6 gene who experienced frequent attacks of positional vertigo at 37 years of age with subsequent staggering gait and night blindness. Retinitis pigmentosa (RP), as well as cerebellar ataxia and vertical antidirectional nystagmus, were detected. The subject's parents were first cousins, and two of his three male cousins, whose parents were also first cousins, had RP without ataxia or nystagmus. The numbers of CAG repeats in the expanded alleles of the SCA6 gene found by molecular analysis were 21 and 21. The genetic results were negative for SCA1, SCA2, SCA3, SCA7 and dentatorubral pallidoluysian atrophy. The retinal degeneration in this patient is most likely to be secondary to a genetic disorder of autosomal or X-linked recessive inheritance rather than SCA6. Other reported cases of patients homozygous for the SCA6 gene are also reviewed.     

遗传性脊髓小脑型共济失调病人SCA_3基因突变检测

1目的　探讨遗传性脊髓小脑型共济失调 (SCA)病人 SCA3基因突变的意义。2方法　应用聚合酶链反应 (PCR)、聚丙烯酰胺凝胶电泳银染法 ,对临床诊断为 SCA的 15个家系的 32例病人及其有亲缘关系的 2 2例正常者 ,进行 SCA3基因内一段包含 CAG三核苷酸重复序列片段扩增。3结果　 5个家系中的 2 1例病人各有 1个 SCA3异常等位基因扩增片段 ,其中 1个家系中 2例病人和 1例“正常者”的 1个等位基因的 CAG三核苷酸重复数目都为 48次。4结论　检测 SCA基因的动态突变是目前诊断 SCA的唯一有效方法。     

Epidemiología de la enfermedad coronaria

Understanding the societal impact and trends of coronary heart disease through basic epidemiological measures is essential to evaluate treatment effectiveness and organize resource distribution. In the following narrative review, data are presented on the prevalence, incidence, and prognosis of coronary heart disease in general and of acute coronary syndrome in particular.     

Characterization of the Zebrafish atxn1/axh Gene Family

In mammals, ataxin-1 (ATXN1) is a member of a family of proteins in which each member contains an AXH domain. Expansion of the polyglutamine tract in ATXN1 causes the neurodegenerative disease, spinocerebellar ataxia type 1 (SCA1) with prominent cerebellar pathology. Toward a further characterization of the genetic diversification of the ATXN1/AXH gene family, we identified and characterized members of this gene family in zebrafish, a lower vertebrate with a cerebellum. The zebrafish genome encodes two ATXN1 homologs, atxn1a and atxn1b, and one ATXN1L homolog, atxn1l. Key biochemical features of the human ATXN1 protein not seen in the invertebrate homologs (a nuclear localization sequence and a site of phosphorylation at serine 776) are conserved in the zebrafish homologs, and all three zebrafish Atxn1/Axh proteins behave similarly to their human counterparts in tissue-culture cells. Importantly, each of the three homologs is expressed in the zebrafish cerebellum, which in humans, is a prominent site of SCA1 pathogenesis. In addition, atxn1a and atxn1b are expressed in the developing zebrafish cerebellum. These data show that in zebrafish, a lower vertebrate, the complexity of the atxn1/axh gene family is more similar to higher vertebrates than invertebrates with a simple central nervous system and suggests a relationship between the diversification of the ATXN1/AXH gene family and the development of a complex central nervous system, including a cerebellum.     

Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations

Although many genes have been identified for the autosomal recessive cerebellar ataxias (ARCAs), several patients are unlinked to the respective loci, suggesting further genetic heterogeneity. We combined homozygosity mapping and exome sequencing in a consanguineous Egyptian family with congenital ARCA, mental retardation and pyramidal signs. A homozygous 5-bp deletion in SPTBN2, the gene whose in-frame mutations cause autosomal dominant spinocerebellar ataxia type 5, was shown to segregate with ataxia in the family. Our findings are compatible with the concept of truncating SPTBN2 mutations acting recessively, which is supported by disease expression in homozygous, but not heterozygous, knockout mice, ataxia in Beagle dogs with a homozygous frameshift mutation and, very recently, a homozygous SPTBN2 nonsense mutation underlying infantile ataxia and psychomotor delay in a human family. As there was no evidence for mutations in 23 additional consanguineous families, SPTBN2-related ARCA is probably rare.     

New method of thrombus preparation using a fluid model for evaluation of thrombectomy devices in a swine model

Background

Mechanical thrombectomy is a promising new modality of interventional stroke treatment. Preparation of thrombus is a very important step for the evaluation of the mechanical thrombectomy devices. The objective of this study was to explore a new method of thrombus preparation with fluid model (FM) for assessment of thrombectomy devices used in the recanalization of acute ischemic stroke.

Methods

Elongation test and catheter injection test were used to evaluate the mechanical properties of thrombi prepared by FM and static model (SM). Histological structures of two artificial clots and specimens of stroke patients were compared. Radiopacity of thrombus made by FM was evaluated in a swine embolization model.

Results

The maximum tensile length of thrombi prepared by FM and SM were significantly higher (4.28 ± 0.23 cm vs 3.16 ± 0.13 cm, P < 0.01) and showed less breakage on catheter injection test (13% vs 60%, P < 0.05). Histological features of thrombi prepared by FM showed mixed thrombus structure, similar to thromboemboli retrieved from acute stroke patients, while clots generated by SM were replete with erythrocytes. A total of twelve vessels in two swine were successfully occluded (TIMI 0 or 1), with sufficient radiopacity of each injected thrombus.

Conclusion

The thrombus prepared by FM had good mechanical stability, sufficient radiopacity, and similar histological structure of thromboemboli retrieved from stroke patients, which make it possible to be used in the evaluation of thrombectomy devices.