Showing papers by "Bing-Wen Soong published in 2009"

The ‘hot cross bun’ sign in the patients with spinocerebellar ataxia

Abstract: Background and purpose: The ‘hot cross bun’ sign (HCBS), typically seen in the patients with multiple system atrophy, refers to a cruciform hyperintensity in the pons on T2-weighted MRI. Little is known about its pathological basis and prevalence in other degenerative cerebellar diseases and healthy population. We investigate the frequency of HCBS in the patients with spinocerebellar ataxia (SCA) and healthy controls. Methods: The presence of HCBS on T2-weighted axial MRIs from 138 SCA patients (three SCA1, 35 SCA2, 76 SCA3, 18 SCA6, one SCA7, three SCA8, and two SCA17) and 102 healthy controls was evaluated retrospectively. Results: The overall prevalence of HCBS in the SCA patients is 8.7%, but the frequency varies in different subtypes: 25.7% in SCA2, 1.3% in SCA3, and none in SCA6 or healthy controls. Notably, one patient with SCA7 and one with SCA8 were also found to have HCBS. Conclusions: The differential list of HCBS should be expanded to include SCA7 and SCA8. The elucidation of frequency of HCBS in various SCA subtypes may help prioritize the genetic testing in late-onset dominant ataxia.

Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese

Abstract: Background and purpose Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disorder caused by NOTCH3 mutations and characterized by recurrent subcortical infarctions, dementia and leukoencephalopathy. So far, most clinical, molecular and neuroimaging information has come from Caucasians. Therefore, we investigated the spectrum of NOTCH3 mutations and MRI features in CADASIL patients of Chinese origin on Taiwan.

The remarkably variable expressivity of CADASIL: report of a minimally symptomatic man at an advanced age.

Abstract: Sir, Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset, dominantly inherited disorder caused by NOTCH3 mutations. It is characterized by recurrent subcortical infarctions, dementia, and less frequently, migraine and psychiatric symptoms. NOTCH3 has 33 exons, and most CADASIL-associated NOTCH3 mutations result in a gain or loss of one cysteine residue within a given extracellular epidermal growth factor (EGF)-like repeat domain and, in Caucasians, with a strong cluster in exon 3–6 encoding the first five EGF-like repeats [1]. The typical MRI features in CADASIL include multi-focal lacunar infarcts and diffuse T2-weighted hyperintensity of cerebral white matter with involvement of the anterior temporal lobes [1]. The presence of granular osmiophilic material (GOM), which is seen in close vicinity to the basement membrane of the smooth muscle cells of the arterioles on electron microscopy (EM), is pathognomonic for CADASIL [1]. Although the penetrance of MRI changes has been reported to be complete by 40 years of age [2], the spectrum of clinical phenotypes has remained elusive. Herein, we report the case of an 86-year-old minimally symptomatic male with CADASIL mutation, representing one extreme of the remarkably variable expressivity of CADASIL. The 86-year-old man had been doing very well before. His past history is only remarkable for heavy cigarette smoking without migraine or psychiatric symptoms. He came to our attention because of a mild numbness in the left hand following two falls 2 months earlier. The neurological examinations revealed only subtly increased deep tendon reflexes in the right biceps and brachioradialis. The brain MRI with gadolinium-enhanced magnetic resonance angiography (MRA) revealed a diffuse leukoencephalopathy without anterior temporal lobe involvement, one single and small lacunar infarct in the left putamen (Fig. 1a), and patent cerebral vessels. Subsequent mutational analysis of NOTCH3 uncovered a missense mutation, c. 1708C [ T, in exon 11, which putatively may result in a substitution of cysteine for arginine at amino acid 544 (R544C). The EM exam of a skin biopsy demonstrated the presence of characteristic GOM (Fig. 1b, c). His family history was unclear because of his early separation, at teenage, from the family and he has no children. He had received 7 years of education. His score of Mini-Mental State Examination (MMSE) was 27 out of 30 and the Cognitive Abilities Screening Instruments (CASI) was 81 out of 100. The cutoff scores of CASI in our population for the diagnosis of dementia in those who received 6 or more years of education is 79/80 [3]. NOTCH3 R544C has previously been reported manifesting typical CADASIL features [4, 5]. In the literature, the clinical manifestations of NOTCH3 mutations are enormously variable [6], with another report of a 14-yearold boy presenting with recurrent hemiplegia [7]. The observation in this patient highlights that, because the clinical manifestations may be extremely subtle, NOTCH3 Y.-C. Lee B.-W. Soong (&) Department of Neurology, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, #155, Sec.2, Li-Nung Street, Peitou District, Taipei 11217, Taiwan, ROC e-mail: bwsoong@vghtpe.gov.tw

SCA8 repeat expansion: large CTA/CTG repeat alleles in neurological disorders and functional implications

Abstract: Spinocerebellar ataxia type 8 (SCA8) involves bidirectional expression of CUG (ATXN8OS) and CAG (ATXN8) expansion transcripts. The pathogenesis of SCA8 is complex and the spectrum of clinical presentations is broad. In the present study, we assessed the SCA8 repeat size ranges in Taiwanese Parkinson’s disease, Alzheimer’s disease and atypical parkinsonism and investigated the genetic variation modulating ATXN8 expression. Thirteen large SCA8 alleles and a novel ATXN8 −62 G/A promoter SNP were found. There is a significant difference in the proportion of the individuals carrying SCA8 larger alleles in atypical parkinsonism (P = 0.044) as compared to that in the control subjects. In lymphoblastoid cells carrying SCA8 large alleles, treatment of MG-132 or staurosporine significantly increases the cell death or caspase 3 activity. Although expressed at low steady-state, ATXN8 expression level is significantly higher (P = 0.012) in cells with SCA8 large alleles than that of the control cells. The ATXN8 transcriptional activity was significantly higher in the luciferase reporter construct containing the −62G allele than that containing the −62A allele in both neuroblastoma and embryonic kidney cells. Therefore, our preliminary results suggest that ATXN8 gene −62 G/A polymorphism may be functional in modulating ATXN8 expression.

Multi-tissue Classification of Diffusion-Weighted Brain Images in Multiple System Atrophy Using Expectation Maximization Algorithm Initialized by Hierarchical Clustering

Abstract: Multiple system atrophy (MSA) is a well-known neurodegenerative disorders that present parkinsonism syndrome and autonomic dysfunction. Patients with MSA who have the combination of parkinsonism and cerebellar ataxia are referred to as MSA-C. Brain diffusion-weighted imaging (DWI) offers the potential for objective criteria in the diagnosis of MSA. We aim to develop an automatic method to segment out the abnormal whole brain area in MSA-C patients based on the 13-direction DWI raw data. The whole brain DWI raw data of fifteen normal subjects and nine MSA-C patients were analyzed. In this study, we proposed a novel method to perform tissue segmentation directly based on the directional information of the DWI images, rather than using the parametric images, such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) as in the previous literatures. Specifically, a hierarchical clustering (HC) technique was first applied on the down-sampled data to initialize the model parameters for each tissue cluster followed by automatic segmentation using the expectation maximization (EM) algorithm. Our results demonstrate that the HC-EM is effective in multi-tissue classification, namely, the cerebrospinal fluid, gray matter, and several areas of white matters, on the DWI raw data. The segmented patterns and the corresponding intensities of thirteen directions of the cerebellum in MSA-C patients showed the decrease of the anisotropy, which were evidently different from the results in normal subjects.