Brain MRI abnormalities in muscular dystrophy due to FKRP mutations

INTRODUCTION: FKRP mutations cause a muscular dystrophy which may present in the neonatal period (MDC1C) or later in life (LGMD2I). Intelligence and brain imaging have been previously reported as being normal in FKRP-associated muscular dystrophy, except in rare cases presenting with mental retardation associated with structural brain abnormalities. PATIENTS AND METHODS: We studied cerebral MRIs in twelve patients with FKRP-associated muscular dystrophy presenting in infancy or early childhood, at ages between 14 months and 43 years. Two patients had severe cognitive deficits, four had mild-moderate mental retardation and the rest were considered to have normal intelligence. All, but one were wheelchair-bound and 7 were mechanically ventilated. RESULTS: Brain MRI was abnormal in 9 of 12 patients. Brain atrophy was seen in 8 patients. One child had isolated ventricular enlargement at 4 years. Cortical atrophy involved predominantly temporal and frontal lobes and was most important at later ages. In two cases with serial images this atrophy seemed progressive. Three patients, two with severe and one with moderate mental retardation, showed structural abnormalities of the posterior fossa with hypoplasia of the vermis and pons, and cerebellar hemispheric cysts. These abnormalities were stable with time. Two of these three patients also showed diffuse white matter abnormalities in early childhood, which regressed with time. CONCLUSIONS: MRI abnormalities are common in patients with FKRP-associated muscular dystrophy presenting at birth or in early childhood. Progressive brain atrophy is the most frequent finding. Posterior fossa malformations and transient white matter changes may be seen in patients with associated mental retardation.     

Refinement of metre perception--training increases hierarchical metre processing

Auditory metre perception refers to the ability to extract a temporally regular pulse and an underlying hierarchical structure of perceptual accents from a sequence of tones. Pulse perception is widely present in humans, and can be measured by the temporal expectancy for prospective tones, which listeners generate when presented with a metrical rhythm. We tested whether musical expertise leads to an increased perception and representation of the hierarchical structure of a metrical rhythm. Musicians and musical novices were tested in a mismatch negativity (MMN) paradigm for their sensitivity to perceptual accents on tones of the same pulse level (metre-congruent deviant) and on tones of a lower hierarchical level (metre-incongruent deviant). The difference between these two perceptual accents was more pronounced in the MMNs of the musicians than in those of the non-musicians. That is, musical expertise includes increased sensitivity to metre, specifically to its hierarchical structure. This enhanced higher-order temporal pattern perception makes musicians ideal models for investigating neural correlates of metre perception and, potentially, of related abstract pattern perception. Finally, our data show that small differences in sensitivity to higher-order patterns can be captured by means of an MMN paradigm.     

Self‐rated health status in spinocerebellar ataxia—Results from a European multicenter study

Patient‐based measures of subjective health status are increasingly used as outcome measures in interventional trials. We aimed to determine the variability and predictors of subjective health ratings in a possible target group for future interventions: the spinocerebellar ataxias (SCAs). A consecutive sample of 526 patients with otherwise unexplained progressive ataxia and genetic diagnoses of SCA1 (117), SCA2 (163), SCA3 (139), and SCA6 (107) were enrolled at 18 European referral centers. Subjective health status was assessed with a generic measure of health related quality of life, the EQ‐5D (Euroqol) questionnaire. In addition, we performed a neurological examination and a screening questionnaire for affective disorders (patient health questionnaire). Patient‐reported health status was compromised in patients of all genotypes (EQ‐5D visual analogue scale (EQ‐VAS) mean 61.45 ± 20.8). Specifically, problems were reported in the dimensions of mobility (86.9% of patients), usual activities (68%), pain/discomfort (49.4%), depression/anxiety (46.4%), and self care (38.2%). Multivariate analysis revealed three independent predictors of subjective health status: ataxia severity, extent of noncerebellar involvement, and the presence of depressive syndrome. This model explained 30.5% of EQ‐VAS variance in the whole sample and might be extrapolated to other SCA genotypes. © 2010 Movement Disorder Society     

Spectrum of head and neck lesions diagnosed by fine-needle aspiration cytology in the pediatric population

Fine-needle aspiration cytology (FNAC) of the head and neck region is well accepted as a diagnostic procedure in the adult population. FNAC in the pediatric population is gaining acceptance as clinicians add this technique to the diagnostic armamentarium. An experience with FNAC of the head and neck region in the pediatric population is described from 2 large inner-city hospitals. Eighty-five cases were retrieved from patients age <18 years. In 52 cases, clinical or surgical follow-up was obtained and among these cases the specificity and sensitivity of FNA was 93% and 100%, respectively. The high specificity of FNAC allows the clinician to be confident of malignancy in a clinically suspicious lesion of the head and neck in a pediatric patient.     

Influence of MMP-2 and MMP-9 promoter polymorphisms on gene expression and clinical outcome of non-small cell lung cancer

Matrix metalloproteinases (MMP) including MMP-2 and MMP-9 play a major role in tumour invasion by proteolysing the extracellular matrix. Their activation, particularly that of MMP-9, is partly dependent on plasmin that is inhibited by TFPI-2 (tissue factor pathway inhibitor-2), a serine protease inhibitor whose gene expression is decreased in about one-third of non-small cell lung cancers (NSCLC). In addition, MMP-2 and MMP-9 are essential in the development of NSCLC and can be regulated by functional promoter polymorphisms. In this study, the -1306C/T MMP-2, -735C/T MMP-2 and -1562C/T MMP-9 polymorphisms were analysed in 90 NSCLC patients and 90 controls. In addition, the promoter region of the TFPI-2 gene was screened for sequence variations in both groups by DHPLC. A -167G/A polymorphism was identified in 3% of controls whereas none of the 90 patients exhibited this genetic variation in the TFPI-2 promoter region. Moreover, no difference in -1306C/T MMP-2, -735C/T MMP-2 and -1562C/T MMP-9 genotypes was found between cases and controls. However, the homozygous -1562CC MMP-9 genotype was more frequent in patients with squamous cell carcinoma than in controls (p=0.018). When genotype distributions were compared to MMP-2 and MMP-9 gene expression in tumours, no relationship was found with the -1306 MMP-2 and -1562 MMP-9 polymorphisms. In contrast, tumour MMP-2 gene expression was lower in homozygous -735CC patients than in those with CT or TT genotypes. In addition, the survival time was longer in patients with the MMP-2 -735T allele than in those with the CC genotype (p=0.02). The relative risk of death was increased 2.6-fold in -735CC patients (p=0.045; 95% CI=1.0-6.7). The results of this study suggest that the -735C/T MMP-2 polymorphism might be an independent prognostic marker in NSCLC, but this should be confirmed in a larger cohort of patients.     

Anti-(apolipoprotein A-1) IgGs are associated with high levels of oxidized low-density lipoprotein in acute coronary syndrome

ApoA-1 (apolipoprotein A-1) is the main component of HDL (high-density lipoprotein) and stabilizes PON-1 (paraoxonase-1), which prevents lipid peroxidation and oxLDL (oxidized low-density lipoprotein) formation. Autoantibodies against apoA-1 [anti-(apoA-1) IgG] have been found in antiphospholipid syndrome and systemic lupus erythematosous, two diseases with an increased risk of thrombotic events, as well as in ACS (acute coronary syndrome). OxLDL levels are also elevated in these diseases. Whether anti-(apoA-1) IgGs exist in other prothrombotic conditions, such as APE (acute pulmonary embolism) and stroke, has not been studied and their potential association with oxLDL and PON-1 activity is not known. In the present study, we determined prospectively the prevalence of anti-(apoA-1) IgG in patients with ACS (n=127), APE (n=58) and stroke (n=34), and, when present, we tested their association with oxLDL levels. The prevalance of anti-(apoA-1) IgG was 11% in the ACS group, 2% in the control group and 0% in the APE and stroke groups. The ACS group had significantly higher median anti-(apoA-1) IgG titres than the other groups of patients. Patients with ACS positive for anti-(apoA-1) IgG had significantly higher median oxLDL values than those who tested negative (226.5 compared with 47.7 units/l; P<0.00001) and controls. The Spearman ranked test revealed a significant correlation between anti-(apoA-1) IgG titres and serum oxLDL levels (r=0.28, P<0.05). No association was found between PON-1 activity and oxLDL or anti-(apoA-1) IgG levels. In conclusion, anti-(apoA-1) IgG levels are positive in ACS, but not in stroke or APE. In ACS, their presence is associated with higher levels of oxLDL and is directly proportional to the serum concentration of oxLDL. These results emphasize the role of humoral autoimmunity as a mediator of inflammation and coronary atherogenesis.