Founder effect and ancestral origin of the spinocerebellar ataxia type 7 (SCA7) mutation in Mexican families

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant disease characterized by progressive cerebellar ataxia and macular degeneration causing progressive blindness. It accounts for 1 to 11.6 % of spinocerebellar ataxias (SCAs) cases worldwide and for 7.4 % of SCA7 cases in Mexico. We identified a cluster of SCA7 families who resided in a circumscribed area of Veracruz and investigated whether the high incidence of the disease in this region was due to a founder effect. A total of 181 individuals from 20 families were studied. Four microsatellite markers and one SNP flanking the ATNX7 gene were genotyped and the ancestral origin and local ancestry analysis of the SCA7 mutation were evaluated. Ninety individuals from 19 families had the SCA7 mutation; all were found to share a common haplotype, suggesting that the mutation in these families originated from a common ancestor. Ancestral origin and local ancestry analysis of SCA7 showed that the chromosomal segment containing the mutation was of European origin. We here present evidence strongly suggesting that the high frequency of SCA7 in Veracruz is due to a founder effect and that the mutation is most likely of European origin with greatest resemblance to the Finnish population.     

Combined PTSD and depressive symptoms interact with post-deployment social support to predict suicidal ideation in Operation Enduring Freedom and Operation Iraqi Freedom veterans

Rates of suicide are alarmingly high in military and veteran samples. Suicide rates are particularly elevated among those with post-traumatic stress disorder (PTSD) and depression, which share overlapping symptoms and frequently co-occur. Identifying and confirming factors that reduce, suicide risk among veterans with PTSD and depression is imperative. The proposed study evaluated, whether post-deployment social support moderated the influence of PTSD–depression symptoms on, suicidal ideation among Veterans returning from Iraq and Afghanistan using state of the art clinical, diagnostic interviews and self-report measures. Operations Enduring and Iraqi Freedom (OEF/OIF) Veterans (n=145) were invited to, participate in a study evaluating returning Veterans? experiences. As predicted, PTSD–depression, symptoms had almost no effect on suicidal ideation (SI) when post-deployment social support was high; however, when, post-deployment social support was low, PTSD–depression symptoms were positively associated with, SI. Thus, social support may be an important factor for clinicians to assess in the context of PTSD and, depressive symptoms. Future research is needed to prospectively examine the inter-relationship, between PTSD/depression and social support on suicidal risk, as well as whether interventions to, improve social support result in decreased suicidality.     

Longitudinal features of stir bright signal in FSHD1

Introduction: Magnetic resonance imaging of muscle shows short tau‐inversion recovery (STIR) brightness in autosomal dominant facioscapulohumeral muscular dystrophy (FSHD1) suggestive of active inflammation/injury. We measured the longitudinal stability/progression of this potential disease biomarker. Methods: Nine subjects underwent calf MRI imaging over 2 years. Two radiologists evaluated qualitative muscle changes. Results: In 3/9 subjects, calf muscles demonstrated moderate/severe STIR hyperintensity at Time 1 that had progressed to fatty replacement 2 years later (Time 2). In the remaining subjects, moderate/severe muscle STIR abnormalities, when present, were consistent between exams. Mild STIR+ elevations had roughly similar patterns between exams. Conclusions: Moderate/severe STIR hyperintensities often foreshadow fatty replacement over a 2‐year interval. Whether longer time courses are required to observe muscle degeneration and fatty replacement in some subjects remains to be explored. Muscle Nerve 49 : 257–260, 2014     

MRI findings of intracranial anomalies associated with cephalocele—a case series

Introduction

Cephalocele is a relatively rare cranial dysraphism characterised by herniation of intracranial structures through the skull. Surgical management is primarily necessary where a risk of infection through communication of the lesion with the intracranial space exists, a risk of rupture, or for cosmetic purposes. Cephalocele is often associated with venous anomalies such as vertical embryonic positioning of the straight sinus, splitting of the superior sagittal sinus, vein of Galen elongation, along with tenting of the tentorium [Morioka et al. Childs Nerv Syst 25:309–315, 2009]

Patients

Here, we report four cases of cephalocele with pre-operative MRI imaging retrospectively studied, demonstrating associated venous anomalies. Three of these patients went on to have uncomplicated, corrective surgery, while one was managed conservatively.

Results

All four cases demonstrated the main venous drainage going through a persistent falcine sinus to drain into the superior sagittal sinus. Upward tenting of the tentorium was observed in three cases (cases 1, 3 and 4). Two of our cases demonstrated other venous anomalies frequently reported in the literature, namely splitting of the superior sagittal sinus and absence of the transverse sinus (case 1) and communication of the cephalocele with the superior sagittal sinus and absence of the straight sinus (case 2).

Conclusion

The association between cephalocele and venous anomalies suggests that pre-operative MRI should be mandatory for a full evaluation of a suspicious midline cranial lesion in order to evaluate the safety of corrective surgery.     

How Tough Is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone

The multiscale hierarchical structure of bone is naturally optimized to resist fractures. In osteogenesis imperfecta, or brittle bone disease, genetic mutations affect the quality and/or quantity of collagen, dramatically increasing bone fracture risk. Here we reveal how the collagen defect results in bone fragility in a mouse model of osteogenesis imperfecta (oim), which has homotrimeric α1(I) collagen. At the molecular level, we attribute the loss in toughness to a decrease in the stabilizing enzymatic cross‐links and an increase in nonenzymatic cross‐links, which may break prematurely, inhibiting plasticity. At the tissue level, high vascular canal density reduces the stable crack growth, and extensive woven bone limits the crack‐deflection toughening during crack growth. This demonstrates how modifications at the bone molecular level have ramifications at larger length scales affecting the overall mechanical integrity of the bone; thus, treatment strategies have to address multiscale properties in order to regain bone toughness. In this regard, findings from the heterozygous oim bone, where defective as well as normal collagen are present, suggest that increasing the quantity of healthy collagen in these bones helps to recover toughness at the multiple length scales. © 2014 American Society for Bone and Mineral Research.     

Cortical Porosity Identifies Women With Osteopenia at Increased Risk for Forearm Fractures

Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high‐resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10‐year fracture probability using the country‐specific fracture risk assessment tool (FRAX) in 68 postmenopausal women with forearm fractures and 70 age‐matched community controls in Olmsted County, MN, USA. Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact‐appearing cortical porosity predicted fracture independent of aBMD; odds ratio (OR) = 1.92 (95% confidence interval [CI] 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with fractures from those without because high porosity was present in 92% and 86% of each group, respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact‐appearing cortex conferred an OR for fracture of 4.00 (95% CI 1.15–13.90). In women with osteoporosis, porosity is captured by aBMD, so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures. © 2014 American Society for Bone and Mineral Research.     

Endoscopic transluminal necrosectomy in necrotising pancreatitis: a systematic review

Objective

We performed a systematic review to assess the outcome of endoscopic transluminal necrosectomy in necrotising pancreatitis with additional focus on indication, disease severity, and methodological quality of studies.

Design

We searched the literature published between January 2005 and June 2013. Cohorts, including patients with (infected) necrotising pancreatitis, undergoing endoscopic necrosectomy were included. Indication, disease severity, and methodological quality were described. The main outcomes were mortality, major complications, number of endoscopic sessions, and definitive successful treatment with endoscopic necrosectomy alone.

Results

After screening 581 papers, 14 studies, including 455 patients, fulfilled the eligibility criteria. All included studies were retrospective analyses except for one randomized, controlled trial. Overall methodological quality was moderate to low (mean 5, range 2–9). Less than 50 % of studies reported on pre-procedural severity of disease: mean APACHE-II score before intervention was 8; organ failure was present in 23 % of patients; and infected necrosis in 57 % of patients. On average, four (range 1–23) endoscopic interventions were performed per patient. With endoscopic necrosectomy alone, definitive successful treatment was achieved in 81 % of patients. Mortality was 6 % (28/460 patients) and complications occurred in 36 % of patients. Bleeding was the most common complication.

Conclusions

Endoscopic transluminal necrosectomy is an effective treatment for the majority of patients with necrotising pancreatitis with acceptable mortality and complication rates. It should be noted that methodological quality of the available studies is limited and that the combined patient population of endoscopically treated patients is only moderately ill.