Magnetic resonance angiography compared to intra-arterial digital subtraction angiography in patients with subarachnoid haemorrhage

Summary In order to evaluate the sensitivity and specificity of magnetic resonance angiography (MRA) in spontaneous subarachnoid haemorrhage, 14 patients with recent haemorrhage verified by CT or lumbar puncture were investigated with both selective intra-arterial digital subtraction angiography (IA-DSA) and MRA by two independent teams, each having the same preangiographic information. The results were compared with each other and whenever possible (all positive cases except one) with those of surgical intervention. Seven patients were identified by MRA and IA-DSA as having a single aneurysm on the circle of Willis, 1 an aneurysm of the posterior inferior cerebellar artery 1 an aneurysm of the internal carotid artery (siphon) and 2 patients with two aneurysms on the circle of Willis. MRA and IA-DSA both failed to demonstrate aneurysms in 2 cases. Three patients had negative results on both methods and no surgical intervention was attempted. The aneurysms ranged from 0.3 to 1.5 cm in size. In most cases there was agreement between MRA and DSA, leading us to believe that, if the proper protocols are followed, MRA is a powerful alternative to other established methods in the detection of intracranial aneurysms. At this stage it will not replace IA-DSA prior to surgery, but the ability to obtain various projections using 3D MRA may improve surgical planning.     

Quality of life in Greek family members living with leg ulcer patients

Leg ulcers have been shown to have a significant impact on a patient's quality of life (QoL). Little is known, however, about the secondary impact of the disease on the QoL of the relatives and partners of patients with leg ulcers. The aim of this study was to explore the impact of chronic leg ulcers on the lives of both patients and their family members. Two hundred sixteen patients with leg ulcers and their family members were recruited. All patients entered were evaluated for QoL using the Dermatology Life Quality Index (DLQI) scale, and family members were similarly evaluated using the Family Dermatology Life Quality Index (FDLQI).The study included 56 female and 52 male patients, and 50 female and 58 male family members. The FDLQI score for the latter group was 14.37 ± 2.46 with over 96% of family members reporting a large effect on their QoL due to their relative's disease. The DLQI score in patients with leg ulcers was 13.18 ± 2.88. A significant positive and high correlation between DLQI and FDLQI scores (r = 0.71, p < 0.001) was documented, while DLQI contributed significantly to the prediction of FDLQI (standardized β = 0.71, p < 0.001). Our study results indicate that the QoL of the family was also affected by the patient's condition of chronic leg ulcers and clearly associated with that of the patients.     

Pediatric golf-related head injuries

Objectives Golf-related head injuries constitute an increasingly common mechanism of head trauma in children. We present our experience with 33 pediatric cases of golf-associated head injury, with special emphasis in the type of injury, management strategy, and outcome.Materials and methods A thorough review of all children admitted to our hospital with golf-related head injury during a period of 10 years (1 January 1994 to 31 December 2003) was undertaken. The patients’ charts, operative reports, imaging studies, and follow-up data were analyzed. A comparison of our findings with those described in the pertinent literature was subsequently performed.Conclusions Pediatric golf-related head trauma is a significant cause of sport-associated head injury, sometimes harboring a very dismal prognosis. The significance of establishing a task force for the prevention of these injuries cannot be overemphasized.     

How reliable is MRCP with an SS-FSE sequence at 3.0 T: comparison between SS-FSE BH and 3D-FSE BH ASSET sequences

PurposeThe purpose of the present study was to evaluate the visibility and the image quality of the biliary and pancreatic duct system on magnetic resonance cholangiopancreatography (MRCP) images based on two breath-hold (BH) methods using array spatial sensitivity technique: a single-shot fast spin-echo (SS-FSE) sequence and a three-dimensional single slab fast spin-echo (3D-FSE) sequence.Materials and methodsIn the present prospective comparative study, 47 patients (22 male and 25 female, mean age=50 years, age range=22–82 years) that were referred for MRCP during a 12-month period are included. All of them were referred with suspected pancreaticobiliary disease. All patients underwent MRCP with both a SS-FSE BH sequence and a 3D-FSE BH sequence. Qualitative evaluation regarding the depiction of three segments of the pancreaticobiliary tree and the frequency of artifacts was performed. Two radiologists graded each sequence of the obtained studies in a blinded fashion. Quantitative evaluation including calculation of relative signal intensity (rSI) and relative contrast (RC) ratios at seven segments of the pancreaticobiliary tree between fluid-filled ductal structures and organ parenchyma at the same ductal segments was performed. In order to evaluate the parameters' differences of the two sequences, either in qualitative or in quantitative analysis, the Wilcoxon paired signed-rank test was performed.ResultsOn quantitative evaluation, both rSI and RC ratios of all segments of the pancreaticobiliary tree at SS-FSE BH sequence were higher than those at 3D-FSE BH sequences. This finding was statistically significant (P< .01). On qualitative evaluation, the two radiologists found intrahepatic ducts and pancreatic ducts to be better visualized with SS-FSE BH than with 3D-FSE BH sequence. This finding was statistically significant (P< .02). One of them found extrahepatic ducts to be significantly better visualized with SS-FSE BH sequence. Moreover, the frequency of artifacts was lower in the SS-FSE sequence, a finding that was of statistical significance. Interobserver agreement analysis found at least substantial agreement (κ>0.60) between the two radiologists.ConclusionThe SS-FSE sequence is performed faster and significantly improves image quality; thus, it should be included into the routine MRCP sequence protocol at 3.0 T. Furthermore, we recommended SS-FSE BH MRCP examination to be applied to uncooperative patients or patients in emergency because of its short acquisition time (1 s).     

Epidural intracranial abscess as a complication of frontal sinusitis: case report and review of the literature

Two cases of epidural abscess as a complication of frontal sinusitis are presented. The diagnoses were suspected on the basis of history and were confirmed by magnetic resonance imaging and computed tomography. Both patients were treated successfully by means of surgery and intravenous antibiotics. One patient developed meningitis in the postoperative course and was treated by changing the antibiotic regimen. However, further follow-up in the outpatient clinic by physical examinations and brain computed tomography scans showed no longterm neurologic complications in either case. Intracranial suppuration, including epidural abscesses, can complicate acute and chronic frontal sinusitis. These complications are diagnosed by maintaining a high index of suspicion and using the appropriate neuroimaging studies without delay.     

α-Synuclein phosphorylation at serine 129 occurs after initial protein deposition and inhibits seeded fibril formation and toxicity

α-Synuclein (α-syn) phosphorylation at serine 129 (pS129–α-syn) is substantially increased in Lewy body disease, such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, the pathogenic relevance of pS129–α-syn remains controversial, so we sought to identify when pS129 modification occurs during α-syn aggregation and its role in initiation, progression and cellular toxicity of disease. Using diverse aggregation assays, including real-time quaking-induced conversion (RT-QuIC) on brain homogenates from PD and DLB cases, we demonstrated that pS129–α-syn inhibits α-syn fibril formation and seeded aggregation. We also identified lower seeding propensity of pS129–α-syn in cultured cells and correspondingly attenuated cellular toxicity. To build upon these findings, we developed a monoclonal antibody (4B1) specifically recognizing nonphosphorylated S129–α-syn (WT–α-syn) and noted that S129 residue is more efficiently phosphorylated when the protein is aggregated. Using this antibody, we characterized the time-course of α-syn phosphorylation in organotypic mouse hippocampal cultures and mice injected with α-syn preformed fibrils, and we observed aggregation of nonphosphorylated α-syn followed by later pS129–α-syn. Furthermore, in postmortem brain tissue from PD and DLB patients, we observed an inverse relationship between relative abundance of nonphosphorylated α-syn and disease duration. These findings suggest that pS129–α-syn occurs subsequent to initial protein aggregation and apparently inhibits further aggregation. This could possibly imply a potential protective role for pS129–α-syn, which has major implications for understanding the pathobiology of Lewy body disease and the continued use of reduced pS129–α-syn as a measure of efficacy in clinical trials.

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are both associated with underlying Lewy body disease, which represents the second most common neurodegenerative disorder after Alzheimer’s disease (1, 2). The neuropathological hallmark of Lewy body disease is the intracellular aggregation of the protein α-synuclein (α-syn) into spherical cytoplasmic inclusions, termed Lewy bodies, but are also observed in neuronal processes as Lewy neurites (LNs) (3).α-Syn is thought to play a central role in the pathobiology of Lewy body disease. Single-point mutations and genetic modifications affecting α-syn expression—through duplications, triplications, or polymorphisms in its promoter—have been linked to both idiopathic and familial forms of Lewy body disease (4–6). Nevertheless, neuropathological studies utilizing pan–α-syn antibodies, recognizing both physiological and pathological forms of the protein, do not consistently report a relationship between the load of Lewy body pathology and clinical disease severity (2). To reconcile the apparent importance of α-syn in Lewy body disease with the difficulty relating Lewy body burdens in the brain to phenotypic severity, continued research has focused on the identification of particularly disease-relevant forms of α-syn. α-Syn undergoes various posttranslational modifications (PTMs)—including acetylation, nitration, ubiquitination, and glycosylation and phosphorylation at serine 129 (pS129)—increases from ∼4% under physiological conditions to 90% in Lewy body disease, suggesting it is associated with the disease state (7–9).Previous studies have reported that pS129 enhances intracellular aggregate formation in SH-SY5Y cells (10), and mediates cell death through activation of the unfolded protein response pathway (11). Furthermore, studies in rodent models have suggested that pS129 exacerbates the rate of pathological protein aggregation and deposition, with subsequent negative effects on neuronal functioning (12). However, these studies are counterbalanced by others reporting a potentially neuroprotective function of phosphorylation in animal models (13, 14) and cellular model systems (15). Additionally, studies have reported neutral findings regarding pS129 modification as neither enhancing nor diminishing cellular toxicity and α-syn aggregation (16, 17). Despite the uncertain pathogenic role of pS129 in Lewy body disease, antibodies against pS129 are widely used, based on the putative view that they label a species of α-syn that is particularly disease-relevant. These studies often employ pS129–α-syn as a marker of the abundance of protein inclusions to stage disease severity and evaluate the relationship between its abundance and important clinical or pathological variables, such as disease duration, phenotypic severity, or cell loss (18). Such studies typically identify that pS129 abundance throughout the brain correlates with disease severity (19–21), though it remains uncertain whether phosphorylation precedes protein aggregation or occurs secondarily to deposition of nonphosphorylated α-syn, and whether pS129 is a key driver of pathogenicity or simply a useful marker of a neurodegenerative process (22, 23). Therefore, although there is a substantial literature on pS129 in Lewy body disease, there is continued controversy regarding its potential contribution to disease states, with numerous studies reporting discordant findings. Despite contradictory findings regarding the disease-relevance of pS129, it is widely viewed as a particularly disease-associated modification, thus necessitating further research to address its importance for Lewy body disease.To address the key questions regarding the pathogenic relevance of pS129–α-syn, the present study aimed to undertake a comprehensive and multidisciplinary project to address this important and pressing question. The key aim of the study was to better understand the role of pS129 in the natural history of Lewy body disease, by determining when pS129 occurs in the development of α-syn aggregates and how it affects the aggregation-propensity and cytotoxicity of α-syn     

Refining the locus of branchio-otic syndrome 2 (BOS2) to a 5.25 Mb locus on chromosome 1q31.3q32.1

In 1991, a large family was described with an autosomal dominant inheritance of otological and branchial manifestations which was termed branchio-otic syndrome type 2 (BOS2). This trait was mapped by linkage analysis in this family to a region of 23–31 Mb on chromosome 1q25.1q32.1. In the present report we describe the clinical features of two patients with a deletion in this region: one patient has a deletion but no otological or branchial manifestations, the other patient manifests mild conductive hearing loss resulting from bilaterally malformed middle ear ossicles, as well as a preauricular pit. Mapping of the deletion breakpoints allowed to delineate the region involved in BOS2 to a 5.25 Mb region containing 27 protein-coding genes. A detailed medical history of both patients is provided and they are compared with the literature on other detected interstitial deletions of 1q25q32. These findings will aid in the identification of the genetic cause underlying BOS2.