Clinical Muscle Testing Compared with Whole-Body Magnetic Resonance Imaging in Facio-scapulo-humeral Muscular Dystrophy.

OBJECTIVE: The objective of this study was to evaluate the clinical usefulness of whole-body magnetic resonance imaging (MRI) in facio-scapulo-humeral muscular dystrophy (FSHD). METHODS: In 20 patients with genetically proven FSHD1, we prospectively assessed muscular involvement and correlated the results of semi-quantitative manual muscle testing and other parameters such as disease duration, creatine kinase (CK) levels and repeat length of the D4Z4 locus with whole-body MRI. RESULTS: Clinical muscle testing revealed the trapezius, pectoralis and infraspinatus as the most severely affected muscles in the shoulder, and the knee flexors and gluteus medius in the hip girdle. MRI revealed the trapezius and serratus anterior muscles in the shoulder, and the hamstrings and adductor muscles in the hip girdle, as the most severely affected muscle groups. Overall, degrees of fatty degeneration on MRI scans correlated significantly with clinical weakness. Moreover, we could detect clear affection of the trunk muscles. Corresponding to earlier reports, asymmetric involvement was frequent in both clinical examination and MRI scoring. Moreover, MRI revealed inhomogeneous muscle degeneration in a considerable proportion of both, muscles and patients. Both clinical and MRI scores significantly correlated to disease duration, but not to fragment size or CK levels. CONCLUSION: Fatty degeneration in whole-body MRI correlates well to clinical muscle testing of the extremities but gives more information on deeper or trunk muscles. It shows structural changes in muscular disorders and may become an excellent tool for assessment of muscle involvement and follow-up studies.

The FRED flow-diverter stent for intracranial aneurysms: clinical study to assess safety and efficacy.

BACKGROUND AND PURPOSE: Flow-diverter stents are emerging for the endovascular treatment of difficult-to-treat or otherwise untreatable cerebral aneurysms (wide-neck, fusiform, dissecting, blisterlike, or giant). We assessed the clinical safety and efficacy of the Flow-Redirection Endoluminal Device. MATERIALS AND METHODS: This was an institutional review board-approved single-center observational clinical study in 29 patients with 34 aneurysms elected to be treated by endovascular intervention. After providing informed consent, patients were included according to the following criteria: aneurysm fundus-to-neck ratio <2 or neck diameter >4 mm, fusiform, dissecting, or giant aneurysms. The primary end point for clinical safety was the absence of death, absence of major or minor stroke, and absence of transient ischemic attack. The primary end point for treatment efficacy was complete angiographic occlusion according to the O'Kelly Marotta grading scale immediately after the procedure and at follow-up after 3 and 6 months (O'Kelly Marotta D: complete occlusion). RESULTS: The Flow-Redirection Intraluminal Device deployment was technically successful in all cases. In 26/29 (89%) of patients, the primary end point of safety was reached; in the 3 remaining patients, 1 disabling ischemic stroke and 2 minor strokes with complete recovery at follow-up were observed. Angiographic (DSA and MRA) and clinical follow-up were available after 3 months in 29/29 (100%) and after 6 months in 25/29 (86%) patients (after 6 months, only MRA follow-up was performed according to our study protocol and institutional standard). At 3-month follow-up, complete occlusion was reached in 19/34 aneurysms (O'Kelly Marotta D: 19/34; 56%). At 6-month follow-up, aneurysm occlusion was complete in 22/30 aneurysms (O'Kelly Marotta D: 22/30; 73%). CONCLUSIONS: Deployment of the Flow-Redirection Intraluminal Device flow-diverter stent is safe and effective in the treatment of difficult-to-treat or otherwise untreatable intracranial aneurysms.

The LVIS Jr. microstent to assist coil embolization of wide-neck intracranial aneurysms: clinical study to assess safety and efficacy.

INTRODUCTION: This study was aimed to assess clinical safety and efficacy of the LVIS Jr. microstent in stent-assisted coil embolization of wide-neck intracranial aneurysms. METHODS: IRB approved single-center interventional clinical study in 22 patients (10 females, 12 males, mean age 55, age range 33-74 years) for the endovascular treatment of wide-neck aneurysms. After obtaining informed consent, patients were included according to the following criteria: aneurysm fundus-to-neck ratio < 2 or neck diameter > 4 mm, and a parent vessel diameter of ≤3.5 mm. Primary end point for clinical safety was absence of death, absence of major or minor stroke, and absence of transient ischemic attack. Primary end point for treatment efficacy was complete angiographic occlusion according to the Raymond-Roy Occlusion Classification (RROC) immediately after the procedure and at follow-up after 3 and 6 months on magnetic resonance imaging (MRI). RESULTS: In 20/22 (91 %) of patients, the primary end point of safety was reached; in the two remaining patients, transient ischemic attack, but no permanent deficit was observed; in 16/22 (73 %), efficient occlusion (RROC1) was reached, and in 6/22 (27 %), a residual neck remained (RROC2). Single [seven with antegrade, two in crossover configuration, and four with "first-balloon-then-stent" (FBTS) technique] or double-stent (eight patients with Y configuration and one patient with X configuration) deployment was technically successful in all cases. CONCLUSION: Deployment of the LVIS Jr. microstent in various single- or double-stent configurations is safe and effective to assist the treatment of intracranial wide-neck aneurysms.

Suppression of proinvasive RGS4 by mTOR inhibition optimizes glioma treatment.

An essential mode of acquired resistance to radiotherapy (RT) appears to be promotion of tumor cell motility and invasiveness in various cancer types, including glioblastoma, a process resembling 'evasive resistance'. Hence, a logical advancement of RT would be to identify suitable complementary treatment strategies, ideally targeting cell motility. Here we report that the combination of focal RT and mammalian target of rapamycin (mTOR) inhibition using clinically relevant concentrations of temsirolimus (CCI-779) prolongs survival in a syngeneic mouse glioma model through additive cytostatic effects. In vitro, the mTOR inhibitor CCI-779 exerted marked anti-invasive effects, irrespective of the phosphatase and tensin homolog deleted on chromosome 10 status and counteracted the proinvasive effect of sublethal irradiation. Mechanistically, we identified regulator of G-protein signaling 4 (RGS4) as a novel target of mTOR inhibition and a key driver of glioblastoma invasiveness, sensitive to the anti-invasive properties of CCI-779. Notably, suppression of RGS4-dependent glioma cell invasion was signaled through both mTOR complexes, mTORC1 and mTORC2, in a concentration-dependent manner, indicating that high doses of CCI-779 may overcome tumor-cell resistance associated with the sole inhibition of mTORC1. We conclude that combined RT and mTOR inhibition is a promising therapeutic option that warrants further clinical investigation in upfront glioblastoma therapy.