Mario Muto

Epidemiology and genetics of intracranial aneurysms

Intracranial aneurysms are acquired lesions (5-10% of the population), a fraction of which rupture leading to subarachnoid hemorrhage with devastating consequences. Until now, the exact etiology of intracranial aneurysms formation remains unclear. The low incidence of subarachnoid hemorrhage in comparison with the prevalence of unruptured IAs suggests that the vast majority of intracranial aneurysms do not rupture and that identifying those at highest risk is important in defining the optimal management. The most important factors predicting rupture are aneurysm size and site. In addition to ambiental factors (smoking, excessive alcohol consumption and hypertension), epidemiological studies have demonstrated a familiar influence contributing to the pathogenesis of intracranial aneurysms, with increased frequency in first- and second-degree relatives of people with subarachnoid hemorrhage. In comparison to sporadic aneurysms, familial aneurysms tend to be larger, more often located at the middle cerebral artery, and more likely to be multiple. Other than familiar occurrence, there are several heritable conditions associated with intracranial aneurysm formation, including autosomal dominant polycystic kidney disease, neurofibromatosis type I, Marfan syndrome, multiple endocrine neoplasia type I, pseudoxanthoma elasticum, hereditary hemorrhagic telangiectasia, and Ehlers-Danlos syndrome type II and IV. The familial occurrence and the association with heritable conditions indicate that genetic factors may play a role in the development of intracranial aneurysms. Genome-wide linkage studies in families and sib pairs with intracranial aneurysms have identified several loci on chromosomes showing suggestive evidence of linkage, particularly on chromosomes 1p34.3-p36.13, 7q11, 19q13.3, and Xp22. For the loci on 1p34.3-p36.13 and 7q11, a moderate positive association with positional candidate genes has been demonstrated (perlecan gene, elastin gene, collagen type 1 A2 gene). Moreover, 3 of the polymorphisms analyzed in 2 genes (endothelial nitric oxide synthase T786C, interleukin-6 G572C, and interleukin-6 G174C) were found to be significantly associated with ruptured/unruptured aneurysms: the endothelial nitric oxide synthase gene single-nucleotide polymorphisms increased the risk, while IL-6 G174C seemed protective. More recently, two genomic loci (endothelin receptor A and cyclin-dependent kinase inhibitor 2BAS) have been found to be significantly associated with intracranial aneurysms in the Japanese population; endothelin-1 is a potent vasoconstrictor produced by the endothelial cells. Until now, there are no diagnostic tests for specific genetic risk factors to identify patients who are at a high risk of developing intracranial aneurysms. Knowledge of the genetic determinants may be useful in order to allow clues on stopping aneurysm formation and obtain diagnostic tools for identifying individuals at increased risk. Further multicenter studies have to be carried out.

Biomechanics of the spine. Part I: Spinal stability

Biomechanics, the application of mechanical principles to living organisms, helps us to understand how all the bony and soft spinal components contribute individually and together to ensure spinal stability, and how traumas, tumours and degenerative disorders exert destabilizing effects. Spine stability is the basic requirement to protect nervous structures and prevent the early mechanical deterioration of spinal components. The literature reports a number of biomechanical and clinical definitions of spinal stability, but a consensus definition is lacking. Any vertebra in each spinal motion segment, the smallest functional unit of the spine, can perform various combinations of the main and coupled movements during which a number of bony and soft restraints maintain spine stability. Bones, disks and ligaments contribute by playing a structural role and by acting as transducers through their mechanoreceptors. Mechanoreceptors send proprioceptive impulses to the central nervous system which coordinates muscle tone, movement and reflexes. Damage to any spinal structure gives rise to some degree of instability. Instability is classically considered as a global increase in the movements associated with the occurrence of back and/or nerve root pain. The assessment of spinal instability remains a major challenge for diagnostic imaging experts. Knowledge of biomechanics is essential in view of the increasing involvement of radiologists and neuroradiologists in spinal interventional procedures and the ongoing development of new techniques and devices. Bioengineers and surgeons are currently focusing on mobile stabilization systems. These systems represent a new frontier in the treatment of painful degenerative spine and aim to neutralize noxious forces, restore the normal function of spinal segments and protect the adjacent segments. This review discusses the current concepts of spine stability.

A Metaanalysis of the Effectiveness and Safety of Ozone Treatments for Herniated Lumbar Discs

PURPOSE To determine statistically significant effects of oxygen/ozone treatment of herniated discs with respect to pain, function, and complication rate. MATERIALS AND METHODS Random-effects metaanalyses were used to estimate outcomes for oxygen/ozone treatment of herniated discs. A literature search provided relevant studies that were weighted by a study quality score. Separate metaanalyses were performed for visual analog scale (VAS), Oswestry Disability Index (ODI), and modified MacNab outcome scales, as well as for complication rate. Institutional review board approval was not required for this retrospective analysis. RESULTS Twelve studies were included in the metaanalyses. The inclusion/exclusion criteria, patient demographics, clinical trial rankings, treatment procedures, outcome measures, and complications are summarized. Metaanalyses were performed on the oxygen/ozone treatment results for almost 8,000 patients from multiple centers. The mean improvement was 3.9 for VAS and 25.7 for ODI. The likelihood of showing improvement on the modified MacNab scale was 79.7%. The means for the VAS and ODI outcomes are well above the minimum clinically important difference and the minimum (significant) detectable change. The likelihood of complications was 0.064%. CONCLUSIONS Oxygen/ozone treatment of herniated discs is an effective and extremely safe procedure. The estimated improvement in pain and function is impressive in view of the broad inclusion criteria, which included patients ranging in age from 13 to 94 years with all types of disc herniations. Pain and function outcomes are similar to the outcomes for lumbar discs treated with surgical discectomy, but the complication rate is much lower (<0.1%) and the recovery time is significantly shorter.

Percutaneous vertebroplasty: Multi-centric results from EVEREST experience in large cohort of patients

PURPOSE The purpose of this study was to prospectively evaluate results and complications of percutaneous vertebroplasty (PV) performed in 6 different Italian Centres belonging to the European VErtebroplasty RESearch Team (E.VE.RES.T) in a large series of patients. MATERIALS AND METHODS Follow-up was obtained in 4547 patients (3211 females and 1336 males; mean age 70.2 years) that underwent PV for a total of 13.437 treated vertebrae. Procedures were performed by using fluoroscopic guidance or combined CT-fluoroscopic guidance. All patients underwent PV in local anaesthesia except for second cervical vertebrae treated with a trans-oral approach that required general anaesthesia. RESULTS 4004 out of 4547 (88.0%) patients reported significant pain relief (difference>or=2 point in pain evaluated with an 11-point visual analogue scale; p<0.0001) within 48 h: an average of 7.7 ± 0.4 dropped to 1.8 ± 0.6 in the osteoporotic patients; 8.3 ± 0.4 to 2.4 ± 0.4 in metastases; 8.3 ± 0.4 to 1.7 ± 1.0 in myeloma; 6.2 ± 3.5 to 0.3 ± 0.2 in angioma and 7.4 ± 0.4 to 1.4 ± 0.9 in trauma. 430 osteoporotic patients (13%) were retreated for a subsequent fracture; in 302/430 patients (70.2%), the new fracture occurred in the contiguous vertebra. No major neurologic complications were reported and the most frequent minor complication was venous leakage (20.5%). CONCLUSIONS This large series of patients confirms that percutaneous vertebroplasty is an effective and safe procedure in the treatment of vertebral fractures. Best results are obtained in the treatment of myeloma and trauma.

Statement of ESMINT and ESNR regarding recent trials evaluating the endovascular treatment at the acute stage of ischemic stroke

Three recent, simultaneous publications report the neutral results of three randomized studies (SYNTHESIS Expansion, Interventional Management of Stroke (IMS) III, and Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE)) comparing IV thrombolysis therapy or standard care (MR RESCUE) to the endovascular treatment (EVT) of acute ischemic stroke (AIS) [1–3]. The results of these three trials might lead to the erroneous conclusion that endovascular treatment has no or little place in the management of AIS. However, careful analysis of the IMS III, SYNTHESIS, and MR RESCUE studies is mandatory prior to assessment of the value of EVT of AIS. Also, the limits of the current and future trials should be outlined. The European Society of Minimally Invasive Neurological Therapy (ESMINT) and European Society of Neuroradiology (ESNR) represent the interventional neuroradiology community in Europe and have engaged in the definition of rules regarding trials evaluating the EVT of AIS [4, 5]. It is clearly their role to provide a precise analysis of recent and future trials. In the last 20 years, treatment of AIS has evolved to include neuroprotection, IV thrombolysis (IVT), and endovascular treatment. Despite numerous studies of a very large number

Percutaneous vertebroplasty or kyphoplasty.

Percutaneous vertebral augmentation techniques performed with vertebroplasty or kyphoplasty are safe and effective for the treatment of osteoporotic vertebral compression fractures, primary or secondary spine tumors, and selected traumatic fractures. This article compares the procedures and outlines their advantages and disadvantages. It concludes that vertebroplasty should be performed in most cases, but kyphoplasty is preferable in selected cases.

A comparison of minimally invasive techniques in percutaneous treatment of lumbar herniated discs. A review.

Low back pain is the commonest spine disease causing absence from work in developed countries. Low back pain with classical irradiation along the course of the nerve root affected is more frequently due to disc disease. In 60–80% of patients with herniated disc, radicular symptoms disappear with conservative treatment after about six weeks, the remainder are treated surgically with a 2–6% of incidence of true recurrence of herniation post-intervention and with failed back surgery syndrome in 15% of cases. Recently minimally invasive techniques have developed as “alternative” treatments to surgical intervention. This review aimed to assess the pathogenesis of low back pain caused by lumbar disc hernia as a basis for action of minimally invasive techniques; to illustrate the techniques already used or currently in use, to compare them in technical guidance, indications and complications, exposing for each of them the inclusion/exclusion criteria in enrolling patients and the imaging guide technique of choice. Minimally invasive techniques can be a valuable alternative to traditional surgery with low cost, low risk of complications, easy feasibility, and in the event of failure they do not exclude subsequent surgery.

Assisted techniques for vertebral cementoplasty: Why should we do it?

Assisted techniques (AT) for vertebral cementoplasty include multiple mini-invasive percutaneous systems in which vertebral augmentation is obtained through mechanical devices with the aim to reach the best vertebral height restoration. As an evolution of the vertebroplasty, the rationale of the AT-treatment is to combine the analgesic and stability effect of cement injection with the restoration of a physiological height for the collapsed vertebral body. Reduction of the vertebral body kyphotic deformity, considering the target of normal spine biomechanics, could improve all systemic potential complications evident in patient with vertebral compression fracture (VCF). Main indications for AT are related to fractures in fragile vertebral osseous matrix and non-osteoporotic vertebral lesions due to spine metastasis or trauma. Many companies developed different systems for AT having the same target but different working cannula, different vertebral height restoration system and costs. Aim of this review is to discuss about vertebral cementoplasty procedures and techniques, considering patient inclusion and exclusion criteria as well as all related minor and/or major interventional complications.

Mid-term and long-term follow-up of intracranial aneurysms treated by the p64 Flow Modulation Device: a multicenter experience

Background Experience with the endovascular treatment of cerebral aneurysms using the p64 Flow Modulation Device is still limited. This study discusses the results and complications of this new flow diverter device. Methods 40 patients (30 women, 10 men) with 50 cerebral aneurysms treated in six Italian neurointerventional centers with the p64 Flow Modulation Device between April 2013 and September 2015 were retrospectively reviewed. Results Complete occlusion was obtained in 44/50 aneurysms (88%) and partial occlusion in 3 (6%). In the other three aneurysms (6%), two cases of asymptomatic in-stent thrombosis and one intraprocedural occlusion of the parent vessel occurred. Technical complications were observed in eight procedures (16%). Permanent morbidity due to acute in-stent thrombosis and consequent ischemic stroke occurred in one patient (2.5%). No delayed aneurysm rupture, subarachnoid or intraparenchymal hemorrhage, or ischemic complications occurred and there were no deaths. Conclusions Endovascular treatment with the p64 Flow Modulation Device is a safe treatment for unruptured cerebral aneurysms, resulting in a high rate of occlusion. As with other flow diverter devices, we recommend this treatment mainly for large-necked aneurysms of the internal carotid artery siphon. However, endovascular treatment with the p64 device should also be encouraged in difficult cases such as aneurysms of the posterior circulation and beyond the circle of Willis.

Vertebroplasty in the Treatment of Spine Disease

We report our experience in the treatment of thoracic and lumbosacral spinal pain due to vertebral bone fractures. This pathology can be related to osteoporosis but also to metastatic disease and less frequently vertebral haemangioma. From April 2001 through December 2004 we treated 238 patients for a total of 455 vertebral bodies. 175 patients had osteoporosis, 70 had metastasis and 13 had vertebral haemangioma. Sacroplasty was performed in six patients to obtain a cement filling of sacral metastasis. The procedures were mostly performed under fluoroscopy and only in cases of metastasis or sacroplasty was CT/fluoroscopy guidance preferred for optimal filling of the area of osteolysis. We evaluated the results at six and 18 months follow-up and analysed the incidence of new vertebral fractures, vascular and disk leakage and the incidence of major and minor complications. Biopsy was performed only in doubtful cases. We obtained different results considering the etiology of the disease. We obtained a 92% success rate at six months follow-up and 89% success at 18 months follow-up in osteoporosis, a 77% and 72% success rate at six and 18 months follow-up in metastastic patients, and no change at six and 18 months follow-up in patients with vertebral haemangioma in which the success rate was of 95%. We noted extravertebral leakage in 41% of vertebral bodies of which 31% were treated at the level of the vascular space and only 10% at the level of the disk space, and symptomatic in only two cases (acute compressive radiculitis, medically treated and resolved within a month). Six patients presented new fractures in the adjacent vertebral body and 30% had a partial recovery in the height of the vertebral body with kyphosis curve reduction. Vertebroplasty is a good technique to obtain spine pain relief and has a low incidence of side effects. Good quality equipment is important to obtain these results.