Role of Advanced Hemodynamic Ultrasound Evaluation in the Differential Diagnosis of Middle Cerebral Artery Stenosis: Introducing Morphological Criteria.

OBJECTIVE: The aim of the work described here was to determine the possible impact of the new technique advanced hemodynamic ultrasound evaluation (AHUSE) in identification of severe intracranial stenosis. Transcranial Doppler (TCD) and transcranial color-coded Doppler (TCCD) provide reliable velocimetric data, the indirect analysis of which allows us to obtain information on the patency of vessels and assumed stenosis range. However, very tight stenoses (>95%) cannot be detected with velocimetric criteria because of spectrum drops and the absence of high velocities, so that the right curve of the Spencer equation cannot be solved. Likewise, high velocities are not detected when analyzing morphologically long stenosis. Furthermore, the current classifications based on velocimetric criteria do not provide any categorization on stenoses with multiple acceleration points (MAPs). METHODS: With this Technical Note we aim to introduce, in addition to velocimetric criteria, more morphological criteria based on TCCD with the algorithm of AHUSE to optimize the characterization of intracranial stenosis (IS). TCCD-AHUSE relies on intensity-based next-generation techniques and can be used to identify IS with MAPs and simultaneously perform a morphological assessment of the stenosis length. RESULTS: We introduce a new technical ultrasound (U) approach that we tested in a sample of four different types of stenoses combining velocimetric data and AHUSE using Esaote Microvascularization (MicroV) technique to the M1 tract of the middle cerebral artery (MCA). CONCLUSION: The authors believe that a multiparametric evaluation is more sensitive and supports the clinician by introducing the morphological concept, not just the velocimetric concept, to differentiate the IS pattern of MCA. The potential for developing a diagnostic/prognostic algorithm is discussed.

Novel pathogenic TGFBR1 and SMAD3 variants identified after cerebrovascular events in adult patients with Loeys-dietz syndrome.

INTRODUCTION: Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder due to heterozygous pathogenic variants in transforming growth factor beta (TGFß) signaling-related genes. LDS types 1-6 are distinguished depending on the involved gene. LDS is characterized by multiple arterial aneurysms and dissections in addition to variable neurological and systemic manifestations. Patient 1: a 68-year-old man was admitted due to an aphasic transient ischemic attack (TIA). Brain CT-scan and CT angiography revealed a chronic and asymptomatic right vertebral artery dissection. Stroke diagnostic panel was unremarkable. His history showed mild stroke familiarity. At age of 49, he was treated for dissecting-aneurysm of the ascending aorta and started anticoagulation therapy. Seven years later, he underwent surgery for dissecting aneurysm involving aortic arch, descending-thoracic aorta, left subclavian artery, and both iliac arteries. Patient 2: a 47-year-old man presented a left hemiparesis due to right middle cerebral artery (MCA) and anterior cerebral artery (ACA) occlusion caused by right internal carotid artery (ICA) dissection after sport activity. Despite i.v. thrombolysis and mechanical thrombectomy, he developed malignant cerebral infarction and underwent decompressive hemicraniectomy. Digital subtraction angiography showed bilateral carotid and vertebral kinking, aneurysmatic dilatation on both common iliac arteries and proximal ectasia of the descending aorta. His father and his uncle died because of an ischemic stroke and a cerebral aneurysm rupture with a subarachnoid hemorrhage (SAH), respectively. DISCUSSION: in both cases, considering the family history and the multiple dissections and aneurysms, LDS molecular analysis was performed. In patient 1, the novel NM_005902.3 (SMAD3): c.840T > G; p.(Asn280Lys) likely pathogenic variant was identified, thus leading to a diagnosis of LDS type 3. In patient 2, the novel NM_004612.2 (TGFBR1): c.1225T > G; p.(Trp409Gly) likely pathogenic variant was found, allowing for a diagnosis of LDS type 1. CONCLUSION: LDS is characterized by genetic and clinical variability. Our report suggests that this genetically-determined connective tissue disorder is probably underestimated, as it might firstly show up with cerebrovascular events, although mild systemic manifestations. These findings could lead to identify people at risk of severe vascular complications (i.e., through genetic consult on asymptomatic relatives), in order to perform adequate vascular assessments and follow-up to prevent complications such as stroke.

Rivaroxaban in cervical and "cervico-cerebral" artery dissections: a new therapeutic option?

Antiplatelet agents and vitamin K antagonists (VKA) are usually used in the treatment of cervical (carotid or vertebral) artery dissections (CADs); however, data about the use of direct oral anticoagulants (DOACs) in these conditions are very limited. DOACs have proven to be effective in stroke reduction in non-valvular atrial fibrillation and, when possible, they are preferred to warfarin because of their better safety profile. We describe four cases of CADs and, firstly in literature, cervico-cerebral (CCADs) in young patients (average age of 42 years) treated with rivaroxaban 20 mg daily. Three of these four dissections had affected the vertebral artery (condition with an unfavorable prognosis and more often complicated by subarachnoid hemorrhages), and the other one was a carotid dissection at the extra-intracranial passage. All patients were followed clinically and with serial neurosonological examinations at 1, 3, and 6 months and with magnetic resonance angiography (MRA) at 6 months. All patients presented a good outcome with vascular recanalization without stroke recurrence or bleedings, even in patients with intracranial vertebral artery involvement. DOACs could be an alternative in young patients with CADs and their use could be considered in intracranial artery dissections too.

Medication-overuse headache: a widely recognized entity amidst ongoing debate.

Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. The burden of disease on individuals and societies is significant due to high costs and comorbidities. In the Third Edition of the International Classification of Headache Disorders, medication-overuse headache is recognized as a separate secondary entity next to mostly primary headache disorders, although many clinicians see the disease as a sole complication of primary headache disorders. In this review, we explore the historical background of medication-overuse headache, its epidemiology, phenomenology, pathophysiology and treatment options. The review explores relevant unanswered questions and summarizes the current debates in medication-overuse headache.