Somatic mutational landscape of extracranial arteriovenous malformations and phenotypic correlations.

BACKGROUND: Somatic genetic variants may be the cause of extracranial arteriovenous malformations, but few studies have explored these genetic anomalies, and no genotype-phenotype correlations have been identified. OBJECTIVES: The aim of the study was to characterize the somatic genetic landscape of extracranial arteriovenous malformations and correlate these findings with the phenotypic characteristics of these lesions. METHODS: This study included twenty-three patients with extracranial arteriovenous malformations that were confirmed clinically and treated by surgical resection, and for whom frozen tissue samples were available. Targeted next-generation sequencing analysis of tissues was performed using a gene panel that included vascular disease-related genes and tumour-related genes. RESULTS: We identified a pathogenic variant in 18 out of 23 samples (78.3%). Pathogenic variants were mainly located in MAP2K1 (n = 7) and KRAS (n = 6), and more rarely in BRAF (n = 2) and RASA1 (n = 3). KRAS variants were significantly (P < 0.005) associated with severe extended facial arteriovenous malformations, for which relapse after surgical resection is frequently observed, while MAP2K1 variants were significantly (P < 0.005) associated with less severe, limited arteriovenous malformations located on the lips. CONCLUSIONS: Our study highlights a high prevalence of pathogenic somatic variants, predominantly in MAP2K1 and KRAS, in extracranial arteriovenous malformations. In addition, our study identifies for the first time a correlation between the genotype, clinical severity and angiographic characteristics of extracranial arteriovenous malformations. The RAS/MAPK variants identified in this study are known to be associated with malignant tumours for which targeted therapies have already been developed. Thus, identification of these somatic variants could lead to new therapeutic options to improve the management of patients with extracranial arteriovenous malformations.

Curriculum for Vestibular Medicine (VestMed) proposed by the Bárány Society.

This document presents the initiative of the Bárány Society to improve diagnosis and care of patients presenting with vestibular symptoms worldwide.The Vestibular Medicine (VestMed) concept embraces a wide approach to the potential causes of vestibular symptoms, acknowledging that vertigo, dizziness, and unsteadiness are non-specific symptoms that may arise from a broad spectrum of disorders, spanning from the inner ear to the brainstem, cerebellum and supratentorial cerebral networks, to many disorders beyond these structures.The Bárány Society Vestibular Medicine Curriculum (BS-VestMed-Cur) is based on the concept that VestMed is practiced by different physician specialties and non-physician allied health professionals. Each profession has its characteristic disciplinary role and profile, but all work in overlapping areas. Each discipline requires good awareness of the variety of disorders that can present with vestibular symptoms, their underlying mechanisms and etiologies, diagnostic criteria and treatment options. Similarly, all disciplines require an understanding of their own limitations, the contribution to patient care from other professionals and when to involve other members of the VestMed community. Therefore, the BS-VestMed-Cur is the same for all health professionals involved, the overlaps and differences of the various relevant professions being defined by different levels of detail and depth of knowledge and skills.The BS-VestMed-Cur defines a Basic and an Expert Level Curriculum. The Basic Level Curriculum covers the VestMed topics in less detail and depth, yet still conveys the concept of the wide net approach. It is designed for health professionals as an introduction to, and first step toward, VestMed expertise. The Expert Level Curriculum defines a Focused and Broad Expert. It covers the VestMed spectrum in high detail and requires a high level of understanding. In the Basic and Expert Level Curricula, the range of topics is the same and runs from anatomy, physiology and physics of the vestibular system, to vestibular symptoms, history taking, bedside examination, ancillary testing, the various vestibular disorders, their treatment and professional attitudes. Additionally, research topics relevant to clinical practice are included in the Expert Level Curriculum. For Focused Expert proficiency, the Basic Level Curriculum is required to ensure a broad overview and additionally requires an expansion of knowledge and skills in one or a few specific topics related to the focused expertise, e.g. inner ear surgery. Broad Expert proficiency targets professionals who deal with all sorts of patients presenting with vestibular symptoms (e.g. otorhinolaryngologists, neurologists, audiovestibular physicians, physical therapists), requiring a high level of VestMed expertise across the whole spectrum. For the Broad Expert, the Expert Level Curriculum is required in which the minimum attainment targets for all the topics go beyond the Basic Level Curriculum. The minimum requirements regarding knowledge and skills vary between Broad Experts, since they are tuned to the activity profile and underlying specialty of the expert. The BS-VestMed-Cur aims to provide a basis for current and future teaching and training programs for physicians and non-physicians. The Basic Level Curriculum could also serve as a resource for inspiration for teaching VestMed to students, postgraduate generalists such as primary care physicians and undergraduate health professionals, or anybody wishing to enter VestMed. VestMed is considered a set of competences related to an area of practice of established physician specialties and non-physician health professions rather than a separate clinical specialty. This curriculum does not aim to define a new single clinical specialty. The BS-VestMed-Cur should also integrate with, facilitate and encourage translational research in the vestibular field.

[The Bárány Classification of vestibular disorders, its clinical implementation and future prospects]. / Die Bárány-Klassifikation vestibulärer Erkrankungen: Grundlagen, klinische Anwendung und zukünftige Perspektiven.

Vestibular diseases often have no or only nonspecific biomarkers. It is therefore necessary to define these disorders using operational criteria based on patterns of symptoms, i.e., the presence of inclusion and exclusion criteria, similar to the situation with headaches or psychiatric diseases. Ten years ago, the Bárány Society embarked upon development of the International Classification of Vestibular Disorders (ICVD). This entails producing the different definitions iteratively according to a structured procedure with an internal review process, resulting in an open-access publication on the diagnostic criteria in each case. It is a multidisciplinary effort, and depending on the topic, cooperation with other scientific societies is sought. The classification encompasses primary vestibular disorders and non-vestibular disorders that may manifest with prominent vestibular symptoms. The following paper describes the procedure and briefly presents definitions which have already been published as well as those presently in elaboration.

Endovascular management of extracranial occlusions at the hyperacute phase of stroke with tandem occlusions.

BACKGROUND AND PURPOSE: The management of cervical artery occlusions in hyperacute stroke with tandem cervical/intracranial occlusions has not yet become standardized, especially when the circle of Willis is effective. METHODS: We retrospectively analyzed the safety and accuracy of current approaches to manage the cervical occlusion in consecutive patients with tandem occlusions addressed for intracranial mechanical thrombectomy (MT) in our department from January 2012 to May 2017. The different approaches that could be performed in a same patient during the same procedure or hospitalization were analyzed separately. RESULTS: We reported 64 approaches to manage the cervical occlusion in 49 patients with tandem occlusion (14% of MT): medical treatment alone in 16/64 (25%), stenting/angioplasty in 16/64 (25%), occlusion with coils in 12/64 (19%), angioplasty alone in 9/64 (14%), stent-retriever in 8/64 (12%), and/or thromboaspiration in 3/64 (5%). Early ipsilateral embolic recurrence occurred after 9/64 (14%) of them. It was strongly associated with the presence of a cervical intraluminal thrombus (P=0.001) and was then lower after occlusion with coils and stent-retriever compared to medical treatment alone and thromboaspiration (P=0.002). Occlusion with coils had a lower rate of radiological intracranial hemorrhage at 48-hour compared to other approaches (P=0.009). The 3-month rates of favorable outcome (P=0.806) and mortality (P=0.878) were similar. One delayed stroke was imputable to an occlusion with coils, for a median (Q1-Q3) follow-up of 10 (3-20) months. CONCLUSIONS: Cervical occlusion with coils and thrombectomy with stent-retrievers may be relevant to prevent early embolic recurrence in cervical occlusions with intraluminal thrombus. Stent-retrievers should be further assessed as a first-line approach, since delayed stroke may occur following occlusion with coils. Medical treatment alone may be sufficient when no cervical intraluminal thrombus is present, the Willis polygon is effective, and the cervical occlusion can be crossed easily to perform the intracranial thrombectomy.

[Diagnostic criteria for Menière's disease according to the Classification Committee of the Bárány Society]. / M. Menière: Diagnostische Kriterien des Internationalen Klassifikationskomitees der Bárány-Gesellschaft.

This paper presents diagnostic criteria for Menière's disease jointly formulated by the Classification Committee of the Bárány Society, The Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology (EAONO), the Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the Korean Balance Society. The classification includes two categories: definite Menière's disease and probable Menière's disease. The diagnosis of definite Menière's disease is based on clinical criteria and requires the observation of an episodic vertigo syndrome associated with low- to medium-frequency sensorineural hearing loss and fluctuating aural symptoms (hearing, tinnitus and/or fullness) in the affected ear. Duration of vertigo episodes is limited to a period between 20 min and 12 h. Probable Menière's disease is a broader concept defined by episodic vestibular symptoms (vertigo or dizziness) associated with fluctuating aural symptoms occurring in a period from 20 min to 24 h.

Vestibular symptoms and history taking.

History taking is an essential part in the diagnostic process of vestibular disorders. The approach to focus strongly on the quality of symptoms, like vertigo, dizziness, or unsteadiness, is not that useful as these symptoms often coexist and are all nonspecific, as each of them may arise from vestibular and nonvestibular diseases (like cardiovascular disease) and do not permit to distinguish potentially dangerous from benign causes. Instead, patients should be categorized if they have an acute, episodic, or chronic vestibular syndrome (AVS, EVS, or CVS) to narrow down the spectrum of differential diagnosis. Typical examples of disorders provoking an AVS would be vestibular neuritis or stroke of peripheral or central vestibular structures, of an EVS Menière's disease, benign paroxysmal positional vertigo, or vestibular migraine and of a CVS long-standing uni- or bilateral vestibular failure or cerebellar degeneration. The presence of triggers should be established with a main distinction between positional (change of head orientation with respect to gravity), head motion-induced (time-locked to head motion regardless of direction) and orthostatic position change as the underlying disorders are quite different. Accompanying symptoms also help to orient to the underlying cause, like aural or neurologic symptoms, but also chest pain or dyspnea.

Parent artery occlusion in large, giant, or fusiform aneurysms of the carotid siphon: clinical and imaging results.

BACKGROUND AND PURPOSE: Parent artery occlusion has long been considered the reference treatment for large/giant or fusiform aneurysms of the carotid siphon. However, meager recent data exist on this technique, which tends to be replaced by stent-assisted reconstructive techniques. In our department since 2004, we have assessed the safety, efficacy, and complication risk factors of parent artery occlusion by using coils for trapping these aneurysms. MATERIALS AND METHODS: We determined retrospectively the complication rate, factors associated with the occurrence of an ischemic event, changes in symptoms of mass effect, evolution of the aneurysmal size, and the growth of an additional aneurysm after treatment. RESULTS: Fifty-six consecutive patients were included, with a median age of 54 years (range, 25-85 years; 92% women), 48% with giant aneurysms and 75% with infraclinoid aneurysms. There was a permanent morbidity rate of 5% exclusively due to ischemia, a zero mortality rate, an aneurysmal retraction rate of 91%, and an improvement rate for pain of 98% and for cranial nerve palsy of 72%, with a median follow-up of >3 years. Para-/supraclinoid topography of the aneurysm (P = .043) and the presence of cardiovascular risk factors (P = .024) were associated with an excessive risk of an ischemic event, whereas the presence of a mural thrombus had a protective role (P = .033). CONCLUSIONS: In this study, parent artery occlusion by using coils to treat large/giant or fusiform aneurysms of the carotid siphon was safe and effective, especially for giant infraclinoid aneurysms. According to recent meta-analyses, these results suggest that the validation of stent-assisted reconstructive treatments for these aneurysms requires controlled studies with parent occlusion artery.

Visuo-proprioceptive interactions in degenerative cervical spine diseases requiring surgery.

Cervical proprioception plays a key role in postural control, but its specific contribution is controversial. Postural impairment was shown in whiplash injuries without demonstrating the sole involvement of the cervical spine. The consequences of degenerative cervical spine diseases are underreported in posture-related scientific literature in spite of their high prevalence. No report has focused on the two different mechanisms underlying cervicobrachial pain: herniated discs and spondylosis. This study aimed to evaluate postural control of two groups of patients with degenerative cervical spine diseases with or without optokinetic stimulation before and after surgical treatment. Seventeen patients with radiculopathy were recruited and divided into two groups according to the spondylotic or discal origin of the nerve compression. All patients and a control population of 31 healthy individuals underwent a static posturographic test with 12 recordings; the first four recordings with the head in 0° position: eyes closed, eyes open without optokinetic stimulation, with clockwise and counter clockwise optokinetic stimulations. These four sensorial situations were repeated with the head rotated 30° to the left and to the right. Patients repeated these 12 recordings 6weeks postoperatively. None of the patients reported vertigo or balance disorders before or after surgery. Prior to surgery, in the eyes closed condition, the herniated disc group was more stable than the spondylosis group. After surgery, the contribution of visual input to postural control in a dynamic visual environment was reduced in both cervical spine diseases whereas in a stable visual environment visual contribution was reduced only in the spondylosis group. The relative importance of visual and proprioceptive inputs to postural control varies according to the type of pathology and surgery tends to reduce visual contribution mostly in the spondylosis group.

Klippel-Trenaunay syndrome and spinal arteriovenous malformations: an erroneous association.

BACKGROUND AND PURPOSE: KTS is a rare limb overgrowth disorder with slow-flow vascular anomalies. This study examines the presumed association between KTS and spinal AVMs. MATERIALS AND METHODS: We performed a MEDLINE search of articles and reviewed textbooks of spinal diseases to study the association between KTS and spinal AVM. Our goal was to ascertain the basis on which the diagnosis of KTS was established and to evaluate the evidence of its association with spinal AVMs. In addition, the data base of the Vascular Anomalies Center at Children's Hospital Boston was queried for patients with KTS, and the association with spinal AVM was investigated. RESULTS: Twenty-four published reports on spinal AVMs in 31 patients with KTS were reviewed. None of these references provided solid evidence of the diagnosis of KTS in any patient. Clinical data were either incompatible with the diagnosis of KTS or were inadequate to establish the diagnosis. Alternative possible diagnoses (CLOVES syndrome and CM-AVM) were suggested by the first author for 9 of the patients reported in these articles. The medical records of 208 patients with the diagnosis of KTS were analyzed; not a single patient had clinical or radiologic evidence of a spinal AVM. CONCLUSIONS: An association between KTS and spinal AVM, as posited in numerous references, is most likely erroneous. The association has neither been reliably proved in the limited published literature nor encountered in a large cohort.

[Pregnancy follow-up and outcome in women with superficial vascular malformations]. / Malformations vasculaires superficielles : impact sur le suivi de grossesse et prise en charge à l'accouchement.

Superficial vascular malformations (MAV), so far called "superficial angioma", are uncommon and often unknown. The last classification, done by the "International Society for the Study of Vascular Anomalies", is essential to avoid diagnostic and therapeutic mistakes. Extramedullar localisations are rare. The coexistence of a pregnancy and a MAV states two problems: the medical and paraclinic supervision of the volume of the MAV and its risk of thrombosis with the choice of thrombosis prevention, and the mode of delivery and type of anaesthesia depending on its anatomical location. We revised the management of pregnant women with a MAV illustrating possible troubles to deal with. We reported the cases of two women having for the first one a pharyngolaryngeal MAV, the second a cutaneous MAV located on the leg and needing a multidisciplinary management with obstetricians, anaesthesists, hematologists, dermatologists, ENT, radiologists and pediatricians.

Abnormalities of the vestibulo-collic reflex are similar in migraineurs with and without vertigo.

The amplitude and habituation of the click-evoked vestibulo-collic reflex (VCR) was found reduced between attacks in migraineurs without complaints of ictal or interictal vertigo or dizziness, compared with healthy subjects. As a next step we recorded VCR in 17 migraine patients (eight with migraine without aura and nine with migraine with aura) who presented ictal migrainous vertigo according to the criteria defined by Neuhauser et al., using a method described previously. Migraineurs with migrainous vertigo have similar VCR abnormalities as patients without vertigo, i.e. a decreased global amplitude and absence of habituation. Potentiation seemed more pronounced in migraineurs with vertigo (7.46 +/- 18.6), but the difference was not significant.

The vestibulo-collic reflex is abnormal in migraine.

Interictal evoked central nervous system responses are characterized in migraineurs by a deficit of habituation, at both cortical and subcortical levels. The click-evoked vestibulo-collic reflex (VCR) allows the assessment of otolith function and an oligosynaptic pathway linking receptors in the saccular macula to motoneurons of neck muscles. Three blocks of 75 averaged responses to monaural 95-dB normal hearing level 3-Hz clicks were recorded over the contracted ipsilateral sternocleidomastoid muscle in 25 migraineurs between attacks and 20 healthy subjects, without vestibular symptoms. Amplitudes, raw and corrected for baseline electromyography, were significantly smaller in migraine patients. Whereas in healthy volunteers the VCR habituated during stimulus repetition (-4.96% +/- 14.3), potentiation was found in migraineurs (4.34% +/- 15.3; P = 0.04). The combination with a reduced mean amplitude does not favour vestibular hyperexcitability as an explanation for the habituation deficit in migraine, but rather an abnormal processing of repeated stimuli in the reflex circuit.

Intracranial vascular anomalies in patients with periorbital lymphatic and lymphaticovenous malformations.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the nature, incidence, and radiologic appearance of intracranial vascular anomalies that occur in association with periorbital lymphatic malformation (LM) and lymphaticovenous malformation (LVM). MATERIALS AND METHODS: We retrospectively reviewed clinical records and imaging studies of 33 patients ranging in age from the neonatal period to 39 years (mean age, 5.1 years; median age, 1.0 year) who were evaluated for orbital LM or LVM at our institution between 1953 and 2002. Imaging studies, including CT, MR imaging, and cerebral angiograms, were evaluated by 2 radiologists to determine morphologic features of orbital LM and to identify associated noncontiguous intracranial vascular and parenchymal anomalies, including arteriovenous malformations (AVM), cerebral cavernous malformations (CCM), developmental venous anomalies (DVA), dural arteriovenous malformations (DAVM), and sinus pericranii (SP). RESULTS: The malformation was left-sided in 70% of patients. Twenty-two patients (70%) had intracranial vascular anomalies: DVA (n = 20; 61%), CCM (n = 2; 6%), DAVM (n = 4; 12%), pial AVM (n = 1; 3%), and SP (n = 1; 3%). Arterial shunts were present in the soft tissues in 2 patients (6%). Three patients had jugular venous anomalies. Three patients (9%) had cerebral hemiatrophy, 2 (6%) had focal cerebral atrophy, and 2 had Chiari I malformation. CONCLUSIONS: Intracranial vascular anomalies, some of which are potentially symptomatic and require treatment, are present in more than two thirds of patients with periorbital LM. Initial imaging of patients with orbital LM should include the brain as well as the orbit.

Occlusion of the middle cerebral artery due to synthetic fibers.

We report an unusual etiology for a thromboembolic complication. Occlusion of the middle cerebral artery occurred before embolization of an intracranial aneurysm. Attempts to recanalize the artery failed by using both fibrinolytics and IIb/IIIa inhibitors but succeeded with mechanical thrombectomy with a micro-snare. Pathologic analysis of the thrombus showed numerous synthetic fibers that were determined to have originated from unsealed gauze that was used during the procedure.

Cost of disorders of the brain in Luxembourg.

Brain disorders (psychiatric, neurological and neurosurgical diseases) are leading causes of disease and disability. According to WHO data they cause 35% of the burden of all diseases in Europe. The present study aims to estimate the cost of defined brain disorders and adds all selected disorders to arrive at the total cost for Luxembourg. A model combining published economic and epidemiological data retrieved from the OECD (Organization for Economic Co-operation and Development) and Eurostat databases on brain disorders in Europe (EU member countries, Iceland, Norway and Switzerland) was used. We transformed and converted data for a defined period into the same currency (Euro 2004) and adjusted country specific economic data for purchasing power and relative size of economy and imputed data where no local data were available. There are an estimated 123000 people in Luxembourg currently living with a brain disorder. The total annual cost of brain disorders is estimated at Euro 500 million in 2004 or an average of Euro 1100 per inhabitant. Mental disorders constitute 62% of the total cost (excluding dementia), followed by neurological diseases (excluding dementia) 22%, neurosurgical diseases excluding herniated discs 2.2%. Direct medical expenditures (outpatient care, hospitalization, drugs) have a share of 32%, direct non-medical costs (social services, informal care, adaptation, transportation) 18% and indirect costs (sick leave, early retirement and premature death) 51%.

Recording click-evoked myogenic potentials (CEMPs) with a setup for brainstem auditory evoked potentials (BAEPs).

AIM OF THE STUDY: Click-evoked myogenic potentials (CEMPs) originate in the sternocleidomastoid (SCM) muscle through a reflex loop involving the sacculus and the vestibular nerve. In this study we suggest that they can be picked up from the mastoid reference used for auditory evoked potential (AEP) recording by using standard filters for brainstem AEPs (BAEPs). They consist of a P13-N20 complex. METHODS: Fifty normal subjects were investigated. Recordings were performed with the same setting as that used for conventional BAEPs but without artifact rejection and using a wide time window (100 ms). Unilateral auditory stimulations were used. All acquisitions were performed in both sitting and supine positions. In nine subjects CEMPs and BAEPs were simultaneously recorded at both earlobe and both SCM muscles. RESULTS: In all subjects, a CEMP P13-N20 component could be evidenced in sitting, but not in supine position at both the ipsilateral earlobe and the ipsilateral SCM muscle. Its latency was 0.7 ms lower at the earlobe. It obeyed the same relationship to stimulus intensity at both earlobe and SCM muscle. CONCLUSION: These results demonstrate the possibility to get simultaneous information on the brainstem auditory pathways and on a reflex probably mediated through the sacculus and the vestibular nerve. Further studies on patients with selective vestibular nerve impairment should be conducted to confirm the clinical utility of this approach.

Facial infantile hemangiopericytoma resembling an arteriovenous malformation.

Malignant highly vascularized tumors such as hemangiopericytomas (HPC) may mimic a benign arteriovenous malformation (AVM) which is sometimes still referred to as "angioma". We describe the clinical and radiological findings of a facial hemangiopericytoma in comparison to an AVM in order to avoid misdiagnosis between these two pathologies since evolution and therapeutic management are completely different. Because hemangiopericytomas in children show malignant behavior requiring aggressive management, early and accurate diagnosis is of significant importance for the clinical outcome.