Hrev_master [page 92] [Emergency Care Journal 2019; 15:8341] Emergency Care Journal 2019; volume 15:8341 Abstract Vertigo represents about 4% of access to the Emergency Department (ED). Several conditions, such as general medical ill- nesses, otovestibular diseases and neurological diseases (including posterior circulation stroke) cause acute vertigo. The incidence of cerebrovascular disease in patients with vertigo in ED varies from 3 to 5%. Although neurosonology studies on acute vestibular syn- drome are scarce, the use of transcranial Doppler (TCD) and tran- scranial color Doppler (TCCD) in the management of vertigo patients has several advantages: it can be performed at the patient's bedside and repeated and, furthermore, its use is low-cost. In an acute stroke, with an experienced doctor, it can help distinguish an ischemic stroke from a hemorrhagic stroke. In acute central vertigo induced by posterior circulation stroke, the TCD or TCCD can be a screening test before angiographic neuroradiological studies for stenosis of vertebral or basal arteries. As a matter of fact, the clin- ical outcome, particularly in the posterior circulation stroke, is mainly related to a rapid diagnosis and subsequent treatment that will be able to quickly restore the blood flow. In conclusion, TCD and TCCD are useful in the differential diagnosis of vertigo in the ED, although we recognize the indisputable importance of clinical examination as a first step in vertigo management. In the evalua- tion of patients with acute central vertigo due to suspected posteri- or circulation stroke, the use of TCD or TCCD can rapidly reveal steno-occlusive disease of the posterior circulation, arterial dissec- tions and give indirect signs of vertebra-basilar insufficiency. Introduction Vertigo is the illusory sense of movement, while unsteadiness is the feeling of being unstable while seated, standing, or walking.1 These symptoms represent the 4% of the access to the Emergency Department (ED)2,3 and they can be related to both benign diseases of the inner ear4 or serious central nervous system diseases, includ- ing posterior circulation stroke.3,5 In this review, we provide an overview of clinical signs vertigo induced by posterior circulation stroke, the use of neuroradiologi- cal examinations and the use of transcranial Doppler (TCD) and transcranial coded color Doppler (TCCD) in the management of patients with vertigo. Methods of research PubMed, Embase, Cochrane library and reference lists were searched for articles published until May 30, 2019 using the key- words: vertigo, insufficiency vertebrobasilar, posterior circulation stroke, transcranial Doppler, transcranial color-coded Doppler. Vertigo in the Emergency Department Several conditions cause acute vertigo such as general medical diseases (including those not related to the cardiovascular system) (about 50%), otovestibular diseases (about 33%) and neurological diseases (including stroke) (about 11%).6 In a prospective single- institution study, Cheung et al.7 reported that 23 of 413 patients (5.6%) referred to the emergency department for dizziness have a diagnosis of central nervous system diseases. Similarly, Navi et al.8 documented that 49 of 907 patients referred to ED for vertigo (5%) have severe neurological disease; 37 of these were cere- brovascular events. In a retrospective study conducted in Germany on 475 patients with vertigo referred to ED, neurologists diagnosed a benign neu- rological disease in 73% of cases and a severe neurological disease (e.g. cerebrovascular diseases and inflammatory disease) in 27% of cases.9 The most common causes of central vertigo are verte- brobasilar insufficiency, stroke, transient ischemic attack (TIA), migraine, multiple sclerosis, posterior fossa tumors, neurodegener- ative disorders, drugs and psychiatric conditions.10 Central vertigo in stroke of posterior circulation may be accompanied by neuro- logical symptoms such as ataxia, dysarthria, diplopia and visual weakness.11 Previous clinical studies suggested that some tests can be used to obtain a differential diagnosis between peripheral and central vertigo: i) gaze test; ii) alternative coverage test; iii) head impulse test; iv) targeted neurological examination, focusing on cranial nerves (including hearing), on cerebellar test and on long- distance signs; and v) gait test.3 The gait test is more important, in Correspondence: Antonio Siniscalchi, Stroke Unit, Department of Neurology, “Annunziata” Hospital, Via F. Migliori 1, 87100 Cosenza, Italy. Tel. +39.0984.681351 - Fax: +39.0984.21631. E-mail: anto.siniscalchi@libero.it Key words: Vertigo; Emergency Department; Posterior circulation stroke; Transcranial Doppler; Transcranial color Doppler. Conflict of interest: the authors declare no potential conflict of interest. Funding: none. Received for publication: 11 June 2019. Revision received: 16 July 2019. Accepted for publication: 8 August 2019. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2019 Licensee PAGEPress, Italy Emergency Care Journal 2019; 15:8341 doi:10.4081/ecj.2019.8341 The role of transcranial Doppler ultrasonography in differential diagnosis of vertigo in the Emergency Department Antonio Siniscalchi,1 Giovanni Malferrari2 1Stroke Unit, Department of Neurology, “Annunziata” Hospital, Cosenza; 2Stroke Unit, Department of Neurology, Local Health Authority - IRCCS, Reggio Emilia, Italy Non -co mmerc ial us e o nly [Emergency Care Journal 2019; 15:8341] [page 93] presence of central vertigo, even if for severely nauseated patients and too symptomatic for walking, is difficult verify the truncal ataxia. Patients requiring assistance for walk or sit, are more likely to have a central stroke (or other central nervous system disease) more than a vestibular neuritis.3 The tandem gait test evaluates the function of midline cerebellar, but in elderly people as well as in patients with peripheral vertigo it can give an uncorrected score. However, in vertigo patients, misdiagnosis can be also related to both inaccurate clinical evaluation,12 and a score of zero to the National Institute of Health Scale of stroke (NIHSS)13-15 as well as an excessive dependence of neuroradiological tests, such as com- puted tomography (CT).3 In a clinical study, a series of questions were asked to patients with vertigo to determine the reliability and consistency of eliminating the quality of symptoms and the timing and triggers of vertigo.16 When the main question was asked again 6 minutes later, half of the patients changed the type of primary vertigo,17 reducing the logic of a diagnostic process based on the type of vertigo.3 Patients with cardiovascular vertigo describe ver- tigo in almost 40% of cases. Patients with benign paroxysmal posi- tional vertigo, commonly elderly patients, often describe non-ver- tiginous vertigo.18,19 Despite these data, most physicians still use a quality symptom approach with vertigo patients regardless of tim- ing and triggers.3 A masked neurologist at the initial ED visit changed the diagnosis during the follow-up in 44% of patients. Benign vestibular diagnoses were found to be erroneous in 58% (n=21 of 36), including 17% (n=6 of 36) with missed ischemic stroke or TIA. The most common reason for misdiagnosis (70%) was an evolution of the clinical course over time.9 This is an inte- gral part of emergency medicine; initially ambiguous symptoms or signs evolve during the time. There has never been (and probably will never be) a direct confrontation between emergency doctors and neurologists who diagnose patients with vertigo in the same phase of treatment, and sometimes the diagnosis of dizziness is complicated, also for physicians with specialized training. Vertigo as posterior circulation stroke The incidence of cerebrovascular disease in patients presenting with vertigo in ED ranges from 3 to 5%.4 This disorder is some- times associated with a failure to diagnose stroke5 that could increase the mortality.20 In particular, previous studies showed that approximately 10% of patients with cerebellar stroke may present, at least initially, symptoms that can mimic vestibular neuritis.4,21 Casani et al.22 reported that about 3% of patients with vertigo had a missed cerebellar stroke. Both younger age and vertebral dissec- tion are risk factors for missed cerebellar stroke. In particular, strokes of the posterior circulation is related to minor deficits and to a NIHSS of zero and therefore is undiagnosed.11,13,15 Unfortunately, the diagnosis of basilar artery occlusion is often delayed, because clinical symptoms may be misinterpreted23,24 and not well quantify neurological deficits after acute posterior circu- lation stroke.13-15,25-27 This may result in a missed or a delayed thrombolytic treatment.11,13,25 In an emergency room of a university hospital and a community, 103 out of 465 patients with ischemic stroke were misdiagnosed. Of these, 33% revealed a stroke in the posterior circulation and 16% a stroke in the anterior circulation.2 Concerning a difficult diagnosis of the posterior circulation stroke, in addition to the sensitivity of the lower NIHSS score,13 also the sensitivity of CT is about 7-16% in the first 24 hours and the sen- sitivity of magnetic resonance imaging (MRI) is about 10-20% during the first 24-48 hours after the onset of the disorder.29-32 Diagnosis of vertigo by neuroimaging Patients with a suspected diagnosis of transient ischemic attacks or vertebrobasilar strokes should undergo neuroimaging testing. Magnetic resonance angiography (MRA) may be used to identify occlusions and stenosis in neck and in large intracranial vessels.33 Nakagawa et al.,34 evaluating patients with vertebrobasi- lar insufficiency and patients with non-sick controls and patients with other peripheral labyrinth diseases, documented that patients with vertebrobasilar insufficiency have focal atherosclerosis that occlude the lumen of the basilar artery (mainly when near the exit of the anterior inferior cerebellar artery, AICA) and the origin of the vertebral artery. Moubayed and Saliba35 reported that 85.7% of patients with dizziness and at least 3 risk factors for stroke have morphological abnormalities in the vertebral arteries. Kim et al.36 performed MRA in 935 patients reported that the prevalence of stenosis gradually increased based on the severity of the disease and the results were statistically significant (P<0.0001 for each comparison performed). The authors also consider the proximal region of the vertebral arteries as the place with a greater preva- lence of occlusion of the posterior circulation compared with those of the distal vertebral/basilar artery. Concerning the posterior cir- culation, studies on healthy patients indicate that angio-tomogra- phy and arteriography have a similar sensitivity and specificity to evaluate the basilar artery.37 With regard to vertebro-basilar circu- lation, other studies on healthy subjects have reported the sensitiv- ity of MRA and transcranial Doppler to 93.9%, 100%, respective- ly, while the specificity rate was 94.8% and 95.2%.38,39 Diagnosis of vertigo using transcranial Doppler TCD or TCCD is an inexpensive, painless and non-invasive test that can measure the speed and direction of blood flow from large intracranial arteries.40-43 The use of TCD or TCCD has several advantages: it can be performed at the bedside and repeated if nec- essary or applied for continuous monitoring; its use also is less expensive. In an acute setting, with an experienced clinician, it can help distinguish an ischemic stroke from a hemorrhagic stroke. Neurosonological investigations can also indicate underlying stroke mechanisms (a diagnosis of macroangiopathic, cardioem- bolic stroke, in artery dissection; or raise suspicion on indirect signs of vascular malformations) and also used in cerebral hemo- dynamic monitoring. TCD or TCCD can be a screening test before angiographic studies. TCD also allows real-time evaluation of average flow velocity, pulsatility and microembolization, informa- tion that is not available with angiography. The limitations of TCD, such as dependence on indirect parameters to identify blood ves- sels, poor spatial resolution, failure to display anatomical land- marks, inaccurate blood velocity metrics and incorrect classifica- tion of specific blood vessels in the presence of normal anatomical variants are exceeded with the use of TCCD.44 Previous clinical studies have reported the usefulness of TCCD in highlighting the stenosis of large cerebral vessels in the presence of an acute ischemic stroke.41,45-49 Unconstrained TCD has been reported to have a sensitivity of 55-81% and a specificity of 96% compared to digital subtraction angiography in patients with basilar or vertebral artery occlusion, while the use of TCCD has both a sensitivity and specificity of 100% related to a stenosis of vertebral or basic arter- ies.43 Most of the data on ischemia in the posterior circulation derive from the posterior circulatory register of New England Medical Center50 consisting of a consecutive series of 407 patients Review Non -co mmerc ial us e o nly with signs and symptoms of ischemia with posterior circulation observed during a 10-year period. Embolism was the most com- mon stroke mechanism (40% of patients included 24% of cardiac origin, 14% intra-arterial, 2% cardiac and arterial). The infarcts included the distal posterior territory of the circulation (rostral brainstem, upper cerebellum and occipital and temporal lobes); the proximal (medulla and inferior part of the cerebellum) and middle (bridge and inferior anterior cerebellum) territories were equally involved. Serious occlusive lesions (>50% stenosis) involved more than one large artery in 148 patients; 134 had an arterial site involved unilaterally or bilaterally. The most common occlusive sites were: intracranial vertebral artery (40 patients, 12 bilateral), basilar artery (46 patients) and 6 patients had proximal vertebral arterial dissection. Intra-arterial embolism was the most common mechanism of cerebral infarction in patients with occlusive disease of the vertebral arteries. Thirty-day mortality was 3.6%. Embolic mechanism, position of the distal territory and occlusive disease of the basilar artery have reported the worst prognosis. The use of ultrasound (TCD or TCCD) in the acute phase in the acute pathol- ogy of the posterior circulation is considerable diagnostic help due to the inherent characteristics of the vertebral-basilar circle by transtemporal and transforaminal windows. In the acute phase the sonological characteristics of steno-occlusion of the vertebro-basi- lar are easy to diagnose, while the sonological characteristics of occlusion of distal vessels such as the inferior cerebellar artery or the AICA are not always easily detected, because are terminal branches (Figure 1). Recently, Microvascularization (MicroV) is an emerging Power Doppler technology that directly assesses the degree of stenosis not only through velocitometric study but also through morphological study.42,51 Regarding the diagnosis of cere- bral hemorrhage, several TCCD studies have shown that the detec- tion of a homogeneously hyperechoic area, clearly delimited by the surrounding brain tissue, may be representative of acute intracere- bral hemorrhage.52 The TCCD can identify complications of stroke such as a hemorrhagic transformation, ventricular bleeding and to monitor the midline shift,44 avoiding repeating serial neuroradio- logical investigations. In patients with space-occupying infarcts, since the midline shift displacement may predict a fatal outcome in patients with malignant cerebral infarcts44 and differentiate between an intracerebral hemorrhage and an ischemic stroke with a sensitivity of 95% and a specificity of 94%.53,54 Therefore, if a CT scan is not readily available, as a first approach to the patient the TCCD can help also in identifying patients with primary cerebral hemorrhage or secondary bleeding complications. The TCCD, not only assesses the hemorrhagic complications of stroke, but can assess the collateral circulation for acute ischemic stroke and in acute middle cerebral artery territory stroke may aim to determine the perfusion of cerebral microvascularization, estimate infarct size and ischemic penumbra with implications for thrombectomy.55 Furthermore, in patients with vertebral-artery occlusion-basilar, the use of TCCD, when complete recanalization was not obtained after treatment with recombinant intravenous tissue (r-tPA; alteplase), could reduce the time for a thrombectomy, anticipating and avoiding a neuroradiological investigation. Limitations of the transcranial Doppler Insufficient acoustic window is the major factor that may hin- der the use of TCCD in the adults. This factor is more common in the elderly, in women and in non-Caucasian races. It represents 10- 20% of the inconclusive tests before the introduction of ultrasound contrast agents that amplify the echo. The use of contrast agents has reduced the abandonment rate to less than 7%.56 The other lim- itation is that TCCD is operator-dependent. This can be mitigated by adequate staff training to improve dexterity and allow diagnosis and safe interventions based on TCD or TCCD. Conclusions Although cerebrovascular ultrasonography can provide useful information in patients with vertebrobasilar insufficiency, we rec- ognize the unquestionable importance of clinical examination as the first step in vertigo management. Although neurosonology studies on acute vestibular syndrome are scarce,56 the transcranial Doppler ultrasonography examination is a useful diagnostic test in patients with suspected vertigo, particularly in an elderly popula- tion with a significant burden of cerebrovascular risk factors. There appears to be sufficient evidence for the inclusion of TCD/TCCD in a standard stroke imaging protocol, especially in resource-poor settings. Its ability to provide complementary infor- mation on cerebral architecture and stroke vasculature serves as a real alternative to CT/MRI for critically ill patients, although low sensitivity57,58 presented limits its value as a screening tool, in par- ticular following the limitation in the evaluation of the disease of small vessels. This technology competes fairly well with more developed CT/MRI technologies. Therefore, as no patient with a suspected stroke would be denied a form of neuroimaging, the use of transcranial Doppler should also be added. The clinical out- come, particularly in posterior circulation stroke, is mainly related to a rapid diagnosis and subsequent treatment that will be able to quickly restore the blood flow in the posterior circulation. 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