Donata Guidetti

The Eligible study: ultrasound assessment in acute ischemic stroke within 3 hours.

Background: Aims of the study: to identify with echo color Doppler ultrasound of the supra-aortic vessels and transcranial color-coded duplex sonography (TCCD) various patterns of vessel occlusion within 3 h from stroke onset, to compare each group defined at the admission with clinical findings and outcome, and to study the recanalization process, independent of therapy. Methods: We enrolled 89 consecutive patients (mean age 68.9 years). Ultrasound evaluation was done within 3 h from stroke onset, and was repeated at 3–6 and 24–36 h, at day 5, and at 3 months. At admission, patients were divided into the following groups: internal carotid artery occlusions and stenoses (<50%, 50–69%, ≧70%, near occlusion), middle cerebral artery stenoses and occlusions, tandem occlusions and T occlusions. Vascular recanalization in each group was evaluated. Subgroups were compared for NIH Stroke Scale (NIHSS) and the outcome measures mortality, Barthel index (BI) and modified Rankin scale (mRS). Favorable outcome was defined as mRS ≤2 and BI ≧90. Results: Each subgroup differed significantly for baseline NIHSS (p < 0.0001), 3-month mortality (p = 0.0235), BI at day 5 (p = 0.0458) and mRS at 3 months (p = 0.0028), even after adjustment for treatment. T and tandem occlusions were the subgroups with the highest NIHSS scores and the poorest outcomes, and the same subgroups had the worst recanalization rates. Conclusions: TCCD in the acute setting of stroke patients allows identification of the presence and site of clots, prediction of outcome and study of the dynamic process of vessel recanalization, in both the acute phase and follow-up.

Migraine and Stroke: “Vascular” Comorbidity

Several comorbidities are associated to migraine. Recent meta-analyses have consistently demonstrated a relationship between migraine and stroke, which is well-defined for ischemic stroke and migraine with aura (MA), even stronger in females on oral contraceptives or smokers. However, there seems to be no clear-cut association between stroke in migraineurs and the common vascular risk factors, at least in the young adult population. Migraineurs also run an increased risk of hemorrhagic stroke, while the association between migraine and cardiovascular disease remains poorly defined. Another aspect is the relationship between migraine and the presence of silent brain lesions. It has been demonstrated that there is an increased frequency of ischemic lesions in the white matter of migraineurs, especially silent infarcts in the posterior circulation territory in patients with at least 10 attacks per month. Although there is a higher prevalence of patent foramen ovale (PFO) in migraineurs, the relationship between migraine and PFO remains controversial and PFO closure is not a recommended procedure to prevent migraine. As an increased frequency of cervical artery dissections has been observed in migrainous patients, it has been hypothesized that migraine may represent a predisposing factor for cervical artery dissection. There still remains the question as to whether migraine should be considered a true “vascular disease” or if the comorbidity between migraine and cerebrovascular disease may have underlying shared risk factors or pathophysiological mechanisms. Although further studies are required to clarify this issue, current evidence supports a clinical management where MA patients should be screened for other concomitant vascular risk factors and treated accordingly.

Ulnar entrapment neuropathy in patients with type 2 diabetes mellitus: an electrodiagnostic study.

AIMS This study aimed to assess the prevalence and electrophysiological features of ulnar entrapment neuropathy in patients with type 2 diabetes mellitus (DM). METHODS Nerve conduction studies (NCS) were performed in a sample of consecutive diabetic patients aged 25-75 years, referred by the Diabetology Unit. NCS of the median, ulnar, radial, peroneal and sural nerves were performed on the non-dominant side. Median entrapment neuropathy at the wrist (MNW) and ulnar neuropathy at the elbow (UNE) and wrist (UNW) were diagnosed according to standard electrodiagnostic criteria. RESULTS Sixty-four patients were enrolled, 28 male (44%), average age 61, average DM duration 14.5 years. Polyneuropathy was diagnosed in 45 subjects (70%). UNE was detected in 22 patients (34%) (4 did not have polyneuropathy), in the abductor digiti minimi in 16, the first interosseus in 14 and in both in 8. UNW was detected in 7 (11%) subjects and MNW in 40 (63%). NCS alterations consistent with ulnar neuropathy were detected in a high proportion of patients (45%), suggesting that the ulnar nerve is very susceptible to focal entrapment in DM. CONCLUSIONS Upper limb sensory and motor NCS, including motor conduction velocity across the elbow, should be considered in the staging of DM patients.

Lemierre syndrome: More than “the forgotten disease”

A 54-year-old woman presented with fever, spasmodic torticollis, ptosis, and chemosis in her left eye. CT venous angiography revealed cavernous sinus thrombosis (CST) and left internal jugular vein thrombosis (IJVT) (figure, A), cervical MRI detected a retropharyngeal abscess and epidural empyema (figure, B and C), and chest X-ray showed multiple pulmonary opacities (figure, D). The clinical/radiologic picture, due to anaerobic septicemia, was consistent with Lemierre syndrome (LS), the so-called “forgotten disease.”1 Extensive neuroimaging studies are mandatory to detect an abscess in the neck of patients with CST and IJVT for early diagnosis and treatment. LS is still relevant today.

Impact on Prehospital Delay of a Stroke Preparedness Campaign: A SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial)

Background and Purpose— Public campaigns to increase stroke preparedness have been tested in different contexts, showing contradictory results. We evaluated the effectiveness of a stroke campaign, designed specifically for the Italian population in reducing prehospital delay. Methods— According to an SW-RCT (Stepped-Wedge Cluster Randomized Controlled Trial) design, the campaign was launched in 4 provinces in the northern part of the region Emilia Romagna at 3-month intervals in randomized sequence. The units of analysis were the patients admitted to hospital, with stroke and transient ischemic attack, over a time period of 15 months, beginning 3 months before the intervention was launched in the first province to allow for baseline data collection. The proportion of early arrivals (within 2 hours of symptom onset) was the primary outcome. Thrombolysis rate and some behavioral end points were the secondary outcomes. Data were analyzed using a fixed-effect model, adjusting for cluster and time trends. Results— We enrolled 1622 patients, 912 exposed and 710 nonexposed to the campaign. The proportion of early access was nonsignificantly lower in exposed patients (354 [38.8%] versus 315 [44.4%]; adjusted odds ratio, 0.81; 95% confidence interval, 0.60–1.08; P=0.15). As for secondary end points, an increase was found for stroke recognition, which approximated but did not reach statistical significance (P=0.07). Conclusions— Our campaign was not effective in reducing prehospital delay. Even if some limitations of the intervention, mainly in terms of duration, are taken into account, our study demonstrates that new communication strategies should be tested before large-scale implementation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01881152.

Mechanical thrombectomy after intravenous thrombolysis for acute ischaemic stroke

We read with interest Serge Bracard and colleagues’ report of THRACE, a multicentre randomised controlled trial comparing the clinical outcomes of intravenous thrombolysis plus mechanical thrombectomy with intravenous thrombolysis alone in 414 patients with acute ischaemic stroke and proximal cerebral artery occlusion. The strengths of THRACE were centralised randomisation, use of a standard dose of alteplase, minimum losses to follow-up, and an intention-to-treat analysis. However, outcome assessors were not masked to treatment assignment, and this is an important potential source of bias. Stent retriever systems, which have been shown to be better than older generation devices, were used for mechanical thrombectomy in 116 (82%) of 141 patients. Angiography and mechanical thrombectomy were cancelled in patients whose National Institutes of Health Stroke Scale score improved by 4 or more points after intravenous thrombolysis. However, the short delay between thrombolysis and randomisation meant that patients were randomly assigned before the effect of thrombolysis was known, and thus, in many cases, thrombectomy had to be cancelled. This process contributed to 59 (29%) of 204 patients assigned to the intervention group not actually receiving thrombectomy, which could have diluted the treatment eff ect. THRACE is the ninth large randomised controlled trial to compare functional outcomes of endovascular thrombectomy with standard medical care. However, what sets THRACE apart is that, beyond demonstration of proximal arterial occlusion on CT or magnetic resonance angiography, imaging criteria were not used to select patients. In this sense, THRACE represents a more pragmatic type of trial, and its results are perhaps more widely generalisable. However, the lack of imaging-based selection criteria, together with crossover of nearly a third of patients in the thrombectomy group to standard medical care and the long time from randomisation to groin puncture, might account for the smaller treatment effect than in other trials. Overall, this is a very welcome addition to the literature.

Metoclopramide-induced facial and palatopharyngeal myoclonus

A 61-year-old woman developed acute dyslalia, dysphonia, dysphagia, and facial rhythmic jerks 8 hours after the intake of 2 tablets of metoclopramide 10 mg, prescribed for nausea during respiratory infection. Examination revealed dysphonia, dyslalia, dysphagia, and myoclonus in the orbicularis oculi (video 1 on the Neurology® Web site at Neurology.org), orbicularis oris, and palatopharyngeal (video 2); no clicking was audible. Brain MRI, angio-MRI, and EEG were unremarkable. Biperidene 4 mg was given per os: palatopharyngeal myoclonus, dysphonia, and dyslalia improved in 30 minutes and disappeared in 12 hours. Palatal myoclonus may be a rare metoclopramide-induced movement disorder.1,2

Carotid ultrasound imaging in a patient with acute ischemic stroke and aortic dissection: a lesson for the management of ischemic stroke?

Dear editor, aortic dissection presenting as an acute ischemic stroke represents an important challenge to neurologists, especially in pain-free dissection (5– 15% of the cases) (1). In this context, thrombolysis is a life-threatening approach for acute ischemic stroke patients. A 60-year-old smoker female, history of hypertension, no other vascular risk factor, was admitted to emergency department (ED) for sudden left hemiparesis (National Institute of Health Stroke Scale, NIHSS 9) appeared 90 mins before, with a normal brain computed tomography (CT). The patient was fully oriented, without pain or any other complaints. Her blood pressure (BP) was 130/70 mmHg, chest X-ray, electrocardiogram (EKG), and cardiac evaluation were normal. Blood tests were also normal. Therefore, the patient was considered eligible for intravenous recombinant tissue plasminogen activator (rt-PA), which was started 125 mins after the onset of the stroke. The patient’s neurological picture improved within 40 mins (NIHSS 3). Four-hours later, her skin became pale and sweaty. Physical examination detected asymmetry of peripheral pulses at the upper extremities, BP dropped to 80/60 in right arm and 110/60 on the left side without any worsening of the neurologic picture or other associated symptoms. An urgent carotid duplex ultrasonography was requested. Extracranial sonography on the longitudinal and axial plane in the right common carotid artery revealed double lumen with moving membrane, attributable to dissection (supporting information Movies S1 and S2). Different flow velocities on pulsed wave analysis were detected within the true and the false lumen with a to-and-fro spectral profile in the latter. The CT angiography of the aorta documented DeBakey type I aortic dissection, which extended to the common iliac arteries and involved the right common carotid artery. An emergency surgical replacement of the ascending aorta was therefore performed 12 h after the onset of the first symptoms. She was discharged 42 days later with left facial and mild upper limb paresis (NIHSS 2). At 12 months, the patient is still independent in her daily life activities. Aortic dissection presenting as an ischemic stroke represents an important challenge to emergency departments. Neurological symptoms at the onset of aortic dissection are not only frequent (17–40%), but often dramatic and may mask underlying conditions (1). This is particularly true in the presence of pain-free dissections with predominant neurological symptoms, where diagnosis of aortic dissection can be difficult, delayed, or missed. In case of aortic dissection, massive use of antiplatelet or anticoagulant drugs is contraindicated (2). Considering that early intravenous thrombolytic therapy in acute ischemic stroke is becoming a common practice in the neurological field, misdiagnosis could be fatal in the case of aortic dissection (1,3). However, current guidelines do not state specifically whether aortic dissection is a contraindication to rt-PA administration (2). The most common mechanism of brain ischemic damage is mechanical obstruction of the common carotid artery due to the dissection. Complete occlusion might be resistant to rt-PA, which is not effective for mechanical occlusion. Therefore, rt-PA for ischemic stroke secondary to aortic dissection might be efficacious only in a minority of patients with thromboembolic mechanism. Moreover, there are reports of suspected myocardial infarction inadvertently treated with thrombolysis, complicated by extension of the dissection into the pericardium, leading to cardiac tamponade and death (3). rt-PA must be administrated within a very brief time window; therefore, it is crucial that major contraindications to this therapy must be detected in a very short time. Whereas rt-PA therapy has been successfully reported in patients with isolated internal carotid artery dissection, the risk of thrombolytic therapy seems to be much higher when dissection occurs in the aorta (4). Because aortic dissection is a very rare cause of ischemic stroke (1), the acute screening for this entity has to be questioned. A timely chest X-ray should be considered as part of acute ischemic patients’ protocols, with special attention to the presence of enlarged mediastinal shadow. Moreover, the presence of hypotension, reduced peripheral pulses, aortic regurgitation murmurs should be always searched before rt-PA therapy. A common or internal carotid artery dissection has been associated in more than 40% of aortic dissection (5). These vessels can be easily investigated by sonography, which should be regarded as a helpful, complementary tool for the current diagnostic workup. The sonographic findings might influence the short-term management of a suspected aortic dissection in any patient entering the emergency department. Correspondence: Nicola Morelli*, Guglielmo da Saliceto Hospital, Neurology Unit and Radiology Unit, Via Taverna 49, Piacenza 29100, Italy. E-mail: n.morelli@inwind.it

CT and MR myelography in superficial siderosis

Dear Editor, A 54-year-old woman presented with subacute spastic and ataxic paraparesis. Sensorineural hearing loss had required a cochlear implant 5 years previously. Laboratory tests for coagulation, liver/kidney functions, and blood ion concentration were all unremarkable. MRI detected a leptomeningeal hemosiderin deposit in the neuraxis (Fig. 1a–d). A spinal epidural fluid collection and dural defect at the T2-T4 level were identified onMR-myelography (MR-m) and ultrafast dynamic CT myelography (ud-CTM) (Fig. 1 e–i). Therefore, superficial siderosis, due to a spinal dural tear, was diagnosed, and subsequent surgical repair was performed, with small sutures and a muscle graft. Superficial siderosis (SS) of the central nervous system (CNS) is due to hemosiderin deposition in the subpial layers of the brain and spinal cord [1], and it is a consequence of recurrent and persistent bleeding into the subarachnoid space. The source of the bleeding often remains undetected, despite extensive neuroimaging. Tumors such as ependymoma, meningioma, oligodendroglioma, pineocytoma, and paraganglioma have been reported in 35% of cases, while vascular abnormalities such as arteriovenous malformations or aneurysms were present in 18% of cases. A previous history of trauma or intradural surgery is a possible finding. Extraarachnoid longitudinally extensive intrathecal fluid-filled collection has frequently been noted in SS patients. The brain’s ability to biosynthesize ferritin and hemosiderin, a defensive mechanism in response to a prolonged hemoglobin iron overload, is an important etiopathogenetic factor in SS. The gliosis and neuronal loss associated with ferritin and hemosiderin deposition may result in an increased signal intensity in the adjacent nervous tissue. Indeed, hemosiderin formation occurs mainly within the microglia, as it can synthesize ferritin so that hemosiderin is taken up selectively by CNS areas rich in microglia and/or by those close to the cerebrospinal fluid (CSF) flow [2]. Notably, the 8th cranial nerve may be considered vulnerable as it is not only particularly rich in microglia, but also, before entering the internal acoustic canal, it travels a relatively long distance outside the brain and is exposed to the damaging effects of a chronic subarachnoid hemorrhage within the CNS. The classical clinical presentation of SS includes adult onset of slowly progressive gait ataxia with cerebellar dysarthria and sensorineural hearing impairment. CT myelography (CTM) may identify a dural defect connecting the intrathecal space to the fluid-filled collection. In CTM, the introduction of iodinated contrast medium (ICM) into the thecal sac allows for specific visualization of the CSF, including the one that has leaked into the epidural space [3]. In cases of high-flow CSF leaks, the contrast agent may spill so quickly from the thecal sac that by the time the images are acquired, myelographic ICM may have spread widely into the epidural space, making a precise localization of the bleeding source almost impossible. However, the ud-CTM, a technique previously described by Thielen and Luetmer [4], provides a sufficient temporal and spatial resolution to overcome this shortcoming and can also detect high-flow leaks. These leaks form a Bfork^ or Bsplitlike^ shape in the column of the flowing myelographic ICM, where the extra-arachnoid ICM continues to flow downwards in a cranial direction. MR-m can also be used to evaluate CSF leaks. A leak on an MR-m is evidenced by a hyperintense fluid collection (T2w) in the epidural space. Heavily T2weighted imaging (steady-state sequences) has been explored to obtain images with a greater contrast between the CSF and background tissues [5]. Compared with CTM, MR-m has the * Nicola Morelli nicola.morelli.md@gmail.com

Musical murmurs on internal carotid artery: sonological herald of vessel dissection?

Musical murmurs (MMs), also known as ‘‘seagull cry’’, are murmurs with a single frequency which sounds like a musical tone. Doppler detections usually show mirrorimage parallel strings, or bands of low/moderate frequency. MMs have been hypothesized to stem from regular vibrations of a cardiac structure with/without turbulent flow, from a vortex shedding due to blood flowing past an obstruction and also from oscillating structures and pressure fluctuations in intracranial cerebral arteries [1–3]. MMs have been mostly described in cardiac murmurs, but rarely in cerebrovascular disease or peripheral arteries [4–6]. Herein, we report a case of a young man with spontaneous internal carotid artery dissection (SCAD), where MMs were detected at transcranial color-coded sonography (TCCS). To the best of our knowledge, this is the first case in the literature to report MMs in SCAD. A 47-year-old man, without vascular risk factors, was admitted for light left frontoparietal headache and ipsilateral palpebral ptosis, of 15-day duration; he had neither recent trauma nor known connective tissue disorders. Neurological examination showed left Horner syndrome without other neurological deficits. Cervical ultrasonography revealed color flow signal in the left internal carotid artery (ICA) and pulsed wave Doppler analysis detected a to-and-fro signal (short systolic peak and a small retrograde flow component). TCCS showed flow inversion in the precommunicating tract of the left anterior cerebral artery (ACA), indicating right intracranial carotid territory supplied by the anterior communicating artery. Furthermore, a loud ‘‘seagull cry’’ was audible during Doppler spectral detection of the left intracranial carotid bifurcation. Spectral analysis displayed mirror-image parallel strings of low to moderate frequency (Fig. 1). Sixty-minute recording by the multigate system on transcranial Doppler detected 34 micro-embolic signals (MES) in the left middle cerebral artery. Cranial MRI and cervical MR angiography documented the left ICA near occlusion in the prepetrous tract, with subacute intramural hematoma, indicating artery dissection and no parenchymal lesions. Low molecular weight heparin (Enoxaparin 100 UI/kg bid) and acetylsalicylic acid (100 mg daily) were administered and carotid recanalisation was documented at duplex scan and cervical MR angiography examinations, 2 months later. Headache and Horner syndrome improved progressively and no pseudoaneurysm was present at the 6-month cervical MR angiography. No MES were detected during anticoagulation treatment. The seagull cry (MMs), an outstanding acoustic phenomenon in duplex ultrasound, may have a purer tone at a site distal to the source than when closer to the source. They might be detected with, or without simultaneous turbulent flows, or very close to a high-intensity frequency (with systolic spindles) turbulent flow. Only a minority of MMs are detected in the extracranial cervical arteries [6], with respect to the intracranial vessels, due to the anatomical features of the cervical arteries (the larger lumen diameters and intima-media thickness, the presence of a soft tissue surrounding the vessel, along with the higher arterial blood flow), which usually cause randomized rather than harmonic vibrations of the vascular walls [6]. MMs N. Morelli (&) E. Rota P. Immovilli D. Guidetti Neurology Unit, Guglielmo da Saliceto Hospital, Via Taverna 49, 29100 Piacenza, Italy e-mail: n.morelli@inwind.it