The Diagnosis of Vertebrobasilar Insufficiency Using Transcranial Doppler Ultrasound

Background. Vertebrobasilar insufficiency (VBI) is a hemodynamic posterior circulation transient ischemic attack (TIA) caused by intermittent vertebral artery occlusion that is induced by a head rotation or extension. VBI may result from large vessel atherosclerotic disease, dissection, cervical compressive lesions, and subclavian steal phenomenon. Diagnostic transcranial Doppler (TCD) of VBI disease and hemodynamic posterior circulation TCD monitoring in symptomatic positions might prove a useful tool in establishing the diagnosis. Patient and Material/Method. A 50-year-old Caucasian man presented with a one-year history of episodic positional vertigo and ataxic gait that were induced by a neck extension and resolved by an upright position or a neck flexion. Computed tomography angiogram (CTA) and TCD confirmed the presence of VBI where no blood flow was detected through posterior cerebral arteries in the symptomatic position (head extension position). Conclusion. TCD is a promising noninvasive technique that might have a role as a diagnostic test in VBI

Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke

Background: Results of our recently published phase III randomized clinical trial of ultrasound-enhanced thrombolysis (sonothrombolysis) using an operator-independent, high frequency ultrasound device revealed heterogeneity of patient recruitment among centers. Methods: We performed a post hoc analysis after excluding subjects that were recruited at centers reporting a decline in the balance of randomization between sonothrombolysis and concurrent endovascular trials. Results: From a total of 676 participants randomized in the CLOTBUST-ER trial we identified 52 patients from 7 centers with perceived equipoise shift in favor of endovascular treatment. Post hoc sensitivity analysis in the intention-to-treat population adjusted for age, National Institutes of Health Scale score at baseline, time from stroke onset to tPA bolus and baseline serum glucose showed a significant (p < 0.01) interaction of perceived endovascular equipoise shift on the association between sonothrombolysis and 3 month functional outcome [adjusted common odds ratio (cOR) in centers with perceived endovascular equipoise shift: 0.22, 95% CI 0.06–0.75; p = 0.02; adjusted cOR for centers without endovascular equipoise shift: 1.20, 95% CI 0.89–1.62; p = 0.24)]. After excluding centers with perceived endovascular equipoise shift, patients randomized to sonothrombolysis had higher odds of 3 month functional independence (mRS scores 0–2) compared with patients treated with tPA only (adjusted OR: 1.53; 95% CI 1.01–2.31; p = 0.04). Conclusion: Our experience in CLOTBUST-ER indicates that increasing implementation of endovascular therapies across major academic stroke centers raises significant challenges for clinical trials aiming to test noninterventional or adjuvant reperfusion strategies

Safety and efficacy of sonothrombolysis for acute ischaemic stroke: a multicentre, double-blind, phase 3, randomised controlled trial

Background: Pulsed-wave ultrasound increases the exposure of an intracranial thrombus to alteplase (recombinant tissue plasminogen activator), potentially facilitating early reperfusion. We aimed to ascertain if a novel operator-independent transcranial ultrasound device delivering low-power high-frequency ultrasound could improve functional outcome in patients treated with alteplase after acute ischaemic stroke. Methods: We did a multicentre, double-blind, phase 3, randomised controlled trial (CLOTBUST-ER) at 76 medical centres in 14 countries. We included patients with acute ischaemic stroke (National Institutes of Health Stroke Scale score ≥10) who received intravenous thrombolysis (alteplase bolus) within 3 h of symptom onset in North America and within 4·5 h of symptom onset in all other countries. Participants were randomly allocated (1:1) via an interactive web response system to either active ultrasound (2 MHz pulsed-wave ultrasound for 120 min [sonothrombolysis]; intervention group) or sham ultrasound (control group). Ultrasound was delivered using an operator-independent device, which had to be activated within 30 min of the alteplase bolus. Participants, investigators, and those assessing outcomes were unaware of group assignments. The primary outcome was improvement in the modified Rankin Scale score at 90 days in patients enrolled within 3 h of symptom onset, assessed in the intention-to-treat population as a common odds ratio (cOR) using ordinal logistic regression shift analysis. This trial is registered with ClinicalTrials.gov, number NCT01098981. The trial was stopped early by the funder after the second interim analysis because of futility. Findings: Between August, 2013, and April, 2015, 335 patients were randomly allocated to the intervention group and 341 patients to the control group. Compared with the control group, the adjusted cOR for an improvement in modified Rankin Scale score at 90 days in the intervention group was 1·05 (95% CI 0·77–1·45; p=0·74). 51 (16%) of 317 patients in the intervention group and 44 (13%) of 329 patients in the control group died (unadjusted OR 1·24, 95% CI 0·80–1·92; p=0·37) and 83 (26%) and 79 (24%), respectively, had serious adverse events (1·12, 0·79–1·60; p=0·53). Interpretation: Sonothrombolysis delivered by an operator-independent device to patients treated with alteplase after acute ischaemic stroke was feasible and most likely safe, but no clinical benefit was seen at 90 days. Sonothrombolysis could be further investigated either in randomised trials undertaken in stroke centres that are dependent on patient transfer for endovascular reperfusion therapies or in countries where these treatments cannot yet be offered as the standard of care

Isolated intermittent vertigo: A presenting feature of persistent trigeminal artery

Embryonic carotid – basilar anastomosis when persistent in adult life can present with a variety of neurological symptoms. We present a patient with isolated intermittent vertigo attributable to the embryonic anastomosis and describe the different types of persistent trigeminal artery. A 76-year-old Caucasian man presented with isolated intermittent vertigo and symptoms suggestive of anterior and posterior circulation strokes. Impaired vasomotor reactivity was demonstrated on insonation of the anterior and posterior cerebral arteries in this patient with a persistent left trigeminal artery and 75% stenosis of the left internal carotid artery (ICA). The symptom of intermittent vertigo resolved with carotid endarterectomy. Decreased flow across the stenotic segment of the ICA which subserved the posterior circulation resulted in basilar insufficiency. Hypoperfusion to the flocculonodular lobe supplied by the anterior inferior cerebellar artery is a likely cause for the intermittent vertigo

Extrapontine Myelinolysis-Induced Parkinsonism in a Patient with Adrenal Crisis

Background. Extrapontine myelinolysis (EPM) has been well described in the presence of rapid correction of hyponatremia. It is seldom reported with adrenal insufficiency. We report a unique case where a patient developed EPM as a result of adrenal insufficiency where the brain MRI revealed symmetrical lesion in the basal ganglia with pallidal sparing. Case Report. A 30-year-old gentleman with panhypopituitarism developed adrenal crisis, hyponatremia, and hyponatremic encephalopathy. Seven days after the rapid correction of hyponatremia, he developed parkinsonism and neuropsychiatric symptoms. MRI showed extrapontine myelinolysis without central pontine myelinolysis. Conclusion. Extrapontine myelinolysis without central pontine myelinolysis is rare and should raise a concern of associated adrenal insufficiency in the right clinical setting. Rapid correction of hyponatremia particularly in steroid-deficient states should be avoided as it can predispose to extrapontine myelinolysis. Magnetic resonance imaging is very helpful in supporting the diagnosis of EPM

A new primary health-care system in the Syrian opposition territories: Good effort but far from being perfect

Objectives: The primary health-care system in Syria has suffered a great deal of damage over the past 6 years. A large number of physicians and health-care providers have left the country. The objectives of this study are to describe our experience in establishing a primary health-care system in the opposition territories (OTs) in Syria and report the most common treated diseases. Methods: The administrative databases of ten primary care centers in the OT from January 2014 to December 2015 were reviewed. All patients' encounters, including children and adults, in these centers were included in the study. Results: Within the study period, the ten centers served 46,039 patients encounter per month (and average of 4600 patients encounters per center per month). A high number of communicable diseases were noted. Cutaneous leishmaniasis was the most common communicable disease (1170 cases a month). Tuberculosis was treated in 14 patients a month. Other infectious diseases that were almost eradicated before the crises were seen increasingly (29 mumps cases/month, 6 measles cases/month, and 34 cases of typhoid fever/month). Conclusion: The primary health-care system in Syria has been greatly damaged, and tremendous efforts are ongoing to provide access to various basic health-care services including primary care services. Despite these efforts, the current system is very vulnerable and not sustainable. This study summarizes basic health services provided by primary health-care centers in Syrian OTs

Association of pretreatment blood pressure with tissue plasminogen activator-induced arterial recanalization in acute ischemic stroke

Background and Purpose - Elevated systolic blood pressure (SBP) and lack of early vessel recanalization are predictors of poor outcome among patients with stroke treated with systemic tissue plasminogen activator (tPA). We aimed to evaluate the potential relationship between pretreatment SBP and tPA-induced recanalization. Methods - Consecutive patients with acute ischemic stroke resulting from intracranial artery occlusion were treated with standard intravenous tPA and assessed with 2-MHz transcranial Doppler for arterial recanalization. Early arterial recanalization was determined with previously validated Thrombolysis in Brain Ischemia flow grading system at 120 minutes after tPA bolus. Functional outcome at 3 months was evaluated using the modified Rankin Scale. Results - A total of 351 patients received intravenous tPA ( mean age: 68.7 +/- 13.4 years, median National Institutes of Health Stroke Scale score 16.5). Patients with complete recanalization (n = 94) had lower mean pretreatment SBP values ( 152 +/- 23 mm Hg) than patients with incomplete or absent recanalization ( n = 257, 160 +/- 22 mm Hg, P = 0.010). Pretreatment SBP levels were inversely associated with complete recanalization ( OR per 10-mm Hg increase: 0.85; 95% CI: 0.74 to 0.98, P = 0.022) after adjustment for demographics, risk factors, stroke severity, pretreatment Thrombolysis in Brain Ischemia grades, and continuous versus intermittent exposure to transcranial Doppler. Although patients with poor functional 3-month outcomes ( modified Rankin Scale > 2) had higher pretreatment SBP values ( 160 +/- 25 mm Hg) than functionally independent patients ( 154 +/- 20 mm Hg, P = 0.027), pretreatment SBP levels were not independently associated with functional outcome on multivariable analysis. Age, complete recanalization, baseline National Institutes of Health Stroke Scale score, and time from symptom onset to tPA bolus were independent ( P < 0.05) predictors of 3-month outcome. Conclusion - Higher pretreatment SBP levels are associated with poor recanalization in patients with acute stroke treated with intravenous tPA

Association of pretreatment ASPECTS scores with tPA-Induced arterial recanalization in acute middle cerebral artery occlusion

BACKGROUND AND PURPOSE The Alberta Stroke Program Early CT-Score (ASPECTS) assesses early ischemic changes within the middle cerebral artery (MCA) and predicts poor outcome and increased risk for thrombolysis-related symptomatic ICH. We evaluated the potential relationship between pretreatment ASPECTS and tPA-induced recanalization in patients with MCA occlusions. SUBJECTS & METHODS Consecutive patients with acute ischemic stroke due to MCA occlusion were treated with standard IV-tPA and assessed with transcranial Doppler (TCD) for arterial recanalization. Early recanalization was determined with previously validated Thrombolysis in Brain Ischemia (TIBI) flow-grading system at 120 minutes after tPA-bolus. All pretreatment CT-scans were prospectively scored by trained investigators blinded to TCD findings. Functional outcome at 3 months was evaluated using the modified Rankin Scale (mRS). RESULTS IV-tPA was administered in 192 patients (mean age 68 +/- 14 years, median NIHSS-score 17). Patients with complete recanalization (n= 51) had higher median pretreatment ASPECTS (10, interquartile range 2) than patients with incomplete or absent recanalization (n = 141; median ASPECTS 9, interquartile range 3, P = .034 Mann-Whitney U-test). An ASPECTS <= 6 was documented in 4% and 17% of patients with present and absent recanalization, respectively (P = .019). Pretreatment ASPECTS was associated with complete recanalization (OR per 1-point increase: 1.54; 95% CI 1.06-2.22, P = .023) after adjustment for baseline characteristics, risk factors, NIHSS-score, pretreatment TIBI grades and site of arterial occlusion on baseline TCD. Complete recanalization (OR: 33.97, 95% CI 5.95-185.99, P < .001) and higher ASPECTS (OR per 1-point increase: 1.91; 95% CI 1.17-3.14, P = .010) were independent predictors of good functional outcome (mRS 0-2). CONCLUSIONS Higher pretreatment ASPECT-scores are associated with a greater chance of complete recanalization and favorable long-term outcome in tPA-treated patients with acute MCA occlusion