Deena M. Nasr

Neurologic Complications of Extracorporeal Membrane Oxygenation

Background and Purpose The rate and outcomes of neurologic complications of patients receiving extracorporeal membrane oxygenation (ECMO) are poorly understood. The purpose of this study was to identify these parameters in ECMO patients. Methods All patients receiving ECMO were selected from the Nationwide Inpatient Sample between 2001-2011. The rate and outcomes of neurologic complications [acute ischemic stroke, intracranial hemorrhage (ICH), and seizures] among these patients was determined. Discharge status, mortality, length of stay, and hospitalization costs were compared between patients with and without neurologic complications using chi-squared tests for categorical variables and Students t-test for continuous variables. Results In total, 23,951 patients were included in this study, of which 2,604 (10.9%) suffered neurologic complications of seizure (4.1%), stroke (4.1%), or ICH (3.6%). When compared to patients without neurologic complications, acute ischemic stroke patients had significantly higher rates of discharge to a long-term facility (12.2% vs. 6.8%, p<0.0001) and a significantly longer mean length of stay (41.6 days vs. 31.9 days, p<0.0001). ICH patients had significantly higher rates of discharge to a long-term facility (9.5% vs. 6.8%, p=0.007), significantly higher mortality rates (59.7% vs. 50.0%, p<0.0001), and a significantly longer mean length of stay (41.8 days vs. 31.9 days) compared to patients without neurologic complications. These outcomes did not differ significantly between seizure patients and patients without neurologic complications. Conclusions Given the increasing utilization of ECMO and the high costs and poor outcomes associated with neurologic complications, more research is needed to help determine the best way to prevent these sequelae in this patient population.

Utilization of intravenous thrombolysis is increasing in the United States

Background Evaluating recombinant tissue plasminogen activator utilization rates is important, as many studies have demonstrated that administration of recombinant tissue plasminogen activator to qualified patients significantly improves prognosis. Aims We investigated recent trends in the utilization and outcomes of administration of intravenous recombinant tissue plasminogen activator in the United States using the National Inpatient Sample between 2001 and 2008. Methods We identified patients with a primary diagnosis of acute ischemic stroke who underwent treatment with intravenous recombinant tissue plasminogen activator and studied utilization rates and clinical outcomes: discharge to long-term facility (morbidity), in-hospital death (mortality), and intracranial hemorrhage. Information on demographics, hospital characteristics, and comorbidities was collected. A multivariate logistic regression analysis was performed to determine independent predictors of morbidity, mortality, and intracranial hemorrhage. Results Intravenous recombinant tissue plasminogen activator utilization increased from 1·3% in 2001 to 3·5% in 2008. On multivariate analysis, variables associated with increased morbidity after intravenous recombinant tissue plasminogen activator administration included advanced age (P < 0·001), female gender (P < 0·001), and comorbidities of atrial fibrillation (P < 0·001) and hypertension (P < 0·001). Increased mortality was associated with increased age (P < 0·001) and comorbidities of atrial fibrillation, congestive heart failure, coronary artery disease, and diabetes (P < 0·001 for all comorbidities). Conclusions Intravenous recombinant tissue plasminogen activator utilization rates increased between 2001 and 2008. Advanced age and atrial fibrillation were significantly associated with increased morbidity and mortality among patients treated with intravenous recombinant tissue plasminogen activator.

Racial and Ethnic Disparities in the Use of Intravenous Recombinant Tissue Plasminogen Activator and Outcomes for Acute Ischemic Stroke

Racial and ethnic disparities in acute stroke care in the United States have been previously reported. This study investigated possible racial and ethnic disparities in the administration and outcome of recombinant tissue plasminogen activator (rtPA) therapy for acute ischemic stroke in whites, blacks, Hispanics, and Asian/Pacific Islanders. Using the National Inpatient Sample for 2001-2008, we selected patients with a primary diagnosis of acute ischemic stroke who received treatment with rtPA. Patient data were stratified by race (white, black, Hispanic, and Asian/Pacific Islander). We analyzed the association of patient race on rtPA utilization rate, in-hospital morbidity (ie, discharge to long-term facility), intracranial hemorrhage (ICH) rate, and in-hospital mortality. We performed a multivariate logistic regression analysis to determine independent predictors of poor outcomes. White patients had a higher rate of tPA utilization than black and Hispanic patients (2.3% vs 1.8% and 2.0%, respectively; P < .0001 for both groups). There was no difference in the rate of tPA utilization between whites and Asian/Pacific Islanders (2.3% vs 2.2% P = .07). Multivariate analysis of morbidity, mortality, and ICH rates found that Asian/Pacific Islanders had significantly higher rates of mortality (odds ratio, 1.22, 95% confidence interval, 1.03-1.44; P = .02) and ICH (odds ratio, 2.01; 95% confidence interval, 1.91-2.11; P < .0001) compared with whites. rtPA utilization was greater in white and Asian/Pacific Islander patients than in black and Hispanic patients. Asian/Pacific Islander race was associated with increased risk of ICH and mortality after rtPA administration.

Clinical Outcomes of Patients with Delayed Diagnosis of Spinal Dural Arteriovenous Fistulas

BACKGROUND AND PURPOSE: Spinal dural arteriovenous fistulas are commonly missed on imaging or misdiagnosed as inflammatory or neoplastic processes. We reviewed a consecutive series of spinal dural arteriovenous fistulas referred to our institution that were missed or misdiagnosed on initial imaging and studied the clinical consequences of missing or misdiagnosing the lesion. MATERIALS AND METHODS: We reviewed spinal dural arteriovenous fistulas diagnosed at our institution between January 1, 2000, and November 1, 2014. A lesion was defined as “misdiagnosed” if initial MR imaging or CT myelography demonstrated characteristic imaging features of spinal dural arteriovenous fistula but the patient was clinically or radiologically misdiagnosed. Outcomes included length of delay of diagnosis, increased disability (increase in mRS or Aminoff motor disability of ≥1 point) between initial imaging evaluation and diagnosis date, and posttreatment disability. RESULTS: Fifty-three consecutive spinal dural arteriovenous fistulas that were initially misdiagnosed despite having characteristic imaging findings on MR imaging or CT myelography were included in our study. Eight patients (18.9%) underwent spinal angiography before referral, which was interpreted as having negative findings but was either incomplete (6 cases) or retrospectively demonstrated the spinal dural arteriovenous fistulas (2 cases). The median time of delayed diagnosis was 6 months (interquartile range, 2–14 months). Fifty-one patients (96.2%) had increased disability between the initial study, which demonstrated features of a spinal dural arteriovenous fistula, and diagnosis. Thirty-two patients (60.4%) developed a new requirement for a walker or wheelchair. Following treatment, 21 patients (41.2%) had an improvement of 1 point on the mRS or Aminoff motor disability scale. CONCLUSIONS: Delayed diagnosis of spinal dural arteriovenous fistula with characteristic imaging features results in high rates of additional disability that are often irreversible despite surgical or endovascular treatment of the fistula.

Imaging Characteristics of Growing and Ruptured Vertebrobasilar Non-Saccular and Dolichoectatic Aneurysms

Background and Purpose— Vertebrobasilar, nonsaccular, and dolichoectatic aneurysms generally have a poor natural history. We performed a study examining the natural history of vertebrobasilar, nonsaccular, and dolichoectatic aneurysms receiving serial imaging and studied imaging characteristics associated with growth and rupture. Methods— We included all vertebrobasilar dolichoectatic, fusiform, and transitional aneurysms with serial imaging follow-up seen at our institution over a 15-year period. Two radiologists and a neurologist evaluated aneurysms for size, type, mural T1 signal, mural thrombus, daughter sac, mass effect, and tortuosity. Primary outcomes were aneurysm growth or rupture. Univariate analysis was performed with chi-squared tests for categorical variables and Student’s t test or analysis of variance for continuous variables. Multivariate logistic regression analysis was performed to identify variables independently associated with aneurysm growth or rupture. Results— One hundred and fifty-two patients with 542 patient-years (mean 3.6±3.5 years) of imaging follow-up were included. Aneurysms were fusiform in 45 cases (29.6%), dolichoectatic in 75 cases (49.3%), and transitional in 32 cases (21.1%). Thirty-five aneurysms (23.0%) grew (growth rate=6.5%/year). Eight aneurysms (5.3%) ruptured (rupture rate=1.5%/year). Variables associated with growth and rupture on univariate analysis were size >10 mm (57.6% versus 16.0%, P<0.0001), mural T1 signal (39.7% versus 16.3%, P=0.001), daughter sac (56.3% versus 21.3%), and mural thrombus (45.5% versus 13.4%, P<0.0001). 26.7% of fusiform aneurysms, 9.3% of dolichoectatic aneurysms, and 59.4% of transitional aneurysms grew or ruptured (P<0.0001). The only variable independently associated with rupture was transitional morphology (P=0.003). Conclusions— Vertebrobasilar, nonsaccular, and dolichoectatic aneurysms are associated with a poor natural history with high growth and rupture rates. Further research is needed to determine the best treatments for this disease.

Clinical outcomes following corticosteroid administration in patients with delayed diagnosis of spinal arteriovenous fistulas.

Background and purpose There have been several previously reported cases of acute progression of myelopathic symptoms in patients with spinal arteriovenous fistula (SAVF) treated with intravenous methylprednisolone. This usually occurs during or immediately following steroid administration. We examined a small case series of patients with SAVF treated with epidural, oral, or intravenous steroids to determine the association between steroid administration and clinical outcomes in these patients. Methods Following Institutional Review Board approval, we conducted a retrospective review of patients with angiographically-confirmed SAVF who received intravenous, oral, or epidural corticosteroids for treatment of their symptoms. We studied patient-reported motor and sensory function following steroid administration using both the modified Rankin Scale and the Aminoff Motor Disability Scale. Results Twenty-one patients with SAVF were included in this study. Thirteen patients (61.9%) had intravenous methylprednisolone administered, four patients (19.0%) had epidural steroid injections, and six patients (28.6%) had oral prednisone. Among patients who received intravenous methylprednisolone, seven (53.8%) reported acute worsening of symptoms during or immediately following steroid administration. Among the patients receiving epidural steroids, none reported worsening and one patient reported short-term relief. Among the patients receiving oral steroids, one reported acute worsening of symptoms. Worsened deficits did not consistently resolve after steroid discontinuation. Conclusions Our study suggests that intravenous methylprednisolone can cause immediate worsening of motor and sensory symptoms when administered to patients with SAVF. Steroid administration should be avoided in patients with a myelopathy secondary to an untreated SAVF because neurological worsening may not be fully reversible.

Spinal epidural arteriovenous fistulas

Spinal epidural arteriovenous fistulas (SEDAVFs) are rare complex lesions often presenting with protean clinical manifestations secondary to compressive symptoms or congestive myelopathy. The imaging manifestations of SEDAVFs on MR angiography/MRI include high T2 signal in the spinal cord, vascular engorgement of the epidural space, and prominent intradural vascular flow voids. Given the complexity of these lesions, they are best characterized anatomically on catheter angiography where careful inspection of arterial feeders and venous drainage patterns can be performed. The imaging hallmark of an SEDAVF on angiography is the presence of a dilated epidural venous pouch through which spinal and paraspinal veins are secondarily opacified. In the lower thoracic and lumbar spine, SEDAVFs are usually located in the ventral epidural space and fed mainly by the anteriorly coursing epidural arteries. In the cervical and upper thoracic spine, SEDAVFs and their feeding arteries are more typically located laterally in the spinal canal. Current treatment options include transarterial or transvenous endovascular embolization with liquid embolic agents or coils, and surgical resection/disconnection of the fistula. Further research is needed to better characterize how and why these lesions form and to identify the best treatment modalities.

Use and In-Hospital Outcomes of Recombinant Tissue Plasminogen Activator in Pediatric Arterial Ischemic Stroke Patients

BACKGROUND Outcomes in pediatric stroke are poorly understood. We sought to determine trends in the use of recombinant tissue plasminogen activator (rt-PA), treatment outcomes, and predictors of mortality for pediatric patients with acute ischemic stroke by using the Nationwide Inpatient Sample. METHODS Using Nationwide Inpatient Sample data from 2001 to 2010, we identified pediatric patients (age 30 days to 18 years) with the primary diagnosis of arterial ischemic stroke. We studied trends of use of intravenous rt-PA and outcomes after thrombolysis. We also analyzed the associations of demographic factors, comorbidities, and complications of arterial ischemic stroke with in-hospital mortality. RESULTS This study included 7044 patients. In-hospital mortality was 4.7%. The comorbidities associated with the greatest rates of in-hospital mortality were mitochondrial disorders (19.5%, P < 0.0001) and hypercoagulable states (11.4%, P < 0.0001). The main complications associated with increased mortality were intracerebral hemorrhage (19.9%, P < 0.0001), sepsis (13.2%, P < 0.0001), and pneumonia (9.3%, P = 0.0007). The rate of rt-PA use was 1.4% (99 patients). rt-PA use increased from 0.9% of patients in 2001-2005 to 2.0% in 2006-2010 (P < 0.0001). Among patients who received rt-PA, the rate of intracerebral hemorrhage was low and without fatalities; however, there was an increased discharge-to-long-term-facilities rate in the rt-PA group (50.8% versus 12.1%, P < 0.0001). CONCLUSION Arterial ischemic stroke in the pediatric population is associated with a greater rate of mortality when related to mitochondrial diseases or hypercoagulability. rt-PA use is increasing in pediatric patients with arterial ischemic stroke. Pediatric patients receiving rt-PA have a low risk of fatal hemorrhage. Although patients receiving rt-PA have a morbidity rate, these individuals may have a worse stroke severity.

Intracranial and Extracranial Neurovascular Manifestations of Takayasu Arteritis

BACKGROUND AND PURPOSE: Takayasu arteritis is a rare, large-vessel vasculitis that presents with symptoms related to end-organ ischemia. While the extracranial neurovascular manifestations of Takayasu arteritis are well-established, little is known regarding the intracranial manifestations. In this study, we characterize the intracranial and cervical neurovascular radiologic findings in patients with Takayasu arteritis. MATERIALS AND METHODS: Patients with Takayasu arteritis who presented to our institution between 2001 and 2016 with intracranial and/or cervical vascular imaging were included in this study. Images were evaluated for the presence of vascular abnormalities, including intracranial or extracranial stenosis, vessel-wall thickening, dissection, subclavian steal, aneurysms, infarcts, and hemorrhages. Descriptive analyses are reported. RESULTS: Seventy-nine patients with Takayasu arteritis met the criteria for inclusion in this study. The most common presenting neurologic symptoms were headache (32.9%) and dizziness (15.2%). Intracranial and extracranial vascular imaging was performed in 84.8% and 89.9% of patients, respectively. Among patients with intracranial vascular imaging, 3 (3.9%) had intracranial aneurysms, 3 (3.9%) had acute large-vessel occlusion, 6 (7.6%) had intracranial vasculitis, and 1 (1.3%) had reversible cerebrovascular constriction syndrome. Among patients with cervical vascular imaging, 42 (53.1%) had some degree of narrowing of the common carotid artery and 18 (22.8%) had narrowing of the ICAs. Seventeen patients (23.6%) had subclavian steal. CONCLUSIONS: Intracranial vascular abnormalities in patients with Takayasu arteritis presenting with neurologic symptoms are not rare, with cerebral vasculitis seen in 7.8% of patients, and stroke secondary to large-vessel occlusion, in 3.9% of patients. Cervical vascular manifestations of Takayasu arteritis were present in most patients in our study.

Clinical and Imaging Characteristics of Diffuse Intracranial Dolichoectasia

The authors retrospectively reviewed a consecutive series of patients with diffuse intracranial dolichoectasia and compared demographics, vascular risk factors, additional aneurysm prevalence, and clinical outcomes with a group of patients with vertebrobasilar dolichoectasia. Twenty-five patients had diffuse intracranial dolichoectasia, and 139 had vertebrobasilar dolichoectasia. Patients with diffuse intracranial dolichoectasia were older than those with vertebrobasilar dolichoectasia and had a higher prevalence of abdominal aortic aneurysms, other visceral aneurysms, and smoking history. Patients with diffuse intracranial dolichoectasia were more likely to have aneurysm growth. They conclude that the natural history of patients with diffuse intracranial dolichoectasia is significantly worse than that in those with isolated vertebrobasilar dolichoectasia. BACKGROUND AND PURPOSE: Among patients with vertebrobasilar dolichoectasia is a subset of patients with disease affecting the anterior circulation as well. We hypothesized that multivessel intracranial dolichoectasia may represent a distinct phenotype from single-territory vertebrobasilar dolichoectasia. The purpose of this study was to characterize clinical characteristics and angiographic features of this proposed distinct phenotype termed “diffuse intracranial dolichoectasia” and compare them with those in patients with isolated vertebrobasilar dolichoectasia. MATERIALS AND METHODS: We retrospectively reviewed a consecutive series of patients with diffuse intracranial dolichoectasia and compared their demographics, vascular risk factors, additional aneurysm prevalence, and clinical outcomes with a group of patients with vertebrobasilar dolichoectasia. “Diffuse intracranial dolichoectasia” was defined as aneurysmal dilation of entire vascular segments involving ≥2 intracranial vascular beds. Categoric and continuous variables were compared by using χ2 and Student t tests, respectively. RESULTS: Twenty-five patients had diffuse intracranial dolichoectasia, and 139 had vertebrobasilar dolichoectasia. Patients with diffuse intracranial dolichoectasia were older than those with vertebrobasilar dolichoectasia (70.9 ± 14.2 years versus 60.4 ± 12.5 years, P = .0002) and had a higher prevalence of abdominal aortic aneurysms (62.5% versus 14.3%, P = .01), other visceral aneurysms (25.0% versus 0%, P < .0001), and smoking (68.0% versus 15.9%, P < .0001). Patients with diffuse intracranial dolichoectasia were more likely to have aneurysm growth (46.2% versus 21.5%, P = .09) and rupture (20% versus 3.5%, P = .007) at follow-up. Patients with diffuse intracranial dolichoectasia were less likely to have good neurologic function at follow-up (24.0% versus 57.6%, P = .004) and were more likely to have aneurysm-related death (24.0% versus 7.2%, P = .02). CONCLUSIONS: The natural history of patients with diffuse intracranial dolichoectasia is significantly worse than that in those with isolated vertebrobasilar dolichoectasia. Many patients with diffuse intracranial dolichoectasia had additional saccular and abdominal aortic aneurysms. These findings suggest that diffuse intracranial dolichoectasia may be a distinct vascular phenotype secondary to a systemic arteriopathy affecting multiple vascular beds.