The use of andexanet alfa vs. 4-factor prothrombin complex concentrates in the setting of life-threatening intracranial hemorrhage.

OBJECTIVE: Andexanet alfa is a targeted reversal agent for life threatening hemorrhage associated with direct acting oral anticoagulants (DOACs), but there is uncertainty regarding the benefit when compared to 4-factor prothrombin complex concentrate (4F-PCC) for this indication. We investigated the clinical outcomes and cost associated with reversal of DOACs in the setting of life-threatening intracranial hemorrhage (ICH). METHODS: A retrospective evaluation was conducted to evaluate patients with ICH in the setting of anticoagulation with DOAC from 9/1/2013 to 4/30/2020. Patients were included in the study if they received reversal with either andexanet alfa or 4F-PCC. RESULTS: Eighty-nine patients were included in the study. There was no statistically significant difference in 30-day mortality between patients who received andexanet alfa or 4F-PCC (52% vs. 35%, P  = 0.14). Radiographic stability of bleed was identified in 57% of patients receiving andexanet alfa vs. 58% of patients receiving 4F-PCC ( P  = 0.93). Median length of stay was not different between the andexanet alfa and 4F-PCC populations (7 days [IQR 6 - 12] vs. 6 days [IQR 3-12], P  = 0.66). Median cost of reversal agent was higher in patients receiving andexanet alfa compared to 4F-PCC ($15 000 [IQR 15 000-$27 000] vs. $11 650 [IQR $8567-$14 149]). CONCLUSION: Among patients with life-threatening intracranial hemorrhage in the setting of DOAC therapy, no clinical differences were observed with respect to selection of reversal agent. Prothrombin complex concentrates remain a viable alternative to reversal of DOAC therapy though multicenter, randomized, prospective studies are needed to further evaluate the role of 4F-PCC in the reversal of DOAC therapy.

Thoracoscopic Left Atrial Appendage Exclusion for Atrial Fibrillation Patients Intolerant to Anticoagulation.

OBJECTIVE: Outcomes associated with isolated epicardial left atrial appendage (LAA) exclusion in atrial fibrillation (AF) patients with a contraindication or intolerance to anticoagulation are not clearly defined, especially in patients with prior stroke. This study evaluated the perioperative safety, medication use, and stroke outcomes for isolated thoracoscopic LAA exclusion for stroke prevention. METHODS: A single-center retrospective study was performed of adults undergoing isolated thoracoscopic LAA exclusion with an epicardial exclusion device without a concomitant surgical procedure. Descriptive statistics were performed. RESULTS: Twenty-five patients met the inclusion criteria. The cohort was 68% male (n = 17) with a mean age of 76.4 ± 6.5 years, a mean preoperative CHA2DS2-VASc score of 4.2 ± 1.4, and a mean preoperative HAS-BLED score of 2.68 ± 1.03. Seventeen patients (68%) had nonparoxysmal AF. There were 11 patients with intolerance of anticoagulation due to intracranial hemorrhage (44%), 6 due to gastrointestinal bleeding (24%), and 4 due to genitourinary bleeding (16%). All procedures were performed thoracoscopically with 100% technical success-the mean LAA stump length was 5.5 ± 2.3 mm on intraoperative transesophageal echocardiography. The median hospital length of stay was 2 (interquartile range [IQR] 1, 6.5) days. The median follow-up time was 430 (IQR 125, 972) days. During follow-up, 1 patient with cerebral angiopathy had temporary neurologic deficits at an outside institution, with brain imaging showing no evidence of ischemic injury. There were no other thromboembolic events over the 38.8 postoperative patient-years examined. All patients were off anticoagulation at last follow-up. CONCLUSIONS: This study shows the perioperative safety, technical success, freedom from anticoagulation, and stroke outcomes of isolated thoracoscopic LAA exclusion in patients with AF at high risk for thromboembolic disease.

Benefits of an interdisciplinary stroke clinic: addressing a gap in physical therapy at post-stroke neurology follow-up.

BACKGROUND AND PURPOSE: An interdisciplinary stroke clinic (ISC) can improve communication and identify people post-stroke who have not reached their full recovery potential. We describe the characteristics of participants who underwent physical therapy (PT) evaluation in addition to their outpatient neurology evaluation and identify the association of assessment scales that predicted referral for additional rehabilitation. METHODS: Participants' post-stroke seen in the ISC were included in the study. The PT evaluation included the Berg Balance Scale (BBS), Ten-Meter Walk Test (10MWT), Six-Minute Walk Test (6MWT), and Short Form-Stroke Impact Scale (SF-SIS). Multivariable logistic regression analysis was performed to identify factors associated with referral for additional rehabilitation. RESULTS: The study consisted of 148 participants with a mean age of 63 (SD ± 15) years; 58% were women and 76% were Whites. Additional rehabilitation was recommended for 59% of participants. In multivariate analysis, reduced speed on comfortable 10MWT (OR = 0.06; 95%CI = 0.01-0.51) and lower SF-SIS score (OR = 0.76; 95%CI = 0.66-0.87) were significantly associated with referral for additional PT or occupational therapy. CONCLUSION: A significant number of post-acute stroke survivors were found to be appropriate for additional rehabilitation when assessed clinically by a neurologic physical therapist in an ISC. The measures that most closely correlated with this in-person clinical evaluation were 10MWT and SF-SIS.IMPLICATIONS FOR REHABILITATIONAn interdisciplinary stroke clinic can improve communication and identify people post-stroke who have not reached their full recovery potential.In a pilot study, a significant number of post-acute stroke survivors were found to be appropriate for additional rehabilitation when assessed clinically by a neurologic physical therapist in an interdisciplinary stroke clinic.Reduced speed on comfortable Ten-Meter Walk Test and lower Short Form-Stroke Impact Scale scores were associated with referral for additional rehabilitation.

Trends of Acute Ischemic Stroke Reperfusion Therapies from 2012 to 2016 in the United States.

BACKGROUND: American Heart Association/American Stroke Association guidelines recommend endovascular stroke therapy (EST) with recombinant tissue plasminogen activator (rt-PA) for eligible patients in acute ischemic stroke (AIS). Using the National Inpatient Sample database, we evaluated trends in treatment with rt-PA and EST for AIS and their outcomes. METHODS: This is a cross-sectional observational study of patients with AIS admitted in US hospitals from 2012 to 2016. Patients were grouped into those who received rt-PA alone, EST alone, and rtPA+EST. Survey statistical procedures were performed. Multivariable regression analysis with pairwise comparisons of each treatment group with no treatment group was performed for discharge outcomes. RESULTS: The study included 2,290,520 patients with AIS with the mean age of 70.46 years. Treatment rates increased from 2012 to 2016 for rt-PA by 7% per year (5.86%-7.67%, odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.05-1.08) and EST by 38% per year (0.55%-1.75%, OR = 1.38, 95% CI: 1.31-1.45) but not rt-PA+EST (0.54%-0.57%, OR = 1.04, 95% CI: 0.99-1.08). The mean length of stay reduced from 2012 to 2016 for rt-PA (6.07-4.91 days, P < 0.0001) and rt-PA+EST (9.19-7.10 days, P = 0.0067) but not for EST (9.61-8.51 days, P = 0.5074). The odds of patients discharged home increased by 8%, 9%, and 15% among patients who received rt-PA alone, EST alone, and rt-PA+EST, respectively, compared with no treatment group. CONCLUSION: The utilization of rt-PA alone and EST alone increased but that of rt-PA+EST remained unchanged from 2012 to 2016 in the National Inpatient Sample.

Bilateral Cerebral Hyperperfusion Syndrome Following Carotid Artery Stenting in Stroke - A Case Report.

BACKGROUND: Revascularization of the symptomatic carotid artery is performed with endarterectomy or stenting. Rarely, patients may develop cerebral hyperperfusion syndrome (CHS) following revascularization. This usually occurs in the cerebral hemisphere ipsilateral to revascularized carotid stenosis. CHS rarely involves the contralateral hemisphere. OBJECTIVE: To present a case of CHS involving bilateral cerebral hemispheres following carotid artery stenting in acute ischemic stroke. CASE DESCRIPTION: A 66-year-old woman presented with right side weakness and aphasia. National Institutes of Health stroke scale score was 27. CT angiogram/perfusion showed high grade left internal carotid artery (ICA) stenosis, left middle cerebral artery (MCA) occlusion, and increased time to peak in left MCA territory. She underwent mechanical thrombectomy with complete reperfusion. Left carotid artery stenting was performed for 85% cervical ICA stenosis with thrombus. She neurologically deteriorated and required intubation after the procedure. Follow-up CT perfusion at 18 hours after thrombectomy showed increased cerebral blood flow and early time to peak in bilateral MCA territories. CT head showed parenchymal hematoma in the left subcortical area with extension to the ventricle. Fluid-attenuated inversion recovery MRI on day 4 showed diffuse white matter hyperintensities in the entire right hemisphere, and left temporal and frontal lobes suggestive of vasogenic edema. CONCLUSION: This case highlights bilateral cerebral hyperperfusion syndrome characterized by neurological worsening, imaging findings of parenchymal hemorrhage, vasogenic edema and increased cerebral blood flow without any new ischemic lesions. The involvement of bilateral hemispheres in the absence of significant contralateral carotid stenosis is unique in this case.

Thoracoscopic Ablation With Appendage Ligation Versus Medical Therapy for Stroke Prevention: A Proof-of-Concept Randomized Trial.

OBJECTIVE: Atrial fibrillation (AF) has a demonstrable effect on quality of life (QOL). Recurrent stroke occurs in 10% of patients with AF. The objective of this study was to demonstrate proof of concept that thoracoscopic pulmonary vein isolation and atrial appendage ligation (TPVIAL) could prevent recurrent stroke and could potentially improve QOL in patients with AF with a previous stroke. METHODS: The study was a National Institutes of Health-funded single-center proof-of-concept design that randomized 23 patients with AF-related stroke to TPVIAL (n = 12) or to medical management (n = 11). Quality of life was the primary outcome variable; secondary end points included restoration of rhythm, recurrent stroke, and surgical morbidity. RESULTS: Quality-of-life subscores at 3 and 6 months revealed improvements in energy and decreases in fatigue in the TPVIAL arm [baseline, 33 (19.8); 3 months, 49.5 (20.6), P = 0.01; 6 months, 55.5 (14.4), P = 0.03]. At 12-month follow-up, there were no recurrent strokes in the TPVIAL group. In the medically treated arm, two patients at 6 months (P = 0.22) and three total patients at 12 months (P = 0.09) had recurrent ischemic stroke. There was one death in the medical management arm. In the TPVIAL arm, no AF recurrence occurred in patients with paroxysmal AF, and one patient had recurrence of persistent and long-standing AF. Seven patients in the TPVIAL arm discontinued warfarin therapy for secondary stroke prevention. CONCLUSIONS: This small proof-of-concept study showed that TPVIAL improved QOL on two subscores and restored normal sinus rhythm in all but one patient, and it showed the potential to prevent secondary stroke. A larger study will be needed.

Recurrence of Lobar Hemorrhage: A Red Flag for Cerebral Amyloid Angiopathy-related Inflammation?

Background. Recurrent lobar intracerebral hemorrhage is more commonly associated with cerebral amyloid angiopathy and less likely associated with hypertension. Cerebral amyloid angiopathy-related inflammation is a subgroup of cerebral amyloid angiopathy that can present with lobar intracerebral hemorrhage, encephalopathy, and seizures; wherein corticosteroids may facilitate favorable outcome. Whether recurrence of lobar intracerebral hemorrhage in cerebral amyloid angiopathy is related to cerebral amyloid angiopathy-related inflammation is unknown. Case presentation. A 68-year-old woman presented with an acute onset of confusion. She was known to have a history of recurrent lobar intracerebral hemorrhage related to cerebral amyloid angiopathy. Brain imaging revealed previous sequelae of cerebral amyloid angiopathy and a new lobar intracerebral hemorrhage. An empirical diagnosis of cerebral amyloid angiopathy-related inflammation was made given the patent's clinical course of recurrence. Utilizing current evidence of criteria used to diagnose cerebral amyloid angiopathy-related inflammation, corticosteroid therapy was initiated with significant improvement in clinical and imaging characteristics. Discussion. Inflammatory pathways incited as a result of cerebrovascular amyloid deposition play a vital role in pathogenesis of cerebral amyloid angiopathy-related inflammation. We highlight the need to consider corticosteroid therapy in patients presenting with recurrent lobar intracerebral hemorrhage in the setting of cerebral amyloid angiopathy since inflammation may play a role in its pathophysiology. Evidence in the literature is sparse to suggest that cerebral amyloid angiopathy-related inflammation might be the root cause for the lobar intracerebral hemorrhage recurrence in cerebral amyloid angiopathy. Further studies are needed to identify mechanisms of recurrent hemorrhage, its correlations with cerebral amyloid angiopathy-related inflammation, and the potential role of corticosteroid therapy.

Isolated middle cerebral artery dissection: a systematic review.

Acute stroke can be missed in the emergency department, particularly in younger patients and in those with more vague symptoms such as headache or dizziness. Cervicocephalic dissections are one group of etiologies for acute stroke in the young. While cervicocephalic dissections are not uncommon in clinical practice, isolated middle cerebral artery dissection (MCAD) has been rarely reported as a cause for stroke. We sought to review the clinical implications and pathophysiology of an isolated MCAD. We searched the medical literature for isolated MCAD in clinical stroke patients using MEDLINE, HighWire, and Google Scholar databases from 1966 to 2013 using the keywords 'middle cerebral artery dissection,' 'intracerebral artery dissection,' and 'middle cerebral artery dissection stroke.' We reviewed cases to learn various characteristics of isolated MCAD. A total of 61 cases (62.3% male, mean age 44.16 ± 19.17 years) were reviewed from 54 publications. Most cases were reported from Asian countries (78.7%). Ischemic strokes were more common than hemorrhagic strokes (68.9%). Digital subtraction angiography was the most common imaging modality used to diagnose isolated MCAD (75.4%). Surgery was the preferred form of therapeutic intervention (39.3%). Males (n = 27/48, p = 0.0008) and those who presented with only ischemic syndromes (n = 22/48, p = 0.0009) had significantly higher rates of favorable outcome. Isolated MCAD is a rare disease that can contribute to the stroke burden of young patients. Further studies are needed to better characterize optimal treatment strategies and define outcomes for this rare condition.

Praxis and writing in a right-hander with crossed aphasia.

Studies of patients with brain lesions have demonstrated that language and praxis are mediated by dissociable networks. However, language has the capacity to influence the selection of purposeful actions. The abilities to use language and to program purposeful movements are often mediated by networks that have anatomic proximity. With hemispheric injury, the diagnosis of apraxia is often confounded by the specific influence of language impairments on the ability to select and produce transitive gestures. We report a patient who illustrates this confound. This patient is a right-handed man who developed global aphasia and neglect after a right hemispheric stroke. His right hand remained deft, and when asked to produce specific transitive gestures (pantomimes), he often performed normally but did make some body part as object and perseverative errors. However, he did not demonstrate the temporal or spatial errors typical of ideomotor apraxia. He also had a perseverative agraphia. Our patient's left hemisphere praxis system appeared to be intact, and the error types demonstrated during production of transitive gestures cannot be attributed to a degradation of postural and movement (praxis) programs mediated by his left hemisphere. The praxis errors types are most consistent with a deficit in the ability to select the necessary praxis programs. Thus, our patient appeared to have dissociation between language and praxis programs that resulted in body part as object and perseverative errors.

Flow failure from intracranial atherosclerotic disease: a rationale for endovascular intervention in a population with recurrent symptoms despite maximal medical therapy.

The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial, the first randomized trial to compare best medical therapies with angioplasty and stenting, was halted prematurely owing to a 30-day stroke rate of 14.7% in the angioplasty and stenting arm compared with 5.8% in the medical management arm. These results have led to a paradigm shift away from interventional therapies and back to dual antiplatelet therapy and aggressive medical therapies only for these patients. However, there appears to be a subset of patients with intracranial atherosclerotic disease (ICAD) who are different from the general SAMMPRIS cohort and are defined by flow failure from severe intracranial arterial stenosis resulting in recurrent ischemic symptoms despite maximal medical therapy. Offering the option of endovascular revascularization seems appropriate in this patient population, given their recurrent ischemic events regardless of aggressive medical therapies. This paper provides a rationale for reconsidering the role of interventional therapies in patients with critical intracranial stenosis and presents four patients with flow failure from ICAD and persistent symptoms of ischemia, regardless of dual antiplatelet and adjuvant medical therapies, who subsequently improved with angioplasty. Consideration of alternative patient populations and treatment paradigms seems to carry particular relevance now as the endovascular treatment of intracranial atheromatous disease is currently receiving intense scrutiny by those medical specialties involved in the care of stroke patients, as well as the public at large.