Physician Approaches to Antithrombotic Therapies for Recently Symptomatic Carotid Stenosis.

BACKGROUND: Whereas the beneficial effect of antiplatelet therapy for recurrent stroke prevention has been well established, uncertainties remain regarding the optimal antithrombotic regimen for recently symptomatic carotid stenosis. We sought to explore the approaches of stroke physicians to antithrombotic management of patients with symptomatic carotid stenosis. METHODS: We employed a qualitative descriptive methodology to explore the decision-making approaches and opinions of physicians regarding antithrombotic regimens for symptomatic carotid stenosis. We conducted semi-structured interviews with a purposive sample of 22 stroke physicians (11 neurologists, 3 geriatricians, 5 interventional-neuroradiologists, and 3 neurosurgeons) from 16 centers on four continents to discuss symptomatic carotid stenosis management. We then conducted thematic analysis on the transcripts. RESULTS: Important themes revealed from our analysis included limitations of existing clinical trial evidence, competing surgeon versus neurologist/internist preferences, and the choice of antiplatelet therapy while awaiting revascularization. There was a greater concern for adverse events while using multiple antiplatelet agents (e.g., dual-antiplatelet therapy (DAPT)) in patients undergoing carotid endarterectomy compared to carotid artery stenting. Regional variations included more frequent use of single antiplatelet agents among European participants. Areas of uncertainty included antithrombotic management if already on an antiplatelet agent, implications of nonstenotic features of carotid disease, the role of newer antiplatelet agents or anticoagulants, platelet aggregation testing, and timing of DAPT. CONCLUSION: Our qualitative findings can help physicians critically examine the rationale underlying their own antithrombotic approaches to symptomatic carotid stenosis. Future clinical trials may wish to accommodate identified variations in practice patterns and areas of uncertainty to better inform clinical practice.

Venous spot sign: Indicator of rapid hematoma expansion in venous thrombosis type of submission: Case reports.

BACKGROUND: The term "spot sign" was coined by Wada et al in 2007 and thought to be due to ongoing arterial bleeding in primary intraparenchymal haemorrhage (IPH).1 Spot sign has also been described in the context of intraventricular haemorrhage (IVH).2 Over the years arterial spot signs have been found to correlate with intraparenchymal hematoma expansion, worse clinical outcomes and increased risk of surgical intervention.3 We are describing a unique instance of a spot sign in venous sinus thrombosis that initially misled the clinical diagnosis. CASE PRESENTATION: An 83-year-old woman on dual antiplatelet therapy, with a history of minor stroke, presented with sudden right-sided weakness and dysarthria. Serial CT brain imaging revealed rapidly enlarging intraparenchymal haemorrhage (IPH). Contrast enhanced CT displayed multiple spot signs typically associated with arterial bleeding pattern. Initially possibility of antithrombotic related IPH was kept, however venogram confirmed venous pathology with focal superior sagittal sinus thrombosis (SSS). Unfortunately, the patient deteriorated and eventually succumbed to the illness before the diagnosis could be made. CONCLUSION: The case exemplifies the potential of venous sinus thrombosis to manifest as a spot sign, thereby emphasizing the need for a broader differential diagnosis. The rarity of venous spot signs may be attributed to patient-specific venous anatomy and poor collateralization in the occluded sinus territory.

Intraluminal Thrombi in the Cervico-Cephalic Arteries.

Background and Purpose- Intraluminal thrombus (ILT) is an uncommon finding among patients with ischemic stroke. We report clinical-imaging manifestations, treatment offered, and outcome among patients with ischemic stroke/transient ischemic attack and ILT in their cervico-cephalic arteries. Methods- Sixty-one of 3750 consecutive patients with acute ischemic stroke/transient ischemic attack (within 24 hours of onset) and ILT on initial arch-to-vertex computed tomography angiography from April 2015 through September 2017 constituted the prospective study cohort. Functional outcome was assessed using the modified Rankin Scale score with functional independence at discharge defined as modified Rankin Scale score ≤2. Results- Prevalence of ILT on computed tomography angiography was 1.6% (95% CI, 1.2%-2.1%). Median age was 67 years (interquartile range, 56-73), and 40 subjects (65%) were male. The initial clinical presentation included transient ischemic attack in 12 (20%) and stroke in 49 patients (80%); most strokes (76%) were mild (National Institutes of Health Stroke Scale ≤5). The most common ILT location was cervical carotid or vertebral artery (n=48 [79%]) followed by intracranial (n=11 [18%]) and tandem lesions (n=2 [3%]). The most common initial treatment strategy was combination antithrombotics (heparin with single antiplatelet agent) among 57 patients (93%). Follow-up computed tomography angiography (n=59), after a median 6 days (interquartile range 4-10 days), revealed thrombus resolution in 44 patients (75% [completely in 27%]). Twenty four of 30 patients (80%) with >50% residual carotid stenosis underwent carotid revascularization (endarterectomy in 15 and stenting in 9 patients) without peri-procedural complications a median of 9 days after symptom onset. In-hospital stroke recurrence occurred in 4 patients (6.6%). Functional independence was achieved in 46 patients (75%) at discharge. Conclusions- Patients presenting with acute stroke/transient ischemic attack with ILT on baseline imaging have a favorable clinical course in hospital with low stroke recurrence, high rate of thrombus resolution, and good functional outcome when treated with combination antithrombotic therapy.

Headache in cerebral venous sinus thrombosis revisited: Exploring the role of vascular congestion and cortical vein thrombosis.

Background and purpose Headache constitutes the most common symptom of cerebral venous sinus thrombosis (CVST), but its pathophysiology is unclear. We sought to investigate the potential mechanism for headache genesis in patients with CVST based on its imaging correlates. Methods A subgroup of CVST patients having headache as the predominant symptom without significant parenchymal lesion were retrospectively analysed for imaging features of vascular congestion (VC), in addition to cortical venous (CVT) and dural sinus thrombosis (DST) on magnetic resonance imaging. Headache and imaging patterns were classified into lateralized and nonlateralized phenotypes and their correlation was sought. Results Among 41 patients included, 28 had lateralized headache (LH group; 15 males; mean age 32.25 ± 9.19 years) while 13 had nonlateralized headache (non-LH group; six males; mean age 27.15 ± 8.65 years). Headache characteristics in both the groups were quite similar. Imaging showed VC in 39 of 41 and CVT among 35 of 41 patients, which were lateralized in 23 of 39 and 18 of 35 patients, respectively. Nearly all lateralized imaging patterns (21 of 23 for VC and 17 of 18 for CVT) occurred in the LH group and ipsilateral to (concordant) headache, while the non-LH group showed lateralized VC and CVT in only two and one patient respectively. Sinus thrombosis was lateralized in both groups irrespective of headache laterality. Whole cohort headache-imaging laterality (including patients with nonlateralized headache and nonlateralized imaging) concordance was 31 of 39, 24 of 35 and 18 of 41 for vascular congestion, cortical vein thrombosis and dural sinus thrombosis respectively. Conclusion Co-localization of VC and CVT with overlying headache might provide a possible explanation of headache and its laterality in patients with CVST.

Natural history of a cohort of Duchenne muscular dystrophy children seen between 1998 and 2014: An observational study from South India.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy. There are no large studies describing its natural course from India. MATERIALS AND METHODS: Immunohistochemically/genetically confirmed DMD patients diagnosed between 1998 and 2014 were ambispectively included. The main aim was to study the natural course of motor milestones, i.e., age at onset of wheelchair status, bedbound state, and age at death, which were considered as primary outcome measures. We also correlated the DMD genotype with the motor milestones and other phenotypic features. RESULTS: A total of 500 DMD patients were included and 275 participated in the study. The mean age at symptom onset was 3.7 ± 1.9 years, mean age at presentation was 8.1 ± 2.5 years, and mean duration of illness was 4.4 ± 2.6 years. On following them over 15 years, 155 (56.4%) had attained at least one of the primary outcome measures. Wheelchair status was attained in 124 (45.1%) [mean age: 10.4 ± 1.6 years] and bedbound state in 24 (8.7%; mean age: 11.8 ± 2.2 years) patients. Seven patients (2.6%) died during the follow-up period (mean age: 15.2 ± 2.4 years). There was no significant impact of the genotypic or phenotypic features on the primary outcome. CONCLUSION: The pattern of major motor milestones (primary outcome measures) in this large cohort is comparable with that of the Western population despite variability in medical care. The genotypic pattern was also similar to other large studies, which suggests that DMD is a more homogeneous disorder with limited ethnic variability in its geno-phenotypic expression.

A comparative study of mPCR, MLPA, and muscle biopsy results in a cohort of children with Duchenne muscular dystrophy: a first study.

BACKGROUND: Multiplex ligation-dependant probe amplification (MLPA) is a highly sensitive and rapid alternative to multiplex polymerase chain reaction (PCR). Muscle biopsy should be reserved for mutation-negative cases. MATERIALS AND METHODS: An attempt was made to compare the sensitivity and pattern of mutations by mPCR and MLPA testing in a cohort with suspected Duchenne muscular dystrophy (DMD). Eighty-three children with DMD were enrolled for mPCR and MLPA testing. MLPA-negative cases underwent muscle immunohistochemistry (IHC) for dystrophin. RESULTS: Mean age of onset was 45.3 ± 25.2 months; and mean duration of illness was - 53.3 ± 30.8 months. About 11.9% patients had delayed mental milestones. Mean creatine kinase (CK) value was 12136.1 ± 8591.1 LU/L. mPCR detected deletions in 60/83 (72.3%). Proximal deletions were found in 8 (8.6%), distal deletions in 51 (54.8%), and, both proximal and distal deletions were found in 1. Majority of the deletions were <5 exons [34(36.6%)]; two showed large deletions of >10 exons (2.2%). Deletions in hot spot region occurred in 83.3%. MLPA in the same 83 samples detected deletions in an additional six cases and duplications in 6 (6.5%). Combined detection rate of deletion was 79.5%. Duplications were found in 7.2% of the whole sample. MLPA showed 14 (15.1%) proximal and 57 (61.3%) distal deletions, and proximal and distal deletion in 1. Large deletions (>10 exons) were seen in 6.5%, and single deletions were observed in 24 (36.4%). Most common multiple exon deletion was seen at 45-52 region in 7 samples (10.6%). Longest duplication extended from exon 60 to 66. In the 11 MLPA-negative cases, IHC confirmed dystrophinopathy in 36.36%, sarcoglycanopathy in 36.36%, and no deficiency in 27.27%. CONCLUSIONS: This is the first study from India and possibly in English literature, comparing the sensitivity and pattern of mutations by both mPCR and MLPA in the same cohort of DMD. It further validates that 36.4% of MLPA-negative cases were confirmed to have DMD by IHC. The clinical accuracy has been very high in our cohort. MLPA-negative samples should be subjected for next-generation sequencing before contemplating a biopsy.

Clinical uncertainty in large vessel occlusion ischemic stroke: does automated perfusion imaging make a difference? An intra-rater and inter-rater agreement study.

BACKGROUND: Limited research exists regarding the impact of neuroimaging on endovascular thrombectomy (EVT) decisions for late-window cases of large vessel occlusion (LVO) stroke. OBJECTIVE: T0 assess whether perfusion CT imaging: (1) alters the proportion of recommendations for EVT, and (2) enhances the reliability of EVT decision-making compared with non-contrast CT and CT angiography. METHODS: We conducted a survey using 30 patients drawn from an institutional database of 3144 acute stroke cases. These were presented to 29 Canadian physicians with and without perfusion imaging. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG). RESULTS: The percentage of EVT recommendations differed by 1.1% with or without perfusion imaging. Individual decisions changed in 21.4% of cases (11.3% against EVT and 10.1% in favor). Inter-rater agreement (κG) among the 29 raters was similar between non-perfusion and perfusion CT neuroimaging (κG=0.487; 95% CI 0.327 to 0.647 and κG=0.552; 95% CI 0.430 to 0.675). The 95% CIs overlapped with moderate agreement in both. Intra-rater agreement exhibited overlapping 95% CIs for all 28 raters. κG was either substantial or excellent (0.81-1) for 71.4% (20/28) of raters in both groups. CONCLUSIONS: Despite the minimal difference in overall EVT recommendations with either neuroimaging protocol one in five decisions changed with perfusion imaging. Regarding agreement we found that the use of automated CT perfusion images does not significantly impact the reliability of EVT decisions for patients with late-window LVO.

Effectiveness of self-administered mirror therapy on upper extremity impairments and function of acute stroke patients: study protocol.

BACKGROUND: Many therapeutic interventions are performed by physiotherapists to improve upper extremity function and/or activities of daily living (ADL) in stroke patients. Mirror therapy (MT) is a simple technique that can be self-administered by the patients with intact cognition following patient education by a skilled physiotherapist. However, the effectiveness of self-administered MT in post-stroke patients in upper extremity function remains unclear. Therefore, the objective of this study is to examine the effectiveness of MT in improving upper extremity function and recovery in acute stroke patients. METHODS: This study is a single-center, prospective, randomized, open-label, controlled trial with blinded outcome evaluation (PROBE design), in which a total of 36 eligible acute stroke patients will be randomly assigned to control (n=18) and experimental group (n=18). Participants in the control group will receive regular rehabilitation interventions whereas participants in the experimental group will receive MT education in addition to their regular interventions for 4 weeks. STUDY OUTCOME: The primary outcome measure will be upper extremity function that will be measured using the Fugl-Meyer Assessment scale and the Wolf Motor Function Test. The secondary outcome measure will be behaviors related to ADL as estimated using the Modified Barthel Index. Outcome measures will be assessed at baseline and at 4 weeks post-rehabilitation intervention/MT. RESULTS: A two-way repeated analysis of variance (ANOVA) with time and group effects will be used to analyze between-group differences. The level of significance will be set at P < 0.05. CONCLUSION: The results of the study will provide critical information to include self-administered MT as an adjuvant to regular interventions and may facilitate recovery of the upper extremity function of stroke patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04542772 . Registered on 9 September 2020. Protocol version: Final 1.0.

Equipoise in Management of Patients With Acute Symptomatic Carotid Stenosis (Hot Carotid).

OBJECTIVE: To explore differences in antithrombotic management of patients with acutely symptomatic carotid stenosis ("hot carotid") awaiting revascularization with endarterectomy or stenting (CEA/CAS). METHODS: We used a worldwide electronic survey with practice-related questions and clinical questions about 3 representative scenarios. Respondents chose their preferred antithrombotic regimen (1) in general, (2) if the patient was already on aspirin, or (3) had associated intraluminal thrombus (ILT) and identified clinical/imaging factors that increased or decreased their enthusiasm for additional antithrombotic agents. Responses among different groups were compared using multivariable logistic regression. RESULTS: We received 668 responses from 71 countries. The majority favored CT angiography (70.2%) to evaluate carotid stenosis, CEA (69.1%) over CAS, an aspirin-containing regimen (88.5%), and a clopidogrel-containing regimen (64.4%) if already on aspirin. Whereas diverse antithrombotic regimens were chosen, monotherapy was favored by 54.4%-70.6% of respondents across 3 scenarios. The preferred dual therapy was low-dose aspirin (75-100 mg) plus clopidogrel (22.2%) or high-dose aspirin (160-325 mg) plus clopidogrel if already on aspirin (12.2%). Respondents favoring CAS more often chose ≥2 agents (adjusted odds ratio [aOR] vs CEA: 2.00, 95% confidence interval 1.36-2.95, p = 0.001) or clopidogrel-containing regimens (aOR: 1.77, 1.16-2.70, p = 0.008). Regional differences included respondents from Europe less commonly choosing multiple agents if already on aspirin (aOR vs United States/Canada: 0.57, 0.35-0.93, p = 0.023), those from Asia more often favoring multiple agents (aOR: 1.95, 1.11-3.43, p = 0.020), vs those from the United States/Canada preferentially choosing heparin-containing regimens with ILT (aOR vs rest: 3.35, 2.23-5.03, p < 0.001). Factors increasing enthusiasm for ≥2 antithrombotics included multiple TIAs (57.2%), ILT (58.5%), and ulcerated plaque (57.4%); 56.3% identified MRI microbleeds as decreasing enthusiasm. CONCLUSIONS: Our results highlight the heterogeneous management and community equipoise surrounding optimal antithrombotic regimens for hot carotids.

Improving care for acute in-hospital ischemic strokes-A narrative review.

In-hospital strokes, that is new strokes occurring among hospitalized patients, account for 6.5-15% of all strokes. Compared to community-onset stroke patients, in-hospital stroke patients tend to have worse functional and mortality outcomes. This review addresses the characteristics of acute in-hospital ischemic strokes, reasons these patients have worse outcomes compared to community-onset stroke patients, and future steps to improve outcomes.

Long-term neurological, vascular, and mortality outcomes after stroke.

Background Despite improved survival and short-term (90-day) outcomes of ischemic stroke patients, only sparse data exist describing the sustained benefits of acute stroke care interventions and long-term prognosis of stroke survivors. Aim We review the contemporary literature assessing long-term (5 years or more) outcomes after stroke and acute stroke treatment. Summary of review Acute stroke unit care and intravenous thrombolysis have sustained benefits over longer follow-up, but few data exist on the long-term outcome after endovascular thrombectomy (EVT). A large proportion of stroke survivors face challenges of residual disability and neuropsychiatric sequelae (especially affective disorders and epilepsy) which affects their quality of life and is associated with poorer prognosis due to increase in stroke recurrences/mortality. Nearly, a quarter of stroke survivors have a recurrent stroke at 5 years, and nearly double that at 10 years. Mortality after recurrent stroke is high, and half of the stroke survivors are deceased at 5 years after stroke and three fourth at 10 years. Long-term all-cause mortality is largely due to conditions other than stroke. Both stroke recurrence and long-term mortality are affected by several modifiable risk factors, and thus amenable to secondary prevention strategies. Conclusions There is a need for studies reporting longer term effects of acute interventions, especially EVT. Better preventive strategies are warranted to reduce the vascular and non-vascular mortality long after stroke.

Unilateral Papilledema in Cerebral Venous Sinus Thrombosis.

In the majority of patients with raised intracranial pressure, the papilledema is bilateral. Unilateral papilledema is rare in conditions causing intracranial hypertension, and it has been described in Foster-Kennedy syndrome and in some cases of idiopathic intracranial hypertension. It has never been reported in cerebral venous thrombosis. We report a young lady presenting with features of subacute onset of headache with seizures, on evaluation she had superior sagittal and bilateral lateral sinus thrombosis. The risk factors found on evaluation were Vitamin B12 deficiency and hyperhomocysteinemia. On optic fundus examination, she had swollen optic disc on the right side with normal fundus on the left side, confirmed with the orbital ultrasound B-scan and optic coherence tomography. Her magnetic resonance imaging showed features of raised intracranial pressure with thrombosis of the superior sagittal and bilateral lateral sinus thrombosis. She was treated with anticoagulation (heparin followed by oral anticoagulants), antiedema measures, and vitamin supplementation for hyperhomocysteinemia. She improved over time and was asymptomatic during follow-up. We discuss the possible mechanisms described in the literature for unilateral papilledema. This report highlights the need for carefully performing bilateral fundus examination so as not to miss the vision or life-threatening causes of a headache.