NIH Stroke Research Articles

The stroke outcome optimization project: Acute ischemic strokes from a comprehensive stroke center

Stroke is a leading cause of disability, and Magnetic Resonance Imaging (MRI) is routinely acquired for acute stroke management. Publicly sharing these datasets can aid in the development of machine learning algorithms, particularly for lesion identification, brain health quantification, and prognosis. These algorithms thrive on large amounts of information, but require diverse datasets to avoid overfitting to specific populations or acquisitions. While there are many large public MRI datasets, few of these include acute stroke. We describe clinical MRI using diffusion-weighted, fluid-attenuated and T1-weighted modalities for 1715 individuals admitted in the upstate of South Carolina, of whom 1461 have acute ischemic stroke. Demographic and impairment data are provided for 1106 of the stroke survivors from this cohort. Our validation demonstrates that machine learning can leverage the imaging data to predict stroke severity as measured by the NIH Stroke Scale/Score (NIHSS). We share not only the raw data, but also the scripts for replicating our findings. These tools can aid in education, and provide a benchmark for validating improved methods.

Abstract #1377584: Brain on Fire: A Case of Hashimoto's Encephalitis in a 29-Year-Old Female

A 29-year-old female presents to the hospital for insomnia, hallucination, and bizarre behavior. The patient had been feeling well until approximately three days early when she became psychotic after fasting from food for three days. She began having auditory and visual hallucinations and then started having seizures. Initially, the patient was admitted to a hospital in another city where she was diagnosed with Autoimmune Encephalitis for which she received IVIg. Brain MRI showed questionable T2 changes around the fourth ventricle on the left during hospital admission. The patient was discharged home after her symptoms improved. However, she was brought to our hospital for psychiatric consultation as her condition deteriorated. Upon arrival at Larkin Community Hospital, the patient was hemodynamically stable, breathing room air, and continued to complain of having delusions and hallucinations. Initial Vital Signs: BP: 122/74 mmHg, HR: 70 bpm, RR: 18, T: 98°F. weight 56.2 kg, BMI 24.21. She was in nonacute distress, although anxious with pressured speech. She was cooperative and able to follow commands and track the examiner. Her NIH Stroke Scale/Score (NIHSS) was 0 and Glasgow Coma Scale (GCS) was 15. She denied using illicit drugs, smoking, and alcohol. Neurology decided to repeat LP CSF r/o NMDA Antibody encephalitis and started empirically a 5-day course of azithromycin to cover for streptococcal infections while awaiting further results. Thyroglobulin antibodies were ordered to rule out Steroids Responsive Encephalopathy and it came back elevated (91.2). She was started on Solu-Medrol 500mg IV daily for 3 days which was increased to 1000mg IV daily to complete 5 days. Even though, she developed tachycardia in the 120s; she started feeling much better as well as improved her symptoms. “Steroid-responsive encephalopathy associated with autoimmune thyroiditis” (SREAT) is an uncommon condition that is associated with Hashimoto thyroiditis. It is also called Hashimoto encephalopathy (HE). This condition was originally described in 1966 by Brain et al1. HE is a rare disorder with an approximate prevalence of 2/100,0002. It affects women more often than men. This diagnosis is typically made when a patient has encephalopathy associated with antithyroid (anti-thyroid peroxidase [TPO]) and/or anti-thyroglobulin (TG) antibodies, when other causes have been excluded. The symptoms typically seen include subacute onset of confusion with altered level of consciousness, seizures, and myoclonus. Based on the literature review of 251 cases of SREAT by Laurent et al3, SREAT has various presentations including coma to isolated psychiatric disorder. This disorder is thought to be immune mediated as opposed to being the result of an altered thyroid state on the nervous system. In most of the reported cases of SREAT, the patients are euthyroid during the presentation of symptoms. However, the exact mechanism of SREAT is still unknown. The diagnosis is made after excluding other toxic, infectious, and metabolic causes of encephalopathy with examination of cerebrospinal fluid and neuroimaging.

Clinical experience: Outcomes of mesenchymal stem cell transplantation in five stroke patients.

Stem cell therapy, which has promising results in acute disorders such as stroke, supports treatment by providing rehabilitation in the chronic stage patients. In acute stroke, thrombolytic medical treatment protocols are clearly defined in neurologic emergencies, but in neurologic patients who miss the "thrombolytic treatment intervention window," or in cases of hypoxic-ischemic encephalopathy, our hands are tied, and we are still unfortunately faced with hopeless clinical implementations. We consider mesenchymal stem cell therapy a viable option in these cases. In recent years, novel research has focused on neuro-stimulants and supportive and combined therapies for stroke. Currently, available treatment options are limited, and only certain patients are eligible for acute treatment. In the scope of our experience, five stroke patients were evaluated in this study, who was treated with a single dose of 1-2 × 106 cells/kg allogenic umbilical cord-mesenchymal stem cells (UC-MSCs) with the official confirmation of the Turkish Ministry of Health Stem Cell Commission. The patients were followed up for 12 months, and clinical outcomes are recorded. NIH Stroke Scale/Scores (NIHSS) decreased significantly (p = 0.0310), and the Rivermead Assessment Scale (RMA) increased significantly (p = 0.0234) for all patients at the end of the follow-up. All the patients were followed up for 1 year within a rehabilitation program. Major clinical outcome improvements were observed in the overall clinical conditions of the UC-MSC treatment patients. We observed improvement in the patients' upper extremity and muscle strength, spasticity, and fine motor functions. Considering recent studies in the literature together with our results, allogenic stem cell therapies are introduced as promising novel therapies in terms of their encouraging effects on physiological motor outcomes.

Clinical Effect of Butylphthalide Combined with Rt-PA Intravenous Thrombolysis in the Treatment of Acute Cerebral Infarction.

Objective To assess the clinical effect of butylphthalide combined with rt-PA intravenous thrombolysis in the treatment of acute cerebral infarction (ACI). Methods Totally, 312 acute cerebral infarction patients were included in this research. Those in the group for experiment received butylphthalide (25 mg QD) combined with rt-PA intravenous thrombolysis (0.9 mg/kg QD), while the control group received rt-PA intravenous (P < 0.05). Moreover, NIHSS (NIH Stroke Scale/Score) and Barthel index scores in the two groups improved, NIHSS score had ameliorated, and Barthel index score was higher than that in the reference group (P < 0.05). Conclusion The combination of butylphthalide and recombination plasminogen activator alteplase (rt-PA) intravenous thrombolysis has a significant clinical effect in the treatment of acute cerebral infarction. It can alleviate the inflammatory symptoms, accelerate the recovery of neurological function, and improve the ability of daily living.

Is COVID-19 Infection also a Silent Killer?

A 59-year-old male had multiple comorbidities such as diabetes, dilated cardiomyopathy, hypertension, ischemic heart disease, and chronic obstructive pulmonary disease. He presented with dyspnea and had ground-glass opacity in the lungs. It was during the pandemic of COVID-19 so repeated Reverse transcription polymerase chain reaction (RT-PCR) was done, but all were negative. He got stabilized within 5 days and we planned discharge. Suddenly, he had right hemiplegia and developed altered sensorium. He had NIH Stroke Scale/Score of 28 and computed tomography-Alberta Stroke Program Early Computed Tomography Score of 10. We used tenecteplase (0.25 mg/kg bodyweight) for thrombolysis within 20 min of onset and planned mechanical thrombectomy for the occlusion of internal carotid artery and beyond. However, in magnetic resonance imaging of the brain, he had an established infarct in the left middle cerebral artery (MCA) territory (within this short time) without significant DWI/FLAIR mismatch. Hence, we continued conservative management. We incidentally detected him to have COVID-19 infection positivity on that day, but all inflammatory and coagulation parameters were normal on that day and later. His monitor did not reveal arrhythmia (during the event and later) and echocardiography failed to reveal evidence of culprit lesion. He had a rapid clinical decline, required hemicraniectomy but expired within 2 days. COVID-19 infection may have negative reports initially, but malignant MCA infarct with normal inflammatory markers makes our case special. The rapidity with which stroke developed underscores the severe nature of the disease process, the absence of arrhythmias (in this in-house stroke), and normal coagulation parameters hints that the exact mechanism of stroke in this type of infection is still an enigma.

An Interesting Case of Acute Stroke: When Many Things Went Wrong, but the Patient Laughed at Last!

A 52-year-old lady with hypertrophic obstructive cardiomyopathy, atrial flutter, and old right hemispheric stroke in the background underwent implantable cardioverter-defibrillator implantation for complete heart block. She was yet to start her regular anticoagulant and presented to hospital emergency with acute right middle cerebral artery (MCA) territory stroke (NIH Stroke Scale/Score of 14). After ruling out absolute contraindications, she was given intravenous thrombolysis (did not have a blood vessel target for endovascular therapy). Post thrombolysis, she had clot mobilization from the internal carotid artery to the MCA and systemic embolization to kidneys and lower limbs. The patient underwent an urgent embolectomy and lower limbs were saved from amputation. Our case highlights the importance of checking peripheral pulses in acute stroke patients post thrombolysis. Though the patient had initial deterioration after thrombolysis, she gradually improved and later achieved satisfactory modified Rankin scale underscoring the ultimate potential benefits of thrombolysis in acute stroke. There is a high chance of thrombus formation in patients with atrial flutter who undergo recent cardiac procedure especially if they are off anticoagulation for even a short period. Hence, unnecessary apprehension of anticoagulant use in proper situations may create life-threatening complications.

Effect of Hip Fracture on Prognosis of Acute Cerebral Infarction

&lt;p&gt;&lt;strong&gt;Background and Objective:&lt;/strong&gt; The guidelines on the factors to determine whether a patient with concomitant stroke and hip fracture is a good candidate for surgical hip repair are still debatable. This study was carried out to investigate the relationship between the management of acute hip fracture and the recovery of neurological function and prognosis in patients with concomitant acute cerebral infarction.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt; Methods:&lt;/strong&gt; Thirty patients with acute cerebral infarction combined with acute hip fracture, who were hospitalized and did not accept surgical treatment, and matched 60 cases as control group having acute cerebral infarction without hip fracture admitted in the same period were selected. The neurological function recovery, hospitalization period, 6 months recovery rate, frequency of complications, and 1 year mortality rate between the groups were compared.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with common acute cerebral infarction patients, the NIH Stroke Scale/Score of acute cerebral infarction group with hip fracture was higher (7.2 &amp;plusmn; 5.4 vs. 5.6 &amp;plusmn; 4.3, p = 0.034). The hospitalization period was prolonged (16.1 &amp;plusmn; 8.9 vs. 12.2 &amp;plusmn; 5.3, p = 0.041), and 6 months recovery rate was lower (26.7% vs. 53.3%, p = 0.016), the frequency of pulmonary infection and lower extremity deep vein thrombosis was higher (30% vs. 11.7%, p = 0.03; 6.7% vs. 0, p = 0.043). The 1-year mortality rate in patients with combined hip fracture was higher than in patients with cerebral infarction only.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; Acute cerebral infarction combined with hip fracture lead to worse neurological recovery, prolonged hospitalization period, increased complications, decreased patient prognosis, and increased 1 year mortality. Surgical treatment of hip fracture with concomitant acute cerebral infarction may improve the prognosis of patients. According to the statistics of neurological function and mortality after 1 year of follow-up, the prognosis of patients with Modified Rankin Scale below 3 was considered good.&lt;/p&gt;

Accurate prediction of clinical stroke scales and improved biomarkers of motor impairment from robotic measurements.

ObjectiveOne of the greatest challenges in clinical trial design is dealing with the subjectivity and variability introduced by human raters when measuring clinical end-points. We hypothesized that robotic measures that capture the kinematics of human movements collected longitudinally in patients after stroke would bear a significant relationship to the ordinal clinical scales and potentially lead to the development of more sensitive motor biomarkers that could improve the efficiency and cost of clinical trials.Materials and methodsWe used clinical scales and a robotic assay to measure arm movement in 208 patients 7, 14, 21, 30 and 90 days after acute ischemic stroke at two separate clinical sites. The robots are low impedance and low friction interactive devices that precisely measure speed, position and force, so that even a hemiparetic patient can generate a complete measurement profile. These profiles were used to develop predictive models of the clinical assessments employing a combination of artificial ant colonies and neural network ensembles.ResultsThe resulting models replicated commonly used clinical scales to a cross-validated R2 of 0.73, 0.75, 0.63 and 0.60 for the Fugl-Meyer, Motor Power, NIH stroke and modified Rankin scales, respectively. Moreover, when suitably scaled and combined, the robotic measures demonstrated a significant increase in effect size from day 7 to 90 over historical data (1.47 versus 0.67).Discussion and conclusionThese results suggest that it is possible to derive surrogate biomarkers that can significantly reduce the sample size required to power future stroke clinical trials.

"Blueprinting" thrombogenicity and antithrombotic drug response at the bedside in patients presenting emergently with symptoms of acute stroke.

Early assessment of thrombogenicity and antithrombotic drug effects may be important for therapeutic decision making in patients presenting with acute stroke. In this prospective, single center, pilot study, a bedside thrombelastography assay (TEG6s) was used to measure thrombogenicity and antithrombotic drug response in serial patients presenting emergently with symptoms of acute stroke (n = 90). TEG6s measures were compared against diagnosis obtained by NIH Stroke Scale/Score and imaging. Acute ischemic stroke (AIS) was diagnosed in 30 patients, intracerebral hemorrhage (ICH) in 19, transient ischemic attack (TIA) in 10 and stroke mimic (SM) in 31. Patients with AIS had a higher prevalence of A-Fib (33.3% vs. 11.6%, p = 0.01), and ACE inhibitor use (56.3% vs. 21.6%, p < 0.001) compared to combined non-AIS group. Time to initial clot formation (R) was shorter in AIS vs. TIA, ICH, and SM (p < 0.05). Comparing patients with AIS and combined non-AIS group the AUC for R was 0.83 (cut point of ≤ 4.8, sensitivity = 67%; specificity = 84%, p < 0.001). In AIS patients, 46% had suboptimal response (< 30% MAAA inhibition) toaspirin and80% of patientson P2Y12 therapy had high platelet reactivity (>50% ADP-induced platelet aggregation). Patients receiving tissue plasminogen activator had significant reduction in clot strength and near complete lysis at 30min which normalized within 2h after treatment (p < 0.001 for both). The rapid bedside measurement of thrombogenicity and antithrombotic drug effects is feasible in patients presenting with symptoms of acute stroke. Our preliminary data suggest that AIS is associated with faster ex-vivo clot formation, and poor antiplatelet response. Future study of the TEG6s to "blueprint" hemostasis is warranted in the stroke population.

Effects of gastrodin on 5-HT and neurotrophic factor in the treatment of patients with post-stroke depression.

Effects of gastrodin on 5-HT and neurotrophic factor in the treatment of patients with post-stroke depression (PSD) were investigated. A total of 78 PSD patients were selected in Binzhou City Center Hospital from September 2013 to December 2016. Patients were randomly divided into the control group and experimental group, 39 patients in each group. Patients in the control group were treated with conventional drug fluoxertine hydrochloride for 2 months, and patients in the experimental group were treated with gastrodin. The levels of 5-HT and neurotrophic factors in blood were measured using the enzyme-linked immunosorbent assay (ELISA) kit before, and at 1 and 2 months after treatment. The Hamilton Depression Scale (HAMD), Activities of Daily Living (ADL) scale, NIH Stroke Scale/Score (NIHSS) and Stroke Impact Scale (SIS) were used to evaluate the efficacy of treatment. Treatment efficacy was compared between the two groups. The levels of 5-HT and neurotrophic factors were significantly higher in the experimental group than those in the control group at 1 and 2 months after treatment (P<0.05), and HAMD, ADL, NIHSS and SIS scores were all better in the experimental group than in the control group (P<0.05). In addition, significantly less side effects were found in the experimental group than that in the control group, and treatment efficacy in the experimental group was significantly better than that in the control group (P<0.05). Gastrodin is effective in the treatment of PSD and should be popularized.

Abstract WP21: Different View on Clinical Application of Tirofiban After Mechanical Arterial Recanalization in Acute Ischemic Stroke

Tirofiban, an antiplatelet drug and glycoprotein-IIb/IIIa inhibitor, widely used in cardiovascular events, appears to be safe and effective in cerebrovascular stroke. However, its efficacy post-endovascular therapy raised concern due to an association with increased risk of fatal intracerebral hemorrhage (ICH) and poor outcome in ischemic patients (Kellert et al. 2013). The success of 5 randomized clinical trials in stroke therapy in 2015 utilizing new generation endovascular intervention prompted this study of continuous intravenous administration of Tirofiban after thrombectomy with the Solitaire stent, one of the two new devices, in patients with acute ischemic stroke. A consecutive series of patients (n=28) who received Solitaire stent thrombectomy from January 2017 to the present was enrolled. 22 of the 28 patients were eligible for intravenous Tirofiban treatment for 24 h after receiving endovascular therapy. 6 patients were excluded because of no vessel recanalization, vessel recanalization achieved by other devices, or ICH after endovascular therapy. The incidence of symptomatic ICH and death was recorded. The number of thrombectomy attempts and device manipulation time within vessels were measured as potential markers for endothelial damage. The NIH stroke and modified Rankin scales were assessed at 7 days and 3 months, respectively. In all 22 patients who received Tirofiban after endovascular therapy, none had symptomatic ICH nor died from treatment. Successful recanalization rate (TICI≥2b) was achieved in 18 (86.4%) of 22 patients after endovascular therapy. As compared to the study by Kellert et al., the lower average device passages (1.2 vs 2.0) and short device manipulation time (56 vs 104 min) together suggested less endothelial damage. Of our patients, 77.3% showed neurological improvement at 7 days and 59.1% patients had favorable outcomes with a Modified Rankin scale of 0 to 2 at 3 months. These favorable outcomes were similar to those achieved in the 5 positive randomized trials. In conclusion, the continuous application of Tirofiban post-Solitaire stent thrombectomy appears to be safe and effective in acute ischemic stroke. Reduced endothelial damage may play a key role in clinical outcomes with Tirofiban application.

Comparison of the response to endovascular reperfusion in relation to site of arterial occlusion

We explored the relationship between the site of vascular occlusion and the response to endovascular treatment in patients with acute ischemic stroke and also considered the impact of mismatch profile. DEFUSE-2 was a prospective cohort study of patients treated with endovascular therapy. Patients with internal carotid artery (ICA) and middle cerebral artery (MCA) involvement were included in this substudy. Mismatch and reperfusion status was assessed on MRI. Favorable clinical response was defined as an improvement of at least 8 points on the NIH Stroke Scale. Reperfusion rates were comparable in both groups (61% for ICA and 59% for MCA). In the setting of reperfusion, percentages of favorable clinical response were similar between patients with stroke due to ICA (65%) and MCA (63%) occlusions. When reperfusion was not achieved, favorable outcomes were less frequent with obstructions of the ICA (9%) than the MCA (52%). Among target mismatch patients, the adjusted odds ratio for favorable clinical response associated with reperfusion was 39.7 (95% confidence interval 1.4-1,132.8) for ICA occlusions vs 5.1 (95% confidence interval 1.4-19.3) for MCA occlusions. Endovascular reperfusion is associated with favorable clinical response regardless of the location of the arterial occlusion. This association is strongest for target mismatch patients with ICA occlusions. Target mismatch patients with either ICA or MCA occlusions appear to be good candidates for endovascular reperfusion therapy.

Impaired Cerebral Autoregulation Is Associated with Brain Atrophy and Worse Functional Status in Chronic Ischemic Stroke

Dynamic cerebral autoregulation (dCA) is impaired following stroke. However, the relationship between dCA, brain atrophy, and functional outcomes following stroke remains unclear. In this study, we aimed to determine whether impairment of dCA is associated with atrophy in specific regions or globally, thereby affecting daily functions in stroke patients.We performed a retrospective analysis of 33 subjects with chronic infarctions in the middle cerebral artery territory, and 109 age-matched non-stroke subjects. dCA was assessed via the phase relationship between arterial blood pressure and cerebral blood flow velocity. Brain tissue volumes were quantified from MRI. Functional status was assessed by gait speed, instrumental activities of daily living (IADL), modified Rankin Scale, and NIH Stroke Score.Compared to the non-stroke group, stroke subjects showed degraded dCA bilaterally, and showed gray matter atrophy in the frontal, parietal and temporal lobes ipsilateral to infarct. In stroke subjects, better dCA was associated with less temporal lobe gray matter atrophy on the infracted side ( = 0.029), faster gait speed ( = 0.018) and lower IADL score (0.002). Our results indicate that better dynamic cerebral perfusion regulation is associated with less atrophy and better long-term functional status in older adults with chronic ischemic infarctions.

Neuron-specific enolase and S 100B protein as predictors of outcome in ischaemic stroke

Background and purposeAs neuron-specific enolase (NSE) and S 100B protein are brain origin proteins, the aim of this study was to assess whether a single NSE and S 100B measure may predict clinical outcome of patients with cerebral ischaemic infarct. Material and methodsSeventy-one patients with ischaemic stroke and 41 controls were studied. All patients had computed tomography of the brain performed after admission and on the third day and volume of the infarct was assessed by the volumetric method from the second examination. NSE and S 100B protein were analysed by immunochemiluminescence on the fourth day after admission. Clinical state of the patients was determined with the NIH stroke, Barthel and Rankin scales on admission, discharge from the hospital, and after one and 3 months from the onset of stroke. ResultsNSE levels in blood were significantly higher in stroke patients than in the control group – 36.9 ± 24.0 vs. 14.3 ± 9.7 μg/L. Also, the levels of the S 100B protein were significantly higher in the patient group (0.85 ± 1.74 vs. 0.10 ± 0.03 μg/L) but only the levels of S 100B protein correlated with the calculated size of the infarct (Spearman coefficient = 0.77). No such correlation was identified for NSE level (Spearman coefficient = 0.25). ConclusionsAlthough significant differences in NSE and S 100B levels between stroke patients and the control group were found, only S 100B protein level correlated with stroke volume, neurological status at admission and functional outcome. NSE did not correlate with stroke volume, neurological status or clinical outcome.

Post‐stroke sexual functioning in first stroke patients

Although physical problems after stroke have been well studied, there is little information on one of the crucial aspects of the quality of life of those patients, namely sexual functioning and satisfaction. The aim of this study was to assess the impact of stroke on sexual functioning in a stable cohort of Turkish stroke patients with mild or no disability and to assess the relationship between post-stroke sexuality and a number of socio-demographic, clinical and laboratory variables. The sexual functioning of 103 Turkish stroke patients with no disability or mild disability was assessed in two consecutive interviews along with clinical and sociodemographic features. NIH stroke, Glasgow coma, Barthel, and Rankin scales were also applied to assess neurologic status and disability. Most of the patients were male (61%) and illiterate (70%). There was a significant difference between the baseline and post-stroke frequency of sexual activity of the patients. The differences between baseline and post-stroke vaginal lubrication, orgasms and satisfaction were all statistically significant. This latter difference was significant for both genders. Frequency of coitus both prior to and after the stroke was significantly different between males and females. Erection and ejaculation of the males was significantly affected by the stroke, and lubrication and orgasm was affected in the females. Interestingly, fear of recurrent stroke did not differ between genders. Our study has shown that Turkish stroke survivors have sexual health needs during the rehabilitation process, though this has not been addressed previously. Sexual health needs seem to be affected by cultural factors and biases.

Peripheral arterial embolism during thrombolysis for stroke

Hemorrhage is a possible complication of thrombolytic therapy for brain infarction that carries high morbidity and mortality.1 In fact, most exclusion criteria refer to situations prone to hemorrhage, such as low platelet count, coagulation abnormalities, a recent major surgery, or gastrointestinal bleeding. Unexpected and seemingly paradoxical is the occurrence of a thromboembolic phenomenon in the setting of thrombolytic therapy. We report a patient who was subject to thrombolytic therapy for ischemic stroke with complete neurologic recovery but who presented a lower limb embolism during the administration of IV tissue plasminogen activator (tPA). A 73-year-old man was admitted to the cardiology department of our hospital for left heart failure and a suspicion of dilated myocardiopathy and was successfully treated with diuretics. Twelve hours after admission, he had acute left-sided hemiplegia with hemianesthesia, visual neglect, and anosognosia. The NIH Stroke …

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