Markus Kneihsl

Serum neurofilament light is sensitive to active cerebral small vessel disease

Objective: To explore whether serum neurofilament light chain protein (NfL) levels are increased in patients with MRI-confirmed recent small subcortical infarcts (RSSI) compared to healthy controls and to determine the subsequent course and determinants of NfL levels in a longitudinal manner. Methods: In a prospectively collected group of symptomatic patients with an RSSI (n = 79, mean age 61 ± 11 years, 67% male), we analyzed brain MRI and serum NfL using a Single Molecule Array (Simoa) assay at baseline and at 3 and 15 months after stroke. Community-dwelling healthy age- and sex-matched individuals with comparable severity of MRI white matter hyperintensities (WMH) (n = 53) served as controls. Results: Patients with an RSSI had higher NfL baseline levels compared to controls (73.45 vs 34.59 pg/mL, p < 0.0001), and they were increasingly higher with the time from stroke symptom onset to blood sampling (median 4 days, range 1–11 days, rs = 0.51, p < 0.0001). NfL levels remained increased at the 3-month follow-up but returned to normal at 15 months after stroke. NfL levels were associated with RSSI size and baseline WMH severity and were especially high in patients with new, clinically silent cerebral small vessel disease (CSVD)–related lesions at follow-up. Conclusions: Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

Poststroke alterations in heart rate variability during orthostatic challenge.

Abstract Older adults following recovery from ischemic stroke have a higher incidence of orthostatic hypotension, syncope, and fall risk, which may be related to impaired autonomic responses limiting the ability to maintain cerebral blood flow. Thus, we investigated cerebrovascular and cardiovascular regulation in 23 adults ≥55 years of age, 10 diagnosed with ischemic stroke, and 13 age-matched healthy controls when sitting at rest and upon standing to compare differences of autonomic variables at ∼7 months (218 ± 41 days) poststroke. Arterial blood pressure via finger plethysmography, muscle-pump baroreflex via electromyography, heart rate variability via 3-lead ECG, and cerebral blood flow velocity via transcranial Doppler were analyzed while sitting for 5 minutes and then during quiet standing for 5 minutes. From the seated to standing position, the stroke group had significantly greater decline in the low frequency component of heart rate variability (164 [79] vs 25 [162] ms2; P = 0.043). All other cardiovascular parameters and assessments of autonomic function were not significantly different between the two groups. Our findings support the hypothesis of continued autonomic dysfunction after recovery from ischemic stroke, with potential attenuation of the cardiovascular response to standing. However, further investigation is required to determine the mechanisms underlying the increased risk of orthostatic hypotension, syncope, and falls poststroke.

Increased middle cerebral artery mean blood flow velocity index after stroke thrombectomy indicates increased risk for intracranial hemorrhage

Background and purpose Cerebral hyperperfusion has been related to the risk of intracranial hemorrhage (ICH) in stroke patients after vessel recanalization therapy. We hypothesized that after successful mechanical thrombectomy for acute anterior circulation stroke, hemodynamics detectable by transcranial Duplex (TCD) sonography would vary, and that increased blood flow velocities would be associated with ICH. Methods We retrospectively identified all ischemic stroke patients with successful endovascular recanalization for anterior circulation vessel occlusion (Thrombolysis in Cerebral Infarction 2b–3) between 2010 and 2017. We reviewed their postinterventional TCD examinations for mean blood flow (MBF) velocities of the recanalized and contralateral middle cerebral artery (MCA) and searched for an association with postinterventional ICH and clinical outcome. Results 123 stroke patients (mean age 63±14 years, 40% women) with successful anterior circulation thrombectomy were analyzed. Of those, 18 patients had postinterventional ICH. ICH patients had an increased MCA MBF velocity index (=MBF velocity of the recanalized divided by the contralateral MCA) compared with non-ICH patients (1.32±0.39 vs 1.02±0.32, P<0.001). In multivariate analysis, a higher MCA MBF velocity index was associated with postinterventional ICH and poor 90 day outcome. Conclusions A high MCA MBF velocity index on TCD after successful recanalization therapy for anterior circulation stroke indicates a risk for postinterventional ICH and worse prognosis.

Orthostatic Challenge Shifts the Hemostatic System of Patients Recovered from Stroke toward Hypercoagulability

Aims: The objective of our study was to assess the effects of orthostatic challenge on the coagulation system in patients with a history of thromboembolic events and to assess how they compared with age-matched healthy controls. Methods: Twenty-two patients with histories of ischemic stroke and 22 healthy age-matched controls performed a sit-to-stand test. Blood was collected prior to- and at the end of- standing in the upright position for 6 min. Hemostatic profiling was performed by determining thrombelastometry and calibrated automated thrombogram values, indices of thrombin generation, standard coagulation times, markers of endothelial activation, plasma levels of coagulation factors and copeptin, and hematocrit. Results: Orthostatic challenge caused a significant endothelial and coagulation activation in patients (Group 1) and healthy controls (Group 2): Plasma levels of prothrombin fragment F1+2 were increased by approximately 35% and thrombin/antithrombin-complex (TAT) increased 5-fold. Several coagulation variables were significantly altered in Group 1 but not in Group 2: Coagulation times (CTs) were significantly shortened and alpha angles, peak rate of thrombin generation (VELINDEX), tissue factor (TF) and copeptin plasma levels were significantly increased (comparison between standing and baseline). Moreover, the shortening of CTs and the rise of copeptin plasma levels were significantly higher in Group 1 vs. Group 2 (comparison between groups). Conclusion: The coagulation system of patients with a history of ischemic stroke can be more easily shifted toward a hypercoagulable state than that of healthy controls. Attentive and long-term anticoagulant treatment is essential to keep patients from recurrence of vascular events.

Adrenomedullin and Galanin Responses to Orthostasis in Older Persons.

Neuroendocrine responses to orthostasis may be critical in the maintenance of mean arterial pressure in healthy individuals. A greater reduction in orthostatic tolerance with age may relate to modulation of hormonal responses such as adrenomedullin and galanin. Thus, we investigated (i) whether adrenomedullin and galanin concentrations increase during orthostatic challenge in older subjects, (ii) whether adrenomedullin and galanin concentrations are higher in older females compared with older males when seated and during orthostatic challenge, and (iii) whether postural changes in plasma concentrations of galanin are correlated with levels of adrenomedullin in either older females or males.

Stroke Referrals from Nursing Homes: High Rate of Mimics and Late Presentation

Background: Stroke has become a treatable condition with increasing evidence of treatment benefits in older people. However, stroke mimics in geriatric patients are especially prevalent, causing incorrect suspicion and consecutive burden to patients and emergency room resources. We therefore examined the dimension of this problem by investigating emergency room admissions from nursing homes for suspected stroke. Methods: We performed a retrospective cohort study of all nursing home residents who were admitted to the neurological emergency room of our primary and tertiary care university hospital between 2013 and 2015. Patients were further divided into those with confirmed stroke and stroke mimics after diagnostic stroke work-up. Results: Of 419 nursing home patients referred to the emergency room, nearly one third had suspected stroke (n = 126; mean age: 78 ± 14 years, polypharmacy rate: 77%). Of those, 43 (34%) had a confirmed stroke (ischaemic: n = 34; haemorrhagic: n = 9) and 83 (66%) had stroke mimics after diagnostic work-up. Only one patient underwent intravenous thrombolysis, followed by mechanical thrombectomy for middle cerebral artery occlusion. Prehospital delay (47%) and multimorbidity-associated contraindications (27%) were the main reasons for withholding recanalization therapy. Among the stroke-mimicking conditions, infectious diseases (24%) and epileptic seizures (20%) were the most frequent. Multivariate analysis identified focal deficits (OR 16.6, 95% CI 4.3–64.0), atrial fibrillation (OR 3.9, 95% CI 1.5–10.5) and previous stroke (OR 3.2, 95% CI 1.2–8.9) as indicators that were associated with stroke. Conclusions: In our region, nursing home referrals for suspected stroke have a high false positive rate and occur delayed, which most often precludes specific stroke treatment in addition to multimorbidity. Such problems may also exist in other centres and highlight the need for targeted educational and organizational efforts. Simple indicators as identified in this study may help to sort out patients with true stroke more efficiently.