scholarly journals Serum neurofilament light is sensitive to active cerebral small vessel disease

Neurology ◽  
2017 ◽  
Vol 89 (20) ◽  
pp. 2108-2114 ◽  
Author(s):  
Thomas Gattringer ◽  
Daniela Pinter ◽  
Christian Enzinger ◽  
Thomas Seifert-Held ◽  
Markus Kneihsl ◽  
...  
Keyword(s):  
Single Molecule ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
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.

scholarly journals Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease

2020 ◽  
Vol 22 (3) ◽  
pp. 369-376
Author(s):  
Nils Peters ◽  
Esther van Leijsen ◽  
Anil M. Tuladhar ◽  
Christian Barro ◽  
Marek J. Konieczny ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Analysis Of Covariance ◽  
Small Vessel ◽  
Cognitive Measures ◽  
Neurofilament Light ◽  
Baseline Serum ◽  
Vessel Disease

Background and Purpose Serum neurofilament light (NfL)-chain is a circulating marker for neuroaxonal injury and is also associated with severity of cerebral small vessel disease (SVD) cross-sectionally. Here we explored the association of serum-NfL with imaging and cognitive measures in SVD longitudinally.Methods From 503 subjects with SVD, baseline and follow-up magnetic resonance imaging (MRI) was available for 264 participants (follow-up 8.7±0.2 years). Baseline serum-NfL was measured by an ultrasensitive single-molecule-assay. SVD-MRI-markers including white matter hyperintensity (WMH)-volume, mean diffusivity (MD), lacunes, and microbleeds were assessed at both timepoints. Cognitive testing was performed in 336 participants, including SVD-related domains as well as global cognition and memory. Associations with NfL were assessed using linear regression analyses and analysis of covariance (ANCOVA).Results Serum-NfL was associated with baseline WMH-volume, MD-values and presence of lacunes and microbleeds. SVD-related MRI- and cognitive measures showed progression during follow-up. NfL-levels were associated with future MRI-markers of SVD, including WMH, MD and lacunes. For the latter, this association was independent of baseline lacunes. Furthermore, NfL was associated with incident lacunes during follow-up (P=0.040). NfL-levels were associated with future SVD-related cognitive impairment (processing speed: β=–0.159; 95% confidence interval [CI], –0.242 to –0.068; P=0.001; executive function β=–0.095; 95% CI, –0.170 to –0.007; P=0.033), adjusted for age, sex, education, and depression. Dementia-risk increased with higher NfL-levels (hazard ratio, 5.0; 95% CI, 2.6 to 9.4; P<0.001), however not after adjusting for age.Conclusions Longitudinally, serum-NfL is associated with markers of SVD, especially with incident lacunes, and future cognitive impairment affecting various domains. NfL may potentially serve as an additional marker for disease monitoring and outcome in SVD, potentially capturing both vascular and neurodegenerative processes in the elderly.

scholarly journals Periodic Limb Movements Syndrome in Patients With Cerebral Small Vessel Disease: Protocol for a Prospective Observational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Ekaterina Spektor ◽  
Ingo Fietze ◽  
Mikhail G. Poluektov
Keyword(s):  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Periodic Limb Movements ◽  
Apnea Hypopnea Index ◽  
Limb Movements ◽  
Vessel Disease

Background: Cerebrovascular diseases are the leading cause of cognitive decline and dementia. Therefore, the investigation of the potential ways to slow down the disease progression is an important research field. Periodic limb movements in sleep (PLMS) are known to be associated with transient changes in heart rate and blood pressure. These changes might influence the course of cerebral small vessel disease (cSVD). Nevertheless, the clinical significance of PLMS, particularly its influence on cardiovascular diseases course, is still controversial and underinvestigated.Methods/design: Patients from 60 to 75 years old diagnosed with cSVD will undergo nocturnal polysomnography. Subjects with apnea/hypopnea index under 5 will be enrolled. Sleep quality and daytime functioning will be assessed at baseline with self-reported questionnaires. Brain MRI and cognitive assessment will be performed at baseline and in the 2-year follow-up. Progression of cSVD markers and cognitive dysfunction will be compared between patients with PLMS index (PLMI) equal to or more than 15 movements per hour of sleep and controls (PLMI &lt;15/h).Discussion: The negative role of PLMS in cSVD progression and related cognitive decline is expected. We suppose that patients with PLMS tend to worsen in cognitive performance more rapidly than age-, gender-, and comorbidity-matched controls. We also expect them to have more rapid white matter hyperintensities and other cSVD marker progression. The limitations of the study protocol are the short follow-up period, the absence of a treatment group, and inability to make a conclusion about causality.

Dawson Fingers in Older Adults with Cerebral Small Vessel Disease: A Population Study

2020 ◽  
Vol 83 (4) ◽  
pp. 421-425
Author(s):  
Oscar H. Del Brutto ◽  
Robertino M. Mera ◽  
Aldo F. Costa ◽  
Patricia Silva ◽  
Victor J. Del Brutto
Keyword(s):  
Older Adults ◽  
White Matter ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Subcortical White Matter ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Vessel Disease ◽  
Community Dwelling Older Adults

Dawson fingers are used to differentiate multiple sclerosis (MS) from other conditions that affect the subcortical white matter. However, there are no studies evaluating the presence of Dawson fingers in subjects with cerebral small vessel disease (cSVD). We aimed to assess prevalence and ­correlates of Dawson fingers in older adults with cSVD-related moderate-to-severe white matter hyperintensities (WMH). Community-dwelling older adults residing in rural Ecuador – identified by means of door-to-door surveys – underwent a brain MRI. Exams of individuals with cSVD-related moderate-to-severe WMH were reviewed with attention to the presence of Dawson fingers. Of 590 enrolled individuals, 172 (29%) had moderate-to-severe WMH. Of these, 18 (10.5%) had Dawson fingers. None had neurological manifestations suggestive of MS. Increasing age was independently associated with Dawson fingers (p = 0.017). Dawson fingers may be less specific for MS than previously thought. Concomitant damage of deep medullary veins may explain the presence of Dawson fingers in cSVD.

scholarly journals Neurofilament light chain predicts future dementia risk in cerebral small vessel disease

2021 ◽  
pp. jnnp-2020-325681
Author(s):  
Marco Egle ◽  
Laurence Loubiere ◽  
Aleksandra Maceski ◽  
Jens Kuhle ◽  
Nils Peters ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cognitive Decline ◽  
Small Vessel Disease ◽  
Surrogate Marker ◽  
Cerebral Small Vessel Disease ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Vessel Disease ◽  
Dementia Risk

ObjectivesSerum neurofilament light chain (NfL) has been proposed as prognostic markers in neurogenerative disease. A cross-sectional study in cerebral small vessel disease (SVD) reported an association with cognition and disability. If NfL is to be used to predict outcome, studies are required to demonstrate baseline NfL predicts future dementia risk. Furthermore, if it is to be used as a surrogate marker in clinical trials, change in NfL over time periods typical of a clinical trial must be linked to clinical progression. In a longitudinal study of patients with lacunar stroke and confluent white matter hyperintensities, we determined whether both baseline, and change, in NfL levels were linked to changes in MRI markers, cognitive decline and dementia risk.MethodsPatients underwent MRI, cognitive testing and blood taking at baseline and annually for 3 years. Clinical and cognitive follow-up continued for 5 years.ResultsNfL data were available for 113 subjects for baseline analysis, and 90 patients for the longitudinal analysis. Baseline NfL predicted cognitive decline (global cognition β=−0.335, SE=0.094, p=0.001) and risk of converting to dementia (HR=1.676 (95% CI 1.183 to 2.373), p=0.004). In contrast to imaging, there was no change in NfL values over the follow-up period.ConclusionsBaseline NfL predicts changes in MRI markers, cognitive decline and dementia rate over a 5 years follow-up period in SVD, suggesting NfL may be a useful prognostic marker. However, change in NfL values was not detected, and therefore NfL may not be a useful surrogate marker in clinical trials in SVD.

scholarly journals Cognitive heterogeneity among community-dwelling older adults with Cerebral Small Vessel Disease

2018 ◽  
Author(s):  
Ayan Dey ◽  
Vessela Stamenova ◽  
Agnes Bacopulos ◽  
Nivethika Jeyakumar ◽  
Gary R. Turner ◽  
...  
Keyword(s):  
White Matter ◽  
Subjective Experience ◽  
Small Vessel Disease ◽  
Neuropsychological Testing ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Vessel Disease ◽  
Age Related ◽  
Subjective Complaints

Some degree of ischemic injury to white matter tracts occurs naturally with age and is visible on magnetic resonance imaging as focal or confluent white matter hyperintensities (WMHs). Its relationship to cognition, however, remains unclear. To explore this, community-dwelling adults between the ages 55-80 years old completed structural imaging, neuropsychological testing, and questionnaires to provide objective measures and subjective experience of executive functioning. Volumetric lesion burden derived from structural MRI identified those with significant WMH burden (~10 cubic cm). Half of those recruited met this criterion and were designated as the cerebral small vessel disease (CSVD) group. Subjective complaints but not objective test scores differentiated adults with and without CSVD. Hierarchical clustering revealed two CSVD subgroups that differentiated those with impaired versus preserved executive function relative to controls. Overall these results provide some explanation for behavioural heterogeneity often observed in studies of age-related white matter changes. They also support the use of questionnaires to assess subjective complaints that may be able to detect subtle effects of pathology not evident on standardized cognitive scores.

Brain MRI in Monogenic Cerebral Small Vessel Diseases: A Practical Handbook

2021 ◽  
Vol 21 ◽  
Author(s):  
Leonardo Ulivi ◽  
Mirco Cosottini ◽  
Gianmichele Migaleddu ◽  
Giovanni Orlandi ◽  
Nicola Giannini ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Next Generation Sequencing ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Next Generation ◽  
Vessel Disease ◽  
Generation Sequencing ◽  
Cerebral Small Vessel Diseases

: Monogenic cerebral small vessel diseases are a topic of growing interest, as several genes responsible have been recently described and new sequencing techniques such as Next generation sequencing are available. Brain imaging is a key exam in these diseases. First, since it is often the first exam performed, an MRI is key in selecting patients for genetic testing and for interpreting Next generation sequencing reports. In addition, neuroimaging can be helpful in describing the underlying pathological mechanisms involved in cerebral small vessel disease. With this review, we aim to provide Neurologists and Stroke physicians with an up-to date overview of the current neuroimaging knowledge on monogenic small vessel diseases.

Abstract TMP119: High Homocysteine Level is not Associated With White Matter Changes, Dementia nor Mortality After Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Susanna Melkas ◽  
Sami Curtze ◽  
Gerli Sibolt ◽  
Niku K Oksala ◽  
Jukka Putaala ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Homocysteine Level ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cross Sectional ◽  
White Matter Changes ◽  
Vessel Disease

Background: Association between high homocysteine level and cerebral small-vessel disease has been implicated in cross-sectional studies, but results from longitudinal studies have been less clear. The aim of this study was to investigate whether homocysteine level at 3-months poststroke relates to the occurrence of white matter changes (WMC), the surrogate of cerebral small-vessel disease. We also investigated whether it relates to the prognosis after ischemic stroke regarding the risk of dementia at 3-months and mortality in long-term follow-up. Methods: A total of 321 consecutive acute ischemic stroke patients aged 55 to 85 were included in the study and followed up to 12 years. Plasma homocysteine level and occurrence of WMC in MRI were measured 3 months poststroke and dementia according to DSM-III was evaluated at the same time. Findings: The median homocysteine level was 13.50 μmol/l (interquartile range [IQR] 10.60-18.50 μmol/l). Total of 81 patients (25.2%) had homocysteine level above 18.50 μmol/l. In logistic regression analysis, homocysteine level above 18.50 μmol/l was not associated with severe WMC nor with dementia at 3 months poststroke. In Kaplan-Meier analysis, homocysteine level above 18.50 μmol/l was not associated with survival in 12-year follow-up. For further analysis, the group was divided in quartiles according to homocysteine level. The quartiles did not differ in occurrence of severe WMC at baseline, in the risk of dementia at 3 months, nor in the risk of mortality in 12-year follow-up. Interpretation: In our poststroke cohort homocysteine level is not associated with WMC. Further, it does not relate to impaired prognosis manifested as dementia at 3 months or mortality in 12-year follow-up.

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