Clinical Lacunar Syndromes Research Articles

Role of Computed Tomography Perfusion in Identification of Acute Lacunar Stroke Syndromes.

Lacunar syndromes correlate with a lacunar stroke on imaging in 50% to 60% of cases. Computed tomography perfusion (CTP) is becoming the preferred imaging modality for acute stroke triage. We aimed to estimate the sensitivity, specificity, and predictive values for noncontrast computed tomography and CTP in lacunar syndromes, and for cortical, subcortical, and posterior fossa regions. A retrospective analysis of confirmed ischemic stroke patients who underwent acute CTP and follow-up magnetic resonance imaging between 2010 and 2018 was performed. Brain noncontrast computed tomography and CTP were assessed independently by 2 stroke neurologists. Receiver operating characteristic curve analysis was performed to estimate sensitivity, specificity, and area under the curve (AUC) for the detection of strokes in patients with lacunar syndromes using different CTP maps. We found 106 clinical lacunar syndromes, but on diffusion-weighted imaging, these consisted of 59 lacunar, 33 cortical, and 14 posterior fossa strokes. The discrimination of ischemia identification was very poor using noncontrast computed tomography in all 3 regions, but good for cortical (AUC, 0.82) and poor for subcortical and posterior regions (AUCs, 0.55 and 0.66) using automated core-penumbra maps. The addition of delay time and mean transient time maps substantially increased subcortical (AUC, 0.80) and slightly posterior stroke detection (AUC, 0.69). Analysis of mean transient time and delay time maps in combination with core-penumbra maps improves detection of subcortical and posterior strokes.

Lacunar syndromes: Are they all equally benign?

AbstractBackgroundThere is a paucity of prognostic data following clinical lacunar syndromes, particularly comparisons between the various lacunar syndromes.AimsTo compare the outcomes, disability at discharge, at 1 and 3 months, use of rehabilitation facilities and duration to return to work/daily activities, between patients with various clinical lacunar syndromes.MethodsIschemic stroke patients with clinical lacunar syndromes were prospectively recruited. Functional outcomes were measured by the modified Rankin Scale (mRS), with unfavorable outcome defined as mRS > 1. Use of rehabilitation facilities and duration to return to work/ daily activities was also ascertained. Logistic regression analyses were performed to determine predictors of outcome measures.ResultsOf the 192 ischemic stroke patients (mean age 62 ± 11 years) with clinical lacunar syndromes, 72(37%) patients had ataxic hemiparesis, 53(28%) patients had pure motor syndrome, 41(21%) had sensorimotor syndrome, 17(9%) had pure sensory syndrome, and 9(5%) had clumsy hand dysarthria syndrome. Compared to pure sensory strokes, patients with pure motor syndrome (OR 7.72 CI 1.5‐38), sensorimotor syndrome (OR 6.06, CI 1.18‐31), and ataxic hemiparesis (OR 18.1 CI 3.79‐91) were more likely to have unfavorable outcome at 1 month, but there was no difference at 3 months. There was no independent association between specific lacunar syndromes with use of rehabilitation facilities and duration to return to work/ daily activities.ConclusionsNearly 1/3 of patients with clinical lacunar syndromes have unfavorable 3‐month functional outcome. There were differences in the functional status at discharge between clinical lacunar syndromes, but not for other outcomes.

Abstract 124: How to Preselect Stroke Patients for Enhanced ECG-Monitoring - Evaluation of Predictors of Paroxysmal Atrial Fibrillation in "Find-AFrandomised"

Background: Detecting concealed paroxysmal atrial fibrillation (pAF) is a major focus of the workup of ischemic-stroke-patients, but requires elaborate ECG-monitoring. We aimed to evaluate pre-specified predictors to determine stroke patients with an increased probability of underlying pAF. We applied cut-off-levels recently suggested by the German Stroke Society 1 . Methods: The Find-AF RANDOMISED -trial (NCT01855035) evaluated 3x10-day Holter-ECG vs. standard-care in 398 patients > 60 years with acute ischemic strokes. The primary endpoint was novel pAF after 6 months. 27 patients in the intervention arm (13.5 %) and 9 patients in the control arm (9.0 %) met the primary endpoint (p=0.002). We used Pearson’s Chi 2 -test and the Mann-Whitney-U-test, as applicable. In variables with p<0.05 we calculated the number-needed-to-screen (NNS). We also performed ROC-analyses to determine the areas-under-the-curve (AUC). Results: Table 1 shows known pAF-risk-factors in relation to whether patients had pAF. The absence of a clinical lacunar syndrome (p=0.007) or lacunar lesions (p=0.018), increased NIHSS-Score (p=0.003), frequent atrial premature beats (APB, p=0.003), prolonged supraventricular runs (p=0.01), enlarged left atria (p=0.07) and increased brain-natriuretic-peptide-levels (p=0.001) were associated with underlying pAF. Frequent APB differentiated best between those with and without pAF (area under the curve, AUC: 0.71). Conclusions: Several of the evaluated markers are useful to preselect stroke patients for enhanced ECG-monitoring. APB and comprehensive measures of both left atrial size and function (LAVI/a’) showed the highest AUC and should be used when preselecting stroke patients for prolonged ECG-monitoring.

Movement Disorders Syndromes Associated With Lacunar Infarcts, Clinical Case Series

Lacunar infarcts are small (<15 mm diameter) subcortical infarcts that results from occlusion of a single penetrating artery. Lacunar infarcts are associated with clinical lacunar syndromes, one of lacunar syndromes is movement disorders syndrome such as chore, dystonia, hemibolismus and asterixis. Several types of movement disorders have been described with small, deep infarct, majority of these syndrome is caused by penetrating small- artery disease. The movement disorder may appear as the only sign of the infarct or may develop later, after an initial syndrome, different in character, has resolved.Hemichorea – hemiballismus is the most common of movement disorder due to lacunar infarcts.The lacunar size infarcts found in different parts of the striatum including in head of the caudate nucleus and adjacent corona radiate, the subthalamic and the thalamus. The onset is typically abrupt and is usually- unaccompanied by other complaints. The chorea usually involves the forearm, hand, and fingers. In some cases, chorea has been delayed by some weeks or months after the initial occurrence of hemiparesis. Dystonia: Two types of dystonia have been described in cases of lacunes, action- induced and focal dystonia.Case I- in a 63 year old woman with lacunar stroke, with abrupt onset of chorea, chorea involves the foream, hand, and fingers, it was accompanied by hemiparesis that faded within 3 months even though the chorea persisted unchanged.Case II- In a 75 years old man chorea was delayed by some weeks after initial occurrence of hemiparesis due to lacunar infarct.Case III- in a 81 years old woman lacunar infarct, whose putaminal lesions was documented by CT scan, suffer choreic movements of the distal parts of the arm and leg that interfered with normal activity and prevented easy walking for more than a weeks, the examination revealed normal strength, sensation and reflexes.Case IV- A 69 years old man , with lacunar infarct in adjacent corona radiate with action – induced dystonia in the left hand. The finger of the affected hand become flexed in to the palm, leaving only the Thumb free, strength of hand was normal . Activity exacerbated the movements. The left hand and forearm showed involuntary movements that produced an unusual posture.

Abstract TP63: Lacunarization After Endovascular Treatment: a Surrogate Marker of Good Functional Outcome

Introduction: Multiple randomized trials have demonstrated that endovascular treatment (EVT) in selected stroke patients is associated with good clinical outcome (90 days mRankin 0-2: 44-60%). However the percentage of good functional outcome could be improved if we consider patients without cortical clinical impairment with presentation of classical lacunar syndrome despite non-lacunar radiological infarct. Methods: Consecutive patients with ischemic stroke who received endovascular reperfusion were retrospectively analyzed between May 2010 and April 2015. On admission NCCT (non-contrast CT) and CTASI (CT Angiography Source Image) were performed in stroke patients according to our hospital guidelines. We independently applied the ASPECT score in all baselines NCCT, CTASI and follow-up NCCT 24H, and magnetic resonance (MR) during hospitalization. Five pure clinical lacunar syndromes (CLS) were recorded within 24h exam after EVT in our stroke unit and 90 days follow-up Results: We review 428 thrombectomies of patients with acute ischemic stroke. Ninety-five percent of occlusions were located in middle cerebral artery or terminal internal carotid, (49% women, mean age 65+/-13 years; NIHSS at admission: 17; baseline mRS 0-1:96%). Successful recanalization (TICI 2b-3) was achieved in 81%. At 3 months good functional outcome (mRS 0-2) was seen in 51% and death occurred in 13%. CLS were indentified in 42% patients within 24h after EVT. This clinical syndromes were associated to ASPECT score in 24 NCCT and CTASI in patients with recanalization 2b-3 (p:0.003), but only 4% had a defined radiological lacunar stroke on MR. CLS turned out to be one of independence predictors of good outcomes (Rankin 0-2 at 90d) after adjustment for ages, sex and baseline NIHSS scores (OR 1.85; CI:1.4-3.1; p:0.001). Also CLS were still present in 34% of patients with Rankin>2 at 90d (Rankin 3:26%; Rankin 4:7%) Conclusions: These results suggest that a neurological exam 24h after EVT with identification of pure lacunar syndrome can predict favorable functional outcome at 90days. This group of patients presents radiological findings with an unusual location and size with regard to CLS. We suggest to consider patients with CLS as good outcome after EVT regardless 90d mRankin>2.

Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease.

Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI’s potential as surrogate marker for SVD.

Pathology of Lacunar Ischemic Stroke in Humans—A Systematic Review

Twenty-five percent of ischemic strokes are lacunar in type, but the cause remains unclear. Pathological descriptions of lacunar lesions are available but have not been systematically assessed. We therefore systematically summarized studies describing lacunar lesions by extracting data on the number of patients and lesions, clinical details, pathological methods, brain regions and/or vessels examined, and both parenchymal and vascular findings. Among 39 papers describing >4000 lesions (>50% from one study), 15 papers examined patients with a clinical lacunar syndrome. Terminology varied, many studies only reported macroscopic pathology and many lesions were cavitated (ie, old). Aside from symptomatic lesions occurring more often in the internal capsule or caudate nucleus, we found no other differences between symptomatic and asymptomatic patients. Perivascular edema and thickening, inflammation and disintegration of the arteriolar wall were common, whereas vessel occlusion was rare. The causal mechanisms of lacunar stroke remain poorly defined because of methodological inconsistencies and challenges. Standardised pathological definitions based on well-characterized post-mortem derived material supported by detailed clinical and imaging data are needed.

Safety of Intravenous Fibrinolysis in Imaging-Confirmed Single Penetrator Artery Infarcts

Hemorrhagic transformation (HT) after fibrinolytic therapy may be less common in patients with acute cerebral ischemia confined to single penetrator artery (SPA) territories than in patients with large artery ischemia. Previous investigations of HT diagnosed small vessel ischemia based on lacunar clinical syndromes, an approach known to yield misdiagnosis in one-third to one-half of cases. Consecutive intravenous tissue plasminogen activator-treated patients in a prospectively maintained hospital registry were analyzed. Patients were classified as having SPA ischemia if they had imaging evidence of: (1) deep location; (2) diameter ≤ 1.5 cm; and (3) distribution in a single penetrator territory, regardless of presenting clinical syndrome. Lacunar clinical syndrome was defined according to the Oxfordshire Community Stroke Project classification. Among 93 intravenous tissue plasminogen activator-treated patients, mean age was 71.5, 62.4% were female, and median pretreatment National Institutes of Health Stroke Scale score was 14. Single penetrator artery ischemia was imaged in 13 (14.0%) and large artery ischemia was imaged in 75 (80.6%), with no visualized ischemic injury in 5 (5.4%). Lacunar clinical syndromes were present in 23 (24.7%), including 10 with SPA ischemia and 9 with large artery ischemia. No patient with imaging-confirmed SPA infarcts experienced any hemorrhagic transformation, whereas any radiological HT occurred in 29.3% of large artery infarcts (P=0.03). Symptomatic intracerebral hemorrhage occurred in 0% of SPA infarcts vs 4.0% of large artery infarcts. HT after lytic therapy in imaging-confirmed SPA infarcts is uncommon. Imaging demonstration of ischemia confined to SPA territory better-identifies this population at low risk for hemorrhagic complications than clinical lacunar syndromes.

Chronic Information-processing Changes in Individuals With a First-ever Clinical Lacunar Syndrome

The aim of this study was to examine whether chronic cognitive changes occur after a first-ever single clinical lacunar syndrome. Patients who have been diagnosed with a first-ever single clinical lacunar syndrome, on the basis of clinical rather than radiologic criteria, perform normally on general clinical neuropsychologic measures. We examined information-processing abilities in 17 first-ever lacunar syndrome participants [lacunar anterior circulation infarct (LACI)], using 2 experimental tasks of information processing. At a group level, LACI participants were significantly impaired relative to stroke-free controls. Specifically, LACI participants had a reduced ability to process information under conditions of increasing attentional demand; this deficit was not caused by a fundamental impairment in speed of information processing. The current findings represent the first evidence of chronically impaired cognition in individuals who have suffered a single clinical lacunar syndrome event, but have no history of other clinical stroke.

Individuals with first‐ever clinical presentation of a lacunar infarction syndrome: Is there an increased likelihood of developing mild cognitive impairment in the first 12 months after stroke?

Patients who have suffered a single clinical lacunar syndrome, in the absence of any previous clinical stroke, have a varying neuroradiological profile. We examined general cognition in 30 nonaphasic first-ever lacunar syndrome participants, using a battery of standard clinical neuropsychological measures. At a group level, stroke participants did not demonstrate any cognitive impairment relative to well-matched community-based controls up to 12 months after stroke. There was also no evidence of increased frequencies of mild cognitive impairment after a single clinical lacunar syndrome relative to matched control participants within the first year post-stroke. The current findings represent the first investigation of the cognitive outcome of nonaphasic individuals who have a first-ever clinical lacunar syndrome. It was concluded that a clinically diagnosed first ever stroke event, presenting as a lacunar syndrome, was not associated with an elevated risk of developing mild cognitive impairment 12 months post-stroke.

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Tissue Plasminogen Activator −7351C/T Polymorphism and Lacunar Stroke

To the Editor: Jannes et al1 reported that a polymorphism in the tissue plasminogen activator (tPA) gene (−7351C/T) was associated with ischemic stroke in an Australian population. Stratification for stroke subtype demonstrated an association with lacunar infarction (OR: 2.7; 95% CI, 1.1 to 6.7), but not with other stroke subtypes. The authors interpreted this result as providing evidence that fibrinolytic factors play an important role in maintaining small vessel patency. The polymorphism is located within the binding site for the transcription factor Sp1, in the enhancer region of the tPA gene,1 and the TT genotype has been associated with significantly reduced vascular tPA release rates.2 This association could give clues to the pathogenesis of lacunar stroke, but first replication in independent populations is important, particularly because the original association was found in a small sample size, with only 43 patients in the lacunar subgroup. Therefore, we attempted to replicate it in a prospectively collected group of patients with well-phenotyped lacunar stroke. In addition, we determined whether the polymorphism predisposed to 1 particular type of lacunar stroke. It has been suggested that patients with larger lacunar infarcts (isolated lacunar infarction [ILI]) without leukoaraiosis may have microatheroma at the origins and proximal portions of the perforating arteries. In contrast, patients with lacunar infarction and confluent leukoaraiosis (ischemic leukoaraiosis [ILA]) may have a diffuse arteriopathy affecting the smaller perforating vessels.3 Previous studies have suggested different genetic associations in the 2 groups.4 Three hundred …

SUBCORTICAL STROKE, 2NDEDITION

SUBCORTICAL STROKE, 2nd edition Edited by Geoffrey Donnan, Bo Norrving, John Bamford and Julien Bogousslavsky 2002. Oxford: Oxford University Press Price £79.50. pp. 364. ISBN 0‐19‐263157 This is the second edition of Subcortical Stroke which testifies to the contribution this book has made in attempting to clarify this complex issue. It is excellent. Subcortical stroke is the subject of much confusion—some regard this term as synonymous with lacunar stroke, which it most definitely is not. The first edition was in fact called Lacunar and Other Subcortical Infarctions . The new title is more all embracing and without preconceptions. Lacunar stroke has been a helpful concept but in my view it is heaped in so much confusion that the term is better avoided. To the clinician, it should describe specific clinical syndromes: it does not mean a mild or small stroke, the deficit can be severe. For the radiologist, although the advent of MRI has greatly helped our understanding of clinical lacunar syndromes, MRI has unfortunately led to abuse of the term lacunar stroke to describe virtually any small non‐cortical stroke. To the pathologist, there are specific features often involving a single penetrating artery with lipohyalinosis causing a small area of infarction: in less than 5% it may be haemorrhagic. Because the term lacunar has been used to mean different things to different specialists, it is better avoided or best reserved for the precise pathological lesion, and the term subcortical stroke or small deep infarction or haemorrhage used as these are purely anatomical and descriptive and without preconceived prejudices. The terms subcortical stroke or small deep infarction then allow one to consider the pathology and pathogenesis in the same way one thinks of cortical stroke. The book starts with a historical …

Clinical lacunar syndromes as predictors of lacunar infarcts. A comparison of acute clinical lacunar syndromes and findings on diffusion-weighted MRI.

To evaluate if patients with acute lacunar syndromes have acute lacunar infarcts or other types of cerebral lesions on diffusion-weighted MRI. Patients with acute lacunar syndromes underwent echo-planar diffusion MRI of the brain within 3 days after stroke onset. Localization and size of lesions with hyperintense signal were determined, compared with clinical characteristics and with findings on follow-up T2-weighted MRI. Twenty-three patients participated in the study. Thirteen patients had pure motor stroke, 1 pure sensory stroke, 8 sensorimotor stroke, and 1 ataxic hemiparesis. Twenty-two patients had at least one lesion with increased signal on diffusion-weighted MR images. These acute lesions were in the internal capsule/ basal ganglia/thalamus in 13 patients, subcortical white matter in 5 patients, brainstem in 2 patients, cortex (multiple small lesions) in 1 patient, and cortex + basal ganglia in 1 patient. The median volume of the lesions was 0.6 ml on the initial examination and on follow-up, of 17 patients after 1 to 5 months, 0.5 ml. Almost all patients with acute ischemic lacunar syndromes have acute lesions on echo-planar diffusion-weighted MRI within 3 days after stroke onset. These lesions are mostly small and subcortical, compatible with lacunar infarcts caused by single penetrating artery occlusion, but in a minor proportion of patients (2 of 23 in our study) a cortical involvement is found.

Predictive value of clinical lacunar syndromes for lacunar infarcts on magnetic resonance brain imaging.

We prospectively investigated the predictive value of clinical and CT-supported lacunar syndromes for lacunar infarcts on magnetic resonance (MR) brain imaging. The 54 prospective, consecutive patients had clinical lacunar syndromes of acute onset and early computed tomography (CT; on admission day, i.e. < or =48 h after onset of symptoms) showing either a small deep infarct or no corresponding lesion. Taking MR (at day 2 to 4 after admission) as the gold standard, the positive predictive value of the CT-supported clinical syndrome for corresponding lacunar lesions was calculated. In 27 (50%) patients, early CT showed a lacunar infarct corresponding to the clinical syndrome, a further 27 (50%) patients had no fresh ischemic lesion. In 51 patients (94%), MR showed a recent lacunar infarct (hyperintense lacune in T2-weighted scans, no demarcation on T1-weighted scans and/or positive gadolinium-enhancement) corresponding to the clinical syndrome (positive predictive value 0.94, 95%, CI: 0.88 to 0.98). In 3 (6%) patients MR was normal. Aside from old unrelated ischemic (macro- and/or microangiopathic) lesions, MR revealed no acute non-lacunar infarct. CT and MR sites of lacunar lesions were matching. Compared to gold standard MR, the sensitivity of early CT for suspected lacunar lesions was 0.53 (95% CI: 0.38 to 0.67). Lacunar syndromes were highly predictive for small deep infarcts on MR. Magnetic resonance brain imaging may be redundant in the setting of a lacunar syndrome supported by a CT that excludes non-ischemic causes of stroke; it may therefore be abandoned in order to reduce costs in the health care system.

Lacunar stroke. A reassessment.

Lacunae are small, deep cerebral infarcts known to occur in hypertensive patients. Although frequently asymptomatic, they sometimes produce characteristic clinical syndromes. Postmortem studies have implicated small-vessel disease in their pathogenesis, and, as a result, conservative management has been advocated. Computed tomography (CT) has provided new insights into the spectrum of lacunar disease. Review of recently acquired information suggests modifications of the approach to these patients. The clinical lacunar syndromes, though nonspecific, do suggest lacunar infarction. In hypertensive patients with these syndromes and CT confirmation of lacunar infarction, a conservative diagnostic posture coupled with medical management of risk factors continues to be indicated.

Computed tomography in patients presenting with lacunar syndromes.

Of 312 stroke patients who had a CT scan, 37 had presented clinically with a lacunar syndrome. In 18 of the 37, lacunar sized infarcts were demonstrated on the scan, 13 had normal scans and in 6 large infarcts were found. Of these 6.5 and a pure motor hemiplegia and one a pure sensory stroke. Clinical evidence and angiography revealed a potential and treatable source of emboli in both the lacunar sized and the large infarcts. Two conclusions are drawn: a clinical lacunar syndrome may be associated with large infarct; demonstration of a lacunar infarct on CT scan does not exclude the need for angiography in appropriate cases to discover a possible source of emboli.