Acute Lacunar Stroke Research Articles

Magnesium for Treatment of Acute Lacunar Stroke Syndromes

A prespecified interaction analysis of the neutral Intravenous Magnesium Efficacy in Stroke (IMAGES) trial revealed significant benefit from magnesium (Mg) in patients with noncortical stroke. Post hoc analysis indicated that this effect was seen in lacunar clinical syndromes (LACS), interaction P=0.005. We have now examined whether this interaction could be explained by confounding baseline factors. LACS was defined on the basis of neurological signs and did not include imaging. We investigated the interaction between baseline variables and Mg treatment on global outcome. We used logistic-regression models to test whether the Mg-LACS interaction remained significant after adjusting for stratification variables, sex, a novel stroke severity score, and baseline variables that had an interaction with treatment (P<0.1). The Mg (n=383) and placebo (n=382) groups of LACS patients were well matched on baseline factors. In addition to LACS, we found an interaction between beneficial Mg treatment effect and younger age (P=0.003), higher baseline diastolic blood pressure (P=0.02), higher mean blood pressure (P=0.02), and absence of ischemic heart disease (P=0.07). Even so, the adjusted Mg-LACS interaction remained significant (odds ratio [OR] 0.57; 95% CI, 0.39 to 0.83; P=0.003). In the LACS subgroup, Mg improved Barthel Index <95 (OR 0.73; 95% CI, 0.55 to 0.98), modified Rankin Scale >1 (OR 0.67; 95% CI, 0.50 to 0.91), and global outcome (OR 0.70; 95% CI, 0.53 to 0.92) but not Barthel Index <60 or mortality. The positive treatment effect of Mg in LACS cannot be ascribed to general issues of severity, time to treatment, blood pressure, or other baseline factors; equally, this finding may be due to chance. A large trial of Mg treatment in LACS appears justified.

Right-to-left shunt and lacunar stroke in patients without hypertension and diabetes

We analyzed the frequency of cardiac embolic sources in 62 patients with acute lacunar stroke vs 50 controls. In post hoc analysis, 11 patients with lacunar stroke having neither hypertension nor diabetes mellitus (non-HDM group) had a higher frequency of right-to-left shunt (RLS) (82%) than patients with risk factors for lacunar stroke. RLS was also independently associated with the non-HDM group. Thus, RLS may contribute to lacunar stroke in patients without risk factors for lacunar stroke.

Subtle Cognitive Deficits in Acute Lacunar Stroke

Cognitive impairment, ranging up to and including dementia, is a known consequence of recurring lacunar strokes. However, the prevalence of subtle

Cognitive impairments in acute lacunar stroke

The present study investigated the prevalence of cognitive deficits in acute lacunar stroke, validated the Mini Mental State Examination (MMSE) in detecting cognitive impairments in lacunar patients, and identified predictors of such deficits. Seventy-one patients with lacunar stroke performed a comprehensive cognitive screening between day 2 and day 7 of their stay. The test battery included Trail Making Test A, Verbal Fluency, Object Learning Test, Ullevål Aphasia Screening, and Assessment of Stroke and other Brain Damage regarding motor apraxia, rational apraxia and visuospatial ability. Exactly 57.7% scored outside cutoff in at least one of the cognitive tests. Using a rigorous cutoff for MMSE (28/29 points) and the test battery as comparison, the sensitivity and specificity of MMSE were 0.69 and 0.67, respectively. Only male sex was significantly related to the presence of cognitive deficits (pathologic score on at least one of the tests--odds ratio 4.41, 95% confidence interval 1.45-13.43). Many lacunar stroke patients suffer cognitive problems. Male patients are at particular risk. MMSE failed to identify 30% of the patients diagnosed with cognitive deficits, and we suggest that lacunar stroke patients be offered a comprehensive cognitive screening, even when MMSE is normal.

Dynamic Cerebral Autoregulation in Acute Lacunar and Middle Cerebral Artery Territory Ischemic Stroke

We addressed whether dynamic cerebral autoregulation (dCA) is affected in middle cerebral artery (MCA) territory (MCAS) and lacunar ischemic stroke (LS). Blood pressure (MAP) and MCA velocity (V) were measured in 10 patients with large MCAS (National Institutes of Health Stroke score, 17+/-2; mean+/-SEM), in 10 with LS (score, 9+/-1), and in 10 reference subjects. dCA was evaluated in time (delay of the MCA Vmean counter-regulation during changes in MAP) and frequency domains (cross-spectral MCA Vmean-to-MAP phase lead). In reference subjects, latencies for MAP increments (5.3+/-0.5 seconds) and decrements (5.6+/-0.5 seconds) were comparable, and low frequency MCA Vmean-to-MAP phase lead was 56+/-5 and 59+/-5 degrees (left and right hemisphere). In MCAS, these latencies were 4.6+/-0.7 and 5.6+/-0.5 seconds in the nonischemic hemisphere and not detectable in the ischemic hemisphere. In the unaffected hemisphere, phase lead was 61+/-6 degrees versus 26+/-6 degrees on the ischemic side (P<0.05). In LS, no latency and smaller phase lead bilaterally (32+/-6 and 33+/-5 degrees) conformed to globally impaired dCA. In large MCAS infarcts, dynamic cerebral autoregulation was impaired in the affected hemisphere. In LS, dynamic cerebral autoregulation was impaired bilaterally, a finding consistent with the hypothesis of bilateral small vessel disease in patients with lacunar infarcts.

Clinical significance of detection of multiple acute brain infarcts on diffusion weighted magnetic resonance imaging

Background: Detection of multiple acute brain infarcts (MABI) by diffusion weighted magnetic resonance imaging (DWI) may provide information about stroke mechanism in (1) acute lacunar stroke, where evidence of MABI...

Progression in Lacunar Stroke Is Related to Elevated Acute Phase Parameters

Background and Purpose: Despite the small size of lacunar infarcts, progression of neurological deficits is a common problem in this stroke subtype. This investigation studied the frequency and the course of neurological deterioration as well as predictors and possible underlying pathomechanisms of early progression in lacunar stroke. Methods: Fourty-six consecutive patients with acute lacunar stroke were prospectively evaluated by daily clinical neurological examination including the National Institutes of Health Stroke Scale (NIHSS) and follow-up using the Barthel Index after 3 months. Progressive neurological deficit was defined as worsening by ≧1 point in the NIHSS for motor function. Progressive and stable patients were compared regarding clinical profile, inflammatory parameters (leukocytes, body temperature, C-reactive protein), coagulation parameters (fibrinogen, D-dimer, vWF, PTT), and glutamate plasma concentration, as well as blood glucose and blood pressure. Results: Eleven patients (23.9%) showed progression of stroke symptoms, 9 of these within the first 24 h after admission. The score on the NIHSS on admission was similar in patients with progressive stroke and stable patients, but significantly higher in the progressive stroke group on days 2 (p = 0.01), 3 (p = 0.001) and at discharge (p = 0.003). Deterioration was significantly associated with a higher leukocyte count (p = 0.012), higher body temperature (p = 0.031) and a higher fibrinogen concentration (p = 0.046) on admission. Barthel Index at discharge (p = 0.001) and after 90 days (p < 0.001) was significantly worse in the progressive stroke group. Conclusions: Progression in lacunar stroke usually occurs within 24 h and may be related to an acute-phase response. The long-term prognosis of progressive stroke patients is persistently worse compared with patients with nonprogressive stroke.

Inflammation-mediated damage in progressing lacunar infarctions: a potential therapeutic target.

The mechanisms underlying neurological deterioration in patients with lacunar infarction are not completely understood. In this study, we sought to investigate the role of proinflammatory molecules in the early worsening and outcome of acute lacunar stroke. We performed a secondary analysis of 113 consecutive patients with lacunar infarction included within the first 24 hours of the onset of symptoms in a previous study aimed at investigating clinical and biochemical factors of early neurological deterioration (END). END was defined as a fall of > or =1 points in the motor items of Canadian Stroke Scale between inclusion and 48 hours. Poor outcome at 3 months was considered death or Barthel Index <85. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and intercellular adhesion molecule-1 (ICAM-1) were determined by enzyme-linked immunoabsorbent assay in blood samples obtained on admission. END was recorded in 27 patients (23.9%); poor outcome was noted in 26 (23%). Median (quartiles) concentrations in plasma of TNF-alpha [16.5 pg/mL (13.7 and 21.2 pg/mL) versus 7.5 pg/mL (6.2 and 9.0 pg/mL)], IL-6 [28.8 pg/mL (22.5 and 35.7 pg/mL) versus 11.5 pg/mL (8.5 and 16.2 pg/mL)], and ICAM-1 [285 pg/mL (219 and 315 pg/mL) versus 158 pg/mL (137 and 187 pg/mL)] were significantly higher in patients who had END than in those with nonprogressing strokes (P< 0.001). Significant differences were also observed between patients with poor and good outcome at 3 months. Logistic regression analysis after adjustment for potential confounders showed that TNF-alpha >14 pg/mL and ICAM-1 >208 pg/mL were independently associated with both END (OR, 511; 95% CI, 17 to 4937; P<0.001; and OR, 315; 95% CI, 17 to 5748; P< 0.001, respectively) and poor outcome at 3 months (OR, 3.0; 95% CI, 1.0 to 8.5; P=0.042; and OR, 4.2; 95% CI, 1.3 to 13.6; P<0.015, respectively). High concentrations of inflammatory markers in blood are associated with END and poor functional outcome in lacunar infarctions. These findings suggest that inflammation contributes to brain injury in lacunar stroke.

Predictors of Progression in Lacunar Stroke

P47 Objective: To identify predictors of deterioration in patients with lacunar syndromes. Methods: We prospectively evaluated 46 consecutive patients (12 women, 34 men; age 64.5 ± 13.7 yrs. [ mean ± SD ] ) with acute lacunar stroke by daily clinical neurological examination including NIHSS and follow-up using the Barthel Index after 3 months. In addition, we determined parameters of inflammation ( C-reactive protein, leukocytes, body temperature), coagulation (d-dimers, fibrinogen, PTT, vWF ), glutamate, as well as blood glucose and blood pressure. Progressive neurological deficit was defined as worsening of the NIHSS by 1 point in one singular item. Results: Eleven patients (23.9 % ) showed a clinical progression of stroke symptoms, 35 patients remained stable or improved. The NIHSS on admission was similar in both groups (4.2 ±2.7 vs. 3.8 ±2.2), but significantly higher in progressive patients on day 2 (5.4 ±3.5 vs. 2.6 ±2.0; p=0.02) and at discharge (3.7 ±3.3 vs. 1.6 ±1.7; p=0.046). Nine of the 11 progressive patients showed deterioration in the first 24 hours after admission. Barthel Index after 90 days was significantly lower in the progressive patients (87 ±18 vs. 95 ±19; p=0.005). Clinical progression was significantly associated with elevated body temperature (p=0.031 ), fibrinogen ( p=0.048 ) and a higher leucocyte count ( p=0.017 ) on admission. Mean blood glucose and blood pressure were also higher in progressive patients, but this difference did not reach the level of significance. There was no significant correlation for the other coagulation parameters, glutamate level on admission, risk factors, age and gender. Conclusions: In lacunar stroke there is a high rate (= 23.9 % ) of neurological worsening, and the long-term prognosis of progressive patients is worse compared to non-progressive patients. Progression usually occurs within 24 hours and may be related to an acute-phase response.

Predictors of Progression in Lacunar Stroke

P47 Objective: To identify predictors of deterioration in patients with lacunar syndromes. Methods: We prospectively evaluated 46 consecutive patients (12 women, 34 men; age 64.5 ± 13.7 yrs. [ mean ± SD ] ) with acute lacunar stroke by daily clinical neurological examination including NIHSS and follow-up using the Barthel Index after 3 months. In addition, we determined parameters of inflammation ( C-reactive protein, leukocytes, body temperature), coagulation (d-dimers, fibrinogen, PTT, vWF ), glutamate, as well as blood glucose and blood pressure. Progressive neurological deficit was defined as worsening of the NIHSS by 1 point in one singular item. Results: Eleven patients (23.9 % ) showed a clinical progression of stroke symptoms, 35 patients remained stable or improved. The NIHSS on admission was similar in both groups (4.2 ±2.7 vs. 3.8 ±2.2), but significantly higher in progressive patients on day 2 (5.4 ±3.5 vs. 2.6 ±2.0; p=0.02) and at discharge (3.7 ±3.3 vs. 1.6 ±1.7; p=0.046). Nine of the 11 progressive patients showed deterioration in the first 24 hours after admission. Barthel Index after 90 days was significantly lower in the progressive patients (87 ±18 vs. 95 ±19; p=0.005). Clinical progression was significantly associated with elevated body temperature (p=0.031 ), fibrinogen ( p=0.048 ) and a higher leucocyte count ( p=0.017 ) on admission. Mean blood glucose and blood pressure were also higher in progressive patients, but this difference did not reach the level of significance. There was no significant correlation for the other coagulation parameters, glutamate level on admission, risk factors, age and gender. Conclusions: In lacunar stroke there is a high rate (= 23.9 % ) of neurological worsening, and the long-term prognosis of progressive patients is worse compared to non-progressive patients. Progression usually occurs within 24 hours and may be related to an acute-phase response.

Cutaneous reflexes in patients with acute lacunar infarctions.

Cutaneous reflex (CR) was measured in 15 patients with acute lacunar stroke and in 15 age- and sex-matched normal subjects. EMG activities were recorded from the first dorsal interosseous muscle with surface electrodes, rectified and averaged. Intensity of the stimulation on the index finger was four times the sensory threshold. Aided by audio- and visual-feedback monitoring, the subjects abducted the index finger. Side-to-side comparison was made on all the subjects. CR abnormalities were found in all of our patients. The early inhibitory (I1) and second excitatory (E2) components were attenuated in 11 of 15 patients. The I1-E2 interpeak amplitude (A2) was significantly reduced in all the patients. Prolonged latency of I1-E2 components was found to be pronounced in six of eight patients with sensory symptoms. Eight patients were followed up 1 month later. By that time, the abnormal CR had reversed to some degree in all of them. CR alternation was still present in two fully recovered patients. Our results implied a thalamic relay in the afferent limb of the CR. CR could be a valuable adjunct for assessing long tract dysfunction and monitoring functional recovery.

3-16-07 Long latency reflex following median nerve stimulation in patients with acute lacunar stroke

3-16-07 Long latency reflex following median nerve stimulation in patients with acute lacunar stroke

Acute Lacunar Stroke in Association With Angiogram-Negative Subarachnoid Hemorrhage

Although there is much speculation regarding the source of bleeding in patients with subarachnoid hemorrhage when no angiographic abnormality is found, little direct evidence has been obtained to document a cause. We report two cases of stroke in the distribution of a perforating or lenticulostriate artery occurring at the time of angiogram-negative subarachnoid hemorrhage. A 68- and a 60-year-old man each presented with acute onset of headache and meningismus. Computed tomography (CT) revealed subarachnoid hemorrhage in a perimesencephalic pattern and in the left sylvian fissure, respectively. In both instances, immediate CT revealed evidence of an early infarction in the distribution of a perforating artery originating at the site of the subarachnoid blood. Both of these strokes were demonstrated to be acute by evolution on serial imaging studies. No source for the subarachnoid blood could be found in either patient in cerebral angiograms repeated at 2 weeks. These observations suggest that in some cases of angiogram-negative subarachnoid hemorrhage the source of blood may be a small artery that is obliterated at the time of hemorrhage. This observation provides an explanation for the low rate of rehemorrhage among patients with angiogram-negative subarachnoid hemorrhage.

Plasma concentrations of atrial natriuretic peptide in cardioembolic stroke with atrial fibrillation.

The aim of the present study was to determine whether the level of plasma atrial natriuretic peptide (ANP), an indicator of atrial stretching, correlates with the formation of a thrombus in the left atrium during cardioembolic stroke with atrial fibrillation. Plasma concentrations of immunoreactive ANP and thrombin-antithrombin III complex (TAT) were measured in five age-matched groups including: 16 patients with acute cardioembolic stroke and atrial fibrillation (group 1), 26 patients with chronic cardioembolic stroke and atrial fibrillation (group 2), 27 patients with atrial fibrillation without previous stroke (group 3), 21 patients with acute lacunar stroke (group 4), and 27 healthy controls. The plasma ANP levels were higher in group 1, regardless of the stage, than those estimated at chronic stage in group 4 and in healthy controls. There were no stage-related differences between groups 1, 2 and 3. Plasma levels of ANP in group 2, a high risk group of cardioembolic stroke, were higher than in group 3, a low risk group. There was no correlation between plasma levels of ANP and mean blood pressure, pulse rate or plasma levels of TAT in any group. These results indicate that the determination of plasma ANP concentration is useful to distinguish a high risk patient from a low risk patient and also a cardioembolic stroke patient from a lacunar stroke patient. They also underscore the difficulties in recognizing left atrial thrombus formation by determining the plasma ANP concentration in cardioembolic stroke.