Monocyte count is an underlying marker of lacunar subtype of hypertensive small vessel disease

Background:  In the hypertensive small vessel disease (HSVD), it remains unclear why some patients develop lacunar infarcts (LIs) whilst others develop deep intracerebral hemorrhages (dICHs). Inflammation might be related to LI, and leukocyte and monocyte counts are regarded as an inflammatory marker of ischemic stroke.
Objective:  We investigated the relationship between leukocyte and monocyte counts determined in the first 24 h after stroke onset in HSVD patients.
Methods:  We prospectively studied 236 patients with first acute stroke because of HSVD (129 LI and 107 dICH). We analyzed demographic data, vascular risk factors, and white blood cell count subtypes obtained in the first 24 h after stroke.
Results:  The multivariate analysis showed that LI subtype of HSVD was correlated with hyperlipidemia ( P  <   0.0001), a higher monocyte count ( P  =   0.002), and showed a trend with current smoking ( P  =   0.051), whereas dICH subtype was correlated with low serum total cholesterol ( P  =   0.003), low serum triglycerides ( P  <   0.0001), and high neutrophil count ( P  =   0.050).
Conclusions:  In patients who developed HSVD-related stroke, high monocyte count, current smoking, and hyperlipidemia are prothrombotic factors related to LI, whereas low cholesterol and triglyceride values are related to dICH. Monocyte count might be an inflammatory risk marker for the occlusion of small vessels in hypertensive patients.     

Higher severity of frontal periventricular white matter and basal ganglia hyperintensities in first-ever lacunar stroke with multiple silent lacunes

Background and purpose:  We investigated whether patients with a lacunar infarct (LI) syndrome exhibiting unique LI or multiple LI on magnetic resonance imaging (MRI) examinations differed in terms of topography and severity of white matter hyperintensities (WMH) ratings.
Methods:  Forty consecutive patients with a first-ever acute LI, who presented a lacunar syndrome according to Miller–Fisher's classification were recruited and were classified into a group presenting isolated LI on MRI ( n  = 17) or multiple LI ( n  = 23).
Results:  Despite equivalent demographic, clinical and cognitive characteristics, patients with multiple LI had increased ratings of WMH in frontal, occipital and subcortical regions. No significant correlations could be evidenced between the number of LI and WMH ratings.
Conclusions:  Present findings provide support to previous hypothesis considering single and multiple LI MRI presentations of lacunar infarct patients as distinct entities.     

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

OBJECTIVE: We prospectively investigated the predictive value of clinical and CT-supported lacunar syndromes for lacunar infarcts on magnetic resonance (MR) brain imaging. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.     

Clinical classification for lacunar infarct. An investigation of 130 consecutive cases of lacunar infarctions]

A lacunar infarct is defined as the occlusion of a single perforating artery. Certain researchers have proposed that patients with lacunar infarcts can be classified into two clinically distinct entities: patients with a single, symptomatic lacunar infarct, and patients with multiple lacunar infarcts together with hypertension and leukoaraiosis. The present study attempted to delineate the characteristics of lacunar infarcts and evaluate the validity of the aforementioned hypothesis. A total of 130 consecutive patients with first-time symptomatic lacunar infarct were studied. All patients were dichotomized into two groups according to two different kinds of models as follows. Model-1: patients with a single lacune and patients with multiple lacunes; and Model-2: patients with large lacune and patients with small lacune. Associated factors for the multiple lacune group compared with the single lacune group as well as the large lacune group compared with the small lacune group, were analyzed by multivariate logistic regression analysis. Associated factors included age, sex, hypertension, diabetes mellitus, dyslipidemia, smoking, extracranial and intra-cranial vascular lesions, extent of lacunes and white matter lesions, progression status and blood pressure in the acute stage, and coagulation markers such as fibrinogen, thrombin-antithrombin complex, D-dimer, beta-thromboglobulin, platelet factor 4. Results for Model-1: hypertension (age-and sex-adjusted OR: 2.58, p = 0.017) and elevated systolic blood pressure (>160mmHg for the mean value during the first post-ictal week; OR: 2.55, p = 0.016) were significantly associated with the multiple lacune group. Large lacunes (>10mm in diameter) were negatively associated with the multiple lacune group (OR: 0.38, p = 0.017). Association between confluent white matter lesions and the multiple lacune group approached significance (OR: 2.16, p = 0.056). Results for Model-2: female sex (OR: 0.39, p = 0.021), mild stenosis of intracranial and extracranial arteries (<25%) (intracranial; OR: 5.42, p = 0.0042, extracranial; OR: 3.30, p = 0.016), progressing stroke (OR: 6.77, p<0.0001), and high levels of TAT (>3ng/ml) (OR: 2.80, p = 0.039) were significantly associated with the large lacune group. Multiple lacunes (OR: 0.38, p = 0.016) and confluent white matter lesions (OR: 0.28, p = 0.007) exhibited a significant negative association with the large lacune group. In conclusion, underlying vasculopathy in the presence of multiple lacunes may correspond to lipohyalinosis resulting from hypertension. Moreover, large lacune may correspond to microatheroma at the orifice of penetrating arteries.     

Polymorphism in the sorbin and SH3-domain-containing-1 (SORBS1) gene and the risk of brain infarction in the Japanese population: the Fukuoka Stroke Registry and the Hisayama study

Background and purpose:  Sorbin and SH3-domain-containing-1 (SORBS1) is an important adaptor protein in insulin-signalling pathway, and its genetic polymorphism may regulate the activity of insulin resistance. We investigated the association between the SORBS1 T228A polymorphism and ischaemic stroke.
Methods:  Genotyping was achieved by a rapid-cycle PCR and melting curve analysis using fluorescent probes in 1049 incident cases of ischaemic stroke and 1049 age- and sex-matched control subjects recruited from the Hisayama study.
Results:  The allele distributions of the SORBS1 T228A polymorphism were similar amongst cases and controls. The multivariate-adjusted odds ratio (OR) of the AA genotype for ischaemic stroke was 2.897 (95% CI, 0.907–8.018) compared with the TT genotype. In terms of stroke subtype, there was a trend toward a difference in the AA genotypes for lacunar infarction, compared with the TT genotype (OR = 8.740, P  = 0.0510), and combined TT and TA genotypes (OR = 8.768, P  = 0.0505). The other polymorphisms genotyped were not associated with any subtypes of ischaemic stroke. T228A polymorphism of SORBS1 was not associated with the prevalence of diabetes.
Conclusions:  The AA genotype of SORBS1 T228A polymorphism may play a role in lacunar infarction in the Japanese population.     

The beneficial effect of statins treatment by stroke subtype

Background and purpose:  Statins have shown some protective effect after ischaemic stroke in observational studies. However, this effect has never been assessed by etiological subtypes.
Methods:  Observational study using data from the Stroke Unit Data Bank from consecutive patients with cerebral infarction. Variables analyzed: demographic data, cardiovascular risk factors, treatment with statins at stroke onset, stroke severity, stroke subtype, in-hospital complications, length of stay, and functional status at discharge (modified Rankin Scale).
Results:  A total of 2742 patients were included, 1539 were men. Mean age was 69.17 years (SD 12.19). Of these, 281 patients (10.2%) were receiving statins when admitted. The logistic regression analyses showed that previous treatment with statins was an independent predictor for better outcome at discharge among all strokes (OR, 2.08; 95% CI, 1.39 to 3.1) as well as for the atherothrombotic (OR, 2.79; 95% CI, 1.33 to 5.84) and lacunar strokes (OR, 2.28; 95% CI, 1.15 to 4.52) after adjustment for demographic data, risk factors, previous treatments, stroke subtypes, stroke severity, in-hospital complications and length of stay. This benefit was not observed either in cardioembolic or in other etiology strokes.
Conclusions:  Previous treatment with statins is an independent factor associated with good outcomes in patients with ischaemic stroke. Atherothrombotic and small vessel strokes show the greatest benefit.     

Prospective study of lacunar infarction using magnetic resonance imaging

Using computed tomography and magnetic resonance imaging, we prospectively studied 100 patients hospitalized with a lacunar infarct. Our aim was to evaluate the capabilities of magnetic resonance imaging in the detection and delineation of lacunes in a project of clinicotopographic correlations. Seventy-nine patients had a classic lacunar syndrome; 35 had pure motor stroke, 26 had ataxic hemiparesis, seven had sensorimotor stroke, and 11 had pure sensory stroke. A miscellaneous group of 21 patients had less typical lacunar syndromes, primarily with brainstem signs and symptoms. Among a total of 153 lacunes, magnetic resonance imaging detected at least one lacune appropriate to the symptoms in 89 patients. In 16 patients at least two lesions correlated with the clinical features, and precise clinicotopographic correlations were possible in 68 patients. Magnetic resonance imaging was more effective when it was performed a few days after the stroke. Lesions causing different types of lacunar syndromes had significantly different volumes, suggesting that the size of the lesion may influence clinical features. Magnetic resonance imaging may be the imaging technique of choice in the study of lacunar syndromes.     

Pure sensory stroke. Clinical-radiological correlates of 21 cases.

BACKGROUND: Although pure sensory stroke is a relatively common lacunar syndrome, the responsible lesions are often unidentified because of their small size. I reported 21 cases of pure sensory stroke in which the lesions could be identified by head computed tomography and/or magnetic resonance imaging and correlated the clinical findings with the radiological lesions. SUMMARY OF REPORT: Eleven patients had thalamic strokes. Lacunes confined to the posterolateral part of the thalamus were found in nine cases, and hemorrhages of relatively large size were found in two. Five patients showed a loss of all sensory modalities, but six with very small lacunes showed minor or restricted sensory changes. Seven patients with lacunes or hemorrhages in the lenticulocapsular region or corona radiata showed abnormalities of spinothalamic tract sensation. Two patients with a small lacune and a hemorrhage in the pontine tegmentum showed a selective sensory deficit of the medial lemniscal type. One patient with a small cortical infarct showed a cortical sensory loss that was preceded by cortical sensory transient ischemic attacks. CONCLUSIONS: Pure sensory stroke can occur with lesions in various areas of the somatosensory system. Hemisensory deficits of all modalities usually are associated with a relatively large lacune or hemorrhage in the lateral thalamus, whereas tract-specific or restricted sensory changes suggest very small strokes in the sensory pathway from the pons to the parietal cortex.     

Coagulation and fibrinolytic activation in lacunar infarct patients]

Lacunar infarcts are related to occlusion of penetrating arteries. Lipohyalinosis affects the smaller arteries 40-200 microns in diameter, and atherosclerosis involves larger arteries 200-850 microns in diameter. We hypothesized that the processes of thrombus formation might be different among these two kinds of lacuner infarcts, including those caused by lipohyalinosis and atherosclerosis. We studied acute coagulation and fibrinolytic activation in lacunar infarct patients which were divided into two groups according to their size: smaller lacunar group and larger lacunar group. Then we divided lacunar infarct patients into two groups in terms of the progression of motor deficits: those who showed the progression and those did not. And coagulation and fibrinolytic activation were compared each other. One hundred and twenty four patients were enrolled in this study, including 34 control subjects, 39 patients with smaller lacune (3 mm-10 mm in diameter), 28 patients with large lacune (10 mm-20 mm), and 23 patients with atherothrombotic infarcts confirmed by angiography. The levels of TAT activity in large lacune and atherothrombotic infarcts were significantly higher than those in control subjects (p = 0.009, p < 0.0001, respectively), whereas those in small lacune were not. Also, the levels of D-dimer activity in large lacune and atherothrombotic infarcts were significantly higher than those in control subjects (p = 0.0003, p < 0.0001, respectively), whereas those in small lacune were not. The progression of motor deficits were more frequently recognized in large lacune than in small lacune: three patients out of 39 small lacune patients and 22 patients out of 28 large lacune patients (difference was significant, p = 0.001). The level of TAT activity in patients who showed progression of motor deficits was significantly higher than that in those who did not (p = 0.0002), whereas the difference of the levels of D-dimer activity in two groups did not reach significant differencial levels. The process of thrombin and fibrin formation in large lacunar infarcts which are related to microatheroma and atheroscrelosis appears to be different from that in small lacunar infarcts. Antiplatelet and anticoagulation therapy should be tailored to large lacunar infarct patients.     

Lacunar stroke attributable to radiation-induced intracranial arteriopathy

We report the rare presentation of lacunar stroke syndrome secondary to single perforator mouth occlusion from radiation-induced middle cerebral artery (MCA) stem arteriopathy. A 30-year-old female had acute-onset right-sided ataxic hemiparesis and dysarthria. As a child, she had a medulloblastoma of the posterior fossa and had surgery followed by cranial radiotherapy. She had no significant vascular risk factors. Acute CT showed extensive bilateral basal ganglia and left thalamic calcification; DWI showed a left internal capsule lacunar infarct; and MRA and CTA showed a 50% stenosis of the proximal left MCA.     

磁共振扩散加权成像在鉴别新陈腔隙性脑白质梗死中的价值

目的分析新陈腔隙性脑白质梗死的T2WI、扩散加权成像(DWI)信号特点，比较两种梗死的病灶与脑白质、病灶与脑脊液对比度及表观扩散系数(ADC)，评价DWI在鉴别新陈腔隙性脑白质梗死方面的作用。方法急性期腔隙性脑白质梗死患者27例，选择43例陈旧腔隙性脑白质梗死患者作对照。测量病灶、正常脑白质、脑脊液信号强度，计算病灶与脑白质、病灶与脑脊液的对比度。测量病灶、正常脑组织、脑脊液的ADC值并比较。结果(1)急性脑白质腔隙性梗死DWI呈高信号，ADC图呈等或低信号。DWI的病灶与脑白质、病灶与脑脊液对比度均优于T2WI。(2)陈旧脑白质腔隙性梗死DWI呈等信号，ADC图呈高信号。DWI的病灶与脑白质对比度不如T2WI。(3)DWI图像上，急性腔隙性脑白质梗死病灶与脑白质、病灶与脑脊液对比度明显高于陈旧病灶，ADC则明显低于陈旧病灶，有助于区分新陈腔隙性梗死。结论DWI的检查时间短，诊断和鉴别意义大，建议在可能的情况下，将DWI作为急性卒中样发作患者的常规检查序列。     

Normal diffusion-weighted MRI during stroke-like deficits.

BACKGROUND: Diffusion-weighted MRI (DWI) represents a major advance in the early diagnosis of acute ischemic stroke. When abnormal in patients with stroke-like deficit, DWI usually establishes the presence and location of ischemic brain injury. However, this is not always the case. OBJECTIVE: To investigate patients with stroke-like deficits occurring without DWI abnormalities in brain regions clinically suspected to be responsible. METHODS: We identified 27 of 782 consecutive patients scanned when stroke-like neurologic deficits were still present and who had normal DWI in the brain region(s) clinically implicated. Based on all the clinical and radiologic data, we attempted to arrive at a pathophysiologic diagnosis in each. RESULTS: Best final diagnosis was a stroke mimic in 37% and a cerebral ischemic event in 63%. Stroke mimics (10 patients) included migraine, seizures, functional disorder, transient global amnesia, and brain tumor. The remaining patients were considered to have had cerebral ischemic events: lacunar syndrome (7 patients; 3 with infarcts demonstrated subsequently) and hemispheric cortical syndrome (10 patients; 5 with TIA, 2 with prolonged reversible deficits, 3 with infarction on follow-up imaging). In each of the latter three patients, the regions destined to infarct showed decreased perfusion on the initial hemodynamically weighted MRI (HWI). CONCLUSIONS: Normal DWI in patients with stroke-like deficits should stimulate a search for nonischemic cause of symptoms. However, more than one-half of such patients have an ischemic cause as the best clinical diagnosis. Small brainstem lacunar infarctions may escape detection. Concomitant HWI can identify some patients with brain ischemia that is symptomatic but not yet to the stage of causing DWI abnormality.     

Clinical study of 39 patients with atypical lacunar syndrome

The aim of this study was to describe the clinical characteristics of atypical lacunar syndrome (ALS) based on data collected from a prospective acute stroke registry. In total, 2500 acute stroke patients were included in a hospital based prospective stroke registry over a 12 year period, of whom 39 were identified as having ALS and radiologically proven (by computed tomography or magnetic resonance imaging) lacunes. ALS accounted for 1.8% of all acute stroke patients, 2.1% of acute ischaemic stroke, and 6.8% of lacunar syndromes. ALS included dysarthria facial paresis (n = 12) or isolate dysarthria (n = 9), isolated hemiataxia (n = 4), pure motor hemiparesis with transient internuclear ophthalmoplegia (n = 4), pure motor hemiparesis with transient subcortical aphasia (n = 3), unilateral (n = 2) or bilateral (n = 3) paramedian thalamic infarct syndrome, and hemichorea hemiballismus (n = 2). Atypical lacunar syndromes were due to small vessel disease in 96% of patients. Atherothrombotic infarction occurred in one patient and cardioembolic infarct in another, both presenting pure dysarthria. Outcome was good (in hospital mortality 0%, symptom free at discharge 28.2%). After multivariate analysis, the variables of speech disturbances, nausea/vomiting, ischaemic heart disease, and sensory symptoms were found to be significantly associated with ALS. In conclusion, atypical lacunar syndrome is an infrequent stroke subtype (one of each 14 lacunar strokes). ALS occurred in 6.8% of lacunar strokes. Isolated dysarthria or dysarthria facial paresis were the most frequent presenting forms. The prognosis of this infrequent non-classic lacunar syndrome is good.     

Lacunar stroke in patients with intermittent claudication

OBJECTIVES: To compare the characteristics of lacunar stroke (LS) in patients with and without intermittent claudication. MATERIAL AND METHODS: Data of 484 consecutive patients with LS were collected from a prospective hospital-based stroke registry in which 2500 patients are included. RESULTS: Of the 142 patients with ischemic stroke and intermittent claudication, 39 (27.5%) had LS (8% of all lacunes). In the multivariate analysis, small centrum ovale topography (odds ratio 7.35), carotid stenosis >50% (odds ratio 3.17), and absence of limitation at discharge (odds ratio 2.01) were independent variables significantly associated with LS in patients with intermittent claudication. CONCLUSION: Only 8% of patients with LS had intermittent claudication. The short-term prognosis is good with a spontaneous early neurological recovery at discharge in 51.3% of patients. LS patients with intermittent claudication showed a striking similarity in risk factors and clinical syndromes in comparison with the LS patients without intermittent claudication.     

Computed tomographic changes in lacunar syndromes

BACKGROUND: Lacunes are small deep infarcts due to occlusion of long-perforating arterial branches. The clinical presentation and outcome are variable. The present study investigates the prognostic value of comparing repeated computed tomographic (CT) scans in patients with a lacunar syndrome (LACS). PATIENTS AND METHODS: From a series of 220 patients, subsequently admitted with a first-ever stroke, 32 were diagnosed as LACS. CT scans without contrast enhancement were performed on day 3 and 10 after onset of the symptoms. A lacune was considered as responsible for the LACS when its location corresponded to the expected cerebral hemisphere and when it changed in size and/or in X-ray attenuation on the CT scans from day 3 to 10. The size of the lacune was also measured and compared on both time points. The patients were divided into two groups according to the modified Rankin (R) scale at 3 months, in those who were independent (R 0-1-2) and in those who remained handicapped (R 3-4-5). RESULTS: The patients who remained disabled at 3 months were older and more severely impaired on admission, and had more frequent cardiac problems and cognitive decline than the independent ones. On CT scans of the brain a higher incidence of leukoaraiosis was observed in this group. Only in three patients of each group no relevant lacune could be observed both on day 3 and 10. The average size of the symptomatic lacune on day 3 and 10 was not statistically different between both groups, when comparing all patients with a LACS. When comparing only those patients with a visible symptomatic lacunar infarct on one of the CT scans, however, the average size of the symptomatic deep infarct was smaller in the independent than the handicapped patients on day 3 as well as on day 10. The lacune decreased in average size from day 3 to 10 in the former group but remained unchanged in the group of disabled patients. CONCLUSION: The outcome of patients with a LACS depends on several factors including age, cognitive and cardiac status, the presence of leukoaraiosis and also the size of the symptomatic lacune.     

Proposing the stroke levity scale: a valid, reliable, simple, and time-saving measure of stroke severity

Background and purpose:  National Institutes of Health Stroke Scale (NIHSS) is long and complex. Our objective was to design a valid, reliable, simple, and time-saving stroke severity scale.
Methods:  About 103 and 100 consecutive stroke patients in Berlin (Germany) and Ibadan (Nigeria), respectively were evaluated using the measures listed below. The Stroke Levity Scale (SLS) was calculated as maximum power (0–5) in the dexterous hand + maximum power in the weaker lower limb + mobility score−1(if aphasia present).
Results:  It took less than 2 min to administer the SLS in contrast to 8 min for the NIHSS. The SLS showed significant correlation to the NIHSS ( ρ  = −0.79, P  < 0.0001), the modified Rankin Scale ( ρ  = −0.79, P  < 0.0001), and the health-related quality of life (QOL) in stroke patient's questionnaire ( ρ  = 0.78, P  < 0.0001). It had Cronbach's α of 0.75 (Ibadan) and 0.71 (Berlin). The κ -value for test-retest reliability was 0.77 with P  < 0.0001.
Conclusions:  The SLS is a concise, valid, and reliable stroke impairment scale that can be used routinely to monitor outcome in stroke patients. Because it is brief and simple to apply, non-neurologists can be taught to administer it in addition to QOL and disability scales for stroke survivors without significantly increasing the respondent burden.     

Diffusion-weighted imaging identifies a subset of lacunar infarction associated with embolic source

BACKGROUND AND PURPOSE: Small infarcts in the territory of penetrator arteries were described as causing a number of distinct clinical syndromes. The vascular pathophysiology underlying such infarcts is difficult to ascertain without careful pathological study. However, the occurrence of multiple, small infarcts, linked closely in time but dispersed widely in the brain, raises the possibility of an embolic mechanism. The current study determines the frequency and clinical characteristics of patients with well-defined lacunar syndromes and the diffusion-weighted imaging (DWI) evidence of multiple acute lesions. METHODS: Sixty-two consecutive patients who presented to the emergency room with a clinically well-defined lacunar syndrome were studied by DWI within the first 3 days of admission. RESULTS: DWI showed multiple regions of increased signal intensity in 10 patients (16%). A hemispheric or brain stem lesion in a penetrator territory that accounted for the clinical syndrome ("index lesion") was found in all. DWI-hyperintense lesions other than the index lesion ("subsidiary infarctions") were punctate and lay within leptomeningeal artery territories in the majority. As opposed to patients with a single lacunar infarction, patients with a subsidiary infarction more frequently (P<0.05) harbored an identifiable cause of stroke. CONCLUSIONS: Almost 1 of every 6 patients presenting with a classic lacunar syndrome has multiple infarctions demonstrated on DWI. This DWI finding usually indicates an identifiable cause of stroke and therefore may influence clinical decisions regarding the extent of etiologic investigations and treatment for secondary prevention.     

The paraoxonase gene polymorphism in stroke patients and lipid profile

Objectives –  The paraoxonase (PON) gene can reduce the risk of developing atherosclerosis. We investigated the associations between PON polymorphisms and ischemic stroke. We also investigated the associations between PON polymorphisms and lipid profile in stroke patients.
Methods –  A total of 350 patients with ischemic stroke and 242 control subjects in Korean population were genotyped for the PON1M55 L, PON1Q192R, PON2A148 G and PON2S311C polymorphisms using melting point analysis with LightCycler real-time polymerase chain reaction (PCR) technology.
Results –  There were no significant differences in genotype and allele distribution of the PON polymorphisms between the ischemic stroke patients and control subjects. The concentration of total homocysteine was significantly different in the PON1M55 L polymorphism ( P  = 0.047), and the apolipoprotein (Apo)B concentration was significantly different in the PON1Q192R polymorphism ( P  = 0.02) in stroke patients. The concentrations of low-density lipoprotein (LDL) cholesterol and ApoB were significantly different between the PON2A148 G ( P  = 0.011, P  = 0.000, respectively) and PON2S311C polymorphisms ( P  = 0.046, P  = 0.003, respectively) in stroke patients.
Conclusions –  This study did not provide association between PON gene polymorphisms and ischemic stroke. However, it confirmed that the PON1L55 L allele is associated with plasma concentration of total homocysteine and that the PON2G148 G and PON2S311S allele is associated with plasma concentrations of LDL cholesterol and ApoB.     

MHC2TA rs4774C and HHV-6A active replication in multiple sclerosis patients

Background and purpose:  In a previous report, a strong gene–environment interaction between human herpesvirus 6A (HHV6A) active replication and MHC2TA rs4774C was demonstrated. The objectives of this study were: (i) to reappraise the association that was found in the previous study; (ii) to evaluate if MS patients with minor allele C and HHV-6A active infection had different clinical behavior; and (iii) to analyze the possible association of MHC2TA rs4774C with Epstein–Barr virus (EBV).
Methods:  A total of 149 MS patients were analyzed both at the MHC2TA locus and by HHV-6A status in serum. We studied a G/C polymorphism (rs4774) by a TaqMan Assay-on-Demand. HHV-6A genomes in serum were evaluated by quantitative PCR. A control group of 562 healthy Spanish individuals was included for comparative purposes in the genetic analyses. A battery of clinical data was collected for all the MS patients included in the study.
Results:  (i) MHC2TA/HHV-6A interaction : we found the same strong association of the rs4774C allele with HHV-6A active replication than in the previous study ( P  =   0.0001). (ii) Clinical data : the two main statistical significant differences for MS patients with HHV-6A active infection and minor allele C were: (a) a significant number of them were not free of progression (EDSS = 0) 2 years after the diagnosis ( P  =   0.01); (b) only a third of them responded to interferon beta treatment ( P  =   0.05).
Conclusions:  This study has verified previous results about the strong gene–environment interaction between HHV6A active replication and MHC2TA rs4774C. Furthermore, a different clinical behavior for MS patients with HHV-6A active infection and minor allele C was found.