Lacunar Infarcts Research Articles

Management of Inherited CNS Small Vessel Diseases: The CADASIL Example: A Scientific Statement From the American Heart Association.

Lacunar infarcts and vascular dementia are important phenotypic characteristics of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, the most common inherited cerebral small vessel disease. Individuals with the disease show variability in the nature and onset of symptoms and rates of progression, which are only partially explained by differences in pathogenic mutations in the NOTCH3 gene. Recognizing the disease early in its course and securing a molecular diagnosis are important clinical goals, despite the lack of proven disease-modifying treatments. The purposes of this scientific statement are to review the clinical, genetic, and imaging aspects of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, contrasting it with other inherited small vessel diseases, and to provide key prevention, management, and therapeutic considerations with the intent of reducing practice variability and encouraging production of high-quality evidence to support future treatment recommendations.

Subcortical infarcts in patients with nonstenotic cervical atherosclerotic disease

BackgroundPrior studies have elucidated a relationship between nonstenotic plaque in patients with cryptogenic embolic infarcts with a largely cortical topology, however, it is unclear if nonstenotic cervical internal carotid artery (ICA) plaque is relevant in subcortical cryptogenic infarct patterns. MethodsA nested cohort of consecutive patients with anterior, unilateral, and subcortical infarcts without an identifiable embolic source were identified from a prospective stroke registry (September 2019 - June 2021). Patients with extracranial stenosis >50% or cardiac sources of embolism were excluded. Patients with computed tomography angiography were included and comparisons were made according to the infarct pattern being lacunar versus non-lacunar. Prevalence estimates for cervical internal carotid artery (ICA) plaque presence were estimated with 95% confidence intervals (CI), and differences in plaque thickness and features were compared between sides. ResultsOf the 1684 who were screened, 141 met inclusion criteria (n=80 due to small vessel disease, n=61 cryptogenic). The median age was 66y (interquartile range, IQR 58-73) and the National Institutes of Health Stroke Scale score was 3 (IQR 1-5). There was a higher probability of finding excess plaque ipsilateral to the stroke (41.1%, 95% CI 33.3-49.3%) than finding excess contralateral plaque (29.1%, 95% CI 22.2-37.1%; p=0.03), but this was driven by patients with non-lacunar infarcts (excess ipsilateral vs. contralateral plaque frequency of 49.2% vs. 14.8%, p<0.001) rather than lacunar infarcts (35.0% vs. 40.0%, p=0.51). ConclusionsThe probability of finding ipsilateral, nonstenotic carotid plaque in patients with subcortical cryptogenic strokes exceeds the probability of contralateral plaque and is driven by larger subcortical infarcts, classically defined as being cryptogenic. Approximately 1 in 3 unilateral anterior subcortical infarcts may be due to nonstenotic ICA plaque.

A Narrative Review of the Neurological Manifestations of Human Adenosine Deaminase 2 Deficiency

Deficiency of human adenosine deaminase type 2 (DADA2) is a complex systemic autoinflammatory disorder characterized by vasculopathy, immune dysregulation, and hematologic abnormalities. The most notable neurological manifestations of DADA2 are strokes that can manifest with various neurological symptoms and are potentially fatal. However, neurological presentations can be diverse. We here present a review of the neurological manifestations of DADA2 to increase clinical awareness of DADA2 as the underlying diagnosis. We reviewed all published cases of DADA2 from 1 January 2014 until 19 July 2022 found via PubMed. A total of 129 articles describing the clinical features of DADA2 were included in the analysis. Six hundred twenty-eight patients diagnosed with DADA2 were included in the review. 50.3% of patients had at least signs of one reported neurological event, which was the initial or sole manifestation in 5.7% and 0.6%, respectively. 77.5% of patients with neurological manifestations had at least signs of one cerebrovascular accident, with lacunar strokes being the most common and 35.9% of them having multiple stroke episodes. There is a remarkable predilection for the brain stem and deep gray matter, with 37.3% and 41.6% of ischemic strokes, respectively. Other neurological involvement included neuropathies, focal neurological deficits, ophthalmological findings, convulsions, and headaches. In summary, neurological manifestations affect a significant proportion of patients with DADA2, and the phenotype is broad. Neurological manifestations can be the first and single manifestation of DADA2. Therefore, stroke, encephalitis, posterior reversible encephalopathy syndrome, mononeuropathy and polyneuropathy, and Behçet’s disease-like presentations should prompt the neurologist to exclude DADA2, especially but not only in childhood.

Effects of intensive blood pressure control on cognitive function in patients with cerebral small vessel disease

ObjectiveThis study aimed to investigate the effects of intensive blood pressure control on cognitive function in elderly patients with cerebral small vessel disease (CSVD). MethodsFrom May 2020 to June 2022, 140 outpatients and inpatients with CSVD and hypertension in the Department of Neurology of Beijing Shijingshan Hospital were selected. They were randomly divided into the standard and intensive blood pressure control groups, and the dosage of antihypertensive drugs was adjusted to reduce the blood pressure to the target level. The patients were followed up for 2 years. The medical records or data at “enrollment” and “2-year follow-up” were analyzed and evaluated. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function. Cranial magnetic resonance imaging was performed to evaluate lacunar infarctions (LIs) and white matter hyperintensity (WMH). Multiple linear regression was used to analyze the correlation between MMSE scores and blood pressure, WMH, and LIs. Results(1) The MMSE and MoCA scores in the standard group were significantly lower than those at enrollment. The WMH score in the standard group was significantly higher than that at enrollment. (2) After the 2-year follow-up, the 24-h systolic blood pressure (SBP), 24-h diastolic blood pressure (DBP), daytime mean SBP, daytime mean DBP, and nighttime mean SBP in the two groups significantly decreased, which had significant statistical significance (P < 0.05). (3) The correlation between blood pressure and MMSE score was analyzed using multiple linear regression analysis. The WMH score, LIs, 24-h SBP, and 24-h DBP were independently correlated with MMSE scores. ConclusionIn elderly patients with hypertension, a decrease in SBP to 126 mmHg, compared with 134 mmHg, can delay cognitive impairment as well as reduce LIs and cerebral WMH lesions in patients with CSVD.

The gut microbial signatures of patients with lacunar cerebral infarction

ABSTRACT Background Emerging evidence revealed that gut microbial dysbiosis is involved in the pathogenesis of multiple neurological diseases, but there is little available data on the relationship between gut microbiota and lacunar cerebral infarction (LCI). Methods Fecal samples from acute LCI patients (n = 65) and matched healthy controls (n = 65) were collected. The compositions and potential functions of the gut microbiota were estimated. Results The results showed that there were significant gut microbial differences between LCI and control groups. Patients with LCI had higher abundances of genus Lactobacillus, Streptococcus, Veillonella, Acidaminococcus, Bacillus, Peptoclostridium, Intestinibacter, Alloscardovia and Cloacibacillus but lower proportions of genus Agathobacter and Lachnospiraceae_UCG-004. Investigating further these microbes such as Lactobacillus and Veillonella were correlated with clinical signs. Moreover, we found that 9 gene functions of gut microbiota were different between LCI patients and controls, which were associated with amino acid metabolism and inflammatory signal transduction. Notably, four optimal microbial markers were determined, and the combination of Streptococcus, Lactobacillus, Agathobacter, Lachnospiraceae_UCG-004 and the three risk factors achieved an area under the curve (AUC) value of 0.854 to distinguish LCI from controls. Conclusion These findings revealed the characterizing of gut microbiota in LCI patients and provided potential microbial biomarkers for clinical diagnosis of LCI.

Relationship between Serum Irisin Levels and MRI-Measured Cerebral Small Vessel Disease in Japanese Men.

Irisin, an exercise-induced myokine, is a potential neurotrophic factor; however, its relationship with cerebral small vessel disease (CSVD) remains unknown. Therefore, we investigated whether serum irisin levels are associated with CSVD in healthy Japanese men. We analyzed data from 720 men free of stroke and participated in this observational study. Serum irisin levels were measured by enzyme-linked immunosorbent assay. CSVD was assessed on deep and subcortical white matter hyperintensities (DSWMHs), periventricular hyperintensities (PVHs), lacunar infarcts (LIs), and cerebral microbleeds (CMBs) on brain magnetic resonance imaging. We calculated the total CSVD score (ranges 0-4) to express the total CSVD burden. We computed the adjusted odds ratios (ORs), with 95% confidence intervals (CIs), of the total CSVD score and individual CSVD features using logistic regression models according to the quartiles of irisin (reference: Q1). Serum irisin levels were associated with lower ORs of higher (vs. zero or lower score) total CSVD score, with the lowest risk (OR, 0.63; 95% CI, 0.41-0.97) being observed in Q3 compared to Q1 after adjustment of potential covariates. Similar results were obtained for younger adults (＜65 years). Among individual CSVD features, irisin was associated with a reduced risk of LIs in the total sample and PVHs, LIs, and CMBs in younger adults. No relationship was observed in older adults (≥ 65 years). Serum irisin levels were associated with less burden of total CSVD in healthy Japanese men. Serum irisin levels were also related with a reduced risk of PVHs, LIs, and CMBs, but not DSWMHs.

71-year Old Male Patient with 20 Hour Onset of Infarct Stroke that was Performed with Intra-Arterial Thrombolysis, Mechanical Thrombectomy, Balloon Angioplasty, and Carotid Stenting: A Case Report

Introduction: For above 2 decades, the definitive management for acute ischemic stroke is intravenous or intra-arterial thrombolysis (IAT), using recombinant tissue-type plasminogen activator. Recently mechanical thrombectomy (MT) was developed to overcome the problem that intravenous thrombolysis is only effective in removing large artery occlusions in the range of 10-30%. Early treatment with intra-arterial thrombolysis, permanent stent insertion and clot extraction devices evolved into the stent-retriever device used in most of the important trials and, recently, emerged aspiration tool. This case report presented 71-year-old male patient with infarct stroke who performed with MT. Case presentation: This case report presented 71-year-old male patient with the main complaint of right limbs weakness. A non-contrast head CT scan found infarction in the cortical-subcortical left parietal lobe, posterior pericornu of the right lateral ventricle and right temporal cornu periventricular; lacunar infarction in the right and left paramedian pons; old lacunar infarction in the left and right centrum semiovale, left corona radiata, right internal capsule, right parietal lobe white matter, left lentiform nucleus, left posterior crus of the internal capsule-thalamus, right thalamus, right lateral ventricular pericornu and left paramedian pons. The patient underwent cerebral digital substraction angiography (DSA), as well as IAT, MT, balloon angioplasty, and carotid stenting with good clinical outcome. Conclusion: With the overwhelming positive results of studies evaluating the safety, efficiency, and efficacy of mechanical thrombectomy; the standard of care for the treatment of patients with anterior circulation vessel occlusion is becoming clear.

The Early Postoperative Course of Cognitive Function and Preoperative Cerebrovascular Reserve.

Patients with severe steno-occlusive disease of a main cerebral artery without causative lesions on magnetic resonance imaging (MRI) often develop cognitive impairment. However, the effects of revascularization surgery and the source of the cognitive impairment remain unclear. Therefore, we investigated the early postoperative course of cognitive function and its association with cerebral blood flow (CBF), cerebrovascular reserve (CVR), white matter disease (WMD), lacunar infarction, and cerebrovascular risk factors. Cognitive function was examined using neurobehavioral cognitive status examination (COGNISTAT) in 52 patients with steno-occlusive disease of a main cerebral artery before and at 6 months after superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis. We examined how cognition changed before and at 1, 3, and 6 months after STA-MCA anastomosis in 27 of 52 patients. CVR and CBF were calculated from 123I-N-isopropyl-p-iodoamphetamine single photon emission computed tomography, in addition to other cerebrovascular risk factors in 34 of 52 patients. Cerebral infarction and WMD (periventricular hyperintensity [PVH] and deep subcortical white matter hyperintensity) were also evaluated preoperatively by MRI. COGNISTAT scores improved at 1 month after STA-MCA anastomosis in patients with severe steno-occlusive disease of a main cerebral artery. Multiple stepwise regression analysis revealed that CVR (regression coefficient = -2.237, p = 0.0020) and PVH (regression coefficient = 2.364, p = 0.0029) were the best predictors of postoperative improvement in COGNISTAT scores (R 2 = 0.415; p = 0.0017). Cognitive function improves in relation to preoperative CVR and PVH early after STA-MCA anastomosis in patients with steno-occlusive disease of a main cerebral artery.

Prospective observational study of stroke in Cayenne, Tours and Besançon: The BECATOUR study

BackgroundStroke is a major public health issue. Its epidemiology is still poorly known in French Guiana. MethodWe conducted a prospective observational study including 100 consecutive patients hospitalized for stroke in Cayenne (in French Guiana), and Tours and Besançon (in metropolitan France). We compared their age, medical history, cardiovascular risk factors, pre-admission Rankin score, Glasgow and NIHSS scores, usual treatments, acute phase management, type of stroke, duration of hospitalization, mechanism of stroke according to TOAST classification, NIHSS and Rankin scores at discharge, discharge treatments, and mode of discharge. ResultsIn French Guiana, the average age of patients was 7years lower (62 y), patients were more frequently affected by hypertension (75%) and diabetes (31%). Lacunar strokes were overrepresented (16.1%), and infarctions of cardioembolic origin were underrepresented (12%). NIHSS entry and Glasgow scores were similar between French Guiana and mainland France. Acute management was different: thrombolysis rate (9.3%) was 3 to 4 times lower, thrombectomy was not available. Fewer patients were transferred to rehabilitation centers and more patients were transferred to home hospitalization. DiscussionIn Tours and Besançon, patients eligible for thrombectomy were overrepresented. This bias explains the overrepresentation of more severe infarctions and probably the overrepresentation of strokes of cardioembolic origin. Infarctions of undetermined origin were more numerous in French Guiana because patients were often discharged from hospital with an incomplete cardiological workup. ConclusionDespite some caveats, the profile of patients admitted for stroke in French Guiana is different from mainland France. The establishment of a stroke unit and an information campaign on the symptoms of stroke would allow better management.

Predictors of congruency between clinical and radiographic Oxfordshire Community Stroke Project Classification subtypes

BackgroundThe Oxfordshire Community Stroke Project (OCSP) classification has been widely used to assess ischemic stroke patients based on clinical characteristics alone. However, the correlation between the clinical presentation evaluated using OCSP and imaging findings is yet to be determined. Our study aimed to describe the baseline characteristics of the OCSP subtypes of patients admitted with ischemic stroke and evaluate the predictors of the relationship between clinical and neuroimaging findings. MethodsPatients with a confirmed diagnosis of ischemic stroke admitted to a comprehensive stroke center in Brazil between February 2015 and October 2017 were eligible for the study. All participants underwent computed tomography (CT) at admission and follow-up neuroimaging within seven days, per the institutional protocol. Trained staff classified patients according to the OCSP at hospital admission. The radiographic OCSP classification was retrospectively assessed based on the last follow-up neuroimaging by investigators unaware of the clinical classification. ResultsThe overall agreement rates ranged from 65.5% to 88.7%. Lower NIHSS scores, absent hyperdense MCA sign, higher ASPECTS, and absent brainstem symptoms were related to a higher risk of misclassification. Treatment with intravenous tPA was associated with reclassification in patients with total anterior circulation syndrome. For predicting radiographic posterior circulation involvement, vertigo (OR 2.9, 95% CI 1.7–5.1, p < 0.001) and brainstem symptoms (OR 35, 95% CI 20.5–60.2, p < 0.001) were directly associated with correct classification, but motor and higher cerebral function were not correlated. ConclusionThe clinical OCSP classification presented good congruency rates with the neuroimaging findings. However, patients with lacunar syndromes are often misclassified when radiological criteria are considered.

Causal Effect of the 25-Hydroxyvitamin D Concentration on Cerebral Small Vessel Disease: A Mendelian Randomization Study.

Previous observational studies reported that a lower serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with a higher burden of cerebral small vessel disease (cSVD). The causality of this association is uncertain, but it would be clinically important, given that 25(OH)D can be a target for intervention. We tried to examine the causal effect of 25(OH)D concentration on cSVD-related phenotypes using a Mendelian randomization approach. Genetic instruments for each serum 25(OH)D concentration and cSVD-related phenotypes (lacunar stroke, white matter hyperintensity, cerebral microbleeds, and perivascular spaces) were derived from large-scale genome-wide association studies. We performed 2-sample Mendelian randomization analyses with multiple post hoc sensitivity analyses. A bidirectional Mendelian randomization approach was also used to explore the possibility of reverse causation. We failed to find any significant causal effect of 25(OH)D concentration on cSVD-related phenotypes (odds ratio [95% CI], 1.00 [0.87-1.16], 1.01 [0.96-1.07], 1.06 [0.85-1.33], 1.00 [0.97-1.03], 1.02 [0.99-1.04], 1.01 [0.99-1.04] for lacunar stroke, white matter hyperintensity, cerebral microbleeds, and white matter, basal ganglia, hippocampal perivascular spaces, respectively). These results were reproduced in the sensitivity analyses accounting for genetic pleiotropy. Conversely, when we examined the effects of cSVD phenotypes on 25(OH)D concentration, cerebral microbleeds were negatively associated with 25(OH)D concentration (0.94 [0.92-0.96]). Given the adequate statistical power (>0.8) of the analyses, our findings suggest that the previously reported association between 25(OH)D concentration and cSVD phenotypes might not be causal and partly attributed to reverse causation.

Acute bilateral multiple subcortical infarcts as manifestation in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterised by recurrent subcortical ischemic events, migraine with aura, dementia and mood disturbance. Strokes are typically lacunar infarcts; however, bilateral multiple subcortical lacunar infarcts have been described only sporadically. We described four CADASIL patients who presented with acute bilateral multiple subcortical infarcts as the first manifestation. We also briefly summarised the case reports detailing the bilateral multiple infarcts in CADASIL. Patient 1 and patient 2 were family members, and they presented with cognitive impairment. Patient 3 and patient 4 presented with slurred speech and hemiparesis. Patients 1, 3 and 4 developed hemodynamic fluctuations before the occurrence of ischemic stroke. Laboratory tests revealed elevated fibrinogen levels in patients 3 and 4. The brain magnetic resonance imaging showed acute bilateral multiple subcortical infarcts on the periventricular white matter in all the patients. CADASIL, with a poor brain hemodynamic reserve, is vulnerable to hemodynamic alterations (e.g. blood pressure fluctuation, dehydration, blood loss and anaemia) and intolerable to ischemia and hypoxia of the brain. Furthermore, blood hypercoagulation may contribute to acute multiple bilateral infarctions in CADASIL. Therefore, it is necessary to avert these predispositions in CADASIL patients in their daily life.

Metabolic Syndrome: A Strange Companion of Atrial Fibrillation; A Blessing in Disguise from the Neuropsychiatric Point of View.

Background: The concept of metabolic syndrome (MetSy) brings together components that individually represent a risk factor for cardiovascular diseases, which over time can prove to be more harmful if a combined effect of these is exhibited. Method: A single-centre retrospective study in an academic medical unit was conducted. We analysed the link between the MetSy and the occurrence of neuropsychic complications among atrial fibrillation (AF) patients. We sifted through the files of the patients admitted during 2015-2016 to the Municipal Emergency University Hospital Timisoara, Romania, with the diagnosis of AF. We divided these AF patients into two groups: the first group comprised patients with atrial fibrillation and MetSy (267 patients), while the second group comprised AF patients without MetSy (843 patients). We analysed the occurrence of neuropsychic changes (stroke, Parkinson's disease, dementia, cognitive impairment, and silent lacunar infarction) among the two groups. Results: Cognitive impairment (p-value = 0.0081) and dementia (p-value < 0.0001) were less frequent in patients with AF and MetSy than in those with AF without MetSy. Regarding the presence of stroke and Parkinson's disease (PD), we could not demonstrate the existence of any statistically significant difference between the two groups. Using logistic regression (enter test), we found that MetSy might have a protective effect (OR = 0.4040, 95% CI [0.2132; 0.7654], p-value = 0.0054) for the occurrence of dementia in those patients. Furthermore, obesity was the only factor with a possible protective effect from all the constituents of the MetSy when analysed together (with a significance level of p-value = 0.0004 for the logistic regression). The protective effect of MetSy against stroke occurrence was supplementarily proven by a longer period of survival without stroke from the AF diagnosis (3.521 years, p = 0.0304) compared to patients with AF without MetSy (3.286 years to first stroke occurrence). Conclusions: Metabolic syndrome might offer protection against the occurrence of dementia among patients with AF, but no effect was noted when compared with the presence of stroke. Further studies on larger cohorts can help us reach a conclusion regarding the positive effects of the metabolic syndrome.

Dietary nitrate intake in relation to the risk of dementia and imaging markers of vascular brain health: a population-based study

BackgroundNitric oxide is a free radical that can be produced from dietary nitrate and positively affects cardiovascular health. With cardiovascular health playing an important role in the etiology of dementia, we hypothesized a link between dietary nitrate intake and the risk of dementia. ObjectivesThis study aimed to find the association of total, vegetable, and nonvegetable dietary nitrate intake with the risk of dementia and imaging markers of vascular brain health, such as total brain volume, global cerebral perfusion, white matter hyperintensity volume, microbleeds, and lacunar infarcts. MethodsBetween 1990 and 2009, dietary intake was assessed using food-frequency questionnaires in 9543 dementia-free participants (mean age, 64 y; 58% female) from the prospective population-based Rotterdam Study. Participants were followed up for incidence dementia until January 2020. We used Cox models to determine the association between dietary nitrate intake and incident dementia. Using linear mixed models and logistic regression models, we assessed the association of dietary nitrate intake with changes in imaging markers across 3 consecutive examination rounds (mean interval between images 4.6 y). ResultsParticipants median dietary nitrate consumption was 85 mg/d (interquartile range, 55 mg/d), derived on average for 81% from vegetable sources. During a mean follow-up of 14.5 y, 1472 participants developed dementia. A higher intake of total and vegetable dietary nitrate was associated with a lower risk of dementia per 50-mg/d increase [hazard ratio (HR): 0.92; 95% confidence interval (CI): 0.87, 0.98; and HR: 0.92; 95% CI: 0.86, 0.97, respectively] but not with changes in neuroimaging markers. No association between nonvegetable dietary nitrate intake and the risk of dementia (HR: 1.15; 95% CI: 0.64, 2.07) or changes in neuroimaging markers were observed. ConclusionsA higher dietary nitrate intake from vegetable sources was associated with a lower risk of dementia. We found no evidence that this association was driven by vascular brain health.

The Role of Mitochondrial Biogenesis in Ischemic Stroke.

Ischaemic stroke is a sudden neurological disorder caused by localised cerebral ischaemia and persistent cerebral infarction. Occlusion of large arteries due to atherothrombosis, cerebral embolism (i.e., embolic infarction), no thrombotic occlusion in small, deep cerebral arteries (i.e., lacunar infarction), and stenosis of proximal arteries due to hypotension leading to decreased cerebral blood flow in arterial supply zones are the most common causes of ischemic stroke (i.e., hemodynamic stroke). It is now known that organelles play an important role in various signaling events and cellular functions. The molecular mechanisms of mitochondria are involved in cerebral ischemia by generating and scavenging reactive oxygen species, apoptosis, biogenesis, mitochondrial dynamics, and inflammation are all examples of electron transport chain dysfunction. More knowledge about the involvement of mitochondria in ischemia-induced neuronal death and neuronal protection will contribute to the development of better treatment programs for stroke syndromes such as ischemic stroke.

Morphological and molecular genetic diagnosis of CADASIL: a rare clinical case

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary autosomal dominant vascular injury of the brain. Currently, the clinical diagnosis of CADASIL is based on the following criteria: the onset of the condition at a relatively young age (4050 years), recurrent lacunar infarcts, gradual progression of encephalopathy with the development of pseudobulbar syndrome and dementia, various emotional disorders, and autosomal dominant inheritance. Having a family history of relatives with similar symptoms. The diagnosis is verified on the basis of the results of the following studies: neuroimaging, instrumental, morphological, and laboratory. The presence of leukoaraiosis and multiple small bilateral infarctions in such anatomical structures as the basal ganglia and white matter of the cerebral hemispheres, visual tubercles and the pons, and brain stem during MRI diagnostics. Histologically, transmission electron microscopy reveals granular osmiophilic inclusions in the adventitial membrane of the blood vessels of the brain, and on the periphery in the adventitia of the vessels of skeletal muscles and somatic nerves and in vascular biopsies of skin flaps. A mutation in the Notch3 gene determines the clinic of the disease and morphological changes in blood vessels and is detected by a molecular genetic method. The article presents a clinical case, which was a manifestation of this rare hereditary microangiopathy. Clinical case description: A 43-year-old patient was admitted to the Department of Neurology of the Republican Clinical Hospital in Simferopol for ischemic stroke in the basin of the left middle cerebral artery. According to the anamnesis, the patient suffered from migraine without aura from a young age and lacunar strokes; examination revealed a decrease in cognitive function, and MRI showed signs of microangiopathy of cerebral vessels. For final diagnosis, the patient underwent an intravital pathomorphological examination of the biopsy of the musculoskeletal flap; the results obtained made it possible to make a reliable diagnosis of CADASIL. Conclusion: Understanding and knowledge of such a rare pathology as CADASIL is crucial for the rapid recognition of a characteristic clinical picture for further appointment and interpretation of the results of morphological and molecular genetic diagnostics, making it possible to make the correct diagnosis and treatment.

EFFICACY OF INTRAVENOUS TIROFIBAN THERAPY IN LACUNAR STROKE PATIENTS

Background: Lacunar ischemic infarcts are small-sized infarcts that develop as a result of occlusion of perforating arteries. Although its pathophysiology differs from other stroke types, there is no separate treatment option from non-cardioembolic strokes. Early neurological worsening in lacunar strokes is a common condition reported up to 41%. There is no effective treatment method to prevent or correct progression. Tirofiban is a reversible receptor antagonist of glycoprotein IIb/IIIa. There are cohort studies with small number of cases related to its use in ischemic stroke. We wanted to evaluate its effectiveness on the progression of lacunar stroke because it is a powerful antiplatelet agent. Objective: Tirofiban is a reversible receptor antagonist of glycoprotein IIb/IIIa. There are cohort studies with small number of cases related to its use in ischemic stroke. We wanted to evaluate its effectiveness on the progression of lacunar stroke because it is a powerful antiplatelet agent. Methods: The data of patients who were followed up in our clinic with the diagnosis of lacunar stroke between August 2020 and May 2022 and who received tirofiban treatment were evaluated retrospectively. Patients' ages, infarct localizations, NIHSS scores at admission, at the beginning and end of tirofiban treatment, and 3rd month mRS scores were recorded. Results: Fifteen patients, 11 male and 4 female, were included in the study. The mean age of the patients was 68.73±9.58 (range, 51-85). Tirofiban was started proactively in 2 patients, after progression in 13 patients. The NIHSS scores were 7.20±2.65 at the start of the infusion, and 4.80±3.93 after the infusion, and the decrease was statistically significant (P=0.010). Conclusion: These findings suggest that intravenous tirofiban therapy is a safe and effective treatment option to stop symptomatic fluctuations and shorten the duration of deficit in patients with progressive lacunar stroke.

CLINICAL CHARACTERISTICS OF LACUNAR ISCHEMIC STROKE PATIENTS

Background: Stroke is the leading causes of death and disability in the world. Ischemic stroke covered 85% of stroke types. Based on the subtypes of ischemic stroke, lacunar ischemic stroke encompassed 20% of them. Knowing the characteristics help physicians to diagnose patients clinically and offer management to treat risk factors. Objective: This study aimed to know the characteristics of lacunar ischemic stroke based on patients risk factors, ischemic location on CT-scan, clinical syndrome, and NIHSS score. Methods: Using retrospective analytical study with cross sectional approach, medical record data from 2019-2022 were collected from RSUP DR. Hasan Sadikin Bandung. Results: From 60 patients, 35% (21) are 55-64 years old. Both sexes are equally distributed. 50 patients (83.3%) have multiple risk factors. Out of 60 patients, 57 (95%) have hypertension, 8 (13.3%) have diabetes mellitus, 44 (73.3%) have dyslipidemia, 6 (10%) have hyperuricemia, and 14 (23.3%) smoke. On admission, out of 60 patients, 34 (56.7%) have mild stroke, 23 (38.3%) have moderate stroke, 2 (3.3%) have moderate to severe stroke, and 1 (1.7%) has severe stroke. 44 (73.3%) out of 60 patients have pure motor hemiparesis. 41 (68.3%) out of 60 patients have basal ganglia ischemic. Conclusion: Lacunar ischemic stroke patients were equally distributed in sex with peak incidence occur between 55-64 years old. Most patients have multiple risk factors, basal ganglia lesion, pure motor hemiparesis, and history of hypertension, dyslipidemia, and smoking. On admission, most patients have mild stroke, followed by moderate stroke.

Brain MRI correlations with disease burden and biomarkers in Fabry disease

ObjectiveTo quantitatively evaluate cerebral small vessel disease (CSVD) in brain magnetic resonance imaging (MRI) and its correlation with disease burden and markers in Fabry disease, a rare X-linked lysosomal storage disease.MethodsWe collected brain MRI data from seventy-one Chinese patients with Fabry disease. CSVD was evaluated using an age-related white matter change rating scale, Fazekas scale, enlarged perivascular spaces grading scale, lacunar infarction scale, Microbleed Anatomical Rating Scale, global cortical atrophy scale, and small-vessel disease score. Factors associated with MRI lesions, including sex, clinical subtype, disease severity, disease burden, genotype, and biomarkers, were also analyzed.ResultsOf 71 patients, 16 (22.5%) experienced ischemic stroke. The incidences of lacunar infarctions, white matter hyperintensities, and cerebral microbleeds were 55%, 62%, and 33%, respectively. The abnormal MRI group had later disease onset, longer disease duration, and a higher Mainz Severity Score Index (p < 0.05) than the normal MRI group. Patients with more severe clinical phenotypes also had higher CVSD-related scores. Sex and GLA mutational type were not closely associated with brain MRI lesions. Of the disease markers, the Mainz Severity Score Index and plasma globotriaosylsphingosine (Lyso-Gb3) were closely correlated with the majority of the MRI scores, whereas α-galactosidase A activity was not.ConclusionBrain MRI revealed progressive lacunar infarctions, white matter hyperintensities, and decreased brain volume in patients with Fabry disease. Brain MRI lesions were closely related to onset-age; disease duration, severity, burden; and plasma Lyso-Gb3. However, they were not associated with sex, α-galactosidase A activity, or GLA mutation type.

The correlation between the severity of cerebral microbleeds and serum HMGB1 levels and cognitive impairment in patients with cerebral small vessel disease.

The study investigated the correlation and predictive value between the severity of cerebral microbleeds (CMBs) and the level of serum High Mobility Group Protein B1 (HMGB1) and the occurrence of cognitive impairment in patients with cerebral small vessel disease (CSVD). A total of 139 patients with CSVD admitted to the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical University from December 2020 to December 2022 were selected as study subjects. The Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function and was divided into the cognitive impairment group and the cognitive normal group. Magnetic Resonance Imaging (MRI) and Susceptibility Weighted Imaging (SWI) were used to screen and assess the severity of CMBs. Serum HMGB1 levels of CSVD patients were measured by enzyme linked immunosorbent assay (ELISA). Multivariable logistic regression analysis was used to explore risk factors for cognitive impairment and CMBs. Pearson correlation analysis was used to investigate the correlation between HMGB1 and cognitive function. Receiver Operating Characteristics (ROC) curves were used to assess the predictive value of HMGB1 for the occurrence of cognitive impairment in patients with CMBs. High Mobility Group Protein B1, uric acid (UA), glycosylated hemoglobin (HbA1c), CMBs, lacunar cerebral infarction (LI), years of education, and history of hypertension were risk factors for cognitive impairment (P < 0.05); HMGB1 was significantly and negatively associated with total MoCA score, visuospatial/executive ability, and delayed recall ability (P < 0.05). HMGB1 was significantly and positively correlated with the number of CMBs (P < 0.05). The area under the ROC curve for HMGB1 predicting cognitive impairment in patients with CMBs was 0.807 (P < 0.001). Serum HMGB1 levels are associated with the development of cognitive impairment in CSVD patients, and serum HMGB1 levels have a high predictive value for the development of cognitive impairment in CSVD patients with combined CMBs, which can be used for early clinical identification and intervention of vascular cognitive impairment.