Tissue plasminogen activator for acute branch atheromatous disease exhibits transient improvement and worsening.

BACKGROUND: Tissue plasminogen activator (tPA) is an effective treatment for acute ischemic stroke. Although initial improvement is observed when administered for branch atheromatous disease (BAD), some cases subsequently worsen. Clinical data on the characteristics of these patients is lacking, and the benefits of tPA are unclear. OBJECTIVE: To analyze rebound cases and elucidate the clinical characteristics and outcomes associated with tPA administration in BAD. METHODS: This multicenter retrospective study was conducted in Japan. Worsening after initial improvement of a condition is termed as rebound, and such cases were compared with other types of ischemic stroke in patients with and without rebound. The characteristics of patients with BAD who rebounded were examined. RESULTS: The study included 93 patients. Among the patients who were administered tPA, the NIHSS scores at 24 h and 7 days post-tPA were significantly higher in patients with BAD than in patients with other types of infarcts. The group with BAD exhibited a significantly higher rate of rebound than other groups (37.5 % vs. 0 %, P < 0.001). However, no differences were observed in outcomes between patients who experienced rebound after tPA administration and those who did not. CONCLUSIONS: Reevaluation and changing the strategy of tPA use in patients with BAD may be necessary. However, this study does not totally discourage its use, as specific patients can benefit.

Cerebral Small Vessel Disease and Infarct Growth in Acute Ischemic Stroke Treated with Intravenous Thrombolysis.

We investigated relations between cerebral small vessel disease (cSVD) markers and evolution of the ischemic tissue from ischemic core to final infarct in people with acute ischemic stroke treated with intravenous thrombolysis. Data from the Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA) were used. Any pre-existing lacunar infarcts and white matter hyperintensities (WMH) were assessed on magnetic resonance (MR) before thrombolytic therapy. Acute ischemic core and final infarct volume were then assessed by two independent radiologists. The relationship among baseline markers of cSVD, acute ischemic core volume, final infarct volume, infarct growth (IG = final infarct - ischemic core), and infarct growth ratio (IGR = final infarct/ischemic core) was then assessed using linear and ordinal regression adjusted for age, sex, onset-to-treatment time, and stroke severity. We included 165 patients, mean (± SD) age 69.5 (± 15.7) years, 74 (45%) males, mean (± SD) ischemic core volume 25.48 (± 42.22) ml, final infarct volume 52.06 (± 72.88) ml, IG 26.58 (± 51.02) ml, IGR 8.23 (± 38.12). Seventy (42%) patients had large vessel occlusion, 20 (12%) acute small subcortical infarct. WMHs were present in 131 (79%) and lacunar infarcts in 61 (37%) patients. Final infarct volumes were 53.8 ml and 45.2 ml (WMHs/no WMHs), p = 0.139, and 24.6 ml and 25.9 ml (lacunar infarcts/no lacunar infarcts), p = 0.842. In linear and ordinal regression analyses, presence of lacunar infarcts was associated with smaller IG (ß = - 0.17; p = 0.024; cOR = 0.52; 95%CI = 0.28-0.96, respectively) and WMHs were associated with smaller IGR (ß = - 0.30; p = 0.004; cOR = 0.27; 95%CI = 0.11-0.69, respectively). In people with acute ischemic stroke treated with intravenous thrombolysis, cSVD features were associated with smaller growth of the acute ischemic area, suggesting less salvageable tissue at time of reperfusion therapy.

Validation of a simple clinical tool for screening of acute lacunar stroke-A substudy of the WAKE-UP trial.

INTRODUCTION: Lacunar stroke represents around a quarter of all ischemic strokes; however, their identification with computed tomography in the hyperacute setting is challenging. We aimed to validate a clinical score to identify lacunar stroke in the acute setting, independently, with data from the WAKE-UP trial using magnetic resonance imaging. METHODS: We analyzed data from the WAKE-UP trial and extracted Oxfordshire Community Stroke Project (OCSP) classification. Lacunar score was defined by National Institutes of Health Stroke Scale (NIHSS) < 7 and OCSP lacunar syndrome. Assessment of lacunar infarct by two independent investigators was blinded to clinical data. We calculated sensitivity, specificity, negative and positive predictive value (NPV and PPV, respectively) of lacunar score. RESULTS: We included 503 patients in the analysis, mean (±SD) age 65.2 (±11.6) years, 325 (65%) males, median (IQR) NIHSS = 6 (4-9); 108 (22%) lacunar infarcts were identified on magnetic resonance (MR), patients fulfilling lacunar score criteria were 120 (24%), of which 47 (44%) had a lacunar infarct. Lacunar score was negative in 322 (82%) of patients without lacunar infarct. Patients with lacunar score had lower NIHSS (4 vs 7, p < 0.001), higher systolic (157 vs 151 mmHg, p = 0.001) and diastolic (86 vs 83 mmHg, p = 0.013) blood pressure and smaller infarct volume (2.4 vs 9.5 mL, p < 0.001). Performance of lacunar score was as follows: sensitivity 0.44; specificity 0.82; PPV 0.39; NPV 0.84; and accuracy 0.73. Assuming a prevalence of lacunar stroke of 13%, PPV lowered to 0.30 but NPV was 0.90. Lacunar score performed better for supratentorial lacunar infarcts. CONCLUSION: Lacunar score had a very good specificity and NPV for screening of lacunar stroke. Implementation of this simple tool into clinical practice may help hyperacute management and guide patient selection in clinical trials. DATA ACCESS STATEMENT: Data supporting the results of this paper are available upon reasonable request to the corresponding author.

New insight on the possible role of statins in Vascular Parkinsonism: A need for presumptive therapy.

Vascular Parkinsonism (VP) is clinical term represents a progressive ischemic changes and subcortical lacunar infarct leading to Parkinsonism mainly in the lower limbs so called lower body Parkinsonism. The VP neuropathology is differed from that of PD neuropathology which rarely associated with basal ganglion lesions. Dopamine transporters are normal in VP but are highly reduced in PD, and dopaminergic agonists had no effective role on VP. The neuropathological mechanisms of VP are related to vascular injury which induces the interruption of the neural connection between basal ganglion and cerebral cortex. Hyperlipidemia and other cardiometabolic risk factors augment VP risk and the related neuropathology. Targeting of these cardiometabolic disorders by lipid-lowering statins may be effective in the management of VP. Therefore, this mini-review aims to clarify the possible role of statins in the management of VP. Statins have neuroprotective effects against different neurodegenerative diseases by anti-inflammatory, antioxidant and antithrombotic effects with enhancement of endothelial function. In conclusion, statins can prevent and treat VP by inhibiting inflammatory and oxidative stress disorders, mitigating of white matter hyperintensities and improving of neuronal signaling pathways. Additional preclinical, clinical trials and prospective studies are warranted in this regard.

Guillain-Barré Syndrome and multiple lacunar infarcts in a COVID-19 patient.

INTRODUCTION: Hyperactivity immune responses to coronavirus disease 2019 (COVID-19) can lead to several manifestations in the human organ. One of the most affected organs is the respiratory system. Not only does it affect the respiratory system, but hyperactivity can also affect the neuromuscular and cerebrovascular systems, though it is scarce for both systems to be affected simultaneously. CASE PRESENTATION: We presented a mild COVID-19 patient with a history of progressive general weakness and dysphagia on day seventh day after patient was first diagnosed with COVID-19, which continued with diplopia and shortness of breath. The patient experienced respiratory failure type 1 and was admitted to an intensive care unit. A head CT scan showed multiple lacunar infarcts in the nucleus lentiform, while the electromyography (EMG) showed Guillain-Barré syndrome (GBS) with the subtype acute inflammatory demyelinating polyneuropathy (AIDP). The patient was reported to have successful therapy with intravenous immunoglobulin (IVIG) for five days and physical rehabilitation for three months. General weakness disappeared after the therapy, and the patient could do regular daily activities. CONCLUSIONS: Various neurological symptoms can manifest in COVID-19 patients. Acute progressive muscle weakness should be considered as an autoimmune and cerebrovascular disease induced by COVID-19. Early diagnosis and treatment can provide a better outcome for the patient.

Regional white matter hyperintensity volume predicts persistent cognitive impairment in acute lacunar infarct patients.

Background: White matter hyperintensity (WMH) is often described in acute lacunar stroke (ALS) patients. However, the specific relationship between regional WMH volume and persistent cognitive impairment remains unclear. Methods: We enrolled patients with ALS who were hospitalized at the First Affiliated Hospital of Soochow University between January 2020 and November 2022. All patients were assessed for global cognitive function using the Montreal Cognitive Assessment (MoCA) scale at 14 ± 2 days and 6 months after the onset of ALS. Manifestations of chronic cerebral small vessel disease (CSVD) were assessed via MRI scan. The distributions of regional WMH were segmented, and their relationship with cognitive impairment was evaluated. Results: A total of 129 patients were enrolled. Baseline frontal WMH volume (OR = 1.18, P = 0.04) was an independent risk factor for long-term cognitive impairment after ALS. Furthermore, the presence of WMH at the genu of the corpus callosum (GCC) at baseline (OR = 3.1, P = 0.033) was strongly associated with persistent cognitive decline. Multivariable logistic regression analysis showed that depression (OR = 6.252, P = 0.029), NIHSS score (OR = 1.24, P = 0.011), and albumin at admission (OR = 0.841, P = 0.032) were also important determinants of long-term cognitive impairment after ALS. Conclusions: Our study found that WMH, especially frontal WMH volume and the presence of WMH at the GCC at baseline, independently contributed to long-term cognitive decline in ALS patients. This study provides new evidence of the clinical relationship between regional WMH volume and cognitive impairment in ALS patients.

Application of the Intracranial Arterial Pulsatility Index for Determination of Prognosis after Lacunar Infarct.

Background: We aimed to investigate the usefulness of intracranial arterial pulsatility index to assess the prognosis of lacunar infarcts. Materials and Methods: Forty-nine patients with confirmed acute lacunar infarct were enrolled in the study. A transcranial color-coded sonography was performed to assess the pulsatility index of bilateral middle cerebral, posterior cerebral, vertebral, and proximal internal carotid arteries. Patients' clinical status was assessed using a modified Rankin scale. Spearman correlation was used for reporting the relation between quantitative data. Statistical significance was defined as a two-tail p-value of less than 0.05. Results: The mean age ± standard deviation was 64.1 ± 9.07 years old, and 57.1% of the patients were male. Upon discharge, only 8.2% of the patients were ranked as 0 on the modified Rankin scale; however, after a 6-month follow-up period, this number increased to 49%. There were no significant differences between the left and right pulsatility index measurements in any of the assessed arteries. Patients with vertebral artery pulsatility indexes >1 on their primary assessment had significantly worse outcomes during the first, third, and sixth months follow-up (all r > 0.3, p-values < 0.01). Pulsatility indexes from other arteries did not predict the prognosis. Conclusion: Sonography-assisted assessment of the vertebral artery blood flow during the early stage of lacunar infarct provides a reliable reference for prognosis estimation.

Cerebral white matter rarefaction has both neurodegenerative and vascular causes and may primarily be a distal axonopathy.

Cerebral white matter rarefaction (CWMR) was considered by Binswanger and Alzheimer to be due to cerebral arteriolosclerosis. Renewed attention came with CT and MR brain imaging, and neuropathological studies finding a high rate of CWMR in Alzheimer disease (AD). The relative contributions of cerebrovascular disease and AD to CWMR are still uncertain. In 1181 autopsies by the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), large-format brain sections were used to grade CWMR and determine its vascular and neurodegenerative correlates. Almost all neurodegenerative diseases had more severe CWMR than the normal control group. Multivariable logistic regression models indicated that Braak neurofibrillary stage was the strongest predictor of CWMR, with additional independently significant predictors including age, cortical and diencephalic lacunar and microinfarcts, body mass index, and female sex. It appears that while AD and cerebrovascular pathology may be additive in causing CWMR, both may be solely capable of this. The typical periventricular pattern suggests that CWMR is primarily a distal axonopathy caused by dysfunction of the cell bodies of long-association corticocortical projection neurons. A consequence of these findings is that CWMR should not be viewed simply as "small vessel disease" or as a pathognomonic indicator of vascular cognitive impairment or vascular dementia.

Association between estimated pulse wave velocity and silent lacunar infarct in a Korean population.

Aims: Previous studies have proposed the estimated pulse wave velocity (ePWV) as a simple and cost-effective measure of arterial stiffness. Since arterial stiffness plays a role in the progression of silent lacunar infarct (SLI), our present work aims to evaluate the association between ePWV and the presence of SLI. Methods: The present work was based on a cross-section study. Our study included 1,011 neurologically healthy Korean participants. The SLI was evaluated using brain magnetic resonance images (MRI). The ePWV was derived from a published equation using age and mean blood pressure (MBP). Logistic regression analyses were performed to investigate the association between ePWV and SLI. The linear relationship and robustness were evaluated using smooth curve fitting and subgroup analyses, respectively. Results: The prevalence of SLI was 11.87%. After fully adjusting for covariates, per 1 m/s increase of ePWV casted 31% additional risk for SLI (P = 0.009). When dividing the ePWV into quartiles, the top quartile had 4.01 times risk compared with the bottom quartile. The increasing trend across the quartiles was statistically significant (P for trend < 0.001). Consistently, smooth curve fitting revealed that the risk of SLI elevated linearly with the increase of ePWV. Finally, subgroup analysis suggested that the association was robust in several sub-populations divided by age, sex, smoking, hypertension, diabetes mellitus (DM), coronary artery occlusive disease (CAOD), hyperlipidemia, and statin medication (all P for interaction > 0.05). Conclusion: The current study revealed an independent and positive association between ePWV and the presence of SLI in a neurologically healthy Korean population.

A Rare Presentation of Late-Onset Mania Following Right-Sided Lacunar Infarct.

Stroke can result in various psychiatric disorders. It is uncommon for people to experience their first episode of mania later in life, amounting to only 1% as compared to post-stroke depression, where the incidence is comparatively high. Significant attention has been paid to the study of post-stroke depression. However, reports of manic episodes following a stroke are uncommon. Just five reported cases of mania or bipolar disorder following a cerebral infarction due to damage to the left hemisphere had been published as of late 1996. There is insufficient evidence to conclude whether late-onset mania has an organic or non-organic basis. There hasn't been a lot of research done in this area. In this report, we present a case of an elderly woman who presented with mania after being treated with an anti-depressant following a chronic cerebral infarction.

The history, current situation and prospect of lacunar infarct / 中华神经科杂志

The modern concept of lacunar infarct is largely based on the meticulous postmortem work of Fisher from the 1950s to 1970s, which forms the basis of the"lacunar hypothesis". Along with the application of CT or MRI techniques and classification of ischemic stroke subtypes, the lacunar infarct was endowed with the profile of imaging diagnosis and stroke subtypes. Thus, the concept of lacunar infarct has far expanded the initial pathological meanings and the terminology and definitions for lacunar infarct vary widely. In this review, the historical pathological findings and the term evolution of lacunar infarct were systemically reviewed, with a focus toward future directions in the complex entity of lacunar infarct.

Electrochemically induced in vitro focal hypoxia in human neurons.

Focalised hypoxia is widely prevalent in diseases such as stroke, cardiac arrest, and dementia. While in some cases hypoxia improves cellular functions, it mostly induces or exacerbates pathological changes. The lack of methodologies that can simulate focal acute hypoxia, in either animal or cell culture, impedes our understanding of the cellular consequences of hypoxia. To address this gap, an electrochemical localised oxygen scavenging system (eLOS), is reported, providing an innovative platform for spatiotemporal in vitro hypoxia modulation. The electrochemical system is modelled showing O2 flux patterns and localised O2 scavenging and hypoxia regions, as a function of distance from the electrode and surrounding flux barriers, allowing an effective focal hypoxia tool to be designed for in vitro cell culture study. O2 concentration is reduced in an electrochemically defined targeted area from normoxia to hypoxia in about 6 min depending on the O2-flux boundaries. As a result, a cell culture-well was designed, where localised O2 scavenging could be induced. The impact of localised hypoxia was demonstrated on human neural progenitor cells (hNPCs) and it was shown that miniature focal hypoxic insults can be induced, that evoke time-dependent HIF-1α transcription factor accumulation. This transcription is "patterned" across the culture according to the electrochemically induced spatiotemporal hypoxia gradient. A basic lacunar infarct model was also developed through the application of eLOS in a purpose designed microfluidic device. Miniature focal hypoxic insults were induced in cellular processes of fully oxygenated cell bodies, such as the axons of human cortical neurons. The results demonstrate experimentally that localised axonal hypoxic stress can lead to significant increase of neuronal death, despite the neurons remaining at normoxia. This suggests that focal hypoxic insult to axons alone is sufficient to impact surrounding neurons and may provide an in vitro model to study the impact of microinfarcts occurring in the deep cerebral white matter, as well as providing a promising tool for wider understanding of acute hypoxic insults with potential to uncover its pathophysiology in multiple diseases.

Scattered cerebral infarction in the corona radiata predicts worse outcomes.

OBJECTIVES: Intracranial branch atheromatous disease often results in progressive motor deficits in the lenticulostriate arteries (LSA). In some patients with LSA infarction, magnetic resonance imaging (MRI) revealed single lesions at the LSA origin from the middle cerebral artery spreading in a scattered manner toward the distal area. This study aimed to elucidate the clinical characteristics of such cases. MATERIALS AND METHODS: This was a single-center, retrospective study comprising 1,840 consecutive patients admitted to the Ina Central Hospital, Japan. Two neurologists selected patients with LSA infarctions on the basis of MRI data. Patients with a single mass of infarct lesion from the origin were classified as the single group, whereas patients with infarct lesions as a single mass at LSA origin but divided and independent as the infarct area extended distally were classified as the scattered group. We compared the clinical characteristics and outcomes in these groups. RESULTS: The single and scattered groups included 119 and 35 patients, respectively. We defined worsening as an increase of one point or more on the National Institute of Health Stroke Scale. Univariate analysis demonstrated that patients in the scattered group showed significantly more worsening after hospitalization compared with those in the single group (48.6% vs. 28.6%; p < .05). Moreover, this can easily lead to increased disease severity (p < .016). In a multivariate analysis, group (odds ratio, 2.5 [95% CI, 1.11-5.74], p < .03) was an independent predictor of symptom worsening. CONCLUSIONS: Scattered infarction in the corona radiata is an aggravating factor leading to worse outcomes.

Ischemic stroke cases presenting with hand weakness mimicking peripheral neuropathy.

Pure motor monoparesis due to ischemic stroke involving a single extremity is a rare condition that can be easily misdiagnosed. Herein, we present three cases with isolated upper extremity monoparesis. All of our patients had weakness in the left hand. They were previously evaluated in other centers and were diagnosed with peripheral neuropathy by electromyography. When patients whose complaints did not resolve were admitted to our clinic, we performed electromyography again and observed that it was normal. Hereupon, we detected ischemic infarctions in cranial magnetic resonance imaging that would explain the patients' complaints. Isolated monoparesis mimicking peripheral neuropathy is a rare symptom in stroke patients. Pure motor monoparesis should be kept in mind in every patient presenting with acute-isolated monoparesis, and neuroradiological imaging should be performed.

Corrigendum: Electrochemically induced in vitro focal hypoxia in human neurons.

[This corrects the article DOI: 10.3389/fcell.2022.968341.].

Risk assessment of lacunar infarct associated with oral conditions: A case control study focused on radiographic bone loss and Eichner classification.

PURPOSE: This study aimed to evaluate whether lacunar infarcts can be predicted from occlusal support and periodontal stage on images. METHODS: Seventy patients with lacunar infarcts and 300 participants without lacunar infarcts who underwent cerebral checkups at our university hospital were retrospectively reviewed. Lacunar infarcts were assessed using magnetic resonance images by a neuroradiologist. The number of teeth, occlusal support, and severity of radiographic bone loss (RBL) were evaluated using computed tomography. Occlusal support was classified according to the Eichner classification. Additionally, patient characteristics were investigated using medical charts and blood test reports. Records of clinical periodontal parameters, such as clinical attachment loss and bleeding on probing, were also evaluated. RESULTS: The severity of RBL and Eichner classification in patients with lacunar infarcts was significantly higher than that in individuals without lacunar infarcts (P<.01). Receiver operating characteristic analysis revealed that the cut-off values for predicting lacunar infarct were ≥ III in the severity of RBL and ≥B1 in the Eichner classification. The corresponding areas under the curve were 0.75 and 0.70, respectively. In multivariate analysis, the factors affecting the severity of RBL (≥ III) (odds ratio [OR], 8.1; 95% confidence interval [CI], 4.1-16.3; P<.001), and Eichner classification (≥B1) (OR, 1.9; 95% CI, 0.86-4.1; P<.05) were significantly associated with the occurrence of lacunar infarcts. CONCLUSION: The severity of RBL and the Eichner classification may be helpful in predicting lacunar infarcts. Therefore, proper periodontal treatment and prosthodontic rehabilitation of missing teeth may prevent lacunar infarcts.

[Current state of cerebral microangiopathy in hypertension]. / Sovremennoe sostoyanie problemy tserebral'noi mikroangiopatii pri arterial'noi gipertenzii.

Hypertension is the main cause and the most important risk factor for both acute cerebrovascular accident and chronic progressive cerebrovascular insufficiency that is accompanied by severe neurological and mental disorders even to the extent of developing dementia. They are based on hypertension-induced pathology of the intracerebral arteries and cerebral microvasculature - cerebral microangiopathy that leads to small deep (lacunar) infarcts (SDIs) and diffuse cerebral white matter diseases. This review highlights the morphology, pathogenesis, clinical and neuroimaging diagnosis of hypertensive SDIs, and their differential diagnosis with atherosclerotic SDIs in the historical aspect. It is emphasized that the lacunar state of the brain in hypertension is a predictor of massive cerebral hemorrhages. Special attention is paid to current studies of the morphology and pathogenesis of diffuse changes in white matter and to the role of blood-brain barrier impermeability in the development of progressive leukoencephalopathy.

Lacunar cerebral infarction following endovascular interventions for phlegmasia cerulea dolens.

Phlegmasia cerulea dolens is a rare presentation of deep venous thrombus treated with catheter directed thrombolysis and pharmacomechanical thrombectomy. This is the case of a 78-year-old woman who underwent catheter directed thrombolysis to treat phlegmasia cerulea dolens and subsequently developed left-sided hemiplegia and expressive aphasia in the setting of an international normalized ratio of 2.0. Further imaging revealed a lacunar infarct in the right thalamus with a middle cerebral artery distribution. Further workup revealed a patent foramen ovale. We highlight the unexpected enigmatic consequence from multimodal endovascular intervention, the consequence of long-term inferior vena cava filters.

Urine retention as presenting manifestation of tuberculous meningitis complicated by lacunar infarction and transverse myelitis: Case report and literature review.

Early diagnosis and management of tuberculous meningitis will prevent lethal and fatal neurological complications such as acute infarction and permanent disability.