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Multifocal cerebral infarction in brain white matter. A 36-year-old woman presented with repeated dizziness and right upper extremity uncoordinated activities three weeks. Neuroimaging showed new multifocal cerebral infarction. A, Multiple hypodensity lesions in bilateral basal ganglia on noncontrast CT. B, Hyperintense lesions in left caudate nucleus, internal capsule and frontal knee on the DWI MR image. C, Demyelinating lesions near the bilateral corn occipitale on the FLAIR MR image. D, No enhancement lesions on the Gd-enhanced MR image. E, Absence of left anterior cerebral artery A1 segment with the right posterior communicating artery opened on the MRA. F, DSA showed normal vascular in anterior circulation area.
Source publication
Background:
Neurological antiphospholipid syndrome (NAPS) is often misdiagnosed or missed. Only limited clinical and neuroimaging information about it is available, and the pathological characteristics was rarely reported before. This study aimed to explore the clinical, neuroimaging, and pathological characteristics of NAPS.
Methods:
We perform...
Context in source publication
Context 1
... NAPS patients underwent Cranial CT and MRI evaluation. Multi- ple new cerebral infarctions were concentrated in the periventricular white matter on CT plain (Fig. 1). Computed tomography angiography (CTA) showed stenosis or occlusion in anterior cerebral artery (ACA), middle cerebral artery (MCA) and posterior cerebral artery (PCA) and their branches. MRI lesions, including lacunar infarctions and large area infarctions, were detected in basal ganglia and cerebral cortex (Fig. 2). Local brain ...
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Citations
... The identification, diagnosis, and treatment of CVST depend more and more on diagnostic imaging. Further MRV screening is necessary when the results of the head CT and cranial MRI are normal, as CVST cannot be completely ruled out [18]. Both the MRV and cranial MRI exams are easy to use and can make up for each other's shortcomings. ...
Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke especially among young adults. The clinical presentation of CVST is diverse, which makes the diagnosis to be challenging. Lower cranial neuropathy is a rare presentation of CVST, with few cases in literature. We are describing a case of 39-year-old male patient, presented with left occipital neuralgia, with left lower cranial neuropathies due to left transverse and sigmoid sinus thrombosis; secondary to antiphospholipid syndrome, with good response to anticoagulation.
... Furthermore, APS patients may present brain MRI with T2 hyperintense brain lesions, which may not be easily differentiated from MS. It may be particularly misleading, as scattered hyperintense subcortical white matter lesions are the most common MRI finding in APS (16). ...
Multiple sclerosis (MS) and anti-phospholipid syndrome (APS) are chronic, immune-mediated, relapsing-remitting disorders
affecting young adults. APS is characterized by thrombosis and pregnancy mortality associated with anti-phospholipid antibodies.
The diagnosis of APS may be difficult, and it is not uncommon for patients with APS to be misdiagnosed with multiple sclerosis.
In this case report, we describe a patient who was diagnosed as having multiple sclerosis for eleven-year. Initially, the patient had
neurological deficits with relapsing-remitting courses, like MS but he had not classic magnetic resonance imaging appearance
of MS and absence of oligoclonal bands in the cerebrospinal fluid. He did not meet the 'dissemination criteria in time and place'
specified in the MS diagnostic criteria. Also, he had an acute myocardial infarction and ischemic stroke at different times. The diagnosis of primary APS was made after the patient had thrombotic attacks, seizure and was positive for anti-phospholipid antibodies (aPLs) twice. Our observations raise awareness about the importance of the early and correct diagnosis of APS. When assessing MS patients, clinicians should consider APS, if the MS has atypical features.
... In respect to superficial vein thrombosis, in a prospective study of patients with SLE and/or aPL, its presence carried a hazard ratio of 7.45 for the occurrence of thromboembolic events, suggesting a possible prognostic significance [27]. Relative to brain white matter lesions, APS patients frequently display abnormalities on neuroimaging studies, most commonly focal subcortical white matter areas of signal hyperintensity [28,29]. It is not always clear whether these lesions represent ischemia or inflammation [28,29], with hints pointing towards an APS diagnosis including smaller lesions on MRI, frequently located in the subcortical area, with stability over time and possible improvement with anticoagulation therapy [30]. ...
... Relative to brain white matter lesions, APS patients frequently display abnormalities on neuroimaging studies, most commonly focal subcortical white matter areas of signal hyperintensity [28,29]. It is not always clear whether these lesions represent ischemia or inflammation [28,29], with hints pointing towards an APS diagnosis including smaller lesions on MRI, frequently located in the subcortical area, with stability over time and possible improvement with anticoagulation therapy [30]. The evidence of a potential impact of these lesions in patients' prognosis gains relevance as their significance is still debated in APS. ...
Background
Seronegative antiphospholipid syndrome (SN-APS) is often defined as the presence of APS criteria manifestations, negative antiphospholipid antibodies (aPL), and coexistence of APS non-criteria manifestations. Nevertheless, the impact of these non-criteria features is still unclear. On a different note, the relevance of one single aPL positive determination in patients with APS manifestations is another domain with limited evidence. We aim to compare the course of SN-APS and single-positive aPL (SP-aPL) patients with that of individuals with APS manifestations without non-criteria features/aPL positivity (controls).
Methods
Retrospective analysis of patients with thrombosis/obstetric morbidity assessed in two European hospitals between 2005 and 2020. Patients were divided into SN-APS, SP-aPL, and control groups. Clinical characteristics, comorbidities, and therapies were compared.
Results
A total of 82 patients were included in the SN-APS group, 88 in the SP-aPL group, and 185 in the control group. In Cox regression model, SN-APS displayed more thrombosis recurrence than controls (HR 3.8, 95% CI 2.2–6.5, p < 0.001) even when adjusting for the presence of hereditary thrombophilia, systemic lupus erythematosus, or contraceptive hormonal treatment. In SP-aPL, the difference in thrombosis recurrence did not reach statistical significance (p = 0.078). Indefinite anticoagulation (p < 0.001 and p = 0.008, respectively) and vitamin K antagonist (VKA) use (p < 0.001 in both cases) were more common in SN-APS/SP-aPL.
Conclusion
SN-APS displayed more thrombosis recurrence, indefinite anticoagulation, and VKA use than controls without non-criteria manifestations. The presence of such features in patients with thrombosis and negative aPL may negatively impact their clinical course.
... A study carried out by Zhu et al. [250] on a cohort of 51 APS patients showed a higher prevalence of headache in those with neurological antiphospholipid syndrome (NAPS), when compared to the rheumatologic form of the disease (RAPS). Interestingly, the authors detected by digital subtraction angiography (DSA) in NAPS patients typically multifocal vascular stenoses. ...
Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion and the trigeminal nucleus caudalis.
The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the Human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine.
The present review summarizes available findings to date from genetic and biomarker studies that have explored the role of inflammation in primary headaches.
... A study carried out by Zhu et al. [250] on a cohort of 51 APS patients showed a higher prevalence of headache in those with neurological antiphospholipid syndrome (NAPS), when compared to the rheumatologic form of the disease (RAPS). Interestingly, the authors detected by digital subtraction angiography (DSA) in NAPS patients typically multifocal vascular stenoses. ...
Several lines of evidence support a role of the immune system in headache pathogenesis, with particular regard to migraine. Firstly, alterations in cytokine profile and in lymphocyte subsets have been reported in headache patients. Secondly, several genetic and environmental pathogenic factors seem to be frequently shared by headache and immunological/autoimmune diseases. Accordingly, immunological alterations in primary headaches, in particular in migraine, have been suggested to predispose some patients to the development of immunological and autoimmune diseases. On the other hand, pathogenic mechanisms underlying autoimmune disorders, in some cases, seem to favour the onset of headache. Therefore, an association between headache and immunological/autoimmune disorders has been thoroughly investigated in the last years. The knowledge of this possible association may have relevant implications in the clinical practice when deciding diagnostic and therapeutic approaches. The present review summarizes findings to date regarding the plausible relationship between headache and immunological/autoimmune disorders, starting from a description of immunological alteration of primary headaches, and moving onward to the evidence supporting a potential link between headache and each specific autoimmune/immunological disease.
... Stroke is one of the most common CNS involvements in APS, accounting for 13.1% of initial manifestations of patients in a cohort of 1000 patients with APS [29]. Previous studies have shown that from 7.1 to 100% of APS patients with CNS manifestations showed brain lesions detected by cerebral CT scan [17], cerebral MRI [30] or electroencephalogram [31] and increased heterogeneity of brain perfusion by single photon emission CT [32]. A missing point in the previous studies is the lack of consideration of persistently aPL-Liyan Wan et al. ...
Objectives
Thrombosis occurring in the central nerve system is common in antiphospholipid syndrome (APS) patients, leading to neuropsychiatric symptoms. We investigated the prevalence of silent brain abnormalities on magnetic resonance imaging (MRI) in primary antiphospholipid syndrome (PAPS) patients and antiphospholipid antibodies (aPL) carriers and assessed the association between the vascular risk factors, aPL profile, clinical manifestations, and MRI abnormalities.
Methods
We consecutively included 44 PAPS patients, 24 aPL carriers and 23 healthy controls with comparable age and gender in a single-center, observational cross-sectional study. None of the patients had a history of stroke, TIA, migraine, dementia, epilepsy and bipolar disorders. On cerebral MRI, we assessed the imaging features and location of abnormality. Multivariate analysis was performed to identify the risk factors contributing to the MRI abnormalities.
Results
38 (55.88%) patients persisted abnormal MRI findings, while only one healthy control showed some abnormalities in the MR findings. Lacunes were the most frequent MRI abnormality in aPL (+) group (31/68, 45.59%), which were followed by white matter hyperintensities (20/68, 29.41%). In all study population, age (OR = 1.086, p= 0.016) and LA positivity (OR = 5.191, p= 0.002) were the independent associated factors with the brain MRI abnormalities. When analyzed only in the aPL (+) group, age (OR = 1.116, p= 0.007), female gender (OR = 7.519, p= 0.025) and thrombocytopenia (OR = 8.336, p= 0.047) were the significant independent risk factors with abnormal MRI.
Conclusions
PAPS patients and aPL carriers showed a high prevalence of brain MRI abnormalities, indicating an increased cerebrovascular risk, which emphasized attention to silent cerebral lesions in persistently aPL positive patients.
... APS is an autoimmune antibody-mediated disease, characterized by recurrent vascular thrombosis (venous, arterial and microvascular), pregnancy morbidity and thrombocytopenia [1][2][3]. A characteristic indicator of APS is the presence of aPL, including LA, as well as IgG and IgM aCL, and anti-b2 glycoprotein-I antibodies Rheumatology key messages . ...
... (anti-b2GPI) [2,4,5], and diagnosis is made in accordance with the International updated Sapporo (Sydney) classification criteria [6]. APS can occur in isolation, where the disease is classified as occurring alone [primary APS (PAPS)], or in the context of other autoimmune conditions [secondary APS (SAPS)], most notably SLE [7]. ...
... Although neuroimaging biomarkers are a potentially powerful way to understand mechanisms of cognitive impairment, evidence summarizing neuroimaging characteristics of APS is also scare [2,14]. One review article described the relationship between cognitive dysfunction and magnetic resonance abnormalities (MRI) specific to patients with SLE [8]. ...
Objectives:
Cognitive dysfunction is common in patients with antiphospholipid antibodies (aPL) (including primary antiphospholipid syndrome (APS) or APS associated with systemic lupus erythematosus (SLE)). Neuroimaging biomarkers may contribute to our understanding of mechanisms of cognitive dysfunction in these cohorts. This review aimed to investigate: (1) the prevalence of cognitive dysfunction in studies including neuroimaging biomarkers; and (2) associations between cognition and neuroimaging biomarkers in patients with APS/aPL.
Methods:
We conducted a systematic search of electronic databases PubMed, Science Direct, Scopus and PsycINFO and included studies with descriptions of neuroimaging findings, cognitive dysfunction, or both, in patients with aPL positivity (lupus anticoagulant, IgG and IgM anticardiolipin and anti-β2 glycoprotein-I antibodies).
Results:
Of 120 search results we included 20 eligible studies (6 APS, 4 SLE with APS/aPL and 10 neuropsychiatric SLE (NPSLE)). We identified a medium risk of bias in 6/11 (54%) of cohort studies and 44% of case-control studies, as well as marked heterogeneity in cognitive assessment batteries, APS and aPL definitions and neuroimaging modalities and protocols. The prevalence of cognitive dysfunction ranged between 11% and 60.5%. Structural MRI was the most common imaging modality, reporting cognitive dysfunction to be associated with white matter hyperintensities, ischaemic lesions and cortical atrophy (4 with cerebral atrophy, 2 with white matter hyperintensities, and 2 with cerebral infarcts).
Conclusion:
Our findings confirm that cognitive impairment is commonly found in patients with aPL (including APS, SLE and NPSLE). The risk of bias, and heterogeneity in cognitive and neuroimaging biomarkers reported does not allow for definitive.
... Studies suggested that CVST is associated with the production of aPLs which targets at cerebral venous and platelet in APS. [23][24][25][26] APLs, namely LAC, aCL, anti-b2-GP1, are a heterogeneous group of auto-antibodies directed against phospholipid binding proteins. The involvement of aPLs in clinically significant normal procoagulant and anticoagulant reactions and on certain cells altering the expression and secretion of various molecules are the basis for possible mechanisms. ...
Antiphospholipid syndrome (APS) with cerebral venous sinus thrombosis (CVST) is a relatively rare phenomenon, and this observational study aimed to investigate the clinical characteristics of APS patients complicated with CVST. We retrospectively investigated the clinical characteristics of CVST events in APS and compared differential characteristics and associated factors between APS patients with and without CVST. Twenty-one CVST patients with APS were enrolled including 14 females (9.4%) and 7 males (5.8%). The median age and disease duration at onset of CVST was 33 years (IQR 28-48) old and 1.3 months (IQR 0.7-4), respectively. Among APS patients with CVST, 12 (57.1%) cases presented with neurologic symptoms of CVST as the initial manifestation. Onset of CVST was mainly chronic (52.4%). Headache (90.5%) was the most common neurological symptom. The common locations of CVST were transverse sinus (76.2%) and superior sagittal sinus (57.1%), with more frequently (76.2%) dual or multiple sinuses involved. All patients with CVST were treated with anticoagulant, and 5 (23.8%) patients received endovascular therapy. Sixteen (84.2%) patients had good outcomes and 3 (15.8%) patients died at last follow-up. There were no significant differences ( P > 0.05) between two groups in the analysis of related APS indicators. There were no significant differences ( P > 0.05) between two groups in the analysis of related APS indicators. Although APS complicated with CVST is rare and predominately chronic developed. The evaluation of CVST should be performed for APS patients with intracranial hypertension syndrome. The routine screening of antiphospholipid antibodies (aPLs) is highly recommended in unexplained CVST patients. Most CVST patients with APS will have a good prognosis after treatment, and endovascular therapy is an alternative treatment.
... Lacunar infarcts in the deep cerebral white matter, as well as ischemic lesions in the spinal cord, may also occur in patients with APS, resembling those found in patients with MS. Multiple subcortical/cortical infarcts with demyelination, involving both lobes of the brain asymmetrically, have been recently classified as the typical brain MRI features of APS, as result of ischemic cerebrovascular disease caused by vascular occlusion [88]. ...
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by arterial, venous, and/or small vessel thrombosis, pregnancy morbidity, and persistently elevated levels of antiphospholipid antibodies (aPL). Cardiovascular disease (CVD) in APS can present as heart valvular disease (HVD), macro-micro-coronary artery disease (CAD), myocardial dysfunction, cardiac thrombi, or pulmonary hypertension. Brain disease presents as stroke or transient ischemic attack (TIA) and less frequently as cerebral venous thrombosis, seizures, cognitive dysfunction, multiple sclerosis (MS)−like syndrome, or chorea. Infarcts and focal white matter hyperenhancement are the commonest brain (MRI) abnormalities, while myocardial ischemia/fibrosis, valvular stenosis/regurgitation, or cardiac thrombi are the main abnormalities detected by cardiovascular magnetic resonance. This review aims to present the existing evidence on brain/heart involvement and their interrelationship in APS and the role of brain/heart MRI in their evaluation. Embolic brain disease, due to HVD, CAD, and/or cardiac thrombus, or brain hypo-perfusion, due to myocardial dysfunction, are among the main brain/heart interactions in APS and they are considered determinants of morbidity and mortality. Currently, there is no evidence to support the use of combined brain/heart MRI in asymptomatic APS patients. Until more data will be available, this approach may be considered in APS patients at high risk for CVD/stroke, such as systemic lupus erythematosus with high-risk aPL profile or high scores in CVD risk prediction models; APS patients with HVD/thrombus, CAD, or heart failure; those with classic and non-criteria neurologic APS manifestations (seizures, cognitive dysfunction, MS-like syndrome); or with aggressive multi-organ disease.
Key Points
• Cardiovascular disease (CVD) in antiphospholipid syndrome (APS) can present as heart valvular disease (HVD), macro-micro-coronary artery disease (CAD), myocardial dysfunction, cardiac thrombi, or pulmonary hypertension.
• Brain disease presents as stroke or transient ischemic attack (TIA), and less frequently as cerebral venous thrombosis, seizures, cognitive dysfunction, and multiple sclerosis (MS).
• A combined brain/heart MRI may be considered in APS patients at high risk for CVD/stroke, such as systemic lupus erythematosus with high-risk aPL profile or high scores in CVD risks; APS patients with HVD/thrombus, CAD, or heart failure; those with classic and non-criteria neurologic APS manifestations (seizures, cognitive dysfunction, MS-like syndrome); or with aggressive multi-organ disease.
... A neurological APS may mimic MS in clinical presentation, and even give similar findings on an MRI [16]. Demyelinating white matter lesions involving the periventricular area and/or both cerebral lobes are characteristic MRI findings in patients who suffer from APS [17][18]. ...
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder with marked thrombotic and inflammatory features driven by the presence of antiphospholipid antibodies (APLA). Here, we report a case of APS with a rare, atypical manifestation and discuss a differential diagnosis.
A 53-year-old male without significant past medical history presented with new onset of episodic tongue stiffness and dysarthria which lasted for about a minute over a period of three months. This was associated with intermittent right retro-orbital sharp pain radiating to the parietal area. He also reported swelling and stiffness of the third and fourth right proximal interphalangeal (PIP) joints lasting throughout the day. A physical exam revealed tongue fasciculations. As the MRI showed patchy white matter hyperintensities neurology initially suspected multiple sclerosis. However, cerebrospinal fluid (CSF) analysis including neuromyelitis optica (NMO) antibodies and oligoclonal antibodies was negative. Rheumatological work up was remarkable for positive antinuclear antibodies (ANA); anticardiolipin antibodies and lupus anticoagulant were positive 12 weeks apart. This, alongside with stable white matter changes on imaging was suspicious for an extra-criteria manifestation of antiphospholipid antibody syndrome.
The most commonly described neurological manifestations of APS are headache, transient ischemic attack (TIA), and stroke. Tongue stiffness as an initial symptom is quite unusual and, to the best of our knowledge has not been reported in medical literature. In patients with isolated neurological findings of unclear etiology, an autoimmune disease such as APS should be considered, and appropriate diagnostic work up should not be postponed. Unfortunately, positive laboratory markers can have a wide differential diagnostic panel. In addition, APS may mimic many diseases both in clinical presentation and MRI findings thus making the correct diagnosis challenging. However, studies show that, unlike multiple sclerosis (MS), white matter changes in APS remain static during the course of the disease. Identification of atypical presentations of APS is critical as prompt and correct medical management can improve patients’ quality of life and clinical outcomes.
