Neurological antiphospholipid syndrome: Clinical, neuroimaging, and pathological characteristics

Zhu, Dezhi; Fu, Jue; Zhang, Yue; Li, Shi-Xu; Zhang, Guang‐Xian; Guan, Yangtai; Dong, Qiang

doi:10.1016/j.jns.2014.08.010

Cited by 27 publications

(21 citation statements)

References 34 publications

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“…In addition, our patient showed chronic ischemic lesions in cortical and sub-cortical areas suggestive of infarcts of small vessels (Fig. 2) [23]. This observation together with the hematological findings confirming the presence of anti-phospholipid antibodies (aPL), allowed the diagnosis of antiphospholipid syndrome type I (APS) in our patient [8].…”

Section: Discussionsupporting

confidence: 59%

“…Herein, we show data from only one patient, so further studies are needed to assess the relationship between mTOR variants and APS, and to demonstrate if it is a general mechanism in mTORopathies or our patient is a particular case. For this purpose, APS assessment (clinical, neuroradiologic and hematologic) should be investigated in patients with mTOR variants, in order to clarify the clinical relationship between mTOR, APS and endothelial injury [23].…”

Section: Discussionmentioning

confidence: 99%

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A novel de novo MTOR gain-of-function variant in a patient with Smith-Kingsmore syndrome and Antiphospholipid syndrome

et al. 2019

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We report the clinical, biochemical and genetic findings from a Spanish girl of Caucasian origin who presented with macrocephaly, dysmorphic facial features, developmental delay, hypotonia, combined oxidative phosphorylation (OxPhos) deficiency, epilepsy and anti-phospholipid antibodies (aPL). Whole-exome sequencing (WES) uncovered a heterozygous variant in the MTOR gene (NM_004958.3: c.7235A>T: p.(Asp2412Val)) that encodes for the Serine/threonine-protein kinase mTOR. The substrates phosphorylation experiments demonstrated that this variant exerts its effect by gain-offunction (GOF) and autosomal dominant mechanism. GOF variants in this protein have been associated with Smith-Kingsmore syndrome (SKS), a rare autosomal dominant disorder characterized by intellectual disability, macrocephaly, seizure, developmental delay and dysmorphic facial features. Furthermore, the mTOR pathway has been demonstrated previously to be involved in many types of endothelium injuries including the antiphospholipid syndrome (APS), a systemic autoimmune disease characterized by the production of aPL with recurrent vascular thrombosis. Therefore, our patient is the first one with an mTOR variant and diagnosed with SKS and APS. In conclusion, our data expand both the genetic and phenotypic spectrum associated with MTOR gene variants.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

A novel de novo MTOR gain-of-function variant in a patient with Smith-Kingsmore syndrome and Antiphospholipid syndrome

et al. 2019

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“…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].…”

Section: Discussionmentioning

confidence: 92%

Tongue Stiffness as Presentation of Antiphospholipid Syndrome: A Case Report

Rajevac

Steed

2020

Cureus

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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 extracriteria 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.

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“…The preferential localization is the subcortical area, and in a recent study, multiple subcortical and cortical infarcts with demyelination, involving both lobes of the brain, have been classified as characteristic MRI features for APS patients. White matter lesions were found in the periventricular area of the brain in almost the totality of the studied cases (Zhu et al, 2014).…”

Section: Current Challenges In the Diagnosis And Management Of The Anmentioning

confidence: 99%

Antiphospholipid Antibodies Overlapping in Isolated Neurological Syndrome and Multiple Sclerosis: Neurobiological Insights and Diagnostic Challenges

D’Angelo

Franch

Fernández-Paredes

et al. 2019

Front. Cell. Neurosci.

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Antiphospholipid syndrome (APS) is characterized by arterial and venous thrombosis, pregnancy morbidity and fetal loss caused by pathogenic autoantibodies directed against phospholipids (PL) and PL-cofactors. Isolated neurological APS may represent a significant diagnostic challenge, as epidemiological, clinical and neuroimaging features may overlap with those of multiple sclerosis (MS). In an open view, MS could be considered as an organ-specific anti-lipid (phospholipid and glycosphingolipid associated proteins) disease, in which autoreactive B cells and CD8+ T cells play a dominant role in its pathophysiology. In MS, diverse autoantibodies against the lipid-protein cofactors of the myelin sheath have been described, whose pathophysiologic role has not been fully elucidated. We carried out a review to select clinical studies addressing the prevalence of antiphospholipid (aPL) autoantibodies in the so-called MS-like syndrome. The reported prevalence ranged between 2% and 88%, particularly aCL and aβ2GPI, with predominant IgM isotype and suggesting worse MS prognosis. Secondarily, an updated summary of current knowledge on the pathophysiological mechanisms and events responsible for these conditions is presented. We draw attention to the clinical relevance of diagnosing isolated neurological APS. Prompt and accurate diagnosis and antiaggregant and anticoagulant treatment of APS could be vital to prevent or at least reduce APS-related morbidity and mortality.

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Neurological antiphospholipid syndrome: Clinical, neuroimaging, and pathological characteristics

Cited by 27 publications

References 34 publications

A novel de novo MTOR gain-of-function variant in a patient with Smith-Kingsmore syndrome and Antiphospholipid syndrome

A novel de novo MTOR gain-of-function variant in a patient with Smith-Kingsmore syndrome and Antiphospholipid syndrome

Tongue Stiffness as Presentation of Antiphospholipid Syndrome: A Case Report

Antiphospholipid Antibodies Overlapping in Isolated Neurological Syndrome and Multiple Sclerosis: Neurobiological Insights and Diagnostic Challenges

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