Central nervous system vasculopathy in neonatal lupus erythematosus

doi:10.1016/0887-8994(96)00159-2

Pediatric Neurology

Volume 15, Issue 2, September 1996, Pages 124-126

https://doi.org/10.1016/0887-8994(96)00159-2 Get rights and content

Abstract

Central nervous system involvement in neonatal lupus erythematosus (NLE) has not been previously reported. We report four patients with NLE, all with complete congenital hearth block and three with cerebral ultrasound and color Doppler flow imaging (CDFI) studies demonstrating evidence of associated vasculopathy in the gangliothalamic vasculature. CDFI confirmed blood flow through the affected vessels, indicating that blood flow was not compromised at this early stage. Short-term follow-up revealed no signs of progression of the vasculopathy, focal ischemia, gangliothalamic atrophy, or neurological impairment. Nevertheless, the implications of this finding with respect to the natural history of NLE remain to be defined, particularly in cases in which the disease develops into systemic lupus erythematosus later in life. Besides specific diagnostic studies for NLE, cerebral ultrasound, and CDFI studies are mandatory in all cases of complete congenital heart block, regardless of whether mothers are diagnosed as having connective-tissue disease or not. Neonates with signs of vasculopathy in the gangliothalamic region should be examined for NLE.

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Cited by (60)

Neonatal lupus: Pathogenesis and clinical approaches
2018, Dubois' Lupus Erythematosus and Related Syndromes
Neonatal lupus (NL) is an autoimmune disease that is acquired in utero after the transplacental passage of maternal autoantibodies reactive against Ro and La antigens. It is characterized by varying degrees of heart block and can be associated with an erythematosus rash. NL occurs in 1% to 2% of babies born to mothers with anti-Ro (also known as anti-SSA) and anti-La (also known as anti-SSB) antibodies. It is not necessary for these women to have clinical manifestations of an autoimmune disease. The most serious complications of NL involve the heart, but other manifestations include the liver as well as cutaneous and hematologic systems. Cardiac involvement includes first-, second-, and third-degree heart block as well as endocardial fibroelastosis in isolation or accompanying conduction system disease. NL is the etiology most commonly associated with isolated congenital heart block, accounting for up to 95% of all cases. This chapter will review the epidemiology, pathophysiology, clinical considerations, candidate biomarkers, and current guidelines regarding management of pregnancies complicated by NL.
Neonatal lupus: Follow-up in infants with anti-SSA/Ro antibodies and review of the literature
2017, Autoimmunity Reviews
Citation Excerpt :
Furthermore, 9 newborns of this study had non-specific CNS anomalies on cerebral US in absence of any clinical neurological signs. Although CNS involvement is a not well-recognized manifestation of NLS, to our knowledge, other studies reported non-specific brain involvement [17,18,38]. Neuroimaging findings are characterized by non-specific lesions that could be considered with a favorable outcome, although long-term sequelae cannot be excluded.
Neonatal Lupus Syndrome (NLS) is a distinct clinical entity caused by transplacental passage of maternal anti-SSA/Ro antibodies (Ab). Mothers may have systemic lupus erythematosus, Sjögren syndrome, or other connective tissue disease, or may be completely healthy at the time of giving birth. NLS includes several clinical manifestations: complete congenital heart block (CCHB) and cutaneous lupus are the most common, while hepatobiliary disease, hematological manifestations and central nervous system involvement may occur.
Data from literature on the incidence of the different clinical manifestations of NLS are difficult to compare because they come mostly from retrospective studies or prospective studies, but up to date no systematic follow-up was carried out. We performed a large prospective single-center study with a systematic clinical and instrumental follow-up until 9 months of life, in order to evaluate the incidence and the clinical impact of NLS features.
From 2004 to 2014 all infants born in our center to mothers with anti-SSA/Ro Ab were enrolled in a specific diagnostic and follow-up (FU) program.
At birth, 50 infants born to mothers with anti-SSA/Ro Ab were found positive for anti-SSA/Ro Ab. Infants were tested for anti SSA/Ro Ab at 3 months of life, if positive they were re-tested at 6 and 9 months. At 9 months anti-SSA/Ro Ab were positive in 10% of children. In two cases (4%) a CCHB was identified during pregnancy and required pacemaker implantation at birth. In 10% of cases a transient ECG alterations was found during follow-up. Hematological NLS features (anemia, neutropenia, thrombocytopenia) were found at birth and during FU in several patients, in all cases without clinical manifestations and in most cases with complete normalization at 9 months. Mild and transient elevation of aminotransferases between 3 and 6 months of life were found in 56% and 40% of patient, respectively; non-specific ultrasound cerebral anomalies in absence of clinical neurological signs were found at birth in 9 patients (18%), subsequently normalized.
Prenatal maternal screening is of primary importance in order to early detect CCHB, which requires maternal treatment and pacemaker implantation at birth. Infants born to mothers with anti-SSA/Ro Ab should be monitored for all NLS features at birth. However, during the first months of life, these infants seem to develop only mild, transient and self-limited clinical manifestations, which in most cases are completely solved at 9 months of life. This consideration, together with the evidence that only 10% of infants had anti-SSA/Ro Ab persistent in blood at 9 months, suggests that follow-up of these children can be performed until 6–9 months of life with good clinical safety. Moreover, a clinical and laboratory monitoring at 3 months of life, when the highest incidence of hematological features and liver tests alterations are observed, is strongly recommended. In the future, it would be clarified if a follow-up until adulthood would be indicated in cases with persistent anti SSA/Ro or in all infants born to mother with anti SSA/Ro.
Neonatal Lupus
2017, The Heart in Rheumatic, Autoimmune and Inflammatory Diseases: Pathophysiology, Clinical Aspects and Therapeutic Approaches
Neonatal lupus is an autoimmune disease that is acquired in utero from antibodies produced by the maternal immune system against Ro and La antigens. It is characterized by varying degrees of heart block and can be associated with an erythematosus rash. Neonatal lupus occurs in 1–2% of babies born to mothers with anti-Ro (also known as anti-SSA) and anti-La (also known as anti-SSB) antibodies. It is not necessary for these women to have clinical manifestations of an autoimmune disease. The most notorious complications of neonatal lupus involve the heart. These include first-, second-, and third-degree heart block as well as endocardial fibroelastosis (EFE). Neonatal lupus is the etiology most commonly associated with isolated congenital heart block, accounting for up to 95% of all cases. This chapter will review the pathophysiology and current guidelines regarding management of pregnancies complicated by neonatal lupus.
The etiology of lenticulostriate vasculopathy and the role of congenital infections
2015, Early Human Development
Citation Excerpt :
Although congenital infections were initially considered as the primary cause of LSV, it is now clear that many other conditions are associated with LSV [5]. These include not only various infectious etiologies (i.e., cytomegalovirus (CMV) [1,5–13], toxoplasmosis [8,11,14], syphilis [1,3,6], rubella [1,6,8,15], rotavirus [7], meningitis [3], and HIV [14,16]), but also several non-infectious etiologies, including asphyxia, hypoxic–ischemic conditions [1,5,11], ischemic brain infarct [17], chromosomal anomalies [1,5,6,9,11,18], fetal alcohol exposure [5], maternal drug abuse [1,5,8,11], congenital anomalies [19], neonatal lupus erythematosus [20,21], maternal diabetes [22], congenital heart disease [11], twin–twin transfusion syndrome [23,24], and congenital hypothyroidism [10]. More recently, it has been suggested LSV may be a transient finding in healthy preterm infants [25].
Lenticulostriate vasculopathy (LSV) refers to increased echogenicity of the penetrating vessels that supply the basal ganglia and segments of the internal capsule seen on cranial ultrasound. Initially identified in infants with congenital infection, LSV has now been associated with a variety of infectious and non-infectious conditions. Although robust epidemiologic studies are lacking, the available evidence does not support broad evaluation for multiple congenital infections when LSV is identified. We propose screening infants with LSV for congenital cytomegalovirus infection and ensuring that prenatal screening included appropriate testing for syphilis, human immunodeficiency virus, and rubella-immune status. Large, prospective observational studies are needed to determine the incidence of LSV and the relative contribution of infectious and non-infectious conditions to LSV in the neonate.
Lenticulostriate vasculopathy in neonates: Perspective of the radiologist
2015, Early Human Development
Citation Excerpt :
LSV can only be diagnosed on neonatal cranial US. Most investigators have based their diagnoses of the LSV on the presence of linear or branching echogenicities in the region of the basal ganglia and/or thalamus, but there are reports where punctate echogenicities were also regarded as LSV [6–9]. However, there is no evidence that punctate echogenicities have the same pathological correlates as the linear or branching echogenicities.
Lenticulostriate vasculopathy (LSV) is a diagnosis dependent on neonatal cranial ultrasound (US). The diagnosis of LSV requires the presence of linear or branching echogenicities in the area of the basal ganglia and/or thalamus on gray scale cranial US. Although the diagnosis of LSV is dependent on cranial US, there are no convincing correlates observed on either computerized tomography or magnetic resonance imaging. Moreover, the radiographic criteria for LSV on cranial US remain vague, and intra-observer correlations are generally reported to be poor. The purpose of this review is to examine the issues associated with the use of cranial US and the diagnosis of LSV, including alternative imaging, clinical abnormalities and the significance of LSV on cranial US.
Lenticulostriate vasculopathy in neonates: Is it a marker of cerebral insult? Critical review of the literature
2015, Early Human Development
Citation Excerpt :
On the other hand, improved ultrasound imaging technology may have enhanced identification, as well as there may be an increase in the frequency of risk factors contributing to the actual presence of LSV. To date, most published reports of LSV are retrospective reviews [6,11,13,19–21,23,24,28,29] or case reports of varying size [7,14,16,30–38] with the diagnosis frequently made by a single radiologist without confirmation. Existing prospective studies are limited in number and sample size, resulting in conflicting observations and conclusions [18,22,26].
Although lenticulostriate vasculopathy (LSV) was recognized nearly 30 years ago, neonatologists and radiologists still question its clinical significance. The diagnosis of LSV may be highly subjective, resulting in many false negatives when the radiologist is not familiar with the lesion or false positive if over-read by those with special interest in this finding. There has been an increase in incidence of LSV since its recognition in 1985 which might reflect nothing more than a growing awareness of this finding on neonatal cranial ultrasound. On the other hand, improved ultrasound imaging technology may have enhanced identification of LSV. Prospective studies evaluating the presence, significance and diagnosis of LSV are limited and have produced conflicting results. Therefore, the associated risk factors and clinical relevance of LSV on cranial ultrasound remain unclear. This review will examine the existing literature.

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Original articleCentral nervous system vasculopathy in neonatal lupus erythematosus

Abstract

J Am Acad Dermatol

J Invest Dermatol

Pediatr Neurol

Pediatr Neurol

Brain Dev

Pediatr Neurol

Pediatr Neurol

J Am Acad Dermatol

Immunogenetics of the neonatal lupus syndrome

Ann Intern Med

Importance of the immune response to the Ro/La particle in the development of congenital heart block and neonatal lupus erythematosus

J Rheumatol

Original article
Central nervous system vasculopathy in neonatal lupus erythematosus