Proton magnetic resonance spectroscopy of systemic lupus erythematosus involving the central nervous system

We examined 13 patients with neurological manifestations of systemic lupus erythematosus (SLE) based on previous and/or current neurological or psychotic episodes by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) together with psychiatric and cognitive assessment. MRI was abnormal in 7 patients, showing high signal lesions in the white matter and/or cerebral atrophy. Proton MRS centred on white matter lesions in 5 patients showed a reduction in theN-acetyl aspartate creatine ratio compared with normal appearing white matter in the SLE group and in 10 healthy controls. This pattern of abnormality does not allow differentiation of SLE lesions from the chronic plaques occurring in multiple sclerosis. There was a very high incidence of current psychiatric morbidity in the SLE group, namely in 12 of the 13 patients. There was no correlation between the presence of current psychiatric involvement and/or cognitive dysfunction and abnormalities detected with MRI or MRS.     

系统性红斑狼疮累及中枢神经系统的临床分析(附93例报告)

目的对系统性红斑狼疮(SLE)的中枢神经系统(CNS)病变特点及临床预后进行总结.方法对93例伴有中枢神经系统损害的SLE患者进行回顾性分析.结果①SLE的CNS损害症状可分为以下几类弥漫性症状(40.9%)、局灶性症状(23.7%)、抽搐(24.7%)、头痛(10.8%).②局灶性症状的患者预后明显差于弥漫性症状者,抽搐和头痛患者的预后与弥漫性症状患者类似.③脑脊液蛋白增高及CNS损害发生早的患者预后差.结论本组SLE患者CNS受累的症状分布与国外报道类似,不同症状患者的预后情况有明显差异.     

Myelitis in systemic lupus erythematosus

SLE-associated acute transverse myelitis (ATM) is a rare, but potentially severe complication of Systemic lupus erythematosus (SLE), and may lead to significant motor, sensory and autonomic dysfunctions in the central nervous system resulting in marked neurological deficits. It is important to recognize its clinical feature to allow timely diagnosis and management of this condition. In this review, we aimed to provide the reader with the understanding of its clinical presentation and classification, the underlying pathological, MRI (magnetic resonance imaging) appearance, and current status of management, with an emphasis on recent discoveries and advancements.     

Cerebral computed tomography and electroencephalography compared with neuropsychological findings in systemic lupus erythematosus

Central nervous system involvement was evaluated in 36 patients with systemic lupus erythematosus (SLE) using cerebral computed tomography (CT), electroencephalography (EEG), and a neuropsychological test battery. The purpose was to investigate whether brain dysfunction as assessed by comprehensive neuropsychological investigation is associated with findings of routine investigation methods such as CT and EEG which are available in most hospitals. Abnormal EEG was found in 19%, and CT revealed cerebral atrophy in 47% of SLE patients. Few neuropsychological functions were affected by the presence of abnormal EEG, cerebral atrophy, or infarcts. Significant associations were found only between cortical atrophy and impairment of tactile spatial problem-solving and motor dexterity, and between cortical infarcts and motor dexterity in the dominant hand. The value of conventional EEG in assessing cerebral SLE is negligible, except for identifying epileptic activity and focal pathology. Cerebral CT has little relevance in predicting brain dysfunction as established by neuropsychological assessment in SLE, except for detecting cortical atrophy and infarcts. Received: 14 September 1998 Received in revised form: 19 January 1999 Accepted: 11 February 1999     

Co-twin control study on cerebral manifestations of systemic lupus erythematosus

All available twin pairs with systemic lupus erythematosus (SLE) derived from the Finnish Twin Cohort were studied by clinical evaluation, magnetic resonance imaging (MRI), anticardiolipin (aCL), and antineurofilament (ANFA) antibodies. One of the five monozygotic and one of the eight dizygotic pairs were concordant for SLE. 10 of the 15 patients showed clinical neurological abnormalities, and 11 had abnormal MRI of the brain. Altogether, 12 patients were considered to have neuropsychiatric lupus (NPSLE). Seven of the 11 patients with long-term corticosteroid treatment had either central or cortical atrophy. High or moderate aCL level was found in eight patients and two co-twins. Of them, six patients had at least two manifestations of the antiphospholipid syndrome. ANFAs were found in five patients and four co-twins. Five co-twins fulfilled some of the SLE criteria. Of them, three MZ twins and one additional DZ co-twin with no ARA criteria had findings suggesting central nervous system (CNS) involvement. The results indicate that the majority of SLE patients has cerebral abnormalities either as a result of SLE, or concomitant risk factors. The co-twins without clinical SLE often have minor signs of SLE, and even they may have neurological and MRI abnormalities. However, their aCL and ANFA levels seem not to correlate with MRI abnormalities.     

Localization of cerebral functional deficits in patients with non-neuropsychiatric systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NP-SLE) is a common complication of systemic lupus erythematosus (SLE), and clinical interventions are of only limited efficacy despite relatively high prevalence. Such complications have been studied extensively, but the pathoetiology of NP-SLE has not yet been elucidated. Diagnosis of NP-SLE focuses primarily on psychological manifestations, and the underlying mechanisms leading to neuropsychiatric complications remain unknown. To address potential changes in brain function before NP-SLE development, we used resting-state functional magnetic resonance imaging (MRI) to compare regional brain activity in SLE patients versus matched controls. We report that regional activity in cerebellum and in areas of the default mode network are attenuated in patients with SLE, and moreover individual alterations in cerebellar activity correlated positively with the disease activity index. These findings provide direct evidence that significant alteration of brain function, resembling that observed in patients with NP-SLE, is already present in SLE patients without neuropsychiatric complications, highlighting the need for early evaluation and intervention in SLE patients. Furthermore, the disease activity rating correlated with regional functional alterations in the cerebellum, suggesting that the cerebellum could play a role in the pathogenesis of NP-SLE.     

Systemic lupus erythematosus presenting with neurological disorders

Summary Six patients are described who developed a wide variety of neurological manifestations heralding systemic lupus erythematosus (SLE), which included epileptic seizures, stroke, peripheral polyradiculoneuro pathy similar to Guillain-Barré syndrome, transverse my elopathy and multifocal disorders with remitting course mimicking multiple sclerosis. The peculiarity of these cases was that the neurological disorders remained the only manifestations of SLE for many years and the nervous system appeared to be the main target even after the development of systemic SLE. In five patients the prognosis was favourable and corticosteroid treatment led to prolonged remission.     

Cognitive impairment in systemic lupus erythematosus: a follow-up study

We evaluated outcome and the clinical value of cognitive impairment in systemic lupus erythematosus (SLE). Fifty-one consecutive SLE subjects with or without overt nervous system involvement received two comprehensive neuropsychiatric and neuropsychological assessments, including the Mental Deterioration Battery, the Mini Mental State Examination (MMSE), and tests from the Wechsler Adult Intelligence Scale. The two neuropsychological assessments were made when subjects were in stable neurological condition. Twenty-seven patients were found to have neuropsychiatric symptoms (NP-SLE) at the first assessment, and three others developed them during the follow-up. Fifteen patients (10 NP-SLE) had cognitive impairment at the first assessment. At retest the cognitive deficit persisted in all patients but one (non-NP-SLE) and had developed in four others. In the cognitively impaired subjects scores on MMSE approached the cutoff for an overt dementing condition. No progressively decreasing scores were found on any of the tests. No relationships were shown between neuropsychological diagnosis and neuropsychiatric disorder, neuroradiological findings, disease activity, or steroid and nonsteroid immunosuppressive therapy. Cognitive impairment thus seems to be a stable symptom of CNS involvement in SLE. It corresponds to the subjective complaint of intellectual difficulties and marginal performance on the MMSE. Intellectual deterioration may occur in patients without other symptoms of NP-SLE. Standardized neuropsychological testing methods should be used routinely to assess SLE patients. Received: 8 March 1999/Received in revised form: /18 November 1999/Accepted: 30 November 1999     

Migraine and headache in systemic lupus erythematosus and their relationship with antibodies against phospholipids

Summary It has been reported that migraine is common in systemic lupus erythematous (SLE) and an association with phospholipid antibodies has been suggested. The incidence of migraine and non-migrainous headache was prospectively studied in 90 patients with SLE and 90 age-and sex-matched controls. A history of migraine was commoner in SLE patients than in controls [31(34%) vs 15(16%);P<0.05], and the mean age of onset was higher in the SLE group (26.8 vs 17.2 years). Within the SLE group an association was found between migraine and SLE disease activity. Non-migrainous headaches were also more common (non-significant) in the SLE group, and there was a close temporal relationship between onset of both headache and SLE in many patients. Both migraine and non-migrainous headaches in SLE patients often responded to specific SLE treatment. No association was found between migraine or other headaches and antibodies to phospholipids.     

Gadolinium-enhanced magnetic resonance imaging of the central nervous system in systemic lupus erythematosus

Summary Gadolinium (Gd)-DTPA enhanced magnetic resonance imaging (MRI) was performed in 15 systemic lupus. erythematosus patients with past (12) or present (3) features suggesting central nervous system (CNS) involvement. Symptomatic Gd-DTPA enhancing lesions were seen in 2 patients, and immunosuppressive treatment was associated with a rapid reversal of enhancement. The pattern of enhancement was different from that usually seen in multiple sclerosis. Gd-DTPA enhanced MRI may sometimes be useful in demonstrating the activity of CNS lupus.     

神经精神性狼疮的临床表现和MRI特点分析

目的分析神经精神性狼疮(NPSLE)患者常见的临床表现并探讨其头颅MRI的特点及应用价值。方法回顾性分析11例经临床确诊的NPSLE患者的临床资料及头颅MRI检查结果。结果 11例患者中表现为狼疮样头痛8例,癫痫发作4例,言语不利3例,精神症状、视物模糊和偏瘫各2例,意识障碍和共济失调各1例。10例行头颅MRI检查的患者中,有6例出现异常信号影,病灶累及脑叶(额顶枕叶)3例,基底节2例,白质(皮质下白质、脑室旁及半卵圆中心)5例。病灶性质包括腔隙性梗死(4例)、脑血栓形成(3例)和脑萎缩(2例)。结论 NPSLE临床表现复杂多样,以狼疮样头痛及癫痫发作最常见;头颅MRI可发现NPSLE患者脑内病灶的部位及性质,是较为敏感的检查方法,结合临床可以协助诊断。     

Neuropsychological functions in systemic lupus erythematosus: a comparison with chronic whiplash patients

A comprehensive battery of neuropsychological tests sampling a wide range of cognitive functions was administrated to 36 patients with systemic lupus erythematosus (SLE), and a control group consisting of 31 patients with persistent symptoms after whiplash injury. Our results demonstrated significant group differences and suggest that cognitive dysfunction is common in SLE and that there are significant abnormalities in the SLE group compared to chronic illness of non-immunological nature. Considerable variability occurred in the neuropsychological profiles for SLE patients. No significant association was found between cognitive dysfunction and use of corticosteroids, except for the two neuropsychological tests Digit span and Seashore rhythm test. Associations were not found between cognitive dysfunction and depression either, except for the Seashore rhythm test. These findings indicate that cognitive dysfunction in SLE reflects CNS involvement, rather than coexisting emotional disturbance. No significant cognitive impairment was found in the whiplash group. However, our results indicate depressed mood among the whiplash group.     

Neurodevelopment in the offspring of Japanese systemic lupus erythematosus patients

Objective: To evaluate pregnancy outcome of systemic lupus erythematosus (SLE) and the neuropsychological outcomes in offspring of SLE mothers. Study design: Pregnancy outcomes of SLE patients from 1989 to 2006 were determined and the neuropsychological development of the children born to SLE patients was examined suited for their age; Bayley Scales of Infant Development up to four years and Kauffmann Assessment Battery for Children from four years onwards. Results: Of the 233 deliveries, 58 (24.7%) were preterm, 72 (30.9%) were low-birth-weight, and 46 (19.7%) were IUGR. Twenty-six children enrolled in this study had normal intelligence. The mean MDI and PDI were 95.8 ± 10.1 and 94.6 ± 14.1, respectively. The mean scores for the Sequential Processing scale, Simultaneous Processing scale, and Mental Processing composite were 103.1 ± 13.3, 104.2 ± 10.2, and 104.2 ± 12.2, respectively. In the children with anti-Ro/SS-A antibody-positive mothers, mean gestational age and birth weight were significantly lower (p < 0.05), as a result, the mean score of Sequential Processing and Mental Processing were significantly lower than that of negative mothers. The presence of maternal antiphospholipid antibody was not related to gestational age, birth weight and any score on the intelligence tests, except for the rate of IUGR. Conclusion: The rates of preterm delivery and IUGR were frequent in the SLE patients and careful monitoring and management of the disease during pregnancy are still necessary. We should examine the neurodevelopment of the children born from mothers with anti-Ro/SS-A antibody prospectively.     

Functional imaging with positron emission tomography in multiple system atrophy

Summary. Although the current guidelines for the clinical diagnosis of multiple system atrophy (MSA) do not require structural or functional brain imaging, investigations utilizing positron emission tomography (PET) have been helpful diagnostically in differentiating between MSA and primary autonomic failure; idiopathic Parkinson’s disease; and sporadic olivopontocerebellar atrophy. These investigations have demonstrated different patterns of cerebral glucose utilization and of nigrostriatal projection abnormalities among these disorders and between the cerebellar and parkinsonian forms of MSA. Most of the studies have focused upon patients with well-established disease and none have examined the utility of PET imaging in early stage patients with follow-up of clinical course and autopsy verification to ensure accuracy of diagnosis and to determine the sensitivity and specificity of PET techniques for diagnosis. Recent PET studies have revealed denervation of myocardial post-ganglionic sympathetic neurons in some MSA patients, indicating that this disorder can affect the peripheral autonomic as well as the central nervous system. Investigations utilizing ligands to quantify central nervous system dopaminergic and cholinergic terminals have begun to provide insight into the neurochemical disorders that may underlie two of the sleep disturbances common in MSA, rapid eye movement sleep behavior disorder and obstructive sleep apnea.     

The sensitivity of 18-fluorodopa positron emission tomography and magnetic resonance imaging in Parkinson''s disease

Parkinson's disease (PD) as the most important movement disorder is characterized by a progressive loss of nigral dopamine neurons and a subsequent degeneration within several other transmitter systems. Functional brain imaging with positron emission tomography (PET) and the radiotracer 18-fluorodopa (FDOPA) is capable to quantify the deficiency of dopamine synthesis and storage within pre-synaptic striatal nerve terminals. Therefore, FDOPA-PET allows the diagnosis of PD in early disease stages and the differentiation of clinically unclear cases from other movement disorders, e.g. essential tremor. Additionally, FDOPA-PET imaging permits the follow-up of disease progression, the assessment of medical and surgical PD therapy strategies with possible neuroprotective properties and the detection of pre-clinical disease in subjects at risk for the disorder. The classical domain of morphological magnetic resonance imaging (MRI) is the differentiation of symptomatic Parkinsonism from PD. However, recent advances in MRI data acquisition and analysis techniques demonstrated MRI to be also a valuable tool for detection of nigral pathology in PD and for differentiation of neurodegenerative disorders with atypical Parkinsonism.     

Computer tomography and magnetic resonance imaging in cvanide poisoning

Summary A 29-year-old chemistry student took 50 ml of a 1% potassium cyanide solution (500 mg) in an attempted suicide. He became comatose, mydriatic, and was admitted to hospital in an apneic state. He woke up after 7 h and developed Parkinsonism in the following weeks. This regressed slowly during the 2 months after the poisoning apart from dysarthria, bradykinesia of the upper limbs, and very brisk monosynaptic reflexes. At 3 weeks after the intoxication, computerized tomography was largely normal, and there was CSF-dense hypodensity in both putamina after 5 months. Sharply delimited signal elevation in T2 corresponding to the two putamina was detected by magnetic resonance imaging 8 weeks and 5 months after ingestion of the poison.     

Acquired activated protein C resistance is associated with IgG antibodies to protein S in patients with systemic lupus erythematosus

The objective of this study was to clarify the roles of anti-phospholipid antibodies (aPLs) in the pathogenesis of acquired activated protein C resistance (APC-R) in patients with systemic lupus erythematosus (SLE). We examined several aPLs levels (lupus anticoagulant, anti-cardiolipin antibodies, anti-β2-glycoprotein I antibodies, anti-protein C antibodies, and anti-protein S antibodies), the APC-R test, and the factor V Leiden test in 85 SLE patients. Acquired APC-R, which was not found in any patient with the factor V Leiden mutation, was present in 26 (30.6%) of 85 patients, and confirmed that acquired APC-R was a significant risk factor for thromboembolic complications [odd ratio (OR), 3.36; 95% confidence interval (CI), 1.24-9.11]. Multivariate logistic analysis revealed that both LA and anti-PS strongly associated with the presence of APC-R, and that the correlation between anti-PS and APC-R was much stronger (OR, 46.7; 95%CI, 6.99-311) than that between LA and APC-R (OR, 11.3; 95%CI, 2.26-57.0). Furthermore, the mean value of APC sensitivity ratios was significantly lower in SLE patients with anti-PS (mean ± SD, 1.68 ± 0.37, p < 0.0001) than in those without anti-PS (2.23 ± 0.40). These results suggest that acquired APC-R is most strongly attributable to functional interference of the APC pathway by anti-PS, which contribute to risk of thromboembolic complications.     

Nervous system involvement in systemic lupus erythematosus, Sjögren syndrome and scleroderma

Introduction. The purpose of this study was to determine, whether there are any differences in the occurrence of nervous system involvement in different systemic rheumatic diseases. The further aim of the present study was to identify and distinguish primary involvement of the nervous system by these diseases and involvement that may be secondary to confounding factors.
Material and methods. The patient population consisted of 122 patients with a connective tissue disease (42 with systemic lupus erythematosus (SLE), 48 with Sjögren's syndrome and 32 with scleroderma). The methods included neurological examination and standard electrophysiological tests.
Results. At least one neurological defect was diagnosed in 69% of SLE patients, in 71% of Sjögren's syndrome patients and in 66% of scleroderma patients. Secondary factors might have contributed to the pathogenesis of neurological symptoms and signs in up to 25–34% of events.
Conclusion. No significant differences were noted in the occurrence of neurological events in patients with SLE, Sjögren's syndrome and scleroderma. The necessity to differentiate between neurological phenomena directly attributed to the systemic rheumatic disease and those which are totally unrelated or secondary events resulting indirectly from involvement of other organ systems is emphasized.     

Regional cerebral blood flow in patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) with or without definite neuropsychiatric symptoms/signs were studied. Technetium-99m (Tc-99m) hexamethylpropylenamine (HMPAO) brain images were used to detect basal ganglion and cerebral cortex regional cerebral blood flow (rCBF) in patients with SLE with brain involvement. One hundred nine female patients with SLE were investigated using Tc-99m HMPAO brain images with fan-beam single-photon emission computed tomography (SPECT) and surface three-dimensional (3D) display. These patients were separated into 2 subgroups: group 1, 74 cases with definite neuropsychiatric symptoms/signs; and group 2, 35 cases without any neuropsychiatric symptoms/signs. Fan-beam SPECT demonstrated unilateral or bilateral hypoperfusion of basal ganglia or thalamus in 22% and 9% of patients in groups 1 and 2, respectively. Local hypoactivity anomalies were found in the brain cortex of 89% and 20% of patients in groups 1 and 2, respectively, using surface 3D display of the brain. In either group 1 or group 2 patients, parietal and frontal lobes are the most common areas and cerebellum and thalamus are the least common areas of brain involvement, respectively. This study suggests that in comparison with traditional brain imaging techniques, Tc-99m HMPAO brain imaging with fan-beam SPECT in combination with surface 3D display may provide objective information for detection of anomalies of rCBF in patients with SLE.