A clinical study of psychopathology in systemic lupus erythematosus]

Thirty patients (24 inpatients and 6 outpatients) with a clinical diagnosis of SLE were examined between September 1, 1998 and August 1, 1999 in the rheumatology clinic of Jichi Medical School Hospital. All of these patients fulfilled the 1982 revised criteria of the American Rheumatism Association for the classification of SLE and had some psychiatric manifestations (psychiatric SLE; P-SLE group). Mean patient age was 38.6 +/- 13.0, and there were 5 males and 25 females. When classified into 5 subgroups according to the most prominent symptoms, the distribution was as follows: consciousness disturbance group: 6 (20%), schizophrenia-like group: 5 (16.7%), mood disorder group: 7 (23.3%), neurosis-like group: 10 (33.3%), and convulsive disorder group: 2 (6.7%). Among all 37 psychiatric episodes, symptoms appeared in 37.8% of cases during the acute phase of SLE (during onset or recurrence) and in 62.9% during the chronic phase (during remission). The profile of the P-SLE group showed that the psychiatric symptoms of the SLE patients were milder and more chronic than those described in previous reports. To begin to comprehend the psychopathology of SLE, we put forward the concept of "Psychiatric basal state" and "psychiatric conjugated state". The former is considered a direct reflection of the acute-phase SLE process on mental condition. It is defined clinically as psychiatric symptoms that parallel the activity of SLE and respond well to steroid therapy. The latter include all other psychiatric problems in which one cannot rule out the effects of pharmacological, somatic, personality, and environmental effects on psychiatric symptoms. Only 3 patients in the P-SLE group fulfilled the criteria for the "psychiatric basal state". All three patients belonged to the consciousness disturbance group, whose clinical features were defined as slight clouding of consciousness, so-called "Amentia" in the sense of the German terminology. The clinical profile of this state is: 1. the patients are young (about 16 years old), 2. the onset of psychiatric symptoms is within 5 years after the onset of SLE, 3. confusion and disorientation are the most characteristic features, and 4. the clinical course of this state is almost 2 months. The experience structure of the "psychiatric basal state" consists of: 1. difficulty in selecting and holding a topic in cognition, 2. confusion and emotional instability as the basal mood, and 3. primitive and floating forms of delusions and hallucinations. Using this concept of the "psychiatric basal state" as a clue, we can hypothesize the continuity of diverse psychiatric symptoms in SLE. The "proper process of SLE (Harada)" has a disintegrating effect on the "ego" and it allows various psychopathological phenomena to emerge in the experience field. Against this background, additional factors, such as secondary organ damage, personality structure, and social environment, induce organization of the "psychiatric conjugated state".     

The clinical significance of microembolic signals in patients with systemic lupus erythematosus

Abstract

Background: Microembolic signals (MES) have been found in about 10% of patients with systemic lupus erythematosus (SLE), and have been associated with neuropsychiatric manifestations (NPSLE), including cerebrovascular damage.

Objective: To determine the frequency of MES in patients with SLE, previous and further risk of neuropsychiatric manifestations.

Methods: One hundred and nine consecutive patients with previous diagnosis of SLE and without acute neurological manifestations were evaluated clinically and by transcranial Doppler monitoring (1 hour) from November 2002 to March 2003. The baseline characteristics and outcomes were compared between patients with and without MES. Patients were followed during a mean time of 4·5 years, to detect the appearance of NPSLE, including stroke and transient ischemic attacks.

Results: MES were detected in 16 patients (14·7%; range: 3-64/h); at baseline, previous neuropsychiatric manifestations were more frequent in patients with MES: 12/16 (75%) versus 46/92 (50%) (p = 0·064), especially for cognitive dysfunction (p = 0·036). Antiphospholipid syndrome and cardiovascular risk factors did not differ between groups at baseline and follow-up, neither the proportion of patients on antiplatelet agents. At follow-up, two patients from the MES positive group and six from the MES negative group developed a new neuropsychiatric manifestation (p = not significant).

Conclusion: This study supports an association of MES and a history of NPSLE, especially cognitive dysfunction. MES were not associated with an increased risk of cerebral ischemia and other neurological manifestations at follow-up.     

A controlled study of peripheral neuropathy in systemic lupus erythematosus

In 34 patients with systemic lupus erythematosus (SLE) and 34 age- and sex-matched healthy controls we performed standardized quantifiable neurological testing for neuropathic symptoms (Neuropathic Symptom Score) and deficits (Neurological Disability Score), as well as nerve conduction velocity studies (NCV) and determination of vibration thresholds (VT). SLE patients had more neuropathic symptoms and deficits than controls. Most quantitative and qualitative NCV attributes showed no difference between patients and controls. However, if categorized as NCV abnormalities of 2 or more nerves in each individual, a frequency of polyneuropathy of 21% was seen in SLE patients compared to 6% in controls. VT indicated a slight, but widespread, diffuse polyneuropathy in patients compared to controls.     

Laboratory and clinical features in systemic lupus erythematosus patients with or without anticardiolipin antibodies

The purpose of this study was to investigate whether the presence of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE) patients was associated with particular laboratory or clinical features. Anticardiolipin antibodies were determined in 63 unselected SLE patients: 32 (50.8%) were found to be aCL positive and this positivity was significantly associated with the presence of lupus anticoagulant (p less than 0.003) and false positive VDRL reaction (p less than 0.001), but not with other haematological or biological markers. Thrombin-antithrombin III (TAT) complexes were found to be increased with disease activity, but no relationship was found between TAT complexes and the presence or absence of aCL. In this study a statistically significant association was found between aCL positivity and arterial thromboembolic events, but not with venous thrombotic complications. In summary half of SLE patients had aCL and the presence of these antibodies was associated with other antiphospholipid antibodies and with arterial thromboembolic events.     

Cognitive impairment in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus: a population-based neuropsychological study

We present a cross-sectional, population-based neuropsychological study of systemic lupus erythematosus (SLE) patients identified within Tampere University Hospital district, Finland with 440,000 inhabitants. Patients with definite SLE in the age range of 16-65 years (n = 46) and matched controls (n = 46) underwent neurological examination and comprehensive neuropsychological testing. On the basis of medical examination, the SLE patients were divided into neuropsychiatric (NP+; n = 15) and nonneuropsychiatric (NP-; n = 31) cases. The neuropsychological test results revealed more prevalent cognitive impairment in the NP+ patients, indicating that this subgroup mostly accounts for neuropsychological changes in SLE. Most characteristic changes in NP+ were observed in domains of memory, psychomotor speed, and complex attention. This suggests nonspecific CNS involvement, which is in line with neurological manifestations of the disease.     

Prevalence of obsessive-compulsive disorder in patients with systemic lupus erythematosus

BACKGROUND: The goal of this pilot study was to investigate the prevalence of obsessive-compulsive disorder (OCD) in a group of patients with systemic lupus erythematosus (SLE). METHOD: Fifty adult patients enrolled in out-patient SLE studies at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (February 1995-October 1996) completed a self-report questionnaire adapted from the Yale-Brown Obsessive Compulsive Scale and an in-person psychiatric clinical interview with a psychiatrist or psychiatric clinical nurse specialist. DSM-IV lifetime diagnosis of OCD was determined by clinical interview. RESULTS: Sixteen subjects (32%) met DSM-IV lifetime diagnostic criteria for OCD and an additional 5 (10%) met criteria for subclinical OCD. Mean +/- SD number of symptoms reported on the self-report questionnaire was significantly higher among subjects diagnosed with OCD on clinical interview (40.7 +/- 23.2) compared with those without OCD (8.9 +/- 11.7; t = 5.8, df = 27, p <.001). CONCLUSION: Obsessive-compulsive disorder was 10 to 15 times more common in this cohort of patients with SLE compared with those in community-based studies of OCD. The use of an OCD self-report rating scale proved helpful in the identification of OCD symptoms among patients with SLE. Results suggest that further studies of OCD in patients with SLE are needed and may provide new insight into the pathophysiology of both disorders.     

Neurological and psychiatric symptoms in patients with systemic lupus erythematosus

Sixty patients (51 women/9 men) with diagnosis of SLE were studied for finding out the frequency of nervous system involvement in SLE, the time of of appearance of neurological involvement after diagnosis establishing, the coexistence of the antiphospholipid syndrome, and the character of changes in MR, CT and CSF. Nervous system involvement was found in 40 cases (67%), with 34 cases (56%) had involvement of the CNS, 6 patients (10%) had symptoms of peripheral nervous system dysfunction, and 3 (5%) had involvement of both systems. In 4 cases polineuropathy and transverse spinal cord lesion, and in 3 cases psychiatric symptoms were the first manifestations of SLE. Changes due to involvement of cerebral vessels (TIA, stroke) were observed in 20 patients (33%), and psychiatric symptoms in 16 cases (26.6%). No difference was found in the occurrence of stroke or TIA between SLE patients with and without antiphospholipid syndrome, and no correlations were noted between the presence of neurological or psychiatric symptoms and other SLE symptoms. CT scans demonstrated corticosubcortical atrophy in 28.3% of cases, while in MRI in T2 images small hyperintense lesions were situated mainly in the white matter (33.9%). In 5 cases oligoclonal band was found in the CSF, but without any correlation with specific neurological symptoms.     

Factors predictive of corticosteroid psychosis in patients with systemic lupus erythematosus

Corticosteroid-induced psychosis occurred in 5% of a prospective cohort of 92 patients with systemic lupus erythematosus (SLE). Psychosis was unpredictable by the routes and dosage of corticosteroid used. Factors predictive of psychosis were low serum levels of albumin, complement, and creatinine; history of anxiety disorders; and a family history of psychiatric illnesses. After multivariate adjustment, only hypoalbuminemia remained significant.     

Detection of cerebral embolic signals in patients with systemic lupus erythematosus

Background

Involvement of the CNS in systemic lupus erythematosus (SLE) is caused by several pathogenic mechanisms including cerebral embolism.

Aim

To measure the frequency of microembolic signals (MES) by using transcranial Doppler (TCD) ultrasound and to assess their association with cerebral infarction, neuropsychological dysfunction, and biochemical, sonographic and clinical variables in an unselected group of patients with SLE.

Methods

A 1‐h TCD recording from the middle cerebral artery was carried out in 55 patients with SLE having a mean age of 46 (SD 13) years. MRI of the brain, carotid artery ultrasonography with intima–media thickness and atherosclerotic plaque assessments were carried out in addition to a broad biochemical and clinical assessment. All patients underwent a neuropsychological assessment.

Results

Of the 55 patients, MES were detected in 5 (9%) and cerebral infarcts were found in 9 (18%). A significant association was found between MES and cerebral infarcts and considerably more neuropsychological deficits were found in MES‐positive patients compared with the negative group. MES were not associated with other clinical, sonographic and biochemical factors believed to be associated with cerebral embolism.

Conclusions

Cerebral embolism may be one of the important mechanisms responsible for the high prevalence of cerebrovascular events and the neuropsychological deficits observed in patients with SLE. Although the number of MES‐positive patients was small, the lack of a significant association between MES and other known risk factors for MES suggests a complex pathogenesis for the embolisation in these patients.CNS symptoms and signs are common in systemic lupus erythematosus (SLE) and as many as 50% of patients with SLE may have neuropsychiatric involvement.^1,2 Well‐known complications include psychosis, seizures, cerebrovascular accidents and cognitive dysfunction. Women with SLE, aged 18–44 years, are eight times as likely to be admitted to hospital because of stroke as controls.³ The pathogenesis of CNS involvement in SLE has not been clarified, and multiple factors may be associated, such as microvascular damage, small‐vessel vasculopathy, antibodies to nervous tissue and immunologically mediated thromboembolism. Postmortem examinations have shown microinfarcts and microhaemorrhages in cortical and subcortical regions. Several factors are associated with the increased risk of stroke in these patients. These include antiphospholipid antibodies, use of corticosteroids, cardiac involvement and other well‐known risk factors for cerebrovascular disease.^2,4,5Transcranial Doppler (TCD) examination, a non‐invasive technique, can detect cerebral embolisation in the major intracranial arteries.⁶ Microembolic signals (MES) have been detected during cardiac surgery and carotid endarterectomy.^7,8 Long‐term TCD monitoring of the intracranial arteries has shown abnormal signals, indicating clinically silent MES in patients with high‐grade carotid stenosis, with prosthetic heart valves or after recent cerebrovascular events.^9,10,11 Cerebral microemboli may cause cognitive dysfunction if they enter the cerebral circulation in considerably large numbers. This has been studied in detail in patients who have had coronary artery bypass surgery.¹² Some instances showing a positive association between cerebral microemboli detected by TCD and postoperative neuropsychological outcome after cardiac surgery have been reported.^7,10Three studies^13,14,15 that used TCD for embolic detection in patients with SLE have showed conflicting results. It is therefore of interest to carry out further studies on the possible importance of cerebral microembolisation in SLE.We measured the occurrence of MES in a group of patients with SLE and assessed the possible association with cerebral infarcts, neuropsychological function, risk factors for cerebrovascular disease, including carotid atherosclerosis, and biochemical variables associated with cerebrovascular disease.     

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。     

Dementia with leukoencephalopathy in systemic lupus erythematosus

Neurologic manifestations, afflicting up to 70% of SLE patients, include psychosis, seizures, chorea, neuropathies, and stroke. MRI is useful in evaluation of lupus patients and several reports have documented cerebral atrophy or focal hyperintensities. We report an unusual MRI appearance in a 56-year-old woman with SLE, diagnosed on the basis of pleuritis, lymphopenia, anti-DNA antibodies, and neurologic involvement. She reported recent onset of Raynaud's phenomenon and generalized macular rash. She presented after two months of gradual deterioration with memory loss, flattened affect, dysphagia, dysarthria, anomia, and somnolence, without focal neurologic signs. Investigations included elevated ESR, reduced complement, normal CSF without oligoclonal bands, negative viral serology, normal hormone and vitamin levels, normal renal and hepatic function. Neuropsychologic testing showed widespread impairment (WAIS-R: FSIQ-63; WMS-69; DRS-98; RCPM-14; WAB AQ-78.8). CT was normal but MRI showed strikingly symmetric, confluent hyperintensities extensively involving cerebral and cerebellar white matter on T1 and T2 weighted scans. Basal ganglia and subependymal and subcortical white matter were spared. Treated with prednisone, the patient made a gradual, but incomplete, recovery. These MRI findings may reflect widespread vasculopathy or direct immunologic brain insult with or without immunologic blood-brain barrier disruption.     

Antibodies directed to protein S in patients with systemic lupus erythematosus: prevalence and clinical significance

Antibodies directed against protein S (anti-ProtS) may be involved in the development of thrombosis in patients with the antiphospholipid syndrome. We assessed the prevalence and clinical significance of anti-ProtS and evaluated their immunological characteristics in 184 patients with SLE and 99 healthy donors. All patients were tested for IgG anti-ProtS by an in-house ELISA. Plasma levels and functional activity of protein S were also tested. Anti-ProtS were found in 57 patients (31%) and 4 healthy controls (4%). Patients with thrombosis had anti-ProtS more frequently than controls (29% vs 4%, OR 9.5 [95% CI 3.07-29.3], p<0.0001). Anti-ProtS were more frequent in patients with venous thrombosis and in those with arterial thrombosis, than in controls (41% vs. 4%, OR 16.5 [95% CI 5-54], p<0.0001 and 23% vs. 4%, OR 7 [95%CI 2.1-23.5], p=0.0008, respectively). Patients with prematurity, preeclampsia and intrauterine growth restriction had anti-ProtS more frequently than the control group (36%, 47% and 44% vs. 4%; OR 13.6 [95% CI 2.8-66], p=0.003, OR 21 [95% CI 5-86], p<0.0001 and OR 19 [95% CI 4-99], p=0.0014, respectively). Plasma levels of free protein S were not statistically different between patients with and without anti-ProtS and controls (77.9% [20.7-100] vs. 83.7% [52.7-100] vs. 89% [62-101], respectively). Free protein S functional activity was no different between subgroups (105% [48-230] in anti-ProtS positive vs. 123% [95-283] in anti-ProtS negative vs. 136% [60-174] in controls). Anti-ProtS are frequent in SLE patients with thrombosis and pregnancy morbidity. These antibodies do not interfere with free protein S in plasma since its level and/or functional activity are not impaired.     

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.     

Stroke in systemic lupus erythematosus

We investigated the clinical and pathologic characteristics of stroke in 234 patients with systemic lupus erythematosus. Thirteen patients (5.6%) developed cerebrovascular disease. Cerebral infarction was noted in eight, cerebral hemorrhage in two, and subarachnoid hemorrhage in three. In seven (54%) of these 13 patients, stroke occurred less than or equal to 5 years after systemic lupus erythematosus was diagnosed. Among the predisposing risk factors for stroke, hypertension was the most important. Lupus anticoagulant was detected in three (38%) and anticardiolipin antibody in three (43% of seven investigated) of the patients with infarction. Evaluation of the clinical manifestations and autoantibodies indicated that renal involvement and high titers of anti-deoxyribonucleic acid antibody were more frequent in the stroke group than in the non-stroke group. Autopsy studies on six of the patients with stroke revealed small infarcts and hemorrhages in all, but in no case was true angiitis observed. Libman-Sacks endocarditis was found in two of the three patients with infarction. In conclusion, the important contributory factor to the development of stroke in patients with systemic lupus erythematosus is considered to be hypertension mediated by immunologic abnormalities. Antiphospholipid antibodies and Libman-Sacks endocarditis are closely associated with occlusive cerebrovascular disease.     

Central nervous system disease in patients with systemic lupus erythematosus.

Central nervous system (CNS) dysfunction in patients with systemic lupus erythematosus (SLE) is highly variable, although it is often described under a single heading of "neuropsychiatric" or "CNS" SLE. To clarify these CNS abnormalities, we studied 91 lupus patients, 63 of whom had CNS symptoms or signs, over 599 patient years. By placing patients in relatively homogeneous clinical groups (stroke, seizure, suicide attempt, hallucination, confusion, decreased alertness) we detected significant (but variable among groups) correlations with other manifestations of SLE, suggesting separate mechanisms for each CNS disorder. These correlations were lost if all "CNS-SLE" was considered as a single group. Patients with decreased alertness often had undetected systemic infections and had a high death rate from infection, rather than from CNS-SLE. The understanding of the pathogenesis and potential treatment of CNS disorders in lupus will depend on classifying the patients into homogeneous groups.