Cerebral blood flow in systemic lupus erythematosus with and without central nervous system involvement.

Regional cerebral blood flow (rCBF) was studied by the intravenous 133Xe method in 38 patients with systemic lupus erythematosus (SLE); 21 patients had neuropsychiatric manifestations (N+) and 17 did not (N-). Twelve of the N+ patients had had neuropsychiatric episodes less than one year before measurement of CBF ("recent" N+), while seven patients in this group had had episodes over a year before measurement ("old" N+). The results were compared with those obtained from a group of 27 age-matched normal healthy subjects. It was found that, in most of the N+ and N- patients, rCBF was evenly distributed bilaterally, but there was a "patchwork" of high/normal and low flow areas. This disturbance of rCBF distribution was significantly greater in "recent" N+ patients than in "old" N- patients, but was not a function of the potential evolution of systemic lupus erythematosus. It was also found that there was a reduction in the physiological high frontal rCBF in the "old" N+ patients. No correlation could be found between rCBF, the topography of the neuropsychological lesions, other neurological investigations or the glucocorticoid dosage and treatment schedules.     

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.     

Abnormal regional cerebral blood flow in systemic lupus erythematosus patients with psychiatric symptoms

OBJECTIVE: Single-photon emission computed tomography (SPECT) studies have demonstrated decreased regional cerebral blood flow (rCBF) in systemic lupus erythematosus (SLE) patients. However, no study has done voxel-based analysis using statistical parametric mapping (SPM) that can evaluate rCBF objectively, and the relationship between rCBF and psychiatric symptoms has not been well investigated. Using L,L-ethyl cysteinate dimer (99mTc ECD) SPECT and SPM, we aimed to clarify the association of rCBF changes with psychiatric symptoms in SLE patients whose magnetic resonance imaging (MRI) showed no morphological abnormalities. METHOD: Twenty SLE patients and 19 healthy volunteers underwent 99mTc ECD SPECT. Data were collected from August 2000 to March 2003. SLE was diagnosed according to American College of Rheumatology criteria, and psychiatric symptoms were diagnosed according to ICD-10 criteria. On the basis of the modified Carbotte, Denburg, and Denburg method, the patients were classified into 3 groups: a group with major psychiatric symptoms (hallucinosis, delusional disorder, and mood disorder), a group with minor psychiatric symptoms (anxiety disorder, dissociative disorder, and emotionally labile disorder), and a group without psychiatric symptoms. Gross organic lesions were ruled out by brain MRI. Group comparisons of rCBF were performed with analysis using SPM99. RESULTS: SLE patients without MRI lesions showed decreased rCBF in the posterior cingulate gyrus and thalamus. The reduction in rCBF was overt in patients with major psychiatric symptoms. CONCLUSION: Our study indicated that SLE patients may have dysfunction in the posterior cingulate gyrus and thalamus and that this may be associated with the severity of psychiatric symptoms.     

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow

Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBF. Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient ^99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15 % was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17 %) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration. Received: 3 November 2000 / Received in revised form: 12 January 2001 / Accepted: 24 January 2001     

Cerebral venous thrombosis in systemic lupus erythematosus

We describe six cases of cerebral venous thrombosis in patients with systemic lupus erythematosus. In one patient, cerebral venous thrombosis was the initial manifestation of lupus; in the five others, it occurred 1-33 years after the diagnosis of lupus. The main clinical features of cerebral venous thrombosis were persistent headache in all six patients, focal symptoms in four, and seizures in three; papilledema was present in only one patient. Cerebral venous thrombosis was diagnosed based on angiography or magnetic resonance imaging. Both the transverse (in five patients) and the superior sagittal (in three) sinuses were involved. Extracranial arterial and/or venous thrombosis were present in three patients, abortion in two, thrombocytopenia in four, and lupus anticoagulant in three. The neurologic symptoms resolved rapidly in five patients treated with steroids and heparin. Cerebral venous thrombosis should be suspected in patients with lupus who complain of persistent headache, especially in the presence of neurologic symptoms.     

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.     

Active necrotizing cerebral vasculitis in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multisystemic disease with varied clinical manifestations. Focal cortical brain infarcts and CNS infections are the most common neuropathological features reported in most studies. This report describes a 32‐year‐old woman who had repeated episodes of strokes over 5 years. In view of polyarthritis, oral ulcers, presence of high titres of serum antinuclear antibodies, high titres of double‐stranded DNA and strokes, she was treated as SLE. Despite prolonged immunosuppressive therapy with azathioprine and pulse cyclophosphamide, she succumbed to a brainstem stroke. Complete body autopsy showed multiple cerebral cortical and brainstem infarcts with fibrinoid necrosis of the vessel wall. Renal infarction with healed vasculitis and systemic vasculitis involving small vessels was seen. Extensive thrombosis was remarkable by its absence. Active necrotizing vasculitis of cerebral and renal vessels is a rare complication of SLE, which contributed to a fatal outcome in this patient.     

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.     

Cerebral vasculitis as presenting symptom of systemic lupus erythematosus

A 42-year-old woman developed right-sided hemiparesis due to left-sided encephalomalacia revealed by CT scan. Subsequent angiography revealed vasculitis of several intra-cranial arteries. The ESR was 65 mm/h. Further laboratory tests revealed no evidence of systemic disease so that no causal diagnosis could be posed. Treatment with prednisone (3 X 30 mg daily) led to complete cure of the hemiparesis within 6 weeks. Sixteen months later, the patient developed cutaneous lesions in the neck. Histological examination of these lesions indicated the presence of systemic lupus erythematosus (SLE). Neurological presentation of SLE is exceptional, while cerebral vasculitis as initial symptom of SLE has never been described before.     

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.     

Cerebral blood flow variations in CNS lupus

We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery.     

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     

Effect of flunarizine on cerebral blood flow in baboons with or without focal cerebral ischaemia

In baboons with or without regional cerebral ischaemia (achieved by transorbital clip of the middle cerebral artery), cerebral blood flow (CBF) was measured using the intra-arterial Xenon-133 technique during steady-state, slight hypotension, and hypocapnia before and after administration of various doses of the calcium antagonist flunarizine (0.5 mg kg^–1, 1.0 mg kg^–1, or 10 μg kg^–1 min^–1 over 30 min). In normal baboons flunarizine did not alter CBF significantly, but at reduced blood pressure it increased CBF by 19.9% owing to exaggerated vasodilatory autoregulation. During hypocapnia flunarizine impaired the physiological reduction in CBF owing to reduced vasoconstriction. In baboons with cerebral ischaemia, CBF measurements were stable and comparable with those in a control group using an arterial clip unless flunarizine was added. In a group of five flunarizine-treated animals, mean CBF after positioning of the clip was higher than in the control group. However, the increase in mean CBF varied significantly between animals, indicating that a secondary reduction in CBF due to postischaemic pathophysiological processes was not prevented consistently.     

Effect of flunarizine on cerebral blood flow in baboons with or without focal cerebral ischaemia

In baboons with or without regional cerebral ischaemia (achieved by transorbital clip of the middle cerebral artery), cerebral blood flow (CBF) was measured using the intra-arterial Xenon-133 technique during steady-state, slight hypotension, and hypocapnia before and after administration of various doses of the calcium antagonist flunarizine (0.5 mg kg-1, 1.0 mg kg-1, or 10 micrograms kg-1 min-1 over 30 min). In normal baboons flunarizine did not alter CBF significantly, but at reduced blood pressure it increased CBF by 19.9% owing to exaggerated vasodilatory autoregulation. During hypocapnia flunarizine impaired the physiological reduction in CBF owing to reduced vasoconstriction. In baboons with cerebral ischaemia, CBF measurements were stable and comparable with those in a control group using an arterial clip unless flunarizine was added. In a group of five flunarizine-treated animals, mean CBF after positioning of the clip was higher than in the control group. However, the increase in mean CBF varied significantly between animals, indicating that a secondary reduction in CBF due to postischaemic pathophysiological processes was not prevented consistently.     

A case of cerebral systemic lupus erythematosus treated with methylprednisolone pulse therapy

A case of cerebral systemic lupus erythematosus is presented. This was characterised by a combination of organic, persecutory and atypical hypomanic features. After a very stormy course on oral steroids, treatment with intravenous methylprednisolone pulse therapy was begun. Subsequently the patient experienced a prolonged remission. This outcome supports the value of such therapy in cerebral systemic lupus erythematosus.