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Epileptic seizures in systemic lupus erythematosus.

Objective: To evaluate the frequency and risk factors of epileptic seizures in a large cohort of patients with systemic lupus erythematosus (SLE). Methods: Five hundred nineteen consecutive patients with SLE were studied, with follow-up ranging from 4 to 7.8 years. The type and frequency of risk factors associated with acute and recurrent epileptic seizures in SLE were determined. Results: Sixty (11.6%) patients with epileptic seizures were identified. Epileptic seizures occurred at the onset of SLE symptoms in 19 (31.6%) and after the onset of SLE in 41 of 60 (68.3%) patients. Fifty-three of 60 (88.3%) patients had acute symptomatic epileptic seizures, and 7 of 60 (11.7%) had recurrent epileptic seizures. Variables associated with acute epileptic seizures at SLE onset were stroke (p = 0.0004) and antiphospholipid antibodies (p = 0.0013). Epileptic seizures during follow-up were related to nephritis (p = 0.001), antiphospholipid antibodies (p = 0.005), and epileptic seizures at disease onset (p = 0.00001). All seven patients who presented recurrent epileptic seizures had antiphospholipid syndrome and interictal epileptic abnormalities on EEG. Conclusions: Epileptic seizures were observed in 11.2% of systemic lupus erythematosus (SLE) patients. Antiphospholipid antibodies and stroke were related to epileptic seizures at SLE disease onset. Patients with renal flares, epileptic seizures at SLE disease onset, and antiphospholipid antibodies were at greater risk for acute symptomatic seizures during follow-up. Recurrence of epileptic seizures occurred in 1.3% of patients and was associated with antiphospholipid syndrome.

Gray matter atrophy associated with duration of temporal lobe epilepsy.

Hippocampal sclerosis is the most common abnormality associated with medial temporal lobe epilepsy (MTLE). Converging evidence supports that hippocampal sclerosis progresses with time. However, it is unclear whether extrahippocampal atrophy in patients with MTLE, similarly to hippocampal sclerosis, is an unremitting progressive process. In this article, we investigate the relationship between duration of epilepsy and gray matter concentration reduction in patients with MTLE within and outside the hippocampus. We employed a voxel-based morphometry study of MRI of the entire brain of 36 patients with drug refractory MTLE and 49 neurologically healthy age-matched controls. We performed a voxel-based parametric and nonparametric investigation of the association between gray matter concentration, age and duration of epilepsy. We complemented the investigation by extracting the gray matter concentration of regions of interest (ROIs) within the limbic system, and we investigated the association between the gray matter concentration on the ROIs and duration of epilepsy. Patients with MTLE exhibited gray matter concentration reduction that is negatively correlated with the duration of epilepsy within the ipsilateral hippocampus, temporal lobes as well as extratemporal limbic structures that are closely connected with the hippocampus. In conclusion, longer duration of refractory epilepsy was associated with a more intense hippocampal and extrahippocampal atrophy in patients with MTLE. The mechanism of progressive neuronal damage in MTLE may be related to active seizure activity within a limbic network, and early seizure control may prevent further brain atrophy in patients with refractory MTLE.

Seizure frequency and lateralization affect progression of atrophy in temporal lobe epilepsy

Background: It is unclear which factors lead to progressive neuronal damage in mesial temporal lobe epilepsy (MTLE). The objective of this study was to evaluate whether progressive hippocampal and extrahippocampal atrophy occur in patients with MTLE and whether this atrophy is related to seizures. Method: We performed 2 MRI scans in 33 patients with clinical and electroencephalographic diagnosis of MTLE and in 24 healthy controls. MRI was performed in a 2-T scanner, and a T1-weighted gradient-echo sequence with 1 mm thickness was used for voxel-based morphometry analysis. Follow-up images were obtained at least 7 months after the first baseline MRI. Comparisons between the patient’s follow-up and baseline MRIs, and between patients and controls, were performed. A corrected p value of 0.05 was set as the threshold for the statistical analysis. Results: Follow-up MRI was performed after a median interval of 39 months (range 7–85 months). Three patients were seizure-free between the first and second MRIs. We observed progressive white and gray matter atrophy (p < 0.05) in patients with MTLE. This progression was more intense in patients with left MTLE compared with right MTLE. A higher frequency of seizures and a longer duration of epilepsy were associated with progression of gray and white matter atrophy in patients with MTLE. Conclusion: The progression of white and gray matter atrophy in patients with mesial temporal lobe epilepsy (MTLE) was more intense in patients with left MTLE and was associated with poorer seizure control and a longer duration of epilepsy.

Asymmetrical extra-hippocampal grey matter loss related to hippocampal atrophy in patients with medial temporal lobe epilepsy

Background: Structural neuroimaging studies have consistently shown a pattern of extra-hippocampal atrophy in patients with left and right drug-refractory medial temporal lobe epilepsy (MTLE). However, it is not yet completely understood how extra-hippocampal atrophy is related to hippocampal atrophy. Moreover, patients with left MTLE often exhibit more intense cognitive impairment, and subtle brain asymmetries have been reported in patients with left MTLE versus right MTLE but have not been explored in a controlled study. Objectives: To investigate the association between extra-hippocampal and hippocampal atrophy in patients with MTLE, and the effect of side of hippocampal atrophy on extra-hippocampal atrophy. Methods: Voxel-based morphometry analyses of magnetic resonance images of the brain were performed to determine the correlation between regional extra-hippocampal grey matter volume and hippocampal grey matter volume. The results from 36 patients with right and left MTLE were compared, and results from the two groups were compared with those from 49 healthy controls. Results: Compared with controls, patients with MTLE showed a more intense correlation between hippocampal grey matter volume and regional grey matter volume in locations such as the contralateral hippocampus, bilateral parahippocampal gyri and frontal and parietal areas. Compared with right MTLE, patients with left MTLE exhibited a wider area of atrophy related to hippocampal grey matter loss, encompassing both the contralateral and ipsilateral hemispheres, particularly affecting the contralateral hippocampus. Conclusions: Our results suggest that left hippocampal atrophy is associated with a larger degree of extra-hippocampal atrophy. This may help to explain the more intense cognitive impairment usually observed in these patients.

Hippocampal atrophy in systemic lupus erythematosus

Objectives: To determine the frequency and progression of hippocampal atrophy in systemic lupus erythematosus (SLE) and the clinical, laboratory and treatment features associated with its occurrence. Methods: 150 patients with SLE and 40 healthy volunteers were enrolled in our study. A complete clinical, laboratory and neurological evaluation was performed. Magnetic resonance imaging was carried out using a 2T scanner (Elscint Prestige) and coronal T1-weighted images were used for manual volumetric measurements. Atrophy was defined as values <2 standard deviations from the means of controls. Results: At entry into the study, the mean right and left hippocampal volumes of patients were significantly smaller than the hippocampal volumes of controls (p<0.001). After the follow-up magnetic resonance imaging, a significant progression of reduction in right and left hippocampal volumes in patients was observed (p<0.001). At entry, atrophy was identified in 43.9% and at follow-up in 66.7% of patients with SLE. Hippocampal atrophy was related to disease duration (p<0.001) total corticosteroid dose (p = 0.01) and history of central nervous system (CNS) manifestations (p = 0.01). Progression of atrophy was associated with cumulative corticosteroid dose (p = 0.01) and number of CNS events (p = 0.01). Patients with cognitive impairment had more severe hippocampal atrophy than those without. Conclusion: Disease duration, total corticosteroid dose and greater number of CNS manifestations were associated with hippocampal atrophy in patients with SLE. A significant progression of hippocampal atrophy related to total corticosteroid dose and number of CNS events was observed. Further studies are necessary to confirm these findings.

Quantitative magnetic resonance imaging analyses and clinical significance of hyperintense white matter lesions in systemic lupus erythematosus patients

To analyze the clinical significance of hyperintense white matter (WM) lesions in both symptomatic and asymptomatic systemic lupus erythematosus (SLE) patients.

The role of Tumor Necrosis Factor-alpha (TNF-α) in the pathogenesis of systemic lupus erythematosus.

The Tumor Necrosis Factor-alpha (TNF-α) is a pleiotropic cytokine that produces different stimuli in various physiological and pathological conditions. TNF-α contributes importantly to the development of T cells, B cells, and dendritic cells. However, TNF-α is also a potent inflammatory mediator and apoptosis inducer. The significance of the TNF-α involvement in the pathogenesis of systemic lupus erythematosus (SLE) remains controversial. From the genetic standpoint, a number of studies suggest that the TNF-α gene polymorphism is involved in the susceptibility of SLE. Moreover, there is a close association between the TNF-α gene expression and clinical manifestations. In addition, the increased serum level of TNF-α is observed in SLE patients and associated with disease activity and certain systemic manifestations. Treatment with anti-TNF agents is, however, controversial in SLE since induction of antinuclear antibodies, anti-dsDNA, anticardiolipin antibodies, and cases of drug-induced lupus have been observed in rheumatoid arthritis patients. In this context, this study reviewed the importance of TNF-α in the pathogenesis of SLE.

Cerebral venous thrombosis: influence of risk factors and imaging findings on prognosis.

PURPOSE To investigate imaging findings, risk factors and outcome in patients with cerebral venous thrombosis (CVT). METHODS Records of all patients with diagnosis of CVT between 1992 and 2002 were reviewed. Patients with CNS infection and with CVT secondary to invasive procedures were excluded. Inherited and acquired thrombophilia were searched in all patients. RESULTS Twenty-four patients (18 women, 6 men) with mean age of 29.5 years (range 3-48 years) were identified. Mean follow-up was 44 months (range 11-145 months). The most common symptoms were headache (75%), vomiting (33%) and impairment of consciousness (21%). Probable causes of CVT could be determined in 21 (88%) patients: pregnancy or puerperium in six (25%), oral contraceptive use in four (17%), head trauma in two (8%), mastoiditis in one (4%), nephrotic syndrome in one (4%), systemic disease in three (13%), and inherited thrombotic risk factors in four (17%) patients. CVT associated with pregnancy, puerperium and use of oral contraceptives had a significant better outcome than CVT caused by inherited thrombophilia or systemic disease (OR=14.4; p=0.02). CT scans were abnormal in 15 (62.5%) patients and MRI with gadolinium was abnormal in all. Those with parenchymal involvement had neurological sequelae during follow-up. All were treated with heparin followed by oral anticoagulants, and none had new or worsening of pre-existing intracerebral hemorrhage. CONCLUSION MRI is superior to conventional CT for diagnosing CVT. Patients with parenchymal lesions, thrombophilia and antiphospholipid syndrome had greater risk to be left with neurological sequelae. Anticoagulant therapy did not predispose to further intracerebral hemorrhage.

Neuropsychiatric Manifestations in Systemic Lupus Erythematosus Epidemiology, Pathophysiology and Management

Systemic lupus erythematosus (SLE) is a relapsing-remitting autoimmune disease with CNS involvement occurring in up to 75% of patients. However, the frequency of neuropsychiatric manifestations in SLE studies varies widely, depending on the type of manifestations included and the method used for evaluation. CNS involvement may be considered primary if directly related to SLE activity in the CNS or secondary when related to treatment, infections, metabolic abnormalities or other systemic manifestations such as uraemia and hypertension. The pathogenesis of neuropsychiatric SLE is as yet unknown, though numerous autoantibodies and cytokines have been suggested as possible mediators. However, independent of the aetiology of the insult, the final common pathway in neuropsychiatric SLE is the involvement of the cerebral microvasculature.The diagnosis of primary CNS involvement by SLE is often difficult, as both focal and diffuse manifestations may occur and there is no gold standard for diagnosis. A high index of clinical suspicion, in addition to laboratory and neuroimaging findings may support the diagnosis. Treatment is mostly empirical, although one randomized controlled trial has shown that cyclophosphamide in addition to methylprednisolone is superior to methylprednisolone alone in severe neuropsychiatric SLE.

The importance of cytokines and autoantibodies in depression

The relationship between depression and immunity has been widely discussed. Cytokines, such as TNF-α, play an important role in immune system; these cytokines interact with virtually every pathophysiologic domain relevant to depression, including neurotransmitter metabolism, neuroendocrine function, and synaptic plasticity. Antibodies have also been implicated in the pathophysiology of depression. The association between decreased serotonin levels and excessive glutamatergic activity forms the first biochemical basis for cytokine-induced depression. Cytokines and antibodies (anti-ribosomal-P and anti-N-methyl-D-aspartate receptor antibodies) are deeply related to pathogenesis of neurodevelopmental disorders, especially depression. Tumor necrosis factor alpha (TNF-α) may underlie the mechanism of depression by an activation of the hypothalamo-pituitary-adrenocortical (HPA) axis, an activation of neuronal serotonin transporters and the stimulation of the indoleamine 2,3-dioxygenase which leads to tryptophan depletion. In the last 20 years since the initial reports of neural-immune interactions in depression, studies have shown a clear association between activation of the immune system mediated by proinflammatory cytokines. Genes encoding cytokines are highly polymorphic and single nucleotide polymorphisms, associated with increased or reduced cytokine production, have been described. To date, there are only few studies that investigated the relationship between depression and proinflammatory cytokines in patients with autoimmune diseases. Although an associative link between neuroinflammation and mood disorders is widely accepted, further studies are necessary to establish the cause-effect relationship. In this paper, we review the role of cytokines, focusing on TNF-α and antibodies in the depression and hypothesize how TNF-α may underlie and mediate the inflammatory process depression in patients with autoimmune disease.