Anti-ganglioside antibodies in a large cohort of European patients with systemic lupus erythematosus: clinical, serological, and HLA class II gene associations. European Concerted Action on the Immunogenetics of SLE

OBJECTIVE: To assay anti-ganglioside antibodies (aGM1) in sera of a large cohort of European patients with systemic lupus erythematosus (SLE) to define the prevalence of these autoantibodies in SLE; to evaluate the association of aGM1 with clinical manifestations and other autoantibodies found in SLE; and to search for aGM1 association with HLA class II alleles. METHODS: Four hundred forty-eight patients with SLE were consecutively enrolled in 8 centers from 6 European countries. All sera were tested for antinuclear antibodies by immunofluorescence on HEp-2 cells as substrate, anti-dsDNA, aGM1, aCL, abeta2-glycoprotein I (abeta2-GPI) antibodies by ELISA, and antineutrophil cytoplasmic antibodies (ANCA) by immunofluorescence and by ELISA. Genomic typing for HLA class II loci was performed by polymerase chain reaction-sequence specific oligonucleotide probe method. Clinical assessment was done at the time of enrolment. RESULTS: We found 41.9% of patients with clinical signs of neuropsychiatric involvement; 15.5% of patients were positive for aGM1, 8% of the IgG isotype and 8.6% of the IgM isotype; aGM1-IgG were associated with neuropsychiatric manifestations (NPM) (RR = 3.7), with migraine (RR = 2.4), with OBS (RR = 7.3), and with peripheral neuropathy (RR = 8.5). aGM1-IgM were associated with NPM (RR = 4) and with depression (RR = 3.4). Furthermore, the genetic study showed that aGM1-IgG were associated with HLA-DQB1*0404 (RR = 7.2) while aGM1-IgM were associated with HLA-DQB1*0605 (RR = 33.3). No associations were found between aGM1 and anti-dsDNA, aCL, abeta2GP1, or ANCA. CONCLUSION: Our results show aGM1 can be found in patients with SLE. aGM1 may play a pathogenetic role for some NPM in this condition.     

Sudden unexpected death in epilepsy: From the lab to the clinic setting

Sudden unexpected death in epilepsy (SUDEP) is defined as sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in a patient with epilepsy. Sudden unexpected death in epilepsy is probably the most common cause of epilepsy-related deaths. Many predisposing and initiating factors may coexist and contribute to SUDEP, but the mechanisms are poorly understood. Cardiac and respiratory deregulation seems to have a major role in SUDEP. Here, we review several advances in understanding the mechanisms involved in SUDEP.This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”.     

Evaluation of nausea and vomiting

A comprehensive history and physical examination can often reveal the cause of nausea and vomiting, making further evaluation unnecessary. Acute symptoms generally are the result of infectious, inflammatory, or iatrogenic causes. Most infections are self-limiting and require minimal intervention; iatrogenic causes can be resolved by removing the offending agent. Chronic symptoms are usually a pathologic response to any of a variety of conditions. Gastrointestinal etiologies include obstruction, functional disorders, and organic diseases. Central nervous system etiologies are primarily related to conditions that increase intracranial pressure, and typically cause other neurologic signs. Pregnancy is the most common endocrinologic cause of nausea and must be considered in any woman of childbearing age. Numerous metabolic abnormalities and psychiatric diagnoses also may cause nausea and vomiting. Evaluation should first focus on detecting any emergencies or complications that require hospitalization. Attention should then turn to identifying the underlying cause and providing specific therapies. When the cause cannot be determined, empiric therapy with an antiemetic is appropriate. Initial diagnostic testing should generally be limited to basic laboratory tests and plain radiography. Further testing, such as upper endoscopy or computed tomography of the abdomen, should be determined by clinical suspicion based on a complete history and physical examination.     

Clinical, histochemical, and ultrastructural correlation in septal endomyocardial biopsies from chronic chagasic patients: detection of early myocardial damage

In order to recognize early signs of myocardial damage, histologic, histochemical, and ultrastructural studies were performed on septal endomyocardial biopsy tissue obtained from 79 chronic chagasic patients and from 18 patients with atypical chest pain (control group). Abnormal biopsy findings were recognized in 9 of 16 (60%) chagasic patients with no clinical evidence of myocardial damage. In cases of segmental asynergy only, biopsies were abnormal in 18 of 19 patients. When signs of advanced myocardial damage were evidenced by clinical examination or ECGs, all biopsies were abnormal. Mitochondrial, nuclear, and cell membrane irregularities were consistent findings. A peculiar dilatation and filling of the T tubule system with a glycoprotein-like substance and a remarkable increase in monoamine oxidase activity were observed early in the disease and progressed in magnitude and frequency as myocardial damage became more evident by other diagnostic methods. Septal endomyocardial biopsy is a sensitive method for detection of early myocardial damage in chronic chagasic patients. Based on these findings, a modification of the currently used classification is proposed.     

Renal vascular damage in systemic sclerosis patients without clinical evidence of nephropathy

Objective. To evaluate the use of color-flow Doppler ultrasonography, a direct, noninvasive technique, for measurement of kidney blood flow in patients with systemic sclerosis (SSc). Methods. Twenty-five normal volunteers and 25 SSc patients (median disease duration 8 years, range 2–21 years) were studied. All were free of clinical symptoms of renal damage. The resistance index (RI) was determined on main, interlobar, and cortical vessels. Results. In SSc patients, the RI was significantly increased at every sampling site examined (P < 0.001). RI values were strongly correlated with disease duration (main artery r = 0.56, P < 0.04; interlobar artery r = 0.63, P < 0.02; cortical artery r = 0.75, P < 0.002). Regression analysis showed no relationship between RI and creatinine clearance values. Conclusion. Color-flow Doppler ultrasonography is a sensitive and noninvasive technique for evaluating vascular damage of the kidney in patients with SSc.     

NK cells in patients with peripheral neuropathy and IgM monoclonal protein reacting with the myelin-associated glycoprotein (MAG)

We studied Leu 7+ cell distribution and natural killer (NK) activity in the peripheral blood of six patients who had peripheral neuropathy and monoclonal IgM protein directed against myelin-associated glycoprotein (anti-MAG IgM). We did not find any difference between patients and control subjects (healthy or polyneuropathic, some with IgM monoclonal paraprotein but without anti-MAG activity). The presence of autologous sera did not interfere with these results. We noted an increase in Leu 11+ cell percentages after pre-incubation of the patient cells with autologous sera but the phenotypes of cells from control subjects did not change after incubation with autologous or patient sera.