Partial volume tolerance of the spinal cord and complications of single-dose radiosurgery

BACKGROUND: Spine radiosurgery causes a rapid dose fall-off within the spinal cord. The tolerance of partial volume of the spinal cord may determine the extent of clinical application. The study analyzed the partial volume tolerance of the human spinal cord to single fraction radiosurgery. METHODS: A total of 230 lesions with spine metastases in 177 patients were treated with radiosurgery with single fraction of 8 to 18 Gy, prescribed to the 90% isodose line that encompassed the target volume. Spinal cord volume was defined as 6 mm above and below the radiosurgery target volume. Spinal cord dose was calculated from the radiation dose/spinal cord volume histogram and correlated with clinical/neurological status and radiographic studies. Median follow-up was 6.4 months (range, 0.5-49 months). The 1-year survival rate was 49%. RESULTS: The average spinal cord volume defined at the treated spinal segment was 5.9 +/- 2.2 mL. The average dose to the 10% spinal cord volume was 9.8 +/- 1.5 Gy, calculated from the dose-volume histogram in the group of 18 Gy prescribed dose. The spinal cord volume that received higher than 80% of the prescribed dose was 0.07 +/- 0.10 mL, which represented 1.3 +/- 1.8% of the cord volume. Among the 86 patients who survived longer than 1 year there was 1 case of radiation-induced cord injury after 13 months of radiosurgery. There were no other cases of spinal cord sequelae. CONCLUSIONS: Whereas the maximum spinal cord tolerance to single-dose radiation is not known, partial volume tolerance of the human spinal cord is at least 10 Gy to 10% of the spinal cord volume defined as 6 mm above and below the radiosurgery target.     

Early Doppler studies in lupus pregnancy.

The management of 56 pregnancies in 54 patients is presented, 52 with systemic lupus erythematosus and two patients with primary antiphospholipid syndrome. All underwent serial Doppler blood flow studies of the umbilical and uterine arteries from 14 weeks of gestation. Drug therapy was directed at disease activity and the fetus and mother monitored intensively to identify optimum time for delivery. End diastolic blood flow (EDF) studies were compared with anticardiolipin antibodies (aCL) and the lupus anticoagulant (LAC) to predict outcome of pregnancy in terms of mortality, Caesarian delivery, hypertension, and gestation. The absence of end-diastolic blood flow predicted Caesarian delivery more accurately. The presence of EDF and the absence of aCL was consistent with a normotensive pregnancy. The presence of LAC was the best of the three in predicting fetal demise.     

Complement factor 2 deficiency: a clinical and serological family study.

Inherited complement deficiencies are associated with a variety of connective tissue diseases. A family with inherited deficiency of complement factor 2 (C2) is described in which two family members with homozygous C2 deficiency developed cutaneous vasculitis and sicca syndrome. The other family members had heterozygous C2 deficiency and each member had the HLA-A25, B18, DR2 (w15) haplotype. The mother had seropositive rheumatoid arthritis. Further studies showed the presence of cryoglobulins, antibodies against endothelial cells, and anticardiolipin antibodies.     

The central nervous system in systemic lupus erythematosus

Summary Management of central nervous system (CNS) involvement is one of the most challenging problems in systemic lupus erythematosus. This article reviews the spectrum of CNS manifestations present in this disease, their diagnosis and pathogenesis, as well as an approach to their treatment and prognostic implications.     

Anti-C1q antibodies in nephritis: correlation between titres and renal disease activity and positive predictive value in systemic lupus erythematosus

OBJECTIVE: To investigate antibodies to complement 1q (anti-C1q) and investigate the correlation between anti-C1q titres and renal disease in systemic lupus erythematosus (SLE). METHODS: 151 SLE patients were studied. In patients with biopsy proven lupus nephritis (n = 77), activity of renal disease was categorised according to the BILAG renal score. Sera were tested for anti-C1q by enzyme immunoassay. Serum samples were randomly selected from 83 SLE patients who had no history of renal disease, and the positive and negative predictive value of the antibodies was studied. RESULTS: Patients with active lupus nephritis (BILAG A or B) had a higher prevalence of anti-C1q than those with no renal disease (74% v 32%; relative risk (RR) = 2.3 (95% confidence interval, 1.6 to 3.3)) (p<0.0001). There was no significant difference in anti-C1q prevalence between SLE without nephritis and SLE with non-active nephritis (BILAG C or D) (32% v 53%, p = 0.06) or between active and non-active nephritis (74% v 53%, p = 0.06). Patients with nephritis had higher anti-C1q levels than those without nephritis (36.0 U/ml (range 4.9 to 401.0) v 7.3 U/ml (4.9 to 401.0)) (p<0.001). Anti-C1q were found in 33 of 83 patients (39%) without history of renal disease. Nine of the 33 patients with anti-C1q developed lupus nephritis. The median renal disease-free interval was nine months. One patient with positive anti-C1q was diagnosed as having hypocomplementaemic urticarial vasculitis syndrome during follow up. CONCLUSIONS: Anti-C1q in SLE are associated with renal involvement. Monitoring anti-C1q and their titres in SLE patients could be important for predicting renal flares.     

Measuring systemic lupus erythematosus activity during pregnancy: validation of the lupus activity index in pregnancy scale

OBJECTIVE: To validate the Lupus Activity Index in Pregnancy (LAI-P) scale as a diagnostic tool for lupus flares during pregnancy and the puerperium. METHODS: The LAI-P is a modified activity scale specific for pregnancy. Thirty-eight pregnant women with systemic lupus erythematosus (SLE) were prospectively followed in 3 clinics specific for lupus in pregnancy. On each visit, LAI-P was calculated. A modified physician global assessment (m-PGA) scale was used as gold standard (0 = no activity, 1 = mild-moderate activity, 2 = severe activity). A change > or = 0.25 in LAI-P was predefined as a flare according to previous studies in nonpregnant patients. For the purposes of the study, each visit was considered as an independent case. RESULTS: During the study period, 158 visits took place for a total 621 patient-weeks. Sensitivity to change was high (standardized response mean for LAI-P = 1.6). We found a significant association between LAI-P and m-PGA (P < 0.002 in all regression models performed). Sensitivity, specificity, and positive and negative predictive values were 0.93, 0.98, 0.88, and 0.99. Positive and negative likelihood ratios were 49 and 0.07, respectively. CONCLUSIONS: LAI-P has a high sensitivity to changes in lupus activity, a significant correlation with m-PGA, and high sensitivity, specificity, predictive values, and likelihood ratios for diagnosing SLE flares during pregnancy and the puerperium.     

Stroke and the antiphospholipid syndrome: consensus meeting Taormina 2002

Ischaemic stroke is the only neurological manifestation accepted as a clinical diagnostic criterion for the antiphospholipid syndrome (APS). This association is reasonably well established in patients first diagnosed with APS but is less clear in randomly selected stroke patients who test positive on one occasion for antiphospholipid antibodies and who have no other evidence of systemic autoimmune disease. We propose a grading system that posits stroke to be definitely, likely or possibly associated with antiphospholipid antibodies (aPL). Further, there are limited prospective data to determine appropriate treatment. There is controversy as to whether the presence of aPL even increases risk of a recurrent stroke or other thromboembolic event, although data point to persistent medium-high titre aCL and/or LA as risk factors for recurrence. In the absence of data to guide clinicians on the best treatment, we cannot make strong recommnendations as to optimal therapy, nor can we propose clear consensus treatment guidelines.     

Combined Radiofrequency Ablation-Cooling Catheter for Reversible Cryothermal Mapping and Ablation

Reversible cryothermal mapping of cardiac arrhythmias has beenperformed intraoperatively. However, a steerable cooling catheter forreversible mapping has not yet been developed. We therefore developed andtested a cooling system consisting of a +15°C hypertonic salinereservoir and a 7F steerable catheter also capable of radiofrequency (RF)ablation. Using excised ovine hearts placed in a 37°C circulating salinebath, we measured the temperatures at depths of 0 mm, 1 mm, and 2 mm. Thetemperature after 90 seconds of cooling was 16.5 ± 2.1°C at 0 mmcompared to 23.9 ± 4.1°C at 1 mm and 31.1 ± 3.9°C at 2mm depth (p < 0.01). These data suggest that a 7F steerable combined RFablation–cooling catheter may achieve temperatures suitable formapping arrhythmias such as atrial tachycardias and right ventricularoutflow tract tachycardias. Further enhancements to achieve lowertemperatures at depth may be needed to reversibly map other arrhythmiassuch as left ventricular tachycardias.     

Antiendothelial cell antibodies in inflammatory myopathies: distribution among clinical and serologic groups and association with interstitial lung disease

OBJECTIVE: To determine the prevalence and associations of antiendothelial cell antibodies (AECA) in a well characterized cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Clinical characteristics, AECA, and myositis-specific autoantibodies were assessed by standard methods in 56 subjects with IIM. RESULTS: AECA were found in 20/56 patients with IIM, were seen in all the major clinical and serologic IIM groups, and were found in 10/15 patients with interstitial lung disease (ILD) (chi squared 6.5, p<0.01 with Yates' correction, relative risk 2.7, specificity 86% and sensitivity 50%). Antisynthetase antibodies, also associated with ILD as described (chi squared = 26.5, p<0.001 with Yates' correction, relative risk 8.7, specificity 95%, sensitivity 77%), did not correlate with the presence of AECA. CONCLUSION: AECA appear to be present in all forms of IIM and are markers for ILD that are independent of anti-synthetase autoantibodies. AECA may be a useful serologic marker for ILD in IIM.