Hypothalamus-Hypophysis-Thyroid Axis, Triidothyronine and Antithyroid Antibodies in Patients with Primary and Secondary Sjo¨gren’s Syndrome

It has been well established that, anti-thyroglobulin antibodies (ATG) and anti-microsomal antibodies (AMC) may be present in various thyroid disorders and other systemic autoimmune diseases, including Sjo¨gren’s syndrome (SS). However, presence of circulating autoantibodies to thyroid hormones, i.e. both to triiodothyronine (T3) and tetraiodothyronine (T4), has not been studied extensively in SS. Autoantibodies to T3 and T4 are very important, because serum T3 and T4 levels may be detected spuriously higher or lower, due to the presence of these autoantibodies. Their presence should be suspected when measured serum thyroid hormone levels are not consistent with clinical status of the patient. SS is a slowly progressive, inflammatory autoimmune disease, affecting primarily the exocrine glands. Thyroid gland, being a target in some autoimmune diseases, is well known to be affected in SS as well. Keeping this possibility in mind, we investigated T3 autoantibody levels and thyroid gland involvement in patients with SS.  Twenty-six SS patients (F/M:22/4) with a mean age of 46,6 years, were recruited in this study.Twelve of them were accepted as primary SS (pSS), while others had secondary SS (sSS) (7 with rheumatoid arthritis (RA), 3 with systemic lupus erythematosus (SLE), 3 with progressive systemic sclerosis (PSS) and 1 with sarcoidosis). Thyroid function tests, including T3, T4, fT3, fT4, TSH, ATG, AMC, T3 antibody measurements, thyroid scintigraphy, thyroid ultrasonography and TRH stimulation tests were performed in all patients. We compared our results with those of the twenty healthy normal controls.  Serum ATG and/or AMC were detected in three patients with pSS (25%) and no patients with sSS. No significant difference could be shown in the other parameters, including T3 autoantibodies and thyroid function tests. TRH stimulation test was also normal, showing that the hypothalamus-hypophysis-thyroid axis was not affected in patients both with pSS and sSS.  In conclusion, we found that T3 autoantibody levels in pSS, were not significantly higher than sSS and normal controls. Received: 18 June 2000 / Accepted: 7 July 2000     

Patient Selection for Stroke Endovascular Therapy— DWI-ASPECTS Thresholds Should Vary among Age Groups: Insights from the RECOST Study

BACKGROUND AND PURPOSE:The purpose of this study was to evaluate the benefits of endovascular intervention in large-vessel occlusion strokes, depending on age class.MATERIALS AND METHODS:A clinical management protocol including intravenous treatment and mechanical thrombectomy was instigated in our center in 2009 (Prognostic Factors Related to Clinical Outcome Following Thrombectomy in Ischemic Stroke [RECOST] study). All patients with acute ischemic stroke with an anterior circulation major-vessel occlusion who presented within 6 hours were evaluated with an initial MR imaging examination and were analyzed according to age subgroups (younger than 50 years, 50–59 years, 60–69 years, 70–79 years; 80 years or older). The mRS score at 3 months was the study end point.RESULTS:One hundred sixty-five patients were included in the analysis. The mean age was 67.4 years (range, 29–90 years). The mean baseline NIHSS score was 17.24 (range, 3–27). The mean DWI-derived ASPECTS was 6.4. Recanalization of TICI 2b/3 was achieved in 80%. At 3 months, 41.72% of patients had a good outcome, with a gradation of prognosis depending on the age subgroup and a clear cutoff at 70 years. Only 19% of patients older than 80 years had a good outcome at 3 months (mean ASPECTS = 7.4) with 28% for 70–79 years (mean ASPECTS = 6.8), but 58% for 60–69 years (mean ASPECTS = 6), 52% for 50–59 years (mean ASPECTS = 5.91), and 72% for younger than 50 years (mean ASPECTS = 6.31). In contrast, the mortality rate was 35% for 80 years and older, and 26% for 70–79 versus 5%–9% for younger than 70 years.CONCLUSIONS:The elderly may benefit from thrombectomy when their ischemic core volume is low in comparison with younger patients who still benefit from acute recanalization despite larger infarcts. Stroke volume thresholds should, therefore, be related and adjusted to the patient''s age group.

Ischemic stroke is the third leading cause of death in France (fourth in the United States^1,2), leading to significant disability.³ The World Health Organization predicts an increasing number of strokes in Europe during the next 10 years.⁴ Intravenous recombinant tissue plasminogen activator for cerebral arterial occlusion is the established therapy to date for acute ischemic stroke. The odds ratio benefit is 1.28–1.7 for a favorable outcome versus a placebo^5,6 within 4.5 hours after stroke onset. Initially, being older than 80 years of age was established as a bad prognostic factor in intravenous treatment^7–10 and even considered an exclusion criterion.⁵ Today, this statement is seen as controversial, with recent studies having shown that elderly patients would still benefit from IV tPA.^11,12 In addition, new therapeutic strategies in stroke units are increasingly involving adjunctive endovascular techniques when fibrinolysis is contraindicated or has failed or when large and proximal intracranial vessels are occluded.^13–17 Previous studies have shown that mechanical thrombectomy by using Stentrievers (Trevo; Stryker, Kalamazoo, Michigan), in particular new stent retrievers,¹⁸ was successful in achieving a high rate of arterial recanalization and favorable clinical outcome in large-vessel occlusion.^19–21 Nevertheless, inclusion and exclusion criteria for these new invasive strategies are still being evaluated and may need to be optimized to avoid futile recanalization, particularly for fragile patients. The purpose of this study was to investigate the benefits and safety of these new recanalization devices according to age subgroups.     

Cyclosporine A-induced neck fibrosis in a patient with adult-onset Still’s disease

Cyclosporine A (CsA) is an immunosuppressive agent used for the prevention of graft rejection during organ and bone marrow transplantation. CsA is also used for the treatment of various inflammatory rheumatic diseases. Although different side effect profiles have been reported, nephrotoxicity, renal vascular damage, hypertension, and gingival hypertrophy are among the most commonly encountered side effects. The development of massive fibrosis in the neck associated with CsA in a 30-year-old male patient with Still’s disease is presented herein. Significant regression was observed after the discontinuation of CsA.     

Dedifferentiated chondrosarcoma of the thumb: a case report

Dedifferentiated chondrosarcoma (DDCS) comprises approximately 10% of all chondrosarcomas and has the worst outcome with 5-year survival of 10%. The preferred localizations are femur, humerus and pelvis. We report a case of DDCS that arose in proximal phalanx of left-hand thumb of a 66-year-old man. He was admitted with a 2-month history of pain and swelling in his thumb. He had experienced a fracture 15 years ago in the same localization with a history of suspected preexisting enchondroma. Plain radiographs showed an expansive osteolytic lesion with milimetric calcifications while magnetic resonance imaging revealed intraosseous focal globular hyperintense spots consistent with chondroid areas as well as a surrounding soft tissue mass with intermediate signal intensity. In biopsy specimen we observed a low-grade chondrosarcoma next to a spindle cell sarcoma with an abrupt transition. He was treated with amputation and died of the disease within 9 months following the surgery. The presence of dedifferented chondrosarcoma in bones of hands was not previously reported. The presented case was provided with the macroscopic and microscopic features observed in amputation specimen in comparison with radiological findings.     

Secondary osteosarcoma arising in fibrous dysplasia,case report

Malignant transformation of fibrous dysplasia is very rare. The frequency is increased in polyostotic forms, in McCune–Albright and Mazabraud’s syndromes and previously irradiated cases. Pain, which is rapidly becoming worse over a short period unrelated to trauma is the most alarming symptom. Early radiological features of sarcomatous transformation are moth-eaten or cystic areas of osteolysis, cortical destruction and gradual formation of a soft tissue mass. The prognosis is unfavorable as most of the cases are in an advanced stage in the time of diagnosis. We present an unusual case of unsuspected secondary osteosarcoma arising in a previously unirradiated, monostotic fibrous dysplasia. A 46-year-old woman was admitted with hip pain, which worsened after a minor trauma occurred 1 year ago. Plain graphies of left femur showed a well-delineated lesion with endosteal scalloping and areas having a ground-glass appearance. The MRI revealed minimal contrast enhancement but no heterogenous signal intensity, cortical destruction, periost reaction or accompanying soft tissue component was noted. The lesion was initially curetted. But being diagnosed as osteosarcoma histologically, classical osteosarcoma protocol pre and postoperative chemotherapy was applied. Resected femur showed areas of fibrous dysplasia admixed with osteosarcoma having fibroblastic, chondroblastic and osteoblastic areas that were focally invading the soft tissue. Tumor viability was estimated as 95%. The clinical course worsened rapidly after the operation. She did not respond to postoperative chemotherapy and lost with pulmonary metastases less than a years’ time after the operation. The case is presented to increase awareness on the possibility of malignant transformation in an otherwise unsuspected fibrous dysplasia.     

The effect of antidepressant treatment on N-acetyl aspartate levels of medial frontal cortex in drug-free depressed patients

The medial frontal cortex has been shown to modulate emotional behavior and stress responses, suggesting that the dysfunction of this region may be involved in the pathogenesis of depressive symptoms. The present study was performed to determine whether there was any effect of antidepressant treatment on the metabolite levels in the left medial frontal cortex as measured by proton magnetic resonance spectroscopy in depressed patients. Twenty patients diagnosed as having major depressive disorder according to DSM-IV and 18 healthy volunteer subjects were included in the study. Twelve of patients had their first episode and were drug-na?ve. Other depressed patients were drug-free for at least 4 weeks. The severity of depression was assessed by HAM-D and Clinical Global Impression Scale-Severity (CGI-S). Single voxel, 8 cm(3), 1H MR spectra of left medial frontal cortex was acquired both before and following antidepressant treatment. The concentrations and ratios of N-acetyl aspartate (NAA), Creatine+Phosphocreatine (Cr+PCr) and Choline (Cho) were measured. Pretreatment NAA/Cr values of patients were lower than those of healthy controls, but this difference did not reach to statistically significant levels (t=1.83, df=36, p=0.07). However, antidepressant treatment had significant effect on NAA/Cr ratios (groupxtreatment interaction: F=9.93 df=1,36, p=0.03). After the treatment, NAA/Cr values of patients increased significantly compared to pretreatment values (t=3.32, df=19, p=0.004). No significant difference was observed between the post-treatment NAA/Cr values of patients and those of controls (t=1.64, df=36, p=0.19). Correlation analysis detected negative correlation between pretreatment CGI-S scores and NAA/Cr ratios (r=-0.51, p=0.02). This preliminary result suggests that there might be a possible defect in the neuronal integrity in the left medial frontal cortex (mainly left anterior cingulate cortex) of depressed patients. Antidepressant treatment with its neurotrophic effects might play a positive role in restoring the neuronal integrity. Further studies are needed to support these initial findings.     

The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels

Objective

To determine the effect of BDNF gene val66met polymorphism on serum BDNF levels in drug-free patients with major depressive disorder (MDD) and healthy subjects, that differ by gender.

Methods

Sixty-six drug-free patients (19 males + 47 females) with non-psychotic MDD and fifty-six healthy controls (18 males + 38 females) were recruited. Three-way ANOVA was employed to analyze the effect of mental health status, met-carriage and gender on Hamilton Depression Rating Scale (HDRS) scores and serum BDNF levels, by using the MIXED Procedure (SAS).

Results

Patients had a lower serum BDNF level than healthy subjects (22.47 vs. 27.49; p < 0.0001). Met-carrier patients had a higher HDRS score than Val homozygote's (25.99 vs. 22.99, p < 0.02). Serum BDNF level for met-carrier subjects (patients + controls) was lower than Val homozygote subjects (23.08 vs. 26.87; p < 0.002). However, there were no effects of two-way interactions of met-carriage and mental health status on HDRS scores and serum BDNF levels. There was no gender effect on HDRS scores in the patients. Overall, male subjects (patients + controls) had a higher serum BDNF level than female subjects (26.87 vs. 23.08; p < 0.002). However, there were no effects of two-way interactions of gender with mental health status and met-carriage on serum BDNF levels.

Conclusions

We replicated the previous findings of lower serum BDNF levels during depression and in females. In addition, we found that met-carriage had an effect in reducing serum BDNF levels, regardless of gender and depression. Further animal and human studies with a larger sample size should investigate whether BDNF val66met polymorphism could alter brain and serum BDNF levels.