Loss of Mickey Mouse Ears' Sign in Progressive Supranuclear Palsy.

ABSTRACT: Progressive supranuclear palsy (PSP) is the most prevalent form of degenerative atypical parkinsonism. Clinical manifestations of PSP commonly encompass deficits in vertical gaze, postural stability, akinesia, and cognitive impairment. The characteristic metabolic pattern observed in PSP through FDG PET displays hypometabolism in the midbrain, striatum, thalamus, and frontal lobe. However, visual interpretation of midbrain hypometabolism poses challenges. In this report, we aim to elucidate a novel observation termed the "loss of Mickey Mouse ears' sign," which signifies midbrain hypometabolism as detected through visual assessment of FDG PET images.

18 F-FDG PET/CT in Synovial Anaplastic Large Cell Lymphoma.

ABSTRACT: Anaplastic large cell lymphoma is an uncommon and aggressive form of peripheral T-cell lymphoma. Synovial anaplastic large cell lymphoma is very rare. We present PET/CT findings in a patient with synovial anaplastic large cell lymphoma. Intense FDG accumulation was found in irregular synovial thickening of the right knee. Biopsy of the synovium was performed and revealed anaplastic large cell lymphoma. This case demonstrates that anaplastic large cell lymphoma should be included as one of the differential diagnoses of FDG-avid synovial lesions.

Prevalence and risk factors of low bone mineral density in Chinese patients with systemic sclerosis: a case-control study.

OBJECTIVE: To study the prevalence and risk factors of low BMD in patients with SSc. METHODS: Consecutive patients with SSc and an equal number of age- and gender-matched healthy subjects were screened for BMD, fat and lean mass by DXA scan. BMD, body composition and osteoporosis risk factors were compared between patients and controls. Associated factors for low BMD in SSc patients were studied by linear regression. RESULTS: A total of 84 patients with SSc were studied [89% women; age 49.4 (11.3) years; 21% diffuse subtype; disease duration 7.8 (6.4) years]. Except for significantly lower BMI (P = 0.001), fat mass (P = 0.02) and lean body mass (P = 0.006) observed in SSc patients, the prevalence of other osteoporosis risk factors was similar to controls. Fourteen (17%) and five (6%) SSc patients had low BMD expected for age (z-score <-2.0) at the lumbar spine and hip, respectively. BMD of the lumbar spine, hip, femoral neck and whole body was significantly lower in SSc patients than controls, adjusted for age, sex, menopause and BMI (P < 0.05 in all; effect size 0.44-0.54). Linear regression revealed increasing age, menopause and low BMI were independently associated with low BMD at the spine or hip in SSc patients. However, BMD did not correlate with the severity of involvement of the skin and other systems. CONCLUSION: BMD of the spine and hip is significantly lower in patients with SSc than in healthy subjects, which is independent of age, sex, menopause, low BMI and altered body composition.

Clinical characteristics of concurrent and sequentially presented lupus-related protein-losing enteropathy: what are their differences?

Our objective was to compare patients with concurrent and sequentially presented systemic lupus erythematosus (SLE)-related protein-losing enteropathy (PLE). Patients with history of SLE admitted for PLE were selected and their clinical, laboratory, endoscopic and imaging characteristics, treatment and outcome were analyzed. From 2001 to 2010, 21 and 27 patients had concurrent and sequentially presented SLE-related PLE, respectively, and their clinical characteristics were comparable except the following: the concurrent group had more pleural effusion (P < 0.01), cutaneous (P < 0.03), neurological (P = 0.02) manifestations, higher creatine phosphokinase (127.6 IU/L vs. 105.7 IU/L, P < 0.05) and lactate dehydrogenase (504.0 IU/L vs. 422.2 IU/L, P < 0.05); whereas the sequential group had higher anti-double strand DNA titer (179.8 vs. 100.4, P < 0.05), 24-h urine protein excretion (1.1 g/d vs. 0.6 g/d, P < 0.05) and increased proteinuria after onset of PLE (0.21 g/d vs. 1.1 g/d, P < 0.04). The endoscopic, histological and radiological features were comparable between the two groups. More patients from the sequential group required more potent immunosuppressive therapy for induction (55.6% vs. 14.3%, P = 0.002) and maintenance (48.2% vs. 9.5%, P < 0.01).The concurrent group associated with better treatment outcomes, with requiring shorter mean time (4.5 months vs. 7.9 months, P = 0.03) for normalbuminemia and more individuals (90.5% vs. 63%, P < 0.02) achieving normalbuminemia in first year. The complications were infrequent: two drug-related adverse events from each group, one patient each from the concurrent group developed shingle and SLE nephropathy. PLE associated with concurrent and sequentially presented of SLE are comparable in clinical behavior; and the immunosuppressive therapy is generally well-responded and tolerated. However, the concurrent group is associated with better disease activity control.

Childhood-onset disease carries a higher risk of low bone mineral density in an adult population of systemic lupus erythematosus.

OBJECTIVE: To study the BMD of patients with SLE according to the age of disease onset. METHODS: Consecutive SLE patients were screened for BMD at the hip, lumbar spine and whole body by the dual-energy X-ray absorptiometry (DXA). Comparison was made between patients who had disease onset in childhood (<18 years) and adulthood (≥18 years). Factors associated with low BMD were studied by linear regression. RESULTS: A total of 395 SLE patients were studied (94% women; 11% childhood-onset disease). Osteoporosis of the lumbar spine and the hip/femoral neck was present in 20 and 10% of the patients, respectively. Childhood-onset SLE patients were less likely to be post-menopausal, but had significantly lower BMI, longer SLE duration and a higher frequency of ever use of high-dose CSs, CYC and AZA. Despite a significantly younger age, the BMD of the hip, femoral neck and lumbar spine was significantly lower in childhood- than adult-onset SLE patients. In linear regression models, childhood-onset disease was an independent factor for lower BMD at the lumbar spine (ß = -0.18; P = 0.002), hip (ß = -0.20; P = 0.001) and femoral neck (ß = -0.16; P = 0.01) after adjustment for age, sex, BMI, smoking, menopause, SLE duration and damage index, duration and current dose of prednisolone treatment and the ever use of high-dose glucocorticoids, other immunosuppressive agents, calcium, vitamin D and the bisphosphonates. CONCLUSIONS: In adult SLE patients, childhood-onset disease carries a higher risk of osteoporosis, which may possibly be related to a higher cumulative dose of glucocorticoids used for more active disease and failure to achieve a normal peak bone mass during puberty.

Raloxifene for prevention of glucocorticoid-induced bone loss: a 12-month randomised double-blinded placebo-controlled trial.

OBJECTIVES: To study the efficacy of raloxifene in preventing bone mineral density (BMD) loss in women receiving long-term glucocorticoids (GC). The study took the form of a parallel-group randomised double-blinded placebo-controlled trial. METHODS: Postmenopausal women without hypercoagulability risk factors who were prevalent GC users were randomised to receive either raloxifene (60 mg/day) or placebo (1 tablet/day) on top of calcium (1000 mg/day) and calcitriol (0.25 µg/day). BMD of the hip and spine (primary outcome), bone turnover markers and new vertebral fractures (secondary outcomes) at month 12 were assessed. RESULTS: Between December 2006 and December 2008, 114 patients were recruited (age 55.3±7.7 years). The duration and dose of prednisolone received was 62.2±64 months and 6.7±5.9 mg/day, respectively. Baseline vertebral fracture was present in six (5%) patients. In all, 57 patients were allocated to each of the treatment arms. Demographic data, osteoporotic risk factors and BMD at various sites were similar between the two groups of patients. At month 12, a significant gain in the lumbar spine (+1.3±0.4%; p=0.004) and total hip BMD (+1.0±0.4%; p=0.01) was observed in patients treated with raloxifene but a significant decrease in BMD of the lumbar spine (-0.9±0.4%; p=0.045) and hip (-0.8±0.3%; p=0.01) occurred in the placebo group. The femoral neck BMD did not change significantly in favour of raloxifene. Three new fractures developed exclusively in the patients treated with placebo. Bone formation (serum osteocalcin and procollagen type I N-terminal) and resorption (urine deoxypyridinoline and type I collagen) markers decreased significantly in the raloxifene group but not in patients treated with placebo. Leg cramps were numerically more frequent in the raloxifene group (7% vs 0%) but thromboembolism was not reported in any patients. CONCLUSIONS: In postmenopausal women receiving long-term GCs, raloxifene is well tolerated and significantly increases spinal and hip BMD after 12 months of treatment.

Denosumab versus alendronate in long-term glucocorticoid users: A 12-month randomized controlled trial.

OBJECTIVES: To compare the efficacy of denosumab and alendronate on raising spine bone mineral density (BMD) in long-term glucocorticoid (GC) users. METHODS: Adult patients receiving long-term prednisolone (≥2.5 mg/day for ≥1 year) were recruited and randomized to either subcutaneous denosumab (60 mg/6 months) or oral alendronate (70 mg/week). BMD (lumbar spine, femoral neck, hip) and bone markers (serum P1NP and CTX) were measured at month 0, 6 and 12. The difference in spine BMD (primary outcome) at month 12 was compared between the two groups. RESULTS: 139 subjects were recruited (age 50.0 ± 12.7 years; 96% women): 69 assigned denosumab and 70 assigned alendronate. At entry, 73(53%) patients were osteoporotic and 82(59%) patients were naive to the bisphosphonates. Baseline clinical characteristics and BMD values were similar in the two groups. At month 12, a significant gain in mean BMD at the lumbar spine (+3.5 ± 2.5%; p<0.001), hip (+0.9 ± 2.8%; p=0.01) and femoral neck (+1.04 ± 4.1%; p=0.047); was observed in denosumab-treated patients, whereas the corresponding change was +2.5 ± 2.9% (p<0.001), +1.6 ± 2.7% (p<0.001) and + 1.5 ± 3.9% (p=0.002) in the alendronate group. The spine, but not the hip or femoral neck, BMD at month 12 was significantly higher in the denosumab than alendronate group after adjustment for baseline BMD values, age, sex, osteoporosis risk factors and the cumulative prednisolone doses received in one year. The drop in P1NP and CTX was significantly higher in the denosumab than alendronate group. Frequency of adverse events (AEs), including infections, was similar in the two treatment arms. Seven patients withdrew from the study but not related to AEs. CONCLUSIONS: In patients receiving long-term GCs, denosumab is superior to alendronate in raising the spine BMD after 12 months. Both drugs are well-tolerated.

Bone mineral density and body composition in men with systemic lupus erythematosus: a case control study.

OBJECTIVE: To study the bone mineral density (BMD) and body composition in men with systemic lupus erythematosus (SLE). METHODS: Consecutive male patients who fulfilled > or =4 ACR criteria for SLE and age-matched healthy men were recruited for measurement of BMD and body composition by DXA scan. Risk factors for low BMD in SLE patients were evaluated. RESULTS: 40 male SLE patients were studied (age 42.6+/-12 years; disease duration 84.7+/-79 months). 34 (85%) patients were treated with long-term glucocorticoids. Compared with 40 controls, SLE patients had a significantly lower BMD at the lumbar spine (0.96+/-0.16 vs 1.03+/-0.11 g/cm2; p=0.02) and the hip (0.87+/-0.14 vs 0.94+/-0.12 g/cm2; p=0.04). At the spine, 12 (30%) SLE patients had Z scores< - 2.0 and 2 (5%) had osteoporotic fractures. At the hip, 3 (7.5%) patients had Z scores< - 2.0 but none had hip fractures. The BMD Z scores at the femoral neck and spine were significantly lower in SLE patients than controls. The total lean body mass was also lower in patients than control subjects (46.4+/-7.3 vs 50.5+/-5.9 kg; p=0.01). Multiple regression revealed increasing age, habitual drinking, lower BMI and use of high-dose prednisolone were unfavorably associated with lower BMD at the spine in SLE patients. CONCLUSIONS: Reduced BMD and lean body mass are prevalent in men with SLE. Appropriate measures against osteoporosis should be undertaken, especially in older patients with low BMI who receive high-dose glucocorticoids.

Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: a 12-month randomized controlled trial.

OBJECTIVES: To evaluate the effect of switching from oral bisphosphonates to denosumab on bone mineral density (BMD) in long-term glucocorticoid users. METHODS: Adult patients who were receiving long-term prednisolone (≥2.5 mg/day for ≥1 year) and oral bisphosphonates (≥2 years) were recruited. Participants were randomized to either continue oral bisphosphonates or switch to denosumab (60 mg subcutaneously every 6 months) for 12 months. Serial BMD (lumbar spine, hip) and bone turnover markers (serum osteocalcin, P1NP, ß-CTX) were measured. RESULTS: 42 women were recruited (age 54.7±12.9 years; 21 shifted to denosumab and 21 continued on bisphosphonates). The duration of prednisolone therapy was 101±66.3 months and the daily dose was 4.4±2.1 mg. Baseline demographic data, osteoporosis risk factors, and BMD at various sites were similar between the two groups of patients. At month 12, BMD of the spine and hip increased by +3.4±0.9% (p=0.002) and +1.4±0.6% (p=0.03), respectively, in the denosumab group; whereas the corresponding change was +1.5±0.4% (p=0.001) and +0.80±0.5% (p=0.12) in the bisphosphonate group. The spinal BMD at month 12 was significantly higher in the denosumab than bisphosphonate group after adjustment for baseline BMD and ß-CTX values, and other confounding factors (p=0.01). Bone turnover markers (ß-CTX and P1NP) were more strongly suppressed by denosumab than the bisphosphonates. Minor infections were more common in denosumab-treated patients while other adverse events occurred at similar frequencies between the two groups. CONCLUSIONS: In patients receiving long-term glucocorticoids, switching from oral bisphosphonates to denosumab resulted in greater gain of the spinal BMD and suppression of bone turnover markers after 12 months of therapy. The results have to be confirmed by a larger clinical trial with fracture as endpoint.

Protein-losing enteropathy associated with or without systemic autoimmune disease: what are the differences?

OBJECTIVE: The aim of our study was to compare protein-losing enteropathy (PLE) associated with or without systemic autoimmune (SA) diseases. METHODS: Patients diagnosed with PLE were selected, and their clinical characteristics, laboratory, endoscopic and imaging characteristics, treatment, and outcome were analyzed. RESULTS: From 2001 to 2010, 74 patients (60 patients with SA disease) with a female predominance were diagnosed with PLE. The SA group tended to be younger, presented early (4.3 vs. 7 weeks, P=0.08), and had significantly more mucocutaneous-articular involvement (16.7 vs. 0%, P<0.05; 50 vs. 0%, P<0.02; 43.3 vs. 0%, P<0.01), compared with the other group, which showed more weight loss (64.3 vs. 25%, P<0.01), malaise and fatigue (57.1 vs. 28.3%, P<0.02), and tended to have more gastrointestinal (GI) symptoms. The SA group was associated with lymphopenia (0.8 vs. 2.7 × 109/l, P<0.01), hyperglobulinemia (43 vs. 31.2 IU/l, P<0.04), lactate dehydrogenase (511.1 vs. 393.5 IU/l, P<0.05), hematuria (48.3 vs. 7.1%, P<0.01), and pyuria (23.3 vs. 0%, P<0.03), whereas the non-SA group had a higher platelet count (402 vs. 262.5 × 109/l, P<0.01) and alkaline phosphatase (111 vs. 78.2 IU/l, P<0.03) on admission. A subgroup analysis of patients with SA disease showed that more lupus patients had pericardial effusion (14.6 vs. 0%, P=0.08), polyarthritis (50 vs. 16.7%, P=0.02), lower C3 level (0.5 vs. 0.85 mg/l, P<0.01), antinuclear factors (89.6 vs. 58.3%, P<0.01), and antiextractable nuclear antigen antibody (73.3 vs. 37.5%, P<0.03), whereas nonlupus patients had higher C-reactive protein (87.9 vs. 40 mg/l, P<0.01) and more antineutrophil cytoplasmic antibody (ANCA) (60 vs. 3%, P=0.00). Thirty-seven (71%) patients with SA disease had diffuse nonerosive erythematous GI mucosa with chronic inflammatory cells in the lamina propria layer, and 12 (85.7%) patients without SA disease had focal lesions. The treatment response was comparable between the two groups. However, the time required to normalize the serum albumin level (6.3 vs. 12.3 months, P=0.02) of patients with SA disease was much shorter than that of the non-SA group and those of inflammatory markers, specifically, C-reactive protein and complement C3, of its own group (6.3 vs. 11.6 vs. 12.1 months, P<0.04). More patients without SA disease had infective episodes during the management period (14.3 vs. 1.7%, P<0.01). CONCLUSION: Patients with PLE associated with SA disease tend to have a distinct clinical syndrome with regard to the extent of clinical manifestations and laboratory, endoscopic, and histological features compared with those without. Patients without SA disease are more prone to develop complications and mortality. However, both can be effectively treated with comparable treatment response.

Raloxifene for postmenopausal women with systemic lupus erythematosus: a pilot randomized controlled study.

OBJECTIVE: To study the effects of raloxifene on disease activity and bone mineral density (BMD) in postmenopausal women with systemic lupus erythematosus (SLE). METHODS: Postmenopausal women with osteopenia and inactive SLE were randomly assigned to receive either raloxifene (60 mg/day) plus elemental calcium (1,200 mg/day) or elemental calcium alone (control). Patients with a history of thromboembolism or antiphospholipid antibody positivity were excluded. BMD at various sites was serially measured, and lupus activity was serially assessed using the Safety of Estrogens in Lupus Erythematosus: National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI). RESULTS: The study group comprised 33 patients (16 assigned to receive raloxifene and 17 controls, mean +/- SD age 53.8 +/- 5.3 years). Age, body mass index, and baseline BMD values did not differ significantly between the 2 groups of patients. All patients were receiving low-dose prednisolone. After 12 months, femoral neck BMD (mean +/- SD -2.6 +/- 1.0%; P = 0.02) and lumbar spine BMD (-3.3 +/- 0.8%; P = 0.001) decreased significantly in the controls but not in the raloxifene group. No patient had a major flare of lupus, but mild/moderate flares occurred in 4 raloxifene-treated and 6 control patients (P = 0.79). The total area under the curve of SELENA-SLEDAI scores was not significantly different between the 2 groups. A significant increase in the high-density lipoprotein cholesterol level and a reduction in the low-density lipoprotein cholesterol level were observed in the raloxifene group but not in controls. One patient in the raloxifene group (6%) withdrew from the study because of hot flushes. No thromboembolic events were reported. CONCLUSION: Raloxifene was well tolerated in Chinese patients with SLE who had inactive disease and in whom hypercoagulability was not identified. Raloxifene maintained femoral neck and spinal BMD in patients receiving corticosteroids.

Segmental renal artery stenosis diagnosed with captopril renography in a child.

A 9-year-old girl with clinical suspicion of renovascular hypertension was referred for captopril renography. This showed a segmental abnormality when the left kidney was analyzed as two separate cortical regions of interest. Subsequent angiography confirmed stenosis in the distal mid and lower pole branches of the left renal artery.

Ictal 99mTc ECD SPECT in paroxysmal kinesigenic choreoathetosis.

Paroxysmal kinesigenic choreoathetosis is a rare neurologic disorder characterized by sudden attacks of brief involuntary dyskinetic movement that are precipitated by voluntary movement. A 14-year-old male who presented with frequent brief attacks of hemidystonia triggered by sudden movement is reported. Investigations, including video electroencephalogram and magnetic resonance imaging of brain, were normal. There was excellent and sustained response to carbamazepine. Ictal single-photon emission computed tomography using 99mTc ethyl cysteinate dimer revealed increased perfusion of the contralateral basal ganglia, which is associated with onset of choreoathetosis attacks. Our findings provide evidence that hyperactivity of the basal ganglia is associated with the dyskinetic attacks in paroxysmal kinesigenic choreoathetosis.