Cerebellar involvement in patients withprimary Sjögren’s syndrome: diagnosis and treatment

The aim of this study is to describe the clinical features of cerebellar involvement in patients with primary Sjögren’s syndrome (pSS). We retrospectively analyzed the manifestations, treatments, and outcomes in patients with pSS-cerebellar complication in Peking Union Medical College Hospital and cases reported in literature. Altogether 13 patients were identified. They were 2 males and 11 females with a mean age at disease onset of 45.2?±?14.6 years. Nine (69.2%) patients went to the clinic because of ataxia, and pSS was not suspected until accidental screening for autoantibodies. Dysarthria (7, 59.8%), limb tremor (4, 30.8%), and nystagmus (2, 15.4%) were the rest symptoms related to cerebellum. Of the patients, 81.8% (9/11) had abnormal cerebrospinal fluid findings, and 11 patients (84.6%) had cerebellar atrophy in the brain MRI. Dry eyes and dry mouth were detected in 9 (69.2%) and 7 (59.8%) patients, while positive objective xerostomia and ocular test in 82.5% (7/8) and 100% (10/10) of the patients, respectively. Anti-Ro/SSA antibody was positive in 12 (92.3%) and anti-La/SSB in 6 (46.2%) patients. Glucocorticoids were applied in 12 patients (92.3%). Cyclophosphamide (3, 20.1%), mycophenolatemofetil (1, 7.7%), and hydroxychloroquine (4, 30.8%) were chosen as immunosuppressants or anti-inflammatory drug. During a median follow-up of 9 months (range, 1–18 months), 8 (61.5%) patients remained stable, 3 (20.1%) patients were in remission, and 2 (15.4%) patients were in progression. Clinical cerebellar complication secondary to pSS was rare, and sometimes pSS was not suspected until accidental screening for autoantibodies. Because the onset of cerebellar manifestation is often insidious and rapid deteriorates, early diagnosis and empirical aggressive glucocorticoid treatment is warranted.     

经颈静脉途径肝内门体分流术（TIPS）治疗门脉高压食管静脉血张出血的临床评估

ＴＩＰＳ术治疗５０例，其中４９例为肝炎后肝硬化，１例为门静脉海绵窦样变，４５例有反复呕血及黑便史，５例无上消化道出血史，均有中－重度食管静脉曲张。１６例有中－大量腹水。结果：（１）４５例门静脉建立有效分流，成功率为９０％。门静脉主干压力从术前的３．９５±０．８５ｋＰａ降至２．３３±０．７２ｋＰａ（Ｐ＜０．００１）。（２）胃镜检查ＴＩＰＳ术后食管静脉曲张消失和基本消失率为４１．４３％，减轻为３７．９％。（３）术后腹水消失或减轻为６２％。（４）并发症与操作有关的为１２％，总发生率为３６％。（５）术后肝功能观察：血清总胆红质升高，血清白蛋白降低。随访１９９３年３月至１９９４年３月置入Ｇｉａｎｔｕｒｃ－ＲｏｓｃｈＺ型、网型支架的２４例患者，随访３个月至２２个月者２０例，支架狭窄、闭塞率半年为２０％，１年为５５％；复发出血８例为４０％。１９９４年４月至１９９５年１月置入ｗａｌｌｓｔｅｎｔ支架的２１例中，尚无支架闭塞及反复出血。全组现共死亡８例，死亡率为１５．６％     

The Clinical Characteristics of Primary Sjogren's Syndrome With Neuromyelitis Optica Spectrum Disorder in China: A STROBE-Compliant Article

The aim of the present study was to analyze the clinical characteristics of primary Sjogren''s syndrome (pSS) with neuromyelitis optica spectrum disorder (NMOSD). We retrospectively reviewed the medical records of 616 patients who were admitted to the Peking Union Medical College Hospital from 1985 to 2013. Of these patients, 43 developed NMOSD. The median duration of symptoms was 60 months and 72% of the patients experienced neurological complications onset in the pSS with NMOSD group. Twenty-one out of 43 patients had neuromyelitis optica (NMO), and 22 exhibited a limited form of NMO. Serum anti-aquaporin-4 (AQP4) antibody positivity was detected in 89.3% of the patients. A total of 60.5% of the patients (26 patients) complained of dry mouth, 72.1% were positive for objective xerostomia, 53.5% complained of dry eyes, and 74.4% had a positive ocular test. Biopsy of the minor salivary glands was performed in 33 patients, 28 of whom (84.8%) had a lymphocytic focus score of ≥1. Anti-Ro/SSA or anti-La/SSB antibodies were detected in 41 patients (95.3%). Compared with the pSS patients without NMOSD, the incidences of xerophthalmia, xerostomia, arthritis, interstitial lung disease, and renal tubular acidosis were significantly lower in the patients with NMOSD.NMOSD is a neurologic complication of pSS. The presence of anti-AQP4 antibody may be a predictor for pSS patients with NMOSD. Neurological manifestations are prominent in these patients. In clinical scenarios involving pSS or NMOSD, rheumatologists and neurologists should be aware of this association and perform the appropriate tests.     

Diagnostic value of single‐photon–emission computed tomography in severe central nervous system involvement of systemic lupus erythematosus: A case‐control study

Objective

To evaluate the diagnostic value of single‐photon–emission computed tomography (SPECT) in severe central nervous system (CNS) involvement of systemic lupus erythematosus (SLE).

Methods

Forty‐three patients with SLE, including 22 with CNS‐SLE and 21 with non–CNS‐SLE, underwent SPECT and magnetic resonance imaging (MRI) examinations. SPECT was repeated 1–2 months after treatment in patients with abnormal findings.

Results

SPECT and MRI abnormalities were detected in 20 (90.9%) and 10 (45.5%) of the 22 patients with CNS‐SLE, respectively (P < 0.01). For 4 patients with cerebral infarction or hemorrhage, SPECT was equally as sensitive as MRI (100%). For the patients with CNS‐SLE with diffuse presentations, SPECT was more sensitive than MRI in revealing abnormalities (16 [88.9%] of 18 patients versus 6 [33.3%] of 18 patients; P < 0.01). In 19 (95.0%) patients, the abnormal SPECT finding manifested as moderate to severe perfusion defect (15 in frontal lobe, 11 in parietal lobe, 11 in basal ganglia, 3 in temporal lobe, and 17 in multiple regions). Although mild perfusion defect was also detected in 4 (19.0%) of the patients with non–CNS‐SLE, it only involved a single region and spared the frontal and parietal lobes. Repeated SPECT after treatment showed that perfusion defect had improved significantly or even disappeared in 11 (84.6%) of 13 patients with diffuse CNS‐SLE with abnormal findings before treatment.

Conclusion

Moderate to severe perfusion defect in SPECT involving multiple regions, especially in the frontal and parietal lobes and basal ganglia, in patients with lupus suggests CNS involvement. SPECT is more sensitive than MRI in revealing damage in diffuse CNS‐SLE, and is useful in followup, especially for monitoring disease severity and guiding treatment.

     

The insulin-like growth factor-I receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastoma to the effects of chemotherapy

Medulloblastoma is the most common malignant tumor of the central nervous system in children. The insulin-like growth factor-I receptor (IGF-IR) is an important growth factor for medulloblastoma. The novel IGF-I receptor (IGF-IR) kinase inhibitor NVP-ADW742 has in vitro activity against tumors. Daoy cells were treated with NVP-ADW742 combined with temozolomide, which is commonly used in the chemotherapy of medulloblastoma. The effects on proliferation were assayed by CCK-8 assay. Cell cycle status and apoptosis were assayed by FACS analysis. The IGF-IR signaling pathway was analyzed by RT2 Profiler? PCR arrays and Western blotting. NVP-ADW742 inhibited IGF-IR-mediated proliferation with an IC50 of 11.12 μmol/l. The PCR array data suggested that 14 genes were down-regulated at the mRNA level after NVP-ADW742 treatment. Western blot analysis suggested that NVP-ADW742 induced early suppression of Akt, P38 and GSK-3β phosphorylation, as well as a decrease in the intracellular levels of PI3K, Akt, P38, GSK-3β and Bcl-2. Combined with NVP-ADW742 (2 μmol/l), IC50 of Daoy to temozolomide was decreased from 452.12 to 256.81 μmol/l. Cell apoptosis was enhanced from 16.18±2.47% to 23.20 ± 2.80%. G phase arrest was also found in both the temozolomide alone group and the temozolomide combined with NVP-ADW742 group. NVP-ADW742 inhibited the activation of PI3K, Akt, P38 and GSK-3β caused by temozolomide. NVP-ADW742 enhanced the chemosensitivity of Daoy to temozolomide in vitro, as a potent anti-tumor agent highly selective against IGF-IR.     

Pulmonary hypertension in primary biliary cirrhosis: A prospective study in 178 patients

Objective. To analyze the incidence, clinical features, and prognosis of patients with primary biliary cirrhosis (PBC) complicated by pulmonary hypertension (PH). Material and methods. A total of 178 consecutive PBC patients, who were admitted to Peking Union Medical College Hospital from January 2001 to March 2007, were included in this prospective study. A structured interview, systemic rheumatological examination, laboratory tests (including autoantibodies), and Doppler echocardiography were conducted for each patient and compared between patients with and without PH. Results. Twenty-one PBC patients (11.8%) had PH. Among them, four patients (19.0%) had moderate to severe PH, and one patient died of right heart failure instead of liver failure. The incidences of Raynaud's phenomenon, interstitial lung disease, Sjögren's syndrome, and portal hypertension, the proportion of patients with a positive anti-SSA, the level of serum IgA, as well as the Mayo risk score in the PH–PBC patients were significantly higher than in the non-PH-PBC group (p = 0.02, 0.001, 0.02, 0.03, 0.006, 0.04 and 0.02, respectively). Conclusions. PH, including moderate to severe PH, is not a rare complication of PBC. This complication is closely associated with portal hypertension and immunological dysregulation and indicates a poor prognosis.     

巩膜瓣下咬切术结合巩膜瓣可调节缝合治疗青光眼临床观察

目的：比较巩膜瓣下咬切结合膜瓣可调节缝线和单纯巩膜瓣下咬切术治疗青光眼的疗效和并发症。方法：采用随机分组平行对照临床验证的方法,将148例（175眼）青光眼分为实验组和对照组,并对其临床资料进行回顾性分析。结果：实验组手术效果优于对照组;实验组术后浅前房、低眼压、无功能性滤过泡形成等并发症发生率均低于对照组（P〈0.05、P〈0.01）。结论：巩膜瓣下咬切术结合可调节缝线能明显减少并发症,提高抗青光眼手术成功率。