Clinical features,prognostic and risk factors of central nervous system infections in patients with systemic lupus erythematosus

The purpose of this study is to describe the etiology, characteristics and outcomes of central nervous system (CNS) infections in patients with systemic lupus erythematosus (SLE), while also identifying prognostic and risk factors. Thirty-eight SLE patients with CNS infections were identified from review of all charts of patients with SLE hospitalized from January 1995 to June 2005. These patients were divided into 3 groups, i.e., Mycobacterium tuberculosis (TB), non-TB bacterial and fungal infection groups. Of the 38 SLE cases with CNS infections, TB was identified in 19 patients, Listeria monocytogenes in 3 patients, Klebsiella pneumoniae in 1 patient, Staphylococcus aureus in 1 patient, Gram’s stain positive bacteria in 1 patient, Cryptococcus neoformans in 12 patients, and Aspergillus fumigatus in 1 patient. The rate of unfavorable outcome in patients with fungal infection was lower than in patients with TB (P=0.028) and non-TB bacterial CNS infections (P=0.046). SLE patients with TB or fungal CNS infections had a more insidious or atypical clinical presentation. Compared to SLE patients without CNS infections, those with CNS infections were more likely to have low serum albumin levels (P=0.048) and have been receiving higher doses of prednisolone at the onset of CNS infection (P=0.015) or higher mean doses of prednisolone within the previous year (P=0.039). In conclusion, low levels of serum albumin and higher doses of received prednisolone are important risk factors for the development of CNS infections in SLE patients. This work was supported by a research grant from Shanghai Leading Academic Discipline Project, Project number: T0203 and a research grant 30371332 from National Natural Science Foundation of China (NSFC).     

系统性红斑狼疮并发中枢神经系统病变的危险因素

目的 探讨系统性红斑狼疮（ＳＬＥ）并发中枢神经系统（ＣＮＳ）病变的危险因素。方法 对４６例并发ＣＮＳ病变的ＳＬＥ患者进行回顾性分析,并与１５２例无ＣＮＳ病变患者做对照。结果 ＳＬＥ的ＣＮＳ表现以癫痫最常见,占５４．３％,其次为精神异常,占３０．４％。与无ＣＮＳ病变的患者对照,两组在发病年龄和病程方面均无显著性差异（Ｐ〉０．０５）。ＳＬＥ病情重者在ＣＮＳ病变组有４３例（９３．５％）,在对照组有４１例     

Geriatric sexuality and chronic diseases

The age-related changes in sexual behavior are often the result of coexisting systemic illness. The elderly as a group are more likely to have chronic diseases. They are prescribed drugs that often interfere with sexual activity. They are also more likely to undergo surgical procedures that may result in bodily disfiguration and that are often accompanied by psychologic sequelae that prevent the patient from achieving sexual satisfaction. In addition to psychosocial sequelae of chronic illness, many diseases alter sexual activity through interference with vascular or neural integrity of the genitalia. In addition, limitation in cardiovascular and pulmonary functions may force the patient to avoid sexual contact. Many elderly patients would benefit if, in addition to optimization of their underlying physical condition, they receive instructions on alternate sexual techniques or coital positions. In many, referral to a specialized sex therapist may be helpful.     

Predictive factors for renal sequelae in adults with Henoch-Schönlein purpura

OBJECTIVE: To examine the outcome and risk factors for renal sequelae in an unselected population of adults with Henoch-Schonlein Purpura (HSP). METHODS: Retrospective study of adult patients (> 20 years) with biopsy proved cutaneous vasculitis diagnosed as having HSP seen at a single center between 1984 and 1998. Patients were classified as having HSP according to proposed criteria. Only those patients with a followup of at least 1 year were included in this study of renal sequelae. RESULTS: Twenty-eight patients with a mean followup of 5.5 years fulfilled the inclusion criteria. When the study was concluded, 10 patients (36%) had renal sequelae and 2 (7%) had renal insufficiency. Men outnumbered women. However, neither a previous history of drugs, gender, nor age at disease onset was associated with a higher risk of permanent renal involvement. Patients with hematuria at disease onset or renal involvement during the course of the disease more commonly developed renal sequelae (p < 0.001). The presence of anemia (p = 0.05) at the time of diagnosis and the onset in summer (p < 0.05) were also more common in those with permanent renal involvement (renal sequelae). Patients with relapses had also a higher trend to develop renal sequelae (p = 0.07). All patients who fulfilled more than 2 of these 5 risk factors developed permanent renal involvement. With this model we were able to predict renal sequelae in 8 of the 10 patients who had this complication. The Goodman-Kruskal gamma test value was 0.92 (95% CI 0.78-1.00). CONCLUSION: In unselected adults with HSP, permanent renal involvement (renal sequelae) is not uncommon. Hematuria at disease onset and persistence of renal manifestations during the course of the disease are significant indicators of possible development of renal sequelae. These manifestations plus other features such as onset in summer, anemia at disease onset, or relapses of the disease may predict the development of renal sequelae in most patients.     

Studies on the Use of "Prophylactic" Intrathecal Amethopterin in Childhood Leukemia

Central nervous system infiltration was studied in a group of 47 childrenwith acute leukemia. CNS involvement was found to occur more frequentlyand appear more rapidly in patients who presented with elevated peripheralWBC counts. CNS infiltration not suspected clinically was identified by spinalfluid examination in a significant minority of children at the time of theinitial diagnosis of leukemia, indicating that lumbar puncture should be aroutine part of the initial evaluation of patients with acute leukemia. Intrathecal amethopterin administered "prophylactically" at the time of initialdiagnosis of leukemia did not prevent or decrease the frequency of occurrenceof CNS infiltration. However, it did delay the onset of CNS involvement in patients with elevated WBC counts. Intrathecal amethopterin administered before the onset of CNS infiltration appears to be useful in delaying morbidityresulting from CNS involvement in children who present with elevated peripheral WBC counts.

Submitted on July 21, 1969 Revised on January 27, 1970 Accepted on February 10, 1970     

Central nervous system manifestations of marginal zone B-cell lymphoma

Primary or secondary central nervous system (CNS) involvement by marginal zone B-cell lymphoma (MZBCL) is rare. A retrospective analysis of patients was done with MZBCL involving the CNS, diagnosed and treated at our institution between 2004 and 2010. We identified 10 MZBCL patients with primary (six) or secondary (four) CNS involvement. Five patients presented with primary dural lymphoma and were treated with surgical resection, whole-brain radiation, or systemic chemotherapy. Only one patient had CNS relapse 5 years later. A single patient with primary intraocular lymphoma achieved clinical remission with ocular radiotherapy and systemic chemotherapy. Four patients had ocular MZBCL within 5 years of the initial diagnosis of primary ocular adnexal MZBCL and primary splenic MZBCL. There was no evidence of local recurrence in all but one who developed systemic relapse after 3 years of follow-up. Primary or secondary CNS involvement by MZBCL display indolent clinical behavior and have a generally favorable prognosis, underlining the importance of their differentiation from aggressive lymphomas that more commonly involve the CNS.     

Acute superior mesenteric venous thrombosis: one disease or two?

OBJECTIVE: The aim of this study was to determine the etiology and natural history of acute superior mesenteric venous thrombosis (MVT) with and without splenic or portal vein involvement. METHODS: A retrospective analysis was carried out of patients with acute superior MVT evaluated between 1979 and 1998. Case records were reviewed and a questionnaire mailed to patients for follow-up evaluation. Also, a search was made to identify etiologies such as malignancy, infection, inflammatory bowel disease, and other risk factors. Patients were divided into two groups, isolated MVT or MVT with splenic or portal vein involvement. RESULTS: A specific etiology (malignancy, thrombophilia, inflammatory bowel disease, or surgery) was found in 35 of 69 patients. Thirty patients had isolated MVT with involvement predominantly of the small mesenteric veins; in the remaining 39 there was also portal or splenic vein involvement. Patients with isolated MVT were less likely to be diagnosed by imaging studies such as ultrasonography and CT and more likely to have bowel necrosis, and they required surgery more frequently. Inherited hypercoagulable disorders were more often found in patients with isolated MVT. During follow-up, six patients had recurrent MVT, and one patient with combined mesenteric and portal vein thrombosis developed variceal bleeding. CONCLUSIONS: Patients with isolated MVT are more likely to have hypercoagulable disorders. Isolated MVT is more difficult to diagnose and more likely to require surgery. Classification of patients with MVT into those with small vessel involvement or those with splenic or portal vein involvement thus has important clinical and prognostic value. Patients surviving the initial period have a good prognosis but definite risk of recurrence. Risk of variceal complications appears low.     

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation for adult histiocytic disorders with central nervous system involvement

We postulated that high-dose chemotherapy (HDC) followed by peripheral autologous hematopoietic stem cell transplantation might help to control refractory central nervous system (CNS) histiocytic disorders. Six patients with histiocytic CNS involvement were treated in this way. Two patients achieved non-active disease status, although one relapsed at 84 months. Two patients had regressive disease, one of whom progressed at 21 months. One patient had progressive disease at 14 months. One patient had extra-CNS progression but CNS regression. After a median follow-up of 22.4 months, only one of the six patients still has non-active disease. Treatment was effective on craniofacial and space-occupying brainstem lesions, and was ineffective on neurodegenerative lesions.     

Late onset systemic lupus erythematosus: no substantial differences using different cut-off ages

To compare the clinical, laboratory and immunological features of a group of Caucasian systemic lupus erythematosus (SLE) patients in relation to age at disease onset. Three groups of patients with different ages at disease onset were analysed and compared: group A (30 patients, ≥65 years); group B (62 patients, 50–64 years) and group C (163 patients, <50 years). All patients were regularly followed-up for a mean period of 6.5 years. Female predominance was reduced in groups A and B. Time-lapse between disease onset and diagnosis was longer in group A and B. There were no statistically significant differences in clinical features. The only relevant difference was observed in peripheral nervous system (PNS) involvement, more frequent in group A. Anti-dsDNA and RF were more frequent in group A. Complement levels were reduced more frequently in group C. No differences were observed in disease activity scores, while SLICC/ACR score was higher in group A. In Caucasian SLE patients, age at disease onset is not associated with differences in clinical features apart from a more frequent PNS involvement in elderly patients. In the same group, the organ damage seems to develop more rapidly mostly due to higher susceptibility to jatrogenic side effects.     

Secondary central nervous system involvement in 599 patients with diffuse large B-cell lymphoma: are there any changes in the rituximab era?

The introduction of rituximab has improved the overall prognosis of diffuse large B-cell lymphoma (DLBCL). However, the impact of rituximab on central nervous system (CNS) involvement in DLBCL remains a matter of debate. Patients with DLBCL and no CNS involvement at initial diagnosis were eligible for this analysis. Patients must have received treatment either with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP). We analyzed the incidence, clinical features and outcomes of CNS involvement that developed during or after completion of therapy. A cohort of 599 patients was eligible for this analysis. With a median follow-up of 26 and 21 months, respectively, 19 of 294 (6.5 %) in the CHOP group and 13 of 305 (4.3 %) in the R-CHOP group developed CNS involvement. Rituximab did not significantly reduce the risk of CNS involvement either in the univariate (P = 0.354) or in the multivariate analysis (RR 0.632, 95 % CI 0.301–1.327, P = 0.225). No patient developed CNS disease after 19 months in the R-CHOP group whereas four patients (21.1 %) in the CHOP group developed CNS disease 2 years after initial diagnosis (range 34–83 months). Systemic disease prior to or coincident with CNS occurrence was more common in the CHOP group than in the R-CHOP group (73.7 versus 38.5 %, P = 0.046). Isolated CNS events were more common in the R-CHOP group than those in the CHOP group (53.8 versus 10.5 %, P = 0.015). This study indicates that isolated CNS events are more common in DLBCL patients treated with R-CHOP than those treated with CHOP alone. Our data also suggest that the time and pattern of CNS events and systemic disease status differ with the addition of rituximab. Better methods for earlier detection and prophylaxis of CNS involvement are needed in the rituximab era.     

New cellular markers at diagnosis are associated with isolated central nervous system relapse in paediatric B‐cell precursor acute lymphoblastic leukaemia

In childhood acute lymphoblastic leukaemia (ALL), central nervous system (CNS) involvement is rare at diagnosis (1–4%), but more frequent at relapse (~30%). Because of the significant late sequelae of CNS treatment, early identification of patients at risk of CNS relapse is crucial. Using microarray‐analysis, we discovered multiple differentially expressed genes between B‐cell precursor (BCP) ALL cells in bone marrow (BM) and BCP‐ALL cells in cerebrospinal fluid (CSF) at the time of isolated CNS relapse. After confirmation by real‐time quantitative polymerase chain reaction, selected genes (including SCD and SPP1) were validated at the protein level by flowcytometric analysis of BCP‐ALL cells in CSF. Further flowcytometric validation showed that a subpopulation of BCP‐ALL cells (>1%) with a ‘CNS protein profile’ (SCD positivity and increased SPP1 expression) was present in the BM at diagnosis in patients who later developed an isolated CNS relapse, whereas this subpopulation was <1% or absent in all other patients. These data indicate that the presence of a (small) subpopulation of BCP‐ALL cells with a ‘CNS protein profile’ at diagnosis (particularly SCD‐positivity) is associated with isolated CNS relapse. Such information can be used to design new diagnostic and treatment strategies that aim at prevention of CNS relapse with reduced toxicity.     

Determination of HBeAg by radioimmunoassay: prognostic implications in hepatitis B.

A radioimmunoassay was used to determine the presence of the hepatitis B e antigen (HBeAg) and anti-HBe in the serum of 12 hepatitis B patients, who were follofed from an early phase of the illness into convalescence. The duration of detectable HBeAg in serum from these patients, in all ow whom the disease ran a normal course, was compared with the persistence of HBeAg in serum of nine patients with a protracted course and persistence of HBsAg in serum for more than 1 year. None of the hepatitis B patients with a normal course of the disease had HBeAg demonstrable for more than 9 weeks after the onset of illness (mean 5.4 weeks), whereas all patients developing chronic hepatitis had HBeAg in serum for more than 1 year after the onset of illness. These findings indicate that the detection of HBeAg in serum by radioimmunoassay for 10 weeks or more after the onset of illness implies a great risk of progression of the hepatitis B infection to chronic liver disease.     

A multidisciplinary treatment strategy that includes high-dose chemotherapy for metastatic retinoblastoma without CNS involvement

The prognosis of patients with metastatic retinoblastoma is poor with conventional chemotherapy and radiation. Since retinoblastoma is highly chemosensitive, dose-escalation of chemotherapeutic agents with stem cell support should be promising. We report our experience with high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) in patients with metastatic retinoblastoma. Five patients with metastatic retinoblastoma underwent HDC with autologous SCT following conventional chemotherapy and local radiation therapy. Stem cells (bone marrow in four and peripheral blood stem cells in one) were collected after marrow involvement was cleared. Melphalan was a key drug in all patients, and was administered in combination with other agents such as cisplatin, cyclophosphamide, carboplatin or thiotepa. Three patients are currently alive disease-free at 113, 107 and 38 months, respectively, from the time of SCT. They had no central nervous system (CNS) involvement. The two patients who died of disease had CNS involvement. No long-term sequelae of HDC have been noted. Our treatment strategy using HDC appears to be effective for treating metastatic retinoblastoma without CNS involvement.     

Primary CNS lymphoma with bilateral symmetric hypothalamic lesions presenting with panhypopituitarism and diabetes insipidus

We present an unusual case of primary central nervous system (CNS) lymphoma presenting with bilateral symmetric hypothalamic lesions causing diabetes insipidus and hypopituitarism. A 50-year-old male presented initially with mental status changes, polyuria and polydipsia. The patient was determined to have diabetes insipidus (DI) and significant anterior pituitary deficiencies resulting in symptomatic pleural and pericardial effusions. Brain MRI with contrast demonstrated bilateral enhancement of his hypothalamus extending to the optic tract. The extensive diagnostic workup that ensued on his initial presentation was non-diagnostic as he had no obvious site of involvement that was easily accessible to biopsy. With close follow-up, the patient had rapid radiographic progression of his disease to his cerebral hemispheres. He therefore underwent brain biopsy and was diagnosed with primary CNS large B cell lymphoma. Chemotherapy has resulted in disease remission with resolution of MRI findings, but the patient has not had resolution of the hypopituitarism or DI. This case highlights the unique diagnostic challenge of patients with isolated hypothalamic lesions.     

Pulmonary manifestations of waldenstrom macroglobulinemia

Waldenstrom macroglobulinemia (WMG), a proliferation of malignant monoclonal IgM secreting plasmacytoid lymphocytes in lymph nodes, spleen, and marrow, usually pursues a chronic clinical course. A patient with WMG for five years who developed pulmonary tumors consisting of plasmacytoid lymphocytes prompted a review of the literature for pulmonary manifestations of WMG. Twenty-six males and 18 females, ranging in age from 33 to 84 years, have been reported with histologically proven pulmonary involvement by WMG. The x-ray findings, evident in most patients when first seen, consisted of masses (22 patients), infiltrates (31 patients), and pleural effusions (19 patients). Most patients (24) had two or more of these manifestations but only five, in addition to our patient, had isolated pulmonary nodules. Isolated pulmonary infiltrates were found in ten patients and isolated pleural effusions in only four. Symptoms at the onset of pulmonary involvement included dyspnea (54%), nonproductive cough (33%), and chest pain (7%); 15% were asymptomatic. Pulmonary manifestations, like other features of WMG, respond to alkylating agents or irradiation and do not appear to affect prognosis adversely. Pulmonary involvement should be suspected in any patient with WMG who develops an abnormal chest x-ray.     

Direct invasion of the central nervous system by Mycoplasma pneumoniae: a report of two cases

We studied two patients with involvement of the central nervous system (CNS) associated with Mycoplasma pneumoniae. One patient had encephalitis and acute cerebellar ataxia, whereas the second had a mixed picture of encephalitic reaction superimposed on a disseminated malignancy of unknown origin. Specific IgM antibodies to M. pneumoniae were detected in the patients' sera but not in their cerebrospinal fluid. M. pneumoniae was repeatedly isolated by cultures from throat swabs and cerebrospinal fluid samples from both patients. Our patients add to previous reports suggesting that CNS involvement may result from direct invasion of the CNS by the pathogen.     

Testing for course patterns in Crohn's disease using clustering analysis

Using clustering analysis, we sought to identify groups of patients on the basis of the disease course among a population of 177 patients with Crohn's disease and followed for 3 years or more, starting from the first frank exacerbation of the disease. The first 36 values of a monthly clinical score represented the active variables of the clustering analysis. This method yielded 2 course groups, A and B, of 95 and 82 patients respectively. The unfavorable course in group A was characterized by the persistence of the clinically active disease at 3 years, whereas group B individuals achieved complete clinical remission within 2 years of onset on the average. Among the initially known clinical data which could explain the course, only the incidence of an occlusive syndrome was higher in group B, which showed a more favorable course. Although we applied clustering analysis to a patient sample over a period of only 3 years, our results do suggest the existence or 2 primary course groups within the population of patients with Crohn's disease. It would appear that the disease course cannot be predicted from the clinical parameters present at the time of onset, but rather becomes apparent during the course of the first 2 years.     

强直性脊柱炎髋关节病变的相关因素分析

目的 探讨强直性脊柱炎(AS)患者髋关节病变的危险因素.方法 将同期住院的102例有髋关节破坏性病变的AS患者(A组)和54例无髋关节破坏性病变的患者(B组)临床资料和治疗方法分别进行单因素和非对称多因素Logistic回归分析.结果 A组患者比B组发病年龄早[(17±8)岁与(24±7)岁]、病程短[(5±4)年与(11±5)年]、幼年发病多见(37.3%与20.4%)、首发髋关节起病较多(38.2%与25.9%),以及外周关节炎重(39.2%与20.4%),差异均有统计学意义(P均＜0.05).A组患者红细胞沉降率(ESR)、C反应蛋白(CRP)、免疫球蛋白(IgG、IgM)水平,以及骶髂关节病变率显著高于B组(P均＜0.05).A组使用糖皮质激素剂量显著多于B组,使用柳氮磺吡啶和沙利度胺剂量显著少于B组(P均＜0.05).Logistic回归分析显示仅有5个髋关节病变相关因素,包括发病年龄、病程、幼年发病、首发髋关节起病以及服用柳氮磺吡啶(P＜0.05或P＜0.01).结论 发病年龄早、幼年发病、病程短以及髋关节起病的AS患者可能易于发生首发髋关节病变,而足量的柳氮磺吡啶可能是AS起病发生髋关节病变的保护因素.     

Fulminant septicaemic syndrome of Bacillus cereus: three case reports

Three patients with acute leukaemia, who were severely neutropenic and iatrogenically immunosuppressed post-chemotherapy, developed rapidly fatal septicaemic shock and coma caused by Bacillus cereus (B. cereus). The illness was marked by two phases: a mild febrile illness lasting 6-14 h and accompanied by subtle symptoms of autonomic sympathetic nervous system overactivity, and a second short fulminant one, marked by high fever of 40-41 degrees C accompanied by major central nervous system disturbances, and ending with deep coma and brain stem dysfunction. One patient developed the sepsis in spite of 4 days of coverage with amikacin. In the other two patients, amikacin was commenced at the earliest phase of the infection, but failed to influence the outcome. This form of B. cereus sepsis in neutropenic patients seems to be caused by strains capable of causing bacteraemia and meningitis and has the ability to produce a substance that causes leptomeningeal and neuronal necrosis. Lack of early clinical and laboratory markers inevitably leads to death. Use of antibiotics effective against B. cereus and capable of achieving high concentrations in the cerebrospinal fluid. and identification and neutralization of the necrotizing substance may hopefully help to reverse this fatal illness.     

Non-01 Vibrio cholerae infections in Cancun, Mexico

To determine the role of Vibrio cholerae as a cause of diarrheal illness in Cancun, Mexico, an investigation was conducted in July and August 1983. Although toxigenic V. cholerae 01 were not found, non-01 V. cholerae were isolated from 22 (16%) of 134 stools from persons with diarrheal illness and none of 22 stools from well persons; 58 (92%) of 63 sewage samples; 12 (86%) of 14 untreated well water samples; a home storage tank for treated water; and 5 (21%) of 24 samples of raw seafood. None of the V. cholerae isolates from patients were toxigenic. The illness occurred mainly in small children, and were characterized principally by diarrhea and abdominal pain. No patient was seriously ill, and all recovered without sequelae. Seven different serotypes of non-01 V. cholerae were isolated from the stool specimens, and Smith serotype 12 accounted for 10 (46%) of the 22 isolates. A matched-pair case-control study found that cases were more likely than controls to have eaten home prepared gelatin (P = 0.03, OR = 5/0) and seafood (P = 0.06, OR = 4/0).