Ocular presentation of primary central nervous system lymphoma: diagnosis and treatment

Primary ocular lymphoma (POL), a lymphoma of the globe, is a restricted form of primary central nervous system lymphoma (PCNSL) that often progresses to the brain and meninges; frequently it is misdiagnosed until central nervous system (CNS) lymphoma develops. The optimal treatment has not yet been identified. We retrospectively reviewed the course and the treatment of POL in 31 patients. Seventeen patients were treated for isolated POL (group A) and 14 were treated only after CNS disease was diagnosed (group B). The treatment in both groups consisted of systemic chemotherapy, chemotherapy plus radiotherapy (RT) or RT alone. In group A, nine patients (53%) developed CNS progression and five (29%) had ocular recurrence. In group B, seven (50%) had CNS progression and three (21%) ocular relapse. To control for diagnostic lead time, median survival was calculated from initial ocular symptoms and was 60 months in group A and 35 months in group B (P < 0.05). Ocular lymphoma responds to a variety of therapies but treatment with chemotherapy and/or ocular radiotherapy (ORT) failed to prevent CNS progression. Patients whose ocular disease was identified and treated before CNS progression had a significantly improved survival.     

原发性中枢神经系统淋巴瘤的诊治进展

原发性中枢神经系统淋巴瘤是一种较罕见的中枢神经系统恶性肿瘤,具有不向中枢神经系统轴以外播散、生物学行为具有侵袭性、病理形态存在异质性、临床无典型性、影像表现多样性、实验室检查无特异性的特点,依靠病理免疫组化及分子生物学方可确诊。对手术切除分歧较大,虽然对放射及化学药物治疗敏感,但缺乏共识方案,较全身及其他部位淋巴瘤预后差。该文就原发性中枢神经系统淋巴瘤的诊治进展作一综述。     

Analysis of Treponema pallidum recombinant antigens for diagnosis of syphilis by western blotting technique.

Three GST fusion recombinant antigen of Treponema pallidum, described as GST-rTp47, GST-rTp17 and GST-rTp15 were analyzed by Western blotting techniques. We have tested 53 serum samples: 25 from patients at different clinical stages of syphilis, all of them presenting anti-treponemal antibody, 25 from healthy blood donors and three from patients with sexually transmitted disease (STD) other than syphilis. Almost all samples from patients with syphilis presented a strong reactivity with GST-rTp17 antigen. Some samples were non-reactive or showed a weak reaction with GST-rTp47 and/or GST-rTp15, and apparently there was no correlation with the stage of disease. There was no seropositivity among blood donors. No sample reacted with purified GST. We concluded that due to their specificity these recombinant antigens can be used as GST fusion protein for development of syphilis diagnostic assays.     

Fuel sensing and the central nervous system (CNS): implications for the regulation of energy balance and the treatment for obesity

This review describes the product of the 3-day International Association for the Study of Obesity (IASO) Stock Conference held in March 2004 and sponsored by Abbott Laboratories. The conference was focused on how the mechanisms by which individual cells sense their own fuel status might influence the energy balance of the entire organism. Whether you are a single-celled organism or a sophisticated mammal with a large cerebral cortex, it is critical that cellular activity be matched to the available fuel necessary for that activity. Rapid progress has been made in the last decade in our understanding of the critical metabolic events that cells monitor to accomplish this critical task. More recent developments have begun to apply this understanding to how critical populations of neurones may monitor similar events to control both food intake and energy expenditure. The picture that emerges is that numerous peripheral fuel sensors communicate to the central nervous system (CNS) via neural and humoral routes. Moreover, it has been known for decades that specific populations of neurones sense changes in ambient glucose levels and adjust their firing rate in response and changes in neuronal glucose metabolism can influence energy balance. The CNS, however, does not just sense glucose but rather appears to be sensitive to a wide range of metabolic perturbations associated with fuel availability. This information is used to adjust both caloric intake and the disposition of fuels in the periphery. Increased understanding of these CNS fuel-sensing mechanisms may lead to novel therapeutic targets for obesity.     

Corticotropin-releasing factor antagonists, binding-protein and receptors: implications for central nervous system disorders

Corticotrophin-releasing factor (CRF; interchangeable with corticotrophin-releasing hormone, CRH) is a neurohormone family of peptides which implements endocrine, physiological and behavioural responses to stressor exposure. Built-in biological diversity and selectivity of CRF system function is provided by multiple endogenous ligands and receptors which are heterogeneously distributed in both brain and peripheral tissues across species. At present, there are at least five distinct targets for CRF with unique cDNA sequences, pharmacology and localization. These fall into three distinct classes, encoded by three different genes and have been termed the CRF1 and CRF2 receptors and the CRF-binding protein. Significant gains in knowledge about the physiological role of CRF binding sites in brain have emerged recently due to the proliferation of novel, high-affinity, receptor-selective pharmacological tools as well as multiple knock-out and knock-in mutant mouse models. These results support a role for CRF binding sites in co-ordinating stress reactivity, emotionality and energy balance over the life-span of the organism.     

Laboratory diagnosis of central nervous system infections.

The laboratory diagnosis of CNS infection is essential for optimal therapy. Acute infection requires rapid turn-around testing with high predictive values, that is, the ability of a test to accurately identify those patients who do or do not have disease caused by a specific etiology. The Gram's stain, fungal stains of direct smears, antigen testing for C. neoformans, and culture of bacteria, fungi, mycobacteria, and some viruses are important tests for the diagnosis of acute infection. The laboratory diagnosis of chronic infection necessitates discussion between the clinician and laboratory technician to allow triaging of testing. Antigen tests for bacteria, fungi, and viruses; antibody tests for multiple microorganisms; and PCR testing for bacteria, M. tuberculosis, and many viruses are all important in limited clinical situations. All testing for acute or chronic disease depends on sufficient specimen that is transported to the laboratory in a manner that will not compromise viability or chemical integrity. Sterile containers that maintain moisture content, exclude oxygen for anaerobic requests, and are stored at proper temperatures (22 degrees C room, 4 degrees C refrigeration, or -20 degrees C freezer depending on pathogen and test) are mandatory. Many laboratory issues addressing the diagnosis of CNS infection are changing or evolving. Most important is the recognition that bacterial antigen testing for the diagnosis of acute bacterial meningitis rarely impacts patient management and is not routinely needed, CSF shunt infections differ from usual meningeal infections and require rapid diagnosis, and TB meningitis remains a difficult disease to diagnosis but may be confirmed first by PCR testing of CSF. In addition, Whipple's disease of the CNS can be confirmed using PCR with CSF; CJD has a marker protein, referred to as 14-3-3 antigen, that can be detected in CSF, and the diagnosis of fungal CNS disease requires careful interpretation of direct smears, antigen and antibody testing, and culture. Most difficult to diagnose among the CNS infections are viral meningitis and encephalitis. The appearance of new etiologies, such as West Nile virus, and the common use of PCR for the herpes viruses and enteroviruses represent important advances. Evolving methods for the laboratory diagnosis of CNS infection represent significant improvements over previous testing; however, the array of tests available demands more attention for appropriate selection, is significantly more expensive, and requires new skills for performance and interpretation. The responsibility for proper use of laboratory testing lies both with the clinician and laboratory technician.     

Highly active antiretroviral therapy as the sole treatment for AIDS-related primary central nervous system lymphoma: a case report with implications for treatment

A 40-year-old male presented to medical attention with Pneumocystis jiroveci pneumonia and HIV infection. His CD4+ count was 18 cells per microliter and his HIV viral load (VL) was more than 400,000 copies milliliter. After 3 weeks of antibiotic therapy, he continued to have global cognitive deficits. A brain imaging study showed a right temporal mass, which on biopsy proved to be primary central nervous system lymphoma (PCNSL). He began highly active antiretroviral therapy (HAART) but declined palliative whole-brain radiotherapy (WBRT). Four months later, his CD4+ count had improved to 153 cells per microliter and his HIV VL was less than 75 copies per milliliter. At 36 months follow-up, he remained in complete remission (CR). Through a literature review, we identified 4 additional PCNSL patients who achieved prolonged remission after the initiation of HAART. One patient required WBRT and ventriculo-peritoneal shunting for signs and symptoms of obstructive hydrocephalus. The other 3 patients presented with stable neurologic findings and were treated with HAART alone. The median initial CD4+ count for these patients was 50 cells per microliter (range, 2 to 220 cells per microliter). All 5 remained in CR with a median follow-up of 23.5 (range, 13 to 36) months. For patients who present with PCNSL as their initial AIDS-defining event, stable neurologic findings, and effective HAART options, initial treatment with HAART alone may be possible, reserving WBRT and corticosteroids for those who show signs of impending neurologic demise. Chemotherapy and other novel approaches could also be considered for selected patients with lesser degrees of immune suppression and high baseline functional status.     

Potential role of apoE in structural plasticity in the nervous system; implications for disorders of the central nervous system

Apolipoprotein E (apoE) is a well characterized 299 amino acid protein that participates in the regulation of plasma cholesterol and lipid metabolism. In humans, apoE has three major protein isoforms: E2 (cys(112), cys(158)); E3 (cys(112), arg(158)); and E4 (arg(112), arg(158)) that are encoded for by a single gene on chromosome 19. Genetic studies have shown that apoE4 is a risk factor for Alzheimer's disease (AD) as well as for poor outcome following certain injuries to the central nervous system (CNS). These genetic data, as well as other data reviewed herein, suggest that apoE may play an important role in the nervous system under certain conditions. This review focuses on studies demonstrating that apoE can modulate neuronal structure and the potential implication of these findings for its role following CNS injury, in AD, and in other neurodegenerative diseases.     

Rapid diagnosis of viral infections in the central nervous system

Rapid diagnosis of viral infections in the central nervous system has become increasingly important. Antiviral treatment, prevention of spread of disease and differentiation from infections caused by agents sensitive to antibiotics may be the important consequences of a virus specific diagnosis gained early in the disease. The diagnosis can be obtained by detection of virus or viral antigen in the human specimen: herpes simplex virus by electron microscopy, immunofluorescence or immunosorbent assays in brain biopsies; rabies virus by immunofluorescence in corneal cells or skin and mucous membranes. The presence of measles or influenza antigens in nasopharyngeal secretions, shown by immunofluorescence or enzyme immunoassays, may diagnose an encephalitis caused by either of these viruses. Where suitable material is not available the detection of virus-specific IgM in a single serum specimen may be used for diagnosis. Mumps specific IgM activity is detected by enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence techniques; tick-borne encephalitis (TBE) specific IgM by immunosorbent assays or by reduction of hemagglutination-inhibition (HI) titer by 2-mercaptoethanol treatment of serum. Reports have been given on the detection of IgM activity by ELISA also in other arboviral infections such as Japanese and LaCrosse encephalitis. The demonstration of an intrathecal production of virus-specific immunoglobulins may reveal the type of virus causing the infection in the central nervous system.     

Acoustic evoked potentials and topical diagnosis in the central nervous system

Acoustic stimulation evokes about 15 waves, the so-called auditory evoked potentials (AEP). According to their appearance in time there are three groups: early auditory evoked potentials, middle latency AEP and late latency AEP. The shorter the latency of a wave, the more precise the coordination to a definable structure in the CNS. Therefore only EAEP allow besides an evaluation of hearing threshold a differential diagnosis between peripheral, neural and central hearing disturbances. Still unclear are questions such as exact origin of waves II to V and the difference of response due to rarefaction and condensation stimuli. The test, however, is a sensitive indicator to evaluate hearing disturbances and brainstem disorders.     

Molecular analysis of the fetal IgM response to Treponema pallidum antigens: implications for improved serodiagnosis of congenital syphilis

Western blot analysis of the fetal IgM response to Treponema pallidum antigens was examined among 39 pairs of maternal/infant sera; this included 12 mothers and infants with active syphilis (group I), 9 mothers with active syphilis and their infants with uncertain infection (group II), and 18 mothers treated for syphilis before delivery and their asymptomatic infants (group III). A fetal IgM response to T. pallidum antigens with apparent molecular masses of 72, 47, 45, 42, 37, 17, and 15 kDa was observed among sera of infants with congenital syphilis. Fractionation of sera into IgM and IgG components by high performance liquid chromatography confirmed that fetal IgM antibodies in every case were directed specifically against a 47-kDa antigen. Two asymptomatic infants from group II also showed serum IgM reactivities with the 47-kDa antigen, thereby appearing to confirm in utero infection. The combined data suggest that fetal serum IgM reactivity with the 47-kDa antigen of T. pallidum can be used as an important molecular marker for the diagnosis of congenital syphilis.     

梅毒螺旋体IgM抗体检测在梅毒诊断中的意义

目的 探讨检测血清梅毒螺旋体IgM抗体在梅毒诊断中的临床意义.方法 北京佑安医院性病门诊就诊者中已确诊为不同临床分期梅毒患者207例,治疗前采用免疫印迹法(TP-IgM-WB)检测血清中的IgM抗体同时进行快速血浆反应素环状卡片试验(RPR).患者规范治疗后,每3个月复查1次,1年后每半年复查1次,随访两年.首次RPR...     

Identification of Glycosylated Protein Antigens of Treponema pallidum and Treponema phagedenis

Comparison of autoradiographies of intrinsically [³⁵S] methionine and [¹⁴C] glucosamine labeled Treponema pallidum (Nichols strain) after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed four glycosylated proteins with molecular weights 30,500, 33,000, 35,000, and 59,000. T. phagedenis (biotype Reiter) was comparatively investigated and showed only two glycosylated proteins with molecular weights 33,000 and 34,000. The at the first time in treponemes identified glycosylated proteins could be precipitated with homologous human antibodies and characterized as antigens. By comparison with ¹²⁵I surface labeling of T. pallidum and T. phagedenis it is suggested that the glycosylated protein antigens are localized on the surface of these treponemes.     

High-dose ketoconazole for treatment of fungal infections of the central nervous system

Mortality and complication rates remain unacceptably high with conventional intravenous and intrathecal therapy for patients with coccidioidal meningitis and intracerebral fungal lesions. We studied the ventricular and lumbar cerebrospinal fluid penetration of ketoconazole and the responses to therapy in two patients receiving ketoconazole orally, 800 mg daily, and amphotericin B intraventricularly for meningeal and extrameningeal coccidioidomycosis. Five patients received only 1200 mg of ketoconazole: one had uncomplicated coccidioidal meningitis, three had obstructive hydrocephalus due to coccidioidal meningitis, and one had a histoplasmal brain abscess. Ketoconazole concentrations in ventricular and lumbar fluid ranged from 0.05 to 1.65 micrograms/mL 4 and 8 hours after the dose. The mean penetration of ketoconazole (+/- SD) was 1.9% +/- 0.8% for ventricular fluid and 5.4% +/- 2.6% for lumbar fluid. Ketoconazole concentrations in cerebrospinal fluid varied directly with those in serum and with cerebrospinal fluid protein content. The encouraging clinical responses, convenience, safety, and the consistent penetration of ketoconazole into obstructed and nonobstructed cerebrospinal fluid support the use of these regimens as alternatives to conventional therapy.     

Linezolid for the treatment of central nervous system infections in neurosurgical patients

We report our experience with linezolid in the treatment of 5 patients with central nervous system infections subsequent to neurosurgical interventions. In all cases, initial antimicrobial treatment regimens, including a glycopeptide, either failed or were associated with significant adverse events. The good clinical outcome and the absence of significant side-effects associated with linezolid suggest that it may be an attractive alternative for the treatment of central nervous system infections, particularly in settings characterized by a high incidence of multiresistant Gram-positive pathogens.